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Sample records for charpy v-notch cvn

  1. Determination of the toughness of a low alloy steel from the Charpy V-notch impact testing

    International Nuclear Information System (INIS)

    Rossoll, A.

    1998-12-01

    Charpy V-notch (CVN) impact testing is widely used to characterize the resistance of a material to brittle fracture, by measuring the energy consumed by a specimen during impact. Notably materials undergoing a ductile-to-brittle transition, e.g. ferritic steels, are quality controlled by means of CVN testing, and their ductile-to-brittle transition temperature can be determined. Charpy testing is also widely used in the toughness assessment of large forged components, e.g. pressure vessels for pressurised water reactors (PWR). However, currently no satisfactory link between the Charpy impact energy CVN and the fracture toughness KIc exists. This study aims to establish a non-empirical relationship between the Charpy V-notch energy CVN, and the fracture toughness KIc, on the lower shelf of fracture toughness and the onset of the ductile-to-brittle transition of a A508 Cl.3 steel. The methodology employed is based on the so-called 'local approach'. Brittle cleavage fracture is modelled in terms of the Beremin (1983) model based on 'weakest link' statistics, whereas ductile crack advance preceding cleavage in the transition region is accounted for with the GTN model (Gurson, 1977; Tvergaard, 1982; Tvergaard and Needleman, 1984). Mechanical testing at different strain rates allowed for the establishment of the constitutive equations of the material in an elastic-viscoplastic formulation. Fracture tests on different specimen geometries provided the large data set necessary for statistical evaluation. All specimen types have been modelled with finite element analysis. However, the dynamic nature of the Charpy test requires special consideration. The origin of these dynamic effects was studied, as well as their implications on interpretation of experimental results and on modeling. After a proper modeling procedure had been defined, the local approach was employed for studying fracture. It is found that the fracture toughness can be predicted from the Charpy impact test

  2. Computer simulation of the Charpy V-notch toughness test

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.

    1977-01-01

    The dynamic Charpy V-notch test was simulated on a computer. The calculational models (for A-533 Grade B class 1 steel) used both a rounded and a flat-tipped striker. The notch stress/strain state was found to be independent of the three-point loading type and was most strongly correlated with notch-opening displacement. The dynamic stress/strain state at the time of fracture initiation was obtained by comparing the calculated deformed shape with that obtained in interrupted Charpy V-notch tests where cracking had started. The calculation was also compared with stress/strain states calculated in other geometries at failure. The distribution and partition of specimen energy was calculated and adiabatic heating and strain rate are discussed

  3. On impact testing of subsize Charpy V-notch type specimens

    International Nuclear Information System (INIS)

    Mikhail, A.S.; Nanstad, R.K.

    1994-01-01

    The potential for using subsize specimens to determine the actual properties of reactor pressure vessel steels is receiving increasing attention for improved vessel condition monitoring that could be beneficial for light-water reactor plant-life extension. This potential is made conditional upon, on the one hand, by the possibility of cutting samples of small volume from the internal surface of the pressure vessel for determination of actual properties of the operating pressure vessel. The plant-life extension will require supplemental surveillance data that cannot be provided by the existing surveillance programs. Testing of subsize specimens manufactured from broken halves of previously tested surveillance Charpy V-notch (CVN) specimens offers an attractive means of extending existing surveillance programs. Using subsize CVN type specimens requires the establishment of a specimen geometry that is adequate to obtain a ductile-to-brittle transition curve similar to that obtained from full-size specimens. This requires the development of a correlation of transition temperature and upper-shelf toughness between subsize and full-size specimens. The present study was conducted under the Heavy-Section Steel Irradiation Program. Different published approaches to the use of subsize specimens were analyzed and five different geometries of subsize specimens were selected for testing and evaluation. The specimens were made from several types of pressure vessel steels with a wide range of yield strengths, transition temperatures, and upper-shelf energies (USEs). Effects of specimen dimensions, including depth, angle, and radius of notch have been studied. The correlation of transition temperature determined from different types of subsize specimens and the full-size specimen is presented. A new procedure for transforming data from subsize specimens was developed and is presented

  4. Material inertia and size effects in the Charpy V-notch test

    DEFF Research Database (Denmark)

    Desandre, D. A.; Benzerga, A. A.; Tvergaard, Viggo

    2004-01-01

    The effect of material inertia on the size dependence of the absorbed energy in the Charpy V-notch test is investigated. The material response is characterized by an elastic-viscoplastic constitutive relation for a porous plastic solid, with adiabatic heating due to plastic dissipation and the re......The effect of material inertia on the size dependence of the absorbed energy in the Charpy V-notch test is investigated. The material response is characterized by an elastic-viscoplastic constitutive relation for a porous plastic solid, with adiabatic heating due to plastic dissipation...

  5. Miniaturized Charpy test for reactor pressure vessel embrittlement characterization

    Energy Technology Data Exchange (ETDEWEB)

    Manahan, M.P. Sr. [MPM Research and Consulting, Lemont, PA (United States)

    1999-10-01

    Modifications were made to a conventional Charpy machine to accommodate the miniaturized Charpy V-Notch (MCVN) specimens which were fabricated from an archived reactor pressure vessel (RPV) steel. Over 100 dynamic MCVN tests were performed and compared to the results from conventional Charpy V-Notch (CVN) tests to demonstrate the efficacy of the miniature specimen test. The optimized sidegrooved MCVN specimens exhibit transitional fracture behavior over essentially the same temperature range as the CVN specimens which indicates that the stress fields in the MCVN specimens reasonably simulate those of the CVN specimens and this fact has been observed in finite element calculations. This result demonstrates a significant breakthrough since it is now possible to measure the ductile-brittle transition temperature (DBTT) using miniature specimens with only small correction factors, and for some materials as in the present study, without the need for any correction factor at all. This development simplifies data interpretation and will facilitate future regulatory acceptance. The non-sidegrooved specimens yield energy-temperature data which is significantly shifted downward in temperature (non-conservative) as a result of the loss of constraint which accompanies size reduction.

  6. Weld investigations by 3D analyses of Charpy V-notch specimens

    DEFF Research Database (Denmark)

    Tvergaard, Viggo; Needleman, Allan

    2005-01-01

    The Charpy impact test is a standard procedure for determining the ductile-brittle transition in welds. The predictions of such tests have been investigated by full three dimensional transient analyses of Charpy V-notch specimens. The material response is characterised by an elastic...... parameters in the weld material differ from those in the base material, and the heat a®ected zone (HAZ) tends to be more brittle than the other material regions. The effect of weld strength undermatch or overmatch is an important issue. Some specimens, for which the notched surface is rotated relative...... to the surface of the test piece, have so complex geometry that only a full 3D analysis is able to account for the interaction of failure in the three different material regions, whereas ther specimens can be approximated in terms of a planar analysis....

  7. Ductile crack initiation in the Charpy V-notch test

    International Nuclear Information System (INIS)

    Server, W.L.; Norris, D.M. Jr.; Prado, M.E.

    1978-01-01

    Initiation and growth of a crack in the Charpy V-notch test was investigated by performing both static and impact controlled deflection tests. Test specimens were deformed to various deflections, heat-tinted to mark crack extension and broken apart at low temperature to allow extension measurements. Measurement of the crack extension provided an estimate of crack initiation as defined by different criteria. Crack initiation starts well before maximum load, and is dependent on the definition of ''initiation''. Using a definition of first micro-initiation away from the ductile blunting, computer model predictions agreed favorably with the experimental results

  8. Results of charpy V-notch impact testing of structural steel specimens irradiated at ∼30 degrees C to 1 x 1016 neutrons/cm2 in a commercial reactor cavity

    International Nuclear Information System (INIS)

    Iskander, S.K.; Stoller, R.E.

    1997-04-01

    A capsule containing Charpy V-notch (CVN) and mini-tensile specimens was irradiated at ∼ 30 degrees C (∼ 85 degrees F) in the cavity of a commercial nuclear power plant to a fluence of 1 x 10 16 neutrons/cm 2 (> 1MeV). The capsule included six CVN impact specimens of archival High Flux Isotope Reactor A212 grade B ferritic steel and five CVN impact specimens of a well-studied A36 structural steel. This irradiation was part of the ongoing study of neutron-induced damage effects at the low temperature and flux experienced by reactor supports. The plant operators shut down the plant before the planned exposure was reached. The exposure of these specimens produced no significant irradiation-induced embrittlement. Of interest were the data on unirradiated specimens in the L-T orientation machined from a single plate of A36 structural steel, which is the same specification for the structural steel used in some reactor supports. The average CVN energy of five unirradiated specimens obtained from one region of the plate and tested at room temperature was ∼ 99 J, while the energy of 11 unirradiated specimens from other locations of the same plate was 45 J, a difference of ∼ 220%. The CVN impact energies for all 18 specimens ranged from a low of 32 J to a high of 111 J. Moreover, it appears that the University of Kansas CVN impact energy data of the unirradiated specimens at the 100-J level are shifted toward higher temperatures by about 20 K. The results were an example of the extent of scatter possible in CVN impact testing. Generic values for the CVN impact energy of A36 should be used with caution in critical applications

  9. Use of forces from instrumented Charpy V-notch testing to determine crack-arrest toughness

    International Nuclear Information System (INIS)

    Iskander, S.K.; Nanstad, R.K.; Sokolov, M.A.; McCabe, D.E.; Hutton, J.T.

    1996-06-01

    The objective of this investigation is an estimation of the crack-arrest toughness, particularly of irradiated materials, from voltage versus time output of an instrumented setup during a test on a Charpy V-notch (CVN) specimen. This voltage versus time trace (which can be converted to force versus displacement) displays events during fracture of the specimen. Various stages of the fracture process can be identified on the trace, including an arrest point indicating arrest of brittle fracture. The force at arrest, F a , versus test temperature, T, relationship is examined to explore possible relationships to other experimental measures of crack-arrest toughness such as the drop-weight nil-ductility temperature (NDT), or crack-arrest toughness, K a . For a wide range of weld and plate materials, the temperature at which F a = 2.45 kN correlates with NDT with a standard deviation, sigma, of about 11 K. Excluding the so-called low upper-shelf energy (USE) welds from the analysis resulted in F a = 4.12 kN and σ = 6.6 K. The estimates of the correlation of the temperature for F a = 7.4 kN with the temperature at 100-MPa√m level for a mean American Society of Mechanical Engineers (ASME) type K Ia curve through crack-arrest toughness values show that prediction of conservative values of K a are possible

  10. Analysis of the Charpy V-notch test for welds

    DEFF Research Database (Denmark)

    Tvergaard, Viggo; Needleman, A.

    2000-01-01

    The ductile-brittle transition for a weld is investigated by numerical analyses of Charpy impact specimens. The material response is characterized by an elastic-viscoplastic constitutive relation for a porous plastic solid, with adiabatic heating due to plastic dissipation and the resulting thermal...... softening accounted for. The onset of cleavage is taken to occur when a critical value of the maximum principal stress is attained. The effect of weld strength undermatch or overmatch is investigated for a comparison material, and analyses are also carried out based on experimentally determined flow...... strength variations in a weldment in a HY100 steel. The predicted work to fracture shows a strong sensitivity to the location of the notch relative to the weld, with the most brittle behavior for a notch close to the narrow heat affected zone. The analyses illustrate the strong dependence of the transition...

  11. Investigation of Ductile-to-Brittle Transition of RPV Materials by using the Pre-cracked Charpy Impact Data

    International Nuclear Information System (INIS)

    Lee, Ho Jin; Lee, Bong Sang; Hong, Jun Hwa

    2005-01-01

    Much recent work in the field of elastic-plastic fracture mechanics has been directed to developing a mechanics-based relationship between the onset of cleavage fracture in structural components and that of Charpy V-notch specimens. The assessing processes of the cracks located in the reactor pressure vessel (RPV) is described in the ASME code Sec. III, App. G and Sec. XI, App. A. The RTNDT obtained from the impact test using standard Charpy V-notch (CVN) specimens is used as a reference temperature to assess the integrity of RPV materials. The initial RTNDT, for the Linde 80 weld, was determined by the 67.8J Charpy impact energy instead of drop weight test. Generally, Linde 80 weld has low upper-shelf energy. The initial RTNDT obtained from the Charpy impact energy curve has been considered overly conservative. Recently, master curve method has been investigated to assess the integrity of RPV materials directly. The initial RTT0 obtained from the master curve method is considered more realistic than the initial RTNDT obtained from impact test for low upper-shelf fracture toughness RPV materials. In this research, the correlation of transition regions between the master curves and the Charpy impact energy curves was investigated using the dynamic fracture toughness curve and the impact energy curve obtained from the impact test of pre-cracked Charpy (PCC) specimens. For the low toughness RPV material the ductile-to-brittle transition corresponding to the static master curve was anticipated using the invested correlation

  12. Laser weld reconstitution of conventional Charpy and Miniaturized Notch Test (MNT) specimens

    International Nuclear Information System (INIS)

    Manahan, M.P.; Williams, J.; Martukanitz, R.P.

    1993-01-01

    As nuclear power plants approach end-of-license (EOL) and consideration is given to license renewal, there is an ever increasing need to expand the amount of data obtainable from the original surveillance specimens. A laser welding technique to reconstitute broken Charpy specimens is being developed to produce both conventional and miniaturized Charpy specimens. This paper reports on early laser welding development efforts and summarizes previous proof-of-principle experiments on a 1/16 scale miniaturized Charpy test. In order to benchmark the laser welding procedure, the laser-reconstituted specimen data have been compared with the original specimen data. In addition, the microstructure after welding has been examined to ensure that the material in the vicinity of the notch is essentially unchanged after the welding process. Data which characterize the thermal transient during welding are obtained by attaching thermocouples to the specimens. Other important considerations include perturbation of the stress field near the notch, dynamic stress waves, and contact of the weld region with the tup. Precise control of welding parameters has been demonstrated, heat-affected zones as small as 0.25 mm can be achieved, and sufficient penetration depth can be obtained to enable welding thick sections (1T or greater) to yield conventional Charpy specimens or fracture toughness specimens and thin sections (∼5 mm) to yield Miniaturized Notch Test (MNT) specimens

  13. Computer model for ductile fracture

    International Nuclear Information System (INIS)

    Moran, B.; Reaugh, J. E.

    1979-01-01

    A computer model is described for predicting ductile fracture initiation and propagation. The computer fracture model is calibrated by simple and notched round-bar tension tests and a precracked compact tension test. The model is used to predict fracture initiation and propagation in a Charpy specimen and compare the results with experiments. The calibrated model provides a correlation between Charpy V-notch (CVN) fracture energy and any measure of fracture toughness, such as J/sub Ic/. A second simpler empirical correlation was obtained using the energy to initiate fracture in the Charpy specimen rather than total energy CVN, and compared the results with the empirical correlation of Rolfe and Novak

  14. Influence of thermal conditioning media on Charpy specimen test temperature

    International Nuclear Information System (INIS)

    Nanstad, R.K.; Swain, R.L.; Berggren, R.G.

    1989-01-01

    The Charpy V-notch (CVN) impact test is used extensively for determining the toughness of structural materials. Research programs in many technologies concerned with structural integrity perform such testing to obtain Charpy energy vs temperature curves. American Society for Testing and Materials Method E 23 includes rather strict requirements regarding determination and control of specimen test temperature. It specifies minimum soaking times dependent on the use of liquids or gases as the medium for thermally conditioning the specimen. The method also requires that impact of the specimen occur within 5 s removal from the conditioning medium. It does not, however, provide guidance regarding choice of conditioning media. This investigation was primarily conducted to investigate the changes in specimen temperature which occur when water is used for thermal conditioning. A standard CVN impact specimen of low-alloy steel was instrumented with surface-mounted and embedded thermocouples. Dependent on the media used, the specimen was heated or cooled to selected temperatures in the range -100 to 100 degree C using cold nitrogen gas, heated air, acetone and dry ice, methanol and dry ice, heated oil, or heated water. After temperature stabilization, the specimen was removed from the conditioning medium while the temperatures were recorded four times per second from all thermocouples using a data acquisition system and a computer. The results show that evaporative cooling causes significant changes in the specimen temperatures when water is used for conditioning. Conditioning in the other media did not result in such significant changes. The results demonstrate that, even within the guidelines of E 23, significant test temperature changes can occur which may substantially affect the Charpy impact test results if water is used for temperature conditioning. 7 refs., 11 figs

  15. Charpy V, an application in Mat lab; Charpy V, una aplicacion en Matlab

    Energy Technology Data Exchange (ETDEWEB)

    Castillo M, J.A.; Torres V, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2003-07-01

    The obtained results with the system Charpy V{sub V}1 designed in Mat lab for the estimate of parameters of three mathematical models are shown. The adjustment of data is used to determine the fracture energy, the lateral expansion and the percentage of ductility of steels coming from the reactor vessels of Laguna Verde, Veracruz. The data come from test tubes type Charpy V of irradiated material and not irradiated. To verify our results they were compared with those obtained by General Electric of data coming from the Laguna Verde nuclear power plant. (Author)

  16. Charpy Impact Test on Polymeric Molded Parts

    Directory of Open Access Journals (Sweden)

    Alexandra Raicu

    2012-09-01

    Full Text Available The paper presents the Charpy impact tests on the AcrylonitrileButadiene-Styrene (ABS polymeric material parts. The Charpy impact test, also known as the Charpy V-notch test, is a standardized strain rate test which determines the amount of energy absorbed by a material during fracture. This is a typical method described in ASTM Standard D 6110. We use for testing an Instron - Dynatup equipment which have a fully integrated hardware and software package that let us capture load information at very high speed from the impact tests.

  17. Characterization by notched and precracked Charpy tests of the in-service degradation of RPV steel fracture toughness

    International Nuclear Information System (INIS)

    Fabry, A.

    1997-01-01

    The current engineering and regulatory practice to estimate fracture toughness safety margins for nuclear reactor pressure vessels (RPVs) relies heavily on the CVN impact test. Techniques to estimate in-service toughness degradation directly using a variety of precracked specimens are under development worldwide. Emphasis is on their miniaturization. In the nuclear context, it is essential to address many issues such as representativity of the surveillance programs with respect to the vessel in terms of materials and environment, transferability of test results to the structure (constraint and size effects), lower bound toughness certification, creadibility relative to trends of exising databases. An enhanced RPV surveillance strategy in under development in Belgium. It combines state-of-the-art micromechanical and damage modelling to the evaluation of CVN load-deflection signals, tensile stress-strain curves and slow-bend tests of reconstituted precracked Charpy specimens. A probabilistic micromechanical model has been established for static and dynamic transgranular cleavage initiation fracture toughness in the ductile-brittle transition temperature range. This model allows to project toughness bounds for any steel embrittlement condition from the corresponding CVN and static tensile properties, using a single scaling factor defined by imposing agreement with toughness tests in a single condition. The outstanding finding incorporated by this toughness transfer model is that the microcleavage fracture stress is affected by temperature in the ductile-brittle transition and that this influence is strongly correlated to the flow stress: this explains the shape of the K Ic n K Id temperature curves as well as the actual magnitude of the strain rate and irradiation effects. Furthermore, CVN crack arrest loads and fracture appearance are also taken advantage of in order to estimate K Ia degradation. Finally, the CVN-tensile load-temperature diagram provides substantial

  18. Modeling and simulation of Charpy impact test of maraging steel 300 using Abaqus

    Science.gov (United States)

    Madhusudhan, D.; Chand, Suresh; Ganesh, S.; Saibhargavi, U.

    2018-03-01

    This work emphasizes the modeling and simulation of Charpy impact test to evaluate fracture energy at different pendulum velocities of armor maraging steel 300 using ABAQUS. To evaluate the fracture energy, V-notch specimen is fractured using the Johnson and Cook Damage model. The Charpy impact tests are of great importance related to fracture properties of steels. The objective of this work is to present absorbed energy variation at pendulum velocities of 5 m/sec, 6 m/sec, 7 m/sec and 9 m/sec in addition to stress distribution at v-notch. Finite Element Method of modeling for three dimensional specimens is used for simulation in commercial software of ABAQUS.

  19. Effects of annealing time on the recovery of Charpy V-notch properties of irradiated high-copper weld metal

    International Nuclear Information System (INIS)

    Iskander, S.K.; Sokolov, M.A.; Nanstad, R.K.

    1994-01-01

    One of the options to mitigate the effects of irradiation on reactor pressure vessels is to thermally anneal them to restore the toughness properties that have been degraded by neutron irradiation. An important issue to be resolved is the effect on the toughness properties of reirradiating a vessel that has been annealed. This paper describes the annealing response of irradiated high-copper submerged-arc weld HSSI 73W. For this study, the weld has been annealed at 454 C (850 F) for lengths of time varying between 1 and 14 days. The Charpy V-notch 41-J (30-ft-lb) transition temperature (TT 41J ) almost fully recovered for the longest period studied, but recovered to a lesser degree for the shorter periods. No significant recovery of the TT 41J was observed for a 7-day anneal at 343 C (650 F). At 454 C for the durations studied, the values of the upper-shelf impact energy of irradiated and annealed weld metal exceeded the values in the unirradiated condition. Similar behavior was observed after aging the unirradiated weld metal at 460 and 490 C for 1 week

  20. Characterization by notched and precracked Charpy tests of the in-service degradation of RPV steel fracture toughness

    Energy Technology Data Exchange (ETDEWEB)

    Fabry, A.

    1997-01-01

    The current engineering and regulatory practice to estimate fracture toughness safety margins for nuclear reactor pressure vessels (RPVs) relies heavily on the CVN impact test. Techniques to estimate in-service toughness degradation directly using a variety of precracked specimens are under development worldwide. Emphasis is on their miniaturization. In the nuclear context, it is essential to address many issues such as representativity of the surveillance programs with respect to the vessel in terms of materials and environment, transferability of test results to the structure (constraint and size effects), lower bound toughness certification, creadibility relative to trends of exising databases. An enhanced RPV surveillance strategy in under development in Belgium. It combines state-of-the-art micromechanical and damage modelling to the evaluation of CVN load-deflection signals, tensile stress-strain curves and slow-bend tests of reconstituted precracked Charpy specimens. A probabilistic micromechanical model has been established for static and dynamic transgranular cleavage initiation fracture toughness in the ductile-brittle transition temperature range. This model allows to project toughness bounds for any steel embrittlement condition from the corresponding CVN and static tensile properties, using a single scaling factor defined by imposing agreement with toughness tests in a single condition. The outstanding finding incorporated by this toughness transfer model is that the microcleavage fracture stress is affected by temperature in the ductile-brittle transition and that this influence is strongly correlated to the flow stress: this explains the shape of the K{sub Ic}n K{sub Id} temperature curves as well as the actual magnitude of the strain rate and irradiation effects. Furthermore, CVN crack arrest loads and fracture appearance are also taken advantage of in order to estimate K{sub Ia} degradation. Finally, the CVN-tensile load-temperature diagram

  1. Computer simulation of plastic deformation in the Charpy V-notch impact test

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.; Quinones, D.F.; Moran, B.

    1978-01-01

    Calculations describe the dynamic stress and strain states in the standard Charpy specimen from impact to the start of cracking. We model A533 Grade B Class 1 nuclear-pressure-vessel steel at 100 0 C with an elastic-plastic constitutive law. Large deformation and rotation of the material are accounted for. The specimen velocity field during the impact transient is presented and how the early wave effects cause separation of the specimen from the striker is shown. The calculations show why correlations between Charpy fracture energy and fracture toughness have been largely unsuccessful and suggest methods to improve these correlations using the same specimen geometry

  2. Charpy V, an application in Mat lab

    International Nuclear Information System (INIS)

    Castillo M, J.A.; Torres V, M.

    2003-01-01

    The obtained results with the system Charpy V V 1 designed in Mat lab for the estimate of parameters of three mathematical models are shown. The adjustment of data is used to determine the fracture energy, the lateral expansion and the percentage of ductility of steels coming from the reactor vessels of Laguna Verde, Veracruz. The data come from test tubes type Charpy V of irradiated material and not irradiated. To verify our results they were compared with those obtained by General Electric of data coming from the Laguna Verde nuclear power plant. (Author)

  3. Statistical evaluation of fracture characteristics of RPV steels in the ductile-brittle transition temperature region

    International Nuclear Information System (INIS)

    Kang, Sung Sik; Chi, Se Hwan; Hong, Jun Hwa

    1998-01-01

    The statistical analysis method was applied to the evaluation of fracture toughness in the ductile-brittle transition temperature region. Because cleavage fracture in steel is of a statistical nature, fracture toughness data or values show a similar statistical trend. Using the three-parameter Weibull distribution, a fracture toughness vs. temperature curve (K-curve) was directly generated from a set of fracture toughness data at a selected temperature. Charpy V-notch impact energy was also used to obtain the K-curve by a K IC -CVN (Charpy V-notch energy) correlation. Furthermore, this method was applied to evaluate the neutron irradiation embrittlement of reactor pressure vessel(RPV) steel. Most of the fracture toughness data were within the 95 percent confidence limits. The prediction of a transition temperature shift by statistical analysis was compared with that from the experimental data. (author)

  4. Dynamic Toughness Testing of Pre-Cracked Charpy V-Notch Specimens. Convention ELECTRABEL - SCK-CEN

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E

    1999-04-01

    This document describes the experimental and analytical procedures which have been adopted at the laboratories of the Belgian Nuclear Research Centre SCK-CEN for performing dynamic toughness tests on pre-cracked Charpy-V specimens. Such procedures were chosen on the basis of the existing literature on the subject, with several updates in the data analysis stages which reflect more recent developments in fracture toughness testing. Qualification tests have been carried out on PCCv specimens of JRQ steel, in order to assess the reliability of the results obtained; straightforward comparisons with reference data have been performed, as well as more advanced analyses using the Master Curve approach. Aspects related to machine compliance and dynamic tup calibration have also been addressed.

  5. Application of computer techniques to charpy impact testing of irradiated pressure vessel steels

    International Nuclear Information System (INIS)

    Landow, M.P.; Fromm, E.O.; Perrin, J.S.

    1982-01-01

    A Rockwell AIM 65 microcomputer has been modified to control a remote Charpy V-notch impact test machine. It controls not only handling and testing of the specimen but also transference and storage of instrumented Charpy test data. A system of electrical solenoid activated pneumatic cylinders and switches provides the interface between the computer and the test apparatus. A command language has been designated that allows the operator to command checkout, test procedure, and data storage via the computer. Automatic compliance with ASTM test procedures is built into the program

  6. Estimation of quasi-static J–R curves from Charpy energy and adaptation to ASTM E 1921 reference temperature estimation of ferritic steels

    International Nuclear Information System (INIS)

    Sreenivasan, P.R.

    2014-01-01

    Many researchers had suggested a sort of scaling procedure for predicting the quasi-static J–R curves from dynamic J–R curves obtained from instrumented Charpy V-notch (CVN) impact tests using key-curve, compliance or other procedures. Chaouadi, based on extensive tests and literature data, had quantitatively formalized the method and suggested general applicability of his method for a class of steels. In this paper, first, the Chauoadi-procedure is tried on some selected data from the literature (including the data used by Chaouadi and other workers) and an adaptation of the method is suggested using Wallin's as well as Landes's lower bound methods for upper-shelf J–R curve estimation from CVN energy. Using Chaouadi and other data as the benchmark, suitable scaling factors have been determined that enable estimation of quasi-static J–R curves from CVN energy alone, without the need for dynamic CVN J–R curves. The final formulae are given. This new method can be called modified Wallin–Landes procedure. Then this method is applied to fracture toughness and reference temperature (T 0 – ASTM E-1921) estimation from the full Charpy-transition data. The results are compared with those from the author's IGC-procedure, and modifications, if any, are suggested. Based on the new results, it is suggested that the IGC-procedure may be modified as: final T Q-est = T Q-IGC for T Q-Sch dy ≤ 20 °C (in the IGC-procedure the dividing temperature was 60 °C); and for T Q-Sch dy > 20 °C, T Q-IGC = T Q-WLm (different from the IGC-procedre and subscript WLm indicating modified Wallin–Landes procedure). For the 59 or more steels examined (including highly irradiated steels), the T Q-WL estimates at higher temperatures are consistent and conservative; a few non-conservative values are acceptably less than 20 °C, whereas other predictions show non-conservatism of up to 40–50 °C. At lower temperatures, T Q-IGC is consistently conservative and not over

  7. Estimation of quasi-static J–R curves from Charpy energy and adaptation to ASTM E 1921 reference temperature estimation of ferritic steels

    Energy Technology Data Exchange (ETDEWEB)

    Sreenivasan, P.R., E-mail: sreeprs@yahoo.co.in

    2014-04-01

    Many researchers had suggested a sort of scaling procedure for predicting the quasi-static J–R curves from dynamic J–R curves obtained from instrumented Charpy V-notch (CVN) impact tests using key-curve, compliance or other procedures. Chaouadi, based on extensive tests and literature data, had quantitatively formalized the method and suggested general applicability of his method for a class of steels. In this paper, first, the Chauoadi-procedure is tried on some selected data from the literature (including the data used by Chaouadi and other workers) and an adaptation of the method is suggested using Wallin's as well as Landes's lower bound methods for upper-shelf J–R curve estimation from CVN energy. Using Chaouadi and other data as the benchmark, suitable scaling factors have been determined that enable estimation of quasi-static J–R curves from CVN energy alone, without the need for dynamic CVN J–R curves. The final formulae are given. This new method can be called modified Wallin–Landes procedure. Then this method is applied to fracture toughness and reference temperature (T{sub 0} – ASTM E-1921) estimation from the full Charpy-transition data. The results are compared with those from the author's IGC-procedure, and modifications, if any, are suggested. Based on the new results, it is suggested that the IGC-procedure may be modified as: final T{sub Q-est} = T{sub Q-IGC} for T{sub Q-Sch}{sup dy} ≤ 20 °C (in the IGC-procedure the dividing temperature was 60 °C); and for T{sub Q-Sch}{sup dy} > 20 °C, T{sub Q-IGC} = T{sub Q-WLm} (different from the IGC-procedre and subscript WLm indicating modified Wallin–Landes procedure). For the 59 or more steels examined (including highly irradiated steels), the T{sub Q-WL} estimates at higher temperatures are consistent and conservative; a few non-conservative values are acceptably less than 20 °C, whereas other predictions show non-conservatism of up to 40–50 °C. At lower temperatures

  8. Small specimen test technology of fracture toughness in structural material F82H steel for fusion nuclear reactors

    International Nuclear Information System (INIS)

    Wakai, Eiichi; Ohtsuka, Hideo; Jitsukawa, Shiro; Matsukawa, Shingo; Ando, Masami

    2006-03-01

    Small specimen test technology (SSTT) has been developed to investigate mechanical properties of nuclear materials. SSTT has been driven by limited availability of effective irradiation volumes in test reactors and accelerator-based neutron and charged particle sources, and it is very useful for the reduction of waste materials produced in nuclear engineering. In this study new bend test machines have been developed to obtain fracture behaviors of F82H steel for very small bend specimens of pre-cracked t/2-1/3CVN (Charpy V-notch) with 20 mm-length and DFMB (deformation and fracture mini bend specimen) with 9 mm-length and disk compact tension of 0.18DCT type, and fracture behaviors were examined to evaluate DBTT (ductile-brittle transition temperature) at temperature from -180 to 25degC. The effect of specimen size on DBTT of F82H steel was also examined by using Charpy type specimens such as 1/2t-CVN, 1/3CVN and t/2-1/3CVN. In this paper, it also provides the information of the specimens irradiated at 250degC and 350degC to about 2 dpa in the capsule of 04M-67A and 04M-68A of JMTR experiments. (author)

  9. Conclusions regarding fracture mechanics testing and evaluation of small specimens - As evidenced by the finnish contribution to the IAEA CRP3 programme

    Energy Technology Data Exchange (ETDEWEB)

    Wallin, K; Valo, M; Rintamaa, R; Torronen, K [Technical Research Centre of Finland, Espoo (Finland); Ahlstrand, R [Imatran Voima Oy (IVO), Helsinki (Finland)

    1994-12-31

    An extensive mechanical property evaluation has been carried out on various specimens (a Japanese steel plate (JRQ), a French forging material (FFA) and a Japanese forging material (JFL)) in the as-received and irradiated conditions. The mechanical properties measured at different temperatures include Charpy-V notch and instrumented pre-cracked Charpy data and static and dynamic elastic-plastic fracture toughness based on the J-integral, with various specimen size and geometry. Test analysis lead to conclusions regarding the use of small specimen fracture mechanical tests for investigating irradiation effects: CVN{sub pc} and RCT type specimens are suitable for determining the materials fracture toughness even in the ductile/brittle transition region provided the elastic-plastic parameter K{sub JC} is applied together with a statistical size correction. These two specimen types yield equivalent results for the fracture toughness transition shift. Charpy-V appears not to be suitable for estimating the static fracture toughness transition shift. 8 refs., 11 figs.

  10. Effect of notch dimension on the fatigue life of V-notched structure

    International Nuclear Information System (INIS)

    Cheng Changzheng; Naman, Recho; Niu Zhongrong; Zhou Huanlin

    2011-01-01

    Highlights: → A novel method is proposed to calculate the SIFs of crack at notch tip. → Effect of notch opening angle on the crack extension and propagation is studied. → Influence of notch depth on the crack extension and propagation is analyzed. → The fatigue life of a welded joint is analyzed by the present method. - Abstract: The stress singularity degree associated to a V-notch has a great influence on the fatigue life of V-notched structure. The growth rate of the crack initiated at the tip of a V-notch depends on the stress singularity of the V-notch. The fatigue life accompanying with this small crack will represent a large amount of the total fatigue life. In this work, boundary element method (BEM) is used to study the propagation of the crack emanating from a V-notch tip under fatigue loading. A comparison of the fatigue life between the crack initiated from V-notch tip and a lateral crack is done by a crack propagation law until these two cracks have the same stress intensity factors (SIFs). The effect of initial crack length, notch opening angle and notch depth on the crack extension and propagation is analyzed. As an example of engineering application, the fatigue life of a welded joint is investigated by the present method. The influence of weld toe angle and initial crack length on the fatigue life of the welded structure is studied. Some suggestions are given as an attempt to improve the fatigue life of welded structures at the end.

  11. Methods and devices for small specimen testing at the Japan Atomic Energy Research Institute

    International Nuclear Information System (INIS)

    Jitsukawa, Shiro; Kizaki, Minoru; Umino, Akira; Shiba, Kiyoyuki; Hishinuma, Akimichi

    1993-01-01

    Devices for a punch test on annular notched specimens, small punch (SP) tests, and miniaturized tension tests in hot cells were developed. A micro-manipulator to handle small specimens and an electro-discharge machine (EDM) to extract miniaturized tension specimens and annular notched specimens from transmission electron microscopy (TEM) disks were also fabricated. These devices were designed and made for remote operation in hot cells. Preliminary tests to evaluate the applicability of test methods were carried out. Correlation between SP test results and tensile properties was not strong. Miniaturized tensile results were reasonably similar to the results with larger specimens. The ductile-brittle transition temperature (DBTT) by the punch test on annular notched specimens was higher than that obtained from the SP test. However, materials dependence of the DBTT was different from that measured by standard Charpy V-notch (CVN) tests. This may be due to a specimen size effect

  12. Use of precracked Charpy and smaller specimens to establish the master curve

    International Nuclear Information System (INIS)

    Sokolov, M.A.; McCabe, D.E.; Nanstad, R.K.; Davidov, Y.A.

    1997-01-01

    The current provisions used in the U.S. Code of Federal Regulations for the determination of the fracture toughness of reactor pressure vessel steels employs an assumption that there is a direct correlation between K Ic lower-bound toughness and the Charpy V-notch transition curve. Such correlations are subject to scatter from both approaches which weakens the reliability of fracture mechanics-based analyses. In this study, precracked Charpy and smaller size specimens are used in three-point static bend testing to develop fracture mechanics based K k values. The testing is performed under carefully controlled conditions such that the values can be used to predict the fracture toughness performance of large specimens. The concept of a universal transition curve (master curve) is applied. Data scatter that is characteristic of commercial grade steels and their weldments is handled by Weibull statistical modeling. The master curve is developed to describe the median K Jc fracture toughness for 1T size compact specimens. Size effects are modeled using weakest-link theory and are studied for different specimen geometries. It is shown that precracked Charpy specimens when tested within their confined validity limits follow the weakest-link size-adjustment trend and predict the fracture toughness of larger specimens. Specimens of smaller than Charpy sizes (5 mm thick) exhibit some disparities in results relative to weakest-link size adjustment prediction suggesting that application of such adjustment to very small specimens may have some limitations

  13. The period analysis of V418 AQL, SU BOO, RV CVn, CR CAS, GV CYG, V432 PER, and BD+42 2782

    International Nuclear Information System (INIS)

    Zasche, P.; Wolf, M.; Kučáková, H.; Uhlař, R.

    2014-01-01

    The minimum timings of eclipsing binaries V418 Aql, SU Boo, RV CVn, CR Cas, GV Cyg, V432 Per, and BD+42 2782 were collected and analyzed. Their long-term behavior was studied via period analysis, revealing a periodic term in eclipse times. We derived 576 new times of minimum. Hence, to describe the periodic variation, a third-body hypothesis was proposed and the resulting orbital periods are as follows: 70, 7.4, 53, 37, 27, 53, and 18 yr, respectively. For the system V432 Per an additional 9.5 yr variation was also found. The predicted minimum masses of these distant bodies were calculated and their detectability discussed. The light curves of SU Boo and RV CVn were analyzed using the PHOEBE program, resulting in physical parameters of the components. New variable stars in the field of V418 Aql were discovered.

  14. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range

    International Nuclear Information System (INIS)

    Tanguy, B.

    2001-07-01

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  15. SCK-CEN Contribution to the''Relation between different measures of exposure-induced shifts in ductile-brittle transition temperatures'' (REFEREE). Progress Report

    International Nuclear Information System (INIS)

    Chaouadi, R.; Van Walle, E.; Fabry, A.; Puzzolante, J.L.

    1998-08-01

    The relationship between Charpy-V (CVN) impact, fracture toughness and tensile properties for selected reactor pressure -vessel steels in the transition temperature range are investigated. Data on the testing of unirradiated material are reported. The applied methods include chemical analysis, Charpy-V impact testing, tensile testing and fracture toughness determination

  16. Analysis of impact energy to fracture un-notched charpy specimens made from railroad tank car steel

    Science.gov (United States)

    2007-09-11

    This paper describes a nonlinear finite element analysis : (FEA) framework that examines the impact energy to fracture : unnotched Charpy specimens by an oversized, nonstandard : pendulum impactor called the Bulk Fracture Charpy Machine : (BFCM). The...

  17. RS CVn binary systems

    International Nuclear Information System (INIS)

    Linsky, J.L.

    1984-01-01

    The author attempts to place in context the vast amount of data obtained in the last few years as a result of X-ray, ultraviolet, optical, and microwave observations of RS CVn and similar spectroscopic binary systems. He concentrates on the RS CVn systems and their long-period analogs, and restricts the scope by attempting to answer on the basis of the recent data and theory following questions: (1) Are the original defining characteristics still valid and still adequate? (2) What is the evidence for discrete active regions? (3) Have we derived any meaningful physical properties for the atmospheres of RS CVn systems? (4) What are the flare observations telling us about magnetic fields in the RS CVn systems? (5) Is there evidence for systematic trends in RS CVn systems with spectral type?

  18. Infrared observations of RS CVn stars

    International Nuclear Information System (INIS)

    Berriman, G.; De Campli, W.M.; Werner, M.W.; Hatchett, S.P.

    1983-01-01

    Infrared photometry is presented of the RS CVn binary stars AR Lac (1.2-10 μm) and MM Her (1.2-3.5 μm) as they egressed from their primary and secondary eclipses; of the eclipsing systems RS CVn and Z Her at maximum light (1.2-10 μm) and of the non-eclipsing systems UX Ari and HR 1099 (1.2-10 μm). An analysis of these and published V data based on flux ratio diagrams (linear analogues of colour-colour diagrams) shows that G and K stars supply the infrared light of these systems. None of these systems shows infrared emission from circumstellar matter. (author)

  19. Next generation self-shielded flux cored electrode with improved toughness for off shore oil well platform structures

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Daya; Soltis, Patrick; Narayanan, Badri; Quintana, Marie; Fox, Jeff [The Lincoln Electric Company (United States)

    2005-07-01

    Self-shielded flux cored arc welding electrodes (FCAW-S) are ideal for outdoor applications, particularly open fabrication yards where high winds are a possibility. Development work was carried out on a FCAW-S electrode for welding 70 and 80 ksi yield strength base materials with a required minimum average Charpy V-Notch (CVN) absorbed energy value of 35 ft-lb at -40 deg F in the weld metal. The effect of Al, Mg, Ti, and Zr on CVN toughness was evaluated by running a Design of Experiments approach to systematically vary the levels of these components in the electrode fill and, in turn, the weld metal. These electrodes were used to weld simulated pipe joints. Over the range of compositions tested, 0.05% Ti in the weld metal was found to be optimum for CVN toughness. Ti also had a beneficial effect on the usable voltage range. Simulated offshore joints were welded to evaluate the effect of base metal dilution, heat input, and welding procedure on the toughness of weld metal. CVN toughness was again measured at -40 deg F on samples taken from the root and the cap pass regions. The root pass impact toughness showed strong dependence on the base metal dilution and the heat input used to weld the root and fill passes. (author)

  20. Comparisons of irradiation-induced shifts in fracture toughness, crack arrest toughness, and Charpy impact energy in high-copper welds

    International Nuclear Information System (INIS)

    Corwin, W.R.; Nanstad, R.K.; Iskander, S.K.

    1991-01-01

    The Heavy-Section Steel Irradiation (HSSI) Program is examining relative shifts and changes in shape of fracture and crack-arrest toughness versus temperature behavior for two high-copper welds. Fracture toughness 100-MPa√m temperature shifts are greater than Charpy 41-J shifts for both welds. Mean curve fits to the fracture toughness data provide mixed results regarding curve shape changes, but curves constructed as lower boundaries indicate lower slopes. Preliminary crack-arrest toughness results indicate that shifts of lower-bound curves are approximately the same as CVN 41-J shifts with no shape changes

  1. ASK Procedure for Instrumented Pre-cracked Charpy-Type Tests

    International Nuclear Information System (INIS)

    Varga, T.; Njo, D.H.; Prantl, G.

    1981-01-01

    The essential technical content of the ASK procedure originated from development work in Switzerland since 1963, and practical experiences gained since 1972. The remainder of the content and the format of the procedure are based on the ASTM E 24.03.03. (Tentative Draft Copy) 'Proposed Method for Pre-cracked Charpy Impact and Slow-Bend Testing of Metallic Materials' by C. E. Harbower, 1973. Two different velocities, 5 m/s and 0.1 m/s were used with a Schnadt-type machine of rigid construction. The stiffness of the machine proved to be very suitable for instrumented testing. The instrumented Schnadt-Type machine was equipped with strain gauges both on the top of the pendulum and on the chisel. A static force calibration was followed by energy calibration, comparing potential energy losses with the area under the force-deflection curve. Deflection was measured using a high frequency eddy current method on the pendulum, and for slow testing by means of an inductive gauge on the chisel. Charpy-Type specimens of 1.0 mm max notch depth and 0.12 mm max notch radius were pre-cracked using a resonant fatigue testing machine, or an eccentric drive machine. Crack propagation rate da/dN was measured using 'Russenberger' measuring gauges. In addition a new technique for the detection of dynamic crack initiation, developed at the Institute of Research and Technology (TVFA) in Vienna is discussed and some results presented

  2. Charpy impact test of oxidized and hydrogenated zircaloy using a thin strip specimen

    International Nuclear Information System (INIS)

    Otsuka, Teppei; Hashizume, Kenichi; Sugisaki, Masayasu

    2004-01-01

    The impact properties of an oxidized and a hydrogenated Zircaloy have been studied with an instrumented Charpy machine by using a strip Charpy V-notch specimen (1 mm thick by 4mm wide). Fracture processes such as crack initiation and propagation were examined using load-displacement curves obtained in this study. In the case of the hydrogenated specimen containing preferentially oriented hydrides, an appreciable decrease in the absorbed energy was observed in the crack propagation rather than in the crack initiation. From results of fractographs of the specimen, it was suggested that the reduction of the crack propagation energy of hydrogenated specimen could be attributed to the change of the stress state in the Zircaloy matrix, which was caused by the fracture of hydride in the inner part of specimen. In the case of the specimen oxidized at 973k for 60 min, on which an oxide layer (4 μm in thickness) and oxygen incursion layer (4μm) were formed, the surface layers affected the crack initiation process. The growing oxygen incursion layer, in particular, resulted in the constraint of plastic deformation of the Zircaloy matrix not only in the crack initiation but also in the crack propagation as its thickness increased. (author)

  3. Critical applied stresses for a crack initiation from a sharp V-notch

    Directory of Open Access Journals (Sweden)

    L. Náhlík

    2014-10-01

    Full Text Available The aim of the paper is to estimate a value of the critical applied stress for a crack initiation from a sharp V-notch tip. The classical approach of the linear elastic fracture mechanics (LELM was generalized, because the stress singularity exponent differs from 0.5 in the studied case. The value of the stress singularity exponent depends on the V-notch opening angle. The finite element method was used for a determination of stress distribution in the vicinity of the sharp V-notch tip and for the estimation of the generalized stress intensity factor depending on the V-notch opening angle. Critical value of the generalized stress intensity factor was obtained using stability criteria based on the opening stress component averaged over a critical distance d from the V-notch tip and generalized strain energy density factor. Calculated values of the critical applied stresses were compared with experimental data from the literature and applicability of the LEFM concept is discussed.

  4. The Evolution of the Maine Lobster V-Notch Practice: Cooperation in a Prisoner's Dilemma Game

    Directory of Open Access Journals (Sweden)

    James Acheson

    2011-03-01

    Full Text Available The Maine lobster industry is experiencing record high catches because, in all probability, of an effective management program. One of the most important conservation measures is the V-notch program that allows fishermen to conserve proven breeding females by notching the tails of egg-bearing lobsters. Such marked lobsters may never be taken. Although thousands of lobster fishermen participate, it is a voluntary practice. The genesis of this practice is not easily explained, because V-notching poses a prisoner's dilemma problem that gives fishermen an incentive to avoid the practice. The most common explanations for ways to overcome prisoner's dilemma problems will not work in the case of the V-notch. An unusual combination of factors explains the V-notch program: (1 a strong belief among those in the industry that the V-notch is effective in conserving the lobster stock; (2 a low discount rate because the long-term gains from V-notching are higher than the one-time gain from defection; (3 a gain in reputation for those who V-notch. At the start of the 20th century, fishermen did not V-notch; by the end of the century, V-notching was common. We explain the change in strategies using a three-parameter evolutionary model that emphasizes the importance of culture change.

  5. Determinación de la tenacidad a la fractura de muestras de Acero 45 fundido, empleando las correlaciones entre el KIC y la energía de impacto medida en el ensayo de Charpy. // Determination of the fracture tenacity of cast Steel grade 45 samples, using th

    Directory of Open Access Journals (Sweden)

    F. Ramos Morales

    2005-05-01

    Full Text Available En el presente trabajo se determinan los valores de tenacidad a la fractura (KIC de muestras de Acero 45 fundido,empleando las correlaciones entre la tenacidad a la fractura y la energía de impacto (CVN obtenida del ensayo de Charpy.Se hace una discusión sobre las correlaciones que más se ajustan en la región de transición y en upper shelf. Se comparanlos valores obtenidos de estas correlaciones a valores de tenacidad a la fractura establecidos en la literatura.Palabras claves: Fractura, energía de impacto, acero fundido.______________________________________________________________________________Abstract.In this paper, the values of fracture toughness (KIC are determined on specimens of cast steel grade 45, using thecorrelations among the fracture toughness (KIC and the impact energy (CVN obtained from a Charpy test. A discussion ismade on the correlations that are better adjusted in the transition region and in upper shelf region. The obtained values arecompared from these correlations to values of fracture toughness (KIC settled down in the literature.Key words. Fracture, impact energy, cast steel.

  6. On the Effectiveness of the Dynamic Force Adjustment for Reducing the Scatter of Instrumented Charpy Results

    International Nuclear Information System (INIS)

    Lucon, E.

    2008-01-01

    One of the key factors for obtaining reliable instrumented Charpy results is the calibration of the instrumented striker. An interesting alternative to the conventional static calibration recommended by the standards is the Dynamic Force Adjustment (DFA), in which forces and displacements are iteratively adjusted until equality is achieved between absorbed energies calculated under the test record (Wt) and measured by the machine encoder (KV). In this study, this procedure has been applied to the instrumented data obtained by 10 international laboratories using notched and precracked Charpy specimens, in the framework of a Coordinated Research Project (CRP8) of IAEA. DFA is extremely effective in reducing the between-laboratory scatter for both general yield and maximum forces. The effect is less significant for dynamic reference temperatures measured from precracked Charpy specimens using the Master Curve procedure, but a moderate reduction of the standard deviation is anyway observed. It is shown that striker calibration is a prominent contribution to the interlaboratory variability of instrumented impact forces, particularly in the case of maximum forces.

  7. On the Effectiveness of the Dynamic Force Adjustment for Reducing the Scatter of Instrumented Charpy Results

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.

    2008-09-15

    One of the key factors for obtaining reliable instrumented Charpy results is the calibration of the instrumented striker. An interesting alternative to the conventional static calibration recommended by the standards is the Dynamic Force Adjustment (DFA), in which forces and displacements are iteratively adjusted until equality is achieved between absorbed energies calculated under the test record (Wt) and measured by the machine encoder (KV). In this study, this procedure has been applied to the instrumented data obtained by 10 international laboratories using notched and precracked Charpy specimens, in the framework of a Coordinated Research Project (CRP8) of IAEA. DFA is extremely effective in reducing the between-laboratory scatter for both general yield and maximum forces. The effect is less significant for dynamic reference temperatures measured from precracked Charpy specimens using the Master Curve procedure, but a moderate reduction of the standard deviation is anyway observed. It is shown that striker calibration is a prominent contribution to the interlaboratory variability of instrumented impact forces, particularly in the case of maximum forces.

  8. Three-dimensional vibrations of cylindrical elastic solids with V-notches and sharp radial cracks

    Science.gov (United States)

    McGee, O. G.; Kim, J. W.

    2010-02-01

    This paper provides free vibration data for cylindrical elastic solids, specifically thick circular plates and cylinders with V-notches and sharp radial cracks, for which no extensive previously published database is known to exist. Bending moment and shear force singularities are known to exist at the sharp reentrant corner of a thick V-notched plate under transverse vibratory motion, and three-dimensional (3-D) normal and transverse shear stresses are known to exist at the sharp reentrant terminus edge of a V-notched cylindrical elastic solid under 3-D free vibration. A theoretical analysis is done in this work utilizing a variational Ritz procedure including these essential singularity effects. The procedure incorporates a complete set of admissible algebraic-trigonometric polynomials in conjunction with an admissible set of " edge functions" that explicitly model the 3-D stress singularities which exist along a reentrant terminus edge (i.e., α>180°) of the V-notch. The first set of polynomials guarantees convergence to exact frequencies, as sufficient terms are retained. The second set of edge functions—in addition to representing the corner stress singularities—substantially accelerates the convergence of frequency solutions. This is demonstrated through extensive convergence studies that have been carried out by the investigators. Numerical analysis has been carried out and the results have been given for cylindrical elastic solids with various V-notch angles and depths. The relative depth of the V-notch is defined as (1- c/ a), and the notch angle is defined as (360°- α). For a very small notch angle (1° or less), the notch may be regarded as a "sharp radial crack." Accurate (four significant figure) frequencies are presented for a wide spectrum of notch angles (360°- α), depths (1- c/ a), and thickness ratios ( a/ h for plates and h/ a for cylinders). An extended database of frequencies for completely free thick sectorial, semi-circular, and

  9. Correlations between Standard and Miniaturised Charpy-V Specimens

    International Nuclear Information System (INIS)

    Lucon, E.; Van Walle, E.; Fabry, A.; Puzzolante, J.-L.; Verstrepen, A.; Vosch, R.; Van de Velde, L.

    1998-12-01

    A total of 565 instrumented impact tests (232 performed on full-size and 333 on sub-size Charpy-V specimens) have been analysed in order to derive meaningful assumptions on the correlations existing between test results obtained on specimens of different size. Nine materials (pressure vessel steels) have been considered, in both as-received and irradiated state, for a total of 19 conditions examined. For the analysis of data, conventional as well novel approaches have been investigated; former ones, based on a review of the existing literature, include predictions of USE values by the use of normalization factors (NF), shifts of index temperatures related to energy/lateral expansion/shear fracture levels, and a combination of both approaches (scaling and shifting of energy curves). More original and recent proposals have also been verified, available in the literature but also proposed by SCK-CEN in the frame of enhanced surveillance of nuclear reactor pressure vessels. Conclusions have been drawn regarding the applicability and reliability of these methodologies, and recommendations have been given for future developments of the activities on this topic

  10. Infrared observations of RS CVn stars

    Science.gov (United States)

    Berriman, G.; De Campli, W. M.; Werner, M. W.; Hatchett, S. P.

    1983-01-01

    The paper presents infrared photometry of the RS CVn binary stars AR Lac (1.2-10 microns) and MM Her (1.2-3.5 microns) as they egressed from their primary and secondary eclipses; of the eclipsing systems RS CVn and Z Her at maximum light (1.2-10 microns) and of the non-eclipsing systems UX Ari and HR 1099 (1.2-10 microns). An analysis of these and published V data based on flux ratio diagrams (linear analogues of color-color diagrams) shows that G and K stars supply the infrared light of these systems. In AR Lac, the combined light of a G5-K0 subgiant and either a late F dwarf or an early F subgiant can account for the observed visual and infrared light curves. None of these systems shows infrared emission from circumstellar matter. This result is simply understood: dust grains would not be expected to form in the physical conditions surrounding the subgiant, and the corona and chromosphere (whose properties have been deduced from spectroscopic X-ray observations) should not produce appreciable infrared emission.

  11. Z CVn - Still mysterious

    Science.gov (United States)

    Skarka, M.; Liška, J.; Dřevěný, R.; Sódor, Á.; Barnes, T.; Kolenberg, K.

    2018-04-01

    We comment on short- and long-term pulsation period variations of Z CVn, a classical RR Lyrae star with the Blazhko effect. Z CVn shows cyclic-like O-C diagram that can be interpreted as a consequence of binarity throught the light travel time effect. We show that this hypothesis is false and that the observed long-term period variations must be caused by some effect that is intrinsic to the star. We also show that the Blazhko period is not simply anti-correlated with the long-term period variations as was suggested by previous authors.

  12. Instrumented impact testing as a way to obtain further information on the behaviour of steel in welded constructions

    International Nuclear Information System (INIS)

    Nielsen, A.

    1976-05-01

    Based on experience gained from instrumented impact testing of ten different mild steels using test pieces of different geometrical shape (Charpy V-notch, Charpy knife-notch, DVM, Schnadt K 0 , Ksub(0.5), K 1 and K 2 ), some general features of the fracture process during impact testing are discussed. Steels can be divided into two main groups that are significantly different with respect to the behaviour during Charpy V-notch testing. The difference vanishes when a crack-like notch is used, and other properties of steel are revealed. It is evident that, even when modified impact testing bears little resemblance to what is happening in an actual steel construction. For the purpose of investigating the fracture conditions in welds, it seems more significant to relate the dynamic aspects to the speed of propagation of the crack when it starts to penetrate the volume considered at a certain stress level. (author)

  13. Investigation on the Crack Initiation of V-Shaped Notch Tip in Precision Cropping

    Directory of Open Access Journals (Sweden)

    Lijun Zhang

    2014-01-01

    Full Text Available The crack initiation of V-shaped notch tip has a very important influence on the cross-section quality and the cropping time for every segment of metal bar in course of low stress precision cropping. By the finite element method, the influence of machining precision of V-shaped notch bottom corner on the crack initiation location is analyzed and it is pointed out that the crack initiation point locates in the place at the maximal equivalent stress change rate on V-shaped notch surface. The judgment criterion of the crack initiation direction is presented and the corresponding crack initiation angle can be calculated by means of the displacement extrapolation method. The factual crack initiation angle of the metal bar has been measured by using the microscopic measurement system. The formula of the crack initiation life of V-shaped notch tip is built, which mainly includes the stress concentration factor of V-shaped notch, the tensile properties of metal material, and the cyclic loading conditions. The experimental results show that the obtained theoretical analyses about the crack initiation location, the crack initiation direction, and the crack initiation time in this paper are correct. It is also shown that the crack initiation time accounts for about 80% of the cropping time for every segment of the metal bar.

  14. Transition Fracture Toughness Characterization of Eurofer 97 Steel using Pre-Cracked Miniature Multi-notch Bend Bar Specimens

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiang [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sokolov, Mikhail A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Linton, Kory D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clowers, Logan N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Katoh, Yutai [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-11-01

    In this report, we present the feasibility study of using pre-cracked miniature multi-notch bend bar specimens (M4CVN) with a dimension of 45mm (length) x 3.3mm (width) x 1.65mm (thickness) to characterize the transition fracture toughness of Eurofer97 based on the ASTM E1921 Master Curve method. From literature survey results, we did not find any obvious specimen size effects on the measured fracture toughness of unirradiated Eurofer97. Nonetheless, in order to exclude the specimen size effect on the measured fracture toughness of neutron irradiated Eurofer97, comparison of results obtained from larger size specimens with those from smaller size specimens after neutron irradiation is necessary, which is not practical and can be formidably expensive. However, limited literature results indicate that the transition fracture toughness of Eurofer97 obtained from different specimen sizes and geometries followed the similar irradiation embrittlement trend. We then described the newly designed experimental setup to be used for testing neutron irradiated Eurofer97 pre-cracked M4CVN bend bars in the hot cell. We recently used the same setup for testing neutron irradiated F82H pre-cracked miniature multi-notch bend bars with great success. Considering the similarity in materials, specimen types, and the nature of tests between Eurofer97 and F82H, we believe the newly designed experimental setup can be used successfully in fracture toughness testing of Eurofer97 pre-cracked M4CVN specimens.

  15. Efecto de la Profundidad sobre la Soldabilidad de Aceros Ferríticos en Ambientes Simulados Unidos por Soldadura Húmeda

    Directory of Open Access Journals (Sweden)

    Fernando Macías López

    Full Text Available Resumen El objetivo de este trabajo fue evaluar el efecto de la profundidad sobre las propiedades en soldaduras de ranura en “V” con varios cordones de relleno. Metal base y electrodos comerciales fueron utilizados (ASTM A36 y AWS E7014 y cuatro diferentes condiciones se utilizaron para desarrollar las soldaduras húmedas como son 10, 20, 30 y 40m de profundidad. Una cámara presurizada con 30 atmósferas de capacidad fue utilizada para simular la profundidad, inundada con agua fresca. Un buzo soldador fue quien realizo las soldaduras. Las propiedades en la sección transversal mediante pruebas de tenacidad CVN (Charpy V-notch, macro ataque y esfuerzo a la tensión fueron determinadas por correlación. Las pruebas mecánicas con mejores resultados se observaron en la condición de 20m de profundidad.

  16. Ultrahigh Charpy impact toughness (~450J) achieved in high strength ferrite/martensite laminated steels

    Science.gov (United States)

    Cao, Wenquan; Zhang, Mingda; Huang, Chongxiang; Xiao, Shuyang; Dong, Han; Weng, Yuqing

    2017-02-01

    Strength and toughness are a couple of paradox as similar as strength-ductility trade-off in homogenous materials, body-centered-cubic steels in particular. Here we report a simple way to get ultrahigh toughness without sacrificing strength. By simple alloying design and hot rolling the 5Mn3Al steels in ferrite/austenite dual phase temperature region, we obtain a series of ferrite/martensite laminated steels that show up-to 400-450J Charpy V-notch impact energy combined with a tensile strength as high as 1.0-1.2 GPa at room temperature, which is nearly 3-5 times higher than that of conventional low alloy steels at similar strength level. This remarkably enhanced toughness is mainly attributed to the delamination between ferrite and martensite lamellae. The current finding gives us a promising way to produce high strength steel with ultrahigh impact toughness by simple alloying design and hot rolling in industry.

  17. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range; Modelisation de l'essai Charpy par l'approche locale de la rupture. Application au cas de l'acier 16MND5 dans le domaine de transition

    Energy Technology Data Exchange (ETDEWEB)

    Tanguy, B

    2001-07-15

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  18. Rupture Predictions of Notched Ti-6Al-4V Using Local Approaches

    Directory of Open Access Journals (Sweden)

    Mirco Peron

    2018-04-01

    Full Text Available Ti-6Al-4V has been extensively used in structural applications in various engineering fields, from naval to automotive and from aerospace to biomedical. Structural applications are characterized by geometrical discontinuities such as notches, which are widely known to harmfully affect their tensile strength. In recent years, many attempts have been done to define solid criteria with which to reliably predict the tensile strength of materials. Among these criteria, two local approaches are worth mentioning due to the accuracy of their predictions, i.e., the strain energy density (SED approach and the theory of critical distance (TCD method. In this manuscript, the robustness of these two methods in predicting the tensile behavior of notched Ti-6Al-4V specimens has been compared. To this aim, two very dissimilar notch geometries have been tested, i.e., semi-circular and blunt V-notch with a notch root radius equal to 1 mm, and the experimental results have been compared with those predicted by the two models. The experimental values have been estimated with low discrepancies by either the SED approach and the TCD method, but the former results in better predictions. The deviations for the SED are in fact lower than 1.3%, while the TCD provides predictions with errors almost up to 8.5%. Finally, the weaknesses and the strengths of the two models have been reported.

  19. Evaluation of toughness deterioration by an electrochemical method in an isothermally-aged N-containing austenitic stainless steel

    International Nuclear Information System (INIS)

    Saucedo-Munoz, Maribel L.; Lopez-Hirata, Victor M.; Avila-Davila, Erika O.; Melo-Maximo, Dulce V.

    2009-01-01

    This work presents the results of an evaluation of the deterioration of cryogenic toughness by means of an electrochemical method in a N-containing austenitic stainless steel (JK2) aged at temperatures of 700, 800 and 900 deg. C for times from 10 to 1000 min. The aging process at 700 and 800 deg. C caused the decrease in the Charpy V-Notch impact energy at - 196 deg. C because of the intergranular precipitation of carbides. Scanning electron micrographs of the Charpy V-Notch test specimens showed the presence of intergranular brittle fracture. The degree of sensitization was determined by the ratio of the maximum current density generated by the reactivation scan to that of the anodic scan, I r /I a , using the double-loop electrochemical potentiokinetic reactivation test. The Charpy V-Notch impact energy decreased with increase in the I r /I a ratio. This relation permits an estimate of the deterioration of cryogenic toughness due to thermal aging in this type of steel

  20. The origin of the RS CVn binaries

    International Nuclear Information System (INIS)

    Biermann, P.

    1976-01-01

    Six possible origins for the RS CVn binaries are considered based on the following possibilities. RS CVn binaries might now be either pre-main-sequence or post-main-sequence. A pre-main-sequence binary might not always have been a binary but might have resulted from fission of a rapidly rotating single pre-main-sequence star. The main-sequence counterparts might be either single stars or binaries. To decide which of the six origins is possible, the following observed data for the RS CVn binaries are considered: total mass, total angular momentum, lack of observed connection with regions of star formation, large space density, kinematical age, and the visual companion of WW Dra. In addition lifetimes and space densities of single stars and other types of binaries are considered. The only origin possible is that the RS CVn binaries are in a thermal phase following fission of a main-sequence single star. In this explanation the single star had a rapidly rotating core which became unstable due to the core contraction which made it begin to evolve off the main sequence. The present Be stars might be examples of such parent single stars. (Auth.)

  1. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range; Modelisation de l'essai Charpy par l'approche locale de la rupture. Application au cas de l'acier 16MND5 dans le domaine de transition

    Energy Technology Data Exchange (ETDEWEB)

    Tanguy, B

    2001-07-15

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  2. Fundamental study of crack initiation and propagation

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.; Reaugh, J.E.; Moran, B.; Quinones, D.F.; Wilkins, M.L.

    1977-01-01

    Objective is to determine the fracture toughness of A533B-1 steel by computer modeling Charpy V-notch tests. A computer model of ductile fracture was developed that predicts fracture initiation. The model contains a set of material-dependent parameters obtained by computer simulations of small specimen tests. The computer calculations give detailed stress and strain histories up to the time of fracture, which are used to determine the model parameter values. The calibrated fracture model, that correctly predicts fracture initiation (and initiation energy) in the Charpy specimen, may then be used to simulate tests of accepted fracture-toughness specimens and hence obtain fracture toughness. The model parameters were calibrated to predict fracture in four different test specimens: two different notched-tension specimens, a simple tension specimen, and a precracked compact-tension specimen. The model was then used in a computer simulation of the Charpy V-notch specimen to initiate and advance a flat fracture. Results were compared with interrupted Charpy tests. Calibration of the model for two additional heat treatments of A533B-1 steel is in progress

  3. An investigation of safety aspects of operating the end-shields in a brittle condition

    International Nuclear Information System (INIS)

    Seth, V.K.; Patwardhan, V.M.

    1975-01-01

    Published data on radiation embrittlement of 3.5% Ni steels (material for RAPP-1, RAPP-2 and MAPP-1 end shields - with charpy V notch value of 2.074 gm at -101 0 C) indicates that the nil ductility transition temperature rise would be of the order of 205 0 C to 260 0 C at the end of 30 year reactor life, against earlier figure of around 120 0 C. Surveillance programme on radiation embrittlement of the end-shields is being conducted to get an idea of the actual condition of the material at any required time. A study has been made to investigate safety aspects of operating the end shields in 'Brittle condition' of the material under the presently designed operating conditions. This study is based on the concept of crack arrest approach (employing fracture analysis diagram; FAD and linear elastic fracture mechanics (using possible correlation between Ksub(Ic) and CVN values). (author)

  4. The double helium-white dwarf channel for the formation of AM CVn binaries

    Science.gov (United States)

    Zhang, Xian-Fei; Liu, Jin-Zhong; Jeffery, C. Simon; Hall, Philip D.; Bi, Shao-Lan

    2018-01-01

    Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by gravitational wave radiation. However, a significant fraction with low mass ratios will survive for a long time as a consequence of stable mass transfer. Such stable mass transfer between two helium white dwarfs (HeWDs) provides one channel for the production of AM CVn binary stars. In previous calculations of double HeWD progenitors, the accreting HeWD was treated as a point mass. We have computed the evolution of 16 double HeWD models in order to investigate the consequences of treating the evolution of both components in detail. We find that the boundary between binaries having stable and unstable mass transfer is slightly modified by this approach. By comparing with observed periods and mass ratios, we redetermine masses of eight known AM CVn stars by our double HeWDs channel, i.e. HM Cnc, AM CVn, V406 Hya, J0926, J1240, GP Com, Gaia14aae and V396 Hya.We propose that central spikes in the triple-peaked emission spectra of J1240, GP Com and V396 Hya and the surface abundance ratios of N/C/O in GP Com can be explained by the stable double HeWD channel. The mass estimates derived from our calculations are used to discuss the predicted gravitational wave signal in the context of the Laser Interferometer Space Antenna (LISA) project.

  5. Charpy impact test results on five materials and NIST verification specimens using instrumented 2-mm and 8-mm strikers

    International Nuclear Information System (INIS)

    Nanstad, R.K.; Sokolov, M.A.

    1995-01-01

    The Heavy-Section Steel Irradiation Program at Oak Ridge National Laboratory is involved in two cooperative projects, with international participants, both of which involve Charpy V-notch impact tests with instrumented strikers of 2mm and 8mm radii. Two heats of A 533 grade B class I pressure vessel steel and a low upper-shelf (LUS) submerged-arc (SA) weld were tested on the same Charpy machine, while one heat of a Russian Cr-Mo-V forging steel and a high upper-shelf (HUS) SA weld were tested on two different machines. The number of replicate tests at any one temperature ranged from 2 to 46 specimens. Prior to testing with each striker, verification specimens at the low, high, and super high energy levels from the National Institute of Standards and Technology (NIST) were tested. In the two series of verification tests, the tests with the 2mm striker met the requirements at the low and high energy levels but not at the super high energy. For one plate, the 2mm striker showed somewhat higher average absorbed energies than those for the 8-mm striker at all three test temperatures. For the second plate and the LUS weld, however, the 2mm striker showed somewhat lower energies at both test temperatures. For the Russian forging steel and the HUS weld, tests were conducted over a range of temperatures with tests at one laboratory using the 8mm striker and tests at a second laboratory using the 2mm striker. Lateral expansion was measured for all specimens and the results are compared with the absorbed energy results. The overall results showed generally good agreement (within one standard deviation) in energy measurements by the two strikers. Load-time traces from the instrumented strikers were also compared and used to estimate shear fracture percentage. Four different formulas from the European Structural Integrity Society draft standard for instrumented Charpy test are compared and a new formula is proposed for estimation of percent shear from the force-time trace

  6. Fundamental study of crack initiation and propagation. Annual progress report, March 1976--March 1977

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.

    1977-01-01

    Ductile fracture in nuclear pressure vessel steel was characterized using a computer model of material damage. The model predicts crack initiation and growth and contains constants that are set by computer simulation of the following fracture tests: the simple tension test, the circumferentially notched round tension test, the blunt-notched compact tension test, and the Charpy V-notch test. The simulations provide the stress and strain states of these tests at fracture. The major goal of our characterization program is to determine the correlation between Charpy toughness and fracture toughness

  7. Effects of thermal aging and neutron irradiation on the mechanical properties of three-wire stainless steel weld overlay cladding

    International Nuclear Information System (INIS)

    Haggag, F.M.; Nanstad, R.K.

    1997-05-01

    Thermal aging of three-wire series-arc stainless steel weld overlay cladding at 288 degrees C for 1605 h resulted in an appreciable decrease (16%) in the Charpy V-notch (CVN) upper-shelf energy (USE), but the effect on the 41-J transition temperature shift was very small (3 degrees C). The combined effect of aging and neutron irradiation at 288 degrees C to a fluence of 5 x 10 19 neutrons/cm 2 (> 1 MeV) was a 22% reduction in the USE and a 29 degrees C shift in the 41-J transition temperature. The effect of thermal aging on tensile properties was very small. However, the combined effect of irradiation and aging was an increase in the yield strength (6 to 34% at test temperatures from 288 to -125 degrees C) but no apparent change in ultimate tensile strength or total elongation. Neutron irradiation reduced the initiation fracture toughness (J Ic ) much more than did thermal aging alone. Irradiation slightly decreased the tearing modulus, but no reduction was caused by thermal aging alone. Other results from tensile, CVN, and fracture toughness specimens showed that the effects of thermal aging at 288 or 343 degrees C for 20,000 h each were very small and similar to those at 288 degrees C for 1605 h. The effects of long-term thermal exposure time (50,000 h and greater) at 288 degrees C will be investigated as the specimens become available in 1996 and beyond

  8. Comparative study on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Bourdiliau, B.; Decroix, G.-M.; Averty, X.; Wident, P.; Bienvenu, Y.

    2011-01-01

    Highlights: → Welding processes are used to reconstitute previously tested Charpy specimens. → Stud welding is preferred for a quick installation, almost immediately operational. → Friction welding produces better quality welds, but requires a development effort. - Abstract: Reconstitution techniques are often used to allow material from previously fractured Charpy-V specimens to be reused for additional experiments. This paper presents a comparative experimental study of various reconstitution techniques and evaluates the feasibility of these methods for future use in shielded cells. The following techniques were investigated: arc stud welding, 6.0 kW CO 2 continuous wave laser welding, 4.5 kW YAG continuous wave laser welding and friction welding. Subsize Charpy specimens were reconstituted using a 400 W YAG pulsed wave laser. The best result was obtained with arc stud welding; the resilience of the reconstituted specimens and the load-displacement curves agreed well with the reference specimens, and the temperature elevation caused by the welding process was limited to the vicinity of the weld. Good results were also obtained with friction welding; this process led to the best quality welds. Laser welding seems to have affected the central part of the specimens, thus leading to different resilience values and load-displacement curves.

  9. Application of subsize specimens in nuclear plant life extension

    International Nuclear Information System (INIS)

    Rosinski, S.T.; Kumar, A.S.; Cannon, N.S.; Hamilton, M.L.

    1993-01-01

    The US Department of Energy is sponsoring a research effort through Sandia National Laboratories and the University of Missouri-Rolla to test a correlation for the upper shelf energy (USE) values obtained from the impact testing of subsize Charpy V-notch specimens to those obtained from the testing of full-size samples. The program involves the impact testing of unirradiated and irradiated full-, half-, and third-size Charpy V-notch specimens. To verify the applicability of the correlation on LWR materials, unirradiated and irradiated full-, half-, and third-size Charpy V-notch specimens of a commercial pressure vessel steel (ASTM A533 Grade B) will be tested. The correlation methodology is based on the partitioning of the USE into crack initiation and crack propagation energies. To accomplish this partition, both precracked and notched-only specimens will be used. Whereas the USE of notched-only specimens is the sum of both crack initiation and crack propagation energies, the USE of precracked specimens reflects only the crack propagation component. The difference in the USE of the two types of specimens represents a measure of the crack initiation energy. Normalizing the values of the crack initiation energy to the fracture volume of the sample produces similar values for the full-, half-, and third-size specimens. In addition, the ratios of the USE and the crack propagation energy are also in agreement for full-, half-, and third-size specimens. These two observations will be used to predict the USE of full-size specimens based on subsize USE data. This paper provides details of the program and presents results obtained from the application of the developed correlation methodology to the impact testing of the unirradiated full-, half-, and third-size A533 Grade B Charpy V-notch specimens

  10. Nuclear reactor pressure vessel integrity insurance by crack arrestability evaluation using load from CVN tests

    International Nuclear Information System (INIS)

    Fabry, A.

    1997-01-01

    The present work is undertaken in the framework of nuclear reactor pressure vessel (RPV) surveillance and aims at revisiting the crack arrest approach to structural integrity insurance. This approach, performed under normal plant operation conditions, can also offer an attractive alternative to the crack initiation philosophy promoted for accidental analysis. To this end, an accidental conservative, cost effective and robust methodology is forwarded and demonstrated: it makes use of the crack arrest information contained in the instrumented Charpy V-notch impact test and/or in the shear fracture appearance of broken samples. Particular attention is paid to the appraisal of uncertainties and the related safety margin. The resulting capability is placed in perspective with the state-of-the-art crack initiation methodology based on the slow bend testing of recracked specimens, presently under standardization world-wide. The investigation leads to highlight three conceptual weaknesses of current enfgineering and regulatory practices. Improved crack arrestability evaluation emerges as an optimal approach to insure safe PWR operation up to design end-of-life and beyond

  11. Nuclear reactor pressure vessel integrity insurance by crack arrestability evaluation using load from CVN tests

    Energy Technology Data Exchange (ETDEWEB)

    Fabry, A.

    1997-10-15

    The present work is undertaken in the framework of nuclear reactor pressure vessel (RPV) surveillance and aims at revisiting the crack arrest approach to structural integrity insurance. This approach, performed under normal plant operation conditions, can also offer an attractive alternative to the crack initiation philosophy promoted for accidental analysis. To this end, an accidental conservative, cost effective and robust methodology is forwarded and demonstrated: it makes use of the crack arrest information contained in the instrumented Charpy V-notch impact test and/or in the shear fracture appearance of broken samples. Particular attention is paid to the appraisal of uncertainties and the related safety margin. The resulting capability is placed in perspective with the state-of-the-art crack initiation methodology based on the slow bend testing of recracked specimens, presently under standardization world-wide. The investigation leads to highlight three conceptual weaknesses of current enfgineering and regulatory practices. Improved crack arrestability evaluation emerges as an optimal approach to insure safe PWR operation up to design end-of-life and beyond.

  12. Adequacy of Current Equivalent Margins Analysis (EMA) Guidance, Data and Methodologies for 60+ Years of Operation

    International Nuclear Information System (INIS)

    Server, W.; Hardin, T.; Cipolla, R.; Hall, B.

    2015-01-01

    In order to assure the structural integrity of reactor pressure vessels (RPVs), the fracture toughness of the ferritic steels used to fabricate the RPV must be shown to be adequate during their entire operating life, including extended license life. The Charpy V-notch (CVN) impact test has been used in the nuclear industry since it uses a small test specimen that can be irradiated in surveillance programs and provides an indirect way of assessing the fracture toughness of RPV steels. The effects of embrittlement typically are characterized by changes to the average Charpy curves measured before and after irradiation: shift of the 30 ft-lb (41 J) index temperature, and decrease in the CVN upper shelf energy (USE). Requirements in the USA for the USE of RPV belt-line materials are codified in Title 10, Code of Federal Regulations, Part 50 (10 CFR 50), Appendix G. Before irradiation, USE in the transverse (T-L) orientation for base materials and crack extension in the welding direction for weld materials must be greater than or equal to 75 ft-lb (102 J), and it is not to become less than 50 ft-lb (68 J) due to radiation embrittlement throughout the license of the RPV. If the projected USE of any RPV belt-line steel falls below 50 ft-lb (68 J), the projected value must be demonstrated to provide a margin of safety against ductile fracture equivalent to that required by Appendix G of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, Section XI. The analytical evaluation method used is called an equivalent margin analysis (EMA). This paper reviews the current status of EMAs and recommends improvements and clarifications that can be made to meet the needs of extended license life to 80 years. Focus is placed on analytical methodology, material property needs and proper implementation. (authors)

  13. Ageing phenomena in ULCB-NiCu steels

    International Nuclear Information System (INIS)

    Lis, A.K.; Lis, J.; Wieczorek, P.

    1999-01-01

    Effect od ageing time and temperature on microstructure development, precipitation of ε C u, advancement of recrystallization process and their influence on yield strength and fracture toughness properties K IC as well as high Charpy V impact energy CVN = 84 J at 120 o C of ultra low carbon bainitic copper bearing steels have ben discussed. (author)

  14. Use of miniature and standard specimens to evaluate effects of irradiation temperature on pressure vessel steels

    International Nuclear Information System (INIS)

    Haggag, F.M.; Nanstad, R.K.; Byrne, S.T.

    1991-01-01

    The effects of neutron irradiation on the steel reactor vessel for the modular high-temperature gas-cooled reactor (MHTGR) are being investigated, primarily because the operating temperatures are low [121 to 210 degrees C (250--410 degrees F)] compared to those for commercial light-water reactors (LWRs) [∼288 degrees C (550 degrees F)]. The need for design data on the reference temperature shift necessitated the irradiation at different temperatures of A 533 grade B class 1 plate. A 508 class 3 forging, and welds used for the vessel shell, vessel closure head, the vessel flange. This paper presents results from the first four irradiation capsules of this program. The four capsules were irradiated in the University of Buffalo Reactor to an effective fast fluence of 1 x10 18 neutron/cm 2 [0.68 x 10 18 neutron/cm 2 (>1 MeV)] at temperatures of 288, 204, 163, and 121 degrees C (550, 400, 325, and 250 degrees F), respectively. The yield and ultimate strengths of both steel plate materials of the MHTGR Program increased with decreasing irradiation temperature. Similarly, the 41-J Charpy V-notch (CVN) transition temperature shift increased with decreasing irradiation temperature (in agreement with the increase in yield strength). The miniature tensile and automated ball indentation (ABI) test results (yield strength and flow properties) were in good agreement with those from standard tensile specimens. The miniature tensile and ABI test results were also used in a model that utilizes the changes in yield strength to estimate the CVN ductile-to-brittle transition temperature shift due to irradiation. The model predictions were compared with CVN test results obtained here and in earlier work. 5 refs., 11 figs., 6 tabs

  15. Observations of the severity of notch-root radius in initiation of subcritical crack growth

    International Nuclear Information System (INIS)

    Reuter, W.G.; Eiholzer, C.R.; Tupper, M.A.

    1981-01-01

    Slow bend tests were conducted on Charpy specimens containing precracks or machined notches of 0.10 or 0.25 mm radius. The test specimens were fabricated from three heats of annealed Type 304 stainless steel. The purpose of these tests was to examine the effects of notch root radius, in very ductile materials, on initiation of subcritical crack growth. In addition, it was intended to establish the critical values of J, COD, etc. for the single-edge notch specimen for comparison with results obtained from specimens containing surface flaws. This paper will briefly describe only those results of the calculation for J. The tests were monitored by acoustic emission to identify the load corresponding to initiation of subcritical crack growth, by a crack-opening displacement gage (COD), by cross-head displacement, and by stop-action photography

  16. Influence of phase transformations on the asymptotic residual stress distribution arising near a sharp V-notch tip

    International Nuclear Information System (INIS)

    Ferro, P

    2012-01-01

    In this work, the residual stress distribution induced by the solidification and cooling of a fusion zone in the vicinity of a sharp V-notch tip is investigated. The intensity of the residual asymptotic stress fields, quantified by the notch stress intensity factors, was studied for two different V-notch specimen geometries under generalized plane-strain conditions. In order to analyze the influence of phase transformations on the obtained results, simulations with and without the effects of phase transformation were carried out on ASTM SA 516 steel plates. Thanks to the possibilities of numerical modelling, additional analyses were performed without taking into account the transformation plasticity phenomenon. It was found that phase transformation effects (both volume change and transformation plasticity) have a great influence on the intensity and sign of the asymptotic stress fields at the sharp V-notch tips. This result is believed to be very important for the correct numerical determination (and future applications) of notch stress intensity factors resulting from asymptotic residual stress distributions induced by transient thermal loads. The analyses were performed with the finite element code SYSWELD. (paper)

  17. Tensile and charpy impact properties of irradiated reduced-activation ferritic steels

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    Tensile tests were conducted on eight reduced-activation Cr-W steels after irradiation to 15-17 and 26-29 dpa, and Charpy impact tests were conducted on the steels irradiated to 26-29 dpa. Irradiation was in the Fast Flux Test Facility at 365{degrees}C on steels containing 2.25-12% Cr, varying amounts of W, V, and Ta, and 0.1%C. Previously, tensile specimens were irradiated to 6-8 dpa and Charpy specimens to 6-8, 15-17, and 20-24 dpa. Tensile and Charpy specimens were also thermally aged to 20000 h at 365{degrees}C. Thermal aging had little effect on the tensile behavior or the ductile-brittle transition temperature (DBTT), but several steels showed a slight increase in the upper-shelf energy (USE). After {approx}7 dpa, the strength of the steels increased and then remained relatively unchanged through 26-29 dpa (i.e., the strength saturated with fluence). Post-irradiation Charpy impact tests after 26-29 dpa showed that the loss of impact toughness, as measured by an increase in DBTT and a decrease in the USE, remained relatively unchanged from the values after 20-24 dpa, which had been relatively unchanged from the earlier irradiations. As before, the two 9Cr steels were the most irradiation resistant.

  18. Crack-arrest tests on two irradiated high-copper welds

    International Nuclear Information System (INIS)

    Iskander, S.K.; Corwin, W.R.; Nanstad, R.K.

    1994-03-01

    The objective of the Heavy-Section Steel Irradiation Program Sixth Irradiation Series is to determine the effect of neutron irradiation on the shift and shape of the lower-bound curve to crack-arrest toughness data. Two submerged-arc welds with copper contents of 0.23 and 0.31 wt % were commercially fabricated in 220-mm-thick plate. Crack-arrest specimens fabricated from these welds were irradiated at a nominal temperature of 288 degrees C to an average fluence of 1.9 x 10 19 neutrons/cm 2 (>1 MeV). This is the second report giving the results of the tests on irradiated duplex-type crack-arrest specimens. A previous report gave results of tests on irradiated weld-embrittled-type specimens. Charpy V-notch (CVN) specimens irradiated in the same capsules as the crack-arrest specimens were also tested, and a 41-J transition temperature shift was determined from these specimens. open-quotes Mean close-quote curves of the same form as the American Society of Mechanical Engineers (ASME) K la curve were fit to the data with only the open-quotes reference temperatureclose quotes as a parameter. The shift between the mean curves agrees well with the 41-J transition temperature shift obtained from the CVN specimen tests. Moreover, the four data points resulting from tests on the duplex crack-arrest specimens of the present study did not make a significant change to mean curve fits to either the previously obtained data or all the data combined

  19. DISCOVERY OF A NEW AM CVn SYSTEM WITH THE KEPLER SATELLITE

    International Nuclear Information System (INIS)

    Fontaine, G.; Brassard, P.; Dufour, P.; Bergeron, P.; Green, E. M.; Hubeny, I.; Guvenen, B.; O'Malley, C. J.; Charpinet, S.; Van Grootel, V.; Steeghs, D.; Marsh, T. R.; Aerts, C.; Oestensen, R. H.; Bloemen, S.; Randall, S. K.; Silvotti, R.; Howell, S. B.; Baran, A.; Kepler, S. O.

    2011-01-01

    We report the discovery of a new AM CVn system on the basis of broadband photometry obtained with the Kepler satellite supplemented by ground-based optical spectroscopy. Initially retained on Kepler target lists as a potential compact pulsator, the blue object SDSS J190817.07+394036.4 (KIC 004547333) has turned out to be a high-state AM CVn star showing the He-dominated spectrum of its accretion disk significantly reddened by interstellar absorption. We constructed new grids of NLTE synthetic spectra for accretion disks in order to analyze our spectroscopic observations. From this analysis, we infer preliminary estimates of the rate of mass transfer, the inclination angle of the disk, and the distance to the system. The AM CVn nature of the system is also evident in the Kepler light curve, from which we extracted 11 secure periodicities. The luminosity variations are dominated by a basic periodicity of 938.507 s, likely to correspond to a superhump modulation. The light curve folded on the period of 938.507 s exhibits a pulse shape that is very similar to the superhump wavefront seen in AM CVn itself, which is a high-state system and the prototype of the class. Our Fourier analysis also suggests the likely presence of a quasi-periodic oscillation similar to those already observed in some high-state AM CVn systems. Furthermore, some very low-frequency, low-amplitude aperiodic photometric activity is likely present, which is in line with what is expected in accreting binary systems. Inspired by previous work, we further looked for and found some intriguing numerical relationships between the 11 secure detected frequencies, in the sense that we can account for all of them in terms of only three basic clocks. This is further evidence in favor of the AM CVn nature of the system.

  20. Application of Instrumented Charpy Method in Characterisation of Materials

    Directory of Open Access Journals (Sweden)

    Željko Alar

    2015-07-01

    Full Text Available Testing of absorbed impact energy according to the Charpy method is carried out to determine the behaviour of a material under the impact load. Instrumented Charpy method allows getting the force displacement curve through the entire test, That curve can be related to force-displacement curve which is obtained by the static tensile test. The purpose of this study was to compare the results of forces obtained by the static tensile test with the forces obtained by the instrumented Charpy method. Experimental part of the work contains testing of the mechanical properties of S275J0 steel by the static tensile test and Impact test on instrumented Charpy pendulum.

  1. Application of Instrumented Charpy Method in Characterisation of Materials

    OpenAIRE

    Alar, Željko; Mandić, Davor; Dugorepec, Andrija; Sakoman, Matija

    2015-01-01

    Testing of absorbed impact energy according to the Charpy method is carried out to determine the behaviour of a material under the impact load. Instrumented Charpy method allows getting the force displacement curve through the entire test, That curve can be related to force-displacement curve which is obtained by the static tensile test. The purpose of this study was to compare the results of forces obtained by the static tensile test with the forces obtained by the instrumented Charpy method...

  2. Effect of groove design on mechanical and metallurgical properties of quenched and tempered low alloy abrasion resistant steel welded joints

    International Nuclear Information System (INIS)

    Sharma, Varun; Shahi, A.S.

    2014-01-01

    Highlights: • Effect of weld groove design on Q and T steel welded joints is investigated. • Groove design influences heat dissipation characteristics of welded joints. • Double-V groove joint possesses maximum yield strength and UTS. • C-groove joint possesses highest impact energy, both at room temperature and 0 °C. • A wide variation in microhardness exists across different zone of the weldments. - Abstract: Experimental investigations were carried out to study the influence of three different groove designs on mechanical and metallurgical properties of 15 mm thick Q and T (quenched and tempered) steel welded joints. Welding heat input variation corresponding to each joint configuration was kept to a minimal such that the objective of investigating, exclusively, the effect of varied weld volume on the mechanical and metallurgical performance of these joints could be accomplished. Mechanical performance of these joints was evaluated by subjecting them to transverse tensile testing, and Charpy V-notch impact testing of the weld zones at room temperature and 0 °C. The results of this study reveal that among all types of groove formations used for welding, double-V groove joint possessed maximum YS (yield strength) and UTS (ultimate tensile strength), besides maximum strength ratio (YS/UTS) that was followed by U-groove joint and C-groove joint, respectively. However, weld zone tested individually, for the cover as well as the root pass of the C-groove joint possessed highest CVN (Charpy V-notch) values, both at room temperature and 0 °C. Extensive microhardness studies of these weldments showed a wide variation in the microhardness values of the weld zone and the HAZ (heat affected zone). It was concluded that each groove formation/design exerted a significant influence on the heat dissipation characteristics of these joints, which is evident from different morphological features as revealed through optical microscopy. Scanning electron microscopic

  3. Postirradiation notch ductility tests of ESR alloy HT-9 and modified 9Cr-1Mo alloy from UBR reactor experiments

    International Nuclear Information System (INIS)

    Hawthorne, J.R.

    1984-01-01

    During this period, irradiation exposures at 300 0 C and 150 0 C to approx. 8 x 10 19 n/cm 2 , E > 0.1 MeV, were completed for the Alloy HT-9 plate and the modified Alloy 9Cr-1Mo plates, respectively. Postirradiation tests of Charpy-V (C/sub v/) specimens were completed for both alloys; other specimen types included in the reactor assemblies were fatigue precracked Charpy-V (PCC/sub v/), half-size Charpy-V, and in the case of the modified 9Cr-1Mo, 2.54 mm thick compact tension specimens

  4. V-notch tip subjected to in-plane mixed mode loading: overview of recent results and possible future outcomes

    Directory of Open Access Journals (Sweden)

    F. Berto

    2017-07-01

    Full Text Available . The fictitious notch rounding concept is applied for the first time to V-notches with root hole subjected to in-plane mixed mode loading. Outof-bisector crack propagation is taken into account. The fictitious notch radius is determined as a function of the real notch radius, the microstructural support length and the notch opening angle. Due to the complexity of the problem, a method based on the simple normal stress failure criterion has been used. It is combined with the maximum tangential stress criterion to determine the crack propagation angle. An analytical method based on Neuber's procedure has been developed. The method provides the values of the microstructural support factor as a function of the mode ratio and the notch opening angle. The support factor is considered to be independent of the microstructural support length. Finally, for comparison, the support factor is determined on a purely numerical basis by iterative analysis of FE models.

  5. Classification of Ap-stars HR 830 and ZI CVn

    International Nuclear Information System (INIS)

    Zverko, J.

    1984-01-01

    Two ambiguously classified Ap-stars, HR 830 and 21 CVn, are studied. The observational data are compared with the data for normal stars αDel and αLyr. Star HR 830 is classified as Ap of type Si based on the enhanced absorption in the Si lines and photometric variability in UBV. 21 CVn is classified as Ap Si based on weaker absorption of helium, the variability of helium lines, photometric periodic variability and the properties of the UV spectrum. It is concluded that the photometric periodic variability is a good indicator of Ap-properties of rapidly rotating A and late B stars. (author)

  6. Statistical analyses of fracture toughness results for two irradiated high-copper welds

    International Nuclear Information System (INIS)

    Nanstad, R.K.; McCabe, D.E.; Haggag, F.M.; Bowman, K.O.; Downing, D.J.

    1990-01-01

    The objectives of the Heavy-Section Steel Irradiation Program Fifth Irradiation Series were to determine the effects of neutron irradiation on the transition temperature shift and the shape of the K Ic curve described in Sect. 6 of the ASME Boiler and Pressure Vessel Code. Two submerged-arc welds with copper contents of 0.23 and 0.31% were commercially fabricated in 215-mm-thick plates. Charpy V-notch (CVN) impact, tensile, drop-weight, and compact specimens up to 203.2 mm thick [1T, 2T, 4T, 6T, and 8T C(T)] were tested to provide a large data base for unirradiated material. Similar specimens with compacts up to 4T were irradiated at about 288 degrees C to a mean fluence of about 1.5 x 10 19 neutrons/cm 2 (>1 MeV) in the Oak Ridge Research Reactor. Both linear-elastic and elastic-plastic fracture mechanics methods were used to analyze all cleavage fracture results and local cleavage instabilities (pop-ins). Evaluation of the results showed that the cleavage fracture toughness values determined at initial pop-ins fall within the same scatter band as the values from failed specimens; thus, they were included in the data base for analysis (all data are designated K Jc )

  7. Effects of Notch Misalignment and Tip Radius on Displacement Field in V-Notch Rail Shear Test as Determined by Photogrammetry

    Science.gov (United States)

    Hill, Charles S.; Oliveras, Ovidio M.

    2011-01-01

    Evolution of the 3D strain field during ASTM-D-7078 v-notch rail shear tests on 8-ply quasi-isotropic carbon fiber/epoxy laminates was determined by optical photogrammetry using an ARAMIS system. Specimens having non-optimal geometry and minor discrepancies in dimensional tolerances were shown to display non-symmetry and/or stress concentration in the vicinity of the notch relative to a specimen meeting the requirements of the standard, but resulting shear strength and modulus values remained within acceptable bounds of standard deviation. Based on these results, and reported difficulty machining specimens to the required tolerances using available methods, it is suggested that a parametric study combining analytical methods and experiment may provide rationale to increase the tolerances on some specimen dimensions, reducing machining costs, increasing the proportion of acceptable results, and enabling a wider adoption of the test method.

  8. Postirradiation fracture toughness tests of ESR alloy HT-9 and modified 9Cr-1Mo alloy from UBR reactor experiments

    International Nuclear Information System (INIS)

    Hawthorne, J.R.; Reed, J.R.; Sprague, J.A.

    1984-01-01

    Alloy HT-9 and Modified 9Cr-1Mo are being evaluated for potential applications as first wall materials in magnetic fusion reactors. Objectives of the current research task were to test fatigue-precracked Charpy-V (PCC/sub v/) specimens from representative plates irradiated in the UBR reactor at 149 0 C or 300 0 C, and, to compare the results against postirradiation notch ductility data developed previously for the materials. Both plates represent electroslag refined (ESR) melt processing. PCC/sub v/ specimens of Alloy HT-9 and Modified 9Cr-1Mo alloy were irradiated at 300 0 C and 149 0 C, respectively, to approx.0.8 X 10 20 n/cm 2 , E > 0.1 MeV. During this period, postirradiation tests for fracture toughness were completed and results compared to notch ductility determinations from standard Charpy-V (C/sub v/) specimens irradiated in the same reactor experiments. Fracture surface examinations by SEM are also reported

  9. Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone

    Directory of Open Access Journals (Sweden)

    Anna Engler

    2018-01-01

    Full Text Available Neurogenesis continues in the ventricular-subventricular zone (V-SVZ of the adult forebrain from quiescent neural stem cells (NSCs. V-SVZ NSCs are a reservoir for new olfactory bulb (OB neurons that migrate through the rostral migratory stream (RMS. To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ.

  10. Mechanical properties of low alloy high phosphorus weathering steel

    Directory of Open Access Journals (Sweden)

    Jena B.K.

    2015-01-01

    Full Text Available Mechanical behaviour of two low alloy steels (G11 and G12 was studied with respect to different phosphorus contents. Tensile strength and yield strength increased while percentage elongation at fracture decreased on increasing phosphorus content. The SEM and light optical photomicrograph of low phosphorus steel (G11 revealed ferrite and pearlite microstructure. On increasing phosphorus content from 0.25 wt.% to 0.42 wt.%, the morphology of grain changed from equiaxed shape to pan-cake shape and grain size also increased. The Charpy V notch (CVN impact energy of G11 and G12 steel at room temperature was 32 J and 4 J respectively and their fractographs revealed brittle rupture with cleavage facets for both the steels. However, the fractograph of G11 steel after tensile test exhibited ductile mode of fracture with conical equiaxed dimple while that of G12 steel containing 0.42 wt. % P exhibited transgranular cleavage fracture. Based on this study, G11 steel containing 0.25 wt. % P could be explored as a candidate material for weathering application purpose where the 20°C toughness requirement is 27 J as per CSN EN10025-2:2004 specification.

  11. Discovery of a New AM CVn System with the Kepler Satellite

    DEFF Research Database (Denmark)

    Fontaine, G.; Brassard, P.; Green, Elizabeth M.

    2011-01-01

    004547333) has turned out to be a high-state AM CVn star showing the He-dominated spectrum of its accretion disk significantly reddened by interstellar absorption. We constructed new grids of NLTE synthetic spectra for accretion disks in order to analyze our spectroscopic observations. From this analysis...... analysis also suggests the likely presence of a quasi-periodic oscillation similar to those already observed in some high-state AM CVn systems. Furthermore, some very low-frequency, low-amplitude aperiodic photometric activity is likely present, which is in line with what is expected in accreting binary...

  12. Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

    Science.gov (United States)

    2013-10-22

    states: The CVN 78 is experiencing cost growth due to “first of class” material availability (i.e., valves, actuators ), construction labor...assessment during IOT &E [initial operational test and evaluation]. • The current TEMP [test and evaluation master plan] does not adequately address...developmental testing significantly raises the likelihood of the discovery of platform-level problems during IOT &E. • The Navy plans to deliver CVN-78 in

  13. High-speed photometry of Gaia14aae: an eclipsing AM CVn that challenges formation models

    Science.gov (United States)

    Green, M. J.; Marsh, T. R.; Steeghs, D. T. H.; Kupfer, T.; Ashley, R. P.; Bloemen, S.; Breedt, E.; Campbell, H. C.; Chakpor, A.; Copperwheat, C. M.; Dhillon, V. S.; Hallinan, G.; Hardy, L. K.; Hermes, J. J.; Kerry, P.; Littlefair, S. P.; Milburn, J.; Parsons, S. G.; Prasert, N.; van Roestel, J.; Sahman, D. I.; Singh, N.

    2018-05-01

    AM CVn-type systems are ultracompact, hydrogen-deficient accreting binaries with degenerate or semidegenerate donors. The evolutionary history of these systems can be explored by constraining the properties of their donor stars. We present high-speed photometry of Gaia14aae, an AM CVn with a binary period of 49. 7 min and the first AM CVn in which the central white dwarf is fully eclipsed by the donor star. Modelling of the light curves of this system allows for the most precise measurement to date of the donor mass of an AM CVn, and relies only on geometric and well-tested physical assumptions. We find a mass ratio q = M2/M1 = 0.0287 ± 0.0020 and masses M1 = 0.87 ± 0.02 M⊙ and M2 = 0.0250 ± 0.0013 M⊙. We compare these properties to the three proposed channels for AM CVn formation. Our measured donor mass and radius do not fit with the contraction that is predicted for AM CVn donors descended from white dwarfs or helium stars at long orbital periods. The donor properties we measure fall in a region of parameter space in which systems evolved from hydrogen-dominated cataclysmic variables are expected, but such systems should show spectroscopic hydrogen, which is not seen in Gaia14aae. The evolutionary history of this system is therefore not clear. We consider a helium-burning star or an evolved cataclysmic variable to be the most likely progenitors, but both models require additional processes and/or fine-tuning to fit the data. Additionally, we calculate an updated ephemeris which corrects for an anomalous time measurement in the previously published ephemeris.

  14. Convection Enhances Magnetic Turbulence in AM CVn Accretion Disks

    Science.gov (United States)

    Coleman, Matthew S. B.; Blaes, Omer; Hirose, Shigenobu; Hauschildt, Peter H.

    2018-04-01

    We present the results of local, vertically stratified, radiation magnetohydrodynamic shearing-box simulations of magnetorotational instability (MRI) turbulence for a (hydrogen poor) composition applicable to accretion disks in AM CVn type systems. Many of these accreting white dwarf systems are helium analogs of dwarf novae (DNe). We utilize frequency-integrated opacity and equation-of-state tables appropriate for this regime to accurately portray the relevant thermodynamics. We find bistability of thermal equilibria in the effective-temperature, surface-mass-density plane typically associated with disk instabilities. Along this equilibrium curve (i.e., the S-curve), we find that the stress to thermal pressure ratio α varied with peak values of ∼0.15 near the tip of the upper branch. Similar to DNe, we found enhancement of α near the tip of the upper branch caused by convection; this increase in α occurred despite our choice of zero net vertical magnetic flux. Two notable differences we find between DN and AM CVn accretion disk simulations are that AM CVn disks are capable of exhibiting persistent convection in outburst, and ideal MHD is valid throughout quiescence for AM CVns. In contrast, DNe simulations only show intermittent convection, and nonideal MHD effects are likely important in quiescence. By combining our previous work with these new results, we also find that convective enhancement of the MRI is anticorrelated with mean molecular weight.

  15. Metallographic study of reconstitution welding in inserts of 1 cm3

    International Nuclear Information System (INIS)

    Romero C, J.; Garcia R, R.; Fernandez T, F.; Perez R, N.; Rocamontes A, M.

    2007-01-01

    In this article, the welding metallographic study carried out in Charpy test tubes reconstituted with notch in 'V', used in the surveillance programs of the vessel in nucleo electric plants is described. Inserts of 1 cm 3 are used, where the inserts are usually rectangular of minimum 18 millimeters of length. The importance of using inserts of 1 cm 3 is that the mechanical properties can be measured in another direction of the vessel steel, when changing the direction or sense of the notch in 'V' or the face where this notch is made in the insert. (Author)

  16. Applicability of the fracture toughness master curve to irradiated reactor pressure vessel steels

    International Nuclear Information System (INIS)

    Sokolov, M.A.; McCabe, D.E.; Alexander, D.J.; Nanstad, R.K.

    1997-01-01

    The current methodology for determination of fracture toughness of irradiated reactor pressure vessel (RPV) steels is based on the upward temperature shift of the American Society of Mechanical Engineers (ASME) K Ic curve from either measurement of Charpy impact surveillance specimens or predictive calculations based on a database of Charpy impact tests from RPV surveillance programs. Currently, the provisions for determination of the upward temperature shift of the curve due to irradiation are based on the Charpy V-notch (CVN) 41-J shift, and the shape of the fracture toughness curve is assumed to not change as a consequence or irradiation. The ASME curve is a function of test temperature (T) normalized to a reference nit-ductility temperature, RT NDT , namely, T-RT NDT . That curve was constructed as the lower boundary to the available K Ic database and, therefore, does not consider probability matters. Moreover, to achieve valid fracture toughness data in the temperature range where the rate of fracture toughness increase with temperature is rapidly increasing, very large test specimens were needed to maintain plain-strain, linear-elastic conditions. Such large specimens are impractical for fracture toughness testing of each RPV steel, but the evolution of elastic-plastic fracture mechanics has led to the use of relatively small test specimens to achieve acceptable cleavage fracture toughness measurements, K Jc , in the transition temperature range. Accompanying this evolution is the employment of the Weibull distribution function to model the scatter of fracture toughness values in the transition range. Thus, a probabilistic-based bound for a given data population can be made. Further, it has been demonstrated by Wallin that the probabilistic-based estimates of median fracture toughness of ferritic steels tend to form transition curves of the same shape, the so-called ''master curve'', normalized to one common specimen size, namely the 1T [i.e., 1.0-in

  17. 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.

  18. Fracture toughness of Charpy-size compound specimens and its application in engineering

    International Nuclear Information System (INIS)

    Zhang, X.P.; Shi, Y.W.

    1994-01-01

    The use of a pre-cracked Charpy-size specimen with a side-groove to evaluate the fracture toughness of materials has been researched and considered. This method not only satisfies the demand for small-size specimens in surveillance tests of fracture toughness but also avoids using complicated physical methods to monitor the initial conditions of crack propagation. For most materials this method has solved the problem in which the small-size specimen did not satisfy the valid conditions of a fracture toughness measurement. In order to obtain more information from neutron-irradiated sample specimens and raise the reliability of fracture toughness surveillance tests, it has been considered more important to repeatedly exploit the broken Charpy-size specimen tested in the surveillance test, and to make it renewable. In this work, on the renewing design and utilization of Charpy-size specimens, nine data on fracture toughness can be obtained from one pre-cracked side-grooved Charpy-size specimen, while at present usually only one to three data on fracture toughness can be obtained from one Charpy-size specimen. Thus, it is found that the new method would improve the reliability of fracture toughness surveillance testing and evaluation. In addition, some factors that affect the optimum design of pre-cracked deep side-groove Charpy-size compound specimens have also been discussed. (author)

  19. Validation Study of Unnotched Charpy and Taylor-Anvil Impact Experiments using Kayenta

    Energy Technology Data Exchange (ETDEWEB)

    Kamojjala, Krishna [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lacy, Jeffrey [Idaho National Lab. (INL), Idaho Falls, ID (United States); Chu, Henry S. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Brannon, Rebecca [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-03-01

    Validation of a single computational model with multiple available strain-to-failure fracture theories is presented through experimental tests and numerical simulations of the standardized unnotched Charpy and Taylor-anvil impact tests, both run using the same material model (Kayenta). Unnotched Charpy tests are performed on rolled homogeneous armor steel. The fracture patterns using Kayenta’s various failure options that include aleatory uncertainty and scale effects are compared against the experiments. Other quantities of interest include the average value of the absorbed energy and bend angle of the specimen. Taylor-anvil impact tests are performed on Ti6Al4V titanium alloy. The impact speeds of the specimen are 321 m/s and 393 m/s. The goal of the numerical work is to reproduce the damage patterns observed in the laboratory. For the numerical study, the Johnson-Cook failure model is used as the ductile fracture criterion, and aleatory uncertainty is applied to rate-dependence parameters to explore its effect on the fracture patterns.

  20. Effects of Range of Stress and of Special Notches on Fatigue Properties of Aluminum Alloys Suitable for Airplane Propellers

    Science.gov (United States)

    Dolan, Thomas J

    1942-01-01

    Laboratory tests were made to obtain information on the load-resisting properties of X76S-T aluminum alloy when subjected to static, impact, and repeated loads. Results are presented from static-load test of unnotched specimens in tension and in torsion and of notched specimens in tension. Charpy impact values obtained from bend tests on notched specimens and tension impact values for both notched and unnotched specimens tested at several different temperatures are included. The endurance limits obtained from repeated bending fatigue tests made on three different types of testing machine are given for unnotched polished specimens, and the endurance limits of notched specimens subjected to six different ranges of bending stress are also reported. The results indicated that: (a) polished rectangular specimens had an endurance limit about 30 percent less than that obtained for round specimens; (b) a comparison of endurance limits obtained from tests on three different types of machine indicated that there was no apparent effect of speed of testing on the endurance limit for the range of speeds used (1,750 to 13,000 rpm). (c) the fatigue strength (endurance limit) of the X76S-T alloy was greatly decreased by the presence of a notch in the specimens; (d) no complete fractures of the entire specimens occurred in notched fatigue specimens when subjected to stress cycles for which the mean stress at the notch during the cycle was a compressive stress; for this test condition a microscopic cracking occurred near the root of the notch and was used as a criterion of failure of the specimen. (e) as the mean stress at the notch was decreased from a tensile (+) stress to a compressive (-) stress, it was found that the alternating stress that could be superimposed on the mean stress in the cycle without causing failure of the specimens was increased.

  1. Metallographic study of reconstitution welding in inserts of 1 cm{sup 3}; Estudio metalografico de soldaduras de reconstitucion en insertos de 1 cm{sup 3}

    Energy Technology Data Exchange (ETDEWEB)

    Romero C, J.; Garcia R, R.; Fernandez T, F.; Perez R, N.; Rocamontes A, M. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    In this article, the welding metallographic study carried out in Charpy test tubes reconstituted with notch in 'V', used in the surveillance programs of the vessel in nucleo electric plants is described. Inserts of 1 cm{sup 3} are used, where the inserts are usually rectangular of minimum 18 millimeters of length. The importance of using inserts of 1 cm{sup 3} is that the mechanical properties can be measured in another direction of the vessel steel, when changing the direction or sense of the notch in 'V' or the face where this notch is made in the insert. (Author)

  2. SHPL: The Scaleable High-Performance LAN on the CVN 71

    National Research Council Canada - National Science Library

    Blackwell, L

    1998-01-01

    ...) Core Technology Program aboard USS Theodore Roosevelt (CVN-71). The program demonstrates advanced concepts in strike planning, visualization, and execution using the latest technology in high speed computing, 3-D graphics, and networking...

  3. Results of crack-arrest tests on irradiated a 508 class 3 steel

    International Nuclear Information System (INIS)

    Iskander, S.K.; Milella, P.P.; Pini, M.A.

    1998-02-01

    Ten crack-arrest toughness values for irradiated specimens of A 508 class 3 forging steel have been obtained. The tests were performed according to the American Society for Testing and Materials (ASTM) Standard Test Method for Determining Plane-Strain Crack-Arrest Fracture Toughness, K la of Ferritic Steels, E 1221-88. None of these values are strictly valid in all five ASTM E 1221-88 validity criteria. However, they are useful when compared to unirradiated crack-arrest specimen toughness values since they show the small (averaging approximately 10 degrees C) shifts in the mean and lower-bound crack-arrest toughness curves. This confirms that a low copper content in ASTM A 508 class 3 forging material can be expected to result in small shifts of the transition toughness curve. The shifts due to neutron irradiation of the lower bound and mean toughness curves are approximately the same as the Charpy V-notch (CVN) 41-J temperature shift. The nine crack-arrest specimens were irradiated at temperatures varying from 243 to 280 degrees C, and to a fluence varying from 1.7 to 2.7 x 10 19 neutrons/cm 2 (> 1 MeV). The test results were normalized to reference values that correspond to those of CVN specimens irradiated at 284 degrees C to a fluence of 3.2 x 10 19 neutrons/cm 2 (> 1 MeV) in the same capsule as the crack-arrest specimens. This adjustment resulted in a shift to lower temperatures of all the data, and in particular moved two data points that appeared to lie close to or lower than the American Society of Mechanical Engineers K la curve to positions that seemed more reasonable with respect to the remaining data. A special fixture was designed, fabricated, and successfully used in the testing. For reasons explained in the text, special blocks to receive the Oak Ridge National Laboratory clip gage were designed, and greater-than-standard crack-mouth opening displacements measured were accounted for. 24 refs., 13 figs., 12 tabs

  4. Crack initiation life in notched Ti-6Al-4V titanium bars under uniaxial and multiaxial fatigue: synthesis based on the averaged strain energy density approach

    Directory of Open Access Journals (Sweden)

    Giovanni Meneghetti

    2017-07-01

    Full Text Available The fatigue behaviour of circumferentially notched specimens made of titanium alloy, Ti-6Al-4V, has been analysed. To investigate the notch effect on the fatigue strength, pure bending, pure torsion and multiaxial bending-torsion fatigue tests have been carried out on specimens characterized by two different root radii, namely 0.1 and 4 mm. Crack nucleation and subsequent propagation have been accurately monitored by using the direct current potential drop (DCPD technique. Based on the results obtained from the potential drop technique, the crack initiation life has been defined in correspondence of a relative potential drop increase V/V0 equal to 1%, and it has been used as failure criterion. Doing so, the effect of extrinsic mechanisms operating during crack propagation phase, such as sliding contact, friction and meshing between fracture surfaces, is expected to be reduced. The experimental fatigue test results have been re-analysed by using the local strain energy density (SED averaged over a structural volume having radius R0 and surrounding the notch tip. Finally, the use of the local strain energy density parameter allowed us to properly correlate the crack initiation life of Ti-6Al-4V notched specimens, despite the different notch geometries and loading conditions involved in the tests

  5. A study on the Charpy-V impact energy and impact properties of stainless steel

    International Nuclear Information System (INIS)

    Han, Gill Young

    1988-01-01

    It has been thought that by analyzing and considering the shock strength and fracture of impact load. We can accurtely determine strength and thus it will be helpful in optimum design. In this experimental study the following results were obtained by using the instrumented impact test for SUS 316 1) The total charpy impact energy is progressively decreased by increasing the shock pressure. 2) The dynamic yield strength is increased by increasing the shock pressure for all test temperatures. 3) The ratio of dynamic yield to static yield strength was found to decrease with increasing shock pressure. (Author)

  6. Microstructural characterization of Charpy-impact-tested nanostructured bainite

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Y.T.; Chang, H.T.; Huang, B.M. [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Huang, C.Y. [Iron and Steel R& D Department, China Steel Corporation, Kaohsiung, Taiwan, ROC (China); Yang, J.R., E-mail: jryang@ntu.edu.tw [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China)

    2015-09-15

    In this work, a possible cause of the extraordinary low impact toughness of nanostructured bainite has been investigated. The microstructure of nanostructured bainite consisted chiefly of carbide-free bainitic ferrite with retained austenite films. X-ray diffractometry (XRD) measurement indicated that no retained austenite existed in the fractured surface of the Charpy-impact-tested specimens. Fractographs showed that cracks propagated mainly along bainitic ferrite platelet boundaries. The change in microstructure after impact loading was verified by transmission electron microscopy (TEM) observations, confirming that retained austenite was completely transformed to strain-induced martensite during the Charpy impact test. However, the zone affected by strained-induced martensite was found to be extremely shallow, only to a depth of several micrometers from the fracture surface. It is appropriately concluded that upon impact, as the crack forms and propagates, strain-induced martensitic transformation immediately occurs ahead of the advancing crack tip. The successive martensitic transformation profoundly facilitates the crack propagation, resulting in the extremely low impact toughness of nanostructured bainite. Retained austenite, in contrast to its well-known beneficial role, has a deteriorating effect on toughness during the course of Charpy impact. - Highlights: • The microstructure of nanostructured bainite consisted of nano-sized bainitic ferrite subunits with retained austenite films. • Special sample preparations for SEM, XRD and TEM were made, and the strain-affected structures have been explored. • Retained austenite films were found to transform into martensite after impact loading, as evidenced by XRD and TEM results. • The zone of strain-induced martensite was found to extend to only several micrometers from the fracture surface. • The poor Charpy impact toughness is associated with the fracture of martensite at a high strain rate during

  7. Recent advances on Charpy specimen reconstitution techniques

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J., E-mail: aandrade@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2017-07-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  8. Recent advances on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J.

    2017-01-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  9. Fracture Toughness Evaluation of Kori-1 RPV Beltline Weld for a Long-Term Operation

    International Nuclear Information System (INIS)

    Lee, Bong-Sang; Kim, Min-Chul; Ahn, Sang-Bok; Kim, Byung-Chul; Hong, Jun-Hwa

    2007-01-01

    Irradiation embrittlement of RPV (reactor pressure vessel) material is the most important aging issue for a long-term operation of nuclear power plants. KORI unit 1, which is the first PWR in Korea, is approaching its initial licensing life of 30 years. In order to operate the reactor for another 10 years and more, it should be demonstrated that the irradiation embrittlement of the reactor will be adequately managed by ensuring that the fracture toughness properties have a certain level of the safety margin. The current regulation requires Charpy V-notch impact data through conventional surveillance tests. It is based on the assumption that Charpy impact test results are well correlated with the fracture toughness properties of many engineering steels. However, Charpy V-notch impact data may not be adequate to estimate the fracture toughness of certain materials, such as Linde 80 welds. During the last decade, a tremendous number of fracture toughness data on many RPV steels have been produced in accordance with the new standard test method, the so-called master curve method. ASTM E1921 represents a revolutionary advance in characterizing fracture toughness of RPV steels, since it permits establishing the ductile to brittle transition portion of the fracture toughness curve with direct measurements on a relatively small number of relatively small specimens, such as pre-cracked Charpy specimens. Actual fracture toughness data from many different RPV steels revealed that the Charpy test estimations are generally conservative with the exception of a few cases. Recent regulation codes in USA permit the master curve fracture toughness methodology in evaluating an irradiation embrittlement of commercial nuclear reactor vessels

  10. Vía de señalización Notch y nuevas estrategias para el tratamiento de cáncer Notch signaling pathway and new strategies in cancer treatment

    Directory of Open Access Journals (Sweden)

    Leticia Santos

    2006-04-01

    Full Text Available La vía de señalización Notch desempeña un papel fundamental en las diferentes etapas del desarrollo celular como la proliferación, crecimiento, diferenciación y apoptosis. Estudios recientes han demostrado que, dependiendo del nivel de expresión y del contexto celular, los receptores de membrana Notch contribuyen en la resistencia a apoptosis en células tumorales. Estos descubrimientos sugieren que componentes de la vía de señalización Notch son un blanco potencial para el desarrollo de terapias más efectivas contra el cáncer. Esta revisión describe la función de la vía Notch y nuevas estrategias utilizadas en la modulación de su señal.The Notch signaling pathway plays a crucial role at different stages of cell development, such as proliferation, growth, differentiation, and apoptosis. Recent studies demonstrate that depending on the expression level and cellular context, the Notch receptors play a role in apoptosis resistance in malignant cells. These findings suggest that Notch signaling components may be a potential target in the development of new cancer therapies. This review describes the function of the Notch pathway and new strategies in the modulation of its signal.

  11. Irradiation, Annealing, and Reirradiation Effects on American and Russian Reactor Pressure Vessel Steels

    International Nuclear Information System (INIS)

    Chernobaeva, A.A.; Korolev, Y.N.; Nanstad, R.K.; Nikolaev, Y.A.; Sokolov, M.A.

    1998-01-01

    One of the options to mitigate the effects of irradiation on reactor pressure vessels (RPVs) is to thermally anneal them to restore the toughness properties that have been degraded by neutron irradiation. Even though a postirradiation anneal may be deemed successful, a critical aspect of continued RPV operation is the rate of embrittlement upon reirradiation. There are insufficient data available to allow for verification of available models of reirradiation embrittlement or for the development of a reliable predictive methodology. This is especially true in the case of fracture toughness data. Under the U.S.-Russia Joint Coordinating Committee for Civilian Nuclear Reactor Safety (JCCCNRS), Working Group 3 on Radiation Embrittlement, Structural Integrity, and Life Extension of Reactor Vessels and Supports agreed to conduct a comparative study of annealing and reirradiation effects on RPV steels. The Working Group agreed that each side would irradiate, anneal, reirradiate (if feasible ), and test two materials of the other. Charpy V-notch (CVN) and tensile specimens were included. Oak Ridge National Laboratory (ORNL) conducted such a program (irradiation and annealing, including static fracture toughness) with two weld metals representative of VVER-440 and VVER-1000 RPVs, while the Russian Research Center-Kurchatov Institute (RRC-KI) conducted a program (irradiation, annealing, reirradiation, and reannealing) with Heavy-Section Steel Technology (HSST) Program Plate 02 and Heavy-Section Steel Irradiation (HSSI) Program Weld 73W. The results for each material from each laboratory are compared with those from the other laboratory. The ORNL experiments with the VVER welds included irradiation to about 1 x 10 19 n/cm 2 (>1 MeV), while the RRC-KI experiments with the U.S. materials included irradiations from about 2 to 18 x 10 19 n/cm 2 (>l MeV). In both cases, irradiations were conducted at ∼290 C and annealing treatments were conducted at ∼454 C. The ORNL and RRC

  12. Computer aided instrumented Charpy test applied dynamic fracture toughness evaluation system

    International Nuclear Information System (INIS)

    Kobayashi, Toshiro; Niinomi, Mitsuo

    1986-01-01

    Micro computer aided data treatment system and personal computer aided data analysis system were applied to the traditional instrumented Charpy impact test system. The analysis of Charpy absorbed energy (E i , E p , E t ) and load (P y , P m ), and the evaluation of dynamic toughness through whole fracture process, i.e. J Id , J R curve and T mat was examined using newly developed computer aided instrumented Charpy impact test system. E i , E p , E t , P y and P m were effectively analyzed using moving average method and printed out automatically by micro computer aided data treatment system. J Id , J R curve and T mat could be measured by stop block test method. Then, J Id , J R curve and T mat were effectively estimated using compliance changing rate method and key curve method on the load-load point displacement curve of single fatigue cracked specimen by personal computer aided data analysis system. (author)

  13. Potential radiation damage: Storage tanks for liquid radioactive waste

    International Nuclear Information System (INIS)

    Caskey, G.R. Jr.

    1992-01-01

    High level waste at SRS is stored in carbon steel tanks constructed during the period 1951 to 1981. This waste contains radionuclides that decay by alpha, beta, or gamma emission or are spontaneous neutronsources. Thus, a low intensity radiation field is generated that is capable of causing displacement damage to the carbon steel. The potential for degradation of mechanical properties was evaluated by comparing the estimated displacement damage with published data relating changes in Charpy V-notch (CVN) impact energy to neutron exposure. Experimental radiation data was available for three of the four grades of carbonsteel from which the tanks were constructed and is applicable to all four steels. Estimates of displacement damage arising from gamma and neutron radiation have been made based on the radionuclide contents for high level waste that are cited in the Safety Analysis Report (SAR) for the Liquid Waste Handling Facilities in the 200-Area. Alpha and beta emissions do not penetrate carbon steel to a sufficient depth to affect the bulk properties of the tank walls but may aggravate corrosion processes. The damage estimates take into account the source of the waste (F- or H-Area), the several types of tank service, and assume wateras an attenuating medium. Estimates of displacement damage are conservative because they are based on the highest levels of radionuclide contents reported in the SAR and continuous replenishment of the radionuclides

  14. Feasibility of correlating V-Cr-Ti alloy weld strength with weld chemistry. CRADA final report

    International Nuclear Information System (INIS)

    Grossbeck, M.L.; Odom, R.W.

    1998-06-01

    The mechanical properties of refractory metals such as vanadium are determined to a large extent by the interstitial impurities in the alloy. In the case of welding, interstitial impurities are introduced in the welding process from the atmosphere and by dissolution of existing precipitates in the alloy itself. Because of the necessity of having an ultra-pure atmosphere, a vacuum chamber or a glove box is necessary. In the V-Cr-Ti system, the titanium serves as a getter to control the concentration of oxygen and nitrogen in solid solution in the alloy. In this project the secondary ion mass spectrometry (SIMS) technique was used to detect, measure, and map the spacial distribution of impurity elements in welds in the alloy V-4Cr-4Ti. An attempt was then made to correlate the concentrations and distributions of the impurities with mechanical properties of the welds. Mechanical integrity of the welds was determined by Charpy V-notch testing. Welds were prepared by the gas-tungsten-arc (GTA) method. Charpy testing established a correlation between weld impurity concentration and the ductile to brittle transition temperature (DBTT). Higher concentrations of oxygen resulted in a higher DBTT. An exception was noted in the case of a low-oxygen weld which had a high hydrogen concentration resulting in a brittle weld. The concentrations and distributions of the impurities determined by SIMS could not be correlated with the mechanical properties of the welds. This research supports efforts to develop fusion reactor first wall and blanket structural materials

  15. 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.

  16. 46 CFR 154.605 - Toughness test.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Toughness test. 154.605 Section 154.605 Shipping COAST....605 Toughness test. (a) Each toughness test under §§ 154.610 through 154.625 must meet Subpart 54.05 of this chapter. (b) If subsize test specimens are used for the Charpy V-notch toughness test, the...

  17. Effects of anisotropic properties on bursting behavior of rectangular cup with a V-notch

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Tai [R and D Center, TERA Co. Ltd., Seoul (Korea, Republic of); Kim, Sang Mok [R and D Center, Hyosung Power and Industrial Systems PG, Changwon (Korea, Republic of); Kang, Beom Soo [Dept. of Aerospace Engineering, Pusan National University, Busan (Korea, Republic of); Ku, Tae Wan [Engineering Research Center of Innovative Technology on Advanced Forming, Pusan National University, Busan (Korea, Republic of)

    2016-09-15

    Effects of mechanical anisotropic properties on bursting failure and its pressure of rectangular deep-drawn cup fabricated by using AA3005-H14 thin sheet are investigated to utilize for electrolyte container of lithium-ion secondary batteries. The V-notch shape with a depth of 0.1 mm and an angle of 20.0 degrees is defined on the rectangular cup, which has a thickness of 0.20 mm on the major surface and that of 0.30 mm on the minor surface. With the measured mechanical properties by uni-axial tensile tests and the defined V-notch geometry, a series of numerical prediction models considering isotropic, planar and normal anisotropic characteristics, are built-up and the bursting simulations are performed. Thereafter, the bursting fracture behavior is investigated by adopting ductile fracture criterion proposed by Cockcroft and Latham. The results predicted for the planar and the normal anisotropic models show that the bursting fracture pressure is well matched to 0.400 MPa, and the isotropic and the planar anisotropic models present a bursting fracture height of about 4.95 mm and 4.92 mm, respectively. A series of experimental investigations are undertaken to verify the bursting deformation that had been predicted. The bursting pressure and its height during experimental verifications are shown to be in good agreement with each variation of about 5.88% and roughly 0.20% with respect to the numerical results obtained using the planar anisotropic model.

  18. CARA CVN: inherently safe fuel element for PHWR power plants

    International Nuclear Information System (INIS)

    Brasnarof, Daniel O.; Lestani, Hector A.; Agueda, Horacio C.; Marino, Armando C.; Florido, Pablo C.; Daverio, Hernando

    2007-01-01

    This paper presents design alternatives of the CARA fuel element with negative void reactivity coefficient (CVN) enhancing the PHWR safety for L-LOCA sequences. This design enhances the safety and the operation performance in Atucha and Embalse without changes in the operation conditions. This new design balances wide performance margins of CARA SEU 0.9% previous design, with new intrinsic safety requirements without economic penalties. (author) [es

  19. Grain size and temperature influence on the toughness of a CuAlBe shape memory alloy

    International Nuclear Information System (INIS)

    Albuquerque, Victor Hugo C. de; Melo, Tadeu Antonio de A; Gomes, Rodinei M.; Lima, Severino Jackson G. de; Tavares, Joao Manuel R.S.

    2010-01-01

    Research highlights: → This work evaluated the capacity of a CuAlBe alloy to absorb energy until rupture. → The V-notch Charpy test was adopted at -150, -100, -50, 0, 50, 100 and 150 deg. C. → Charpy tests were complemented by DSC, DSC with optical microscope and by SEM. → First work to analyze the toughness of a CuAlBe alloy based on the Charpy test. → The results are of relevant value to enhance the understanding of the CuAlBe alloy. - Abstract: This work is a study of the influence of grain size and temperature on the toughness of CuAlBe shape memory alloys with (CuAlBeNbNi) and without NbNi (CuAlBe) grain refiner elements. The toughness analysis was based on the V-notch Charpy impact test under temperatures of -150, -100, -50, 0, 50, 100 and 150 deg. C. A statistical analysis of the results led to the conclusion that the toughness of both alloys was influenced by temperature and grain size. The CuAlBeNbNi alloy absorbed higher impact energy than the CuAlBe alloy showing that the refining elements improved the toughness of the alloy. To confirm and complement these findings, the fracture surfaces were evaluated by stereomicroscopy. Smooth homogeneous surfaces and rough heterogonous surfaces were detected for the CuAlBeNbNi and CuAlBe alloys, respectively. Predominately brittle zones were confirmed by scanning electron microscopy in both alloys. Furthermore, to determine the phase transformation temperatures and the associated microstructures, the alloys were assessed by conventional differential scanning calorimetry (DSC) and DSC with optical microscopy.

  20. Grain size and temperature influence on the toughness of a CuAlBe shape memory alloy

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Victor Hugo C. de, E-mail: victor.albuquerque@fe.up.pt [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia Mecanica (DEM), Laboratorio de Solidificacao Rapida LSR, Cidade Universitaria, S/N 58059-900 Joao Pessoa, PB (Brazil); Melo, Tadeu Antonio de A, E-mail: tadeu@lsr.ct.ufpb.br [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia Mecanica (DEM), Laboratorio de Solidificacao Rapida LSR, Cidade Universitaria, S/N 58059-900 Joao Pessoa, PB (Brazil); Gomes, Rodinei M., E-mail: gomes@lsr.ct.ufpb.br [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia Mecanica (DEM), Laboratorio de Solidificacao Rapida LSR, Cidade Universitaria, S/N 58059-900 Joao Pessoa, PB (Brazil); Lima, Severino Jackson G. de, E-mail: jackson@lsr.ct.ufpb.br [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia Mecanica (DEM), Laboratorio de Solidificacao Rapida LSR, Cidade Universitaria, S/N 58059-900 Joao Pessoa, PB (Brazil); Tavares, Joao Manuel R.S., E-mail: tavares@fe.up.pt [Faculdade de Engenharia da Universidade do Porto (FEUP), Departamento de Engenharia Mecanica (DEMec)/Instituto de Engenharia Mecanica e Gestao Industrial INEGI, Rua Dr. Roberto Frias, S/N 4200-465 Porto (Portugal)

    2010-11-25

    Research highlights: {yields} This work evaluated the capacity of a CuAlBe alloy to absorb energy until rupture. {yields} The V-notch Charpy test was adopted at -150, -100, -50, 0, 50, 100 and 150 deg. C. {yields} Charpy tests were complemented by DSC, DSC with optical microscope and by SEM. {yields} First work to analyze the toughness of a CuAlBe alloy based on the Charpy test. {yields} The results are of relevant value to enhance the understanding of the CuAlBe alloy. - Abstract: This work is a study of the influence of grain size and temperature on the toughness of CuAlBe shape memory alloys with (CuAlBeNbNi) and without NbNi (CuAlBe) grain refiner elements. The toughness analysis was based on the V-notch Charpy impact test under temperatures of -150, -100, -50, 0, 50, 100 and 150 deg. C. A statistical analysis of the results led to the conclusion that the toughness of both alloys was influenced by temperature and grain size. The CuAlBeNbNi alloy absorbed higher impact energy than the CuAlBe alloy showing that the refining elements improved the toughness of the alloy. To confirm and complement these findings, the fracture surfaces were evaluated by stereomicroscopy. Smooth homogeneous surfaces and rough heterogonous surfaces were detected for the CuAlBeNbNi and CuAlBe alloys, respectively. Predominately brittle zones were confirmed by scanning electron microscopy in both alloys. Furthermore, to determine the phase transformation temperatures and the associated microstructures, the alloys were assessed by conventional differential scanning calorimetry (DSC) and DSC with optical microscopy.

  1. Long-term photometric behaviour of outbursting AM CVn systems

    OpenAIRE

    Levitan, David; Groot, Paul J.; Prince, Thomas A.; Kulkarni, Shrinivas R.; Laher, Russ; Ofek, Eran O.; Sesar, Branimir; Surace, Jason

    2015-01-01

    The AM CVn systems are a class of He-rich, post-period minimum, semidetached, ultracompact binaries. Their long-term light curves have been poorly understood due to the few systems known and the long (hundreds of days) recurrence times between outbursts. We present combined photometric light curves from the Lincoln Near Earth Asteroid Research, Catalina Real-Time Transient Survey, and Palomar Transient Factory synoptic surveys to study the photometric variability of these systems over an almo...

  2. Unravelling the Nature of HD 81032 – A New RS CVn Binary

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... ... component solar-abundance coronal plasma model, but implies either the presence of two or more plasma components, non-solar abundances, or a combination of both of these properties. All of the above properties of HD 81032 suggest that it is a newly identified, evolved RS CVn binary.

  3. Evaluation and uncertainty estimates of Charpy-impact data

    International Nuclear Information System (INIS)

    Stallman, F.W.

    1982-01-01

    Shifts in transition temperature and upper-shelf energy from Charpy tests are used to determine the extent of radiation embrittlement in steels. In order to determine these parameters reliably and to obtain uncertainty estimates, curve fitting procedures need to be used. The hyperbolic tangent or similar models have been proposed to fit the temperature-impact-energy curve. These models are not based on the actual fracture mechanics and are indeed poorly suited in many applications. The results may be falsified by forcing an inflexible curve through too many data points. The nonlinearity of the fit poses additional problems. In this paper, a simple linear fit is proposed. By eliminating data which are irrelevant for the determination of a given parameter, better reliability and accuracy can be achieved. Additional input parameters like fluence and irradiation temperature can be included. This is important if there is a large variation of fluence and temperature in different test specimens. The method has been tested with Charpy specimens from the NRC-HSST experiments

  4. Assessment of the effects of neutron fluence on Swedish nuclear pressure vessels

    International Nuclear Information System (INIS)

    Rao, S.

    1980-11-01

    Nuclear pressure vessels are subject to neutron irradiation during service causing embrittlement. This is one important factor in the overall problem of reactor vessel integrity. At present the irradiation effects are mainly assessed by the Charpy V-notch test. Two measures of embrittlement are defined: the increase of the ductile/brittle transition temperature and the decrease in the upper-shelf energy. The object of the present work is to assess these changes for the Swedish nuclear pressure vessels. On the basis of data from irradiations carried out in other countries and Swedish surveillance programmes, the expected end of life embrittlement is estimated for Swedish vessels. The results show that the embrittlement of most reactor vessels is expected to be quite small. Oskarshamn 1 and PWR-vessels, however, will probably show moderate changes, the former due to the higher copper content, and the latter due to the high end of life fluences. Some of the vessel materials which exhibit marginal properties in the upper-shelf energy, as measured by the Charpy V-notch impact test, are identified. It is recommended that fracture mechanics analyses be applied in these cases. (author)

  5. Relationships between Charpy impact shelf energies and upper shelf Ksub(IC) values for reactor pressure vessel steels

    International Nuclear Information System (INIS)

    Witt, F.J.

    1983-01-01

    Charpy shelf data and lower bound estimates of Ksub(IC) shelf data for the same steels and test temperatures are given. Included are some typical reactor pressure vessel steels as well as some less tough or degraded steels. The data were evaluated with shelf estimates of Ksub(IC) up to and exceeding 550 MPa√m. It is shown that the high shelf fracture toughness representative of tough reactor pressure vessel steels may be obtained from a knowledge of the Charpy shelf energies. The toughness transition may be obtained either by testing small fracture toughness specimens or by Charpy energy indexing. (U.K.)

  6. The adhesion force of Notch with Delta and the rate of Notch signaling.

    Science.gov (United States)

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-12-20

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

  7. Multivariable modeling of pressure vessel and piping J-R data

    International Nuclear Information System (INIS)

    Eason, E.D.; Wright, J.E.; Nelson, E.E.

    1991-05-01

    Multivariable models were developed for predicting J-R curves from available data, such as material chemistry, radiation exposure, temperature, and Charpy V-notch energy. The present work involved collection of public test data, application of advanced pattern recognition tools, and calibration of improved multivariable models. Separate models were fitted for different material groups, including RPV welds, Linde 80 welds, RPV base metals, piping welds, piping base metals, and the combined database. Three different types of models were developed, involving different combinations of variables that might be available for applications: a Charpy model, a preirradiation Charpy model, and a copper-fluence model. In general, the best results were obtained with the preirradiation Charpy model. The copper-fluence model is recommended only if Charpy data are unavailable, and then only for Linde 80 welds. Relatively good fits were obtained, capable of predicting the values of J for pressure vessel steels to with a standard deviation of 13--18% over the range of test data. The models were qualified for predictive purposes by demonstrating their ability to predict validation data not used for fitting. 20 refs., 45 figs., 16 tabs

  8. Prediction of fracture toughness K/sub Ic/ of steel from Charpy impact test results

    Energy Technology Data Exchange (ETDEWEB)

    Iwadate, Tadao; Tanaka, Yasuhiko; Takemata, Hiroyuki; Terashima, Shuhei

    1986-08-01

    This paper presents a method to predict the fracture toughness K/sub Ic/ and/or K/sub Id/ of steels using their Charpy impact test results and tensile properties. The fracture toughness, Charpy impact and tensile properties of 2 1/4 Cr-1Mo, ASTM A508 Cl.1, A508 Cl.2 A508 Cl.3 and A533 Gr.B Cl.1 steels were measured and analysed on the basis of the excess temperature (test temperature minus FATT) and Rolfe-Novak correlation. The relationship between K/sub Ic//K/sub Ic-us/ and the excess temperature, where K/sub Ic-us/ is the upper-shelf fracture toughness K/sub Ic/ predicted by Rolfe-Novak correlation, discloses that the K/sub Ic/ transition curves of several steels are representable by only one trend curve of K/sub Ic//K/sub Ic-us/ or K/sub Id//K/sub Id-us/ versus excess temperature relation. This curve is denoted as a ''master curve''. By using this curve, the fracture toughness of steel can be predicted using Charpy impact and tensile test results. By taking account of the scattering of both the fracture toughness and Charpy impact test results, the confidence limits of the master curve were also determined. Another approach to develop more general procedure of predicting the fracture toughness K/sub Ic/ is also discussed.

  9. Characteristics of the IAEA correlation monitor material for surveillance programmes

    International Nuclear Information System (INIS)

    Wallin, K.; Valo, M.; Rintamaa, R.; Toerroenen, K.

    1989-08-01

    Within the IAEA Coordinated Research Programme on optimizing of reactor pressure vessel surveillance programmes and their analysis, phase 3, a specially tailored 'radiation sensitive' correlation monitor material has been fabricated. This material will serve as a reference to the IAEA programme for future vessel surveillance programmes throughout the world. An extensive evaluation of the correlation monitor material in the as-received condition has been carried out in Finland and the results are presented here. The mechanical properties measured at different temperatures include Charpy V notch and instrumented precracked Charpy data, and elastic-plastic fracture toughness (J). The specimen size and geometry have been varied in the tests. Correlation between different fracture properties are evaluated and discussed

  10. The interpretation of Charpy impact test data using hyper-logistic fitting functions

    International Nuclear Information System (INIS)

    Helm, J.L.

    1996-01-01

    The hyperbolic tangent function is used almost exclusively for computer assisted curve fitting of Charpy impact test data. Unfortunately, there is no physical basis to justify the use of this function and it cannot be generalized to test data that exhibits asymmetry. Using simple physical arguments, a semi-empirical model is derived and identified as a special case of the so called hyper-logistic equation. Although one solution of this equation is the hyperbolic tangent, other more physically interpretable solutions are provided. From the mathematics of the family of functions derived from the hyper-logistic equation, several useful generalizations are made such that asymmetric and wavy Charpy data can be physically interpreted

  11. Short-period AM CVn systems as optical, X-ray and gravitational-wave sources

    NARCIS (Netherlands)

    Nelemans, G.; Yungelson, L.; Portegies Zwart, S.F.

    2004-01-01

    We model the population of AM CVn systems in the Galaxy and discuss the detectability of these systems with optical, X-ray and gravitational-wave detectors. We concentrate on the short-period (P < 1500 s) systems, some of which are expected to be in a phase of direct-impact accretion. Using a

  12. A cautionary tale of interpreting O-C diagrams: period instability in a classical RR Lyr Star Z CVn mimicking as a distant companion

    Science.gov (United States)

    Skarka, M.; Liška, J.; Dřevěný, R.; Guggenberger, E.; Sódor, Á.; Barnes, T. G.; Kolenberg, K.

    2018-02-01

    We present a comprehensive study of Z CVn, an RR Lyrae star that shows long-term cyclic variations of its pulsation period. A possible explanation suggested from the shape of the O-C diagram is the light travel-time effect, which we thoroughly examine. We used original photometric and spectroscopic measurements and investigated the period evolution using available maximum times spanning more than one century. If the binary hypothesis is valid, Z CVn orbits around a black hole with minimal mass of 56.5 M_{⊙} on a very wide (Porbit = 78.3 yr) and eccentric orbit (e = 0.63). We discuss the probability of the formation of a black hole-RR Lyrae pair, and, although we found it possible, there is no observational evidence of the black hole in the direction to Z CVn. However, the main objection against the binary hypothesis is the comparison of the systemic radial velocity curve model and spectroscopic observations that clearly show that Z CVn cannot be bound in such a binary. Therefore, the variations of pulsation period are likely intrinsic to the star. This finding represents a discovery/confirmation of a new type of cyclic period changes in RR Lyrae stars. By the analysis of our photometric data, we found that the Blazhko modulation with period of 22.931 d is strongly dominant in amplitude. The strength of the phase modulation varies and is currently almost undetectable. We also estimated photometric physical parameters of Z CVn and investigated their variations during the Blazhko cycle using the inverse Baade-Wesselink method.

  13. The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Sung Hee Choi

    Full Text Available Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL, in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.

  14. A 15.7-Minute AM CVn Binary Discovered in K2

    Science.gov (United States)

    Green, M. J.; Hermes, J. J.; Marsh, T. R.; Steeghs, D. T. H.; Bell, Keaton J.; Littlefair, S. P.; Parsons, S. G.; Dennihy, E.; Fuchs, J. T.; Reding, J. S.; Kaiser, B. C.; Ashley, R. P.; Breedt, E.; Dhillon, V. S.; Gentile Fusillo, N. P.; Kerry, P.; Sahman, D. I.

    2018-04-01

    We present the discovery of SDSS J135154.46-064309.0, a short-period variable observed using 30-minute cadence photometry in K2 Campaign 6. Follow-up spectroscopy and high-speed photometry support a classification as a new member of the rare class of ultracompact accreting binaries known as AM CVn stars. The spectroscopic orbital period of 15.65 ± 0.12 minutes makes this system the fourth-shortest period AM CVn known, and the second system of this type to be discovered by the Kepler spacecraft. The K2 data show photometric periods at 15.7306 ± 0.0003 minutes, 16.1121 ± 0.0004 minutes and 664.82 ± 0.06 minutes, which we identify as the orbital period, superhump period, and disc precession period, respectively. From the superhump and orbital periods we estimate the binary mass ratio q = M2/M1 = 0.111 ± 0.005, though this method of mass ratio determination may not be well calibrated for helium-dominated binaries. This system is likely to be a bright foreground source of gravitational waves in the frequency range detectable by LISA, and may be of use as a calibration source if future studies are able to constrain the masses of its stellar components.

  15. Significance of Charpy and COD tests in the determination of fracture toughness of welds

    International Nuclear Information System (INIS)

    Caminha Junior, H.M.; Bastian, F.L.

    1983-01-01

    A comparison is made between the Charpy and crack opening displacement (COD) tests used to acess the fracture toughness of metallic materials. The main problems inherent in these tests are discussed, such as scatter of results and their advantages and limitations. The chief experimental difficulties when they are applied to welds are indicated and the various methods available for calculating the COD from a test graph are described. Comments are made on the use of the Charpy test and the methods of calculating the COD in determing critical defect sizes in welded structures. (Author) [pt

  16. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  17. 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.

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

    International Nuclear Information System (INIS)

    Chan, Kwai S.

    2015-01-01

    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. (paper)

  19. Experimental study on variations in Charpy impact energies of low carbon steel, depending on welding and specimen cutting method

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhaorui; Kang, Hansaem; Lee, Young Seog [Chung-Ang University, Seoul (Korea, Republic of)

    2016-05-15

    This paper presents an experimental study that examines variations of Charpy impact energy of a welded steel plate, depending upon the welding method and the method for obtaining the Charpy specimens. Flux cored arc welding (FCAW) and Gas tungsten arc welding (GTAW) were employed to weld an SA516 Gr. 70 steel plate. The methods of wire cutting and water-jet cutting were adopted to take samples from the welded plate. The samples were machined according to the recommendations of ASTM SEC. II SA370, in order to fit the specimen dimension that the Charpy impact test requires. An X-ray diffraction (XRD) method was used to measure the as-weld residual stress and its redistribution after the samples were cut. The Charpy impact energy of specimens was considerably dependent on the cutting methods and locations in the welded plate where the specimens were taken. The specimens that were cut by water jet followed by FCAW have the greatest resistance-to-fracture (Charpy impact energy). Regardless of which welding method was used, redistributed transverse residual stress becomes compressive when the specimens are prepared using water-jet cutting. Meanwhile, redistributed transverse residual stress becomes tensile when the specimens are prepared using wire cutting.

  20. Influence of Striking Edge Radius (2 mm versus 8 mm) on Instrumented Charpy Data and Absorbed Energies

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.

    2008-08-15

    The most commonly used test standards for performing Charpy impact tests (ISO 148 and ASTM E 23) envisage the use of strikers having different radii of the striking edge, i.e. 2 mm (ISO) and 8 mm (ASTM). The effect of striker geometry on Charpy results was extensively studied in the past in terms of absorbed energy measured by the machine encoder, but few investigations are available on the influence of striker configuration on the results of instrumented Charpy tests (characteristic forces, displacements and integrated energy). In this paper, these effects are investigated based on the analysis of published results from three interlaboratory studies and some unpublished Charpy data obtained at SCK-CEN. The instrumented variables which are the most sensitive to the radius of the striking edge are the maximum force and its corresponding displacement, with 8mm-strikers providing systematically higher values. Absorbed energies, obtained both from the instrumented trace and from the pendulum encoder, are almost insensitive to the type of striker up to 200 J. For higher energy levels, the values obtained from 8mm strikers become progressively larger. Data scatter is generally higher for 2mm-strikers.

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

    NARCIS (Netherlands)

    Li, Haiying; Koo, Yeon; Mao, Xicheng; Sifuentes-Dominguez, Luis; Morris, Lindsey L.; Jia, Da; Miyata, Naoteru; Faulkner, Rebecca A.; van Deursen, Jan M.; Vooijs, Marc; Billadeau, Daniel D.; van de Sluis, Bart; Cleaver, Orane; Burstein, Ezra

    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

  2. A Study on the Low Temperature Brittleness by Cyclic Cooling-Heating of Low Carbon Hot Rolled Steel Plate

    International Nuclear Information System (INIS)

    Lee, Hyo Bok

    1979-01-01

    The ductile-brittle transition phenomenon of low carbon steel has been investigated using the standard Charpy V-notch specimen. Dry ice and acetone were used as refrigerants. Notched specimens were cut from the hot rolled plate produced at POSCO for the Olsen impact test. The effect of cyclic cooling and heating of 0.14% carbon steel on the embrittlement was extensively examined. The ductile-brittle transition temperature was found to be approximately-30 .deg. C. The transition temperature was gradually increased as the number of cooling-heating cycles increased. On a typical V-notch fracture surface it was found that the ductile fracture surface showed a thick and fibrous structure, while the brittle fracture surface a small and light grain with irregular disposition. As expected, the transition temperature was also increased as the carbon content of steel increased. Compared with the case of 0.14% carbon steel, the transition temperature of 0.17% carbon steel was found to be increased about 12 .deg. C

  3. Star-spot distributions and chromospheric activity on the RS CVn type eclipsing binary SV Cam

    Science.gov (United States)

    Şenavcı, H. V.; Bahar, E.; Montes, D.; Zola, S.; Hussain, G. A. J.; Frasca, A.; Işık, E.; Yörükoǧlu, O.

    2018-06-01

    Using a time series of high-resolution spectra and high-quality multi-colour photometry, we reconstruct surface maps of the primary component of the RS CVn type rapidly rotating eclipsing binary, SV Cam (F9V + K4V). We measure a mass ratio, q, of 0.641(2) using our highest quality spectra and obtain surface brightness maps of the primary component, which exhibit predominantly high-latitude spots located between 60° - 70° latitudes with a mean filling factor of ˜35%. This is also indicated by the R-band light curve inversion, subjected to rigourous numerical tests. The spectral subtraction of the Hα line reveals strong activity of the secondary component. The excess Hα absorption detected near the secondary minimum hints to the presence of cool material partially obscuring the primary star. The flux ratios of Ca II IRT excess emission indicate that the contribution of chromospheric plage regions associated with star-spots is dominant, even during the passage of the filament-like absorption feature.

  4. The adhesion force of Notch with Delta and the rate of Notch signaling

    OpenAIRE

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-01-01

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of ...

  5. Illegitimate V(D)J recombination-mediated deletions in Notch1 and Bcl11b are not sufficient for extensive clonal expansion and show minimal age or sex bias in frequency or junctional processing

    Energy Technology Data Exchange (ETDEWEB)

    Champagne, Devin P., E-mail: devin.champagne@uvm.edu; Shockett, Penny E., E-mail: pshockett@selu.edu

    2014-03-15

    Highlights: • Examines illegitimate V(D)J deletion junctions in Notch1 and Bcl11b. • Suggests little influence of deletions alone on clonal outgrowth in wild-type mice. • No age or sex biases in frequency, clonality, or junctional processing observed. • Contrasts with previous results at TCRβ and HPRT1 loci. • Deletions in Bcl11b may be tolerated more easily than those in Notch1. - Abstract: Illegitimate V(D)J recombination at oncogenes and tumor suppressor genes is implicated in formation of several T cell malignancies. Notch1 and Bcl11b, genes involved in developing T cell specification, selection, proliferation, and survival, were previously shown to contain hotspots for deletional illegitimate V(D)J recombination associated with radiation-induced thymic lymphoma. Interestingly, these deletions were also observed in wild-type animals. In this study, we conducted frequency, clonality, and junctional processing analyses of Notch1 and Bcl11b deletions during mouse development and compared results to published analyses of authentic V(D)J rearrangements at the T cell receptor beta (TCRβ) locus and illegitimate V(D)J deletions observed at the human, nonimmune HPRT1 locus not involved in T cell malignancies. We detect deletions in Notch1 and Bcl11b in thymic and splenic T cell populations, consistent with cells bearing deletions in the circulating lymphocyte pool. Deletions in thymus can occur in utero, increase in frequency between fetal and postnatal stages, are detected at all ages examined between fetal and 7 months, exhibit only limited clonality (contrasting with previous results in radiation-sensitive mouse strains), and consistent with previous reports are more frequent in Bcl11b, partially explained by relatively high Recombination Signal Information Content (RIC) scores. Deletion junctions in Bcl11b exhibit greater germline nucleotide loss, while in Notch1 palindromic (P) nucleotides are more abundant, although average P nucleotide length is

  6. Notch constraint effects on the dynamic fracture toughness of an unaged beta titanium alloy

    International Nuclear Information System (INIS)

    Rack, H.J.

    1975-01-01

    The influence of notch included angle and root radius on the apparent dynamic fracture toughness of an unaged metastable beta titanium alloy, Ti--3Al--8V--6Cr--4Zr--4Mo, has been examined. The apparent fracture toughness, K/sub Id/(rho), increases with both notch radius, rho and included angle, ω. These results have been compared with the theoretical predictions of Tetelman, et al. and Smith. The comparisons show that neither theory accurately describes the effect of varying notch constraint on the apparent dynamic fracture toughness. Although preliminary considerations indicate that qualitative descriptions of notch acuity effects may be given by recent finite element analysis of the stress and strain distributions below a notch root, there is presently no quantitative basis for determining the true dynamic fracture toughness of materials from the results of blunt notch experiments. (auth)

  7. SISTEMA DE AQUISIÇÃO DE DADOS PARA A MÁQUINA DE IMPACTO CHARPY

    Directory of Open Access Journals (Sweden)

    Jermana Lopes Moraes

    2014-08-01

    Full Text Available Este trabalho tem o objetivo de implementar e desenvolver um sistema de aquisição de dados para a máquina de impacto Charpy. Assim, é realizado um estudo da máquina de impacto Charpy, do ensaio de impacto e das ferramentas necessárias para desenvolvimento do projeto. Utiliza-se um acelerômetro para determinar a aceleração nos eixos x e y do pêndulo Charpy durante a realização do ensaio. Para leitura e interpretação dos dados enviados pelo acelerômetro utiliza-se a plataforma de hardware Arduino UNO com software específico. Os dados enviados ao Arduino são apresentados em uma interface gráfica desenvolvida no Matlab. Nesta interface é possível inserir os dados iniciais de ensaio Charpy e apresentar ao usuário final os resultados finais de ensaio, como a energia de impacto, a resistência de impacto e a força necessária para romper o corpo de prova. Além disso, é apresentado ao usuário um gráfico da aceleração ao longo da realização do ensaio e o gráfico de força ao longo do tempo. Desta forma, registram-se os dados em um arquivo específico para análise e estudo posterior. A porcentagem de erro entre o valor medidor no mostrador da máquina e o resultado automatizado não ultrapassa o limite de 8 %.

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

    Directory of Open Access Journals (Sweden)

    Miguel Aste-Amézaga

    2010-02-01

    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

  9. Influence of Loading Rate on the Calibration of Instrumented Charpy Strikers

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.; Scibetta, M.; McColskey, D.; McCowan, C.

    2009-01-15

    One of the key factors for obtaining reliable instrumented Charpy results is the calibration of the instrumented striker. The conventional approach for establishing an analytical relationship between strain gage output and force applied to the transducer is the static calibration, which is preferably performed with the striker installed in the pendulum assembly. However, the response of an instrumented striker under static force application may sometimes differ significantly from its dynamic performance during an actual Charpy test. This is typically reflected in a large difference between absorbed energy returned by the pendulum encoder (KV) and calculated under the instrumented force/displacement test record (Wt). Such difference can be either minimized by optimizing the striker design or analytically removed by adjusting forces and displacements until KV = Wt (the so-called 'Dynamic Force Adjustment'). This study investigates the influence of increasing force application rates on the force/voltage characteristics of two instrumented strikers, one at NIST in Boulder, CO and one at SCK-CEN in Mol, Belgium.

  10. Maximum mass ratio of AM CVn-type binary systems and maximum white dwarf mass in ultra-compact X-ray binaries

    Directory of Open Access Journals (Sweden)

    Arbutina Bojan

    2011-01-01

    Full Text Available AM CVn-type stars and ultra-compact X-ray binaries are extremely interesting semi-detached close binary systems in which the Roche lobe filling component is a white dwarf transferring mass to another white dwarf, neutron star or a black hole. Earlier theoretical considerations show that there is a maximum mass ratio of AM CVn-type binary systems (qmax ≈ 2/3 below which the mass transfer is stable. In this paper we derive slightly different value for qmax and more interestingly, by applying the same procedure, we find the maximum expected white dwarf mass in ultra-compact X-ray binaries.

  11. Irradiation effects in strain aged pressure vessel steel

    Energy Technology Data Exchange (ETDEWEB)

    Grounes, M; Myers, H P

    1962-02-15

    Tensile specimens, Charpy-V notch and subsize impact specimens of an aluminium killed carbon manganese steel, have been irradiated at 160 - 190 deg C in the reactor G1. The total neutron dose received was 2.4 x 10{sup 18} n/cm{sup 2} (> 1 MeV). Specimens were prepared from normalized plate and from strain aged material from the same plate. It was found that the changes in brittle ductile transition temperature due to neutron irradiation and those due to strain ageing must be considered additive.

  12. Irradiation and annealing behavior of 15Kh2MFA reactor pressure vessel steel

    International Nuclear Information System (INIS)

    Popp, K.; Bergmann, U.; Bergner, F.; Hampe, E.; Leonhardt, W.D.; Schuetzler, H.P.; Viehrig, H.W.

    1992-01-01

    This work deals with the mechanical properties of RPV steels used WWER-440. The materials under investigation were a forging (base metal 15Kh2MFA) and the corresponding weld. Charpy V-notch specimens and tensile test specimens were irradiated in the WWER-2 Rheinsberg at about 270 C up to the two neutron fluence levels of 4 x 10 18 and 5 x 10 19 n/cm 2 (E>1MeV). Post-irradiation annealing heat treatments were performed, among others a 475 C/152 h treatment of technical interest. (orig.)

  13. Fracture toughness evaluation of small notched specimen in consideration of notch effect and loading rate

    International Nuclear Information System (INIS)

    Lee, Baik Woo; Kwon, Dong Il; Jang, Jae Il

    2000-01-01

    Notch effect and loading rate dependency on fracture toughness were considered when evaluating fracture toughness of small notched specimens using the instrumented impact test. Notch effect was analyzed into stress redistribution effect and stress relaxation with a viewpoint of stress triaxiality. Stress redistribution effect was corrected by introducing effective crack length, which was the sum of actual crack length and plastic zone size. Stress relaxation effect was also corrected using elastic stress concentration factor, which would decrease if plastic deformation occurred. As a result, corrected fracture toughness of the notched specimen was very consistent with the reference fracture toughness obtained using precracked specimen. In addition, limiting notch root radius, below which fracture toughness was independent of notch radius, was observed and discussed. Loading rate dependency on fracture toughness, which was obtained from the static three point bending test and the instrumented impact test, was also discussed with stress field in plastic zone ahead of a notch and fracture based on stress control mechanism. (author)

  14. Development of a reconstitution system of Charpy probes for the surveillance of vessels in nucleo electric plants

    International Nuclear Information System (INIS)

    Romero C, J.; Hernandez, R.; Fernandez, F.; Gonzalez M, A.

    2007-01-01

    This work describes the development of a welding system, for the rebuilding of halves of Charpy test tubes, the rebuilding consists on welding two implants in those ends of these halves of test tubes, in these welding the main requirement is not to alter the mechanical properties in a minimum volume of 1 cm 3 , the rebuilding is medullary in the surveillance programs of the reactor vessel. In these programs, the mechanical state of the vessel is evaluated, for it there are surveillance capsules with a Charpy witness test tubes series, subjected to a neutron flow similar or bigger to that of the vessel. The objective is to evaluate in advance on the vessel fragilization grade its life design. However the number of capsules with the witness test tubes it is only for the plant design life and at the moment the nucleo electric, negotiates an extension of life of these, until for 20 more years, of there the importance of this material witness's that stores the information of the damage accumulated by the neutron flow. This material requires to be taken advantage it after being rehearsed and the normative one settles down as obligatory to qualify the rebuilding process with all the requirements settled down in the ASTM Designation: E 1253-99 'Standard Guide for Reconstitution of irradiated Charpy-Sized Specimens', to obtain other reconstituted Charpy test tubes that are again introduced in the reactor. When being reconstituted the halves of the original test tubes it is obtained double reconstituted Charpy test tubes. Half of the test tubes they are used in the surveillance program of the vessel, with the surpluses test tubes, it can determine the fracture toughness, property of the material used in the extension methodology of life of vessel. (Author)

  15. Radiation embrittlement in pressure vessels of power reactors

    International Nuclear Information System (INIS)

    Kempf, Rodolfo; Fortis, Ana M.

    2007-01-01

    It is presented the project to study the effect of lead factors on the mechanical behavior of Reactor Pressure Vessel steels. It is described the facility designed to irradiate Charpy specimens with V notch of SA-508 type 3 steel at power reactor temperature, installed in the RA-1 reactor. The objective is to obtain the fracture behavior of irradiated specimens with different lead factors and to know their dependence with the diffusion of alloy elements. (author) [es

  16. 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

  17. Coastal dune dynamics in response to excavated foredune notches

    Science.gov (United States)

    Ruessink, B. G.; Arens, S. M.; Kuipers, M.; Donker, J. J. A.

    2018-04-01

    Dune management along developed coasts has traditionally focussed on the suppression of the geomorphic dynamics of the foredune to improve its role in sea defence. Because a stabilized foredune acts as an almost total barrier to aeolian transport from the beach, the habitat diversity in the more landward dunes has degraded. With the overarching objective to mitigate this undesirable loss in biodiversity, dune management projects nowadays increasingly intend to restore aeolian dynamics by reconnecting the beach-dune system with notches excavated through the foredune. Here, we use repeat topographic survey data to examine the geomorphic response of a coastal dune system in the Dutch National Park Zuid-Kennemerland to five notches excavated in 2012-2013 within an 850-m stretch of the 20-m high established foredune. The notches were dug in a V-shape (viewed onshore), with a width between approximately 50 and 100 m at the top, a (cross-dune) length between 100 and 200 m, and excavation depths between 9 and 12.5 m. The 1 × 1 m digital terrain models, acquired with airborne Lidar and UAV photogrammetry, illustrate that during the 3-year survey period the notches developed into a U-shape because of wall deflation, and that up to 8-m thick and 150-m long depositional lobes formed landward of the notches. Sand budget computations showed that the sand volume of the entire study area increased by about 22,750 m3/year, which, given the 850-m width of the study area, corresponds to an aeolian input from the beach of approximately 26.5 m3/m/year. Between 2006 and 2012 all wind-blown beach sand deposited on the seaward side of the foredune; since 2013, the notches have caused 75% of the sand to be deposited landward of the foredune. This highlights that the notches are highly effective conduits for aeolian transport into the back dunes. Future monitoring is required to determine for how long the notches will stimulate aeolian dynamics and if (and when) vegetation eventually

  18. Quantification of the toughness distribution in a heavy section submerged arc multilayer reactor pressure vessel weldment

    International Nuclear Information System (INIS)

    Cerjak, H.; Prader, R.

    1999-01-01

    In a working procedure qualification test weld representing a heavy section circumferential reactor pressure vessel (RPV) weld tested in 1968, lower toughness values were observed in the top layer region compared to those found in the filler region. Gleeble simulation, extensive microscopic evaluation, diligent Charpy V-notch testing and modelling of the bead sequence and distribution of alloying elements was applied to explain this effect. It could be revealed that the microstructure of the weld metal is the most important factor influencing the toughness. When an 'as welded' microstructure is partly or fully reaustenitised by the adjacent multilayer beads, the microstructure transforms and the toughness increases. In the filler region, 85% of the cross-section consists from transformed microstructure, whereas in the top layer only 20% are transformed. It is quite evident that, accidentally, the notch tip of Charpy samples in 1968 were placed in untransformed microstructures. When the top layer on the inner surface of the RPV is weld cladded by austenitic stainless steel, full transformation occurs and the toughness representing the filler region can be taken into account for safety evaluations. (orig.)

  19. THE HOT COMPONENTS OF AM CVn HELIUM CATACLYSMICS

    International Nuclear Information System (INIS)

    Sion, Edward M.; Godon, Patrick; Ballouz, Ronald-Louis; Linnell, Albert P.

    2011-01-01

    We present the results of a multi-component synthetic spectral analysis of the archival far-ultraviolet spectra of the hot components of several AM CVn double degenerate interacting binaries with known distances from trigonometric parallaxes. Our analysis was carried out using the code BINSYN, which takes into account the donor companion star, the shock front which forms at the disk edge, and the FUV and NUV energy distribution. We fixed the distance of each system at its parallax-derived value and adopted appropriate values of orbital inclination and white dwarf (WD) mass. We find that the accretion-heated 'DO/DB' WDs are contributing significantly to the FUV flux in five of the systems (ES Ceti, CR Boo, V803 Cen, HP Lib, GP Com). In three of the systems, GP Com, ES Ceti, and CR Boo, the WD dominates the FUV/NUV flux. We present model-derived accretion rates which agree with the low end of the range of accretion rates derived earlier from blackbody fits over the entire spectral energy distribution. We find that the WD in ES Ceti is very likely not a direct impact accretor but has a small disk. The WD in ES Ceti has T eff ∼ 40, 000 ± 10, 000 K. This is far cooler than the previous estimate of Espaillat et al.. We find that the WD in GP Com has T eff = 14, 800 ± 500 K, which is hotter than the previously estimated temperature of 11,000 K. We present a comparison between our empirical results and current theoretical predictions for these systems.

  20. Re-utilization by '' Stud Welding'' of capsules charpy-V belonged to surveillance programs

    International Nuclear Information System (INIS)

    Lapena, J.; Perosanz, F. J.; Gachuz, M.

    1998-01-01

    The perspectives of nuclear plants life extension that are approximating to their end of design life compels to make new surveillance programs. The re-utilization of specimens belonging to surveillance capsules already tested in these new surveillance programs seems be a solution worldwide accepted. The two possible re-utilization processes of this irradiated material are: Subsized specimens and Reconstitution. While the first alternative (Subsized specimens) outlines serious problems for apply the results, the reconstitution eliminates this problem, since the resulting specimens after of the reconstruction procedure would be of the same dimensions that the original. The reconstruction process involves welds, and therefore it has associated the specific problems of this type of joints. Furthermore, by be tried to material irradiated with certain degree of internal damage, that is the variable to evaluate, requires that the heat contribution to the piece not originate local thermal treatments that alter its mechanical qualities. In this work has been followed the evolution by the variables of the weld process and their influence on the quality by the union from metallographic al point of view as well as mechanical for a weld procedure by Stud Welding. The principal objective is to optimize said parameters to assure a good mechanical continuity, without detriment of the microstructural characteristics of the original material. To verify this last have been accomplished with metallographical tests, temperature profile, hardness and will be carried out also Charpy tests. (Author)

  1. Notch sensitivity of aliphatic polyketone terpolymers

    NARCIS (Netherlands)

    Zuiderduin, W.C.J.; Huetink, Han; 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

  2. Study of the ultrasonic technique of elapsed time of notch

    International Nuclear Information System (INIS)

    Gomes, L.C.F.L.; Rebello, J.M.A.

    1989-01-01

    The study of the ultrasonic technique of elapsed time in the dimensionment of notch inclined of 15 and 30 degree and of depth of 5 and 10 mm using the superficial Rayleigh wave and the mode conversion, with a headstock transmitter and other receiver. The dimensionment of notch and of the binding of the piece were made with headstock in different positions. Between the various results obtained can be mentioned the increase of the dimensionment, by two techniques, with the increase of the angle and/or of the depth. (V.R.B.)

  3. Fractographic examination of HT-9 and 9Cr-1Mo Charpy specimens irradiated in the AD-2 test

    International Nuclear Information System (INIS)

    Gelles, D.S.; Hu, W.L.

    1983-01-01

    Fracture surface topologies have been examined using scanning electron microscopy for 20 selected half sized Charpy impact specimens of HT-9 and Modified 9Cr-1Mo in order to provide improved understanding of fracture toughness degradation as a result of irradiation for Path E alloys. The specimen matrix included unirradiated specimens and specimens irradiated in EBR-II in the AD-2 experiment. Also, hardness measurements have been made on selected irradiated Charpy specimens. The results of examinations indicate that irradiation hardening due to G-phase formation at 390 0 C is responsible for the large shift in ductile-to-brittle transition temperature (DBTT) found in HT-9. Toughness degradation in HT-9 observed following higher temperature irradiations is attributed to precipitation at delta ferrite stringers. Reductions in toughness as a consequence of irradiation in Modified 9Cr-1Mo are attributed to in-reactor precipitation of (V,Nb)C and M 23 C 6 . It is shown that crack propagation rates for ductile and brittle failure modes can be measured, that they differ by over an order of magnitude and that unexpected multiple shifts in fracture mode from ductile to brittle failure can be attributed to the effect of delta ferrite stringers on crack propagation rates

  4. Gravitational waves from double white dwarfs and AM CVn binaries

    International Nuclear Information System (INIS)

    Nelemans, Gijs

    2003-01-01

    I give a brief overview of our model for the galactic population of compact binaries that is used to predict the low-frequency gravitational wave signal from the galaxy, and discuss recent observational developments that will enable us to test and improve this model. The SPY project will discover some 150 new close double white dwarfs and, recently, two ROSAT sources turned out to be new AM CVn candidates, one with an orbital period of only 5 min. I give an update on the expected binaries that will be resolved by LISA and discuss what we can learn about the galactic population of compact binaries once LISA gives her first results

  5. Effect of delaminations on improvement of notch toughness at low temperatures

    International Nuclear Information System (INIS)

    Zhou, W.; Loh, N.L.

    1996-01-01

    The notched-bar impact test is often used to assess the notch toughness of engineering materials. The principle of the test is that a material absorbs a certain amount of energy when it breaks; the energy thus absorbed is an indication of the material's resistance to impact fracture. If the material is brittle, it breaks easily with a small amount of absorbed energy. If it is tough, it will absorb more energy to fracture. It has been well recognized that most engineering materials undergo a transition from notch tough to notch brittle behavior when the temperature is reduced. In the present study, however, an abnormal trend in the transition behavior was found for an austenitic stainless steel. V-notched specimens of the steel were tested under impact loading in a wide temperature range from -196 C to room temperature. Contrary to expectation, the impact energy values obtained at low temperatures were found to be much higher than those obtained at room temperature, indicating that the steel became tougher rather than more brittle when the test temperature was lowered. This intriguing phenomenon cannot be explained simply according to the tensile stress fracture criterion. Strong evidence has been obtained in the present study to show that the improvement of notch toughness at low temperatures is caused by delaminations

  6. A Metallurgical Evaluation of the Powder-Bed Laser Additive Manufactured 4140 Steel Material

    Science.gov (United States)

    Wang, Wesley; Kelly, Shawn

    2016-03-01

    Using laser powder bed fusion (PBF-L) additive manufacturing (AM) process for steel or iron powder has been attempted for decades. This work used a medium carbon steel (AISI 4140) powder to explore the feasibility of AM. The high carbon equivalent of 4140 steel (CEIIW ≈ 0.83) has a strong tendency toward cold cracking. As such, the process parameters must be carefully controlled to ensure the AM build quality. Through an orthogonally designed experimental matrix, a laser-welding procedure was successfully developed to produce 4140 steel AM builds with no welding defects. In addition, the microstructure and micro-cleanliness of the as-welded PBF-L AM builds were also examined. The results showed an ultra-fine martensite lath structure and an ultra-clean internal quality with minimal oxide inclusion distribution. After optimizing the PBF-L AM process parameters, including the laser power and scan speed, the as-welded AM builds yielded an average tensile strength higher than 1482 MPa and an average 33 J Charpy V-notch impact toughness at -18°C. The surface quality, tensile strength, and Charpy V-notch impact toughness of AM builds were comparable to the wrought 4140 steel. The excellent mechanical properties of 4140 steel builds created by the PBF-L AM AM process make industrial production more feasible, which shows great potential for application in the aerospace, automobile, and machinery industries.

  7. Irradiation Effects at 160-240 deg C in Some Swedish Pressure Vessel Steels

    Energy Technology Data Exchange (ETDEWEB)

    Grounes, M [AB Atomenergi, Nykoeping (Sweden); Myers, H P [Chalmers Institute of Technology, Goeteborg (Sweden); Hannerz, N E [Motala Verkstads AB, Motala (Sweden)

    1967-09-15

    Tensile specimens, Charpy impact specimens and miniature impact specimens of six steels in different conditions were irradiated to 2.8 x 10{sup 18} and 5.6 x 10{sup 18} n/cm{sup 2} (> 1 MeV) at 160-240 deg C. The steels investigated were SIS 142103, 2103/R3, NO 345, Fortiweld, Fortiweld HS and OK 54 P. There is no correlation between the increase in transition temperature and initial transition temperature. However, changes in strength and ductility can be correlated to the initial yield strength. The increases in transition temperature due to strain aging and irradiation are approximately additive. The irradiation-induced changes in 2103/R3 and Fortiweld HS steels do not vary with position in the thickness of the plate. Different tempering treatments in Fortiweld HS steel do not change the extent of irradiation effects. Normal Charpy V-notch impact specimens and miniature specimens give the same irradiation-induced increase in transition temperature.

  8. Irradiation Effects at 160-240 deg C in Some Swedish Pressure Vessel Steels

    International Nuclear Information System (INIS)

    Grounes, M.; Myers, H.P.; Hannerz, N.E.

    1967-09-01

    Tensile specimens, Charpy impact specimens and miniature impact specimens of six steels in different conditions were irradiated to 2.8 x 10 18 and 5.6 x 10 18 n/cm 2 (> 1 MeV) at 160-240 deg C. The steels investigated were SIS 142103, 2103/R3, NO 345, Fortiweld, Fortiweld HS and OK 54 P. There is no correlation between the increase in transition temperature and initial transition temperature. However, changes in strength and ductility can be correlated to the initial yield strength. The increases in transition temperature due to strain aging and irradiation are approximately additive. The irradiation-induced changes in 2103/R3 and Fortiweld HS steels do not vary with position in the thickness of the plate. Different tempering treatments in Fortiweld HS steel do not change the extent of irradiation effects. Normal Charpy V-notch impact specimens and miniature specimens give the same irradiation-induced increase in transition temperature

  9. Synchrotron analysis of toughness anomalies in nanostructured bainite

    International Nuclear Information System (INIS)

    Fielding, L.C.D.; Jones, N.G.; Walsh, J.; Van Boxel, S.; Blackmur, M.S.; Lee, P.D.; Withers, P.J.; Stone, H.J.; Bhadeshia, H.K.D.H.

    2016-01-01

    High-resolution synchrotron X-ray diffraction has been used to characterise the notch root regions of Charpy impact test specimens of a superbainitic steel, both before and after loading. The changes in the volume fraction of austenite induced by the application of a three-point-bending load were quantified. Analysis of diffraction peak shifts revealed the extent of residual tensile and compressive strains present due to both machining and an applied load. The results lend support to the hypothesis that the comparatively low energies absorbed during Charpy impact testing of superbainitic steels, <7 J, are due to the formation of stress-induced martensite at the notch root, prior to crack initiation.

  10. Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

    Science.gov (United States)

    Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

    2018-01-17

    Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

  11. Band-notched spiral antenna

    Science.gov (United States)

    Jeon, Jae; Chang, John

    2018-03-13

    A band-notched spiral antenna having one or more spiral arms extending from a radially inner end to a radially outer end for transmitting or receiving electromagnetic radiation over a frequency range, and one or more resonance structures positioned adjacent one or more segments of the spiral arm associated with a notch frequency band or bands of the frequency range so as to resonate and suppress the transmission or reception of electromagnetic radiation over said notch frequency band or bands.

  12. Influence of Mo addition on the tempered properties of 13Cr martensitic stainless steel

    International Nuclear Information System (INIS)

    Jung, Byong Ho; Ahn, Yong Sik

    1998-01-01

    In order to investigate the effect of Mo addition on the mechanical properties of 13Cr-0.2C martensitic stainless steel, tensile test and Charpy V-notch test were performed after tempering at the temperature range of 200∼700 .deg. C following austenitizing at 1100 .deg. C. The yield strength and hardness of the steel were increased with the increase of Mo content at all tempering conditions, because Mo causes retardation of precipitation and coarsening of carbides and solid solution strengthening of matrix. Except 500 .deg. C of tempering temperature, the Charpy impact energy was significantly increased with Mo content and showed the highest value at 1.5 wt% addition. The increase of impact energy of the steel containing Mo is thought to be caused by δ-ferrite formed in the tempered martensitic matrix. At 500 .deg. C tempering, Charpy impact energy was decreased drastically due to temper embrittlement and it was not possible to prevent it even though Mo was added up to 1.5 wt%

  13. Effect of neutron irradiation on the impact properties of A533B steel

    International Nuclear Information System (INIS)

    Schubert, L.E.; Kumar, A.S.; Rosinski, S.T.; Hamilton, M.L.

    1994-01-01

    A new methodology is proposed to correlate the upper shelf energy (USE) of full size and subsize Charpy specimens of a nuclear reactor pressure vessel plate material, ASTM type A 533 Grade B (A533B) having a low USE (USE 19 n/cm 2 (E > 1 MeV) by 78 degree, 83 degree, and 70 degree C for full, half, and third size specimens, respectively. These shifts in DBTT appeared to be independent of specimen size and notch geometry

  14. Fractography evaluation of impact and tensile specimens from the HFBR [High Flux Beam Reactor

    International Nuclear Information System (INIS)

    Czajkowski, C.J.

    1989-10-01

    The Materials Technology Group of the Department of Nuclear Energy (DNE) at Brookhaven National Laboratory (BNL) has performed a fractographic examination of neutron irradiated and unirradiated tensile and Charpy ''V'' notch specimens. The evaluation was carried out using a scanning electron microscope (SEM) to evaluate the fracture mode. Photomicrographs were then evaluated to determine the extent of ductility present on the fracture surfaces of the unirradiated specimens. Ductility area measurements ranged from 4.6--9.5% on typical photomicrographs examined. 12 figs

  15. Detection of ductile crack initiation by acoustic emission testing

    International Nuclear Information System (INIS)

    Richter, H.; Boehmert, J.; Viehrig, H.W.

    1998-08-01

    A Charpy impact test equipment is described permitting simultaneous measurement of impact force, crack tip opening, acoustic emissions and magnetic emissions. The core of the equipment is an inverted pendulum ram impact testing machine and the tests have been performed with laterally notched, pre-fatigue ISO-V specimens made of steels of various strength and toughness properties. The tests are intended to ascertain whether the acoustic emission method is suitable for detecting steady crack initiation in highly ductile steels. (orig./CB) [de

  16. Neutron embrittlement of the reactor vessel in Borssele as determined from Charpy specimens

    International Nuclear Information System (INIS)

    Oosterkamp, W.J.; Dufour, L.B.

    1983-01-01

    Two sets of Charpy specimens have been retrieved from the reactor in the nuclear power plant at Borssele after two and four cycles of operation, respectively. The neutron fluxes at the sample positions and at the vessel wall have been calculated with a point-kernel method and S 2 calculations. The calculated fluxes at the two specimen positions are in fair agreement with fluences measured by threshold detectors. The Reference Temperature of Nil Ductility has been determined from the Charpy tests by a tan-h fit procedure. An extrapolation to a 40-year vessel life has been made on the basis of a square-root dependence of the change in the reference temperature with effective full-power years. Under these assumptions the heat-affected zone material will reach 296 K. The other materials will remain below 280 K. The vessel life therefore is not limited by embrittlement. (orig.)

  17. Analysis of the irradiation data for A302B and A533B correlation monitor materials

    International Nuclear Information System (INIS)

    Wang, J.A.

    1996-04-01

    The results of Charpy V-notch impact tests for A302B and A533B-1 Correlation Monitor Materials (CMM) listed in the surveillance power reactor data base (PR-EDB) and material test reactor data base (TR-EDB) are analyzed. The shift of the transition temperature at 30 ft-lb (T 30 ) is considered as the primary measure of radiation embrittlement in this report. The hyperbolic tangent fitting model and uncertainty of the fitting parameters for Charpy impact tests are presented in this report. For the surveillance CMM data, the transition temperature shifts at 30 ft-lb (ΔT 30 ) generally follow the predictions provided by Revision 2 of Regulatory Guide 1.99 (R.G. 1.99). Difference in capsule temperatures is a likely explanation for large deviations from R.G. 1.99 predictions. Deviations from the R.G. 1.99 predictions are correlated to similar deviations for the accompanying materials in the same capsules, but large random fluctuations prevent precise quantitative determination. Significant scatter is noted in the surveillance data, some of which may be attributed to variations from one specimen set to another, or inherent in Charpy V-notch testing. The major contributions to the uncertainty of the R.G. 1.99 prediction model, and the overall data scatter are from mechanical test results, chemical analysis, irradiation environments, fluence evaluation, and inhomogeneous material properties. Thus in order to improve the prediction model, control of the above-mentioned error sources needs to be improved. In general the embrittlement behavior of both the A302B and A533B-1 plate materials is similar. There is evidence for a fluence-rate effect in the CMM data irradiated in test reactors; thus its implication on power reactor surveillance programs deserves special attention

  18. Notch Inhibits Osteoblast Differentiation and Causes Osteopenia

    Science.gov (United States)

    Zanotti, Stefano; Smerdel-Ramoya, Anna; Stadmeyer, Lisa; Durant, Deena; Radtke, Freddy; Canalis, Ernesto

    2008-01-01

    Notch receptors are determinants of cell fate decisions. To define the role of Notch in the adult skeleton, we created transgenic mice overexpressing the Notch intracellular domain (NICD) under the control of the type I collagen promoter. First-generation transgenics were small and osteopenic. Bone histomorphometry revealed that NICD caused a decrease in bone volume, secondary to a reduction in trabecular number; osteoblast and osteoclast number were decreased. Low fertility of founder mice and lethality of young pups did not allow the complete establishment of transgenic lines. To characterize the effect of Notch overexpression in vitro, NICD was induced in osteoblasts and stromal cells from Rosanotch mice, in which a STOP cassette flanked by loxP sites is upstream of NICD, by transduction with an adenoviral vector expressing Cre recombinase (Cre) under the control of the cytomegalovirus (CMV) promoter (Ad-CMV-Cre). NICD impaired osteoblastogenesis and inhibited Wnt/β-catenin signaling. To determine the effects of notch1 deletion in vivo, mice in which notch1 was flanked by loxP sequences (notch1loxP/loxP) were mated with mice expressing Cre recombinase under the control of the osteocalcin promoter. Conditional null notch1 mice had no obvious skeletal phenotype, possibly because of rescue by notch2; however, 1-month-old females exhibited a modest increase in osteoclast surface and eroded surface. Osteoblasts from notch1loxP/loxP mice, transduced with Ad-CMV-Cre and transfected with Notch2 small interfering RNA, displayed increased alkaline phosphatase activity. In conclusion, Notch signaling in osteoblasts causes osteopenia and impairs osteo-blastogenesis by inhibiting the Wnt/β-catenin pathway. PMID:18420737

  19. Notch-strengthening in two-dimensional foams

    NARCIS (Netherlands)

    Onck, P.R.

    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

  20. Charpy impact test pada kampas rem hybrid komposit phenolic resin matrik dengan penguat serbuk basalt-Alumina-kulit kerang

    Directory of Open Access Journals (Sweden)

    I N. G. Suma Wijaya

    2017-03-01

    Full Text Available Abstrak: Penelitian ini adalah difokuskan untuk mengamati ketahanan impact dari material kampas rem kendaraan bermotor. Kampasrem yang diujikan adalah kampas yang terbuat dari material hybrid komposit dengan penguat serbuk basalt – serbuk kulitkerang dan alumina dan pengikat phenolic resin. Material kampas rem hibrid komposit diproses melalui proses sinteringdengan penekanan 2 ton, temperatur 150ºC selama 30 menit. Tujuan penelitian adalah menginvestigasi kekuatan impact daripada bahan hybrid komposit untuk masing – masing variasi terhadap perlakuan impact charpy yang didasarkan pada standarASTM D6110–04. Pengujian dilakukan dengan menganalisa nilai energy yang mampu diserap oleh bahan akibat bebanimpact, selanjutnya patahan impact charpy dianalisa dengan SEM. Diperoleh hasil pengujian charpy impact untuk masing –masing variasi hybrid komposit adalah nilai kekuatan yang tinggi terjadi pada hibrid komposit variasi 2 (HK2 dengan nilai0,000339547 J/mm2, ini disebabkan karena mempunyai ikatan antara metrik dan basalt yang lebih kuat dan sempurnadibandingkan dengan hibrid komposit lainnya. Untuk nilai hibrid komposit variasi 1 (HK1 adalah 0,000304851 J/mm², hibridkomposit variasi 3 (HK3 adalah 0,000334516 J/mm², hibrid komposit variasi 4 (HK4 adalah 0,000325059 J/mm², hibridkomposit variasi 5 (HK5 adalah 0,0003327 J/mm². (2 Dari perbandingan antara kampas rem dipasaran dengan kampas remhibrid komposit maka didapat nilai kekuatannya berbeda pada hibrid komposit variasi 2 (HK2 dengan kampas pembanding(KP yang memiliki nilai kekuatannya lebih besar yaitu, 0,000374867 J/mm².Kata kunci : Kampas rem, Impact charpy, Hibrid komposit, Basalt, Aluminium, Kulit Kerang Abstract: This research is focused to observe the impact resistance of motor vehicles brake lining material. Brake tested are canvasmade of hybrid composite materials with basalt powder reinforced – seashells, alumina powder, and a phenolic resin matrix.Hybrid composite brake

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

    NARCIS (Netherlands)

    Sjöqvist, M.; Antfolk, D.; Ferraris, S.; Rraklli, V.; Haga, C.; Antila, C.; Mutvei, A.; Imanishi, S.Y.; Holmberg, J.; Jin, S.; Eriksson, J.E.; Lendahl, U.; Sahlgren, C.M.

    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

  2. Notch filters for port-Hamiltonian systems

    NARCIS (Netherlands)

    Dirksz, D.A.; Scherpen, J.M.A.; van der Schaft, A.J.; Steinbuch, M.

    2012-01-01

    In this paper a standard notch filter is modeled in the port-Hamiltonian framework. By having such a port-Hamiltonian description it is proven that the notch filter is a passive system. The notch filter can then be interconnected with another (nonlinear) port-Hamiltonian system, while preserving the

  3. Structural integrity of water reactor pressure boundary components. Progress report ending 29 February 1976

    International Nuclear Information System (INIS)

    Loss, F.J.

    1976-01-01

    The report describes progress in the following areas: (a) fatigue crack propagation in reactor pressure vessel steels in an air environment, (b) dynamic fracture toughness of 1-in. (25-mm) and precracked Charpy-V bend specimens under impact loading, (c) postirradiation notch ductility and properties recovery in reactor vessel steels, (d) factors contributing to variable resistance of structural steels to radiation embrittlement, and (e) the initial program plan to investigate the phenomena of warm prestress and plastic net ligament in support of thermal shock studies

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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

  5. Instrumentation of a Charpy-pendulum. Additional data obtained from it and its application to nuclear reactor pressure vessels surveillance programs; Instrumentacion de un pendulo Charpy. Datos adicionales obtenidos a partir de la misma y su aplicacion a programas de vigilancia de centrales nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Chomik, Enrique P; Dhers, Horacio; Iorio, Antonio F [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Materiales; Ciriani, Dario F [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Combustibles Nucleares

    1999-07-01

    Charpy test gives information about a material dynamic fracture behavior. In a plain Charpy test, this information is the absorbed energy during fracture of the specimen, lateral deformation and the percentage of ductile fracture of the specimen. These parameters can then be used for the determination of the material response to a dynamic applied load, and are used at present to determine the brittle-ductile transition temperature of a material. However, there is a lot of additional information that can be obtained from a Charpy test, which is vital for the case of surveillance programs of nuclear power plants, where it is necessary to get the most available information from the specimens to be tested, because each one of them was irradiated for many years under temperature and neutronic flux conditions similar to that of the internal surface of the reactor pressure vessel, which converts these specimens in unique and very expensive ones. This additional information can be obtained from the curve that determines the evolution of the applied force to the specimen throughout the time involved in its fracture. It was possible to instrument a Charpy pendulum at a fraction of the cost necessary to buy an instrumentation package like the ones available in the market, and since the instrumentation equipment obtained is easy to transport. It has the additional advantage that can be used to instrument any other pendulum replacing only the hammer of the pendulum with a instrumented one for that pendulum. (author)

  6. Eddy current standards - Cracks versus notches

    Science.gov (United States)

    Hagemaier, D. J.; Collingwood, M. R.; Nguyen, K. H.

    1992-10-01

    Eddy current tests aimed at evaluating cracks and electron-discharge machined (EDM) notches in 7075-T6 aluminum specimens are described. A comparison of the shape and amplitude of recordings made from both transverse and longitudinal scans of small EDM notches and fatigue cracks showd almost identical results. The signal amplitude and phase angle increased with an increase of EDM notch and crak size. It is concluded that equivalent eddy current results obtained from similar-size surface cracks and notches in aluminum can be used to establish a desired sensitivity level for inspection.

  7. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

    Science.gov (United States)

    Bernasconi-Elias, P; Hu, T; Jenkins, D; Firestone, B; Gans, S; Kurth, E; Capodieci, P; Deplazes-Lauber, J; Petropoulos, K; Thiel, P; Ponsel, D; Hee Choi, S; LeMotte, P; London, A; Goetcshkes, M; Nolin, E; Jones, M D; Slocum, K; Kluk, M J; Weinstock, D M; Christodoulou, A; Weinberg, O; Jaehrling, J; Ettenberg, S A; Buckler, A; Blacklow, S C; Aster, J C; Fryer, C J

    2016-11-24

    Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

  8. DOL behaviour of end-notched beams

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  9. Effect of tempering temperature on the microstructure and mechanical properties of a reactor pressure vessel steel

    Energy Technology Data Exchange (ETDEWEB)

    Li, C.W.; Han, L.Z.; Luo, X.M.; Liu, Q.D.; Gu, J.F., E-mail: gujf@sjtu.edu.cn

    2016-08-15

    The microstructure and mechanical properties of reactor pressure vessel (RPV) steel were investigated after tempering at different temperatures ranging from 580 to 700 °C for 5 h. With increasing tempering temperature, the impact toughness, which is qualified by Charpy V-notch total absorbed energy, initially increases from 142 to 252 J, and then decreases to 47 J, with a maximum value at 650 °C, while the ultimate tensile strength varies in exactly the opposite direction. Comparing the microstructure and fracture surfaces of different specimens, the variations in toughness and strength with the tempering temperature were generally attributed to the softening of the bainitic ferrite, the agminated Fe{sub 3}C carbides that resulted from decomposition of martensite/austenite (M/A) constituents, the precipitation of Mo{sub 2}C carbides, and the newly formed M/A constituents at the grain boundaries. Finally, the correlation between the impact toughness and the volume fraction of the M/A constituents was established, and the fracture mechanisms for the different tempering conditions are explained. - Highlights: • The dependence of the deterioration of impact toughness on tempering temperature has been analysed. • The instrumented Charpy V-notch impact test has been employed to study the fracture mechanism. • The influence of M/A constituents on different fracture mechanisms based on the hinge model has been demonstrated. • A correlation between the mechanical properties and the amount of M/A constituents has been established.

  10. Biochemical characterization and cellular effects of CADASIL mutants of NOTCH3.

    Directory of Open Access Journals (Sweden)

    He Meng

    Full Text Available 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 muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4. R90C and C49Y mutant NOTCH3 form complexes which are more resistant to detergents than wild type NOTCH3 complexes. Using quantitative NOTCH3-luciferase clearance assays, we found significant inhibition of mutant NOTCH3 clearance. In coculture assays of NOTCH function, overexpressed wild type and mutant NOTCH3 significantly repressed NOTCH-regulated smooth muscle transcripts and potently impaired the activity of three independent smooth muscle promoters. Wildtype and R90C recombinant NOTCH3 proteins applied to cell cultures also blocked canonical Notch fuction. We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells.

  11. Analysis list: NOTCH1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NOTCH1 Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTC...H1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NOTCH1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  12. Impact strength of the uranium-6 weight percent niobium alloy between -1980 and +2000C

    International Nuclear Information System (INIS)

    Anderson, R.C.

    1981-09-01

    A study was conducted to determine if a ductile-to-brittle transition wxisted for the uranium-6 wt % niobium (U-6Nb) alloy. Standard V-notched Charpy bars were made from both solution-quenched and solution-quenched and aged U-6Nb alloy and were tested between -198 0 and +200 0 C. It was found that a sharp ductile-brittle transition does not exist for the alloy. A linear relationship existed between test temperature and impact strength, and the alloy retained a significant amount of impact strength even at very low temperatures. 9 figures

  13. Evaluation of fracture toughness in dental ceramics using indentation and SEVNB (Single Edge V-Notched Beam)-method; Avaliacao da tenacidade a fratura de ceramicas dentarias atraves do metodo de entalhe - SEVNB (Single Edge V-Notched Beam)

    Energy Technology Data Exchange (ETDEWEB)

    Santos, L.A.; Santos, C.; Souza, R.C.; Ribeiro, S. [Universidade de Sao Paulo (DEMAR/EEL/USP), Lorena, SP (Brazil). Escola de Engenharia de Lorena. Dept. de Engenharia de Materiais. Polo Urbo-Industrial; Strecker, K. [Universidade Federal de Sao Joao del-Rei (DME/UFSJ), MG (Brazil). Dept. de Materiais Eletricos; Oberacker, R. [Karlsruhe Univ. (Germany)

    2009-07-01

    In this work, the fracture toughness of different ceramics based on Al{sub 2}O{sub 3} and ZrO{sub 2} were evaluated using, comparatively two methods, Vickers indentation and SEVNB (Single Edge V-Notched Beam) method. Al{sub 2}O{sub 3}, ZrO{sub 2}(3%Y{sub 2}O{sub 3}) micro-particled and ZrO{sub 2}(3%Y{sub 2}O{sub 3}) nanometric, ZrO{sub 2}-Al{sub 2}O{sub 3} and Al{sub 2}O{sub 3}-ZrO{sub 2} composites were sintered at different temperatures. Samples were characterized by relative density, X-ray diffraction, SEM, and mechanical evaluation by hardness, bending strength and fracture toughness obtained by ickers indentation and SEVNB-method. The results were presented comparing the densification and microstructural results. Furthermore, the advantages and limitations of each method were discussed. (author)

  14. Dependence of hardness and impact energy on cooling time Δt8/5and temperature for S960QL

    OpenAIRE

    Samardžić, I.; Dunđer, M.; Vuherer, T.

    2015-01-01

    The paper deals with research into dependence of hardness and impact energy of thermal cycle simulated specimens of fine-grained structural steel S960QL on cooling time from 800 to 500 °C and on tested temperature. Results were obtained by measuring hardness of HV 10 and by experimental testing of Charpy notched tubes on instrumented Charpy hammer. Total impact energy, initiation energy and fracture propagation energy needed for occurrence of fracture is also elaborated. Key words:

  15. Survey of postirradiation heat treatment as a means to mitigate radiation embrittlement of reactor vessel steels

    International Nuclear Information System (INIS)

    Hawthorne, J.R.

    1979-01-01

    Nuclear-radiation service typically produces a progressive reduction in the notch ductility of low-alloy steels. The reduction is manifested by a decrease in Charpy-V (Csub(v)) upper-shelf energy level and by an elevation in temperature of the ductile-to-brittle transition. Post irradiation heat treatment (annealing) is being investigated as a method for the reversal of these detrimental radiation effects for reactor-vessel steels. This study was undertaken to analyze factors which could affect annealing response, report data available to qualify suspected influences on annealing, and summarize experimental results generated for many commercially produced reactor materials and companion materials produced in the laboratory

  16. 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.

  17. Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

    Science.gov (United States)

    Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

    2011-01-01

    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. PMID:21750738

  18. Evaluation of fracture toughness in dental ceramics using indentation and SEVNB (Single Edge V-Notched Beam)-method

    International Nuclear Information System (INIS)

    Santos, L.A.; Santos, C.; Souza, R.C.; Ribeiro, S.

    2009-01-01

    In this work, the fracture toughness of different ceramics based on Al 2 O 3 and ZrO 2 were evaluated using, comparatively two methods, Vickers indentation and SEVNB (Single Edge V-Notched Beam) method. Al 2 O 3 , ZrO 2 (3%Y 2 O 3 ) micro-particled and ZrO 2 (3%Y 2 O 3 ) nanometric, ZrO 2 -Al 2 O 3 and Al 2 O 3 -ZrO 2 composites were sintered at different temperatures. Samples were characterized by relative density, X-ray diffraction, SEM, and mechanical evaluation by hardness, bending strength and fracture toughness obtained by ickers indentation and SEVNB-method. The results were presented comparing the densification and microstructural results. Furthermore, the advantages and limitations of each method were discussed. (author)

  19. Notch Signaling: Piercing a Harness of Simplicity

    NARCIS (Netherlands)

    Helbig, Christina; Amsen, Derk

    2015-01-01

    The Notch pathway is an attractive therapeutic target for treatment of cancer and T cell-mediated pathology, but Notch inhibition leads to many side effects. Pinnell et al. (2015) demonstrate that oncogenic functions can be separated biochemically from other functions of Notch, opening new options

  20. Instrumentation of a Charpy-pendulum. Additional data obtained from it and its application to nuclear reactor pressure vessels surveillance programs

    International Nuclear Information System (INIS)

    Chomik, Enrique P.; Dhers, Horacio; Iorio, Antonio F.; Ciriani, Dario F.

    1999-01-01

    Charpy test gives information about a material dynamic fracture behavior. In a plain Charpy test, this information is the absorbed energy during fracture of the specimen, lateral deformation and the percentage of ductile fracture of the specimen. These parameters can then be used for the determination of the material response to a dynamic applied load, and are used at present to determine the brittle-ductile transition temperature of a material. However, there is a lot of additional information that can be obtained from a Charpy test, which is vital for the case of surveillance programs of nuclear power plants, where it is necessary to get the most available information from the specimens to be tested, because each one of them was irradiated for many years under temperature and neutronic flux conditions similar to that of the internal surface of the reactor pressure vessel, which converts these specimens in unique and very expensive ones. This additional information can be obtained from the curve that determines the evolution of the applied force to the specimen throughout the time involved in its fracture. It was possible to instrument a Charpy pendulum at a fraction of the cost necessary to buy an instrumentation package like the ones available in the market, and since the instrumentation equipment obtained is easy to transport. It has the additional advantage that can be used to instrument any other pendulum replacing only the hammer of the pendulum with a instrumented one for that pendulum. (author)

  1. Notch3 signalling promotes tumour growth in colorectal cancer.

    Science.gov (United States)

    Serafin, Valentina; Persano, Luca; Moserle, Lidia; Esposito, Giovanni; Ghisi, Margherita; Curtarello, Matteo; Bonanno, Laura; Masiero, Massimo; Ribatti, Domenico; Stürzl, Michael; Naschberger, Elisabeth; Croner, Roland S; Jubb, Adrian M; Harris, Adrian L; Koeppen, Hartmut; Amadori, Alberto; Indraccolo, Stefano

    2011-08-01

    Increased Notch1 activity has been observed in intestinal tumours, partially accomplished by β-catenin-mediated up-regulation of the Notch ligand Jagged-1. Whether further mechanisms of Notch activation exist and other Notch receptors might be involved is unclear. Microarray data indicated that Notch3 transcript levels are significantly up-regulated in primary and metastatic CRC samples compared to normal mucosa. Moreover, Notch3 protein was expressed at strong/moderate levels by 19.7% of 158 CRC samples analysed, and at weak levels by 51.2% of the samples. Intrigued by these findings, we sought to investigate whether Notch3 modulates oncogenic features of CRC cells. By exploiting xenografts of CRC cells with different tumourigenic properties in mice, we found that the aggressive phenotype was associated with altered expression of components of the Notch pathway, including Notch3, Delta-like 4 (DLL4), and Jagged-1 ligands. Stimulation with immobilized recombinant DLL4 or transduction with DLL4-expressing vectors dramatically increased Notch3 expression in CRC cells, associated with accelerated tumour growth. Forced expression of an active form of Notch3 mirrored the effects of DLL4 stimulation and increased tumour formation. Conversely, attenuation of Notch3 levels by shRNA resulted in perturbation of the cell cycle followed by reduction in cell proliferation, clonogenic capacity, and inhibition of tumour growth. Altogether, these findings indicate that Notch3 can modulate the tumourigenic properties of CRC cells and contributes to sustained Notch activity in DLL4-expressing tumours. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. A potentiometric biosensor for the detection of notch 3 using functionalized ZnO nanorods.

    Science.gov (United States)

    Ibupoto, Z H; Khun, K; Liu, X; Willander, M

    2014-09-01

    The notch signalling plays a vital and radical role for the activity of cellular proliferation, differentiation and apoptosis. In this study, for the first time a particular biosensor is developed for the detection of notch 3. ZnO nanorods were fabricated on the gold coated glass substrate by hydrothermal method and afterwards were decorated with the gold nanoparticles by electrodepositing technique. Scanning electron microscopy (SEM) has shown the perpendicular to the substrate growth pattern of ZnO nanorods. X-ray diffraction (XRD) studies showed the c-axis oriented growth direction with wurtzite crystal structure of ZnO nanorods. X-ray Photoelectron Spectroscopy (XPS) and energy dispersive X-ray (EDX) techniques have shown the presence of Zn, O and Au atoms in the prepared functional material. Furthermore, the anti-notch 3 was physically adsorbed on the gold nanoparticles functionalized ZnO nanorods. The developed potentiometric immunosensor has shown response to the wide range of notch 3 molecules. The detected range included 1.00 x 10(-5)-1.50 x 10(0 ) μg/mL with a sensitivity of 23.15 ± 0.31 mV/decade. The analytical parameters including reproducibility, stability, and selectivity were also investigated and the observed results indicate the acceptable performance of the notch 3 biosensor. Moreover, the proposed notch 3 biosensor exhibited a fast response time of 10 s.

  3. Excessive Anteversion Leads to Failure at 3 Years Due to Impingement as Evidenced by Twin Notches in Ti6A4V Stem

    Directory of Open Access Journals (Sweden)

    Thomas Donaldson

    2015-08-01

    Full Text Available A 63-year old female with bilateral hip replacements was referred to our clinic for pain and elevated metal ions. Her left hip had been revised earlier. The right hip had an SROM Ti6Al4V stem implanted with a 28mm head, a 28mm CoCr liner and Pinnacle Ti6Al4V shell. The patient reported pain, numbness, tingling, and repeated clicking and popping sensations with gait. She specifically noted that her hip would freeze while walking and could pop rising from a chair. Repeated metal ion levels showed Co (blood17ppb, Cr (serum 21ppb, and Ti (blood at 69ppb. CT-images of right hip revealed femoral stem anteversion was 43° and cup anteversion was 40°, for a combined anteversion of 83°. The right hip was revised 3.5 years postoperatively for persistent pain and elevated metal ions. At surgery, large twin notches were evident on her posterior femoral neck and 10mm-wide scalloped damage was evident in the rim of the Ti6A4V shell. SEM-imaging revealed contaminating layers on CoCr head containing elements Al, V and Ti. These indicated that titanium-alloy particles liberated by cup-to-neck impingements had transferred to the CoCr bearings. Our intent in this case was not to document that a MOM bearing produced impingement damage, because this case clearly implicated adverse surgical positioning. Rather, the intent was to document sequelae likely in a THA case that has a metal cup impinging on a metal femoral neck. In particular, twin notches on the femoral neck indicated that this patient was routinely impinging her Ti6Al4V shell against the Ti6Al4V neck and also subluxing her femoral head out of the cup. These signs are a clear indication that one or both components must be revised, as opposed to simply replacing the CoCr liner with a revision polyethylene liner.

  4. Charpy impact behavior of manganese-stabilized martensitic steels

    International Nuclear Information System (INIS)

    Hu, W.L.; Gelles, D.S.

    1986-05-01

    Tests were conducted to evaluate the irradiation-induced shift in ductile-to-brittle transition behavior of two manganese stabilized martensitic steels. Miniature Charpy specimens were fabricated from two heats of steel similar in composition to HT-9 but with 0.1% C and Mn contents ranging from 3.3 to 6.6.%. The 3.3% Mn steel showed a transition temperature similar to that of HT-9 in both the unirradiated condition and in specimens irradiated to 11.3 dpa. The steel containing 6.6% Mn exhibited a higher transition temperature after irradiation than the steel containing 3.3% Mn. The upper shelf energy (USE) after irradiation for the manganese stabilized alloys was much higher than for HT-9. 6 refs., 3 figs., 2 tabs

  5. Effects of helium on ductile brittle transition behavior of reduced activation ferritic steels after high concentration he implantation at high temperature

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, A.; Ejiri, M.; Nogami, S.; Ishiga, M.; Abe, K. [Tohoku Univ., Dept. of Quantum Science and Energy Engr, Sendai (Japan); Kasada, R.; Kimura, A. [Kyoto Univ., Institute of Advanced Energy (Japan); Jitsukawa, S. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan)

    2007-07-01

    Full text of publication follows: Influence of Helium (He) on fracture behavior of reduced activation ferritic/martensitic steels including Oxide Dispersion Strengthening (ODS) steels and F82H were examined. To study the He effects on fracture behavior of these steels after He bubble formation conditions, higher concentration of He implantation at around 550 C were performed and examined the relationship between microstructure evolution and fracture behavior of the steels. The 1.5CVN mini size Charpy specimens were used to evaluate impact test behavior. Reduced activation ferritic ODS steels, 9Cr-ODS and 12Cr-ODS steels were examine. F82H was also examined as reference material. Helium implantation was performed by a cyclotron of Tohoku University with a beam of 50 MeV {alpha}-particles at temperature around 550 C. A tandem-type energy degrader system was used to implant He into the specimen from the irradiated surface to the range of 50 MeV {alpha}-particles, that was about 380 {mu}m in iron. Implanted He concentration were about 1000 appm. Charpy impact test was performed using a instrumented impact test apparatus in Oarai branch of IMR, Tohoku University. Analyses of absorbed energy change and fracture surface were carried out. Vickers hardness test was also carried out on He implanted area of the 1.5CVN specimen to estimate irradiation hardening. Microstructural observation was performed by TEM. In the case of F82H, DBTT increased by the 1000 appm He implantation condition was about 80 C and grain boundary fracture surface was only observed in the He implanted area of all the ruptured specimens in brittle manner. On the other hand, DBTT shift and fracture mode change of He implanted 9Cr-ODS steel was not observed after He implantation. Microstructural observation showed that He bubble formation on the lath boundaries and grain boundaries were significant in F82H, but the bubble segregation on grain boundary in ODS steel was not apparent. The bubble formation

  6. Notch signaling and progenitor/ductular reaction in steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Carola M Morell

    Full Text Available Persistent hepatic progenitor cells (HPC activation resulting in ductular reaction (DR is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis.Steatohepatitis was generated using methionine-choline deficient (MCD diet. For hepatocyte lineage tracing, R26R-YFP mice were infected with AAV8-TBG-Cre.MCD diet promoted a strong HPC/DR response that progressively diffused in the lobule, and correlated with increased fibrosis and TGF-β1 expression. Notch signaling was unchanged in laser-capture microdissected HPC/DR, whereas Notch receptors were down regulated in hepatocytes. However, in-vivo lineage tracing experiments identified discrete hepatocytes showing Notch-1 activation and expressing (the Notch-dependent Sox9. Stimulation of AML-12 hepatocyte-cell line with immobilized Jag1 induced Sox9 and down-regulated albumin and BSEP expression. TGF-β1 treatment in primary hepatic stellate cells (HSC induced Jag1 expression. In MCD diet-fed mice, αSMA-positive HSC were localized around Sox9 expressing hepatocytes, suggesting that Notch activation in hepatocytes was promoted by TGF-β1 stimulated HSC. In-vivo Notch inhibition reduced HPC response and fibrosis progression.Our data suggest that Notch signaling is an important regulator of DR and that in steatohepatitis, hepatocytes exposed to Jag1-positive HSC, contribute to pathologic DR by undergoing Notch-mediated differentiation towards an HPC-like phenotype. Given the roles of Notch in fibrosis and liver cancer, these data suggest mesenchymal expression of Jag1 as an alternative therapeutic target.

  7. Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.

    Science.gov (United States)

    Chiang, Mark Y; Radojcic, Vedran; Maillard, Ivan

    2016-07-01

    This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein-protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. Notch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.

  8. 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.

  9. Rapid measurement of auditory filter shape in mice using the auditory brainstem response and notched noise.

    Science.gov (United States)

    Lina, Ioan A; Lauer, Amanda M

    2013-04-01

    The notched noise method is an effective procedure for measuring frequency resolution and auditory filter shapes in both human and animal models of hearing. Briefly, auditory filter shape and bandwidth estimates are derived from masked thresholds for tones presented in noise containing widening spectral notches. As the spectral notch widens, increasingly less of the noise falls within the auditory filter and the tone becomes more detectible until the notch width exceeds the filter bandwidth. Behavioral procedures have been used for the derivation of notched noise auditory filter shapes in mice; however, the time and effort needed to train and test animals on these tasks renders a constraint on the widespread application of this testing method. As an alternative procedure, we combined relatively non-invasive auditory brainstem response (ABR) measurements and the notched noise method to estimate auditory filters in normal-hearing mice at center frequencies of 8, 11.2, and 16 kHz. A complete set of simultaneous masked thresholds for a particular tone frequency were obtained in about an hour. ABR-derived filter bandwidths broadened with increasing frequency, consistent with previous studies. The ABR notched noise procedure provides a fast alternative to estimating frequency selectivity in mice that is well-suited to high through-put or time-sensitive screening. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

    Science.gov (United States)

    Fabbri, Giulia; Holmes, Antony B; Viganotti, Mara; Scuoppo, Claudio; Belver, Laura; Herranz, Daniel; Yan, Xiao-Jie; Kieso, Yasmine; Rossi, Davide; Gaidano, Gianluca; Chiorazzi, Nicholas; Ferrando, Adolfo A; Dalla-Favera, Riccardo

    2017-04-04

    Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival, and signal transduction. In particular, we show that NOTCH1 transactivates MYC via binding to B-cell-specific regulatory elements, thus implicating this oncogene in CLL development. These results significantly extend the role of NOTCH1 in CLL pathogenesis, and have direct implications for specific therapeutic targeting.

  11. Essential Role of Endothelial Notch1 in Angiogenesis

    Science.gov (United States)

    Limbourg, Florian P.; Takeshita, Kyosuke; Radtke, Freddy; Bronson, Roderick T.; Chin, Michael T.; Liao, James K.

    2009-01-01

    Background Notch signaling influences binary cell fate decisions in a variety of tissues. The Notch1 receptor is widely expressed during embryogenesis and is essential for embryonic development. Loss of global Notch1 function results in early embryonic lethality, but the cell type responsible for this defect is not known. Here, we identify the endothelium as the primary target tissue affected by Notch1 signaling. Methods and Results We generated an endothelium-specific deletion of Notch1 using Tie2Cre and conditional Notch1flox/flox mice. Mutant embryos lacking endothelial Notch1 died at approximately embryonic day 10.5 with profound vascular defects in placenta, yolk sac, and embryo proper, whereas heterozygous deletion had no effect. In yolk sacs of mutant embryos, endothelial cells formed a primary vascular plexus indicative of intact vasculogenesis but failed to induce the secondary vascular remodeling required to form a mature network of well-organized large and small blood vessels, which demonstrates a defect in angiogenesis. These vascular defects were also evident in the placenta, where blood vessels failed to invade the placental labyrinth, and in the embryo proper, where defective blood vessel maturation led to pericardial and intersomitic hemorrhage. Enhanced activation of caspase-3 was detected in endothelial and neural cells of mutant mice, which resulted in enhanced apoptotic degeneration of somites and the neural tube. Conclusions These findings recapitulate the vascular phenotype of global Notch1-/- mutants and indicate an essential cell-autonomous role of Notch1 signaling in the endothelium during vascular development. These results may have important clinical implications with regard to Notch1 signaling in adult angiogenesis. PMID:15809373

  12. Void coalescence and fracture behavior of notched and un-notched tensile tested specimens in fine grain dual phase steel

    Energy Technology Data Exchange (ETDEWEB)

    Saeidi, N., E-mail: navidsae@gmail.com [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Ashrafizadeh, F.; Niroumand, B. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Forouzan, M.R.; Mohseni mofidi, S. [Department of Mechanical Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Barlat, F. [Materials Mechanics Laboratory (MML), Graduate Institute of Ferrous Technology (GIFT), Pohang University of Science and Technology POSTECH, San 31 Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784 (Korea, Republic of)

    2015-09-17

    Due to growing global concern about the environmental issues, steel developers have been forced by automobile makers to produce more efficient steel grades with high strength to weight ratios along with high crashworthiness performance. In order to find deficiencies of the existing steels and develop superior steel products, detailed understanding of deformation and damage behavior in the existing steels is needed. In the present research, deformation and damage evolution during room temperature uniaxial tensile test of a modern high strength Dual Phase Steel, i.e. DP780, were studied. Detailed scanning electron microscopy (SEM) examination of the microstructures of notched and un-notched tensile fractured specimens revealed that in notched specimen, plastic deformation was concentrated more within the notched region. Therefore, much higher reduction in thickness with a high reduction gradient occurred in this region, In the un-notched specimen, however, plastic deformation was more uniformly distributed in larger parts of the gauge length, and therefore, thickness reduction happened with a lower gradient. Although geometric notch on the specimen did not change the void nucleation and growth mechanisms, the kinetics of these phenomena was influenced. On the other hand, voids linkage mechanism tended to change from void coalescence in the un-notched specimen to void sheeting in the notched specimen. Moreover, three different models developed by Brown & Embury (BM), Thomason and Pardoen were employed to predict the final fracture strain. It was revealed that, BM model showed much more accurate predictions for the studied DP steel in comparison with those of Thomason and Pardoens’ models.

  13. Void coalescence and fracture behavior of notched and un-notched tensile tested specimens in fine grain dual phase steel

    International Nuclear Information System (INIS)

    Saeidi, N.; Ashrafizadeh, F.; Niroumand, B.; Forouzan, M.R.; Mohseni mofidi, S.; Barlat, F.

    2015-01-01

    Due to growing global concern about the environmental issues, steel developers have been forced by automobile makers to produce more efficient steel grades with high strength to weight ratios along with high crashworthiness performance. In order to find deficiencies of the existing steels and develop superior steel products, detailed understanding of deformation and damage behavior in the existing steels is needed. In the present research, deformation and damage evolution during room temperature uniaxial tensile test of a modern high strength Dual Phase Steel, i.e. DP780, were studied. Detailed scanning electron microscopy (SEM) examination of the microstructures of notched and un-notched tensile fractured specimens revealed that in notched specimen, plastic deformation was concentrated more within the notched region. Therefore, much higher reduction in thickness with a high reduction gradient occurred in this region, In the un-notched specimen, however, plastic deformation was more uniformly distributed in larger parts of the gauge length, and therefore, thickness reduction happened with a lower gradient. Although geometric notch on the specimen did not change the void nucleation and growth mechanisms, the kinetics of these phenomena was influenced. On the other hand, voids linkage mechanism tended to change from void coalescence in the un-notched specimen to void sheeting in the notched specimen. Moreover, three different models developed by Brown & Embury (BM), Thomason and Pardoen were employed to predict the final fracture strain. It was revealed that, BM model showed much more accurate predictions for the studied DP steel in comparison with those of Thomason and Pardoens’ models

  14. Notch effects in uniaxial tension specimens

    International Nuclear Information System (INIS)

    Delph, T.J.

    1979-03-01

    Results of a literature survey on the effect of notches on the time-dependent failure of uniaxial tension specimens at elevated temperatures are presented. Particular attention is paid to the failure of notched specimens containing weldments

  15. 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 ...

  16. Charpy trend-curve development based on PWR surveillance date

    International Nuclear Information System (INIS)

    Guthrie, G.L.

    1983-01-01

    The formulas given in the text provide a useful method of predicting the irradiation induced increase in the 41 joule Charpy transition temperature for plate and weld material. The standard deviations for the least squares fits are 26.4 0 F for the weld equation and 15.6 0 F for the plat relationship. The current method of derivation produces an unbiased estimate of the fluence exponent, resulting in increased reliability for fluence extrapolations. The method given for error estimation provides a relatively rigorous procedure for calculating uncertainties and takes proper account of the effects of uncertainties in the independent variables in any given application of the formulas. 11 refs., 4 figs., 4 tabs

  17. Comparison between instrumented precracked Charpy and compact specimen tests of carbon steels

    International Nuclear Information System (INIS)

    Nanstad, R.K.

    1980-01-01

    The General Atomic Company High Temperature Gas-Cooled Reactor (HTGR) is housed within a prestressed concrete reactor vessel (PCRV). Various carbon steel structural members serve as closures at penetrations in the vessel. A program of testing and evaluation is underway to determine the need for reference fracture toughness (K/sub IR/) and indexing procedures for these materials as described in Appendix G to Section III, ASME Code for light water reactor steels. The materials of interest are carbon steel forgings (SA508, Class 1) and plates (SA537, Classes 1 and 2) as well as weldments of these steels. The fracture toughness behavior is characterized with instrumented precracked Charpy V-votch specimens (PCVN) - slow-bend and dynamic - and compact specimens (10-mm and 25-mm thicknesses) using both linear elastic (ASTM E399) and elastic-plastic (equivalent Energy and J-Integral) analytical procedures. For the dynamic PCVN tests, force-time traces are analyzed according to the procedures of the Pressure Vessel Research Council (PVRC)/Metal Properties Council (MPC). Testing and analytical procedures are discussed and PCVN results are compared to those obtained with compact specimens

  18. Effect of weld metal toughness on fracture behavior under ultra-low cycle fatigue loading (earthquake)

    Energy Technology Data Exchange (ETDEWEB)

    Kermajani, M. [School of Materials Engineering, College of Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ghaini, F. Malek, E-mail: Fmalek@modares.ac.ir [School of Materials Engineering, College of Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Miresmaeili, R. [School of Materials Engineering, College of Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Aghakouchak, A.A. [School of Civil Engineering, College of Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Shadmand, M. [Department of Research and Development, MAPNA Electric and Control (MECO) Company, Karaj (Iran, Islamic Republic of)

    2016-06-21

    Results from 12 ultra-low cycle fatigue tests performed on the weld metals of both toughness and non-toughness rated grades are presented. Fracture resistance under these loadings seemed to be dependent on materials' toughness, displacement amplitude, and stress state triaxiality, while the toughness effect was more highlighted at high stress levels and concentrations. To study the effect of microstructures on these failures, supporting ancillary tests including all-weld tension coupons, Charpy V-notched impact tests, and optical and scanning electron microscope analyses were performed. The favored microstructures appeared to be those which absorbed energy by plastic deformation and, hence, hindered void formation and/or could avoid crack propagation by deflection. Considering the response of the tested materials to cyclic loadings and the requirements of the materials specified in AISC341 Provisions could question the adequacy of these requirements for weld metals. However, the role of microstructural features like inclusions would be the same in both the Charpy impact tests and ultra-low cycle loadings.

  19. Degradation of impact fracture during accelerated aging of weld metal on microalloyed steel

    International Nuclear Information System (INIS)

    Vargas-Arista, B.; Hallen, J. M.; Albiter, A.; Angeles-Chavez, C.

    2008-01-01

    The effect of accelerated aging on the toughness and fracture of the longitudinal weld metal on an API5L-X52 line pipe steel was evaluated by Charpy V-notch impact test, fracture analysis and transmission electron microscopy. Aging was performed at 250 degree centigrade for 100 to 1000 h. The impact results indicated a significant reduction in the fracture energy and impact toughness as a function of aging time, which were achieved by the scanning electron microscope fractography that showed a decrease in the vol fraction of microvoids by Charpy ductile failure with the aging time, which favored the brittle fracture by transgranular cleavage. The minimum vol fraction of microvoids was reached at 500 h due to the peak aged. The microstructural analysis indicated the precipitation of transgranular iron nano carbides in the aged specimens, which was related to the deterioration of toughness and change in the ductile to brittle behavior. (Author) 15 refs

  20. The flow effect in the irradiation embrittlement in pressure vessel steels of nuclear power plants

    International Nuclear Information System (INIS)

    Kempf, Rodolfo A.; Cativa Tolosa, Sebastian; Fortis, Ana M.

    2009-01-01

    This paper deals with the advances in the study of the mechanical behavior of the Reactor Pressure Vessel steels under accelerate irradiations. The objective is to study the effect of lead factors on the interpretation of the mechanisms that induced the embrittlement of the RPV, like those of the reactors Atucha II and CAREM. It is described a device designed to irradiate Charpy specimens with V notch of SA-508 type 3 steel at power reactor temperature, installed in the RA-1 reactor. It is presented also an automatic digital image processing technique for partitioning Charpy fracture surface into regions with a clear physical meaning and appropriate for the work in hot cells. The aim is to obtain the fracture behavior of irradiated specimens with different lead factors in the range of high fluencies and to know the dependence with the composition of the alloy and with the diffusion of other alloy elements. (author)

  1. Degradation of impact fracture during accelerated aging of weld metal on microalloyed steel; Degradacion de la tenacidad al impacto durante el envejecimiento acelerado de soldadura en acero microaleado

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Arista, B.; Hallen, J. M.; Albiter, A.; Angeles-Chavez, C.

    2008-07-01

    The effect of accelerated aging on the toughness and fracture of the longitudinal weld metal on an API5L-X52 line pipe steel was evaluated by Charpy V-notch impact test, fracture analysis and transmission electron microscopy. Aging was performed at 250 degree centigrade for 100 to 1000 h. The impact results indicated a significant reduction in the fracture energy and impact toughness as a function of aging time, which were achieved by the scanning electron microscope fractography that showed a decrease in the vol fraction of microvoids by Charpy ductile failure with the aging time, which favored the brittle fracture by transgranular cleavage. The minimum vol fraction of microvoids was reached at 500 h due to the peak aged. The microstructural analysis indicated the precipitation of transgranular iron nano carbides in the aged specimens, which was related to the deterioration of toughness and change in the ductile to brittle behavior. (Author) 15 refs.

  2. Material properties characterization of low carbon steel using TBW and PWHT techniques in smooth-contoured and U-shaped geometries

    International Nuclear Information System (INIS)

    Aloraier, Abdulkareem S.; Joshi, Suraj; Price, John W.H.; Alawadhi, Khaled

    2013-01-01

    This paper investigates the effects of the temper bead welding (TBW) technique and post weld heat treatment (PWHT) on mechanical properties of multi-layer welding on low carbon steel specimens using Charpy V-notch impact testing and tensile testing. Several samples of two different weld geometries, viz. (i) smooth-contoured, and (ii) U-shaped were made with multiple bead layers using both TBW and PWHT techniques. Impact testing showed that at room temperature and below, TBW gave an impact toughness in the Heat Affected Zone (HAZ) better than both PWHT and the parent material. At temperatures higher than the room temperature but below 60 °C, PWHT gave better impact toughness in the HAZ. Above 60 °C, both TBW and PWHT showed impact toughness lower than that of the parent material. In tensile testing, both TBW and PWHT weld metal specimens produced acceptable results; however, TBW gave yield and tensile strengths closer to that of the actual material than PWHT. -- Highlights: • Effects of post weld heat treatment (PWHT) and temper bead welding (TBW) on properties are tested. • Charpy V-notch impact and tensile testing was performed on multi-layer welding of low carbon steel. • At room temperature and below, TBW gave better impact toughness than both PWHT and parent material. • Above room temperature but below 60 °C, PWHT gave better impact toughness than TBW. • Above 60 °C, both TBW and PWHT showed impact toughness lower than that of parent material

  3. Nuclear reactor pressure vessel surveillance capsule examinations. Application of American Society for Testing and Materials Standards

    International Nuclear Information System (INIS)

    Perrin, J.S.

    1978-01-01

    A series of pressure vessel surveillance capsules is installed in each commercial nuclear power plant in the United States. A capsule typically contains neutron dose meters, thermal monitors, tensile specimens, and Charpy V-notch impact specimens. In order to determine property changes of the pressure vessel resulting from irradiation, surveillance capsules are periodically removed during the life of a reactor and examined. There are numerous standards, regulations, and codes governing US pressure vessel surveillance capsule programmes. These are put out by the US Nuclear Regulatory Commission, the Boiler and Pressure Vessel Committee of the American Society of Mechanical Engineers, and the American Society for Testing and Materials (ASTM). A majority of the pertinent ASTM standards are under the jurisdiction of ASTM Committee E-10 on Nuclear Applications and Measurements of Radiation Effects. The standards, regulations, and codes pertaining to pressure vessel surveillance play an important role in ensuring reliability of the nuclear pressure vessels. ASTM E 185-73 is the Standard Recommended Practice for Surveillance Tests for Nuclear Reactors. This standard recommends procedures for both the irradiation and subsequent testing of surveillance capsules. ASTM E 185-73 references many additional specialized ASTM standards to be followed in specific areas of a surveillance capsule examination. A key element of surveillance capsule programmes is the Charpy V-notch impact test, used to define curves of fracture behaviour over a range of temperatures. The data from these tests are used to define the adjusted reference temperature used in determining pressure-temperature operating curves for a nuclear power plant. (author)

  4. Review of in-service thermal annealing of nuclear reactor pressure vessels

    International Nuclear Information System (INIS)

    Server, W.L.

    1984-01-01

    Radiation embrittlement of ferritic pressure vessel steels increases the ductile-brittle transition temperature and decreases the upper-shelf level of toughness as measured by Charpy impact tests. A thermal anneal cycle well above the normal operating temperature of the vessel can restore most of the original Charpy V-notch energy properties. A test reactor pressure vessel has been wet annealed at less than 343 0 C (650 0 F), and annealing of the Belgian BR-3 reactor vessel has recently taken place. An industry survey indicates that dry annealing a reactor vessel in-place is feasible, but solvable engineering problems do exist. The materials with highest radiation sensitivity in the older reactor vessels are submerged-arc weld metals with high copper and nickel concentrations. The limited Charpy V-notch and fracture toughness data available for five such welds were reviewed. The review suggested that significant recovery results from annealing at 454 0 C (850 0 F) for one week. Two of the main concerns with a localized heat treatment at 454 0 C (850 0 F) are the degree of distortion that may occur after the annealing cycle and the extent of residual stresses. A thermal and structural analysis of a reactor vessel for distortions and residual stresses found no problems with the reactor vessel itself but did indicate a rotation at the nozzle region of the vessel that would plastically deform the attached primary piping. Further analytical studies are needed. An American Society for Testing and Materials (ASTM) task group is upgrading and revising the ASTM Recommended Guide for In-Service Annealing of WaterCooled Nuclear Reactor Vessels (E 509-74) with emphasis on the materials and surveillance aspects of annealing rather than system engineering problems. System safety issues are the province of organizations other than ASTM (for example, the American Society of Mechanical Engineers Boiler and Pressure Vessel Code body)

  5. Correlation of irradiation-induced transition temperature increases from C sub v and K sub Jc /K sub Ic data

    Energy Technology Data Exchange (ETDEWEB)

    Hiser, A.L. (Materials Engineering Associates, Inc., Lanham, MD (USA))

    1990-03-01

    Reactor pressure vessel (RPV) surveillance capsules contain Charpy-V (C{sub v}) specimens, but many do not contain fracture toughness specimens; accordingly, the radiation-induced shift (increase) in the brittle-to-ductile transition region ({Delta}T) is based upon the {Delta}T determined from notch ductility (C{sub v}) tests. Since the ASME K{sub Ic} and K{sub IR} reference fracture toughness curves are shifted by the {Delta}T from C{sub v}, assurance that this {Delta}T does not underestimate {Delta}T associated with the actual irradiated fracture toughness is required to provide confidence that safety margins do not fall below assumed levels. To assess this behavior, comparisons of {Delta}T's defined by elastic-plastic fracture toughness and C{sub v} tests have been made using data from RPV base and weld metals in which irradiations were made under test reactor conditions. Using as-measure'' fracture toughness values (K{sub Jc}), average comparisons between {Delta}T(C{sub v}) and {Delta}T(K{sub Jc}) are: (a) All data: {Delta}T(K{sub Jc} 100 MPa{radical}{bar m}) = {Delta}T(C{sub v} 41 J) +10{degree}C; (b) Plates only: {Delta}T(K{sub Jc} 100 MPa{radical}{bar m}) = {Delta}T(C{sub v} 41 J) +15{degree}C; and (c) Welds only: {Delta}T(K{sub Jc} 100 MPa{radical}{bar m}) = {Delta}T(C{sub v} 41 J) {minus}1{degree}C. Fluence rate is found to have no significant effect on the relationship between {Delta}T(C{sub v}) and {Delta}T(K{sub Jc}). 12 refs., 12 figs., 5 tabs.

  6. Prediction of the brittle fracture toughness value of a RPV steel from the analysis of a limited set of Charpy results

    International Nuclear Information System (INIS)

    Forget, P.; Marini, B.; Verdiere, N.

    2001-01-01

    Our objective is to establish a method to be able to determine fracture toughness of a reactor pressure vessel (RPV) by using the small number of Charpy specimens used in the reactor surveillance program. Previous studies have shown that it is possible to determine fracture toughness from Charpy tests. Another point is to determine if statistical effects are compatible with a restricted number of specimens, this paper deals with this point and presents a methodology that is applicable to the case of irradiated materials from the surveillance program. Several conclusions can be drawn from this study: -) When determining failure parameters, we gain most accuracy by increasing the number of samples from 3 to about 6; -) it is possible to evaluate brittle fracture toughness using local approach, either by using Beremin or Renevey model; -) The effect of using a small number of Charpy specimens to determine fracture toughness in brittle fracture is evaluated. The error in the evaluation of fracture toughness is much smaller than the experimental dispersion itself. (A.C.)

  7. Specimen size effects in Charpy impact testing

    International Nuclear Information System (INIS)

    Alexander, D.J.; Klueh, R.L.

    1989-01-01

    Full-size , half-size, and third-size specimens from several different steels have been tested as part of an ongoing alloy development program. The smaller specimens permit more specimens to be made from small trail heats and are much more efficient for irradiation experiments. The results of several comparisons between the different specimen sizes have shown that the smaller specimens show qualitatively similar behavior to large specimens, although the upper-shelf energy level and ductile-to-ductile transition temperature are reduced. The upper-shelf energy levels from different specimen sizes can be compared by using a simple volume normalization method. The effect of specimen size and geometry on the ductile-to-ductile transition temperature is more difficult to predict, although the available data suggest a simple shift in the transition temperature due to specimen size changes.The relatively shallower notch used in smaller specimens alters the deformation pattern, and permits yielding to spread back to the notched surface as well as through to the back. This reduces the constraint and the peak stresses, and thus the initiation of cleavage is more difficult. A better understanding of the stress and strain distributions is needed. 19 refs., 3 figs., 3 tabs

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-20

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

  9. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  10. Magnetoresistance effect in permalloy nanowires with various types of notches

    Science.gov (United States)

    Gao, Y.; You, B.; Wang, J.; Yuan, Y.; Wei, L. J.; Tu, H. Q.; Zhang, W.; Du, J.

    2018-05-01

    Suppressing the stochastic domain wall (DW) motion in magnetic nanowires is of great importance for designing DW-related spintronic devices. In this work, we have investigated the pinning/depinning processes of DWs in permalloy nanowires with three different types of notches by using longitudinal magnetoresistance (MR) measurement. The averaged MR curves demonstrate that the stochastic DW depinning is suppressed partly or even completely by a transversely asymmetric notch. The single-shot MR curves show that how the resistance changes with the applied field also depends strongly on the notch type while the DW is pinned around the notch. In the case of two depinning fields, larger (smaller) change of resistance always corresponds to larger (smaller) depinning field, regardless of the notch type. These phenomena can be understood by that the spin structure around the notch changes differently with the notch type when the DW is traveling through the notch.

  11. 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

  12. Heavy-section steel irradiation program. Semiannual progress report, September 1993--March 1994

    International Nuclear Information System (INIS)

    Corwin, W.R.

    1995-04-01

    Maintaining the integrity of the reactor pressure vessel (RPV) in a light-water-cooled nuclear power plant is crucial in preventing and controlling severe accidents that have the potential for major contamination release. The RPV is the only component in the primary pressure boundary for which, if it should rupture, the engineering safety systems cannot assure protection from core damage. It is therefore imperative to understand and be able to predict the capabilities and limitations of the integrity inherent in the RPV. In particular, ft is vital to fully understand the degree of irradiation-induced degradation of the RPV's fracture resistance that occurs during service. The Heavy-Section Steel (HSS) Irradiation Program has been established; its primary goal is to provide a thorough, quantitative assessment of the effects of neutron irradiation on the material behavior, and in particular the fracture toughness properties of typical pressure-vessel steels, as they relate to light-water RPV integrity. The program includes the direct continuation of irradiation studies previously conducted within the HSS Technology Program augmented by enhanced examinations of the accompanying microstructural changes. During this period, the report on the duplex-type crack-arrest specimen tests from Phase 11 of the K la program was issued, and final preparations for testing the large, irradiated crack-arrest specimens from the Italian Committee for Research and Development of Nuclear Energy and Alternative Energies were completed. Tests on undersize Charpy V-notch (CVN) energy specimens in the irradiated and annealed weld 73W were completed. The results are described in detail in a draft NUREG report. In addition, the ORNL investigation of the embrittlement of the High Flux Isotope RPV indicated that an unusually large ratio of the high-energy gamma-ray flux to fast-neutron flux is most likely responsible for the apparently accelerated embrittlement

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

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    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.

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

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    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.

  15. High levels of Notch signaling down-regulate Numb and Numblike

    NARCIS (Netherlands)

    Chapman, G.; Liu, L.; Sahlgren, C.; Dahlqvist, C.; Lendahl, U.

    2006-01-01

    Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch,

  16. Magnetoresistance effect in permalloy nanowires with various types of notches

    Directory of Open Access Journals (Sweden)

    Y. Gao

    2018-05-01

    Full Text Available Suppressing the stochastic domain wall (DW motion in magnetic nanowires is of great importance for designing DW-related spintronic devices. In this work, we have investigated the pinning/depinning processes of DWs in permalloy nanowires with three different types of notches by using longitudinal magnetoresistance (MR measurement. The averaged MR curves demonstrate that the stochastic DW depinning is suppressed partly or even completely by a transversely asymmetric notch. The single-shot MR curves show that how the resistance changes with the applied field also depends strongly on the notch type while the DW is pinned around the notch. In the case of two depinning fields, larger (smaller change of resistance always corresponds to larger (smaller depinning field, regardless of the notch type. These phenomena can be understood by that the spin structure around the notch changes differently with the notch type when the DW is traveling through the notch.

  17. 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.

  18. The pathological significance of Notch1 in oral squamous cell carcinoma.

    Science.gov (United States)

    Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

    2013-10-01

    Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

  19. Testing of irradiated and annealed 15H2MFA materials

    International Nuclear Information System (INIS)

    Gillemot, F.; Uri, G.

    1994-01-01

    A set of surveillance samples made from 15H2MFA material has been studied in the laboratory of AEKI. Miniature notched tensile specimens were cut from some remnants of irradiated and broke surveillance charpy remnants. The Absorbed Specific Fracture Energy (ASFE) was measured on the specimens. A cutting machine and testing technique were elaborated for the measurements. The second part of the Charpy remnants was annealed at 460 deg. C and 490 deg. C for 6-8 hours. The specimens were tested similarity and the results were compared. (author). 5 refs, 9 figs

  20. A mechanical property and stress corrosion evaluation of VIM-ESR-VAR work strengthened and direct double aged Inconel 718 bar material

    Science.gov (United States)

    Montano, J. W.

    1986-01-01

    Presented are the mechanical properties and the stress corrosion resistance of triple melted vacuum induction melted (VIM), electro-slag remelted (ESR), and vacuum arc remelted (VAR), solution treated, work strengthened and direct double aged Inconel 718 alloy bars 4.00 in. (10.16) and 5.75 in. (14.60 cm) diameter. Tensile, charpy v-notched impact, and compact tension specimens were tested at ambient temperature in both the longitudinal and transverse directions. Longitudinal tensile and yield strengths in excess of 220 ksi (1516.85 MPa) and 200 ksi (1378.00 MPa) respectively, were realized at ambient temperature. Additional charpy impact and compact tension tests were performed at -100 F (-73 C). Longitudinal charpy impact strength equalled or exceeded 12.0 ft-lbs (16.3 Joules) at ambient and at -100 F(-73 C) while longitudinal compact (LC) tension fracture toughness strength remained above 79 ksi (86.80 MPa) at ambient and at -100 F(-73 C) temperatures. No failures occurred in the longitudinal or transverse tensile specimens stressed to 75 and 100 percent of their respective yield strengths and exposed to a salt fog environment for 180 days. Tensile tests performed after the stress corrosion test indicated no mechanical property degradation.

  1. Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina.

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    Galina Dvoriantchikova

    Full Text Available The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3 to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+ progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14 and postnatal day 0 (P0. To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5 and activators (Dll3, Atoh7, Otx2 of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05 more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors--since they heavily express both pro-ganglion cell (Atoh7

  2. Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

    Science.gov (United States)

    Gao, Wei; Sweeney, Catherine; Connolly, Mary; Kennedy, Aisling; Ng, Chin Teck; McCormick, Jennifer; Veale, Douglas J; Fearon, Ursula

    2012-07-01

    To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. Our

  3. 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...

  4. Expresión de los genes Serrate1 y Notch1 durante el desarrollo del tercio medio facial del embrión de pollo.

    Directory of Open Access Journals (Sweden)

    Daniel Mauricio Meza Lasso

    2016-01-01

    Full Text Available La vía de señalización Notch se caracteriza por mediar la comunicación célula-célula, regulando diferentes procesos celulares como proliferación, apoptosis y definición del destino celular. Esta vía ha sido implicada en el desarrollo de estructuras craneofaciales como paladar, diente y bóveda craneal. El objetivo de esta investigación fue identificar los patrones de expresión de los genes componentes de la vía Notch, Serrate1 y Notch1, durante el desarrollo del tercio medio facial. Se utilizaron embriones de pollo (Gallus gallus seleccionados de acuerdo a los criterios de Hamilton y Hamburger y sobre los cuales se realizó hibridación in situ con ribosondas marcadas con Digoxigenina (DIG, para luego ser detectadas con anticuerpos Anti-Dig. Los resultados mostraron expresión de los genes evaluados, en las prominencias maxilares (pmx y frontonasal (pfn durante el desarrollo del tercio medio facial. Estos resultados sugieren una probable participación de la vía Notch a través de estos genes, en los diferentes procesos celulares que determinan la morfogénesis y el desarrollo del tercio medio facial.

  5. 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.

  6. Plane-stress fields for sharp notches in pressure-sensitive materials

    International Nuclear Information System (INIS)

    Al-Abduljabbar, Abdulhamid

    2003-01-01

    The effect of pressure sensitive yield on materials toughness can be determined by investigating stress fields around cracks and notches. In this work, fully-developed plastic stress fields around sharp wedge-shaped notches of perfectly-plastic pressure-sensitive materials are investigated for plane-stress case and Mode 1 loading condition. The pressure-sensitive yielding behavior is represented using the Drucker-Prager criterion. Using equilibrium equations, boundary conditions, and the yield criterion, closed-form expressions for stress fields are derived. The analysis covers the gradual change in the notch angle and compares it with the limiting case of a pure horizontal crack. Effects of notch geometry and pressure sensitivity on stress fields are examined by considering different specimen geometries, as well as different levels of pressure sensitivity. Results indicate that while the stress values directly ahead of the notch-tip are not affected, the extent of stress sector at notch front is reduced, thereby causing increase in the radial stress value around the notch. As the pressure sensitivity increases the reduction of the stress sector directly ahead of the notch tip is more evident. Also, for high pressure sensitivity values, introduction of the notch angle reduces the variation of the stress levels. Results are useful for design of structural components. (author)

  7. 3D analyses of the effect of weld orientation in Charpy specimens

    DEFF Research Database (Denmark)

    Tvergaard, Viggo; Needleman, A.

    2004-01-01

    . The onset of cleavage is taken to occur when the average of the maximum principal stress over a specified volume attains a critical value. The weld analyzed here is overmatched, so that the yield strength for the weld is larger than that of the base material. Analyses are carried out for specimens where...... the notch is cut parallel to the surface of the test piece, as well as more complex geometries where the notched surface of the specimen is rotated relative to the surface of the test piece. It is found that even for a homogeneous material the brittle-ductile transition can be much affected by three...... dimensional effects; for example, curvature of the deformed free surface gives rise to a stress increase that promotes cleavage. Furthermore, for the rotated specimens the weld geometry relative to the notched specimen surface is so complex that only a full 3D analysis is able to account for the interaction...

  8. Modifiers of notch transcriptional activity identified by genome-wide RNAi

    Directory of Open Access Journals (Sweden)

    Firnhaber Christopher B

    2010-10-01

    Full Text Available Abstract Background The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription. Results Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components. Conclusions The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.

  9. On short cracks that depart from elastoplastic notch tips

    Directory of Open Access Journals (Sweden)

    Verônica Miquelin Machado

    2017-07-01

    Full Text Available The behavior of short cracks that depart from elastoplastic notch tips is modeled to estimate the stresses required to initiate and to propagate cracks in notched structural components, and to evaluate the size of tolerable crack-like defects under general loading conditions. This analysis can model both fatigue and environmentally assisted cracking problems; can evaluate notch sensitivity in both cases; and can as well be used to establish design or acceptance criteria for tolerable non-propagating crack-like defects in such cases. The growth of short cracks is assumed driven by the applied stresses and by the stress gradient ahead the notch tip, and supported by the material resistances to crack initiation and to long crack propagation by fatigue or EAC. In the elastoplastic case, the stress gradient ahead of the notch tip is quantified by a J-field to consider the short crack behavior. The tolerable short crack predictions made by this model are evaluated by suitable fatigue and EAC tests of notched specimens specially designed to start nonpropagating cracks from the notch tips, both under elastic and elastoplastic conditions.

  10. Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

    Science.gov (United States)

    Idowu, Jessica; Home, Trisha; Patel, Nisha; Magenheimer, Brenda; Tran, Pamela V; Maser, Robin L; Ward, Christopher J; Calvet, James P; Wallace, Darren P; Sharma, Madhulika

    2018-02-20

    Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

  11. Proteolytic regulation of Notch1 receptor activity in cancer

    NARCIS (Netherlands)

    van Tetering, Geert

    2011-01-01

    The Notch receptor is part of a highly conserved signaling pathway essential in development and disease in embryos and adults. Notch proteins coordinate cell-cell communication through receptor-ligand interactions between adjacent cells. First Notch is cleaved in the Golgi by furin at Site-1 (S1)

  12. Significance of a notch in the otoacoustic emission stimulus spectrum.

    Science.gov (United States)

    Grenner, J

    2012-09-01

    To explain a clinical observation: a notch in the stimulus spectrum during transient evoked otoacoustic emission measurement in ears with secretory otitis media. The effects of tympanic under-pressure were investigated using a pressure chamber. A model of the ear canal was also studied. Tympanic membrane reflectance increased as a consequence of increased stiffness, causing a notch in the stimulus spectrum. In an adult, the notch could be clearly distinguished at an under-pressure of approximately -185 daPa. The sound frequency of the notch corresponded to a wavelength four times the ear canal length. The ear canal of infants was too short to cause a notch within the displayed frequency range. The notch was demonstrated using both Otodynamics and Madsen equipment. A notch in the otoacoustic emission stimulus spectrum can be caused by increased stiffness of the tympanic membrane, raising suspicion of low middle-ear pressure or secretory otitis media. This finding is not applicable to infants.

  13. 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.

  14. Effect of microstructure on the susceptibility of a 533 steel to temper embrittlement

    International Nuclear Information System (INIS)

    Raoul, S.; Marini, B.; Pineau, A.

    1998-01-01

    In ferritic steels, brittle fracture usually occurs at low temperature by cleavage. However the segregation of impurities (P, As, Sn etc..) along prior γ grain boundaries can change the brittle fracture mode from transgranular to intergranular. In quenched and tempered steels, this segregation is associated with what is called the temper-embrittlement phenomenon. The main objective of the present study is to investigate the influence of the as-quenched microstructure (lower bainite or martensite) on the susceptibility of a low alloy steel (A533 cl.1) to temper-embrittlement. Dilatometric tests were performed to determine the continous-cooling-transformation (CCT) diagram of the material and to measure the critical cooling rate (V c ) for a martensitic quench. Then subsized Charpy V-notched specimens were given various cooling rates from the austenitization temperature to obtain a wide range of as-quenched microstructures, including martensite and bainite. These specimens were subsequently given a heat treatment to develop temper embrittlement and tested to measure the V-notch fracture toughness at -50 C. The fracture surfaces were examined by SEM. It is shown that martensitic microstructures are more susceptible to intergranular embrittlement than bainitic microstructures. These observed microstructural influences are briefly discussed. (orig.)

  15. Frequency and distribution of Notch mutations in tumor cell lines

    International Nuclear Information System (INIS)

    Mutvei, Anders Peter; Fredlund, Erik; Lendahl, Urban

    2015-01-01

    Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context. In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico. Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors. Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context. The online version of this article (doi:10.1186/s12885-015-1278-x) contains supplementary material, which is available to authorized users

  16. The importance of Notch signaling in peripheral T-cell lymphomas

    DEFF Research Database (Denmark)

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

    2014-01-01

    Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL...... cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment...... with Notch inhibitors has cytotoxic effects....

  17. Aplicación del ensayo miniatura de embutido para la evaluación de la tenacidad a temperaturas criogénicas de aceros inoxidables austeníticos envejecidos isotérmicamente

    Directory of Open Access Journals (Sweden)

    Saucedo-Muñoz, M. L.

    2003-10-01

    Full Text Available Two types of austenitic stainless steels JJl and JNl were isothermally aged at temperatures from 873 to 1173 K for 10 to 1000 min in order to study the microstructural evolution and its effect on fracture toughness at cryogenic temperatures. The Charpy V-Notch (CVN and Small-Punch (SPTesting methods were conducted at 77 K to evaluate the toughness of both solution treated and aged specimens. The fracture energy at 77 K determined for both methods showed a significant decrease with aging time for both steels. A linear correlation between the fracture energies of both methods was found. The intergranular precipitation of carbides and nitrides was responsible for the fracture toughness deterioration. The scanning electron microscope fractographs showed an intergranular brittle fracture and its fraction also increased with aging time and temperature. The presence of a more abundant intergranular precipitation resulted in a more rapid decrease in fracture toughness with aging time in JNl steel due to its higher content of C and N, compared to that of JJl steel.

    Dos tipos de aceros inoxidables austeníticos, JJl y JNl, se envejecieron isotérmicamente a temperaturas entre 873 y 1.173 K por tiempos de 10 a 1.000 min, para estudiar la evolución microestructural y su efecto sobre la tenacidad a la fractura a temperaturas criogénicas. Los métodos de ensayo de impacto Charpy y el ensayo miniatura de embutido se llevaron a cabo a 77 K para evaluar la tenacidad de las muestras tratadas térmicamente. La energía de fractura determinada por ambos métodos mostró una disminución con el tiempo de envejecido para ambos aceros. Se encontró una relación lineal entre ambos valores de energía. La precipitación intergranular de carburos y nitruros fue la responsable de la pérdida de la tenacidad en las muestras envejecidas. La fractografía indicó que la fractura intergranular se incrementa con la temperatura y el tiempo de envejecido. La presencia

  18. High NOTCH activity induces radiation resistance in non small cell lung cancer

    International Nuclear Information System (INIS)

    Theys, Jan; Yahyanejad, Sanaz; Habets, Roger; Span, Paul; Dubois, Ludwig; Paesmans, Kim; Kattenbeld, Bo; Cleutjens, Jack; Groot, Arjan J.; Schuurbiers, Olga C.J.; Lambin, Philippe; Bussink, Jan; Vooijs, Marc

    2013-01-01

    Background and purpose: Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance. Materials and methods: NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immunohistochemistry. Results: Patients with high NOTCH activity in tumors showed significantly worse disease-free survival. In vitro, NOTCH activity did not affect the proliferation or intrinsic radiosensitivity of NSCLC cells. In contrast, xenografts with blocked NOTCH activity grew slower than wild type tumors. Tumors with high NOTCH activity grew significantly faster, were more hypoxic and showed a radioresistant phenotype. Conclusions: We demonstrate an important role for NOTCH in tumor growth and correlate high NOTCH activity with poor prognosis and radioresistance. Blocking NOTCH activity in NSCLC might be a promising intervention to improve outcome after radiotherapy

  19. Notched audiograms and noise exposure history in older adults.

    Science.gov (United States)

    Nondahl, David M; Shi, Xiaoyu; Cruickshanks, Karen J; Dalton, Dayna S; Tweed, Ted S; Wiley, Terry L; Carmichael, Lakeesha L

    2009-12-01

    Using data from a population-based cohort study, we compared four published algorithms for identifying notched audiograms and compared their resulting classifications with noise exposure history. Four algorithms: (1) , (2) , (3) , and (4) were used to identify notched audiograms. Audiometric evaluations were collected as a part of the 10-yr follow-up examinations of the Epidemiology of Hearing Loss Study, in Beaver Dam, WI (2003-2005, N = 2395). Detailed noise exposure histories were collected by interview at the baseline examination (1993-1995) and updated at subsequent visits. An extensive history of occupational noise exposure, participation in noisy hobbies, and firearm usage was used to evaluate consistency of the notch classifications with the history of noise exposure. The prevalence of notched audiograms varied greatly by definition (31.7, 25.9, 47.2, and 11.7% for methods 1, 2, 3, and 4, respectively). In this cohort, a history of noise exposure was common (56.2% for occupational noise, 71.7% for noisy hobbies, 13.4% for firearms, and 81.2% for any of these three sources). Among participants with a notched audiogram, almost one-third did not have a history of occupational noise exposure (31.4, 33.0, 32.5, and 28.1% for methods 1, 2, 3, and 4, respectively), and approximately 11% did not have a history of exposure to any of the three sources of noise (11.5, 13.6, 10.3, and 7.6%). Discordance was greater in women than in men. These results suggest that there is a poor agreement across existing algorithms for audiometric notches. In addition, notches can occur in the absence of a positive noise history. In the absence of an objective consensus definition of a notched audiogram and in light of the degree of discordance in women between noise history and notches by each of these algorithms, researchers should be cautious about classifying noise-induced hearing loss by notched audiograms.

  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. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Mauro Di Ianni

    2018-04-01

    Full Text Available To investigate chronic lymphocytic leukemia (CLL-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs. In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  2. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

    Science.gov (United States)

    Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

    2018-01-01

    To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  3. Static and Fatigue Behavior Investigation of Artificial Notched Steel Reinforcement

    Directory of Open Access Journals (Sweden)

    Yafei Ma

    2017-05-01

    Full Text Available Pitting corrosion is one of the most common forms of localized corrosion. Corrosion pit results in a stress concentration and fatigue cracks usually initiate and propagate from these corrosion pits. Aging structures may fracture when the fatigue crack reaches a critical size. This paper experimentally simulates the effects of pitting morphologies on the static and fatigue behavior of steel bars. Four artificial notch shapes are considered: radial ellipse, axial ellipse, triangle and length-variable triangle. Each shape notch includes six sizes to simulate a variety of pitting corrosion morphologies. The stress-strain curves of steel bars with different notch shape and depth are obtained based on static tensile testing, and the stress concentration coefficients for various conditions are determined. It was determined that the triangular notch has the highest stress concentration coefficient, followed by length-variable triangle, radial ellipse and axial ellipse shaped notches. Subsequently, the effects of notch depth and notch aspect ratios on the fatigue life under three stress levels are investigated by fatigue testing, and the equations for stress range-fatigue life-notch depth are obtained. Several conclusions are drawn based on the proposed study. The established relationships provide an experimental reference for evaluating the fatigue life of concrete bridges.

  4. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    Directory of Open Access Journals (Sweden)

    Matthew R. Broadus

    2016-05-01

    Full Text Available Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD, which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box. We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.

  5. NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Hayashi, Yoshihiro; Osanai, Makoto; Lee, Gang-Hong

    2015-10-01

    The NOTCH family of membranous receptors plays key roles during development and carcinogenesis. Since NOTCH2, yet not NOTCH1 has been shown essential for murine hepatogenesis, NOTCH2 rather than NOTCH1 may be more relevant to human hepatocarcinogenesis; however, no previous studies have supported this hypothesis. We therefore assessed the role of NOTCH2 in human hepatocellular carcinoma (HCC) by immunohistochemistry and cell culture. Immunohistochemically, 19% of primary HCCs showed nuclear staining for NOTCH2, indicating activated NOTCH2 signaling. NOTCH2-positive HCCs were on average in more advanced clinical stages, and exhibited more immature cellular morphology, i.e. higher nuclear-cytoplasmic ratios and nuclear densities. Such features were not evident in NOTCH1‑positive HCCs. In human HCC cell lines, abundant NOTCH2 expression was associated with anaplasia, represented by loss of E-cadherin. When NOTCH2 signaling was stably downregulated in HLF cells, an anaplastic HCC cell line, the cells were attenuated in potential for in vitro invasiveness and migration, as well as in vivo tumorigenicity accompanied by histological maturation. Generally, inverse results were obtained for a differentiated HCC cell line, Huh7, manipulated to overexpress activated NOTCH2. These findings suggested that the NOTCH2 signaling may confer aggressive behavior and immature morphology in human HCC cells.

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

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2009-08-01

    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.

  7. 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...

  8. 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.

  9. 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'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

    Science.gov (United States)

    Platonova, Natalia; Manzo, Teresa; Mirandola, Leonardo; Colombo, Michela; Calzavara, Elisabetta; Vigolo, Emilia; Cermisoni, Greta Chiara; De Simone, Daria; Garavelli, Silvia; Cecchinato, Valentina; Lazzari, Elisa; Neri, Antonino; Chiaramonte, Raffaella

    2015-06-06

    The pathways of NOTCH and PI3K/AKT are dysregulated in about 60% and 48% of T-cell acute lymphoblastic leukemia (T-ALL) patients, respectively. In this context, they interact and cooperate in controlling tumor cell biology. Here, we propose a novel mechanism by which the PI3K/AKT pathway regulates NOTCH1 in T-ALL, starting from the evidence that the inhibition of PI3K/AKT signaling induced by treatment with LY294002 or transient transfection with a dominant negative AKT mutant downregulates NOTCH1 protein levels and activity, without affecting NOTCH1 transcription. We showed that the withdrawal of PI3K/AKT signaling was associated to NOTCH1 phosphorylation in tyrosine residues and monoubiquitination of NOTCH1 detected by Ubiquitin capture assay. Co-immunoprecipitation assay and colocalization analysis further showed that the E3 ubiquitin ligase c-Cbl interacts and monoubiquitinates NOTCH1, activating its lysosomal degradation. These results suggest that the degradation of NOTCH1 could represent a mechanism of control by which NOTCH1 receptors are actively removed from the cell surface. This mechanism is finely regulated by the PI3K/AKT pathway in physiological conditions. In pathological conditions characterized by PI3K/AKT hyperactivation, such as T-ALL, the excessive AKT signaling could lead to NOTCH1 signaling dysregulation. Therefore, a therapeutic strategy directed to PI3K/AKT in T-ALL could contemporaneously inhibit the dysregulated NOTCH1 signaling. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. The histone deacetylase HDAC1 positively regulates Notch signaling during Drosophila wing development

    Directory of Open Access Journals (Sweden)

    Zehua Wang

    2018-02-01

    Full Text Available The Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development. Depletion of HDAC1 causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.

  12. A three-dimensional analysis of the sigmoid notch

    Directory of Open Access Journals (Sweden)

    Evan D. Collins

    2011-12-01

    Full Text Available Fractures of the distal radius are among the most common injuries of the upper extremity, though treatment has traditionally focused on restoration of the radiocarpal joint and late sequelae may persist. X-ray imaging underestimates sigmoid notch involvement following distal radius fractures. No classification system exists for disruption patterns of the sigmoid notch of the radius associated with distal radius fractures. This study quantifies the anatomy of the sigmoid notch and identifies the landmarks of the articular surface and proximal boundaries of the distal radioulnar joint (DRUJ capsule. Computed tomography scans of freshly frozen cadaveric hands were used - followed by dissection, and three-dimensional reconstruction of the distal radius and sigmoid notch. The sigmoid notch surface was divided into two surfaces and measured. The Anterior Posterior (AP and Proximal Distal (PD widths of the articulating surface were reviewed, along with the radius of curvature, version angle and depth. The study showed that the sigmoid notch is flatter than previously believed - and only the distal 69% of its surface is covered by cartilage. On average, it has about nine degrees of retroversion, and its average inclination is almost parallel to the anatomical axis of the radius. Clinical implications exist for evaluation of the DRUJ involvement in distal radius fractures or degenerative diseases and for future development and evaluation of hemiarthroplasty replacement of the distal radius.

  13. Far infrared promotes wound healing through activation of Notch1 signaling.

    Science.gov (United States)

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  14. Mandibular Ramus Notching As a Tool for Sexual Dimorphism

    Directory of Open Access Journals (Sweden)

    Bibhuti Bhusana Panda

    2016-02-01

    Full Text Available Sex determination from a single or a part of bone is always difficult in absence of other bones of the same individual. The current study is an attempt to know the sex of an individual from the study of posterior ramus of mandible. The study was done from December, 2014 to August, 2015 in various Medical Colleges of the state of Odisha, India with the use of morbid anatomical specimen of mandibles and simple measuring instruments. The posterior ramus of adult mandibles were studied for presence or absence of any notching and if present its position in relation to occlusal plane. The study resulted, that there was a role of notch position in sex determination. The presence or absence of the notch though was not a consistent finding of all the mandibles. Males had frequent notching at the level of occlusal plane (P< 0.01 and females had frequent notching above the occlusal plane (P < 0.01. Notch present below the occlusal plane had no relation with sex. Accuracy of sexing mandible from the posterior ramus notch position was 61%, which was more for males (68.57% as compared to females (43.33%. So the posterior ramus of mandible could be considered for determination of sex of mandible but this should not be the sole criteria and should be correlated with the other standard criteria.

  15. 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.

  16. Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.

    Directory of Open Access Journals (Sweden)

    Hong-Mei Zhang

    Full Text Available Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.

  17. Effects of irradiation on strength and toughness of commercial LWR vessel cladding

    International Nuclear Information System (INIS)

    Haggag, F.M.; Corwin, W.R.; Alexander, D.J.; Nanstad, R.K.

    1987-01-01

    The potential for stainless steel cladding to improve the fracture behavior of an operating nuclear reactor pressure vessel, particularly during certain overcooling transients, may depend greatly on the properties of the irradiated cladding. Therefore, weld overlay cladding irradiated at temperatures and to fluences relevant to power reactor operation was examined. The cladding was applied to a pressure vessel steel plate by the three-wire series-arc commercial method. Cladding was applied in three layers to provide adequate thickness for the fabrication of test specimens. The three-wire series-arc procedure, developed by Combustion Engineering, Inc., Chattanooga, Tennessee, produced a highly controlled weld chemistry, microstructure, and fracture properties in all three layers of the weld. Charpy V-notch and tensile specimens were irradiated at 288 0 C to fluence levels of 2 and 5 x 10 19 neutrons/cm 2 (>1 MeV). Postirradiation testing results show that, in the test temperature range from -125 to 288 0 C, the yield strength increased by 8 to 30%, ductility insignificantly increased, while there was almost no change in ultimate tensile strength. All cladding exhibited ductile-to-brittle transition behavior during Charpy impact testing, due to the dominance of delta-ferrite failures at low temperatures. On the upper shelf, energy was reduced, due to irradiation exposure, 15 and 20%, while the lateral expansion was reduced 43 and 41%, at 2 and 5 x 10 19 neutrons/cm 2 (>1 MeV), respectively. In addition, radiation damage resulted in 13 and 28 0 C shifts of the Charpy impact transition temperature at the 41-J level for the low and high fluences, respectively

  18. Ductile growth of crack like flawing during hydrotest; Propagacao dutil de defeitos planares durante teste hidrostatico

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Jose C; Donato, Guilherme V [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES); Silva, Marcinei S. da; Bastian, Fernando L [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE); Lima, Romulo S. de [PETROBRAS/AB-RE, Rio de Janeiro, RJ (Brazil)

    2003-07-01

    In this paper effects of hydrostatic testing on ductile propagation of crack like flaw defects were evaluated in API X-60 steel. The model used was based on the J-tearing theory, supported by elastic - plastic fracture mechanics. The J-initiation resistance values (JIc) were determined by fracture mechanic tests using potential drop technique and compact test specimen. The JIc values were also determined from flow stress and Charpy V-notch at plateau, which are both usually available in mill-test data. Despite of being based on small database it seems it could be extended and it will be useful for future analysis. (author)

  19. Weldability of thermally grain-refined Fe-12Ni-0.25Ti for cryogenic structural applications

    International Nuclear Information System (INIS)

    Williams, D.E.

    1980-02-01

    The weldability of a research alloy designed for structural use in liquid helium temperature, cryogenic environments was investigated. Plates of iron-12 weight percent nickel-0.25 weight percent titanium were grain refined by the four-step, grain refining thermal treatment developed for this alloy and welded with Inconel Number 92 weld wire using the Gas Metal Arc (GMA) welding process with argon-15% helium gas shielding. Both a single pass and a double-sided, 2 pass electron beam (EB) weld were also made without filler metal addition. Weldments were radiographed and sectioned and the charpy V-notch specimens removed were tested at liquid nitrogen and helium temperatures

  20. Mechanical properties and examination of cracking in TMI-2 pressure vessel lower head material

    International Nuclear Information System (INIS)

    Diercks, D.R.; Neimark, L.A.

    1993-09-01

    Mechanical tests have been conducted on material from 15 samples removed from the lower head of the Three Mile Island unit 2 nuclear reactor pressure vessel. Measured properties include tensile properties and hardness profiles at room temperature, tensile and creep properties at temperatures of 600 to 1200 degrees C, and Charpy V-notch impact properties at -20 to +300 degrees C. These data, which were used in the subsequent analyses of the margin-to-failure of the lower head during the accident, are presented here. In addition, the results of metallographic and scanning electron microscope examinations of cladding cracking in three of the lower head samples are discussed

  1. Liability and lifetime of metallic components and structures

    International Nuclear Information System (INIS)

    Tanguy, B.

    2009-12-01

    In this overview of his research activity, the author describes the ductile damage process in structures subjected to high rate loadings, notably for tank steels and gas pipeline high resistance steels. Then, he describes the cleavage fracture process in bainitic steels by means of a local fracture approach. He proposes a modelling of the Charpy v-notch impact test of the resilience-to-toughness transition during the ductile-brittle transition for bainitic steels, the developed method being used to interpret resilience and toughness tests performed on an irradiated material. He finally discusses these works, describes the current ones, and discusses research perspectives within his Nuclear Material Department

  2. Half bead welding technique

    International Nuclear Information System (INIS)

    Canonico, D.A.; Holz, P.P.

    1978-05-01

    The ORNL has employed the Section XI half-bead procedure for six repair welds. Table 2 identifies the repairs and the components upon which they were accomplished. The weld repairs were performed to permit us to evaluate material properties, residual stresses, weld repair procedures, and structural behavior of repaired pressure vessels. As a consequence of our study we concluded that when the half bead procedure is correctly applied: (1) there is no metallurgical degradation of the base material, (2) residual stresses of yield point magnitude will be present, and (3) the structural integrity of the pressure vessel is not impaired at Charpy V-notch upper shelf temperatures

  3. Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

    Directory of Open Access Journals (Sweden)

    Floriane Auderset

    Full Text Available The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+ T helper (Th 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1 and Notch2 (N2 are expressed on activated CD4(+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

  4. 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.

  5. Femoral intercondylar notch shape and dimensions in ACL-injured patients

    NARCIS (Netherlands)

    van Eck, Carola F.; Martins, Cesar A. Q.; Vyas, Shail M.; Celentano, Umberto; van Dijk, C. Niek; Fu, Freddie H.

    2010-01-01

    The femoral intercondylar notch has been an anatomic site of interest as it houses the anterior cruciate ligament (ACL). The objective of this study was to arthroscopically evaluate the femoral notch in patients with known ACL injury. This evaluation included establishing a classification for notch

  6. Determination of ASTM 1016 structural welded joints fracture toughness through J integral

    International Nuclear Information System (INIS)

    Martins, Geraldo de Paula; Villela, Jefferson Jose; Terra, Jose Lucio; Rabello, Emerson Giovani; Martins, Geraldo Antonio Scoralick; Carneiro, Jose Rubens Goncalves

    2009-01-01

    Fracture toughness is an important parameter for studies of materials behavior in nuclear and conventional industry. Crack propagation resistance is, in general, evaluate using one of the fracture mechanics parameters K IC , for the case of the materials that exhibits a linear elastic behavior, the CTOD (crack tip opening displacement) and J IC , the critical value of J Integral, for the case of materials with elastic-plastic behavior. On this work the fracture mechanics parameters of the ASTM 1016 structural steel welded joints were obtained, using the J Integral. Charpy V tests at several temperatures were also obtained, with the purpose to obtain the curves of ductile-brittle of the regions of the welded joints: Base Metal, (MB), and Melted Zone (MZ). The joints were welded by Gas Metal Arc Welding (GMAW) with V bevel for evaluation the MZ toughness properties. The tests were accomplished at temperatures varying from -100 deg C to 100 deg C using the technical of compliance variation for J IC determination, the critical value that defines the initial stable crack growth, that applies to brittle and ductile materials. The J Integral alternative specimens has square cross section 10mmX10mm, according ASTM E 1820, with notch localized respectively at the BM and MZ. After the tests, the specimens fractured were analyzed in a scanning microscopic electronic (SME) for verification of the fracture surface. The fractography of the specimens at elevated temperatures presented dimples at the region of stable crack growth, characteristic of ductile fracture. The results of J Integral and Charpy V presented a good correlation between these two parameters. From these correlations it can be concluded that in some applications, the use Charpy V energy to infer fracture toughness can be substitute the Integral J tests. (author)

  7. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

    Directory of Open Access Journals (Sweden)

    Xun Yuan

    Full Text Available Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07 and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS to invasive cancer (OR=3.75; 95% CI, 1.8-7.78. Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43. Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

  8. A perspective on thermal annealing of reactor pressure vessel materials from the viewpoint of experimental results

    International Nuclear Information System (INIS)

    Iskander, S.K.; Sokolov, M.A.; Nanstad, R.K.

    1996-01-01

    It is believed that in the next decade or so, several nuclear reactor pressure vessels (RPVs) may exceed the reference temperature limits set by the pressurized thermal shock screening criteria. One of the options to mitigate the effects of irradiation on RPVs is to thermally anneal them to restore the toughness properties that have been degraded by neutron irradiation. This paper summarizes recent experimental results from work performed at the Oak Ridge National Laboratory to study the annealing response, or ''recovery'' of several irradiated RPV steels. The fracture toughness is one of the important properties used in the evaluation of the integrity of RPVs. Optimally, the fracture toughness is measured directly by fracture toughness specimens, such as compact tension or precracked Charpy specimens, but is often inferred from the results of Charpy V-notch impact specimens. The experimental results are compared to the predictions of models for embrittlement recovery which have been developed by Eason et al. Some of the issues in annealing that still need to be resolved are discussed

  9. Effect of aging on impact properties of ASTM A890 Grade 1C super duplex stainless steel

    International Nuclear Information System (INIS)

    Martins, Marcelo; Forti, Leonardo Rodrigues Nogueira

    2008-01-01

    Super duplex stainless steels in the solution annealed condition are thermodynamically metastable systems which, when exposed to heat, present a strong tendency to 'seek' the most favorable thermodynamic condition. The main purpose of this study was to characterize the microstructure of a super duplex stainless steel in the as cast and solution annealed conditions, and to determine the influence of aging heat treatments on its impact strength, based on Charpy impact tests applied to V-notched test specimens. The sigma phase was found to begin precipitating at heat treatment temperatures above 760 deg. C and to dissolve completely only above 1040 deg. C, with the highest peak concentration of this phase appearing at close to 850 deg. C. Heat treatments conducted at temperatures of 580 deg. C to 740 deg. C led to a reduction of the energy absorbed in the Charpy impact test in response to the precipitation of a particulate phase with particle sizes ranging from 0.5 μm to 1.0 μm, with a chromium and iron-rich chemical composition

  10. Functional studies on the role of Notch signaling in Hydractinia development.

    Science.gov (United States)

    Gahan, James M; Schnitzler, Christine E; DuBuc, Timothy Q; Doonan, Liam B; Kanska, Justyna; Gornik, Sebastian G; Barreira, Sofia; Thompson, Kerry; Schiffer, Philipp; Baxevanis, Andreas D; Frank, Uri

    2017-08-01

    The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAPT, a drug that inhibits Notch signaling. To address this apparent discrepancy, we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage-specific loss of Notch dependence in neurogenesis in hydrozoans. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. Cell proliferation control by Notch signalling during imaginal discs development in Drosophila

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    2015-02-01

    Full Text Available The Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.

  13. Optical stress investigations of notched bars with superimposed types of loads

    International Nuclear Information System (INIS)

    Richard, H.A.; Theis, W.

    1982-01-01

    Starting from the notch effect for various types of load, notch stresses are determined by optical methods for superimposed tensile and shearing stress and for superimposed tensile and bending stress. The superimposed stresses are induced by a device developed at the Technical Mechanics Department of Kaiserslautern University; only tensile stress needs to be applied to this testing device. The investigations have shown that in notched bars subject to superimposed tensile and shearing stress, stress increases will be higher than the maximum values of the two types of stress. For superimposed tensile and bending stress, notches on the outer side of the test piece and eccentric notches on the inner side may lead to a considerable stress increase. However, the stress distribution can be improved by an optimum arrangement of notches. (orig.) [de

  14. Stress intensity factors and weight functions for cracks in front of notches

    International Nuclear Information System (INIS)

    Fett, T.

    1993-12-01

    The knowledge of stress intensity factors for cracks at notch roots is important for the fracture mechanical treatment of real components. Stress intensity factor solutions are available only for special notches and externally applied loads. For the treatment of more complex loadings as thermal stresses near the notch root the weight function is needed in addition. In the first part of this report weight functions for cracks in front of internal notches are derived from stress intensity factor solutions under external loading available in the literature. The second part deals with cracks in front of edge notches. Limit cases of stress intensity factors are derived which allow to estimate stress intensity factors for cracks in front of internal elliptical notches with arbitrary aspect ratio of the ellipse and for external notches. (orig.) [de

  15. 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.

  16. Evaluation of ductile-brittle transition behavior with neutron irradiation in nuclear reactor pressure vessel steels using small punch test

    International Nuclear Information System (INIS)

    Kim, M. C.; Lee, B. S.; Oh, Y. J.

    2003-01-01

    A Small Punch (SP) test was performed to evaluate the ductile-brittle transition temperature before and after neutron irradiation in Reactor Pressure Vessel (RPV) steels produced by different manufacturing (refining) processes. The results were compared to the standard transition temperature shifts from the Charpy test and Master Curve fracture toughness test in accordance with the ASTM standard E1921. The samples were taken from 1/4t location of the vessel thickness and machined into a 10x10x0.5mm dimension. Irradiation of the samples was carried out in the research reactor at KAERI (HANARO) at about 290 .deg. C of the different fluence levels respectively. SP tests were performed in the temperature range of RT to -196 .deg. C using a 2.4mm diameter ball. For the materials before and after irradiation, SP transition temperatures (T sp ), which are determined at the middle of the upper and lower SP energies, showed a linear correlation with the Charpy index temperature, T 41J . T sp from the irradiated samples was increased as the fluence level increased and was well within the deviation range of the unirradiated data. The TSP had a correlation with the reference temperature (T 0 ) from the master curve method using a pre-cracked Charpy V-notched (PCVN) specimen

  17. Role of Notch Signaling in Human Breast Cancer Pathogenesis

    Science.gov (United States)

    2006-11-01

    transform HMLE cells. Similarly, overexpression of ErbB2, a receptor tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers ...Assess Notch-Ras cooperation in breast cancers in vivo: Since the major observation in this project has been the cooperation of Notch and Ras in HMLE ...metastasis. The in vitro cooperation between Notch and Ras in HMLE cells is mimicked in naturally arising breast cancers in vivo. Further dissection of the

  18. PTM Modeling of Dredged Suspended Sediment at Proposed Polaris Point and Ship Repair Facility CVN Berthing Sites - Apra Harbor, Guam

    Science.gov (United States)

    2017-09-01

    sedimentation outside of the channel footprint. For example, dredging near the edge of the footprint can be confined to time periods when tidal currents...Cases 1 or 2 due to the lower loss rate. Sedimentation rates outside the channel prism are further reduced because all sediment is introduced in the...ER D C/ CH L TR -1 7- 16 PTM Modeling of Dredged Suspended Sediment at Proposed Polaris Point and Ship Repair Facility CVN Berthing

  19. 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.

  20. 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.

  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. Notch inhibition counteracts Paneth cell death in absence of caspase-8.

    Science.gov (United States)

    Jeon, M K; Kaemmerer, E; Schneider, U; Schiffer, M; Klaus, C; Hennings, J; Clahsen, T; Ackerstaff, T; Niggemann, M; Schippers, A; Longerich, T; Sellge, G; Trautwein, C; Wagner, N; Liedtke, C; Gassler, N

    2018-05-16

    Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8 ∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8 ∆int mice. The secretory cell metaplasia in DBZ-treated casp8 ∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8 ∆int background. Our data suggest that casp8 acts in the intestinal Notch network.

  3. 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

    Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... 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...

  4. Evaluation of notch effects in low cycle fatigue of alloy 718 using critical distances

    Directory of Open Access Journals (Sweden)

    Eriksson Robert

    2018-01-01

    Full Text Available Gas turbine disks contain many notch-like features acting as stress raisers. The fatigue life based on the notch root stress may be overly conservative as the steep stress gradient in front of the notch may give rise to so-called notch support. In the current work, the theory of critical distances was applied to the prediction of the total fatigue life of low cycle fatigued, notched specimens made from alloy 718. The fatigue tests were performed at 450 °C and 550 °C. It was found that, for lives shorter than 5000–10000 cycles, the notched specimens had longer lives than would have been expected based on the notch root strain. For lives longer than 5000–10000 cycles, there were no notch support. The life prediction for notched specimens could be significantly improved by basing the prediction on the strain chosen some distance from the notch (the critical distance. An expression for calculating the critical distance based on the notch root strain was suggested.

  5. Effect of multiple repairs in girth welds of pipelines on the mechanical properties

    International Nuclear Information System (INIS)

    Vega, O.E.; Hallen, J.M.; Villagomez, A.; Contreras, A.

    2008-01-01

    This work presents the results of multiple weld repairs in the same area in seamless API X-52 microalloyed steel pipe. Four conditions of shielded metal arc welding repairs and one as-welded specimen of the girth weld were characterized to determine changes in the microstructure, grain size in the heat affected zone, and to evaluate their effect on the mechanical properties of the weld joints. The mechanical properties by means of tension tests, Charpy-V impact resistance and Vickers hardness of the welds were analyzed. The results indicate that significant changes are not generated in the microstructural constituents of the heat affected zone. Grain growth in the heat affected zone at the specimen mid-thickness with the number of repairs was observed. Tensile strength of the weld joints meets the requirement of the API 1104 standard even after the fourth weld repair. Significant reduction in Charpy-V impact resistance with the number of weld repairs was found when the notch location was in the intersection of the fusion line with the specimen mid-thickness. A significant increase in the Vickers hardness of the heat affected zone occurred after the first repair and a gradual decrease in the Vickers hardness occurred as the number of repairs increases

  6. Visual interface for the automation of the instrumented pendulum of Charpy tests used in the surveillance program of reactors vessel of nuclear power plants; Interfase visual para la automatizacion del pendulo instrumentado de pruebas Charpy utilizado en el programa de vigilancia de la vasija de reactores de centrales nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Rojas S, A.S.; Sainz M, E.; Ruiz E, J.A. [ININ, Carretera Mexico-Toluca Km.36.5, Mpio. de Ocoyoacac, Estado de Mexico (Mexico)]. E-mail: asrs@nuclear.inin.mx; esm@nuclear.inin.mx; jare@nuclear.inin.mx

    2004-07-01

    Inside the Programs of Surveillance of the nuclear power stations periodic information is required on the state that keep the materials with those that builds the vessel of the reactor. This information is obtained through some samples or test tubes that are introduced inside the core of the reactor and it is observed if its physical characteristics remain after having been subjected to the radiation changes and temperature. The rehearsal with the instrumented Charpy pendulum offers information on the behavior of fracture dynamics of a material. In the National Institute of Nuclear Research (ININ) it has an instrumented Charpy pendulum. The operation of this instrument is manual, having inconveniences to carry out rehearsals with radioactive material, handling of high and low temperatures, to fulfill the normative ones for the realization of the rehearsals, etc. In this work the development of a computational program is presented (virtual instrument), for the automation of the instrumented pendulum. The system has modules like: Card of data acquisition, signal processing, positioning system, tempered system, pneumatic system, compute programs like it is the visual interface for the operation of the instrumented Charpy pendulum and the acquisition of impact signals. This system shows that given the characteristics of the nuclear industry with radioactive environments, the virtual instrumentation and the automation of processes can contribute to diminish the risks to the personnel occupationally exposed. (Author)

  7. Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.

    Science.gov (United States)

    Shaya, Oren; Binshtok, Udi; Hersch, Micha; Rivkin, Dmitri; Weinreb, Sheila; Amir-Zilberstein, Liat; Khamaisi, Bassma; Oppenheim, Olya; Desai, Ravi A; Goodyear, Richard J; Richardson, Guy P; Chen, Christopher S; Sprinzak, David

    2017-03-13

    During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area. This relationship extends across contact diameters ranging from micrometers to tens of micrometers. Mathematical modeling predicts that dependence of signaling on contact area can bias cellular differentiation in Notch-mediated lateral inhibition processes, such that smaller cells are more likely to differentiate into signal-producing cells. Consistent with this prediction, analysis of developing chick inner ear revealed that ligand-producing hair cell precursors have smaller apical footprints than non-hair cells. Together, these results highlight the influence of cell morphology on fate determination processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Partial-Isothermally-Treated Low Alloy Ultrahigh Strength Steel with Martensitic/Bainitic Microstructure

    Science.gov (United States)

    Luo, Quanshun; Kitchen, Matthew; Patel, Vinay; Filleul, Martin; Owens, Dave

    We introduce a new strengthening heat treatment of a Ni-Cr-Mo-V alloyed spring steel by partial isothermal salt-bath and subsequent air-cooling and tempering. Detailed isothermal treatments were made at temperatures below or above the Ms point (230°C). The salt bath time was controlled between 10 and 80 minutes. Through the new treatment, the candidate steel developed ultrahigh tensile strength 2,100 MPa, yield strength 1,800 MPa, elongation 8-10 %, hardness 580-710 HV, and V-notch Charpy toughness 10-12 J. Optical and electron microscopic observations and X-ray diffraction revealed multi-phase microstructures of bainitic/martensitic ferrites, fine carbide precipitates and retained austenite. Carbon partitioning during the bainitic/martensitic transformation was investigated for its remarkable influence on the strengthening mechanism.

  9. Effect of notch and alloying on steel properties during extension

    International Nuclear Information System (INIS)

    Vinokur, B.B.; Pilyushenko, U.L.; Kasatkin, O.G.

    1985-01-01

    A study was made on change of strength and plastic characteristics during extension of notched steel samples of 15 compositions containing often-used alloying elements in various amounts and combinations. The notch causes increase of strength and decrease of plastic properties of structural steels during extension. The most pronounced change of properties takes place for the notched sample with expansion angle close to 180 deg. Reduction of notch expansion angle below 150 deg causes slower decrease of the rate of property change. Nickel alloying and vanadium, titanium microalloying assist the improvement of steel plasticity despite the increase of strength properties. Introduction of these elements in steel compensate partially for the negative notch effect. Alloying by silicon, molybdenum and tungsten results in steel strengthening and chromium alloying causes some loss of strength. Manse, chromium, silicon, molybdenum and tungsten cause decrease of plasticity, which intensifies the negative notch effect. When determining concentration ranges of carbon and alloying elements within the limits of quality composition it is necessary to consider both technology and possibility of sufficient change of properties especially in the case of stress concentrator presence in structures

  10. Insensible is a novel nuclear inhibitor of Notch activity in Drosophila.

    Directory of Open Access Journals (Sweden)

    Franck Coumailleau

    Full Text Available Notch signalling regulates a wide range of developmental processes. In the Drosophila peripheral nervous system, Notch regulates a series of binary fate decisions that lead to the formation of regularly spaced sensory organs. Each sensory organ is generated by single sensory organ precursor cell (SOP via a series of asymmetric cell divisions. Starting from a SOP-specific Cis-Regulatory Module (CRM, we identified insensible (insb, a.k.a CG6520, as a SOP/neuron-specific gene encoding a nuclear factor that inhibits Notch signalling activity. First, over-expression of Insb led to the transcriptional repression of a Notch reporter and to phenotypes associated with the inhibition of Notch. Second, while the complete loss of insb activity had no significant phenotype, it enhanced the bristle phenotype associated with reduced levels of Hairless, a nuclear protein acting as a co-repressor for Suppressor of Hairless. In conclusion, our work identified Insb as a novel SOP/neuron-specific nuclear inhibitor of Notch activity in Drosophila.

  11. Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer.

    Science.gov (United States)

    Yi, Fuming; Amarasinghe, Baru; Dang, Thao P

    2013-01-01

    Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch's response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.

  12. 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.

  13. Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states.

    Science.gov (United States)

    LeBon, Lauren; Lee, Tom V; Sprinzak, David; Jafar-Nejad, Hamed; Elowitz, Michael B

    2014-09-25

    The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.

  14. Study of crack propagation mechanisms during Charpy impact toughness tests on both equiaxed and lamellar microstructures of Ti–6Al–4V titanium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Buirette, Christophe, E-mail: christophe.buirette@ensiacet.fr [Institut Carnot CIRIMAT, ENSIACET, 4 allée Emile Monso, 31030 Toulouse (France); Huez, Julitte, E-mail: julitte.huez@ensiacet.fr [Institut Carnot CIRIMAT, ENSIACET, 4 allée Emile Monso, 31030 Toulouse (France); Gey, Nathalie, E-mail: Nathalie.gey@univ-lorraine.fr [Laboratoire d’Etude des Microstructures et de Mécanique des Matériaux (LEM3), UMR CNRS 7239, Université de Lorraine, Île du Saulcy, 57045 METZ Cedex 1 (France); DAMAS, Laboratory of Excellence on Design of Alloy Metals for Low-Mass Structures, Université de Lorraine (France); Vassel, Alain, E-mail: alain.vassel@titane.asso.fr [Association Française du Titane, 16 quai Ernest Renaud, BP 70515, 44105 Nantes Cedex 4 (France); Andrieu, Eric, E-mail: eric.andrieu@ensiacet.fr [Institut Carnot CIRIMAT, ENSIACET, 4 allée Emile Monso, 31030 Toulouse (France)

    2014-11-17

    The impact toughness of two highly textured rolled plates of Ti–6Al–4V alloy with an α equiaxed and an α lamellar microstructures has been investigated. The results show a strong anisotropy of the fracture energy for both materials and underline that a coincidence of the prismatic planes with the shear bands at the notch tip is favorable for higher fracture energies. Moreover, it is pointed out, as it was already done by previous studies, that the α lamellar microstructure presents higher fracture energy than the α equiaxed one. Thanks to electron back scattering diffraction, and tensile tests, local microstructure heterogeneities, called macrozones, have been observed and characterized. Their size depends on microstructure element and is larger for α lamellar microstructure than for the α equiaxed. High strain is localized on the macrozones favorably oriented for prismatic slip with respect to the direction of impact and leads to a particular dimple free zone on the fracture surface. The contribution of these macrozones in the fracture behavior, and more precisely on the crack propagation rate was evaluated; thus the effects of the macroscopic texture and of the microstructure element on the impact toughness are discussed separately.

  15. 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.

  16. Effect of microstructure on the susceptibility of a 533 steel to temper embrittlement

    Energy Technology Data Exchange (ETDEWEB)

    Raoul, S.; Marini, B. [CEA Centre d`Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service de Recherches Metallurgiques Appliquees; Pineau, A. [CNRS, Evry (France). Centre de Materiaux

    1998-11-01

    In ferritic steels, brittle fracture usually occurs at low temperature by cleavage. However the segregation of impurities (P, As, Sn etc..) along prior {gamma} grain boundaries can change the brittle fracture mode from transgranular to intergranular. In quenched and tempered steels, this segregation is associated with what is called the temper-embrittlement phenomenon. The main objective of the present study is to investigate the influence of the as-quenched microstructure (lower bainite or martensite) on the susceptibility of a low alloy steel (A533 cl.1) to temper-embrittlement. Dilatometric tests were performed to determine the continous-cooling-transformation (CCT) diagram of the material and to measure the critical cooling rate (V{sub c}) for a martensitic quench. Then subsized Charpy V-notched specimens were given various cooling rates from the austenitization temperature to obtain a wide range of as-quenched microstructures, including martensite and bainite. These specimens were subsequently given a heat treatment to develop temper embrittlement and tested to measure the V-notch fracture toughness at -50 C. The fracture surfaces were examined by SEM. It is shown that martensitic microstructures are more susceptible to intergranular embrittlement than bainitic microstructures. These observed microstructural influences are briefly discussed. (orig.) 11 refs.

  17. TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells

    Directory of Open Access Journals (Sweden)

    Lee Norman H

    2010-07-01

    Full Text Available Abstract Background The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11 is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Results Global gene expression profiling after downregulation of TLX1 and inhibition of the NOTCH pathway in ALL-SIL cells revealed that TLX1 synergistically regulated more than 60% of the NOTCH-responsive genes. Structure-function analysis demonstrated that TLX1 binding to Groucho-related TLE corepressors was necessary for maximal transcriptional regulation of the NOTCH-responsive genes tested, implicating TLX1 modulation of the NOTCH-TLE regulatory network. Comparison of the dataset to publicly available biological databases indicated that the TLX1/NOTCH-coregulated genes are frequently targeted by MYC. Gain- and loss-of-function experiments confirmed that MYC was an essential mediator of TLX1/NOTCH transcriptional output and growth promotion in ALL-SIL cells, with TLX1 contributing to the NOTCH-MYC regulatory axis by posttranscriptional enhancement of MYC protein levels. Functional classification of the TLX1/NOTCH-coregulated targets also showed enrichment for genes associated with other human cancers as well as those involved in developmental processes. In particular, we found that TLX1, NOTCH and MYC coregulate CD1B and RAG1, characteristic markers of early cortical thymocytes, and that concerted downregulation of the TLX1 and NOTCH pathways resulted in their irreversible repression. Conclusions We found that TLX1 and NOTCH synergistically regulate transcription in T-ALL, at least in part via the sharing of a TLE corepressor and by augmenting expression of MYC. We conclude that

  18. Generic analyses for evaluation of low Charpy upper-shelf energy effects on safety margins against fracture of reactor pressure vessel materials

    International Nuclear Information System (INIS)

    Dickson, T.L.

    1993-07-01

    Appendix G to 10 CFR Part 50 requires that reactor pressure vessel beltline material maintain Charpy upper-shelf energies of no less than 50 ft-lb during the plant operating life, unless it is demonstrated in a manner approved by the Nuclear Regulatory Commission (NRC), that lower values of Charpy upper-shelf energy provide margins of safety against fracture equivalent to those in Appendix G to Section XI of the ASME Code. Analyses based on acceptance criteria and analysis methods adopted in the ASME Code Case N-512 are described herein. Additional information on material properties was provided by the NRC, Office of Nuclear Regulatory Research, Materials Engineering Branch. These cases, specified by the NRC, represent generic applications to boiling water reactor and pressurized water reactor vessels. This report is designated as HSST Report No. 140

  19. The Role of Notch Signaling Pathway in Breast Cancer Pathogenesis

    Science.gov (United States)

    2005-07-01

    breast cancer cells, I tested whether ErbB2 overexpression will cooperate with Notch in HMLE cells. While overexpression of activated Notch1 failed to...tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers , also failed to transform HMLE cells. These observations suggested...cooperation between Notch1IC and ErbB2 signaling in transforming HMLE cells. Breast cancers typically do not harbor oncogenic Ras mutations; nevertheless

  20. Mechanical properties of 1950's vintage 304 stainless steel weldment components after low temperature neutron irradiation

    International Nuclear Information System (INIS)

    Sindelar, R.L.; Caskey, G.R. Jr.; Thomas, J.K.; Hawthorne, J.R.; Hiser, A.L.; Lott, R.A.; Begley, J.A.; Shogan, R.P.

    1991-01-01

    The reactor vessels of the nuclear production reactors at the Savannah River Site (SRS) were constructed in the 1950's from Type 304 stainless steel plates welded with Type 308 stainless steel filler using the multipass metal inert gas process. An irradiated mechanical properties database has been developed for the vessel with materials from archival primary coolant system piping irradiated at low temperatures (75 to 150 degrees C) in the State University of New York at Buffalo reactor (UBR) and the High Flux Isotope Reactor (HFIR) to doses of 0.065 to 2.1 dpa. Fracture toughness, tensile, and Charpy-V impact properties of the weldment components (base, weld, and weld heat-affected-zone (HAZ)) have been measured at temperatures of 25 degrees C and 125 degrees C in the L-C and C-L orientations for materials in both the irradiated and unirradiated conditions for companion specimens. Fracture toughness and tensile properties of specimens cut from an SRS reactor vessel sidewall with doses of 0.1 and 0.5 dpa were also measured at temperatures of 25 and 125 degrees C. The irradiated materials exhibit hardening with loss of work hardenability and a reduction in toughness relative to the unirradiated materials. The HFIR-irradiated materials show an increase in yield strength between about 20% and 190% with a concomitant tensile strength increase between about 15% to 30%. The elastic-plastic fracture toughness parameters and Charpy-V energy absorption both decrease and show only a slight sensitivity to dose. The irradiation-induced decrease in the elastic-plastic fracture toughness (J def at 1 mm crack extension) is between 20% to 65%; the range of J 1C values are 72.8 to 366 kJ/m 2 for the irradiated materials. Similarly, Charpy V-notch results show a 40% to 60% decrease in impact energies

  1. The effect of microstructural change on the Charpy impact properties of the high-strength ferritic/martensitic steel (PNC-FMS) irradiated in JOYO/MARICO-1

    International Nuclear Information System (INIS)

    Yano, Yasuhide; Akasaka, Naoaki; Yoshitake, Tsunemitsu; Abe, Yasuhiro

    2004-03-01

    It is well known that the irradiation embrittlement is one of the most important issues to apply ferritic steels for FBR core materials, although ferritic steels have been considered to be candidate core materials of the commercialized FBR core material because of their superior swelling resistance. In order to evaluate the effects of microstructural changes during irradiation on the Charpy impact properties of the high-strength ferritic/martensitic steel (PNC-FMS), microstructural observations were performed with transmission electron microscopy on ruptured halves of the half-sized Charpy specimens of PNC-FMS irradiated in the JOYO/MARICO-1. The results obtained in this study are as follows: (1) There was remarkable disappearance of the lath of martensite in the samples irradiated at 650degC, although there was no significant change in microstructures, especially the lath of martensite between the samples irradiated at 500degC and unirradiated. The disappearance of martensitic lath in the samples irradiated at 650degC was larger than that of the samples thermally aged at 650degC. (2) The ductile-brittle transition temperature (DBTT) of irradiated PNC-FMS is judged to increase with the disappearance of martensitic lath and to decrease with the recovery in dislocations. (3) The decrease in the upper shelf energy (USE) of irradiated PNC-FMS is significantly accompanied by the change of precipitation behavior. (4) The Charpy impact properties and microstructures of PNC-FMS irradiated at 500degC were superior under these irradiation conditions. In future, it is necessary to establish how to evaluate Charpy impact properties in a high fluence region, based on theoretical methods introduced from the data gained in low fluence experiments, in addition to expanding the data area widely. (author)

  2. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  3. Down-regulation of Notch-1 by γ-secretase inhibitor suppress the ...

    African Journals Online (AJOL)

    Notch-1 signaling is crucial for stem cell maintenance and in a variety of tissues. Previous research has demonstrated that Notch-1 activity plays a key role in prostate tumorigenesis. However, the function of Notch-1 signaling in tumorigenesis can be either oncogene or suppressor gene. In our paper, γ- secretase inhibitor ...

  4. Fatigue crack growth from blunt notches

    International Nuclear Information System (INIS)

    Rhodes, D.

    1982-01-01

    A number of methods have been proposed, by which the formation and early growth of fatigue cracks at blunt notches may be predicted. In this report, four methods are compared - i.e. analysis of the crack tip plastic deformation, the cyclic contour integral, δJ, the strain in a critical volume of material, and the notch root plastic strain range. It is shown that these approaches have fundamental elements in common, and that all are compatable with linear elastic fracture mechanics. Early results from a continuing experimental programme are reported. (orig.) [de

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

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → 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.

  6. 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.

  7. Verification of the effect of surface preparation on Hot Isostatic Pressing diffusion bonding joints of CLAM steel

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yanyun [University of Science and Technology of China, Hefei, Anhui 230027 (China); Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Li, Chunjing, E-mail: chunjing.li@fds.org.cn [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Huang, Bo; Liu, Shaojun [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Huang, Qunying [University of Science and Technology of China, Hefei, Anhui 230027 (China); Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

    2014-12-15

    Hot Isostatic Pressing (HIP) diffusion bonding with CLAM steel is the primary candidate fabrication technique for the first wall (FW) of DFLL-TBM. Surface state is one of the key factors for the joints quality. The effect of surface state prepared with grinder and miller on HIP diffusion bonding joints of CLAM steel was investigated. HIP diffusion bonding was performed at 140 MPa and 1373 K within 3 h. The mechanical properties of the joints were investigated with instrumented Charpy V-notch impact tests and the microstructures of the joints were analyzed with scanning electron microscopy (SEM). The results showed that the milled samples with fine surface roughness were more suitable for CLAM steel HIP diffusion bonding.

  8. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    International Nuclear Information System (INIS)

    Dontu, Gabriela; Jackson, Kyle W; McNicholas, Erin; Kawamura, Mari J; Abdallah, Wissam M; Wicha, Max S

    2004-01-01

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  9. Droplet digital PCR analysis of NOTCH1 gene mutations in chronic lymphocytic leukemia.

    Science.gov (United States)

    Minervini, Angela; Francesco Minervini, Crescenzio; Anelli, Luisa; Zagaria, Antonella; Casieri, Paola; Coccaro, Nicoletta; Cumbo, Cosimo; Tota, Giuseppina; Impera, Luciana; Orsini, Paola; Brunetti, Claudia; Giordano, Annamaria; Specchia, Giorgina; Albano, Francesco

    2016-12-27

    In chronic lymphocytic leukemia (CLL), NOTCH1 gene mutations (NOTCH1mut) have been associated with adverse prognostic features but the independence of these as a prognostic factor is still controversial. In our study we validated a c.7541-7542delCT NOTCH1 mutation assay based on droplet digital PCR (ddPCR); we also analyzed the NOTCH1mut allelic burden, expressed as fractional abundance (FA), in 88 CLL patients at diagnosis to assess its prognostic role and made a longitudinal ddPCR analysis in 10 cases harboring NOTCH1mut to verify the FA variation over time. Our data revealed that with the ddPCR approach the incidence of NOTCH1mut in CLL was much higher (53.4%) than expected. However, longitudinal ddPCR analysis of CLL cases showed a statistically significant reduction of the NOTCH1mut FA detected at diagnosis after treatment (median FA 11.67 % vs 0.09 %, respectively, p = 0.01); the same difference, in terms of NOTCH1mut FA, was observed in the relapsed cases compared to the NOTCH1mut allelic fraction observed in patients in complete or partial remission (median FA 4.75% vs 0.43%, respectively, p = 0.007). Our study demonstrated a much higher incidence of NOTCH1mut in CLL than has previously been reported, and showed that the NOTCH1mut allelic burden evaluation by ddPCR might identify patients in need of a closer clinical follow-up during the "watch and wait" interval and after standard chemotherapy.

  10. An Investigation on the Wear Resistance and Fatigue Behaviour of Ti-6Al-4V Notched Members Coated with Hydroxyapatite Coatings

    Directory of Open Access Journals (Sweden)

    Reza H Oskouei

    2016-02-01

    Full Text Available In this study, surface properties of Ti-6Al-4V alloy coated with hydroxyapatite coatings were investigated. Wear resistance and fatigue behaviour of samples with coating thicknesses of 10 and 50 µm as well as uncoated samples were examined. Wear experiments demonstrated that the friction factor of the uncoated titanium decreased from 0.31 to 0.06, through a fluctuating trend, after 50 cycles of wear tests. However, the friction factor of both the coated samples (10 and 50 µm gradually decreased from 0.20 to 0.12 after 50 cycles. At the end of the 50th cycle, the penetration depth of the 10 and 50 µm coated samples were 7.69 and 6.06 µm, respectively. Fatigue tests showed that hydroxyapatite coatings could improve fatigue life of a notched Ti-6Al-4V member in both low and high cycle fatigue zones. It was understood, from fractography of the fracture surfaces, that the fatigue zone of the uncoated specimens was generally smaller in comparison with that of the coated specimens. No significant difference was observed between the fatigue life of coated specimens with 10 and 50 µm thicknesses.

  11. 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...... notch filter ensures an attenuation level of 19.3 dB to 27.3 dB in the frequency range from 360–480 MHz. The measured passband ripple of the combined filter is less than 0.5 dB, while the insertion loss for the simplest design is less than 1.7 dB only 10 MHz from the notch frequency. Even though...... the wavelength on the selected substrate (εr = 3.55) is approximately 45 cm, the outer dimensions of the final filter only measure 10×10 cm2....

  12. ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.

    Science.gov (United States)

    Larrivée, Bruno; Prahst, Claudia; Gordon, Emma; del Toro, Raquel; Mathivet, Thomas; Duarte, Antonio; Simons, Michael; Eichmann, Anne

    2012-03-13

    Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morphogenesis that may be relevant to the pathogenesis of HHT vascular lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Passive notch circuit for pulsed-off compression fields

    International Nuclear Information System (INIS)

    Nunnally, W.C.

    1976-06-01

    The operation and simulated results of a passive notch circuit used to pulse off the field in a multiturn, fusion-power system, compression coil are presented. The notch circuit permits initial plasma preparation at field zero, adiabatic compression as the field returns to its initial value, and long field decay time for plasma confinement. The major advantages and disadvantages of the notch circuit are compared with those of a standard capacitor power supply system. The major advantages are that: (1) slow-rising fields can be used for adiabatic compression, (2) solid-state switches can be used because of the inherent current and voltage waveforms, and (3) long field decay times are easier to attain than with single-turn coils

  14. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  15. Time-series photometric spot modeling. 2: Fifteen years of photometry of the bright RS CVn binary HR 7275

    Science.gov (United States)

    Strassmeier, K. G.; Hall, D. S.; Henry, G. W.

    1994-01-01

    We present a time-dependent spot modeling analysis of 15 consecutive years of V-band photometry of the long-period (P(sub orb) = 28.6 days) RS CVn binary HR 7275. This baseline in time is one of the longest, uninterrupted intervals a spotted star has been observed. The spot modeling analysis yields a total of 20 different spots throughout the time span of our observations. The distribution of the observed spot migration rates is consistent with solar-type differential rotation and suggests a lower limit of the differential-rotation coefficient of 0.022 +/-0.004. The observed, maximum lifetime of a single spot (or spot group) is 4.5 years, the minimum lifetime is approximately one year, but an average spot lives for 2.2 years. If we assume that the mechanical shear by differential rotation sets the upper limit to the spot lifetime, the observed maximum lifetime in turn sets an upper limit to the differential-rotation coefficient, namely 0.04 +/- 0.01. This would be differential rotation just 5 to 8 times less than the solar value and one of the strongest among active binaries. We found no conclusive evidence for the existence of a periodic phenomenon that could be attributed to a stellar magnetic cycle.

  16. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality

    DEFF Research Database (Denmark)

    Boskovski, Marko T; Yuan, Shiaulou; Pedersen, Nis Borbye

    2013-01-01

    to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either...... by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio...... of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking...

  17. 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.

  18. 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...

  19. A VERY BRIGHT, VERY HOT, AND VERY LONG FLARING EVENT FROM THE M DWARF BINARY SYSTEM DG CVn

    Energy Technology Data Exchange (ETDEWEB)

    Osten, Rachel A. [Space Telescope Science Institute (United States); Kowalski, Adam [U. Md/GSFC (United States); Drake, Stephen A. [USRA/CRESST and NASA/GSFC (United States); Krimm, Hans [USRA/CRESST (United States); Page, Kim [X-ray and Observational Astronomy Group, Department of Physics and Astronomy, University of Leicester, Leicester, LE1 7RH (United Kingdom); Gazeas, Kosmas [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR-15784 Zografos, Athens (Greece); Kennea, Jamie [Penn State (United States); Oates, Samantha [Instituto de Astrofsica de Andalucía (IAA-CSIC), Glorieta de la Astronomía s/n, E-18008, Granada (Spain); Page, Mathew [Mullard Space Science Laboratory, University College London, Holmbury St. Mary, Dorking RH5 6NT (United Kingdom); De Miguel, Enrique [Departamento de Fisica Aplicada, Facultad de Ciencias Experimentales, Universidad de Huelva, E-21071 Huelva (Spain); Novák, Rudolf [Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 3, 625 00 Brno (Czech Republic); Apeltauer, Tomas [Brno University of Technology, Faculty of Civil Engineering, Veveri 331/95, 602 00 Brno (Czech Republic); Gehrels, Neil, E-mail: osten@stsci.edu [NASA/GSFC (United States)

    2016-12-01

    On 2014 April 23, the Swift satellite responded to a hard X-ray transient detected by its Burst Alert Telescope, which turned out to be a stellar flare from a nearby, young M dwarf binary DG CVn. We utilize observations at X-ray, UV, optical, and radio wavelengths to infer the properties of two large flares. The X-ray spectrum of the primary outburst can be described over the 0.3–100 keV bandpass by either a single very high-temperature plasma or a nonthermal thick-target bremsstrahlung model, and we rule out the nonthermal model based on energetic grounds. The temperatures were the highest seen spectroscopically in a stellar flare, at T{sub X} of 290 MK. The first event was followed by a comparably energetic event almost a day later. We constrain the photospheric area involved in each of the two flares to be >10{sup 20} cm{sup 2}, and find evidence from flux ratios in the second event of contributions to the white light flare emission in addition to the usual hot, T  ∼ 10{sup 4} K blackbody emission seen in the impulsive phase of flares. The radiated energy in X-rays and white light reveal these events to be the two most energetic X-ray flares observed from an M dwarf, with X-ray radiated energies in the 0.3–10 keV bandpass of 4 × 10{sup 35} and 9 × 10{sup 35} erg, and optical flare energies at E{sub V} of 2.8 × 10{sup 34} and 5.2 × 10{sup 34} erg, respectively. The results presented here should be integrated into updated modeling of the astrophysical impact of large stellar flares on close-in exoplanetary atmospheres.

  20. Notch pathway signaling in the skin antagonizes Merkel cell development.

    Science.gov (United States)

    Logan, Gregory J; Wright, Margaret C; Kubicki, Adam C; Maricich, Stephen M

    2018-02-15

    Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. On the use of the instrumented Charpy-V impact signal for assessment of RPVS embrittlement

    Energy Technology Data Exchange (ETDEWEB)

    Fabry, A.; Van Walle, E.; Van de Velde, J.; Chauoadi, R.; Puzzolante, J.L.; Van Ransbeeck, Th.; Verstrepen, A.

    1995-12-01

    In the context of LWR pressure vessel surveillance, the significance of the Cv notch impact test instrumented by strain gages has been revised. The load diagram (general yield, maximum, brittle fracture and arrest loads versus temperature ) is the most fundamental feature of the test. It is directly correlated to the appearance (percentage shear) of the fracture surface and also constitutes a straightforward experimental expression of the Davidenkov diagram, by which ductile-brittle transition temperature shifts are linked to irradiation damage mechanisms. In combination with static uniaxial tensile tests, it allows quantification of strain rate effects on the yielding and work hardening capacity of the steel. By contrast, the bulk of the absorbed energy and lateral expansion stems from ductile stable crack growth associated with plastic deformation under conditions, unrepresentative of the constraints and stress-strain field near the tip of a sharp crack in a pressure vessel. It is shown that the temperature at which fixed energy is absorbed in the test (41 or 68 Joules) cannot always trace to acceptable accuracy the effect of steel service exposure on the ductile - brittle transition temperature and on cleavage fracture toughness. It is contented that this can be done more reliably by using characteristic temperatures of the load diagram. An attempt to determine the engineering and regulatory implications of this physically-grounded fracture toughness approach is made.

  2. On the use of the instrumented Charpy-V impact signal for assessment of RPVS embrittlement

    International Nuclear Information System (INIS)

    Fabry, A.; Van Walle, E.; Van de Velde, J.; Chauoadi, R.; Puzzolante, J.L.; Van Ransbeeck, Th.; Verstrepen, A.

    1995-12-01

    In the context of LWR pressure vessel surveillance, the significance of the Cv notch impact test instrumented by strain gages has been revised. The load diagram (general yield, maximum, brittle fracture and arrest loads versus temperature ) is the most fundamental feature of the test. It is directly correlated to the appearance (percentage shear) of the fracture surface and also constitutes a straightforward experimental expression of the Davidenkov diagram, by which ductile-brittle transition temperature shifts are linked to irradiation damage mechanisms. In combination with static uniaxial tensile tests, it allows quantification of strain rate effects on the yielding and work hardening capacity of the steel. By contrast, the bulk of the absorbed energy and lateral expansion stems from ductile stable crack growth associated with plastic deformation under conditions, unrepresentative of the constraints and stress-strain field near the tip of a sharp crack in a pressure vessel. It is shown that the temperature at which fixed energy is absorbed in the test (41 or 68 Joules) cannot always trace to acceptable accuracy the effect of steel service exposure on the ductile - brittle transition temperature and on cleavage fracture toughness. It is contented that this can be done more reliably by using characteristic temperatures of the load diagram. An attempt to determine the engineering and regulatory implications of this physically-grounded fracture toughness approach is made

  3. Dangerous Liaisons: Deviant Endothelium NOTCHes toward Tumor Metastasis.

    Science.gov (United States)

    Guo, Peipei; Rafii, Shahin

    2017-03-13

    In this issue of Cancer Cell, Wieland et al. uncover a feedback loop in which tumor cells, by augmenting Notch signaling, provoke a senescent and pro-inflammatory state in endothelial cells, promoting neutrophil infiltration, tumor cell adhesion, and metastasis. Interfering with this Notch-dependent crosstalk may be a therapeutic approach to block metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Experimental analysis of compressive notch strengthening in closed-cell aluminum alloy foam

    NARCIS (Netherlands)

    Antoniou, A; Onck, PR; Bastawros, Ashraf F.

    2004-01-01

    The notch strengthening effect is studied experimentally in closed cell aluminum foams. The limit loads, net section strength were found for a set of double-edge-notched (DEN) and single-edge-notched (SEN) specimens loaded in compression. In addition, the evolution of the deformation is monitored

  5. Notch size effects on high cycle fatigue limit stress of Udimet 720

    International Nuclear Information System (INIS)

    Ren Weiju; Nicholas, Theodore

    2003-01-01

    Notch size effects on the high cycle fatigue (HCF) limit stress of Ni-base superalloy Udimet 720 were investigated on cylindrical specimens with three notch sizes of the same stress concentration factor K t =2.74. The HCF limit stress corresponding to a life of 10 6 cycles was experimentally determined at a stress ratio of 0.1 and a frequency of 25 Hz at room temperature. The stresses were calculated using finite element analysis (FEA) and the specimens analyzed using scanning electron microscopy (SEM). Test results show that at the same K t value, notch size can slightly affect the HCF limit stress of U720 when notch root plasticity occurs. FEA and SEM results reveal that the notch size effects are influenced by a complicated combination of the stress and plastic strain fields at the notch tip, the nominal stress, and the effects of prior plastic deformation on fatigue crack initiation

  6. An Evolutionary-Conserved Function of Mammalian Notch Family Members as Cell Adhesion Molecules

    Science.gov (United States)

    Murata, Akihiko; Yoshino, Miya; Hikosaka, Mari; Okuyama, Kazuki; Zhou, Lan; Sakano, Seiji; Yagita, Hideo; Hayashi, Shin-Ichi

    2014-01-01

    Notch family members were first identified as cell adhesion molecules by cell aggregation assays in Drosophila studies. However, they are generally recognized as signaling molecules, and it was unclear if their adhesion function was restricted to Drosophila. We previously demonstrated that a mouse Notch ligand, Delta-like 1 (Dll1) functioned as a cell adhesion molecule. We here investigated whether this adhesion function was conserved in the diversified mammalian Notch ligands consisted of two families, Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and Jag2). The forced expression of mouse Dll1, Dll4, Jag1, and Jag2, but not Dll3, on stromal cells induced the rapid and enhanced adhesion of cultured mast cells (MCs). This was attributed to the binding of Notch1 and Notch2 on MCs to each Notch ligand on the stromal cells themselves, and not the activation of Notch signaling. Notch receptor-ligand binding strongly supported the tethering of MCs to stromal cells, the first step of cell adhesion. However, the Jag2-mediated adhesion of MCs was weaker and unlike other ligands appeared to require additional factor(s) in addition to the receptor-ligand binding. Taken together, these results demonstrated that the function of cell adhesion was conserved in mammalian as well as Drosophila Notch family members. Since Notch receptor-ligand interaction plays important roles in a broad spectrum of biological processes ranging from embryogenesis to disorders, our finding will provide a new perspective on these issues from the aspect of cell adhesion. PMID:25255288

  7. 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

    necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

  8. Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide

    DEFF Research Database (Denmark)

    Xiao, Binggang; Li, Sheng-Hua; Xiao, Sanshui

    2016-01-01

    Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN and satel......Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN...

  9. Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.

    Science.gov (United States)

    Semerci, Fatih; Choi, William Tin-Shing; Bajic, Aleksandar; Thakkar, Aarohi; Encinas, Juan Manuel; Depreux, Frederic; Segil, Neil; Groves, Andrew K; Maletic-Savatic, Mirjana

    2017-07-12

    Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe ( Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

  10. Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

    Science.gov (United States)

    Eberl, Markus; Mangelberger, Doris; Swanson, Jacob B; Verhaegen, Monique E; Harms, Paul W; Frohm, Marcus L; Dlugosz, Andrzej A; Wong, Sunny Y

    2018-02-12

    Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh + /Notch + suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh +++ /Notch - basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The effect of residual stresses induced by prestraining on fatigue life of notched specimens

    Science.gov (United States)

    Sadeler, R.; Ozel, A.; Kaymaz, I.; Totik, Y.

    2005-06-01

    The effect of tensile prestraining-induced residual stress on the fatigue life of notched steel parts was investigated. The study was performed on AISI 4140 steel. Rotating bending fatigue tests were carried out on semicircular notched specimens with different notch radii in the as-quenched and tempered conditions. Metallography of the specimens was performed by means of light optical microscopy. The finite-element method was used to evaluate the residual stress distribution near the notch region. Fatigue tests revealed fatigue life improvement for notched specimens, which changes depending on the notch radii and applied stress. Scanning electron microscopy was used to examine the fracture surfaces of the specimens.

  12. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    OpenAIRE

    Broadus, Matthew R.; Chen, Tony W.; Neitzel, Leif R.; Ng, Victoria H.; Jodoin, Jeanne; Lee, Laura A.; Salic, Adrian; Robbins, David J.; Capobianco, Anthony J.; Patton, James G.; Huppert, Stacey S.; Lee, Ethan

    2016-01-01

    Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box...

  13. Evaluation of Notch and Hypoxia Signaling Pathways in Chemically ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is a common worldwide malignancy. Notch signaling pathway contributes to the genesis of diverse cancers, however, its role in HCC is unclear. Hypoxia is a common feature of HCC. Signal integration between Notch and hypoxia may be involved in HCC. The aim of this study was to ...

  14. 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)

  15. Failure of a porous solid from a deep notch

    DEFF Research Database (Denmark)

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

    1997-01-01

    A finite strain finite element method is used to examine the stress state near the tip of a deep notch in an elastic-plastic porous solid. The notch is loaded in mode I plane strain tension and small scale yielding is assumed. Two rate independent strain hardening material models are used...

  16. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.

    Directory of Open Access Journals (Sweden)

    Yidong Wang

    Full Text Available Endocardial to mesenchymal transformation (EMT is a fundamental cellular process required for heart valve formation. Notch, Wnt and Bmp pathways are known to regulate this process. To further address how these pathways coordinate in the process, we specifically disrupted Notch1 or Jagged1 in the endocardium of mouse embryonic hearts and showed that Jagged1-Notch1 signaling in the endocardium is essential for EMT and early valvular cushion formation. qPCR and RNA in situ hybridization assays reveal that endocardial Jagged1-Notch1 signaling regulates Wnt4 expression in the atrioventricular canal (AVC endocardium and Bmp2 in the AVC myocardium. Whole embryo cultures treated with Wnt4 or Wnt inhibitory factor 1 (Wif1 show that Bmp2 expression in the AVC myocardium is dependent on Wnt activity; Wnt4 also reinstates Bmp2 expression in the AVC myocardium of endocardial Notch1 null embryos. Furthermore, while both Wnt4 and Bmp2 rescue the defective EMT resulting from Notch inhibition, Wnt4 requires Bmp for its action. These results demonstrate that Jagged1-Notch1 signaling in endocardial cells induces the expression of Wnt4, which subsequently acts as a paracrine factor to upregulate Bmp2 expression in the adjacent AVC myocardium to signal EMT.

  17. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation.

    Directory of Open Access Journals (Sweden)

    Jerry S Chen

    2014-06-01

    Full Text Available Notch-Delta signaling is a fundamental cell-cell communication mechanism that governs the differentiation of many cell types. Most existing mathematical models of Notch-Delta signaling are based on a feedback loop between Notch and Delta leading to lateral inhibition of neighboring cells. These models result in a checkerboard spatial pattern whereby adjacent cells express opposing levels of Notch and Delta, leading to alternate cell fates. However, a growing body of biological evidence suggests that Notch-Delta signaling produces other patterns that are not checkerboard, and therefore a new model is needed. Here, we present an expanded Notch-Delta model that builds upon previous models, adding a local Notch activity gradient, which affects long-range patterning, and the activity of a regulatory microRNA. This model is motivated by our experiments in the ascidian Ciona intestinalis showing that the peripheral sensory neurons, whose specification is in part regulated by the coordinate activity of Notch-Delta signaling and the microRNA miR-124, exhibit a sparse spatial pattern whereby consecutive neurons may be spaced over a dozen cells apart. We perform rigorous stability and bifurcation analyses, and demonstrate that our model is able to accurately explain and reproduce the neuronal pattern in Ciona. Using Monte Carlo simulations of our model along with miR-124 transgene over-expression assays, we demonstrate that the activity of miR-124 can be incorporated into the Notch decay rate parameter of our model. Finally, we motivate the general applicability of our model to Notch-Delta signaling in other animals by providing evidence that microRNAs regulate Notch-Delta signaling in analogous cell types in other organisms, and by discussing evidence in other organisms of sparse spatial patterns in tissues where Notch-Delta signaling is active.

  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. Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling.

    Directory of Open Access Journals (Sweden)

    Mozhgan Farshbaf

    Full Text Available Early studies demonstrated the involvement of ubiquitination of the Notch intracellular domain for rapid turnover of the transcriptional complex at Notch target genes. It was shown that this ubiquitination was promoted by the co-activator Mastermind like 1 (MAML1. MAML1 also contains numerous lysine residues that may also be ubiquitinated and necessary for protein regulation. In this study, we show that over-expressed MAML1 is ubiquitinated and identify eight conserved lysine residues which are required for ubiquitination. We also show that p300 stimulates ubiquitination and that Notch inhibits ubiquitination. Furthermore, we show that a mutant MAML1 that has decreased ubiquitination shows increased output from a HES1 reporter gene assay. Therefore, we speculate that ubiquitination of MAML1 might be a mechanism to maintain low levels of the protein until needed for transcriptional activation. In summary, this study identifies that MAML1 is ubiquitinated in the absence of Notch signaling to maintain low levels of MAML1 in the cell. Our data supports the notion that a precise and tight regulation of the Notch pathway is required for this signaling pathway.

  1. A Novel Notch-YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma.

    Science.gov (United States)

    Slemmons, Katherine K; Crose, Lisa E S; Riedel, Stefan; Sushnitha, Manuela; Belyea, Brian; Linardic, Corinne M

    2017-12-01

    Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival rate of statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS). Here, the cross-talk between these pathways and the impact on eRMS tumorigenesis is reported. Using human eRMS cells grown as three-dimensional (3D) rhabdospheres, which enriches in stem cells, it was found that Notch signaling transcriptionally upregulates YAP1 gene expression and YAP activity. Reciprocally, YAP transcriptionally upregulates the Notch ligand genes JAG1 and DLL1 and the core Notch transcription factor RBPJ This bidirectional circuit boosts expression of key stem cell genes, including SOX2 , which is functionally required for eRMS spheres. Silencing this circuit for therapeutic purposes may be challenging, because the inhibition of one node (e.g., pharmacologic Notch blockade) can be rescued by upregulation of another (constitutive YAP expression). Instead, dual inhibition of Notch and YAP is necessary. Finally, supporting the existence of this circuit beyond a model system, nuclear Notch and YAP protein expression are correlated in human eRMS tumors, and YAP suppression in vivo decreases Notch signaling and SOX2 expression. Implications: This study identifies a novel oncogenic signaling circuit driving eRMS stemness and tumorigenesis, and provides evidence and rationale for combination therapies co-targeting Notch and YAP. Mol Cancer Res; 15(12); 1777-91. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Immunohistochemical expression of Notch signaling in the lining epithelium of periapical cysts.

    Science.gov (United States)

    Meliou, Eleni; Kerezoudis, Nikolaos; Tosios, Konstantinos; Lafkas, Daniel; Kiaris, Hippokratis

    2011-02-01

    In this study we evaluated the immunohistochemical expression of the receptors Notch 1 and Notch 2, the ligand Delta 1, and the transcription factors HES 1 and HES 5 in the epithelium of well-defined periapical cysts. Immunohistochemistry was carried out on 55 formalin-fixed and paraffin-embedded, well-defined periapical cysts with minimum inflammation, obtained from the archival tissue database of the Department of Oral Pathology and Surgery. Western blotting was performed to evaluate the specificity of the anti-Notch antibody and the expression of Notch signaling in 5 fresh-frozen periapical cysts. The levels of staining intensity were estimated by the performance of a semiautomated image analysis system. Descriptive statistic of mean values obtained by computerized image analysis method was performed. Immunostaining reaction of all Notch signaling components was observed in the cytoplasm and/or the cytoplasmic membrane in the majority of epithelial cells of periapical cysts. Nuclear staining was observed occasionally in all cases. Notch 2 showed strong staining in 52.83% of the cases, followed by Notch 1 (35.85%), HES 1 and HES 5 moderate staining in 72.73% and 57.69% of the cases, respectively, and Delta 1 weak staining in 58.33% of the cases. No statistical correlation was found between the antibodies and the sex or the age of the study group. Notch is an evolutionarily conserved signaling mechanism that regulates cell fate decisions during development and postnatal life in organisms as diverse as worms, flies, and humans. The present observations indicate that Notch pathway is active downstream in the lining epithelium of periapical cysts, suggesting an involvement of this pathway in periapical cyst growth and expansion. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Visual interface for the automation of the instrumented pendulum of Charpy tests used in the surveillance program of reactors vessel of nuclear power plants

    International Nuclear Information System (INIS)

    Rojas S, A.S.; Sainz M, E.; Ruiz E, J.A.

    2004-01-01

    Inside the Programs of Surveillance of the nuclear power stations periodic information is required on the state that keep the materials with those that builds the vessel of the reactor. This information is obtained through some samples or test tubes that are introduced inside the core of the reactor and it is observed if its physical characteristics remain after having been subjected to the radiation changes and temperature. The rehearsal with the instrumented Charpy pendulum offers information on the behavior of fracture dynamics of a material. In the National Institute of Nuclear Research (ININ) it has an instrumented Charpy pendulum. The operation of this instrument is manual, having inconveniences to carry out rehearsals with radioactive material, handling of high and low temperatures, to fulfill the normative ones for the realization of the rehearsals, etc. In this work the development of a computational program is presented (virtual instrument), for the automation of the instrumented pendulum. The system has modules like: Card of data acquisition, signal processing, positioning system, tempered system, pneumatic system, compute programs like it is the visual interface for the operation of the instrumented Charpy pendulum and the acquisition of impact signals. This system shows that given the characteristics of the nuclear industry with radioactive environments, the virtual instrumentation and the automation of processes can contribute to diminish the risks to the personnel occupationally exposed. (Author)

  4. Effect of Notches on Creep-Fatigue Behavior of a P/M Nickel-Based Superalloy

    Science.gov (United States)

    Telesman, Jack; Gabb, Timothy P.; Ghosn, Louis J.; Gayda, John, Jr.

    2015-01-01

    A study was performed to determine and model the effect of high temperature dwells on notched low cycle fatigue (NLCF) and notch stress rupture behavior of a fine grain LSHR powder metallurgy (PM) nickel-based superalloy. It was shown that a 90 second dwell applied at the minimum stress (min dwell) was considerably more detrimental to the NLCF lives than similar dwell applied at the maximum stress (max dwell). The short min dwell NLCF lives were shown to be caused by growth of small oxide blisters which caused preferential cracking when coupled with high concentrated notch root stresses. The cyclic max dwell notch tests failed mostly by a creep accumulation, not by fatigue, with the crack origin shifting internally to a substantial distance away from the notch root. The classical von Mises plastic flow model was unable to match the experimental results while the hydrostatic stress profile generated using the Drucker-Prager plasticity flow model was consistent with the experimental findings. The max dwell NLCF and notch stress rupture tests exhibited substantial creep notch strengthening. The triaxial Bridgman effective stress parameter was able to account for the notch strengthening by collapsing the notched and uniform gage geometry test data into a singular grouping.

  5. Low temperature impact testing of welded structural wrought iron

    Science.gov (United States)

    Rogers, Zachary

    During the second half of the 19th century, structural wrought iron was commonly used in construction of bridges and other structures. Today, these remaining structures are still actively in use and may fall under the protection of historic preservation agencies. Continued use and protection leads to the need for inspection, maintenance, and repair of the wrought iron within these structures. Welding can be useful to achieve the appropriate repair, rehabilitation, or replacement of wrought iron members. There is currently very little published on modern welding techniques for historic wrought iron. There is also no pre-qualified method for this welding. The demand for welding in the repair of historic structural wrought iron has led to a line of research investigating shielded metal arc welding (SMAW) of historic wrought iron at the University of Colorado Denver. This prior research selected the weld type and other weld specifications to try and achieve a recognized specific welding procedure using modern SMAW technology and techniques. This thesis continues investigating SMAW of historic wrought iron. Specifically, this thesis addresses the toughness of these welds from analysis of the data collected from performing Charpy V-Notch (CVN) Impact Tests. Temperature was varied to observe the material response of the welds at low temperature. The wrought iron used in testing was from a historic vehicle bridge in Minnesota, USA. This area, and many other areas with wrought iron structures, can experience sustained or fluctuating temperatures far below freezing. Investigating the toughness of welds in historic wrought iron at these temperatures is necessary to fully understand material responses of the existing structures in need of maintenance and repair. It was shown that welded wrought iron is tougher and more ductile than non-welded wrought iron. In regards to toughness, welding is an acceptable repair method. Information on wrought iron, low temperature failure

  6. On the Use of the Instrumented Charpy-V Impact Signal for Assessment of RPVS Embrittlement

    Energy Technology Data Exchange (ETDEWEB)

    Fabry, A; van Walle, E; Van de Velde, J; Chaouadi, R; Puzzolante, J L; Van Ransbeeck, Th; Verstrepen, A

    1994-04-01

    In the context of LWR pressure vessel surveillance, the significance of the Cv notch impact test, instrumented by strain gages, has been revisited. The load diagram - general yield, maximum, brittle fracture and arrest loads versus temperature - is the most fundamental feature of the test. It is directly correlated to the appearance (percentage shear) of the fracture surface, and also constitutes a straightforward expression of the davidenkov diagram, by which DBTT shifts are linked to damage mechanisms. In combination with static uniaxial tensile tests, it allows to quantify strain rate effects on the yielding and work hardening capability of the steel. By contrast, the bulk of the absorbed energy and lateral expansion stems from plastic deformation, associated to ductile stable crack growth under conditions unrepresentative of the constraints and stress-strain field near the tip of a sharp crack in a pressure vessel. It has been shown that the temperature at which a fixed energy is absorbed in the test (41 or 68 J) cannot always trace, to acceptable accuracy, the effect of steel service exposure on the ductile-brittle transition temperature DBTT and on cleavage fracture toughness. It is contented that this can be done more reliably by using characteristic temperatures of the load diagram. The engineering and regulatory implications of this physically- grounded dynamic fracture toughness indexation approach are reported. Some related findings relative to damage mechanisms and strain ageing effects are outlined.

  7. On the Use of the Instrumented Charpy-V Impact Signal for Assessment of RPVS Embrittlement

    International Nuclear Information System (INIS)

    Fabry, A.; van Walle, E.; Van de Velde, J.; Chaouadi, R.; Puzzolante, J.L.; Van Ransbeeck, Th.; Verstrepen, A.

    1994-04-01

    In the context of LWR pressure vessel surveillance, the significance of the Cv notch impact test, instrumented by strain gages, has been revisited. The load diagram - general yield, maximum, brittle fracture and arrest loads versus temperature - is the most fundamental feature of the test. It is directly correlated to the appearance (percentage shear) of the fracture surface, and also constitutes a straightforward expression of the davidenkov diagram, by which DBTT shifts are linked to damage mechanisms. In combination with static uniaxial tensile tests, it allows to quantify strain rate effects on the yielding and work hardening capability of the steel. By contrast, the bulk of the absorbed energy and lateral expansion stems from plastic deformation, associated to ductile stable crack growth under conditions unrepresentative of the constraints and stress-strain field near the tip of a sharp crack in a pressure vessel. It has been shown that the temperature at which a fixed energy is absorbed in the test (41 or 68 J) cannot always trace, to acceptable accuracy, the effect of steel service exposure on the ductile-brittle transition temperature DBTT and on cleavage fracture toughness. It is contented that this can be done more reliably by using characteristic temperatures of the load diagram. The engineering and regulatory implications of this physically- grounded dynamic fracture toughness indexation approach are reported. Some related findings relative to damage mechanisms and strain ageing effects are outlined

  8. Comparison of BR3 Surveillance and Vessel Plates to the Surrogate Plates Representative of the Yankee Rowe PWR Vessel

    Energy Technology Data Exchange (ETDEWEB)

    Fabry, A.; Chaouadi, R.; Puzzolante, J.L.; Van de Velde, J.; Biemiller, E.C.; Rosinski, S.T.; Carter, R.G

    1998-07-01

    The sister pressure vessels at the BR3 and Yankee Rowe PWR plants were operated at lower-than-usual temperature ( 260 degrees Celsius) and their plates were austenitized a higher-than-usual temperature (970 degrees Celsius) - a heat treatment leading to a coarser microstructure than is typical for the fine grain plates considered in development of USNRC Regulatory Guide 1.99. The surveillance programs provided by Westinghouse for the two plants were limited to the same A302-B plate representative of the Rowe vessel upper shell plate; this material displayed outlier behaviour characterized by a 41 J Charpy-V Notch shift significantly larger than predicted by Regulatory Guide 1.99. Because lower irradiation temperature and nickel alloying are generally considered detrimental to irradiation sensitivity, there was a major concern that the nickel-modified lower Rate plate and the nickel-modified BR3 plate may become too embrittled to satisfy the toughness requirements embodied in the PTS screening criterion. This paper compares free complementary studies undertaken to clarify these uncertainties: (1) The accelerated irradiation and test program launched in 1990 by Yankee Atomic Electric Company using typical vessel plate materials containing 0.24% copper at two nickel levels: YA1, 0.63 % (A533-B) and YA9, 0.19 (A302-B). These were heat-treated to produce the coarse and fine grain microstructures representative of the Yankee/BR3 and the Regulatory Guide plates, respectively; (2) The BR3 surveillance and vessel testing program: this vessel was wet-annealed in 1984, relicensed for operation till the plant shutdown in 1987, and was trepanned in early 1995; (3) The accelerated irradiations in the Belgian test reactor BR2 of the Yankee coarse grain plates YA1 and YA9 together with BR3 vessel specimens extracted at nozzle elevation, a location with negligible radiation exposure. It is contended that the PTS screening criterion was never attained by the BR3 and Rowe plates, and

  9. Comparison of BR3 Surveillance and Vessel Plates to the Surrogate Plates Representative of the Yankee Rowe PWR Vessel

    International Nuclear Information System (INIS)

    Fabry, A.; Chaouadi, R.; Puzzolante, J.L.; Van de Velde, J.; Biemiller, E.C.; Rosinski, S.T.; Carter, R.G.

    1998-07-01

    The sister pressure vessels at the BR3 and Yankee Rowe PWR plants were operated at lower-than-usual temperature ( 260 degrees Celsius) and their plates were austenitized a higher-than-usual temperature (970 degrees Celsius) - a heat treatment leading to a coarser microstructure than is typical for the fine grain plates considered in development of USNRC Regulatory Guide 1.99. The surveillance programs provided by Westinghouse for the two plants were limited to the same A302-B plate representative of the Rowe vessel upper shell plate; this material displayed outlier behaviour characterized by a 41 J Charpy-V Notch shift significantly larger than predicted by Regulatory Guide 1.99. Because lower irradiation temperature and nickel alloying are generally considered detrimental to irradiation sensitivity, there was a major concern that the nickel-modified lower Rate plate and the nickel-modified BR3 plate may become too embrittled to satisfy the toughness requirements embodied in the PTS screening criterion. This paper compares free complementary studies undertaken to clarify these uncertainties: (1) The accelerated irradiation and test program launched in 1990 by Yankee Atomic Electric Company using typical vessel plate materials containing 0.24% copper at two nickel levels: YA1, 0.63 % (A533-B) and YA9, 0.19 (A302-B). These were heat-treated to produce the coarse and fine grain microstructures representative of the Yankee/BR3 and the Regulatory Guide plates, respectively; (2) The BR3 surveillance and vessel testing program: this vessel was wet-annealed in 1984, relicensed for operation till the plant shutdown in 1987, and was trepanned in early 1995; (3) The accelerated irradiations in the Belgian test reactor BR2 of the Yankee coarse grain plates YA1 and YA9 together with BR3 vessel specimens extracted at nozzle elevation, a location with negligible radiation exposure. It is contended that the PTS screening criterion was never attained by the BR3 and Rowe plates, and

  10. Comparison of BR3 surveillance and vessel plates to the surrogate plates representative of the Yankee Rowe PWR vessel

    International Nuclear Information System (INIS)

    Fabry, A.; Chaouadi, R.; Puzzolante, J.L.; Van de Velde, J.; Biemiller, E.C.; Rosinski, S.T.; Carter, R.G.

    1999-01-01

    The sister pressure vessels at the BR3 and Yankee Rowe PWR plants were operated at lower-than-usual temperature (∼260 C) and their plates were austenitized at higher-than-usual temperature (∼970 C) -- a heat treatment leading to a coarser microstructure than is typical for the fine grain plates considered in development of USNRC Regulatory Guide 1.99. The surveillance programs provided by Westinghouse for the two plants were limited to the same A302-B plate representative of the Rowe vessel upper shell plate; this material displayed outlier behavior characterized by a 41J. Charpy-V Notch shift significantly larger than predicted by Regulatory Guide 1.99. Because lower irradiation temperature and nickel alloying are generally considered detrimental to irradiation sensitivity, there was a major concern that the nickel-modified lower Rowe plate and the nickel-modified BR3 plate may become too embrittled to satisfy the toughness requirements embodied in the PTS screening criterion. This paper compares three complementary studies undertaken to clarify these uncertainties: (1) The accelerated irradiation and test program launched in 1990 by Yankee Atomic Electric Company using typical vessel plate materials containing 0.24% copper at two nickel levels: YA1, 0.63% (A533-B) and YA9, 0.19% (A302-B). These were heat-treated to produce the coarse and fine grain microstructures representative of the Yankee/BR3 and the Regulatory Guide plates, respectively; (2) The BR3 surveillance and vessel testing program; this vessel was wet-annealed in 1984, relicensed for operation till the plant shutdown in 1987, and was trepanned in early 1995; (3) The accelerated irradiations in the Belgian test reactor BR2 of the Yankee coarse grain plates YA1 and YA9 together with BR3 vessel specimens extracted at nozzle elevation, a location with negligible radiation exposure. It is contended that the PTS screening criterion was never attained by the BR3 and Rowe plates, and that the BR3 vessel

  11. Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.

    Directory of Open Access Journals (Sweden)

    Murni Tio

    Full Text Available In Drosophila, dopaminergic (DA neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development. Furthermore, we show that loss of function (l-o-f mutations of genes of the apical complex proteins in the asymmetric cell division (ACD machinery, such as inscuteable and bazooka result in supernumerary DA neurons, whereas l-o-f mutations of genes of the basal complex proteins such as numb result in loss or reduction of DA neurons. In addition, when Notch signaling is reduced or abolished, additional DA neurons are formed and conversely, when Notch signaling is activated, less DA neurons are generated. Our data demonstrate that both ACD and Notch signaling are crucial mechanisms for DA neuronal specification. We propose a model in which ACD results in differential Notch activation in direct siblings and in this context Notch acts as a repressor for DA neuronal specification in the sibling that receives active Notch signaling. Our study provides the first link of ACD and Notch signaling in the specification of a neurotransmitter phenotype in Drosophila. Given the high degree of conservation between Drosophila and vertebrate systems, this study could be of significance to mechanisms of DA neuronal differentiation not limited to flies.

  12. Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch*

    Science.gov (United States)

    Harvey, Beth M.; Rana, Nadia A.; Moss, Hillary; Leonardi, Jessica; Jafar-Nejad, Hamed; Haltiwanger, Robert S.

    2016-01-01

    Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O-glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the β3-N-acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID:27268051

  13. Effect of He implantation on fracture behavior and microstructural evolution in F82H

    Energy Technology Data Exchange (ETDEWEB)

    Yabuuchi, Kiyohiro, E-mail: kiyohiro.yabuuchi@qse.tohoku.ac.jp [Department of Quantum Science and Energy Engineering, Tohoku University, 6-6-01-2, Aramaki-Aza-Aoba, Aobaku, Sendai, Miyagi 980-8579 (Japan); Sato, Kiminori; Nogami, Shuhei; Hasegawa, Akira [Department of Quantum Science and Energy Engineering, Tohoku University, 6-6-01-2, Aramaki-Aza-Aoba, Aobaku, Sendai, Miyagi 980-8579 (Japan); Ando, Masami; Tanigawa, Hiroyasu [Japan Atomic Energy Agency, 2-166, Oaza-Obuchi-Aza-Omotedate, Rokkasho-mura, Kamikita-gun, Aomori 039-3212 (Japan)

    2014-12-15

    Reduced-activation ferritic/martensitic steels (RAFMs) are the primary candidate structural materials for fusion reactor blanket components. He bubbles, which formed under 14 MeV neutron irradiation, is considered to cause some mechanical property changes. In a previous study, Hasegawa et al. investigated the fracture behavior using Charpy impact test of He implanted F82H by 50 MeV α-particles with cyclotron accelerator, and the ductile brittle transition temperature (DBTT) was increased and intergranular fracture (IGF) was observed. However, the cause of the IGF was not shown in the previous study. To clarify the cause of the IGF of the He implanted F82H by 50 MeV α-particles with cyclotron accelerator, the microstructure of the He implanted F82H was investigated. After Charpy impact test at 233 K, the brittle fracture surface of the He implanted specimen was observed by SEM and TEM. By SEM observation, grain boundary surface was clearly observed from the bottom of the notch to a depth of about 400 μm. This area correspond to the He implanted region. On the other hand, at unimplanted region, river pattern was observed and transgranular fracture occurred. TEM observation revealed the He bubbles agglomeration at dislocations, lath boundaries, and grain boundaries, and the coarsening of precipitates on grain boundaries. IGF of the He implanted F82H was caused by both He bubbles and coarsening precipitates.

  14. Weldability investigation steel P 91 by weld thermal cycle simulation

    Directory of Open Access Journals (Sweden)

    M. Dunđer

    2015-07-01

    Full Text Available This paper elaborates results of hardness and impact energy of thermal cycle simulated specimens of high-alloy steel P 91 and their dependence on cooling time from 800 to 500 °C. Results were obtained by measuring hardness HV 1 and by experimental testing of Charpy notched specimens. Metallographic analysis of samples was performed on scanning electronic microscope.

  15. 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

  16. Morphometric study of suprascapular notch in Indian dry scapulae with specific reference to the incidence of completely ossified superior transverse scapular ligament.

    Science.gov (United States)

    Kannan, Usha; Kannan, N S; Anbalagan, J; Rao, Sudha

    2014-03-01

    The suprascapular notch, a depression on the lateral part of the superior border of the scapula, medial to the coracoid process, is bridged by the superior transverse scapular ligament, which is sometimes ossified and the foramen which is thus completed, transmits the suprascapular nerve to the supraspinatus fossa. Variations in the morphology of suprascapular notch have been identified as one of the causes of suprascapular nerve entrapment. Rengachary et al. classified this notch into six types, based on its shape. To study morphological variations of suprascapular notch in Indian dry scapulae and to analyze the incidence of completely ossified superior transverse scapular ligament with other ethnic populations which have been cited earlier. A total of 400 human dry scapulae which were obtained from the Department of Anatomy of selected eight medical colleges were analyzed. The type of suprascapular notch was noted and it was recorded as per the description given by Rengachary et al. The results of the present study were compared with the results of previous authors in different populations. In our study, out of 400 scapulae, 40 (10%), were identified to have completely ossified superior transverse scapular ligaments. The frequencies of various types of suprascapular notches were: Type I -20%, Type II -10%, Type III -52%, Type IV -4%, Type V -4%, Type VI -10%. Since the suprascapular nerve entrapment syndrome might be caused by complete ossification of superior transverse scapular ligament with formation of suprascapular foramen and other morphometric variations of suprascapular notch, the knowledge on such variations is essential for clinicians, for making a proper diagnosis and for planning the most suitable surgical intervention.

  17. Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature

    DEFF Research Database (Denmark)

    Kristoffersen, Karina; Nedergaard, Mette Kjølhede; Villingshøj, Mette

    2014-01-01

    BACKGROUND: Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in the devastating brain tumor glioblastoma multiforme (GBM). bCSC are proposed a central role in tumor initiation, progression, treatment resistance and relapse and as such present...... a promising target in GBM research. The Notch signaling pathway is often deregulated in GBM and we have previously characterized GBM-derived bCSC cultures based on their expression of the Notch-1 receptor and found that it could be used as predictive marker for the effect of Notch inhibition. The aim...... of the present project was therefore to further elucidate the significance of Notch pathway activity for the tumorigenic properties of GBM-derived bCSC. METHODS: Human-derived GBM xenograft cells previously established as NSC-like neurosphere cultures were used. Notch inhibition was accomplished by exposing...

  18. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Directory of Open Access Journals (Sweden)

    Richa Tripathi

    Full Text Available Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis.This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting.80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively.These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

  19. Effect of lead factors on the embrittlement of RPV SA-508 cl 3 steel

    Energy Technology Data Exchange (ETDEWEB)

    Kempf, Rodolfo, E-mail: kempf@cnea.gov.ar [CNEA, Unidad Actividad Combustibles Nucleares, División Caracterización, Avda. Gral Paz 1499, C.P.B1650KNA, San Martín, Buenos Aires (Argentina); Troiani, Horacio, E-mail: troiani@cab.cnea.gov.ar [Centro Atómico Bariloche (CNEA) e Instituto Balseiro (UNCU), CONICET, Av. Bustillo 9500, CP 8400, Rio Negro (Argentina); Fortis, Ana Maria, E-mail: fortis@cnea.gov.ar [CNEA, Departamento Estructura y Comportamiento, UNSAM, Avda. Gral Paz 1499, C.P.B1650KNA, San Martín, Buenos Aires (Argentina)

    2013-03-15

    This paper presents a project to study the effect of lead factors on the mechanical behaviour of the SA-508 type 3 Reactor Pressure Vessel (RPV) steel used in the reactor under construction Atucha II in Argentina. Charpy-V notch specimens of this steel were irradiated at the RA1 experimental reactor at a temperature of 275 °C with two lead factors (186 and 93). The neutron flux was 3.71 × 10{sup 15} n m{sup −2} s{sup −1} and 1.85 × 10{sup 15} n m{sup −2} s{sup −1} (E > 1 MeV) respectively. In both cases, the fluence was 6.6 × 10{sup 21} n m{sup −2}, which is equivalent to that received by the PHWR Atucha II RPV in 10 years of full power irradiation. The results of Charpy tests revealed significant embrittlement both in the ΔT = 14 °C and ΔT = 21 °C shifts of the ductile–brittle transition temperatures (DBTT) and in the reduction of the maximum energy absorbed. This result shows that the shift of the DBTT with a lead factor of 93 is larger than that obtained with a lead factor of 186. Then, the results of irradiation in experimental reactors (MTR) with high lead factors may not be conservative with respect to the actual RPV embrittlement.

  20. AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Neeta Bala Tannan

    2018-01-01

    Full Text Available AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

  1. AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster.

    Science.gov (United States)

    Bala Tannan, Neeta; Collu, Giovanna; Humphries, Ashley C; Serysheva, Ekatherina; Weber, Ursula; Mlodzik, Marek

    2018-01-01

    AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

  2. Application and validation of the notch master curve in medium and high strength structural steels

    Energy Technology Data Exchange (ETDEWEB)

    Cicero, Sergio; Garcia, Tiberio [Universidad de Cantabria, Santander (Spain); Madrazo, Virginia [PCTCAN, Santander (Spain)

    2015-10-15

    This paper applies and validates the Notch master curve in two ferritic steels with medium (steel S460M) and high (steel S690Q) strength. The Notch master curve is an engineering tool that allows the fracture resistance of notched ferritic steels operating within their corresponding ductile-to-brittle transition zone to be estimated. It combines the Master curve and the Theory of critical distances in order to take into account the temperature and the notch effect respectively, assuming that both effects are independent. The results, derived from 168 fracture tests on notched specimens, demonstrate the capability of the Notch master curve for the prediction of the fracture resistance of medium and high strength ferritic steels operating within their ductile-to-brittle transition zone and containing notches.

  3. Theoretical and experimental study of Chen chaotic system with notch filter feedback control

    International Nuclear Information System (INIS)

    Ming, Zhang Xiao; Jian-Hua, Peng; Ju-Fang, Chen

    2010-01-01

    Since the past two decades, the time delay feedback control method has attracted more and more attention in chaos control studies because of its simplicity and efficiency compared with other chaos control schemes. Recently, it has been proposed to suppress low-dimensional chaos with the notch filter feedback control method, which can be implemented in a laser system. In this work, we have analytically determined the controllable conditions for notch filter feedback controlling of Chen chaotic system in terms of the Hopf bifurcation theory. The conditions for notch filter feedback controlled Chen chaoitc system having a stable limit cycle solution are given. Meanwhile, we also analysed the Hopf bifurcation direction, which is very important for parameter settings in notch filter feedback control applications. Finally, we apply the notch filter feedback control methods to the electronic circuit experiments and numerical simulations based on the theoretical analysis. The controlling results of notch filter feedback control method well prove the feasibility and reliability of the theoretical analysis. (general)

  4. Mutations in the estrogen receptor alpha hormone binding domain promote stem cell phenotype through notch activation in breast cancer cell lines.

    Science.gov (United States)

    Gelsomino, L; Panza, S; Giordano, C; Barone, I; Gu, G; Spina, E; Catalano, S; Fuqua, S; Andò, S

    2018-04-24

    The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behavior of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44 + /CD24 - ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities. Mutant clones exhibited high expression of NOTCH receptors/ligands/target genes and blockade of NOTCH signaling reduced MFE and migratory potential. Mutant BCSC activity was dependent on ERα phosphorylation at serine 118, since its inhibition decreased MFE and NOTCH4 activation only in mutant cells. Collectively, we demonstrate that the expression of HBD-ESR1 mutations may drive BC cells to acquire stem cell traits through ER/NOTCH4 interplay. We propose the early detection of HBD-ESR1 mutations as a challenge in precision medicine strategy, suggesting the development of tailored-approaches (i.e. NOTCH inhibitors) to prevent disease development and metastatic spread in BC mutant-positive patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Genetic screens to identify new Notch pathway mutants in Drosophila.

    Science.gov (United States)

    Giagtzoglou, Nikolaos

    2014-01-01

    Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

  6. Effect of rhenium and osmium on mechanical properties of a 9Cr-2W-0.25V-0.07Ta-0.1C steel

    International Nuclear Information System (INIS)

    Klueh, R.L.; Alexander, D.J.; Sokolov, M.A.

    2000-01-01

    The nuclear transmutation of tungsten to rhenium and osmium in a tungsten-containing steel irradiated in a fission or fusion reactor will change the chemical composition of the steel. To determine the possible consequences of such compositional changes on the mechanical properties, tensile and Charpy impact properties were measured on five 9Cr-2W-0.25V-0.07Ta-0.1C steels that contained different amounts of rhenium, osmium, and tungsten. The mechanical properties changes caused by these changes in composition were minor. Observations were also made on the effect of carbon concentration. The effect of carbon on tensile behavior was minor, but there was a large effect on Charpy properties. Several of the steels showed little effect of tempering temperature on the Charpy transition temperature, a behavior that was tentatively attributed to the low silicon and/or manganese concentration of the experimental steels

  7. 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.

  8. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    Science.gov (United States)

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

  9. Applicability and interpretation of fracture test methods for metals

    International Nuclear Information System (INIS)

    Langford, W.J.

    1978-05-01

    Fracture tests are conducted usually out of a conviction (sometimes only vaguely defined) that they will guarantee a certain level of protecton from metal failure. Qualitative tests, such as the Charpy V-notch, produce results which cannot be rigorously related to a measure of fracture tolerance: rather, they indicate metal quality so that fracture tolerance may be inferred. Quantitative tests on the other hand provide parameters which may be used directly in equations to determine the likelihood of fracture. Both types of tests have limitations which should be understood: the paper tries to provide guidance on the relative merits of either approach for a particular purpose, and gives an insight into near-future test methods which will extend the range of usefullness of quantitative tests. (author)

  10. A survey of tests for protection against non-ductile failure

    International Nuclear Information System (INIS)

    Girotra, C.C.

    1975-01-01

    A study of the various tests available to test susceptibility to brittle fracture - their advantages, limitations has been made and the present status of data available to engineers has been surveyed. Due to the limitations of the charpy V-notch impact testing method - LEFM based Ksub(Ic) test and GYFM based COD test have been receiving recognition. ASME Section III has recently recommended Ksub(Ic) test as an alternative test for the selection of (ferritic) materials for class 1 pressure vessels. COD test proposed by British research workers, however, is yet to gain recognition for pressure vessel code particles, although it has existed as a tentative specification for more than 2 years and is more relevant to the materials with average strength. (author)

  11. Identification of 11-amino acid peptides that disrupt Notch-mediated processes in Drosophila

    Directory of Open Access Journals (Sweden)

    Yeh Hsiao-Fong

    2011-06-01

    Full Text Available Abstract Background The conserved Notch signaling pathway regulates cell fate decisions and maintains stem cells in multicellular organisms. Up-regulation of Notch signaling is observed in several types of cancer and is causally involved in proliferation and survival of cancer cells. Thus, it is of great interest to look for anti-Notch reagents for therapeutic purposes. In model animal Drosophila, Notch signaling restricts selection of sensory organ precursors (SOPs during external sensory (ES organ development. To look for novel genes that can suppress Notch signaling, we performed a gain-of-function modifier screen to look for genes that enhance the phenotype of ectopic ES organs induced by overexpression of phyllopod, a gene required for SOP specification. Results From the gain-of-function screen, we discovered that overexpression of polished rice/tarsal-less (pri/tal increases the numbers of ES organs as well as SOPs. pri/tal is a polycistronic gene that contains four short open reading frames encoding three 11-amino acid and one 32-amino acid peptides. Ectopic expression of the 11 amino-acid peptides recapitulates the pri/tal misexpression phenotype in ectopic ES organ formation. In situ hybridization experiment reveals that pri/tal mRNA is expressed in the SOPs of the chemosensory organs and the stretch-sensing chordotonal organs. In Drosophila wing development, the Notch signaling pathway mediates the formation of the dorsal-ventral (DV compartmental boundary and the restriction of the vein width from the primordial veins, the proveins. We also found that pri/tal mRNA is expressed in the DV boundary and the longitudinal proveins, and overexpression of Pri/Tal peptides disrupts the DV boundary formation and helps to expand the width of the wing vein. Genetic analyses further show that a Notch loss-of-function allele strongly enhances these two phenotypes. Cut and E(splmβ are target genes of the Notch pathway in DV boundary formation and

  12. Tensile behavior of unnotched and notched tungsten--copper laminar composites

    International Nuclear Information System (INIS)

    Hoffman, C.A.

    1976-06-01

    Relations were studied between the tensile strengths of unnotched and of notched, and elastic moduli of unnotched laminar sheet or foil composites and the amounts of reinforcement. Tungsten was used as the reinforcement and copper as the matrix, and the tests were run at room temperature. Three thicknesses of tungsten (i.e., 0.00254, 0.0127, and 0.0254 cm (0.001, 0.005, and 0.010 in) were used, and the nominal volume fraction of tungsten was varied from about 0.05 to 0.95. It was found that the tensile strength of the unnotched specimens could be related to the amount of reinforcement, as could the elastic moduli, and that these values could be predicted by use of the rule of mixtures. The tensile strengths of the notched laminar composites could be predicted by use of the rule of mixtures using strengths for notched constituents, provided notch effects did not predominate. (Author)

  13. Some observations on the nature of the audiometric 4000 hz notch: data from 3430 veterans.

    Science.gov (United States)

    Wilson, Richard H

    2011-01-01

    Pure-tone, air-conduction audiograms notched at 4000 Hz have long been considered the signature configuration for noise-induced hearing loss even though there is an extensive literature that does not mesh with this simple explanation. There are many reports of notched audiograms from individuals with no history of noise exposure and, conversely, reports of audiograms with no notches from individuals with a history of noise exposure. Recent reports increasingly suggest that unilateral 4000 Hz notches are common. The prevalence of notched audiograms at 4000 Hz is dependent on the definition of the notch and the population under study. To examine the prevalence and characteristics of audiograms that are notched at 4000 Hz. Retrospective, descriptive. The participants were 3430 veterans evaluated in the Audiology Clinic at the VA Medical Center, Mountain Home, Tennessee. The mean age was 62.3 yr. Data Collection and Analyses: The data were collected in the course of a 60 min, routine audiological evaluation. In addition to pure-tone audiometry, a history, otoscopy, speech audiometry in quiet and in noise, and aural-acoustic immittance measures were included in the clinic protocol but were not evaluated in this report. A notch was defined when the 4000 Hz threshold minus the 2000 Hz threshold and the 4000 Hz threshold minus the 8000 Hz threshold both were ≥10 dB. Overall the mean LE (left ear) thresholds at 2000, 3000, and 4000 Hz were at hearing levels 2-3 dB higher than the hearing levels for the corresponding mean RE (right ear) thresholds; the differences were significant. A notched audiogram was observed in 40.6% of the participants in at least one ear with 15.4% having bilateral notches, 28.8% LE notches, and 27.1% RE notches. Unilateral 4000 Hz notches were almost twice as prevalent as bilateral 4000 Hz notches. Viewed as a function of age, notched audiograms were most common (∼35% of the participants) in the 40 and 50 yr groups with a diminishing prevalence

  14. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    Science.gov (United States)

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  15. 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.

  16. Notching of samples for fracture toughness' measurements via SEVNB Method of brittle ceramics

    International Nuclear Information System (INIS)

    Ribeiro, S.; Atilio, I.; Oliveira, M.R.; Garcia, G.C.R.; Rodrigues, J.A.

    2012-01-01

    The goal of this work is to present a notching machine to produce notches in ceramic bodies as well the choice and how to make the notches, using SiC produced by liquid phase sintering as experimental material. For the liquid sintering a mixture of Al 2 O 3 and Yb 2 O 3 as additive was applied. It was developed and built by an enterprise sited in Sao Carlos-SP an equipment, which permits to obtain polished notches in ceramic specimens to be fractured afterwards. That is to facilitate the measurement of K IC via the SEVNB method. Specimens of 10% of (Al 2 O 3 +Yb 2 O 3 ) containing SiC were sintered at 1950 deg C. Those specimens were machined and notched using razor blades and diamond pastes of 15, 9, 6, 3, 1 and 0.25 μm of particle size. The built machine to notch specimens is installed at DEMAR-EEL-USP, and it is said to be the first of that type in Brazil. The results showed that depending on the thickness of the razor blade and the size of the diamond particles, it can be curried out notches with distinct tip radius and notch depth values. (author)

  17. RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice.

    Science.gov (United States)

    Schouwey, K; Aydin, I T; Radtke, F; Beermann, F

    2011-01-20

    The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jκ-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jκ, as it is rescued in mice lacking RBP-Jκ in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jκ. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.

  18. Stress concentration factors for an internally pressurized circular vessel containing a radial U-notch

    International Nuclear Information System (INIS)

    Carvalho, E.A. de

    2005-01-01

    This paper evaluates the stress concentration factors for an internally pressurized cylinder containing a radial U-notch along its length. This work studies the cases where the external to internal radius ratio (Ψ) is equal to 1.26, 1.52, 2.00, and 3.00 and the notch radius to internal radius ratio (Φ) is fixed and equal to 0.026. The U-notch depth varies from 0.1 to 0.6 of the wall thickness. Results are also presented for a fixed size semi-circular notch. Hoop stresses at the external wall are presented, showing regions where the stress matches the nominal one and the favourable places to install strain sensors. The finite element method is used to determine the stress concentration factors (K t ) for the above described situations and for a special case where a varying semi-circular notch is present with Ψ=3.00. This notch depth varies from 0.013 to 0.3 of the wall thickness. It is pointed out that even relatively small notches introduce large stress concentrations and disrupt the hoop stress distribution all over the cross section. Results are also compared to an example found in the literature for semi-circular notches and K t curves for both cases present the same shape

  19. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  20. Definition of the minimum longitude of insert in the rebuilding of Charpy test tubes for surveillance and life extension of vessels in Mexico; Definicion de la longitud minima de inserto en la reconstitucion de probetas Charpy para vigilancia y extension de vida de vasijas en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Romero C, J.; Hernandez C, R.; Rocamontes A, M., E-mail: jesus.romero@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    In the National Institute of Nuclear Research (Mexico) a welding system for the rebuilding of Charpy test tubes has been developed, automated, qualified and used for the surveillance of the mechanical properties (mainly embrittlement) of the vessel. This system uses the halves of the rehearsed Charpy test tubes of the surveillance capsules extracted of the reactors, to obtain, of a rehearsed test tube, two reconstituted test tubes. This rebuilding process is used so much in the surveillance program like in the potential extension of the operation license of the vessel. To the halves of Charpy test tubes that have been removed the deformed part by machine are called -insert- and in a very general way the rebuilding consists in weld with the welding process -Stud Welding- two metallic implants in the ends of the insert, to obtain a reconstituted test tube. The main characteristic of this welding are the achieved small dimensions, so much of the areas welded as of the areas affected by the heat. The applicable normative settles down that the minim longitude of the insert for the welding process by Stud Welding it should be of 18 mm, however according to the same normative this longitude can diminish if is demonstrated analytic or experimentally that the central volume of 1 cm{sup 3} in the insert is not affected. In this work the measurement of the temperature profiles to different distances of the welding interface is presented, defining an equation for the maximum temperatures reached in function of the distance, on the other hand the real longitude affected in the test tube by means of metallography is determined and this way the minimum longitude of the insert for this developed rebuilding system was determined. (Author)

  1. Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration.

    Directory of Open Access Journals (Sweden)

    Eun-Ryeong Hahm

    Full Text Available D, L-Sulforaphane (SFN, a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G(2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell

  2. Precipitation and impact toughness of Nb–V stabilised 18Cr–2Mo ferritic stainless steel during isothermal aging

    International Nuclear Information System (INIS)

    Han, Jian; Li, Huijun; Barbaro, Frank; Jiang, Laizhu; Zhu, Zhixiong; Xu, Haigang; Ma, Li

    2014-01-01

    The effect of isothermal aging on precipitation behaviour and Charpy impact toughness of Nb–V stabilised 18Cr–2Mo ferritic stainless steel was investigated by means of Thermo-Calc prediction, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Charpy impact toughness testing. The results show that, niobium, vanadium carbides and nitrides, Fe 2 Nb (Laves phase) and Cr 23 C 6 formed after 2 h aging at 800 °C, and the equilibrium solvus temperature of Fe 2 Nb phase increases to above 750 °C, higher than the calculated temperature (730 °C) using Thermo-Calc. After isothermal aging at 750–950 °C, 2 h aging resulted in a decrease in toughness due to the formation of precipitation, especially (Nb,V)(C,N) and Fe 2 Nb. When isothermally aged at 800 °C for up to 24 h, the coarsening rate of Fe 2 Nb particle is much higher than that of (Nb,V)(C,N), and the impact toughness of the steel is dependent on quantity and sizes of (Nb,V)(C,N) and Fe 2 Nb particles

  3. Precipitation and impact toughness of Nb–V stabilised 18Cr–2Mo ferritic stainless steel during isothermal aging

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jian, E-mail: jh595@uowmail.edu.au [School of Mechanical, Materials and Mechatronic Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); Li, Huijun [School of Mechanical, Materials and Mechatronic Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); Barbaro, Frank [School of Mechanical, Materials and Mechatronic Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); CBMM Technology Suisse, 14, Rue du Rhone, Geneve 1204 (Switzerland); Jiang, Laizhu [Baoshan Iron and Steel Co., Ltd., Shanghai 200431 (China); Zhu, Zhixiong [School of Mechanical, Materials and Mechatronic Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); Xu, Haigang; Ma, Li [Baoshan Iron and Steel Co., Ltd., Shanghai 200431 (China)

    2014-08-26

    The effect of isothermal aging on precipitation behaviour and Charpy impact toughness of Nb–V stabilised 18Cr–2Mo ferritic stainless steel was investigated by means of Thermo-Calc prediction, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Charpy impact toughness testing. The results show that, niobium, vanadium carbides and nitrides, Fe{sub 2}Nb (Laves phase) and Cr{sub 23}C{sub 6} formed after 2 h aging at 800 °C, and the equilibrium solvus temperature of Fe{sub 2}Nb phase increases to above 750 °C, higher than the calculated temperature (730 °C) using Thermo-Calc. After isothermal aging at 750–950 °C, 2 h aging resulted in a decrease in toughness due to the formation of precipitation, especially (Nb,V)(C,N) and Fe{sub 2}Nb. When isothermally aged at 800 °C for up to 24 h, the coarsening rate of Fe{sub 2}Nb particle is much higher than that of (Nb,V)(C,N), and the impact toughness of the steel is dependent on quantity and sizes of (Nb,V)(C,N) and Fe{sub 2}Nb particles.

  4. Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

    Directory of Open Access Journals (Sweden)

    Silvia Fre

    Full Text Available The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

  5. 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....

  6. Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium.

    Science.gov (United States)

    Elmadhun, Nassrene Y; Sabe, Ashraf A; Lassaletta, Antonio D; Chu, Louis M; Kondra, Katelyn; Sturek, Michael; Sellke, Frank W

    2014-09-01

    Impaired angiogenesis is a known consequence of metabolic syndrome (MetS); however, the mechanism is not fully understood. Recent studies have shown that the notch signaling pathway is an integral component of cardiac angiogenesis. We tested, in a clinically relevant swine model, the effects of MetS on notch and apoptosis signaling in chronically ischemic myocardium. Ossabaw swine were fed either a regular diet (control [CTL], n = 8) or a high-cholesterol diet (MetS, n = 8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, the wine underwent cardiac harvest of the ischemic myocardium. Downregulation of pro-angiogenesis proteins notch2, notch4, jagged2, angiopoietin 1, and endothelial nitric oxide synthase were found in the MetS group compared with the CTL group. Also, upregulation of pro-apoptosis protein caspase 8 and downregulation of anti-angiogenesis protein phosphorylated forkhead box transcription factor 03 and pro-survival proteins phosphorylated P38 and heat shock protein 90 were present in the MetS group. Cell death was increased in the MetS group compared with the CTL group. Both CTL and MetS groups had a similar arteriolar count and capillary density, and notch3 and jagged1 were both similarly concentrated in the smooth muscle wall. MetS in chronic myocardial ischemia significantly impairs notch signaling by downregulating notch receptors, ligands, and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling, and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, suggesting that inhibition of notch signaling might underlie the decreased angiogenesis in later stages of MetS. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  7. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  8. Damage Study in Notched Particulate Composie Specimens Under Nonuniform Strain Loading

    National Research Council Canada - National Science Library

    Kwon, Y

    1999-01-01

    .... The numerical specimen considered had a semi-circular notch with a linearly varying length. The initial crack size occurring at the notch tip was modeled and predicted using a micro/macro-approach along with a damage model...

  9. Charpy impact test results of four low activation ferritic alloys irradiated at 370{degrees}C to 15 DPA

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, L.E.; Hamilton, M.L.; Gelles, D.S. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    Miniature CVN specimens of four low activation ferritic alloys have been impact tested following irradiation at 370{degrees}C to 15 dpa. Comparison of the results with those of control specimens indicates that degradation in the impact behavior occurs in each of these four alloys. The 9Cr-2W alloy referred to as GA3X and the similar alloy F82H with 7.8Cr-2W appear most promising for further consideration as candidate structural materials in fusion energy system applications. These two alloys exhibit a small DBTT shift to higher temperatures but show increased absorbed energy on the upper shelf.

  10. Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide

    DEFF Research Database (Denmark)

    Xiao, Binggang; Li, Sheng-Hua; Xiao, Sanshui

    2016-01-01

    Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN and satel...... and satellite communication signals. Due to planar structures proposed here, it is easy to integrate in the microwave integrated systems, which can play an important role in the microwave communication circuit and system.......Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN...

  11. Limit load and fully plastic stress analysis for circular notched plates and bars using fully plastic analysis

    International Nuclear Information System (INIS)

    Oh, Chang Kyun; Myung, Man Sik; Kim, Yun Jae; Park, Jin Moo

    2005-01-01

    For the last four decades, tension test of notched bars has been performed to investigate the effect of stress triaxiality on ductile fracture. To quantify the effect of the notch radius on stress triaxiality, the Bridgman equation is typically used. However, recent works based on detailed finite element analysis have shown that the Bridgman equation is not correct, possibly due to his assumption that strain is constant in the necked ligament. Up to present, no systematic work has been performed on fully plastic stress fields for notched bars in tension. This paper presents fully plastic results for tension of notched bars and plates in plane strain, via finite element limit analysis. The notch radius is systematically varied, covering both un-cracked and cracked cases. Comparison of plastic limit loads with existing solutions shows that existing solutions are accurate for notched plates, but not for notched bars. Accordingly new limit load solutions are given for notched bars. Variations of stress triaxiality with the notch radius and depth are also given, which again indicates that the Bridgman solution for notched bars is not correct and inaccuracy depends on the notch radius and depth

  12. Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway.

    Science.gov (United States)

    Gao, Feng; Yao, Min; Cao, Yanping; Liu, Shuxia; Liu, Qingjuan; Duan, Huijun

    2016-05-01

    The Notch pathway is known to be linked to diabetic nephropathy (DN); however, its underlying mechanism was poorly understood. In the present study, we examined the effect of Valsartan, an angiotensin II type 1 receptor antagonist, on the Notch pathway and podocyte loss in DN. Diabetes was induced in mice by an intraperitoneal injection of streptozotocin and and this was followed by treatment with Valsartan. Levels of blood glucose, kidney weight and body weight, as well as proteinuria were measured. Samples of the kidneys were also histologically examined. The relative levels of Jagged1, Notch1, Notch intracellular domain 1 (NICD1), Hes family BHLH transcription factor 1 (Hes1) and Hes-related family BHLH transcription factor with YRPW motif 1 expression (Hey1) in the glomeruli were determined by immunohistochemical analysis, western blot analysis and RT-qPCR. The B-Cell CLL/Lymphoma 2 (Bcl-2) and p53 pathways were examined by western blot analysis. Apoptosis and detachment of podocytes from the glomerular basement membrane were examined using a TUNEL assay, flow cytometric analysis and ELISA. The number of podocytes was quantified by measuring Wilms tumor-1 (WT-1) staining. We noted that the expression of Jagged1, Notch1, NICD1, Hes1 and Hey1 was increased in a time-dependent manner in the glomeruli of mice with streptozotocin (STZ)-induced diabetes. Moreover, in diabetic mice, Valsartan significantly reduced kidney weight and proteinuria, and mitigated the pathogenic processes in the kidneys. Valsartan also inhibited the activation of Notch, Bcl-2 and p53 pathways and ameliorated podocyte loss in the glomeruli of mice with STZ-induced diabetes. Taken together, these findings indicated that Valsartan exerted a beneficial effect on reducing podocyte loss, which is associated with inhibition of Notch pathway activation in the glomeruli of diabetic mice.

  13. Fracture Mechanics Assessment for Different Notch Sizes Using Finite Element Analysis Based on Ductile Failure Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Keun Hyung; Jeon, Jun Young; Han, Jae Jun; Nam, Hyun Suk; Lee, Dae Young; Kim, Yun Jae [Korea Univ., Seoul (Korea, Republic of)

    2016-08-15

    In this study, notch defects are evaluated using fracture mechanics. To understand the effects of notch defects, FE analysis is conducted to predict the limit load and J-integral for middle-cracked and single-edge cracked plates with various sizes of notch under tension and bending. As the radius of the notch increases, the energy release rate also increases, although the limit load remains constant. The values of fracture toughness(J{sub IC}) of SM490A are determined for various notch radii through FE simulation instead of conducting an experiment. As the radius of the notch increases, the energy release rate also increases, together with a more significant increase in fracture toughness. To conclude, as the notch radius increases, the resistance to crack propagation also increases.

  14. Role of Notch signalling pathway in cancer and its association with ...

    Indian Academy of Sciences (India)

    The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organ- ... Abnormal Notch signalling is seen in many cancers like T-cell acute ...... Morgan T. H. 1917 The theory of the gene.

  15. Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Tognon, Emiliana; Kobia, Francis; Busi, Ilaria

    2016-01-01

    16-1 expression follows differentiation of proneural regions of the disc. These regions, that will form sensory organs in the adult, appear to possess a distinctive endo-lysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endo-lysosomal function...

  16. Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages.

    Science.gov (United States)

    Palaga, Tanapat; Ratanabunyong, Siriluk; Pattarakankul, Thitiporn; Sangphech, Naunpun; Wongchana, Wipawee; Hadae, Yukihiro; Kueanjinda, Patipark

    2013-09-01

    Macrophages are cellular targets for infection by bacteria and viruses. The fate of infected macrophages plays a key role in determining the outcome of the host immune response. Apoptotic cell death of macrophages is considered to be a protective host defense that eliminates pathogens and infected cells. In this study, we investigated the involvement of Notch signaling in regulating apoptosis in macrophages treated with tuberculin purified protein derivative (PPD). Murine bone marrow-derived macrophages (BMMs) treated with PPD or infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) induced upregulation of Notch1. This upregulation correlated well with the upregulation of the anti-apoptotic gene mcl-1 both at the transcriptional and translational levels. Decreased levels of Notch1 and Mcl-1 were observed in BMM treated with PPD when a gamma secretase inhibitor (GSI), which inhibits the processing of Notch receptors, was used. Moreover, silencing Notch1 in the macrophage-like cell line RAW264.7 decreased Mcl-1 protein expression, suggesting that Notch1 is critical for Mcl-1 expression in macrophages. A significant increase in apoptotic cells was observed upon treatment of BMM with PPD in the presence of GSI compared to the vehicle-control treated cells. Finally, analysis of the mcl-1 promoter in humans and mice revealed a conserved potential CSL/RBP-Jκ binding site. The association of Notch1 with the mcl-1 promoter was confirmed by chromatin immunoprecipitation. Taken together, these results indicate that Notch1 inhibits apoptosis of macrophages stimulated with PPD by directly controlling the mcl-1 promoter.

  17. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Science.gov (United States)

    Tripathi, Richa; Rath, Gayatri; Jawanjal, Poonam; Sharma, Shweta; Singhal, Pallavi; Bhambhani, Suresh; Hussain, Showket; Bharadwaj, Mausumi

    2014-01-01

    Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98), precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. 80% (24/30) were found to be positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001) and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001) obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; pcervix tissue (0.95±0.20, 0.70±0.20; pcancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

  18. Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

    Science.gov (United States)

    Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

    2012-09-21

    The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

  19. 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.

  20. Recent progress on gas tungsten arc welding of vanadium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Grossbeck, M.L.; King, J.F.; Alexander, D.J. [Oak Ridge National Lab., TN (United States)] [and others

    1997-08-01

    Emphasis has been placed on welding 6.4 mm plate, primarily by gas tungsten arc (GTA) welding. The weld properties were tested using blunt notch Charpy testing to determine the ductile to brittle transition temperature (DBTT). Erratic results were attributed to hydrogen and oxygen contamination of the welds. An improved gas clean-up system was installed on the welding glove box and the resulting high purity welds had Charpy impact properties similar to those of electron beam welds with similar grain size. A post-weld heat treatment (PWHT) of 950{degrees}C for two hours did not improve the properties of the weld in cases where low concentrations of impurities were attained. Further improvements in the gas clean-up system are needed to control hydrogen contamination.

  1. Effects of mineral content on the fracture properties of equine cortical bone in double-notched beams.

    Science.gov (United States)

    McCormack, Jordan; Stover, Susan M; Gibeling, Jeffery C; Fyhrie, David P

    2012-06-01

    We recently developed a method to measure cortical bone fracture initiation toughness using a double-notched beam in four-point bending. This method was used to test the hypothesis that mineralization around the two notch roots is correlated with fracture toughness and crack extension (physical damage). Total energy absorbed to failure negatively correlated with average mineralization of the beam (r(2)=0.62), but not with notch root mineralization. Fracture initiation toughness was positively correlated to mineralization at the broken notch root (r(2)=0.34). Crack length extension at the unbroken notch was strongly negatively correlated with the average mineralization of the notch roots (r(2)=0.81) whereas crack length extension at the broken notch did not correlate with any of the mineralization measurements. Mineralization at the notch roots and the average mineralization contributed independently to the mechanical and damage properties. The data are consistent with a hypothesis that a) high notch root mineralization results in less stable crack length extension but high force to initiate unstable crack propagation while b) higher average mineralization leads to low post-yield (and total) energy absorption to failure. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Ultra-Wideband Notched Characteristic Fed by Coplanar Waveguide

    Directory of Open Access Journals (Sweden)

    Rastanto Hadinegoro

    2015-02-01

    Full Text Available In this paper, a novel Ultra-Wide Band (UWB notch patch antenna with co-planar waveguide (CPW fed is presented. This antenna only used one layer and the patch antenna is constructed on the first layer and back to back with CPW fed and bottom part is ground plane. The width notch is used to achieve the UWB characteristic. The results shown that the impedance bandwidth is 1130 MHz (1.662–2.792 GHz or about 50.7% for VSWR <2.

  3. Effect on fast neutron irradiation to 4 dpa at 400{degrees}C on the properties of V-(4-5)Cr-(4-5)Ti alloys

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Alexander, D.J.; Robertson, J.P. [Oak Ridge National Lab., TN (United States)] [and others

    1997-04-01

    Tensile, Charpy impact and electrical resistivity measurements have been performed at ORNL on V-4Cr-4Ti and V-5Cr-5Ti specimens that were prepared at ANL and irradiated in the lithium-bonded X530 experiment in the EBR-II fast reactor. All of the specimens were irradiated to a damage level of about 4 dpa at a temperature of {approximately}400{degrees}C. A significant amount of radiation hardening was evident in both the tensile and Charpy impact tests. The irradiated V-4Cr-4Ti yield strength measured at {approximately}390{degrees}C was >800 MPa, which is more than three times as high as the unirradiated value. The uniform elongations of the irradiated tensile specimens were typically {approximately}1%, with corresponding total elongations of 4-6%. The ductile to brittle transition temperature of the irradiated specimens was less than the unirradiated resistivity, which suggests that hardening associated with interstitial solute pickup was minimal.

  4. Estimations of creep behavior and failure life for a circumferentially notched specimen

    International Nuclear Information System (INIS)

    Kobayashi, Ken-ichi; Yokobori, Toshimitsu; Kikuchi, Kenji.

    1997-01-01

    No method with which to characterize and/or illustrate total creep behavior for specimens with notches, holes or cracks has been proposed. In this paper it is proposed that most creep curves can be drawn with a master curve for each creep test whenever test conditions and failure modes are similar to each other, and the lifetime ratio normalized by the rupture time is introduced. Using smooth and circumferentially notched specimens of 2.25 Cr-1 Mo steel, creep tests were performed at 600degC for examination of this concept. Furthermore, a θ projection method was used to describe creep curves for notched specimens and to extrapolate longer creep lives. Then, the whole creep curve shape for notched specimens could be easily drawn, except for that in the vicinity of the rupture point. However, longer creep lives of notched specimens were underestimated in comparison with a simple extrapolation of the experimental data. This resulted from the negative dependence of the parameter of θ 3 on the applied stress. (author)

  5. 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...

  6. Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros.

    Science.gov (United States)

    Naylor, Richard W; Jones, Elizabeth A

    2009-11-01

    Previous studies have highlighted a role for the Notch signalling pathway during pronephrogenesis in the amphibian Xenopus laevis, and in nephron development in the mammalian metanephros, yet a mechanism for this function remains elusive. Here, we further the understanding of how Notch signalling patterns the early X. laevis pronephros anlagen, a function that might be conserved in mammalian nephron segmentation. Our results indicate that early phase pronephric Notch signalling patterns the medio-lateral axis of the dorso-anterior pronephros anlagen, permitting the glomus and tubules to develop in isolation. We show that this novel function acts through the Notch effector gene hrt1 by upregulating expression of wnt4. Wnt-4 then patterns the proximal pronephric anlagen to establish the specific compartments that span the medio-lateral axis. We also identified pronephric expression of lunatic fringe and radical fringe that is temporally and spatially appropriate for a role in regulating Notch signalling in the dorso-anterior region of the pronephros anlagen. On the basis of these results, along with data from previous publications, we propose a mechanism by which the Notch signalling pathway regulates a Wnt-4 function that patterns the proximal pronephric anlagen.

  7. 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....

  8. Notch and hydrogen effects on sensitized 21-6-9 stainless steel

    International Nuclear Information System (INIS)

    Caskey, C.R. Jr.

    1979-01-01

    Type 21-6-9 stainless steel alloy is slightly notch sensitive in the solution annealed condition, a behavior that is aggravated by sensitization anneal at 920 0 K. The lower toughness of the sensitized alloy is a measure of microstructural embrittlement associated with carbide precipitation in grain boundaries. The tendency toward grain boundary fracture in the sensitized alloy is accentuated by stress concentration at the notch. Also, there is an increase in notch sensitivity when the alloy is tested in a high pressure (69 MPa) hydrogen environment, due to susceptibility of the grain boundaries to hydrogen embrittlement

  9. Thermally induced high frequency random amplitude fatigue damage at sharp notches

    International Nuclear Information System (INIS)

    Lewis, M.W.J.

    1992-01-01

    Experiments have been performed using the SUPERSOMITE facility to investigate the initiation and growth of fatigue cracks at the tips of sharp surface notches subjected to random thermally-induced stress. The experimental situation is complex involving plasticity, random amplitude loading and heat transfer medium/surface coupling. Crack initiation and growth prediction have been considered using the Creager and Neuber methods to compute the strain ranges in the vicinity of the notch root. Good agreement has been obtained between the experimental results and theoretical predictions. The paper reports the results of the analysis of the notch behavior

  10. Instrumented impact testing machine with reduced specimen oscillation effects

    International Nuclear Information System (INIS)

    Rintamaa, R.; Rahka, K.; Wallin, K.

    1984-07-01

    Owing to small and inexpensive specimens the Charpy impact test is widely used in quality control and alloy development. Limitations in power reactor survellance capsules it is also widely used for safety analysis purposes. Instrumenting the tup and computerizing data acquisition, makes dynamic fracture mechanics data measurement possible and convenient. However, the dynamic effects (inertia forces, specimen oscillations) in the impact test cause inaccuracies in the recorded load-time diagram and hence diminish the reliability of the calculated dynamic fracture mechanics parameters. To decrease inaccuracies a new pendulum type of instrumented impact test apparatus has been developed and constructed in the Metals Laboratory of the Technical Research Centre of Finland. This tester is based on a new principle involving inverted test geometry. The purpose of the geometry inversion is to reduce inertia load and specimen oscillation effects. Further, the new impact tester has some other novel features: e.g. the available initia impact energy is about double compared to the conventional standard (300 J) impact tester allowing the use of larger (10 x 20 x 110 mm) bend specimens than normal Charpy specimens. Also, the rotation asix in the three point bending is nearly stationary making COD-measurements possible. An experimental test series is described in which the inertia effects and specimen oscillations are compared in the conventional and new impact tester utilizing Charpy V-notch specimens. Comparison of the two test geometries is also made with the aid of an analytical model using finite element method (FEM) analysis. (author)

  11. Ductile Fracture Behaviour of Hot Isostatically Pressed Inconel 690 Superalloy

    Science.gov (United States)

    Cooper, A. J.; Brayshaw, W. J.; Sherry, A. H.

    2018-04-01

    Herein we assess the differences in Charpy impact behavior between Hot Isostatically Pressed and forged Inconel 690 alloy over the temperature range of 300 °C to - 196 °C. The impact toughness of forged 690 exhibited a relatively small temperature dependence, with a maximum difference of ca. 40 J measured between 300 °C and - 196 °C, whereas the HIP'd alloy exhibited a difference of approximately double that of the forged alloy over the same temperature range. We have conducted Charpy impact testing, tensile testing, and metallographic analyses on the as-received materials as well as fractography of the failed Charpy specimens in order to understand the mechanisms that cause the observed differences in material fracture properties. The work supports a recent series of studies which assess differences in fundamental fracture behavior between Hot Isostatically Pressed and forged austenitic stainless steel materials of equivalent grades, and the results obtained in this study are compared to those of the previous stainless steel investigations to paint a more general picture of the comparisons between HIP vs forged material fracture behavior. Inconel 690 was selected in this study since previous studies were unable to completely omit the effects of strain-induced martensitic transformation at the tip of the Chary V-notch from the fracture mechanism; Inconel 690 is unable to undergo strain-induced martensitic transformation due to the alloy's high nickel content, thereby providing a sister study with the omission of any martensitic transformation effects on ductile fracture behavior.

  12. Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

    Directory of Open Access Journals (Sweden)

    Angelo Sparaneo

    2016-01-01

    Full Text Available The transcription factor Nrf2 (NF-E2 related factor 2 is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

  13. 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...

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

    International Nuclear Information System (INIS)

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-01-01

    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.

  15. 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.

  16. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    International Nuclear Information System (INIS)

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

    2005-01-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

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

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

    Full Text Available 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.

  18. Acoustic emission during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches

    International Nuclear Information System (INIS)

    Mukhopadhyay, C.K.; Jayakumar, T.; Baldev Raj

    1996-01-01

    Acoustic emission generated during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches has been studied. The extent of acoustic activity generated depends on notch tip severity, notch tip blunting and tearing of the notches. The equation N=AK m applied to the acoustic emission data of the notched specimens has shown good correlation. Acoustic emission technique can be used to estimate the size of an unknown notch. (author)

  19. Power spectra decomposition of 36 RS CVn UBV photometric light curves from the first two years of the automatic photoelectric telescope

    International Nuclear Information System (INIS)

    Nelson, E.R.

    1988-01-01

    The first search for multiple periodic structure of a major subset of the RS CVn class of interacting binary stars systems, using a rigorous numerical approach appropriate to unevenly-spaced gapped data, is presented. The main intent of this dissertation is to characterize properly the power spectral content of RS CVn binary light curves and describe how this information can constrain the current models for the systems. If the light curve can be considered as a tracer of stellar surface activity, then the photometric distortions can be used to characterize magnetic activity cycles and add to the understanding of stellar dynamics. Most of the systems exhibit multiple periodic structure, 40% of which show changes in the photometric period on a time scale of a few hundred days. A preference is observed for photometric periods with time scales near the orbital and half orbital periods. The effect is particularly strong for the shorter period systems and is interpreted as evidence for synchronous, or near synchronous, rotation. A strong linear correlation in the periods for the multiply periodic systems is observed which indicates a preferential pairing of spot groups on the stellar surface. No correlation is found for the relative phases of the multiple periodic signals. Changes in the photometric period are associated with variations in the amplitude of the distortion wave, which would indicate the growth and decay of spot groups. The growth and decay of pairs of spot groups, arbitrarily separated in phase, on a differentially rotating star is the model most consistent with the results of my analysis

  20. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  1. Fibre Optic Notch Filter For The Antiproton Decelerator Stochastic Cooling System

    CERN Document Server

    Simmonds, Max Vincent John

    2016-01-01

    The project scope included reverse engineering, upgrading, and recovering the operational conditions of an existing fibre optic notch filter. Once operational, tests were to be preformed to confirm the performance of the temperature stabilisation. The end goal is to use said notch filter in the Antiproton Decelerator (AD) facility at CERN to help aid antimatter research. The notch filter was successfully reverse engineered and then documented. Changes were made in order to increase performance and reliability, and also allow easy integration into the AD. An additional phase was added whereby the notch filter was to be controller via a touchscreen computer, situated next to the filter, allowing engineers to set-up each of the electronic devices used. While one of the devices (Motorised Delay Line) can be controlled by the touchscreen computer, the other two cannot.Due to time constraints and difficulties with the Beckhoff TwincatII programming language, the USB devices were not able to be controlled via the To...

  2. Notch signaling in embryology and cancer

    National Research Council Canada - National Science Library

    Reichrath, J; Reichrath, Sandra

    2012-01-01

    "The goal of this volume is to comprehensively cover a highly readable overview on our present knowledge of the role of Notch signalling for embryology and cancer, with a focus on new findings in molecular biology...

  3. Conditions for crack initiation in an orthotropic bi-material notch

    Czech Academy of Sciences Publication Activity Database

    Klusák, Jan; Profant, T.; Kotoul, M.

    2012-01-01

    Roč. 19, č. 4 (2012), s. 302-307 ISSN 1537-6494 R&D Projects: GA ČR GA101/08/0994; GA ČR GAP108/10/2049 Institutional support: RVO:68081723 Keywords : General singular stress concentrators * Fracture mechanics * Notch es * Bi-material notch es * Fracture mechanics Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.701, year: 2012

  4. On the notch ductility of a magnesium-rare earth alloy

    Energy Technology Data Exchange (ETDEWEB)

    Kondori, B., E-mail: bkondori.13034@tamu.edu [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Benzerga, A.A. [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Department of Aerospace Engineering, Texas A& M University, College Station, TX 77843 (United States)

    2015-10-28

    The room-temperature notch ductility of magnesium-rare earth alloy WE43 is investigated for two loading orientations. This material is endowed with quasi-isotropic plastic flow properties, higher strength and similar uniaxial ductility in comparison with other commercially available Mg alloys. The authors have recently shown that the notch ductility of a Mg–Al–Zn alloy is greater than its uniaxial ductility over a wide range of notch geometries. This paper investigates whether the same trends hold for WE43, discusses the orientation dependence of ductility and the propensity for intergranular fracture at high levels of hydrostatic tension. The latter mode of fracture is analyzed by means of detailed fractography in order to elucidate the role of grain-boundary particles and precipitates in the fracture process.

  5. Effects of irradiation on initiation and crack-arrest toughness of two high-copper welds and on stainless steel cladding

    International Nuclear Information System (INIS)

    Nanstad, R.K.; Iskander, S.K.; Haggag, F.M.

    1990-01-01

    The objective of the study on the high-copper welds is to determine the effect of neutron irradiation on the shift and shape of the ASME K Ic and K Ia toughness curves. Two submerged-arc welds with copper contents of 0.23 and 0.31 wt % were commercially fabricated in 220-mm-thick plate. Compact specimens fabricated from these welds were irradiated at a nominal temperature of 288 degree C to fluences from 1.5 to 1.9 x 10 19 neutrons/cm 2 (>1 MeV). The fracture toughness test results show that the irradiation-induced shifts at 100 MPa/m were greater than the Charpy 41-J shifts by about 11 and 18 degree C. Mean curve fits indicate mixed results regarding curve shape changes, but curves constructed as lower boundaries to the data do indicate curves of lower slopes. A preliminary evaluation of the crack-arrest results shows that the neutron-irradiation induced crack-arrest toughness temperature shift is about the same as the Charpy V-notch impact temperature shift at the 41-J energy level. The shape of the lower bound curves (for the range of test temperatures covered), compared to those of the ASME K Ia curve did not appear to have been altered by the irradiation. Three-wire stainless steel weld overlay cladding was irradiated at 288 degree C to fluences of 2 and 5 x 10 19 neutrons/cm 2 (>1 MeV). Charpy 41-J temperature shifts of 13 and 28 degree C were observed, respectively. For the lower fluence only, 12.7-mm thick compact specimens showed decreases in both J Ic and the tearing modulus. Comparison of the fracture toughness results with typical plate and a low upper-shelf weld reveals that the irradiated stainless steel cladding possesses low ductile initiation fracture toughness comparable to the low upper-shelf weld. 8 refs., 12 figs., 2 tabs

  6. The effect of electric discharge machined notches on the fracture toughness of several structural alloys

    International Nuclear Information System (INIS)

    Joyce, J.A.; Link, R.E.

    1993-09-01

    Recent computational studies of the stress and strain fields at the tip of very sharp notches have shown that the stress and strain fields are very weakly dependent on the initial geometry of the notch once the notch has been blunted to a radius that is 6 to 10 times the initial root radius. It follows that if the fracture toughness of a material is sufficiently high so that fracture initiation does not occur in a specimen until the crack-tip opening displacement (CTOD) reaches a value from 6 to 10 times the size of the initial notch tip diameter, then the fracture toughness will be independent of whether a fatigue crack or a machined notch served as the initial crack. In this experimental program the fracture toughness (J Ic and J resistance (J-R) curve, and CTOD) for several structure alloys was measured using specimens with conventional fatigue cracks and with EDM machined notches. The results of this program have shown, in fact, that most structural materials do not achieve initiation CTOD values on the order of 6 to 10 times the radius of even the smallest EDM notch tip presently achievable. It is found furthermore that tougher materials do not seem to be less dependent on the type of notch tip present. Some materials are shown to be much more dependent on the type of notch tip used, but no simple pattern is found that relates this observed dependence to the material strength toughness, or strain hardening rate

  7. Fractographic examination of reduced activation ferritic/martensitic steel charpy specimens irradiated to 30 dpa at 370{degrees}C

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S.; Hamilton, M.L. [Pacific Northwest National Lab., Richland, WA (United States); Schubert, L.E. [Univ. of Missouri, Rolla, MO (United States)

    1996-10-01

    Fractographic examinations are reported for a series of reduced activation ferritic/Martensitic steel Charpy impact specimens tested following irradiation to 30 dpa at 370{degrees}C in FFTF. One-third size specimens of six low activation steels developed for potential application as structural materials in fusion reactors were examined. A shift in brittle fracture appearance from cleavage to grain boundary failure was noted with increasing manganese content. The results are interpreted in light of transmutation induced composition changes in a fusion environment.

  8. Experimental and Numerical Analysis of Notched Composites Under Tension Loading

    Science.gov (United States)

    Aidi, Bilel; Case, Scott W.

    2015-12-01

    Experimental quasi-static tests were performed on center notched carbon fiber reinforced polymer (CFRP) composites having different stacking sequences made of G40-600/5245C prepreg. The three-dimensional Digital Image Correlation (DIC) technique was used during quasi-static tests conducted on quasi-isotropic notched samples to obtain the distribution of strains as a function of applied stress. A finite element model was built within Abaqus to predict the notched strength and the strain profiles for comparison with measured results. A user-material subroutine using the multi-continuum theory (MCT) as a failure initiation criterion and an energy-based damage evolution law as implemented by Autodesk Simulation Composite Analysis (ASCA) was used to conduct a quantitative comparison of strain components predicted by the analysis and obtained in the experiments. Good agreement between experimental data and numerical analyses results are observed. Modal analysis was carried out to investigate the effect of static damage on the dominant frequencies of the notched structure using the resulted degraded material elements. The first in-plane mode was found to be a good candidate for tracking the level of damage.

  9. Notch root strain measurement of WE43-T6 magnesium alloy using electronic speckle pattern interferometry

    International Nuclear Information System (INIS)

    Liew, H.L.; Ahmad, A.; Ramesh, S.; Purbolaksono, J.

    2013-01-01

    Highlights: • The use of ESPI for measuring total strains at the notch root of specimens. • Fine meshing in micron scale at the notch root regions. • The maximum elastic strain is shifted to be further away from the notch root tip. - Abstract: The notch root elasto-plastic strains of circumferentially grooved round specimen of cast magnesium WE43-T6 were experimentally measured using the electronic speckle pattern interferometry (ESPI) and numerically evaluated using the finite element analysis (FEA). The specimens have notch radii of 1.6 mm and 0.8 mm and an opening angle of 60°. The technique of ESPI showed its accuracy in measuring three-dimensional surface deformations on large negatively curved manifolds. The measured nominal stress for rupture is well beyond the ultimate strength, suggesting the existence of significant biaxial stress at the notch root region. The ESPI-based strains on the notch tips were shown to be in agreement with those evaluated by the FEA. The FEA also showed that the maximum elastic strain is shifted away from the notch root surface as the plastic strain is predominant

  10. The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

    Science.gov (United States)

    Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

    2001-01-01

    An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. Without definitions or examples of optic disc rim notching, the glaucoma

  11. Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

    NARCIS (Netherlands)

    Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

    2008-01-01

    Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

  12. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Science.gov (United States)

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

    Directory of Open Access Journals (Sweden)

    Chen-Yuan Tseng

    2014-12-01

    Full Text Available Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs, and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  14. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  15. Design of UWB Filter with WLAN Notch

    Directory of Open Access Journals (Sweden)

    Harish Kumar

    2012-01-01

    Full Text Available UWB technology- (operating in broad frequency range of 3.1–10.6 GHz based filter with WLAN notch has shown great achievement for high-speed wireless communications. To satisfy the UWB system requirements, a band pass filter with a broad pass band width, low insertion loss, and high stop-band suppression are needed. UWB filter with wireless local area network (WLAN notch at 5.6 GHz and 3 dB fractional bandwidth of 109.5% using a microstrip structure is presented. Initially a two-transmission-pole UWB band pass filter in the frequency range 3.1–10.6 GHz is achieved by designing a parallel-coupled microstrip line with defective ground plane structure using GML 1000 substrate with specifications: dielectric constant 3.2 and thickness 0.762 mm at centre frequency 6.85 GHz. In this structure a λ/4 open-circuited stub is introduced to achieve the notch at 5.6 GHz to avoid the interference with WLAN frequency which lies in the desired UWB band. The design structure was simulated on electromagnetic circuit simulation software and fabricated by microwave integrated circuit technique. The measured VNA results show the close agreement with simulated results.

  16. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  17. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-01-01

    Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

  18. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

    Science.gov (United States)

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-04-01

    Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. The significance of the neurovascular structures passing through the spinoglenoid notch

    International Nuclear Information System (INIS)

    Atekin, Mustafa; Demiryiirek, Deniz; Bayramoglu, Alp; Tuccar, Eray

    2003-01-01

    To define the detailed anatomy of the neurovascular bundle at the spinoglenoid notch and to report the dimensions of these structures in cadavers. In the present study, the external diameters of suprascapular artery, vein and nerve were measured at the spinoglenoid region in 18 formalin fixed cadavers (36 soulders) by using a caliper. The study was carried out in the dissection laboratory of Anatomy Department of Hacettepe University ,Ankara University, Ankara and Mersin University ,Mersin,Turkey, between2002 and 2003.The average external diameter for suprascapular vein was 2.6 mmand nerve was 2.2 mm. The spinoglenoid notch was roofed by the spinoglenoid ligament and appeared as a fibroosseous foramen in all cadavers. We found that vascular structures (suprascapular artery and vein )occupied 68.5% and the suprascapular nerve occupied 31.5% of this foramen. Although the diameters of the vascular structures at the spinoglenoid notch measured by magnetic resonance imaging have been reported,to our knowledge, external diameters of these structures at the spinoglenoid notch have not been described in cadavers. We believe that detailed anatomy of suprascapular neurovascular bundle at the spinoglenoid notch should be appreciated for better understanding of risk factors possibly causing the sprascapular nerve entrapment syndrome specially for those who are involved in voilent ovehead sports activities such as volleyball and baseball. (author)

  1. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    Directory of Open Access Journals (Sweden)

    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  2. In-place thermal annealing of nuclear reactor pressure vessels

    International Nuclear Information System (INIS)

    Server, W.L.

    1985-04-01

    Radiation embrittlement of ferritic pressure vessel steels increases the ductile-brittle transition temperature and decreases the upper shelf level of toughness as measured by Charpy impact tests. A thermal anneal cycle well above the normal operating temperature of the vessel can restore most of the original Charpy V-notch energy properties. The Amry SM-1A test reactor vessel was wet annealed in 1967 at less than 343 0 C (650 0 F), and wet annealing of the Belgian BR-3 reactor vessel at 343 0 C (650 0 F) has recently taken place. An industry survey indicates that dry annealing a reactor vessel in-place at temperatures as high as 454 0 C (850 0 F) is feasible, but solvable engineering problems do exist. Economic considerations have not been totally evaluated in assessing the cost-effectiveness of in-place annealing of commercial nuclear vessels. An American Society for Testing and Materials (ASTM) task group is upgrading and revising guide ASTM E 509-74 with emphasis on the materials and surveillance aspects of annealing rather than system engineering problems. System safety issues are the province of organizations other than ASTM (e.g., the American Society of Mechanical Engineers Boiler and Pressure Vessel Code body)

  3. Size effect in radiation damage

    International Nuclear Information System (INIS)

    Brumovsky, M.

    1979-01-01

    Radiation embrittlement of nuclear reactor pressure vessel steels is mostly measured using small standard specimens in dynamic bend tests. Their dimensions are much smaller than those of the reactor. The increase in the critical temperature (transition temperature from the brittle-to-ductile fracture) is normally measured using standard Charpy-V type specimens or small CT-type specimens. This increase is then used as the main parameter for the pressure vessel safety evaluation. The philosophy of experiments is discussed used for the nonirradiated and irradiated pressure vessel steels. A comparison of the increase in the transition temperature measured in different types of specimens using various testing methods (static and dynamic bend tests with notch or crack) is also made. The results of this comparison and another study showed a relatively good agreement. (author)

  4. Evaluations of the criterion for lateral expansion of steels for nuclear components

    International Nuclear Information System (INIS)

    Susukida, H.; Satoh, M.; Fukuhara, A.

    1980-01-01

    The Charpy V notch impact tests were performed on Japanese made ferritic steels for nuclear components and their lateral expansions were investigated. The correlations of lateral expansion and absorbed energy with yield strength, and the correlation between lateral expansion and fracture toughness were also studied. The correlation at each lateral expansion level between absorbed energy and yield strength almost agreed with that published by the US PVRC. It was confirmed that lateral expansion could be used as a criterion for the toughness of the steels corresponding to changes in their yield strength, and that the lateral expansion criterion adopted in the ASME Code Section III was appropriate. Further, the correlation between fracture toughness and lateral expansion and that between fracture toughness and absorbed energy, were evaluated, and respective equations of correlation were proposed. (author)

  5. The effect of plasma arc process parameters on the properties of dissimilar AISI 1040/AISI 304 steel plate welds

    Energy Technology Data Exchange (ETDEWEB)

    Kilic, Musa; Kirik, Ihsan; Orhan, Nuri [Firat Univ., Elazig (Turkey); Celik, Ferkan [Science Industry and Technology Ministry of Turkey (Turkey)

    2012-11-01

    In this study, 10 mm thick AISI 1040 and AISI 304 steel plates were welded in the butt position without pretreatment by plasma transferred arc (PTA) welding technique. Therefore, mechanical behaviour, microstructure, penetration depth and length were investigated. After welding, microstructural changes in the interface regions of the welded specimens were examined by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). Micro-hardness as well as V-notch Charpy tests were performed to determine the mechanical properties of the welds. The influence of the welding parameters on the dimension and shape of the joints has been found out. From the results, it was derived that with the parameters used, a partly keyhole weld bead formed with a penetration depth of 10 mm and a width of 11 mm in butt position. (orig.)

  6. Toughness testing and high-temperature oxidation evaluations of advanced alloys for core internals

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Lizhen [ORNL; Pint, Bruce A [ORNL; Chen, Xiang [ORNL

    2016-09-16

    Alloy X-750 was procured from Carpenter Technology and Bodycote in this year. An appropriate TMT was developed on Alloy 439 to obtain materials with refined grain size for property screening tests. Charpy V-notch impact tests were completed for the three ferritic steels Grade 92, Alloy 439, and 14YWT. Fracture toughness tests at elevated temperatures were completed for 14YWT. The tests will be completed for the other alloys in next fiscal year. Steam oxidation tests of the three ferritic steels, 316L, and Zr–2.5Nb have been completed. The steam tests of the Ni-based superalloys and the other austenitic stainless steels will be continued and finished in next fiscal year. Performance ranking in terms of steam oxidation resistance and impact/fracture toughness of the alloys will be deduced.

  7. Reactor pressure vessel structural integrity research in the US Nuclear Regulatory Commission HSST and HSSI Programs

    International Nuclear Information System (INIS)

    Pennell, W.E.; Corwin, W.R.

    1994-01-01

    This report discusses development on the technology used to assess the safety of irradiation-embrittled nuclear reactor pressure vessels containing flaws. Fracture mechanics tests on reactor pressure vessel steel have shown that local brittle zones do not significantly degrade the material fracture toughness, constraint relaxation at the crack tip of shallow surface flaws results in increased fracture toughness, and biaxial loading reduces but does not eliminate the shallow-flaw fracture toughness elevation. Experimental irradiation investigations have shown that the irradiation-induced shift in Charpy V-notch versus temperature behavior may not be adequate to conservatively assess fracture toughness shifts due to embrittlement and the wide global variations of initial chemistry and fracture properties of a nominally uniform material within a pressure vessel may confound accurate integrity assessments that require baseline properties

  8. Application of FIB technique to introduction of a notch into a carbon fiber for direct measurement of fracture toughness

    International Nuclear Information System (INIS)

    Ogihara, S; Imafuku, Y; Yamamoto, R; Kogo, Y

    2009-01-01

    For the direct measurement of the fracture toughness of the carbon fiber, a new technique was proposed and examined its applicability. At first, machining condition of the notch was examined. The notch was introduced using focused ion beam (FIB). The ion beam can be electronically scanned to introduce a sharp notch on the carbon fiber. Notches with various notch width and length were introduced by changing beam and scanning conditions. Tensile tests on notched carbon fibers were carried out following the test method for carbon fiber monofilaments. Fractured specimens were successfully corrected without secondary damage using protection films. SEM observations revealed that a crack propagated from a notch-tip, and notch size was able to be determined successfully. Effect of notch root radius was also examined to investigate the validity of the fracture toughness obtained by this method.

  9. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    NARCIS (Netherlands)

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal.

  10. Sequestration of latent TGF-β binding protein 1 into CADASIL-related Notch3-ECD deposits.

    Science.gov (United States)

    Kast, Jessica; Hanecker, Patrizia; Beaufort, Nathalie; Giese, Armin; Joutel, Anne; Dichgans, Martin; Opherk, Christian; Haffner, Christof

    2014-08-13

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents the most common hereditary form of cerebral small vessel disease characterized by early-onset stroke and premature dementia. It is caused by mutations in the transmembrane receptor Notch3, which promote the aggregation and accumulation of the Notch3 extracellular domain (Notch3-ECD) within blood vessel walls. This process is believed to mediate the abnormal recruitment and dysregulation of additional factors including extracellular matrix (ECM) proteins resulting in brain vessel dysfunction. Based on recent evidence indicating a role for the transforming growth factor-β (TGF-β) pathway in sporadic and familial small vessel disease we studied fibronectin, fibrillin-1 and latent TGF-β binding protein 1 (LTBP-1), three ECM constituents involved in the regulation of TGF-β bioavailability, in post-mortem brain tissue from CADASIL patients and control subjects. Fibronectin and fibrillin-1 were found to be enriched in CADASIL vessels without co-localizing with Notch3-ECD deposits, likely as a result of fibrotic processes secondary to aggregate formation. In contrast, LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates. We also detected increased levels of the TGF-β prodomain (also known as latency-associated peptide, LAP) indicating dysregulation of the TGF-β pathway in CADASIL development. In vitro analyses revealed a direct interaction between LTBP-1 and Notch3-ECD and demonstrated a specific co-aggregation of LTBP-1 with mutant Notch3. We propose LTBP-1 as a novel component of Notch3-ECD deposits and suggest its involvement in pathological processes triggered by Notch3-ECD aggregation.

  11. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.

    Science.gov (United States)

    Goh, Gerald; Walradt, Trent; Markarov, Vladimir; Blom, Astrid; Riaz, Nadeem; Doumani, Ryan; Stafstrom, Krista; Moshiri, Ata; Yelistratova, Lola; Levinsohn, Jonathan; Chan, Timothy A; Nghiem, Paul; Lifton, Richard P; Choi, Jaehyuk

    2016-01-19

    Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. To define the genetic basis of MCCs, we performed exome sequencing of 49 MCCs. We show that MCPyV-negative MCCs have a high mutation burden (median of 1121 somatic single nucleotide variants (SSNVs) per-exome with frequent mutations in RB1 and TP53 and additional damaging mutations in genes in the chromatin modification (ASXL1, MLL2, and MLL3), JNK (MAP3K1 and TRAF7), and DNA-damage pathways (ATM, MSH2, and BRCA1). In contrast, MCPyV-positive MCCs harbor few SSNVs (median of 12.5 SSNVs/tumor) with none in the genes listed above. In both subgroups, there are rare cancer-promoting mutations predicted to activate the PI3K pathway (HRAS, KRAS, PIK3CA, PTEN, and TSC1) and to inactivate the Notch pathway (Notch1 and Notch2). TP53 mutations appear to be clinically relevant in virus-negative MCCs as 37% of these tumors harbor potentially targetable gain-of-function mutations in TP53 at p.R248 and p.P278. Moreover, TP53 mutational status predicts death in early stage MCC (5-year survival in TP53 mutant vs wild-type stage I and II MCCs is 20% vs. 92%, respectively; P = 0.0036). Lastly, we identified the tumor neoantigens in MCPyV-negative and MCPyV-positive MCCs. We found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantigens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses. Collectively, these data support the use of immunotherapies for virus-negative MCCs.

  12. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Jian Liu

    Full Text Available Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

  13. ADAM10 regulates Notch function in intestinal stem cells of mice.

    Science.gov (United States)

    Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

    2014-10-01

    A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Science.gov (United States)

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  15. The role of uric acid in the pathogenesis of diabetic retinopathy based on notch pathway.

    Science.gov (United States)

    Zhu, Dan-Dan; Wang, Yun-Zhi; Zou, Chen; She, Xin-Ping; Zheng, Zhi

    2018-06-19

    Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown. We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively. In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly

  16. An obligatory role of mind bomb-1 in notch signaling of mammalian development.

    Directory of Open Access Journals (Sweden)

    Bon-Kyoung Koo

    2007-11-01

    Full Text Available The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood.Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2(-/- mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants.Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.

  17. Notch Filter Analysis and Its Application in Passive Coherent Location Radar (in English

    Directory of Open Access Journals (Sweden)

    Li Ji-chuan

    2015-01-01

    Full Text Available The Normalized Least-Mean-Squares (NLMS algorithm is widely used to cancel the direct and multiple path interferences in Passive Coherent Location (PCL radar systems. This study proposes that the interference cancelation using the NLMS algorithm and the calculation of the radar Cross Ambiguity Function (CAF can be modeled as a notch filter, with the notch located at zero Doppler frequency in the surface of the radar CAF. The analysis shows that the notch’s width and depth are closely related to the step size of the NLMS algorithm. Subsequently, the effect of the notch in PCL radar target detection is analyzed. The results suggest that the detection performance of the PCL radar deteriorates because of the wide notch. Furthermore, the Nonuniform NLMS (NNLMS algorithm is proposed for removing the clutter with the Doppler frequency by using notch filtering. A step-size matrix is adopted to mitigate the low Doppler frequency clutter and lower the floor of the radar CAF. With the step-size matrix, can be obtained notches of different depths and widths in different range units of the CAF, which can filter the low Doppler frequency clutter. In addition, the convergence rate of the NNLMS algorithm is better than that of the traditional NLMS algorithm. The validity of the NNLMS algorithm is verified by experimental results.

  18. Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    Science.gov (United States)

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-07-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  19. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Science.gov (United States)

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. 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/.

  20. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Kuang, Shao-Qing; Fang, Zhihong; Zweidler-McKay, Patrick A; Yang, Hui; Wei, Yue; Gonzalez-Cervantes, Emilio A; Boumber, Yanis; Garcia-Manero, Guillermo

    2013-01-01

    The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA)/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL). We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2'-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

  1. Definition of the minimum longitude of insert in the rebuilding of Charpy test tubes for surveillance and life extension of vessels in Mexico

    International Nuclear Information System (INIS)

    Romero C, J.; Hernandez C, R.; Rocamontes A, M.

    2011-11-01

    In the National Institute of Nuclear Research (Mexico) a welding system for the rebuilding of Charpy test tubes has been developed, automated, qualified and used for the surveillance of the mechanical properties (mainly embrittlement) of the vessel. This system uses the halves of the rehearsed Charpy test tubes of the surveillance capsules extracted of the reactors, to obtain, of a rehearsed test tube, two reconstituted test tubes. This rebuilding process is used so much in the surveillance program like in the potential extension of the operation license of the vessel. To the halves of Charpy test tubes that have been removed the deformed part by machine are called -insert- and in a very general way the rebuilding consists in weld with the welding process -Stud Welding- two metallic implants in the ends of the insert, to obtain a reconstituted test tube. The main characteristic of this welding are the achieved small dimensions, so much of the areas welded as of the areas affected by the heat. The applicable normative settles down that the minim longitude of the insert for the welding process by Stud Welding it should be of 18 mm, however according to the same normative this longitude can diminish if is demonstrated analytic or experimentally that the central volume of 1 cm 3 in the insert is not affected. In this work the measurement of the temperature profiles to different distances of the welding interface is presented, defining an equation for the maximum temperatures reached in function of the distance, on the other hand the real longitude affected in the test tube by means of metallography is determined and this way the minimum longitude of the insert for this developed rebuilding system was determined. (Author)

  2. The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele.

    Science.gov (United States)

    Zanotti, Stefano; Canalis, Ernesto

    2016-05-01

    Activation of Notch1 in osteocytes of Rosa(Notch) mice, where a loxP-flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling. To determine whether Sost downregulation mediates the effects of Notch activation in osteocytes, Rosa(Notch) mice were crossed with transgenics expressing Cre recombinase or SOST under the control of the dentin matrix protein (Dmp)1 promoter. Dmp1-SOST transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous Dmp1-Cre transgenics heterozygous for the Rosa(Notch) allele (Dmp1-Cre;Rosa(Notch)) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in Dmp1-Cre;Rosa(Notch) mice hemizygous for the Dmp1-SOST transgene. The effect was associated with downregulated Notch signaling and suppressed Dmp1 and Rosa26 expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from Dmp1-Cre;Rosa(Notch) mice or from Rosa(Notch) control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed Dmp1, but not Cre or Rosa26, expression. These findings suggest that prevention of the Dmp1-Cre;Rosa(Notch) skeletal phenotype by Dmp1-SOST is not secondary to SOST expression but to interactions among the Dmp1-SOST and Dmp1-Cre transgenes and the Rosa26 locus. In conclusion, the Dmp1-SOST transgene suppresses the expression of the Dmp1-Cre transgene and of Rosa26. © 2015 Wiley Periodicals, Inc.

  3. Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors.

    Directory of Open Access Journals (Sweden)

    Xinzhu Deng

    Full Text Available Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202, a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202 is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

  4. A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B- and T-cell malignancies.

    Science.gov (United States)

    Ortega, M; Bhatnagar, H; Lin, A-P; Wang, L; Aster, J C; Sill, H; Aguiar, R C T

    2015-04-01

    Growing evidence suggests that microRNAs (miRNAs) facilitate the cross-talk between transcriptional modules and signal transduction pathways. MYC and NOTCH1 contribute to the pathogenesis of lymphoid malignancies. NOTCH induces MYC, connecting two signaling programs that enhance oncogenicity. Here we show that this relationship is bidirectional and that MYC, via a miRNA intermediary, modulates NOTCH. MicroRNA-30a (miR-30a), a member of a family of miRNAs that are transcriptionally suppressed by MYC, directly binds to and inhibits NOTCH1 and NOTCH2 expression. Using a murine model and genetically modified human cell lines, we confirmed that miR-30a influences NOTCH expression in a MYC-dependent fashion. In turn, through genetic modulation, we demonstrated that intracellular NOTCH1 and NOTCH2, by inducing MYC, suppressed miR-30a. Conversely, pharmacological inhibition of NOTCH decreased MYC expression and ultimately de-repressed miR-30a. Examination of genetic models of gain and loss of miR-30a in diffuse large B-cell lymphoma (DLBCL) and T-acute lymphoblastic leukemia (T-ALL) cells suggested a tumor-suppressive role for this miRNA. Finally, the activity of the miR-30a-NOTCH-MYC loop was validated in primary DLBCL and T-ALL samples. These data define the presence of a miRNA-mediated regulatory circuitry that may modulate the oncogenic signals originating from NOTCH and MYC.

  5. Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients.

    Science.gov (United States)

    Li, Qifeng; Zhang, Hui; Yu, Liang; Wu, Chao; Luo, Xinhui; Sun, He; Ding, Jianbing

    2018-01-01

    Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and cytokines of IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR or immunoblotting. Our results showed that DAPT effectively inhibited the protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, Th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. In conclusion, our results suggest that blocking Notch signaling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients. Copyright © 2017. Published by Elsevier B.V.

  6. Notch and VEGF Interactions in Breast Cancer

    National Research Council Canada - National Science Library

    Shawber, Carrie J

    2006-01-01

    The proposal objective is to define Notch and VEGFR-3 in breast cancer. We investigated this relationship in primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts...

  7. Delta-like Ligand-4-Notch Signaling Inhibition Regulates Pancreatic Islet Function and Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Fabienne Billiard

    2018-01-01

    Full Text Available Although Notch signaling has been proposed as a therapeutic target for type-2 diabetes, liver steatosis, and atherosclerosis, its direct effect on pancreatic islets remains unknown. Here, we demonstrated a function of Dll4-Notch signaling inhibition on the biology of insulin-producing cells. We confirmed enhanced expression of key Notch signaling genes in purified pancreatic islets from diabetic NOD mice and showed that treatment with anti-Dll4 antibody specifically abolished Notch signaling pathway activation. Furthermore, we showed that Notch inhibition could drive proliferation of β-islet cells and confer protection from the development of STZ-induced diabetes. Importantly, inhibition of the Dll4 pathway in WT mice increased insulin secretion by inducing the differentiation of pancreatic β-islet cell progenitors, as well as the proliferation of insulin-secreting cells. These findings reveal a direct effect of Dll4-blockade on pancreatic islets that, in conjunction with its immunomodulatory effects, could be used for unmet medical needs hallmarked by inefficient insulin action.

  8. Plastic deformation and failure mechanisms in nano-scale notched metallic glass specimens under tensile loading

    Science.gov (United States)

    Dutta, Tanmay; Chauniyal, Ashish; Singh, I.; Narasimhan, R.; Thamburaja, P.; Ramamurty, U.

    2018-02-01

    In this work, numerical simulations using molecular dynamics and non-local plasticity based finite element analysis are carried out on tensile loading of nano-scale double edge notched metallic glass specimens. The effect of acuteness of notches as well as the metallic glass chemical composition or internal material length scale on the plastic deformation response of the specimens are studied. Both MD and FE simulations, in spite of the fundamental differences in their nature, indicate near-identical deformation features. Results show two distinct transitions in the notch tip deformation behavior as the acuity is increased, first from single shear band dominant plastic flow localization to ligament necking, and then to double shear banding in notches that are very sharp. Specimens with moderately blunt notches and composition showing wider shear bands or higher material length scale characterizing the interaction stress associated with flow defects display profuse plastic deformation and failure by ligament necking. These results are rationalized from the role of the interaction stress and development of the notch root plastic zones.

  9. Engineered Biomaterials Control Differentiation and Proliferation of Human-Embryonic-Stem-Cell-Derived Cardiomyocytes via Timed Notch Activation

    Directory of Open Access Journals (Sweden)

    Jason C. Tung

    2014-03-01

    Full Text Available For cell-based treatments of myocardial infarction, a better understanding of key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required. Manipulation of Notch signaling has promise as it plays an important role during cardiovascular development, but previous studies presented conflicting results that Notch activation both positively and negatively regulates cardiogenesis. We developed surface- and microparticle-based Notch-signaling biomaterials that function in a time-specific activation-tunable manner, enabling precise investigation of Notch activation at specific developmental stages. Using our technologies, a biphasic effect of Notch activation on cardiac differentiation was found: early activation in undifferentiated human embryonic stem cells (hESCs promotes ectodermal differentiation, activation in specified cardiovascular progenitor cells increases cardiac differentiation. Signaling also induces cardiomyocyte proliferation, and repeated doses of Notch-signaling microparticles further enhance cardiomyocyte population size. These results highlight the diverse effects of Notch activation during cardiac development and provide approaches for generating large quantities of cardiomyocytes.

  10. Experimental assessments of notch ductility and tensile strength of stainless steel weldments after 1200C neutron irradiation

    International Nuclear Information System (INIS)

    Hawthorne, J.R.; Menke, B.H.; Awadalla, N.G.; O'Kula, K.R.

    1986-01-01

    The Charpy-V (C/sub v/) properties of AISI 300 series stainless steel plate, weld, and weld heat-affected zone (HAZ) materials from commercial production weldments in 406-mm-diameter pipe (12.7-mm wall) were investigated in unirradiated and irradiated conditions. Weld and HAZ tensile properties were also assessed in the two conditions. The plates and weld filler wires represent different steel melts; the welds were produced using the multipass MIG process. Weldment properties in two test orientations were evaluated. Specimens were irradiated in the UBR reactor to 1 x 10 20 n/cm 2 , E >0.1 MeV in a controlled temperature assembly. Specimen tests were performed at 25 0 C and 125 0 C. The radiation-induced reductions in C/sub v/ energy absorption at 25 0 C were about 42 percent for the weld and HAZ materials evaluated. A trend of energy increase with temperature was observed. The concomitant elevation in yield strength was about 53%. In contrast, the increase in tensile strength was only 16%. The postirradiation yield strength of the axial test orientation in the pipe was less than that of the circumferential test orientation. Results for the HAZ indicate that this component may be the weakest link in the weldment from a fracture resistant viewpoint

  11. The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt.

    Directory of Open Access Journals (Sweden)

    Sophie K Kay

    2017-02-01

    Full Text Available The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch's interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes. Chemical reaction network theory (CRNT is a powerful, generalised framework which assesses the capacity of our model for monostability or multistability, by analysing properties of the underlying network structure without recourse to specific parameter values or functional forms for reaction rates. CRNT highlights the role of β-catenin in stabilising the Notch pathway and damping oscillations, demonstrating that Wnt-mediated actions on the Hes1 promoter can induce dynamic transitions in the Notch system, from multistability to monostability. Time-dependent model simulations of cell pairs reveal the stabilising influence of Wnt upon the Notch pathway, in which β-catenin- and Dsh-mediated action on the Hes1 promoter are key in shaping the subcellular dynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notch oscillation and maintenance of fate flexibility; Wnt-mediated transcription of Hes1 favours bistability akin to cell fate selection. Cells could therefore regulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoter to coordinate the timing of cell fate selection as they migrate through the intestinal epithelium and are subject to reduced Wnt stimuli. Furthermore, mutant cells characterised by hyperstimulation of the Wnt pathway may, through coupling with Notch, invert cell fate in neighbouring healthy cells, enabling an aberrant

  12. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  13. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

    Science.gov (United States)

    Feng, Shufang; Shi, Tianyao; Qiu, Jiangxia; Yang, Haihong; Wu, Yan; Zhou, Wenxia; Wang, Wei; Wu, Haitao

    2017-10-01

    It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) + neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 -/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. © FASEB.

  14. Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment.

    Science.gov (United States)

    Katsushima, Keisuke; Natsume, Atsushi; Ohka, Fumiharu; Shinjo, Keiko; Hatanaka, Akira; Ichimura, Norihisa; Sato, Shinya; Takahashi, Satoru; Kimura, Hiroshi; Totoki, Yasushi; Shibata, Tatsuhiro; Naito, Mitsuru; Kim, Hyun Jin; Miyata, Kanjiro; Kataoka, Kazunori; Kondo, Yutaka

    2016-12-06

    Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.

  15. Notch Signaling Is Associated With ALDH Activity And An Aggressive Metastatic Phenotype In Murine Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong eMu

    2013-06-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone, and pulmonary metastatic disease accounts for nearly all mortality. However, little is known about the biochemical signaling alterations that drive the progression of metastatic disease. Two murine OS cell populations, K7M2 and K12, are clonally related but differ significantly in their metastatic phenotypes and therefore represent excellent tools for studying metastatic OS molecular biology. K7M2 cells are highly metastatic, whereas K12 cells display limited metastatic potential. Here we report that the expression of Notch genes (Notch1, 2, 4 are up-regulated, including downstream targets Hes1 and Stat3, in the highly metastatic K7M2 cells compared to the less metastatic K12 cells, indicating that the Notch signaling pathway is more active in K7M2 cells. We have previously described that K7M2 cells exhibit higher levels of aldehyde dehydrogenase (ALDH activity. Here we report that K7M2 cell ALDH activity is reduced with Notch inhibition, suggesting that ALDH activity may be regulated in part by the Notch pathway. Notch signaling is also associated with increased resistance to oxidative stress, migration, invasion, and VEGF expression in vitro. However, Notch inhibition did not significantly alter K7M2 cell proliferation. In conclusion, we provide evidence that Notch signaling is associated with ALDH activity and increased metastatic behavior in OS cells. Both Notch and ALDH are putative molecular targets for the treatment and prevention of OS metastasis.

  16. Effects of irradiation on crack-arrest toughness of two high-copper welds

    International Nuclear Information System (INIS)

    Iskander, S.K.; Corwin, W.R.; Nanstad, R.K.

    1990-01-01

    The objective of this study is to determine the effect of neutron irradiation on the shift and shape of the lower-bound curve to crack-arrest data. Two submerged-arc welds with copper contents of 0.23 and 0.31 wt % were commercially fabricated in 220-mm-thick plate. Crack-arrest specimens fabricated from these welds were irradiated at a nominal temperature of 288 degree C to an average fluence of 1.9 x 10 19 neutrons/cm 2 (>1 MeV). A preliminary evaluation of the results shows that the neutron-irradiation induced crack-arrest toughness temperature shift is about the same as the Charpy V-notch impact temperature shift at the 41-J energy level. The shape of the lower-bound curves, (for the range of test temperatures covered), compared to those of the ASME K Ia -curve did not seem to have been altered by irradiation. 10 refs., 9 figs., 7 tabs

  17. Results of crack-arrest tests on two irradiated high-copper welds

    International Nuclear Information System (INIS)

    Iskander, S.K.; Corwin, W.R.; Nanstead, R.K.

    1990-12-01

    The objective of this study was to determine the effect of neutron irradiation on the shift and shape of the lower-bound curve to crack-arrest data. Two submerged-arc welds with copper contents of 0.23 and 0.31 wt % were commercially fabricated in 220-mm-thick plate. Crack-arrest specimens fabricated from these welds were irradiated at a nominal temperature of 288 degree C to an average fluence of 1.9 x 10 19 neutrons/cm 2 (>1 MeV). Evaluation of the results shows that the neutron-irradiation-induced crack-arrest toughness temperature shift is about the same as the Charpy V-notch impact temperature shift at the 41-J energy level. The shape of the lower-bound curves (for the range of test temperatures covered) did not seem to have been altered by irradiation compared to those of the ASME K Ia curve. 9 refs., 21 figs., 10 tabs

  18. Change of Charpy impact fracture behavior of precracked ferritic specimens due to thermal aging in sodium

    International Nuclear Information System (INIS)

    Hu, W.L.

    1985-12-01

    A series of tests were conducted to evaluate the effect of sodium on the impact fracture behavior of precracked Charpy specimens made of HT-9 weldment. One set of samples was precracked prior to sodium aging and the other set was precracked after aging in sodium. Both set of specimens exhibited the same DBTT. Samples precracked prior to sodium exposure, however, showed a 40% reduction in the upper shelf energy (USE) as compared to the set precracked after aging. The results suggest that the fracture toughness of the material may be reduced if an existing crack was soaked in sodium at elevated temperature for a period of time

  19. Mind bomb-1 in dendritic cells is specifically required for Notch-mediated T helper type 2 differentiation.

    Directory of Open Access Journals (Sweden)

    Hyun-Woo Jeong

    Full Text Available In dendritic cell (DC-CD4(+ T cell interaction, Notch signaling has been implicated in the CD4(+ T cell activation, proliferation, and subset differentiation. However, there has been a lot of debate on the exact role of Notch signaling. Here, we observed that expression of Mind bomb-1 (Mib1, a critical regulator of Notch ligands for the activation of Notch signaling, increases gradually as precursor cells differentiate into DCs in mice. To clarify the role of Mib1 in DC-CD4(+ T cell interactions, we generated Mib1-null bone marrow-derived DCs. These cells readily expressed Notch ligands but failed to initiate Notch activation in the adjacent cells. Nevertheless, Mib1-null DCs were able to prime the activation and proliferation of CD4(+ T cells, suggesting that Notch activation in CD4(+ T cells is not required for these processes. Intriguingly, stimulation of CD4(+ T cells with Mib1-null DCs resulted in dramatically diminished Th2 cell populations, while preserving Th1 cell populations, both in vitro and in vivo. Our results demonstrate that Mib1 in DCs is critical for the activation of Notch signaling in CD4(+ T cells, and Notch signaling reinforces Th2 differentiation, but is not required for the activation or proliferation of the CD4(+ T cells.

  20. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

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    Frampton, Gabriel; Coufal, Monique [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Li, Huang [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ramirez, Jonathan [Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States); DeMorrow, Sharon, E-mail: demorrow@medicine.tamhsc.edu [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States)

    2010-05-15

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the {gamma}-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-{gamma}-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the {gamma}-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.