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

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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.

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

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.

Effects of Oxygen Content on Tensile and Fatigue Performance of Ti-6Al-4 V Manufactured by Selective Laser Melting

Science.gov (United States)

Quintana, Oscar A.; Tong, Weidong

2017-12-01

We investigated the selective laser melting (SLM) process for development of Ti-6Al-4 V solid material with oxygen content corresponding to the extra low interstitial (ELI) and non-ELI conditions. The microstructure, chemistry, and tensile properties of samples in as-built and hot isostatically pressed (HIPed) condition were evaluated for both material types, while fatigue performance was evaluated by rotating bending fatigue tests on both smooth and notched SLM ELI and non-ELI Ti-6Al-4 V samples in HIPed condition.

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.

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

The effect of post-weld heat treatment on the microstructure and notched tensile fracture of Ti–15V–3Cr–3Al–3Sn to Ti–6Al–4V dissimilar laser welds

Energy Technology Data Exchange (ETDEWEB)

Hsieh, C.T.; Shiue, R.K. [Department of Materials Science and Engineering, National Taiwan University, Taipei 106, Taiwan, ROC (China); Huang, R.-T. [Institute of Materials Engineering, National Taiwan Ocean University, Keelung 202, Taiwan, ROC (China); Tsay, L.W., E-mail: b0186@mail.ntou.edu.tw [Institute of Materials Engineering, National Taiwan Ocean University, Keelung 202, Taiwan, ROC (China)

2016-01-20

A CO{sub 2} laser was applied for dissimilar welding of Ti–15V–3Cr–3Al–3Sn (Ti–15–3) to Ti–6Al–4V (Ti–6–4) alloys. The microstructures and notched tensile strength (NTS) of the dissimilar welds were investigated in the as-welded and post-weld heat treatment (PWHT) conditions, and the results were compared with Ti–6–4 and Ti–15–3 homogeneous laser welds with the same PWHT. The results indicated that predominant α″ with a few α and β phases was formed in the as-welded fusion zone (FZ). Furthermore, the FZ hardness was susceptible to the PWHT and showed a plateau for the specimens aged in the temperature range from 426 to 482 °C/4 h. In comparison with the homogeneous Ti–15–3 weld under the same PWHT conditions, the dilution of Ti–15–3 with Ti–6–4 caused a slight increase in the Al equivalent (Al{sub EQ}) of the FZ, resulting in a further rise in FZ hardness. With the PWHT at/below 538 °C, the dissimilar welds were associated with low NTS or high notch brittleness.

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

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....

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.

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

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

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...

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

Evaluation of impacts of stress triaxiality on plastic deformability of RAFM steel using various types of tensile specimen

Energy Technology Data Exchange (ETDEWEB)

Kato, Taichiro, E-mail: kato.taichiro@jaea.go.jp [Japan Atomic Energy Agency, 2-166, Obuchi-omotedate, Rokkasho, Aomori 039-3212 (Japan); Ohata, Mitsuru [Osaka University, 2-1, Yamada-Oka, Suita, Osaka 565-0871 (Japan); Nogami, Shuhei [Tohoku University, 6-6-01-2, Aramaki-aza-Aoba, Aoba-ku, Sendai, Miyagi 980-8579 (Japan); Tanigawa, Hiroyasu [Japan Atomic Energy Agency, 2-166, Obuchi-omotedate, Rokkasho, Aomori 039-3212 (Japan)

2016-11-01

Highlights: • The fracture ductility is lower as the stress triaxiality is higher. • Voids of the interrupted RB1 specimen were observed along grain boundaries and expanded parallel to the tensile axis. • Voids of interrupted R0.2 specimen were rounded shape than those of RB1. • The fracture surface of specimens were observed the elongated and the equiaxed dimples. • The decrease of plastic deformability of the notched specimen was caused by the process of voids formation and crack growth due to the effect of plastic constraint of the notch. - Abstract: A case study on a fusion blanket design such as DEMO indicated that there could be some sections with high stress triaxiality, a parameter to evaluate the magnitude of plastic constraint, in the case of plasma disruption or coolant loss accident. Therefore, it is necessary to accurately understand the ductility loss limit of structural material in order to conduct the structural design assessment of the irradiated and embrittled fusion reactor blanket. Tensile tests were conducted by using three kinds of tensile specimen shapes to investigate of the plastic deformability of F82H. From the results, the fracture ductility is lower as the stress triaxiality is higher. Voids of the interrupted RB1 specimen were observed along grain boundaries and expanded parallel to the tensile axis. That of interrupted R0.2 specimen was rounded shape compared with those of RB1. The fracture surface of RB1 and R0.2 specimens were observed the elongated dimples and the equiaxed dimples without so much elongation, respectively. It is considered that the decrease of plastic deformability for the notched specimen was caused by the process of voids formation and crack growth due to the effect of plastic constraint of the notch.

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.

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)

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...

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.

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

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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.

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.

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)

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.

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.

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.

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.

Microstructure-Tensile Properties Correlation for the Ti-6Al-4V Titanium Alloy

Science.gov (United States)

Shi, Xiaohui; Zeng, Weidong; Sun, Yu; Han, Yuanfei; Zhao, Yongqing; Guo, Ping

2015-04-01

Finding the quantitative microstructure-tensile properties correlations is the key to achieve performance optimization for various materials. However, it is extremely difficult due to their non-linear and highly interactive interrelations. In the present investigation, the lamellar microstructure features-tensile properties correlations of the Ti-6Al-4V alloy are studied using an error back-propagation artificial neural network (ANN-BP) model. Forty-eight thermomechanical treatments were conducted to prepare the Ti-6Al-4V alloy with different lamellar microstructure features. In the proposed model, the input variables are microstructure features including the α platelet thickness, colony size, and β grain size, which were extracted using Image Pro Plus software. The output variables are the tensile properties, including ultimate tensile strength, yield strength, elongation, and reduction of area. Fourteen hidden-layer neurons which can make ANN-BP model present the most excellent performance were applied. The training results show that all the relative errors between the predicted and experimental values are within 6%, which means that the trained ANN-BP model is capable of providing precise prediction of the tensile properties for Ti-6Al-4V alloy. Based on the corresponding relations between the tensile properties predicted by ANN-BP model and the lamellar microstructure features, it can be found that the yield strength decreases with increasing α platelet thickness continuously. However, the α platelet thickness exerts influence on the elongation in a more complicated way. In addition, for a given α platelet thickness, the yield strength and the elongation both increase with decreasing β grain size and colony size. In general, the β grain size and colony size play a more important role in affecting the tensile properties of Ti-6Al-4V alloy than the α platelet thickness.

Use of notched beams to establish fracture criteria for beryllium

International Nuclear Information System (INIS)

Mayville, R.A.

1980-01-01

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

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

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.

Notched Strength of Woven Fabric Kenaf Composite Plates with Different Stacking Sequences and Hole Sizes

Directory of Open Access Journals (Sweden)

Hans Romayne Anders

2016-01-01

Full Text Available Advantages of using kenaf fibres over synthetic fibres in composites manufacturing are relatively cheap, less abrasive and hazardous during handling, and renewable materials. Current work investigates parametric effects on notched strength of woven fabric kenaf polymer composites plates with variation of lay-up types, notch sizes and plate thickness. Testing coupons are prepared using hand lay-up technique and circular notch were drilled prior to mechanical testing. Stress concentration at the notch edge promotes micro-damage event as tensile loading was applied leading to crack initiation and propagations across the plate width. It is suggested that woven fabric kenaf polymer composites are potentially used in low and medium load bearing applications.

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.

The effect of electron beam irradiation on the mechanical properties of pineapple leaf fibre (PALF) reinforced high impact polystyrene (HIPS) composites

Science.gov (United States)

Siregar, J. P.; Sapuan, S. M.; Rahman, M. Z. A.; Zaman, H. M. D. K.

2010-05-01

The effects of electron beam irradiation on the mechanical properties of pineapple leaf fibre reinforced high impact polystyrene (HIPS) composites were studied. Two types of crosslinking agent that has been used in this study were trimethylolpropane triacrylate (TMPTA) and tripropylene gylcol diacrylate (TPGDA). A 50 wt.% of PALF was blended with HIPS and crosslinking agent using Brabender melt mixer at 165 °C. The composites were then irradiated using a 3 MeV electron beam accelerator with dosage of 0-100 kGy. The tensile strength, tensile modulus, flexural strength, flexural modulus, notched and unnotched impat and hardness of composites were measured and the effects of crosslinking agent were also compared.

The effect of electron beam irradiation on the mechanical properties of pineapple leaf fibre (PALF) reinforced high impact polystyrene (HIPS) composites

Energy Technology Data Exchange (ETDEWEB)

Siregar, J P; Sapuan, S M [Department of Mechanical and Manufacturing Engineering, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Rahman, M Z A [Department of Chemistry, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Zaman, H M D K, E-mail: januarjasmine@yahoo.com [Radiation Processing Technology Division, Malaysia Nuclear Agency, Bangi 43000 Kajang, Selangor (Malaysia)

2010-05-15

The effects of electron beam irradiation on the mechanical properties of pineapple leaf fibre reinforced high impact polystyrene (HIPS) composites were studied. Two types of crosslinking agent that has been used in this study were trimethylolpropane triacrylate (TMPTA) and tripropylene gylcol diacrylate (TPGDA). A 50 wt.% of PALF was blended with HIPS and crosslinking agent using Brabender melt mixer at 165 deg. C. The composites were then irradiated using a 3 MeV electron beam accelerator with dosage of 0-100 kGy. The tensile strength, tensile modulus, flexural strength, flexural modulus, notched and unnotched impat and hardness of composites were measured and the effects of crosslinking agent were also compared.

The effect of electron beam irradiation on the mechanical properties of pineapple leaf fibre (PALF) reinforced high impact polystyrene (HIPS) composites

International Nuclear Information System (INIS)

Siregar, J P; Sapuan, S M; Rahman, M Z A; Zaman, H M D K

2010-01-01

The effects of electron beam irradiation on the mechanical properties of pineapple leaf fibre reinforced high impact polystyrene (HIPS) composites were studied. Two types of crosslinking agent that has been used in this study were trimethylolpropane triacrylate (TMPTA) and tripropylene gylcol diacrylate (TPGDA). A 50 wt.% of PALF was blended with HIPS and crosslinking agent using Brabender melt mixer at 165 deg. C. The composites were then irradiated using a 3 MeV electron beam accelerator with dosage of 0-100 kGy. The tensile strength, tensile modulus, flexural strength, flexural modulus, notched and unnotched impat and hardness of composites were measured and the effects of crosslinking agent were also compared.

Tensile and fracture behavior of polymer foams

International Nuclear Information System (INIS)

Kabir, Md. E.; Saha, M.C.; Jeelani, S.

2006-01-01

Tensile and mode-I fracture behavior of cross-linked polyvinyl chloride (PVC) and rigid polyurethane (PUR) foams are examined. Tension tests are performed using prismatic bar specimens and mode-I fracture tests are performed using single edge notched bend (SENB) specimens under three-point bending. Test specimens are prepared from PVC foams with three densities and two different levels of cross-linking, and PUR foam with one density. Tension and quasi-static fracture tests are performed using a Zwick/Rowell test machine. Dynamic fracture tests are performed using a DYNATUP model 8210 instrumented drop-tower test set up at three different impact energy levels. Various parameters such as specimen size, loading rate, foam density, cross-linking, crack length, cell orientation (flow and rise-direction) and solid polymer material are studied. It is found that foam density and solid polymer material have a significant effect on tensile strength, modulus, and fracture toughness of polymer foams. Level of polymer cross-linking is also found to have a significant effect on fracture toughness. The presence of cracks in the rise- and flow direction as well as loading rate has minimal effect. Dynamic fracture behavior is found to be different as compared to quasi-static fracture behavior. Dynamic fracture toughness (K d ) increases with impact energy. Examination of fracture surfaces reveals that the fracture occurs in fairly brittle manner for all foam materials

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.

1987-01-01

The Charpy-V (C/sub V/) properties of American Iron and Steel Institute (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 metal inert gas (MIG) process. Weldment properties in two test orientations were evaluated. Specimens were irradiated in a light water cooled and moderated reactor to 1 x 10/sup 20/ n/cm/sup 2/, E > 0.1 MeV, using a controlled temperature assembly. Specimen tests were performed at 25 and 125 0 C. The radiation-induced reductions in C/sub V/ energy absorption at 25 0 C were about 42% for the weld and the HAZ materials evaluated. A trend of energy increase with temperature was observed. The concomitant elevation in yield strength was about 53%. The increase in tensile strength in contrast 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 resistance viewpoint

Development of Tensile Softening Model for Plain Concrete

Energy Technology Data Exchange (ETDEWEB)

Lee, S.K.; Song, Y.C. [Korea Electric Power Research Institute, Taejon (Korea)

2002-07-01

Large-scale direct tensile softenng tests using plate concrete specimens(4000, 5000psi) with notch were performed under uniaxial stress. There were presented the basic physical properties and the complete load-CMOD(Crack Mouth Opening Displacement) curves for them And them the fracture energy was evaluated using the complete load-CMOD curves respectively, and there was presents optimal tensile softening model which is modified by a little revision of an existing one. Therefore, here provided the real verification data through the tests for developing other nonlinear concrete finite element models. (author). 32 refs., 38 figs., 4 tabs.

Use of a 33 MJ high-energy rotary impact testing machine for investigations into material behaviour under impact loads

International Nuclear Information System (INIS)

Issler, W.

1989-01-01

To investigate material behaviour under impact loads, previously very different testing machines have been developed. One of these concepts is the rotary impact testing machine which stores rotational energy and on which a tension impact test can be performed with almost unchanged trigger speed. With this device maximum trigger speeds can be achieved by using mechanical, elastically stored or hydraulic energy. Usable sample geometries include in particular smooth or notched round or flat tensile specimen up to 30 mm in diameter and CT10 or CT15 mechanical strength test specimen, permitting a direct comparison with results from quasi-static tests. For present speeds of load application the elastic modulus of steel can be considered as being constant. For Poisson's ratio, measurements indicated changes by approximately -8% to +20%. Early tests to investigate the strain rate showed that the strain rate under purely elastic loads applied to smooth round tensile specimen is approximately 3-10 times slower than the strain rate under plastic deformation, while this ratio may have an order of magnitude of 1:100 for notched tensile specimen. Therefore it is unreasonable to indicate only one value for the strain rate as a test characterising parameter. (orig./MM) [de

Selective Laser Melting Produced Ti-6Al-4V: Post-Process Heat Treatments to Achieve Superior Tensile Properties.

Science.gov (United States)

Ter Haar, Gerrit M; Becker, Thorsten H

2018-01-17

Current post-process heat treatments applied to selective laser melting produced Ti-6Al-4V do not achieve the same microstructure and therefore superior tensile behaviour of thermomechanical processed wrought Ti-6Al-4V. Due to the growing demand for selective laser melting produced parts in industry, research and development towards improved mechanical properties is ongoing. This study is aimed at developing post-process annealing strategies to improve tensile behaviour of selective laser melting produced Ti-6Al-4V parts. Optical and electron microscopy was used to study α grain morphology as a function of annealing temperature, hold time and cooling rate. Quasi-static uniaxial tensile tests were used to measure tensile behaviour of different annealed parts. It was found that elongated α'/α grains can be fragmented into equiaxial grains through applying a high temperature annealing strategy. It is shown that bi-modal microstructures achieve a superior tensile ductility to current heat treated selective laser melting produced Ti-6Al-4V samples.

Fracture behavior of nuclear graphites under tensile impact loading

International Nuclear Information System (INIS)

Ugachi, Hirokazu; Ishiyama, Shintaro; Eto, Motokuni

1994-01-01

Impact tensile strength test was performed with two kinds of HTTR graphites, fine grained isotropic graphite, IG-11 and coarse grained near isotropic graphite, PGX and deformation and fracture behavior under the strain rate of over 100s -1 was measured and the following results were derived: (1) Tensile strength for IG-11 graphite does not depend on the strain rate less than 1 s -1 , but over 1 s -1 , tensile strength for IG-11 graphite increase larger than that measured under 1 s -1 . At the strain rate more than 100 s -1 , remarkable decrease of tensile strength for IG-11 graphite was found. Tensile strength of PGX graphite does not depend on the strain rate less than 1 s -1 , but beyond this value, the sharp tensile strength decrease occurs. (2) Under 100 s -1 , fracture strain for both graphites increase with increase of strain rate and over 100 s -1 , drastic increase of fracture strain for IG-11 graphite was found. (3) At the part of gage length, volume of specimen increase with increase of tensile loading level and strain rate. (4) Poisson's ratio for both graphites decrease with increase of tensile loading level and strain rate. (5) Remarkable change of stress-strain curve for both graphites under 100 s -1 was not found, but over 100 s -1 , the slope of these curve for IG-11 graphite decrease drastically. (author)

Factors Influencing Dwell Fatigue Cracking in Notches of Powder Metallurgy Superalloys

Science.gov (United States)

Gabb, T. P.; Telesman, J.; Ghosn, L.; Garg, A.; Gayda, J.

2011-01-01

The influences of heat treatment and cyclic dwells on the notch fatigue resistance of powder metallurgy disk superalloys were investigated for low solvus high refractory (LSHR) and ME3 disk alloys. Disks were processed to produce material conditions with varied microstructures and associated mechanical properties. Notched specimens were first subjected to baseline dwell fatigue cycles having a dwell at maximum load, as well as tensile, stress relaxation, creep rupture, and dwell fatigue crack growth tests at 704 C. Several material heat treatments displayed a bimodal distribution of fatigue life with the lives varying by two orders-of-magnitude, while others had more consistent fatigue lives. This response was compared to other mechanical properties, in search of correlations. The wide scatter in baseline dwell fatigue life was observed only for material conditions resistant to stress relaxation. For selected materials and conditions, additional tests were then performed with the dwells shifted in part or in total to minimum tensile load. The tests performed with dwells at minimum load exhibited lower fatigue lives than max dwell tests, and also exhibited early crack initiation and a substantial increase in the number of initiation sites. These results could be explained in part by modeling evolution of peak stresses in the notch with continued dwell fatigue cycling. Fatigue-environment interactions were determined to limit life for the fatigue cycles with dwells.

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

Selective Laser Melting Produced Ti-6Al-4V: Post-Process Heat Treatments to Achieve Superior Tensile Properties

Directory of Open Access Journals (Sweden)

Gerrit M. Ter Haar

2018-01-01

Full Text Available Current post-process heat treatments applied to selective laser melting produced Ti-6Al-4V do not achieve the same microstructure and therefore superior tensile behaviour of thermomechanical processed wrought Ti-6Al-4V. Due to the growing demand for selective laser melting produced parts in industry, research and development towards improved mechanical properties is ongoing. This study is aimed at developing post-process annealing strategies to improve tensile behaviour of selective laser melting produced Ti-6Al-4V parts. Optical and electron microscopy was used to study α grain morphology as a function of annealing temperature, hold time and cooling rate. Quasi-static uniaxial tensile tests were used to measure tensile behaviour of different annealed parts. It was found that elongated α’/α grains can be fragmented into equiaxial grains through applying a high temperature annealing strategy. It is shown that bi-modal microstructures achieve a superior tensile ductility to current heat treated selective laser melting produced Ti-6Al-4V samples.

Postirradiation tensile properties of Mo and Mo alloys irradiated with 600 MeV protons

International Nuclear Information System (INIS)

Mueller, G.V.; Gavillet, D.; Victoria, M.; Martin, J.L.

1994-01-01

Tensile specimens of pure Mo and Mo-5 Re, Mo-41 Re and TZM alloys have been irradiated with 600 MeV protons in the PIREX facility at 300 and 660 K to 0.5 dpa. Results of the postirradiation tensile testing show a strong radiation hardening and a severe loss of ductility for all the materials tested at room temperature. ((orig.))

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.

Post-Impact and Open Hole Tensile Of Kenaf Hybrid Composites

Science.gov (United States)

Yunus, S.; Salleh, Z.; Masdek, N. R. N. M.; Taib, Y. M.; Azhar, I. I. S.; Hyie, K. M.

2018-03-01

Nowadays, kenaf hybrid glass composites has been used for a vast field of study throughout the globe. There are several compositions and orientation of kenaf hybrid glass composites that has been studied. With regards to the study that has been done, this study will be focussing on a 90FG/0/90/90/0/90FG orientation of kenaf hybrid glass composites. Polyester resin is used as a matrix to these hybrid composites. Impacted and open hole specimens were then analyzed through tensile test. All specimens were fabricated by using the cold press hand lay-up technique. The results revealed that the hybrid composites were hardly affected by the impact up to 6J. After 6J the impacted specimens experienced a significant damage for both strength and modulus. The same goes to open hole specimens where the same trend of tensile properties were observed as impacted specimens.

Tensile properties of V-Cr-Ti alloys after exposure in hydrogen-containing environments

International Nuclear Information System (INIS)

Natesan, K.; Soppet, W.K.

1998-01-01

A systematic study has been initiated at Argonne National Laboratory to evaluate the performance of several V-Cr-Ti alloys after exposure to environments containing hydrogen at various partial pressures. The goal is to correlate the chemistry of the exposure environment with hydrogen uptake in the samples and its influence on the microstructure and tensile properties of the alloys. At present, the principal effort has focused on the V-4Cr-4Ti alloy of heat identified as BL-71; however other alloys (V-5Cr-5Ti alloy of heats BL-63, and T87, plus V-4Cr-4Ti alloy from General Atomics [GA]) are also being evaluated. Other variables of interest are the effect of initial grain size on the tensile behavior of the alloys. Experiments conducted on specimens of various V-Cr-Ti alloys exposed to pH 2 levels of 0.01 and 3 x 10 -6 torr showed negligible effect of H 2 on either maximum engineering stress or uniform and total elongation. However, uniform and total elongation decreased substantially when the alloys were exposed to 1.0 torr H 2 pressure. Preliminary data from sequential exposures of the materials to low-pO 2 and several low-pH 2 environments did not reveal an adverse effect on the maximum engineering stress or on uniform and total elongation. Further, tests in H 2 environments on specimens annealed at different temperatures showed that grain-size variation by a factor of ∼2 had little or no effect on tensile properties

Notched Strength of Woven Fabric Kenaf Composites with Different Fiber Orientations

Directory of Open Access Journals (Sweden)

Ahmad Hilton

2017-01-01

Full Text Available The awareness of implementing sustainable materials in construction industry is gaining good attention among engineers worldwide. Kenaf fibers are local renewable materials to combine with epoxy polymers matrix in producing lightweight composite materials which may replace imported synthetic fiber composites especially in developing countries. Other benefits of using kenaf fiber composites are relatively cheap, less abrasive and less hazardous during fabrication handling. Current study investigates parametric study on notched strength of woven fabric kenaf composite plates with different fiber orientations and circular hole sizes. Stress concentration occurred at the notch edge promotes to micro-damage events such as matrix cracking and fiber fracture as remote tensile loading applied. Current study showed that 0° fiber orientation gives optimum notched strength, plates with larger fiber tilting than 0° are associated with further strength reduction. Kenaf fibers give an alternative to material designers to opt woven fabric kenaf composites in low and medium load bearing applications.

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.

Tensile Instability and Artificial Stresses in Impact Problems in SPH

International Nuclear Information System (INIS)

Mehra, Vishal; Sijoy C D; Mishra, Vinayak; Chaturvedi, Shashank

2012-01-01

The smooth particle hydrodynamics (SPH) is a meshless computational technique that is popular in the modeling of impact and penetration problems. However, SPH is liable to a tensile instability that manifests itself as a bunching of nodes and formation of artificial voids and no generally accepted formulation exists to counter this instability. We examine the performance of two methods that have been proposed to deal with the tensile instability— the Monaghan artificial stresses and the Godunov-type SPH. The impact and penetration of 0.5 cm radii steel spheres on 2 mm thick aluminium plate at 3.1 km/s is chosen for comparison. We show that the artificial void formation in St-Al impact is suppressed but not eliminated by using Monaghan stresses while the void formation is entirely eliminated by using Godunov-type formulation of SPH that was proposed by Parshikov and Medin.

Change of notch impact strength depending on radiation dose and test temperature

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Martin Bednarik

2017-01-01

Full Text Available The main purpose of this paper has been determine the effect of radiation crosslinking on the notch impact strength of polyamides filled with fiberglass. These properties were examined in dependence on the dosage of the ionizing beta radiation (non-irradiated samples and those irradiated by dosage 66 and 132 kGy were compared and on the test temperature (23–150 °C.

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.

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

Multiscale Static Analysis of Notched and Unnotched Laminates Using the Generalized Method of Cells

Science.gov (United States)

Naghipour Ghezeljeh, Paria; Arnold, Steven M.; Pineda, Evan J.; Stier, Bertram; Hansen, Lucas; Bednarcyk, Brett A.; Waas, Anthony M.

2016-01-01

The generalized method of cells (GMC) is demonstrated to be a viable micromechanics tool for predicting the deformation and failure response of laminated composites, with and without notches, subjected to tensile and compressive static loading. Given the axial [0], transverse [90], and shear [+45/-45] response of a carbon/epoxy (IM7/977-3) system, the unnotched and notched behavior of three multidirectional layups (Layup 1: [0,45,90,-45](sub 2S), Layup 2: [0,60,0](sub 3S), and Layup 3: [30,60,90,-30, -60](sub 2S)) are predicted under both tensile and compressive static loading. Matrix nonlinearity is modeled in two ways. The first assumes all nonlinearity is due to anisotropic progressive damage of the matrix only, which is modeled, using the multiaxial mixed-mode continuum damage model (MMCDM) within GMC. The second utilizes matrix plasticity coupled with brittle final failure based on the maximum principle strain criteria to account for matrix nonlinearity and failure within the Finite Element Analysis--Micromechanics Analysis Code (FEAMAC) software multiscale framework. Both MMCDM and plasticity models incorporate brittle strain- and stress-based failure criteria for the fiber. Upon satisfaction of these criteria, the fiber properties are immediately reduced to a nominal value. The constitutive response for each constituent (fiber and matrix) is characterized using a combination of vendor data and the axial, transverse, and shear responses of unnotched laminates. Then, the capability of the multiscale methodology is assessed by performing blind predictions of the mentioned notched and unnotched composite laminates response under tensile and compressive loading. Tabulated data along with the detailed results (i.e., stress-strain curves as well as damage evolution states at various ratios of strain to failure) for all laminates are presented.

Strain redistribution around holes and notches in fiber-reinforced cross-woven brittle matrix composites

DEFF Research Database (Denmark)

Jacobsen, Torben Krogsdal; Brøndsted, Povl

1997-01-01

Mechanics, and an identification procedure based on a uni-axial tensile test and a shear test the strain redistribution around a hole or a notch due to matrix cracking can be predicted. Damage due to fiber breakage is not included in the model. Initial matrix damage in the C-f/SiCm material has...

Validatin of miniaturised tensile testing on DMLS TI6AL4V (ELI specimens

Directory of Open Access Journals (Sweden)

Van Zyl, Ian

2016-11-01

Full Text Available Direct metal laser sintering (DMLS is a relatively new technology that is developing rapidly. Since DMLS material is created by melting/solidifying tracks and layers from powder, even building geometry can influence the mechanical properties. To certify a material, the testing specimens must be designed and manufactured according to the appropriate standards. Miniaturised tensile DMLS samples could be a good alternative for express quality control, and could reduce the cost of DMLS-specific testing. In this study, as-built and stress-relieved miniaturised tensile DMLS Ti6Al4V (ELI specimens with different surface qualities were investigated. The fracture surfaces and mechanical properties of the mini-tensile specimens were analysed and compared with standard full-sized specimens also manufactured by DMLS. The obtained data showed the applicability of mini-tensile tests for the express analysis of DMLS objects if a correction factor is applied for the calculation of the load-bearing cross-section of the specimen.

The effect of notches and pits on corrosion fatigue strength

Science.gov (United States)

Tatner, Ian

An investigation has been undertaken to examine the fatigue behaviour of two martensitic steels in air and aggressive environments. The steels studied are, 18% Ni marageing steel and FV520B, the later being a stainless steel turbine blade material and the former being a marageing steel that suffers general corrosion in mild environments. Both steels were heat treated to give similar tensile strength.The design and manufacture of an autoclave allowed push-pull fatigue tests to be conducted in aggressive environments at elevated temperatures.Corrosion potential was monitored using a three electrode cell and was controlled during testing. Base-line fatigue tests were conducted with a range of constant corrosion potentials, using both notched and plain FV520B specimens. In addition fatigue tests with pulsed corrosion potential were performed to asses the effect of transient corrosion conditions on the corrosion fatigue strength. The pulsed tests were designed to simulate service transients in the oxygen content and general chemical hostility in the condensing steam environment during start-up and shut down of the steam turbine.Post test examination of fractured samples was performed using Scanning Electron Microscopy (SEM) and optical microscope techniques. The fractography results were used to quantify microstructural and fracture features of the steels.A model based on the size and geometry of the initial corrosion pitting has been proposed to asses the fatigue life of FV520B in an aggressive environment.The effect of pitting on the corrosion fatigue strength of FV520B has been modelled using linear elastic fracture mechanics (LEFM) type approach. The model has shown a good correlation between predicted fatigue lives with experimental results.The results suggest that the fatigue life is governed by the mechanical stress concentrating effect of the pits rather than the electrochemical damage caused by the environment.Finite Element Analysis (FEA) of the notch allowed

Tensile and fracture toughness properties of MA957: implications to the development of nanocomposited ferritic alloys

International Nuclear Information System (INIS)

Alinger, M.J.; Odette, G.R.; Lucas, G.E.

2002-01-01

A study to explore approaches to optimizing nanocomposited ferritic alloys was carried out on dispersion strengthened mechanically alloyed (MA) MA957, in the form of extruded bar stock. Previous studies had indicated that this alloy manifested superior high temperature strength and radiation stability, but was extremely brittle in notch impact tests. Thus our objective was to develop a combination of tensile, fracture toughness and microstructural data to clarify the basis for this brittle behavior. To this end, tensile properties and fracture toughness were characterized as a function of temperature in various orientations relative to the grain and inclusion structures. This database along with extensive fractography suggests that brittleness is due to the presence of a large volume fraction of impurity alumina stringers. In orientations where the effects of the stringers are reduced, much higher toughness was observed. These results provide a path for alloy development approach to achieve high strength and toughness

Tensile and fracture toughness properties of MA957: implications to the development of nanocomposited ferritic alloys

Science.gov (United States)

Alinger, M. J.; Odette, G. R.; Lucas, G. E.

2002-12-01

A study to explore approaches to optimizing nanocomposited ferritic alloys was carried out on dispersion strengthened mechanically alloyed (MA) MA957, in the form of extruded bar stock. Previous studies had indicated that this alloy manifested superior high temperature strength and radiation stability, but was extremely brittle in notch impact tests. Thus our objective was to develop a combination of tensile, fracture toughness and microstructural data to clarify the basis for this brittle behavior. To this end, tensile properties and fracture toughness were characterized as a function of temperature in various orientations relative to the grain and inclusion structures. This database along with extensive fractography suggests that brittleness is due to the presence of a large volume fraction of impurity alumina stringers. In orientations where the effects of the stringers are reduced, much higher toughness was observed. These results provide a path for alloy development approach to achieve high strength and toughness.

Revised ANL-reported tensile data for unirradiated and irradiated (FFTF, HFIR) V-Ti and V-Cr-Ti alloys

International Nuclear Information System (INIS)

Billone, M.C.

1998-01-01

The tensile data for all unirradiated and irradiated vanadium alloys samples tested at Argonne National Laboratory (ANL) have been critically reviewed and, when necessary, revised. The review and revision are based on reanalyzing the original load-displacement strip chart recordings by a methodology consistent with current ASTM standards. For unirradiated alloys (162 samples), the revised values differ from the previous values as follows: -11±19 MPa (-4±6%) for yield strength (YS), -3±15 MPa (-1±3%) for ultimate tensile strength (UTS), -5±2% strain for uniform elongation (UE), and -4±2% strain for total elongation (TE). Of these changes, the decrease in -1±6 MPa (0±1%) for UTS, -5±2% for UE, and -4±2% for TE. Of these changes, the decrease in UE values for alloys irradiated and tested at 400--435 C is the most significant. This decrease results from the proper subtraction of nongauge-length deformation from measured crosshead deformation. In previous analysis of the tensile curves, the nongauge-length deformation was not correctly determined and subtracted from the crosshead displacement. The previously reported and revised tensile values for unirradiated alloys (20--700 C) are tabulated in Appendix A. The revised tensile values for the FFTF-irradiated (400--600 C) and HFIR-irradiated (400 C) alloys are tabulated in Appendix B, along with the neutron damage and helium levels. Appendix C compares the revised values to the previously reported values for irradiated alloys. Appendix D contains previous and revised values for the tensile properties of unirradiated V-5Cr-5Ti (BL-63) alloy exposed to oxygen

Effect of post weld heat treatment on tensile properties and microstructure characteristics of friction stir welded armour grade AA7075-T651 aluminium alloy

OpenAIRE

Sivaraj, P.; Kanagarajan, D.; Balasubramanian, V.

2014-01-01

This paper reports the effects of post weld heat treatments, namely artificial ageing and solution treatment followed by artificial ageing, on microstructure and mechanical properties of 12 mm thick friction stir welded joints of precipitation hardenable high strength armour grade AA7075-T651 aluminium alloy. The tensile properties, such as yield strength, tensile strength, elongation and notch tensile strength, are evaluated and correlated with the microhardness and microstructural features....

Tensile properties of V-5Cr-5Ti alloy after exposure in air environment

Energy Technology Data Exchange (ETDEWEB)

Natesan, K.; Soppet, W.K. [Argonne National Lab., IL (United States)

1997-04-01

Oxidation studies were conducted on V-5Cr-5Ti alloy specimens in an air environment to evaluate the oxygen uptake behavior of the alloy as a function of temperature and exposure time. The oxidation rates, calculated from parabolic kinetic measurements of thermogravimetric testing and confirmed by microscopic analysis of cross sections of exposed specimens, were 5, 17, and 27 {mu}m per year after exposure at 300, 400, and 500{degrees}C, respectively. Uniaxial tensile tests were conducted at room temperature and at 500{degrees}C on preoxidized specimens of the alloy to examine the effects of oxidation and oxygen migration on tensile strength and ductility. Correlations were developed between tensile strength and ductility of the oxidized alloy and microstructural characteristics such as oxide thickness, depth of hardened layer, depth of intergranular fracture zone, and transverse crack length.

Effect of helium and DPA's on tensile properties of V-5Ti and V-3Ti-1Si

International Nuclear Information System (INIS)

Witzenburg, W. van; Vries, E. de.

1991-02-01

Specimens of the alloys V-5Ti and V-3Ti-1Si were irradiated in a mixed-spectrum fission reactor in reactor grade liquid sodium to a fast neutron fluence of 3.8 x 10 25 m -2 (E>0.1 MeV), which corresponds to 6.2 dpa. Irradiation temperatures were 500, 600 and 700 deg C. Some of the specimens were pre-injected with helium to 100 appm at approx 50 deg C by means of a cyclotron. In addition, part of the specimens were doped with boron-10 to concentrations of 100 and 600 appm. Tensile testing, at temperatures equal to the irradiation temperatures and at a strain rate of 10 -4 s -1 , showed an increase in strength and reduced elongation at 500 deg C and to a lesser extent at 600 deg C. These changes are caused by displacement damage. Helium, pre-injected as well as produced by transmutation of boron-10, did not have a significant influence on the tensile properties. Cavities seen in the irradiated materials at low concentrations, were not preferentially located on grain boundaries. There was no apparent deleterious effect of lithium, which is also a transmutation product of boron-10. (author). 12 refs.; 8 figs.; 3 tabs

Influence of heat treatments on the microstructure and tensile behaviour of selective laser melting-produced TI-6AL-4V parts

Directory of Open Access Journals (Sweden)

Ter Haar, Gerrit Matthys

2016-11-01

Full Text Available In industry, post-process heat treatments of Ti-6Al-4V are performed with the aim of improving its tensile behaviour. While heat treatments of wrought Ti6Al4V have been standardised (e.g., Aerospace Material Specification H-81200, heat treatments of selective laser melting (SLM-produced Ti-6Al-4V lacks research and understanding. Significant concern exists about SLM Ti6-Al-4V’s achievable ductility attributed to its martensitic (α’ phase. In this research, heat treatments at a range of temperatures are applied to SLM-produced Ti-6Al-4V tensile samples. Microstructural analysis (both optically and through electron backscatter diffraction was used to identify links between heat treatments and microstructure. Subsequently, uniaxial tensile tests were performed to determine the respective tensile properties of all samples. Correlations in the data show a significant loss in strength with respect to an increase in annealing temperature due to grain growth, while no noticeable trend was observed for fracture strain with regard to annealing temperatures.

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.

Residual stresses caused by head-on and 45° foreign object damage for a laser shock peened Ti–6Al–4V alloy aerofoil

International Nuclear Information System (INIS)

Zabeen, S.; Preuss, M.; Withers, P.J.

2013-01-01

This paper investigates the effect on the residual stresses of foreign object damage (FOD) to a previously laser shock peened (LSP) leading edge (LE). FOD was introduced onto the LE of the aerofoil-shaped specimen through ballistic impacts of a cube edge at angles of 0° and 45° to the leading edge. The residual stress distribution was mapped around the FOD notch by synchrotron X-ray diffraction. The results suggest that for both impact angles, the FOD event superimposed a significant additional residual stress on top of the pre-existing stress associated with the LSP process. In particular, the compressive stress was found to be largest directly beneath the notch and the tensile region, seen previously for unpeened aerofoils beneath the compressive zone, was absent due to the pre-existing peening stress field. This may help to explain the improved fatigue strength observed previously. It is shown that the FOD notch created by 45° impact was asymmetric in shape and smaller in depth compared to that created at 0°. The residual stresses were somewhat larger for the 0° impact condition than for 45° partly due to the larger notch depth introduced in the former case.

Effect of the interfacial adhesion on the tensile and impact properties of carbon fiber reinforced polypropylene matrices

Directory of Open Access Journals (Sweden)

Clara Leal Nogueira

2005-03-01

Full Text Available Thermoplastic composites have been applied in a wide variety of industrial products, showing recently a great potential to be used in aeronautical field. The objectives of this work were to evaluate the fiber/matrix interface of carbon fiber reinforced polypropylene-based matrices after tensile and impact tests and also to compare the mechanical test results of the manufactured laminates. The laminates were prepared by stacking carbon fiber fabric style Plain Weave (CF and films of four different polypropylene matrices, described as (a polypropylene-PP, (b polypropylene-polyethylene copolymer-PP-PE, (c PP-PE with an interfacial compatibilizer-AM1 and (d PP-PE containing an elastomeric modifier-AM2. The composites were processed using hot compression molding. The mechanical testing results showed that the CF-AM1 laminate family presented the lowest impact strength and the highest tensile strength values when compared to the other laminates. SEM analysis observations of both tensile and impact fractured specimens of the CF-PP/PE-AM1 specimens revealed a stronger fiber/matrix interface. The CF-PP/PE-AM2 laminate showed a lower tensile strength and higher impact strength values when compared to the CF-PP/PE-AM1 one. PP-PE and PP laminates presented the lowest impact strength values.

An engineering method for estimating notch-size effect in fatigue tests on steel

Science.gov (United States)

Kuhn, Paul; Hardrath, Herbert F

1952-01-01

Neuber's proposed method of calculating a practical factor of stress concentration for parts containing notches of arbitrary size depends on the knowledge of a "new material constant" which can be established only indirectly. In this paper, the new constant has been evaluated for a large variety of steels from fatigue tests reported in the literature, attention being confined to stresses near the endurance limit. Reasonably satisfactory results were obtained with the assumption that the constant depends only on the tensile strength of the steel. Even in cases where the notches were cracks of which only the depth was known, reasonably satisfactory agreement was found between calculated and experimental factors. It is also shown that the material constant can be used in an empirical formula to estimate the size effect on unnotched specimens tested in bending fatigue.

STUDY ON IMPACT AND TENSILE PROPERTIES OF CONCRETE WITH COCONUT SHELL AS COARSE AGGREGATE

OpenAIRE

R. Ranjith*

2017-01-01

The mechanical properties of coconut shell aggregate concrete (CSAC) namely splitting tensile strength, impact strength have been determined and a comparison is made with conventional granite aggregate concrete (CGAC) in the 30 days short-term experimental investigation. From the test results it is observed that coconut shell aggregate concrete has considerably sufficient strength. But the splitting tensile strength of coconut shell aggregate concrete is 50 % less than that of conventional gr...

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.

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.

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

Tensile properties of V-Cr-Ti alloys after exposure in helium and low-partial-pressure oxygen environments

Energy Technology Data Exchange (ETDEWEB)

Natesan, K.; Soppet, W.K. [Argonne National Lab., IL (United States)

1997-04-01

A test program is in progress to evaluate the effect of oxygen at low pO{sub 2} on the tensile properties of V-(4-5)wt% Cr-(4-5)wt% Ti alloys. Some of the tensile specimens were precharged with oxygen at low pO{sub 2} at 500{degrees}C and reannealed in vacuum at 500{degrees}C in environments with various pO{sub 2} levels and subsequently tensile tested at room temperature. The preliminary results indicate that both approaches are appropriate for evaluating the effect of oxygen uptake on the tensile properties of the alloys. The data showed that in the relatively short-time tests conducted thus far, the maximum engineering stress slightly increased after oxygen exposure but the uniform and total elongation values exhibited significant decrease after exposure in oxygen-containing environments. The data for a specimen exposed to a helium environment were similar to those obtained in low pO{sub 2} environments.

Tensile properties of V-Cr-Ti alloys after exposure in helium and low-partial-pressure oxygen environments

International Nuclear Information System (INIS)

Natesan, K.; Soppet, W.K.

1997-01-01

A test program is in progress to evaluate the effect of oxygen at low pO 2 on the tensile properties of V-(4-5)wt% Cr-(4-5)wt% Ti alloys. Some of the tensile specimens were precharged with oxygen at low pO 2 at 500 degrees C and reannealed in vacuum at 500 degrees C in environments with various pO 2 levels and subsequently tensile tested at room temperature. The preliminary results indicate that both approaches are appropriate for evaluating the effect of oxygen uptake on the tensile properties of the alloys. The data showed that in the relatively short-time tests conducted thus far, the maximum engineering stress slightly increased after oxygen exposure but the uniform and total elongation values exhibited significant decrease after exposure in oxygen-containing environments. The data for a specimen exposed to a helium environment were similar to those obtained in low pO 2 environments

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.

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)

Tensile properties and bend ductility of (Fe,Ni)3V long-range-ordered alloys after irradiation in HFIR

International Nuclear Information System (INIS)

Braski, D.N.

1984-01-01

The objective of this work was to determine the effect of neutron irradiation on the tensile properties and bend ductility of (Fe,Ni) 3 V long-range-ordered (LRO) alloys. Several (Fe,Ni) 3 V LRO alloys were irradiated in HFIR-CTR-42 and -43 at 400 to 600 0 C, to approximately 10 dpa and approximately 1000 at. ppm He. Additions of cerium or carbon and the use of cold-worked microstructures did not improve the embrittlement resistance of the LRO alloys. The LRO-37-5RS alloy, with a microstructure produced by rapid solidification, exhibited the highest ductilities, and further study of the RS microstructure is warranted. The correlation between bend ductility and tensile ductility was poor

Fracture toughness versus micro-tensile bond strength testing of adhesive-dentin interfaces.

Science.gov (United States)

De Munck, Jan; Luehrs, Anne-Katrin; Poitevin, André; Van Ende, Annelies; Van Meerbeek, Bart

2013-06-01

To assess interfacial fracture toughness of different adhesive approaches and compare to a standard micro-tensile bond-strength (μTBS) test. Chevron-notched beam fracture toughness (CNB) was measured following a modified ISO 24370 standard. Composite bars with dimensions of 3.0×4.0×25 mm were prepared, with the adhesive-dentin interface in the middle. At the adhesive-dentin interface, a chevron notch was prepared using a 0.15 mm thin diamond blade mounted in a water-cooled diamond saw. Each specimen was loaded until failure in a 4-point bend test setup and the fracture toughness was calculated according to the ISO specifications. Similarly, adhesive-dentin micro-specimens (1.0×1.0×8-10 mm) were stressed in tensile until failure to determine the μTBS. A positive correlation (r(2)=0.64) was observed between CNB and μTBS, which however was only nearly statistically significant, mainly due to the dissimilar outcome of Scotchbond Universal (3M ESPE). While few μTBS specimens failed at the adhesive-dentin interface, almost all CNB specimens failed interfacially at the notch tip. Weibull moduli for interfacial fracture toughness were much higher than for μTBS (3.8-11.5 versus 2.7-4.8, respectively), especially relevant with regard to early failures. Although the ranking of the adhesives on their bonding effectiveness tested using CNB and μTBS corresponded well, the outcome of CNB appeared more reliable and less variable. Fracture toughness measurement is however more laborious and requires specific equipment. The μTBS nevertheless appeared to remain a valid method to assess bonding effectiveness in a versatile way. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

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

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

Tensile and impact testing of an HFBR [High Flux Beam Reactor] control rod follower

International Nuclear Information System (INIS)

Czajkowski, C.J.; Schuster, M.H.; Roberts, T.C.; Milian, L.W.

1989-08-01

The Materials Technology Group of the Department of Nuclear Energy (DNE) at Brookhaven National Laboratory (BNL) undertook a program to machine and test specimens from a control rod follower from the High Flux Beam Reactor (HFBR). Tensile and Charpy impact specimens were machined and tested from non-irradiated aluminum alloys in addition to irradiated 6061-T6 from the HFBR. The tensile test results on irradiated material showed a two-fold increase in tensile strength to a maximum of 100.6 ksi. The impact resistance of the irradiated material showed a six-fold decrease in values (3 in-lb average) compared to similar non-irradiated material. Fracture toughness (K I ) specimens were tested on an unirradiated compositionally and dimensionally similar (to HFBR follower) 6061 T-6 material with K max values of 24.8 ± 1.0 Ksi√in (average) being obtained. The report concludes that the specimens produced during the program yielded reproducible and believable results and that proper quality assurance was provided throughout the program. 9 figs., 6 tabs

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 ...

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

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)

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

Effect of post weld heat treatment on tensile properties and microstructure characteristics of friction stir welded armour grade AA7075-T651 aluminium alloy

Directory of Open Access Journals (Sweden)

P. Sivaraj

2014-03-01

Full Text Available This paper reports the effects of post weld heat treatments, namely artificial ageing and solution treatment followed by artificial ageing, on microstructure and mechanical properties of 12 mm thick friction stir welded joints of precipitation hardenable high strength armour grade AA7075-T651 aluminium alloy. The tensile properties, such as yield strength, tensile strength, elongation and notch tensile strength, are evaluated and correlated with the microhardness and microstructural features. The scanning electron microscope is used to characterie the fracture surfaces. The solution treatment followed by ageing heat treatment cycle is found to be marginally beneficial in improving the tensile properties of friction stir welds of AA7075-T651 aluminium alloy.

A comparative study on the tensile and impact properties of Kevlar, carbon, and S-glass/epoxy composites reinforced with SiC particles

Science.gov (United States)

Bulut, Mehmet; Alsaadi, Mohamad; Erkliğ, Ahmet

2018-02-01

Present study compares the tensile and impact characteristics of Kevlar, carbon and glass fiber reinforced composites with addition of microscale silicon carbide (SiC) within the common matrix of epoxy. The variation of tensile and impact strength values was explored for different content of SiC in the epoxy resin by weight (0, 5, 10, 15 and 20 wt%). Resulting failure characteristics were identified by assisting Charpy impact tests. The influence of interfacial adhesion between particle and fiber/matrix on failure and tensile properties was discussed from obtained results and scanning electron microscopy (SEM) figures. It is concluded from results that the content of SiC particles, and fiber types used as reinforcement are major parameters those effecting on tensile and impact resistance of composites as a result of different interface strength properties between particle-matrix and particle-fiber.

Analyses and results from standard surveillance programmes of WWER 440/V-213C reactor pressure vessels

Energy Technology Data Exchange (ETDEWEB)

Falcnik, M; Brumovsky, M; Pav, T [Czech Nuclear Society, Prague (Czech Republic)

1994-12-31

In Czech and Slovak republics, six units of WWER 440/C type reactors are monitored by surveillance specimens programmes; the specimens are determined for static tensile testing, impact notch toughness testing and fracture toughness evaluation. Results of mechanical properties of these specimens after irradiation in intervals between 1 and 5 years of operation, are summarized and discussed with respect to the effect of individual heats and welded joints, radiation embrittlement, and annealing recovery. (authors). 3 refs., 11 figs., 2 tabs.

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.

Standard practice for verification of testing frame and specimen alignment under tensile and compressive axial force application

CERN Document Server

American Society for Testing and Materials. Philadelphia

2005-01-01

1.1 Included in this practice are methods covering the determination of the amount of bending that occurs during the application of tensile and compressive forces to notched and unnotched test specimens in the elastic range and to plastic strains less than 0.002. These methods are particularly applicable to the force application rates normally used for tension testing, creep testing, and uniaxial fatigue testing.

Standard practice for verification of testing frame and specimen alignment under tensile and compressive axial force application

CERN Document Server

American Society for Testing and Materials. Philadelphia

2014-01-01

1.1 Included in this practice are methods covering the determination of the amount of bending that occurs during the application of tensile and compressive forces to notched and unnotched test specimens in the elastic range and to plastic strains less than 0.002. These methods are particularly applicable to the force application rates normally used for tension testing, creep testing, and uniaxial fatigue testing.

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.

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)

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

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

Selective Electron Beam Manufacturing of Ti-6Al-4V Strips: Effect of Build Orientation, Columnar Grain Orientation, and Hot Isostatic Pressing on Tensile Properties

Science.gov (United States)

Wang, J.; Tang, H. P.; Yang, K.; Liu, N.; Jia, L.; Qian, M.

2018-03-01

Many novel designs for additive manufacturing (AM) contain thin-walled (≤ 3 mm) sections in different orientations. Selective electron beam melting (SEBM) is particularly suited to AM of such thin-walled titanium components because of its high preheating temperature and high vacuum. However, experimental data on SEBM of Ti-6Al-4V thin sections remains scarce because of the difficulty and high cost of producing long, thin and smooth strip tensile specimens (see Fig. 1). In this study, 80 SEBM Ti-6Al-4V strips (180 mm long, 42 mm wide, 3 mm thick) were built both vertically (V-strips) and horizontally (H-strips). Their density, microstructure and tensile properties were investigated. The V-strips showed clearly higher tensile strengths but lower elongation than the H-strips. Hot isostatic pressing (HIP) produced the same lamellar α-β microstructures in terms of the average α-lath thickness in both types of strips. The retained prior-β columnar grain boundaries after HIP showed no measurable influence on the tensile properties, irrespective of their length and orientation, because of the formation of randomly distributed fine α-laths.[Figure not available: see fulltext.

A new tensile impact test for the toughness characterization of sheet material

Science.gov (United States)

Könemann, Markus; Lenz, David; Brinnel, Victoria; Münstermann, Sebastian

2018-05-01

In the past, the selection of suitable steels has been carried out primarily based on the mechanical properties of different steels. One of these properties is the resistance against crack propagation. For many constructions, this value plays an important role, because it can compare the impact toughness of different steel grades easily and gives information about the loading capacity of the specific materials. For thin sheets, impact toughness properties were usually not considered. One of the reasons for this is that the Charpy-impact test is not applicable for sheets with thicknesses below 2 mm. For a long time, this was not relevant because conventional steels had a sufficient impact toughness in a wide temperature range. However, since new multiphase steel grades with improved mechanical property exploitations are available, it turned out that impact toughness properties need to be considered during the component design phase, as the activation of the cleavage fracture mechanism is observed under challenging loading conditions. Therefore, this work aims to provide a new and practical testing procedure for sheet material or thin walled structures. The new testing procedure is based on tensile tests conducted in an impact pendulum similar to the Charpy impact hammer. A new standard geometry is provided, which enables a comparison between different steels or steel grades. A connection to the conventional Charpy test is presented using a damage mechanics model, which predicts material failure with consideration of to the stress state at various temperatures. Different specimen geometries are analysed to cover manifold stress states. A special advantage of the damage mechanics model is also the possibility to predict the materials behaviour in the transition area. To verify the method a conventional steel was tested in Charpy tests as well as in the new tensile impact test.

Investigation and microstructural analyses of massive LSP impacts with coverage area on crack initiation location and tensile properties of AM50 magnesium alloy

Energy Technology Data Exchange (ETDEWEB)

Luo, K.Y.; Wang, C.Y. [School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China); Sun, G.F. [School of Mechanical Engineering, Southeast University, Nanjing 211189 (China); Cui, C.Y.; Sheng, J. [School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China); Lu, J.Z., E-mail: blueesky2005@163.com [School of Mechanical Engineering, Jiangsu University, Zhenjiang 212013 (China)

2016-01-05

The influence of massive laser shock peening (LSP) impacts with coverage area on tensile properties of AM50 magnesium alloy was investigated using MTS880-10 servo-hydraulic material testing machine system. Microstructure in the surface layer and fracture morphologies of as-machined and LSPed tensile specimens were also characterized and analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and cross-sectional optical microscopy (OM). Special attention is paid to the crack initiation location as a function of LSPed coverage area in the gauge part of tensile specimen. Experimental results and analysis indicate that coverage area significantly influenced tensile properties of the tensile specimen. In addition, the grain refinement process in the top surface layer of AM50 magnesium alloy caused by massive LSP impacts is presented. Furthermore, the underlying influence mechanism of LSPed coverage area on tensile properties and crack initiation location of tensile specimen was clearly revealed.

Investigation and microstructural analyses of massive LSP impacts with coverage area on crack initiation location and tensile properties of AM50 magnesium alloy

International Nuclear Information System (INIS)

Luo, K.Y.; Wang, C.Y.; Sun, G.F.; Cui, C.Y.; Sheng, J.; Lu, J.Z.

2016-01-01

The influence of massive laser shock peening (LSP) impacts with coverage area on tensile properties of AM50 magnesium alloy was investigated using MTS880-10 servo-hydraulic material testing machine system. Microstructure in the surface layer and fracture morphologies of as-machined and LSPed tensile specimens were also characterized and analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and cross-sectional optical microscopy (OM). Special attention is paid to the crack initiation location as a function of LSPed coverage area in the gauge part of tensile specimen. Experimental results and analysis indicate that coverage area significantly influenced tensile properties of the tensile specimen. In addition, the grain refinement process in the top surface layer of AM50 magnesium alloy caused by massive LSP impacts is presented. Furthermore, the underlying influence mechanism of LSPed coverage area on tensile properties and crack initiation location of tensile specimen was clearly revealed.

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

High strain rate and quasi-static tensile behaviour of Ti-6Al-4V after cyclic damage

Directory of Open Access Journals (Sweden)

Verleysen P.

2012-08-01

Full Text Available It is common that energy absorbing structural elements are subjected to a number of loading cycles before a crash event. Several studies have shown that previous fatigue can significantly influence the tensile properties of some materials, and hence the behaviour of structural elements made of them. However, when the capacity of absorbing energy of engineering materials is determined, fresh material without any fatigue damage is most often used. This study investigates the effect of fatigue damage on the dynamic tensile properties of Ti-6Al-4V in thin-sheet form. Results are completed with tests at quasi-static strain rates and observations of the fracture surfaces, and compared with results obtained from other alloys and steel grades. The experiments show that the dynamic properties of Ti-6Al-4V are not affected by a number of fatigue loading cycles high enough to significantly reduce the energy absorbing capabilities of EDM machined samples.

Tensile strength and impact resistance properties of materials used in prosthetic check sockets, copolymer sockets, and definitive laminated sockets.

Science.gov (United States)

Gerschutz, Maria J; Haynes, Michael L; Nixon, Derek M; Colvin, James M

2011-01-01

Prosthetic sockets serve as the interface between people with amputations and their prostheses. Although most materials used to make prosthetic sockets have been used for many years, knowledge of these materials' properties is limited, especially after they are subjected to fabrication processes. This study evaluated tensile and impact properties of the current state-of-the-art materials used to fabricate prosthetic check sockets, copolymer sockets, and definitive laminated sockets. Thermolyn Rigid and Orfitrans Stiff check socket materials produced significantly lower tensile strength and impact resistance than polyethylene terephthalate glycol (PETG). Copolymer socket materials exhibited greater resistance to impact forces than the check socket materials but lower tensile strengths than PETG. The heated molding processes, for the check socket and copolymer materials, reduced both tensile strength and elongation at break. Definitive laminated sockets were sorted according to fabrication techniques. Nyglass material had significantly higher elongation, indicating a more ductile material than carbon-based laminations. Carbon sockets with pigmented resin had higher tensile strength and modulus at break than nonpigmented carbon sockets. Elongation at yield and elongation at break were similar for both types of carbon-based laminations. The material properties determined in this study provide a foundation for understanding and improving the quality of prosthetic sockets using current fabrication materials and a basis for evaluating future technologies.

Effect of irradiation on the tensile properties of niobium-base alloys

International Nuclear Information System (INIS)

Grossbeck, M.L.; Heestand, R.L.; Atkin, S.D.

1986-11-01

The alloys Nb-1Zr and PWC-11 (Nb-1Zr-0.1C) were selected as prime candidate alloys for the SP-100 reactor. Since the mechanical properties of niobium alloys irradiated to end-of-life exposure levels of about 2 x 10 26 neutrons/m 2 (E > 0.1 MeV) at temperatures above 1300 K were not available, an irradiation experiment (B-350) in EBR-II was conducted. Irradiation creep, impact properties, bending fatigue, and tensile properties were investigated; however, only tensile properties will be reported in this paper. The tensile properties were studied since they easily reveal the common irradiation phenomena of hardening and embrittlement. Most attention was directed to testing at the irradiation temperature. Further testing was conducted at lower temperatures in order to scope the behavior of the alloys in cooldown conditions

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

Tensile properties of aluminized V-5Cr-5Ti alloy after exposure in air environment

Energy Technology Data Exchange (ETDEWEB)

Natesan, K.; Soppet, W.K. [Argonne National Lab., IL (United States)

1997-08-01

The objectives of this task are to (a) develop procedures to modify surface regions of V-Cr-Ti alloys in order to minimize oxygen uptake by the alloys when exposed to environments that contain oxygen, (b) evaluate the oxygen uptake of the surface-modified V-Cr-Ti alloys as a function of temperature an oxygen partial pressure in the exposure environment, (c) characterize the microstructures of oxide scales and oxygen trapped at the grain boundaries of the substrate alloys, and (d) evaluate the influence of oxygen uptake on the tensile properties of the modified alloys at room and elevated temperatures.

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.)

Dynamic tensile behavior of electron beam additive manufactured Ti6Al4V

International Nuclear Information System (INIS)

Rodriguez, O.L.; Allison, P.G.; Whittington, W.R.; Francis, D.K.; Rivera, O.G.; Chou, K.; Gong, X.; Butler, T.M.; Burroughs, J.F.

2015-01-01

High rate and quasi-static tensile experiments examined strain rate dependence on flow stress and strain hardening of additive manufactured Ti6Al4V. Variations on strain-hardening coefficient indicate that the rate of thermal softening is greater than strain hardening during plastic deformation. Strain rate sensitivity calculations within the plastic strain regime suggest changes in deformation mechanisms. Fractography revealed cup-and-cone fracture for quasi-static samples and shear mechanisms for high rate samples. As-deposited microstructure consisted of bimodal α+β with the presence of secondary martensitic phase

Dynamic tensile behavior of electron beam additive manufactured Ti6Al4V

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, O.L. [Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487 (United States); Allison, P.G., E-mail: pallison@eng.ua.edu [Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487 (United States); Whittington, W.R.; Francis, D.K. [Department of Mechanical Engineering, Mississippi State University, Starkville, MS 35759 (United States); Rivera, O.G.; Chou, K.; Gong, X. [Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487 (United States); Butler, T.M. [Department of Metallurgical Engineering, University of Alabama, Tuscaloosa, AL 35487 (United States); Burroughs, J.F. [Geotechnical & Structures Laboratory, US Army ERDC, Vicksburg, MS 39180 (United States)

2015-08-12

High rate and quasi-static tensile experiments examined strain rate dependence on flow stress and strain hardening of additive manufactured Ti6Al4V. Variations on strain-hardening coefficient indicate that the rate of thermal softening is greater than strain hardening during plastic deformation. Strain rate sensitivity calculations within the plastic strain regime suggest changes in deformation mechanisms. Fractography revealed cup-and-cone fracture for quasi-static samples and shear mechanisms for high rate samples. As-deposited microstructure consisted of bimodal α+β with the presence of secondary martensitic phase.

Impact of tensile strain on the thermal transport of zigzag hexagonal boron nitride nanoribbon: An equilibrium molecular dynamics study

Science.gov (United States)

Navid, Ishtiaque Ahmed; Intisar Khan, Asir; Subrina, Samia

2018-02-01

The thermal conductivity of single layer strained hexagonal boron nitride nanoribbon (h-BNNR) has been computed using the Green—Kubo formulation of Equilibrium Molecular Dynamics (EMD) simulation. We have investigated the impact of strain on thermal transport of h-BNNR by varying the applied tensile strain from 1% upto 5% through uniaxial loading. The thermal conductivity of h-BNNR decreases monotonically with the increase of uniaxial tensile strain keeping the sample size and temperature constant. The thermal conductivity can be reduced upto 86% for an applied uniaxial tensile strain of 5%. The impact of temperature and width variation on the thermal conductivity of h-BNNR has also been studied under different uniaxial tensile strain conditions. With the increase in temperature, the thermal conductivity of strained h-BNNR exhibits a decaying characteristics whereas it shows an opposite pattern with the increasing width. Such study would provide a good insight on the strain tunable thermal transport for the potential device application of boron nitride nanostructures.

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.

Heat treatment effects on tensile properties of V-(4-5) wt.% Cr-(4-5) wt.% Ti alloys

Energy Technology Data Exchange (ETDEWEB)

Natesan, K.; Soppet, W.K. [Argonne National Lab., IL (United States)

1997-08-01

Effects of thermomechanical treatments on microstructures and mechanical properties are of interest for long term application of V-Cr-Ti alloys in fusion reactor systems. Influence of thermal annealing at 1050{degrees}C on stress/strain behavior, maximum engineering strength, and uniform and total elongation were evaluated. The results show that multiple annealing has minimal effect on the tensile properties of V-(4-5)Cr-(4-5)Ti alloys tested at room temperature and at 500{degrees}C.

Influence of circumferential notch and fatigue crack on the mechanical integrity of biodegradable magnesium-based alloy in simulated body fluid.

Science.gov (United States)

Bobby Kannan, M; Singh Raman, R K; Witte, F; Blawert, C; Dietzel, W

2011-02-01

Applications of magnesium alloys as biodegradable orthopaedic implants are critically dependent on the mechanical integrity of the implant during service. In this study, the mechanical integrity of an AZ91 magnesium alloy was studied using a constant extension rate tensile (CERT) method. The samples in two different geometries that is, circumferentially notched (CN), and circumferentially notched and fatigue cracked (CNFC), were tested in air and in simulated body fluid (SBF). The test results show that the mechanical integrity of the AZ91 magnesium alloy decreased substantially (∼50%) in both the CN and CNFC samples exposed to SBF. Fracture surface analysis revealed secondary cracks suggesting stress corrosion cracking susceptibility of the alloy in SBF. Copyright © 2010 Wiley Periodicals, Inc.

Tensile properties in zircaloy-II after 590 MeV proton irradiation

Energy Technology Data Exchange (ETDEWEB)

Dai, Y. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Victoria, M. [Ecole Polytechnique Federale, Lausanne (Switzerland)

1997-09-01

In order to investigate radiation potential damage effects on the SINQ Zircaloy-rod target, four Zircaloy-II tensile specimens were irradiated at the PIREX facility in 1995 to a proton fluence about 3x10{sup 20} p/cm{sup 2}, which produced a radiation damage of about 1.35 displacements per atom (dpa). Tensile test results show that, although there is some reduction in tensile elongation, substantial ductility still exists after such irradiation dose which corresponds to the peak value obtained in the SINQ target for 23 days operation at 1 mA. (author) 1 fig., 2 refs.

Fatigue limit prediction of ferritic-pearlitic ductile cast iron considering stress ratio and notch size

Science.gov (United States)

Deguchi, T.; Kim, H. J.; Ikeda, T.

2017-05-01

The mechanical behavior of ductile cast iron is governed by graphite particles and casting defects in the microstructures, which can significantly decrease the fatigue strength. In our previous study, the fatigue limit of ferritic-pearlitic ductile cast iron specimens with small defects ((\\sqrt{{area}}=80˜ 1500{{μ }}{{m}})) could successfully be predicted based on the \\sqrt{{area}} parameter model by using \\sqrt{{area}} as a geometrical parameter of defect as well as the tensile strength as a material parameter. In addition, the fatigue limit for larger defects could be predicted based on the conventional fracture mechanics approach. In this study, rotating bending and tension-compression fatigue tests with ferritic-pearlitic ductile cast iron containing circumferential sharp notches as well as smooth specimens were performed to investigate quantitatively the effects of defect. The notch depths ranged 10 ˜ 2500 μm and the notch root radii were 5 and 50 μm. The stress ratios were R = -1 and 0.1. The microscopic observation of crack propagation near fatigue limit revealed that the fatigue limit was determined by the threshold condition for propagation of a small crack emanating from graphite particles. The fatigue limit could be successfully predicted as a function of R using a method proposed in this study.

Tensile and impact properties of TZM and Mo-5% Re

International Nuclear Information System (INIS)

Filacchioni, G.; Casagrande, E.; Angelis, U. de; Santis, G. de; Ferrara, D.

1994-01-01

Some aspects of the mechanical behaviour of two molybdenum alloys, one belonging to the precipitation hardened sub-family (TZM) and the other is a solid solution Mo 5% rhenium-bearing alloy, have been investigated. Experimental data (tensile mechanical strength, ductility and impact properties of unirradiated materials) show that a difference in behaviour exists between the precipitation hardened and the solid solution strengthened alloy, but at the same time a serious discrepancy has been found between the present results and previously reported ductile to brittle transition temperature values for Mo alloys. ((orig.))

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.

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.

Characterization of the deformation texture after tensile test and cold rolling of a Ti-6Al-4V sheet alloy

International Nuclear Information System (INIS)

Mehdi, B; Badji, R; Azzeddine, H; Alili, B; Bradai, D; Ji, V

2015-01-01

The deformation texture after cold rolling and tensile test of an industrial Ti-6Al-4V sheet alloy was studied using X-ray diffraction. The alloy was subjected to a cold rolling to different thickness reductions (from 20% to 60%) and then tensile tests have been carried out along three directions relatively to the rolling direction (0°, 45° and 90°). The experimental results were compared to the existing literature and discussed in terms of active plastic deformation mechanisms. (paper)

Influence of the final temperature of investment healting on the tensile strength and Vickers hardness of CP Ti and Ti-6Al-4V alloy

Directory of Open Access Journals (Sweden)

Pedro César Garcia Oliveira

2007-02-01

Full Text Available The aim of the work was to evaluate the influence of the temperature of investment healting on the tensile strength and Vickers hardness of CP Ti and Ti-6Al-4V alloy casting. Were obtained for the tensile strength test dumbbell rods that were invested in the Rematitan Plus investment and casting in the Discovery machine cast. Thirty specimens were obtained, fiftten to the CP Titanium and fifteen to the Ti-6Al-4V alloy, five samples to each an of the three temperatures of investment: 430ºC (control group, 480ºC and 530ºC. The tensile test was measured by means of a universal testing machine, MTS model 810, at a strain of 1.0 mm/min. After the tensile strenght test the specimens were secctioned, embedded and polished to hardness measurements, using a Vickers tester, Micromet 2100. The means values to tensile tests to the temperatures 430ºC, 480 and 530: CP Ti (486.1 - 501.16 - 498.14 -mean 495.30 MPa and Ti-6Al-4V alloy (961.33 - 958.26 - 1005.80 - mean 975.13 MPa while for the Vickers hardness the values were (198.06, 197.85, 202.58 - mean 199.50 and (352.95, 339.36, 344.76 - mean 345.69, respectively. The values were submitted to Analysis of Variance (ANOVA and Tukey,s Test that indicate differences significant only between the materials, but not between the temperature, for both the materias. It was conclued that increase of the temperature of investment its not chance the tensile strength and the Vickers hardness of the CP Titanium and Ti-6Al-4V alloy.

Improving High-Temperature Tensile and Low-Cycle Fatigue Behavior of Al-Si-Cu-Mg Alloys Through Micro-additions of Ti, V, and Zr

Science.gov (United States)

Shaha, S. K.; Czerwinski, F.; Kasprzak, W.; Friedman, J.; Chen, D. L.

2015-07-01

High-temperature tensile and low-cycle fatigue tests were performed to assess the influence of micro-additions of Ti, V, and Zr on the improvement of the Al-7Si-1Cu-0.5Mg (wt pct) alloy in the as-cast condition. Addition of transition metals led to modification of microstructure where in addition to conventional phases present in the Al-7Si-1Cu-0.5Mg base, new thermally stable micro-sized Zr-Ti-V-rich phases Al21.4Si4.1Ti3.5VZr3.9, Al6.7Si1.2TiZr1.8, Al2.8Si3.8V1.6Zr, and Al5.1Si35.4Ti1.6Zr5.7Fe were formed. The tensile tests showed that with increasing test temperature from 298 K to 673 K (25 °C to 400 °C), the yield stress and tensile strength of the present studied alloy decreased from 161 to 84 MPa and from 261 to 102 MPa, respectively. Also, the studied alloy exhibited 18, 12, and 5 pct higher tensile strength than the alloy A356, 354 and existing Al-Si-Cu-Mg alloy modified with additions of Zr, Ti, and Ni, respectively. The fatigue life of the studied alloy was substantially longer than those of the reference alloys A356 and the same Al-7Si-1Cu-0.5Mg base with minor additions of V, Zr, and Ti in the T6 condition. Fractographic analysis after tensile tests revealed that at the lower temperature up to 473 K (200 °C), the cleavage-type brittle fracture for the precipitates and ductile fracture for the matrix were dominant while at higher temperature fully ductile-type fracture with debonding and pull-out of cracked particles was identified. It is believed that the intermetallic precipitates containing Zr, Ti, and V improve the alloy performance at increased temperatures.

Measurements of the tensile and compressive properties of micro-concrete used in the Winfrith missile impact experiments

International Nuclear Information System (INIS)

Wilson, P.A.

1982-10-01

Tests to determine the tensile and compressive properties of a micro-concrete mix are described. The material is a nominally 40MPa ultimate compressive strength concrete used in impact tests with scale models in the prediction of responses in prototype concrete structures. Compressive tests were intended to give complete stress-strain relationships beyond initial failure. Tensile properties were measured by the Brazilian splitting technique and direct tension dog-bone specimens for comparison reasons. (U.K.)

Tensile and fracture properties of primary heat transport system piping material

International Nuclear Information System (INIS)

Singh, P.K.; Chattopadhyay, J.; Kushwaha, H.S.

1997-07-01

The fracture mechanics calculations in leak-before-break analysis of nuclear piping system require material tensile data and fracture resistance properties in the form of J-R curve. There are large variations in fracture parameters due to variation in chemical composition and process used in making the steel components. Keeping this in view, a comprehensive program has been planned to generate the material data base for primary heat transport system piping using the specimens machined from actual pipes used in service. The material under study are SA333 Gr.6 (base as well as weld) and SA350 LF2 (base). Since the operating temperatures of 500 MWe Indian PHWR PHT system piping range from 260 degC to 304 degC the test temperature chosen are 28 degC, 200 degC, 250 degC and 300 degC. Tensile and compact tension specimens have been fabricated from actual pipe according to ASTM standard. Fracture toughness of base metal has been observed to be higher compared to weld metal in SA333 Gr.6 material for the temperature under consideration. Fracture toughness has been observed to be higher for LC orientation (notch in circumferential direction) compared to CL orientation (notch is in longitudinal direction) for the temperature range under study. Fracture toughness value decreases with increase in temperature for the materials under study. Finally, chemical analysis has been carried out to investigate the reason for high toughness of the material. It has been concluded that low percentage of carbon and nitrogen, low inclusion rating and fine grain size has enhanced the fracture toughness value

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

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.

Tensile properties and microstructure of direct metal laser-sintered TI6AL4V (ELI alloy

Directory of Open Access Journals (Sweden)

Moletsane, M. G.

2016-11-01

Full Text Available Direct metal laser sintering (DMLS is an additive manufacturing technology used to melt metal powder by high laser power to produce customised parts, light-weight structures, or other complex objects. During DMLS, powder is melted and solidified track-by-track and layer-by-layer; thus, building direction can influence the mechanical properties of DMLS parts. The mechanical properties and microstructure of material produced by DMLS can depend on the powder properties, process parameters, scanning strategy, and building geometry. In this study, the microstructure, tensile properties, and porosity of DMLS Ti6Al4V (ELI horizontal samples were analysed. Defect analysis by CT scans in pre-strained samples was used to detect the crack formation mechanism during tensile testing of as-built and heat-treated samples. The mechanical properties of the samples before and after stress relieving are discussed.

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

Study of austenitic stainless steel welded with low alloy steel filler metal. [tensile and impact strength tests

Science.gov (United States)

Burns, F. A.; Dyke, R. A., Jr.

1979-01-01

The tensile and impact strength properties of 316L stainless steel plate welded with low alloy steel filler metal were determined. Tests were conducted at room temperature and -100 F on standard test specimens machined from as-welded panels of various chemical compositions. No significant differences were found as the result of variations in percentage chemical composition on the impact and tensile test results. The weldments containing lower chromium and nickel as the result of dilution of parent metal from the use of the low alloy steel filler metal corroded more severely in a marine environment. The use of a protective finish, i.e., a nitrile-based paint containing aluminum powder, prevented the corrosive attack.

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

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.

Tensile properties of helium-injected V-15Cr-5Ti after irradiation in EBR-II

International Nuclear Information System (INIS)

Grossbeck, M.L.; Horak, J.A.

1985-01-01

Miniature specimens of V-15Cr-5Ti were prepared in the annealed condition and with 10, 20, and 30% cold work. The annealed specimens were cyclotron injected with helium and irradiated in sodium in EBR-II. The cold-worked specimens were irradiated in EBR-II but not helium injected. The specimens were irradiated at 400, 525, 625, and 700 0 C and received a fluence of 4.1 to 5.5 x 10 26 neutrons/m 2 (E > 0.1 meV). Tensile testing revealed very significant embrittlement as a result of the neutron irradiation but a much smaller change, mostly at 400 0 C, resulting from helium injection. 5 references, 9 figures, 2 tables

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

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

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

On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

Science.gov (United States)

Zhao, Ziyu; Liu, Jinxing; Soh, Ai Kah

2018-01-01

In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials' amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

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.

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.

Microstructure and tensile properties of selectively laser-melted and of HIPed laser-melted Ti–6Al–4V

International Nuclear Information System (INIS)

Qiu, Chunlei; Adkins, Nicholas J.E.; Attallah, Moataz M.

2013-01-01

Ti–6Al–4V samples have been prepared by selective laser melting (SLM) with varied processing conditions. Some of the samples were stress-relieved or hot isostatically pressed (HIPed). The microstructures of all samples were characterised using optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD) and the tensile properties measured before and after HIPing. It was found that the porosity level generally decreased with increase of laser power and laser scanning speed. Horizontally built samples were found to have a higher level of porosity than vertically built samples. The as-fabricated microstructure was dominated by columnar grains and martensites. HIPing closed the majority of the pores and also fully transformed the martensite into α and β phases. The as-fabricated microstructure exhibits very high tensile strengths but poor ductility with elongation generally smaller than 10%. The horizontally built samples show even lower elongation than vertically built samples. HIPing considerably improved ductility but led to a reduction in strength. With HIPing, the SLMed samples were found to show tensile properties comparable with those thermomechanically processed and annealed samples

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.

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...

Revised ANL-reported tensile data for V-Ti and V-Cr-Ti alloys

Energy Technology Data Exchange (ETDEWEB)

Billone, M.C. [Argonne National Lab., IL (United States)

1997-08-01

The tensile for all irradiated vanadium alloy samples and several unirradiated vanadium alloys tested at Argonne National Laboratory (ANL) have been critically reviewed and revised, as necessary. The review and revision are based on re-analyzing the original load-displacement strip-chart recording using a methodology consistent with current ASTM standards. No significant difference has been found between the newly-revised and previously-reported values of yield strength (YS) and ultimate tensile strength (UTS). However, by correctly subtracting the non-gauge-length displacement and linear gauge-length displacement from the total cross-head displacement, the uniform elongation (UE) of the gauge length decreases by 4-9% strain and the total elongation (TE) of the gauge length decreases by 1-7% strain. These differences are more significant for lower-ductility irradiated alloys than for higher-ductility alloys.

Revised ANL-reported tensile data for V-Ti and V-Cr-Ti alloys

International Nuclear Information System (INIS)

Billone, M.C.

1997-01-01

The tensile for all irradiated vanadium alloy samples and several unirradiated vanadium alloys tested at Argonne National Laboratory (ANL) have been critically reviewed and revised, as necessary. The review and revision are based on re-analyzing the original load-displacement strip-chart recording using a methodology consistent with current ASTM standards. No significant difference has been found between the newly-revised and previously-reported values of yield strength (YS) and ultimate tensile strength (UTS). However, by correctly subtracting the non-gauge-length displacement and linear gauge-length displacement from the total cross-head displacement, the uniform elongation (UE) of the gauge length decreases by 4-9% strain and the total elongation (TE) of the gauge length decreases by 1-7% strain. These differences are more significant for lower-ductility irradiated alloys than for higher-ductility alloys

Anisotropy influence on the failure of Ti6Al4V sheets deformed at room and elevated temperature

Science.gov (United States)

Wang, Q. L.; Ghiotti, A.; Bruschi, S.

2018-05-01

Ti6Al4V sheets are usually difficult-to-form at room temperature as a consequence of their strong basal texture and hcp crystal lattice. The heating of the alloy below the beta transus temperature is recognized to enhance its formability, reducing the flow stress and increasing the ductility. However, the influence of the sheet anisotropy on the material failure hasn't been studied yet. To this aim, the paper presents the anisotropy influence on the failure characteristics of Ti6Al4V titanium alloy sheets making use of tensile tests carried out at room temperature and 600°C on smooth, notched and shear samples in order to have various stress states. The fracture strain is measured and the effect of the sample orientation and stress state is identified. To determine the actual stress state for each sample geometry, a numerical model is set up and calibrated using elasto-plastic data from uni-axial tensile tests on smooth samples. Finally, the fracture surfaces are observed through SEM analysis to explain the failure characteristics.

Microstructure and tensile properties of Ti-6Al-4V alloys manufactured by selective laser melting with optimized processing parameters

Science.gov (United States)

Wang, L.; Ma, C.; Huang, J.; Ding, H. Y.; Chu, M. Q.

2017-11-01

Selective laser melting (SLM) is a precise additive manufacturing process that the metallic powders without binder are melted layer by layer to complex components using a high bright fiber laser. In the paper, Ti-6Al-4V alloy was fabricated by SLM and its microstructure and mechanical properties were investigated in order to evaluate the SLM process. The results show that the microstructure exists anisotropy between the horizontal and vertical section due to the occurrence of epitaxial growth, and the former microstructure seems equal-axis and the latter is column. Moreover, there is little difference in tensile test between the horizontal and vertical sections. Furthermore, the tensile properties of fabricated Ti-6Al-4V alloy by SLM are higher than the forged standard ones. However, the fatigue results show that there are some scatters, which need further investigation to define the fatigue initiation.

All-solid-state carbon nanotube torsional and tensile artificial muscles.

Science.gov (United States)

Lee, Jae Ah; Kim, Youn Tae; Spinks, Geoffrey M; Suh, Dongseok; Lepró, Xavier; Lima, Mácio D; Baughman, Ray H; Kim, Seon Jeong

2014-05-14

We report electrochemically powered, all-solid-state torsional and tensile artificial yarn muscles using a spinnable carbon nanotube (CNT) sheet that provides attractive performance. Large torsional muscle stroke (53°/mm) with minor hysteresis loop was obtained for a low applied voltage (5 V) without the use of a relatively complex three-electrode electromechanical setup, liquid electrolyte, or packaging. Useful tensile muscle strokes were obtained (1.3% at 2.5 V and 0.52% at 1 V) when lifting loads that are ∼25 times heavier than can be lifted by the same diameter human skeletal muscle. Also, the tensile actuator maintained its contraction following charging and subsequent disconnection from the power supply because of its own supercapacitor property at the same time. Possible eventual applications for the individual tensile and torsional muscles are in micromechanical devices, such as for controlling valves and stirring liquids in microfluidic circuits, and in medical catheters.

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.

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 ...

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.

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

Notch Sensitivity of Fatigue Behavior of a Hi-Nicalon™/SiC-B4C Composite at 1,200 °C in Air and in Steam

Science.gov (United States)

Ruggles-Wrenn, M. B.; Kurtz, G.

2013-10-01

The effect of holes on the fatigue life of a non-oxide ceramic composite processed via chemical vapor infiltration (CVI) was examined at 1,200 °C in laboratory air and in steam. The effect of holes on tensile strength at 1,200 °C was also evaluated. The composite comprised laminated woven Hi-Nicalon™ fibers in an oxidation inhibited matrix, which consisted of alternating layers of silicon carbide and boron carbide. Fiber preforms had pyrolytic carbon fiber coating with boron carbon overlay applied. Unnotched specimens and specimens with a center hole having a radius to width ratio of 0.24 were tested in tension-tension fatigue at 0.1 Hz and at 1.0 Hz. The fatigue stresses ranged from 100 to 140 MPa in air and in steam. Fatigue run-out was defined as 105 cycles at 0.1 Hz and as 2 × 105 cycles at 1.0 Hz. The net-section strength was less than the unnotched ultimate tensile strength. Comparison of notched and unnotched data also revealed that the fatigue performance was notch insensitive in both air and steam environments. Composite microstructure, as well as damage and failure mechanisms were investigated.

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

International Nuclear Information System (INIS)

Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

2015-01-01

Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch ICN-TG ). Following exposure of adult Notch ICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch ICN-TG offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch ICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Energy Technology Data Exchange (ETDEWEB)

Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D., E-mail: laiosa@uwm.edu

2015-03-01

Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

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)

On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

Directory of Open Access Journals (Sweden)

Ziyu Zhao

2018-01-01

Full Text Available In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials’ amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

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.

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

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)

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

The Effect of Constant and Pulsed Current Gas Tungsten Arc Welding on Joint Properties of 2205 Duplex Stainless Steel to 316L Austenitic Stainless Steel

Science.gov (United States)

Neissi, R.; Shamanian, M.; Hajihashemi, M.

2016-05-01

In this study, dissimilar 316L austenitic stainless steel/2205 duplex stainless steel (DSS) joints were fabricated by constant and pulsed current gas tungsten arc welding process using ER2209 DSS as a filler metal. Microstructures and joint properties were characterized using optical and electron scanning microscopy, tensile, Charpy V-notch impact and micro-hardness tests, and cyclic polarization measurements. Microstructural observations confirmed the presence of chromium nitride and delta ferrite in the heat-affected zone of DSS and 316L, respectively. In addition, there was some deviation in the austenite/ferrite ratio of the surface welding pass in comparison to the root welding pass. Besides having lower pitting potential, welded joints produced by constant current gas tungsten arc welding process, consisted of some brittle sigma phase precipitates, which resulted in some impact energy reduction. The tensile tests showed high tensile strength for the weld joints in which all the specimens were broken in 316L base metal.

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.

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.

Metallurgical interpretation of the change of notched bar impact strength in the heat-affected zone of weldable structural steels

International Nuclear Information System (INIS)

Forch, K.; Forch, U.; Piehl, K.H.

1978-01-01

Notched bar impact energy in the heat-affected zone of joint welds of the steels StE 36, StE 51 and 20 MnMoNi55. Manual arc welding and submerged arc welding with heat input between 10,000 and 35,000 J/cm, stress relieving between 530 and 600 0 C. Significance of the structure in the heat-affected zone, the effect of heat treatment, the precipitation processes and of temper embrittlement. (orig.) [de

Mechanical properties of as-cast microalloyed steels produced via investment casting

International Nuclear Information System (INIS)

Najafi, H.; Rassizadehghani, J.; Norouzi, S.

2011-01-01

Tensile and room temperature Charpy V-notch impact tests were used to evaluate the variations in the as-cast mechanical properties of a low-carbon steel produced via shell mould investment casting and containing combinations of vanadium, niobium and titanium. Tensile results indicate that the yield strength and ultimate tensile strength (UTS) have increased up to respectively 615 MPa and 770 MPa due to the fine-scale microalloy precipitates in the microalloyed samples. Room temperature impact test results show that while addition of vanadium individually has not changed the impact energy, Nb has decreased it considerably. However, examination of fracture surfaces reveals that all microalloyed samples have failed by transgranular cleavage. Based on the transmission electron microscope (TEM) studies, it seems that carbonitrides being greater than 50 nm in size and formed along prior austenite grain boundaries before γ transformation are responsible for the observed reduction in impact energies and brittle fracture. In comparison to sand mould casting, the yield and UTS obtained from investment casting are superior. Furthermore, although the impact energies of Nb-containing alloys are approximately the same as those obtained from sand moulds, the impact energy of the alloy containing only vanadium has improved considerably.

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.

Multilinear stress-strain and failure calibrations for Ti-6Al-4V.

Energy Technology Data Exchange (ETDEWEB)

Corona, Edmundo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2018-02-01

This memo concerns calibration of an elastic-plastic J₂ material model for Ti-6Al-4V (grade 5) alloy based on tensile uniaxial stress-strain data obtained in the laboratory. In addition, tension tests on notched specimens provided data to calibrate two ductile failure models: Johnson-Cook and Wellman's tearing parameter. The tests were conducted by Kim Haulen- beek and Dave Johnson (1528) in the Structural Mechanics Laboratory (SML) during late March and early April, 2017. The SML EWP number was 4162. The stock material was a TIMETALR® 6-4 Titanium billet with 9 in. by 9 in. square section and length of 137 in. The product description indicates that it was a forging delivered in annealed condition (2 hours @ 1300oF, AC at the mill). The tensile mechanical properties reported in the material certi cation are given in Table 1, where σ_o represents the 0.2% strain offset yield stress, σ_u the ultimate stress, ε_f the elongation at failure and R.A. the reduction in area.

Seismic characteristics of tensile fracture growth induced by hydraulic fracturing

Science.gov (United States)

Eaton, D. W. S.; Van der Baan, M.; Boroumand, N.

2014-12-01

Hydraulic fracturing is a process of injecting high-pressure slurry into a rockmass to enhance its permeability. Variants of this process are used for unconventional oil and gas development, engineered geothermal systems and block-cave mining; similar processes occur within volcanic systems. Opening of hydraulic fractures is well documented by mineback trials and tiltmeter monitoring and is a physical requirement to accommodate the volume of injected fluid. Numerous microseismic monitoring investigations acquired in the audio-frequency band are interpreted to show a prevalence of shear-dominated failure mechanisms surrounding the tensile fracture. Moreover, the radiated seismic energy in the audio-frequency band appears to be a miniscule fraction (<< 1%) of the net injected energy, i.e., the integral of the product of fluid pressure and injection rate. We use a simple penny-shaped crack model as a predictive framework to describe seismic characteristics of tensile opening during hydraulic fracturing. This model provides a useful scaling relation that links seismic moment to effective fluid pressure within the crack. Based on downhole recordings corrected for attenuation, a significant fraction of observed microseismic events are characterized by S/P amplitude ratio < 5. Despite the relatively small aperture of the monitoring arrays, which precludes both full moment-tensor analysis and definitive identification of nodal planes or axes, this ratio provides a strong indication that observed microseismic source mechanisms have a component of tensile failure. In addition, we find some instances of periodic spectral notches that can be explained by an opening/closing failure mechanism, in which fracture propagation outpaces fluid velocity within the crack. Finally, aseismic growth of tensile fractures may be indicative of a scenario in which injected energy is consumed to create new fracture surfaces. Taken together, our observations and modeling provide evidence that

Solution Treatment Effect on Tensile, Impact and Fracture Behaviour of Trace Zr Added Al-12Si-1Mg-1Cu Piston Alloy

Science.gov (United States)

Kaiser, Md. Salim

2018-04-01

The effects of T6 solution treatment on tensile, impact and fracture properties of cast Al-12Si-1Mg-1Cu piston alloys with trace of zirconium were investigated. Cast alloys were given precipitation strengthening treatment having a sequence of homogenizing, solutionizing, quenching and ageing. Both cast and solutionized samples are isochronally aged for 90 min at different temperatures up to 300 °C. Tensile and impact properties of the differently processed alloys have been studied to understand the precipitation strengthening of the alloys. Fractograpy of the alloys were observed to understand the mode of fracture. It is observed that the improvement in tensile properties in the aged alloys through heat treatment is mainly attributed to the formation of the Al2Cu and Mg2Si precipitates within the Al matrix. Solution treatment improves the tensile strength for the reason that during solution treatment some alloying elements are re-dissolved to produce a solute-rich solid solution. Impact energy decreases with ageing temperature due to formation of GP zones, β' and β precipitates. The fractography shows large and small dimple structure and broken or cracked primary Si, particles. Microstructure study of alloys revealed that the solution treatment improved distribution of silicon grains. The addition of Zr produces an improvement in the tensile properties as a result of its grain refining action and grain coarsening resistance in the matrix at a higher temperature.

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.

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.

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.

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.

Tensile and impact properties of three-component PP/wood/elastomer composites

Directory of Open Access Journals (Sweden)

B. Pukanszky

2012-03-01

Full Text Available Polypropylene (PP was reinforced with wood flour and impact modified with elastomers to increase stiffness and impact resistance simultaneously. Elastomer content changed in four (0, 5, 10 and 20 wt%, while that of wood content in seven steps, the latter from 0 to 60 wt% in 10 wt% steps. Structure and adhesion were controlled by the addition of functionalized (maleated polymers. Composites were homogenized in a twin-screw extruder and then injection molded to tensile bars. Fracture resistance was characterized by standard and instrumented impact tests. The results showed that the components are dispersed independently of each other even when a functionalized elastomer is used for impact modification, at least under the conditions of this study. Impact resistance does not change much as a function of wood content in PP/wood composites, but decreases drastically from the very high level of the PP/elastomer blend to almost the same value obtained without impact modifier in the three-component materials. Increasing stiffness and fiber related local deformation processes led to small fracture toughness at large wood content. Micromechanical deformation processes depend mainly on the strength of PP/wood interaction; debonding and pull-out take place at poor adhesion, while fiber fracture dominates when adhesion is strong. Composites with sufficiently large impact resistance cannot be prepared in the usual range of wood contents (50–60 wt%.

Microstructure and tensile properties after thermohydrogen processing of Ti-6 Al-4V.

Science.gov (United States)

Guitar, A; Vigna, G; Luppo, M I

2009-04-01

Thermohydrogen processing (THP), a technique in which hydrogen is used as a temporary alloying element, can refine the microstructure and improve the final mechanical properties of the Ti-6 Al-4V alloy. THP allows microstructural modification of titanium alloys near net shape such as biomaterial components obtained by powder metallurgy and castings, since it does not require mechanical working. Two THP, called THP-A and THP-B, have been evaluated in samples of Ti-6Al-4V with a coarse and lamellar microstructure typical of castings and powder metallurgy. The THP-A is based in the eutectoid decomposition of the beta(H) phase to alpha phase and hydride phase. The THP-B is based in the isothermal decomposition of alpha('') martensite phase, obtained by quenching of hydrogenated samples. The refinement of the microstructure due to THP has been evaluated by means of optical and electron microscopy. Tensile tests showed that while both processes were able to increase the strength of the alloy as compared with the starting material, the ductility in samples subjected to THP-B was severely reduced.

An energetic criterion for a micro-crack of finite length initiated in orthotropic bi-material notches

Czech Academy of Sciences Publication Activity Database

Profant, T.; Klusák, Jan; Ševeček, O.; Hrstka, M.; Kotoul, M.

2013-01-01

Roč. 110, SEP (2013), s. 396-409 ISSN 0013-7944 R&D Projects: GA ČR(CZ) GAP108/10/2049; GA ČR(CZ) GA101/09/1821 Institutional support: RVO:68081723 Keywords : crack initiation * bi-material notch * orthotropic bi-material notch * singular stress concentrator Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 1.662, year: 2013

Fatigue failure analysis of V-4Ti-4Cr alloy

International Nuclear Information System (INIS)

Aglan, H.; Gan, Y.X.; Grossbeck, M.

1999-01-01

In the present work, the fatigue fracture and failure behavior of a V-4Ti-4Cr has been studied. Static tests were conducted to study the overloading behavior and to select the magnitude of the stress level for the fatigue studies. Fatigue tests were performed using single edge notched (SEN) specimens under tension-tension load control conditions. Fatigue crack propagation (FCP) data such as the crack length, number of cycles, and hysteresis loops were recorded to calculate the crack speed, the energy release rate, and the change in work expended on damage formation and dissipative processes within the material. Parameters characterizing the fatigue fracture resistance of V-4Ti-4Cr alloy, namely the specific energy of damage (γ'), and the dissipative coefficient (β'), were determined from the fatigue data using the modified crack layer (MCL) theory. Fracture surface examination using scanning electron microscopy (SEM) revealed ductile failure mechanisms under tensile overloading conditions. The fatigue fracture surface of the V-4Ti-4Cr consists of three distinct regions, corresponding to the threshold, stable and unstable crack propagation stages. (orig.)

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.

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

Tensile Behaviour of Open Cell Ceramic Foams

Czech Academy of Sciences Publication Activity Database

Řehořek, Lukáš; Dlouhý, Ivo; Chlup, Zdeněk

2009-01-01

Roč. 53, č. 4 (2009), s. 237-241 ISSN 0862-5468 R&D Projects: GA ČR GA101/09/1821; GA ČR GD106/09/H035 Institutional research plan: CEZ:AV0Z20410507 Keywords : Tensile test * Ceramics foam * Open porosity * Tensile strength Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass Impact factor: 0.649, year: 2009

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

Modelling the mechanical behaviour of heterogeneous Ta/TA6V welded joints: behaviour and failure criteria; Modelisation du comportement mecanique des liaisons soudees heterogenes Ta/TA6V: comportement et critere de rupture

Energy Technology Data Exchange (ETDEWEB)

Paris, Th

2008-12-15

As laser welding of two different materials (heterogeneous welding) leads to a joint having a characteristic size close to the millimetre, i.e. much smaller than that of a structure, and as such a junction displays completely different mechanical properties because of the metallurgical transformations induced by intense thermal loading, the aim of this research thesis is to develop a behaviour model, flexible and robust enough, to represent all together the mechanical behaviours of the Ta, the TA6V and the melted zone. This model must be able to take plasticity and visco-plasticity into account, and also to provide a failure criterion through damage mechanics and its coupling with the behaviour. The author first reports the experimental characterization of the base materials (Ta and TA6V) by using tensile tests under different strain rates and different directions, relaxation tests and fatigue shear tests. He also characterizes the melted zone by describing the influence of a thermal treatment (induced by welding) on the formation of the melted zone, and by using different tests: four point bending on notched specimens, nano-indentation test, and longitudinal tensile test. In a second part, the author develops the model within the framework of continuum thermodynamics, and explores the numerical issues. The last part deals with the validation of the model for the concerned materials (Ta and TA6V) and melted zone.

Tensile properties of several 800 MeV proton-irradiated bcc metals and alloys

International Nuclear Information System (INIS)

Brown, R.D.; Wechsler, M.S.; Tschalar, C.

1987-01-01

A spallation neutron source for the 600-MeV proton accelerator facility at the Swiss Institute for Nuclear Research (SIN) consists of a vertical cylinder filled with molten Pb-Bi. The proton beam enters the cylinder, passing upward through a window in contact with the Pb-Bi eutectic liquid that must retain reasonable strength and ductility upon irradiation at about 673 K to fluence of about 1 x 10/sup 25/ protons/m/sup 2/. Investigations are underway at the 800-MeV proton accelerator at the Los Alamos Meson Physics Facility (LAMPF) to test the performance of candidate SIN window materials under appropriate conditions of temperature, irradiation, and environment. Based on considerations of chemical compatibility with molten Pb-Bi, as well as interest in identifying fundamental radiation damage mechanisms, Fe, Ta, Fe-2.25Cr-1Mo, and Fe-12Cr-1Mo(HT-9) were chosen as candidate materials. Sheet tensile samples, 0.5-mm thick, of the four materials were fabricated and heat treated. The samples were sealed inside capsules containing Pb-Bi and were proton-irradiated at LAMPF to two fluences, 4.8 and 54 x 10/sup 23/ p/m/sup 2/. The beam current was approximately equal to the 1 mA anticipated for the upgraded SIN accelerator. The power deposited by the proton beam in the capsules was sufficient to maintain sample temperatures of about 673 K. Post-irradiation tensile tests were conducted at room temperature at a strain rate of 9 x 10/sup -4/s/sup -1/. The yield and ultimate strengths increased upon irradiation in all materials, while the ductility decreased, as indicated by the uniform strain. The pure metals, Ta and Fe, exhibited the greatest radiation hardening and embrittlement. The HT-9 alloy showed the smallest changes in strength and ductility. The increase in strength following irradiation is discussed in terms of a dispersed-barrier hardening model, for which the barrier sizes and formation cross sections are calculated

Effects of low doses of 14-MeV neutrons on the tensile properties of three binary copper alloys

International Nuclear Information System (INIS)

Heinisch, H.L.; Pintler, J.S.

1986-12-01

Miniature tensile specimens of high purity copper and copper alloyed respectively with five atom percent of Al, Mn, and Ni were irradiated with D-T fusion neutrons in the RTNS-II to fluences up to 1.3 x 10 18 n/cm 2 at 90 0 C. To compare fission and fusion neutron effects, some specimens were also irradiated at the same temperature to similar damage levels in the Omega West Reactor (OWR). Tensile tests were performed at room temperature, and the radiation-induced changes in tensile properties were examined as functions of displacements per atom (dpa). The irradiation-induced strengthening of Cu5%Mn is greater than that of Cu5%Al and Cu5%Ni, which behave about the same. However, all the alloys sustain less irradiation-induced strengthening by 14 MeV neutrons than pure copper, which is in contrast to the reported results of earlier work using hardness measurements. The effects of fission and fusion neutrons on the yield stress of Cu5%Al and Cu5%Ni correlate well on the basis of dpa, but the data for Cu5%Mn suggest that dpa may not be a good correlation parameter for this alloy in this fluence and temperature range

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 ...

Strain localization during tensile Hopkinson bar testing of commercially pure titanium and Ti6Al4V titanium alloy

Directory of Open Access Journals (Sweden)

Moćko Wojciech

2015-01-01

Full Text Available The goal of the analysis was to determine the strain localization for various specimen shapes (type A and type B according to PN-EN ISO 26203-1 standard and different loading conditions, i.e. quasi- static and dynamic. Commercially pure titanium (Grade 2 and titanium alloy Ti6Al4V (Grade 5 were selected for the tests. Tensile loadings were applied out using servo-hydraulic testing machine and tensile Hopkinson bar with pre-tension. The results were recorded using ARAMIS system cameras and fast camera Phantom V1210, respectively at quasi-static and dynamic loading conditions. Further, specimens outline was determined on the basis of video data using TEMA MOTION software. The strain distribution on the specimen surface was estimated using digital image correlation method. The larger radius present in the specimen of type B in comparison to specimen of type A, results in slight increase of the elongation for commercially pure titanium at both quasi-static and dynamic loading conditions. However this effect disappears for Ti6Al4V alloy. The increase of the elongation corresponds to the stronger necking effect. Material softening due to increase of temperature induced by plastic work was observed at dynamic loading conditions. Moreover lower elongation at fracture point was found at high strain rates for both materials.

Tensile properties of vanadium alloys irradiated at 390{degrees}C in EBR-II

Energy Technology Data Exchange (ETDEWEB)

Chung, H.M.; Tsai, H.C.; Nowicki, L.J. [Argonne National Lab., IL (United States)] [and others

1997-08-01

Vanadium alloys were irradiated in Li-bonded stainless steel capsules to {approx}390{degrees}C in the EBR-II X-530 experiment. This report presents results of postirradiation tests of tensile properties of two large-scale (100 and 500 kg) heats of V-4Cr-Ti and laboratory (15-30 kg) heats of boron-doped V-4Cr-4Ti, V-8Cr-6Ti, V-5Ti, and V-3Ti-1Si alloys. Tensile specimens, divided into two groups, were irradiated in two different capsules under nominally similar conditions. The 500-kg heat (No. 832665) and the 100-kg heat (VX-8) of V-4Cr-4Ti irradiated in one of the subcapsules exhibited complete loss of work-hardening capability, which was manifested by very low uniform plastic strain. In contrast, the 100-kg heat of V-4Cr-4Ti irradiated in another subcapsule exhibited good tensile properties (uniform plastic strain 2.8-4.0%). A laboratory heat of V-3Ti-1Si irradiated in the latter subcapsule also exhibited good tensile properties. These results indicate that work-hardening capability at low irradiation temperatures varies significantly from heat to heat and is influenced by nominally small differences in irradiation conditions.

Methods for evaluation of hydrogen effect on service behaviour of titanium base alloys

International Nuclear Information System (INIS)

Mal'kov, A.V.; Kolachev, B.A.

1979-01-01

A comparative evaluation of the effect of hydrogen upon the service ability of α, β, α+β and pseudo-α titanium alloys is carried out using the results of various mechanical tests. Presented are the values of the critical concentration of hydrogen, determined by impact strength tests, tensile tests of notched specimens, fracture toughness tests, slow failure tests and the determination of the energy of failure. A hypothesis is advanced that the failure energy of titanium alloys depends directly upon the type of stressed state. This hypothesis explains the S shapes of the curves describing the dependences of the impact strength, the coefficient of stress intensity and the ratios of the tensile strength of smooth and notched specimens upon the hydrogen content

The postirradiation tensile properties and microstructure of several vanadium alloys

International Nuclear Information System (INIS)

Braski, D.N.

1988-01-01

Tensile specimens of V-15Cr-5Ti, Vanstar-7, V-3Ti-1si, and V-20Ti were irradiated at 420/degrees/C in FFTF-MOTA to a damage level of 82 dpa. Helium was preimplanted to levels up to 480 appm in selected specimens using a modified tritium trick. Irradiation hardening was the dominant effect influencing the postirradiation tensile properties, and it markedly increased the yield strength and reduced the total elogation. The V-15Cr-5Ti alloy was very sensitive to helium embrittlement, but Vanstar-7 and V-3Ti-1Si were only slightly affected. Without helium, negligible swelling (<1%) were measured in V-3Ti-1Si and V-20Ti. Preimplanted helium increased swelling in V-3Ti-1Si by increasing cavity nucleation. 11 refs., 11 figs., 3 tabs

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.)

Prediction of Tensile Behavior of UHSFRC Considering the Flow Field in the Placing Dominated by Shear Flow.

Science.gov (United States)

Moon, Joon-Shik; Kang, Su-Tae

2018-01-26

Considering the case of fabricating a UHSFRC (ultra-high strength fiber-reinforced concrete) beam with the method of one end placing and self-flowing to the other end, it was intended to simulate the variation of the fiber orientation distribution according to the flow distance and the variation of the resultant tensile behaviors. Then the validity of the simulation approach was shown by comparing the simulated results with experimental ones. A three-point bending test with a notched beam was adopted for the experiment and a finite element analysis was performed to obtain the simulated results for the bending test considering the flow-dependent tensile behavior of the UHSFRC. From the simulation for the fiber orientation distribution according to the flow distance, it could be found that the major change in the fiber orientation distribution took place within a short flow distance and most of the fibers became nearly aligned to the flow direction. After some flow distance, there was a not-so-remarkable variation in the fiber orientation distribution that could influence the tensile behavior of the composite. For this flow region, the consistent flexural test results, regardless of flow distance, demonstrate the reliability of the simulation.

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.

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.

Possibility of obtaining reliable information on component safety by means of large-scale tensile samples with Orowan-Soete flaws

International Nuclear Information System (INIS)

Aurich, D.; Wobst, K.; Kafka, H.

1984-01-01

The aim of the paper is to review the present knowledge regarding the ability of wide plate tensile specimen with saw cut trough center flaws of providing accurate information on component reliability; it points out the advantages and disadvantages of this specimen geometries. The effect of temperature, specimen geometry, ligament size and notch radii are discussed in comparison with other specimen geometries. This is followed by a comparison of the results of such tests with tests on inside stressed tanks. Conclusions: wide-plate tensile specimen are generally appropriate for assessing welded joints. However, they result in a more favourable evaluation of low-toughness steels from the point of view of crack growth than of high-toughness and soft steels in case of stresses with incipient cracks, as compared with the results obtained with three-point bending samples. (orig.) [de

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

Notch1 and 4 Signaling Responds to an Increasing Vascular Wall Shear Stress in a Rat Model of Arteriovenous Malformations

Directory of Open Access Journals (Sweden)

Jian Tu

2014-01-01

Full Text Available Notch signaling is suggested to promote the development and maintenance of cerebral arteriovenous malformations (AVMs, and an increasing wall shear stress (WSS contributes to AVM rupture. Little is known about whether WSS impacts Notch signaling, which is important for understanding the angiogenesis of AVMs. WSS was measured in arteriovenous fistulas (AVF surgically created in 96 rats at different time points over a period of 84 days. The expression of Notch receptors 1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene target Hes1 was quantified in “nidus” vessels. The interaction events between Notch receptors and their ligands were quantified using proximity ligation assay. There was a positive correlation between WSS and time (r=0.97; P<0.001. The expression of Notch receptors and their ligands was upregulated following AVF formation. There was a positive correlation between time and the number of interactions between Notch receptors and their ligands aftre AVF formation (r=0.62, P<0.05 and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (r=0.87, P<0.005. In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling.

RPV steel embrittlement: Damage modeling and micro-mechanics in an engineering perspective

Energy Technology Data Exchange (ETDEWEB)

Fabry, A; Walle, E V; Chaouadi, R; Wannijn, J P; Werstrepen, A; Puzzolante, J L; VanRansbeeck, T H; VandeVelde, J [Sofia Univ. (Bulgaria)

1994-12-31

A new, consolidated strategy for improved Light Water Reactor pressure vessel surveillance is proposed. The methodology includes statistical fracture mechanics and damage modeling, while taking maximum advantage of the data generated by conventional surveillance practices. Available reconstitution and miniaturization allow to implement such strategy with minimal material inventory. The themes of the paper are: general philosophy of Belgian surveillance R D program; ductile-brittle transition temperature by use of instrumented C{sub v} load-time traces; towards an enhanced surveillance practice by combined use of instrumented C{sub v} load-time traces and uniaxial tensile tests; constraint, size and strain rate effects for C{sub v} notch impact test. 109 refs., 27 figs.

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.

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

Dynamic plastic behaviour of a notched free-free beam subjected to step-loading at one end

International Nuclear Information System (INIS)

Zhang, Y.; Yang, J.L.

2002-01-01

A rigid perfectly plastic model is developed to study the initial, small deflection response of a free-free beam with an initial notch along its span under a concentrated step-loading suddenly applied at one end of the beam. Complete solutions are obtained for various combinations of the magnitude of the load, the location of the notch and its defect-severity. The partitioning of the initial energy dissipation rates is discussed for some typical situations. It is concluded that: (i) the different initial deformation mechanisms and the initial energy dissipation rate of the beam depend not only on the magnitude of the load but also on the defect-severity and location of the notch; (ii) because of the influence of the notch, the structural response of the beam is far more complicated than that of the un-notched free-free beam; and (iii) for some cases the maximum rate of energy dissipation in plastic hinges will be more than 1/3 of the total input energy rate, while for an un-notched free-free beam, it has been demonstrated that the plastic dissipated energy is always less than 1/3 of the input energy [Int. J. Impact Engng 21 (1998) 165

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

Directory of Open Access Journals (Sweden)

Vanessa de Oliveira-Carlos

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

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.

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,

Effect of fiber orientation on tensile and impact properties of Zalacca Midrib fiber-HDPE composites by compression molding

Science.gov (United States)

Lasikun, Ariawan, Dody; Surojo, Eko; Triyono, Joko

2018-02-01

The research aims to investigate the fiber orientation effect on the tensile and impact properties of zalacca midrib fiber /HDPE composites. The composites were produced by compression molding with pressing temperature at 150°C, pressing pressure at 50 bar, and holding time of 25 minutes. The fiber orientations applied in composites were 0°, 15°, 30°, 45°, 60°, 75°, and 90°, at 10% fiber volume fraction. The samples were evaluated by using: Tensile test and Izod impact test according to ASTM D638 and ASTM D5941, respectively. The result of experiments indicate that the orientation of zalacca midrib fiber influences the characteristics of HDPE composite-zalacca midrib fiber. The composite mechanical strength decline with the increase of orientation fibers from 0° to 90°. The composite failure mode of composites are observed by Scanning Electron Microscope (SEM).

Tensile testing

CERN Document Server

2004-01-01

A complete guide to the uniaxial tensile test, the cornerstone test for determining the mechanical properties of materials: Learn ways to predict material behavior through tensile testing. Learn how to test metals, alloys, composites, ceramics, and plastics to determine strength, ductility and elastic/plastic deformation. A must for laboratory managers, technicians, materials and design engineers, and students involved with uniaxial tensile testing. Tensile Testing , Second Edition begins with an introduction and overview of the test, with clear explanations of how materials properties are determined from test results. Subsequent sections illustrate how knowledge gained through tensile tests, such as tension properties to predict the behavior (including strength, ductility, elastic or plastic deformation, tensile and yield strengths) have resulted in improvements in materals applications. The Second Edition is completely revised and updated. It includes expanded coverage throughout the volume on a variety of ...

Magnetoresistance effect in permalloy nanowires with various types of notches

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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.

Effect of tungsten on tensile properties and flow behaviour of RAFM steel

Energy Technology Data Exchange (ETDEWEB)

Vanaja, J., E-mail: jvanaja@igcar.gov.in [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Laha, K.; Nandagopal, M. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Sam, Shiju [Institute for Plasma Research, Gandhinagar 382 428, Gujarat (India); Mathew, M.D.; Jayakumar, T. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Rajendra Kumar, E. [Institute for Plasma Research, Gandhinagar 382 428, Gujarat (India)

2013-02-15

Effect of tungsten in the range of 1–2 wt.% on tensile properties and flow behaviour of 9Cr–W–Ta–V Reduced Activation Ferritic–Martensitic (RAFM) steel has been investigated. The tungsten in the investigated range was found to have only minor effect on the tensile properties of the steel over the temperature range of 300–873 K and at a strain rate of 3 × 10{sup −3} s{sup −1}. The tensile flow behaviour of the RAFM steels was adequately described by the Voce’s constitutive equation. The tensile strength of the steels were predicted well from the parameters of the Voce’s constitutive equation. The Voce’s strain hardening parameter ‘n{sub v}’ was found to be quite sensitive to the tungsten content and predicted the onset of dislocation climbing process at relatively higher testing temperature with the increase in tungsten content. The equivalence between tensile and creep deformations and the influence of tungsten have been discussed.

Effect of tungsten on tensile properties and flow behaviour of RAFM steel

International Nuclear Information System (INIS)

Vanaja, J.; Laha, K.; Nandagopal, M.; Sam, Shiju; Mathew, M.D.; Jayakumar, T.; Rajendra Kumar, E.

2013-01-01

Effect of tungsten in the range of 1–2 wt.% on tensile properties and flow behaviour of 9Cr–W–Ta–V Reduced Activation Ferritic–Martensitic (RAFM) steel has been investigated. The tungsten in the investigated range was found to have only minor effect on the tensile properties of the steel over the temperature range of 300–873 K and at a strain rate of 3 × 10 −3 s −1 . The tensile flow behaviour of the RAFM steels was adequately described by the Voce’s constitutive equation. The tensile strength of the steels were predicted well from the parameters of the Voce’s constitutive equation. The Voce’s strain hardening parameter ‘n v ’ was found to be quite sensitive to the tungsten content and predicted the onset of dislocation climbing process at relatively higher testing temperature with the increase in tungsten content. The equivalence between tensile and creep deformations and the influence of tungsten have been discussed

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.

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.

Modelling the mechanical behaviour of heterogeneous Ta/TA6V welded joints: behaviour and failure criteria

International Nuclear Information System (INIS)

Paris, Th.

2008-12-01

As laser welding of two different materials (heterogeneous welding) leads to a joint having a characteristic size close to the millimetre, i.e. much smaller than that of a structure, and as such a junction displays completely different mechanical properties because of the metallurgical transformations induced by intense thermal loading, the aim of this research thesis is to develop a behaviour model, flexible and robust enough, to represent all together the mechanical behaviours of the Ta, the TA6V and the melted zone. This model must be able to take plasticity and visco-plasticity into account, and also to provide a failure criterion through damage mechanics and its coupling with the behaviour. The author first reports the experimental characterization of the base materials (Ta and TA6V) by using tensile tests under different strain rates and different directions, relaxation tests and fatigue shear tests. He also characterizes the melted zone by describing the influence of a thermal treatment (induced by welding) on the formation of the melted zone, and by using different tests: four point bending on notched specimens, nano-indentation test, and longitudinal tensile test. In a second part, the author develops the model within the framework of continuum thermodynamics, and explores the numerical issues. The last part deals with the validation of the model for the concerned materials (Ta and TA6V) and melted zone

The effect of tungsten on the tensile and creep rupture strength of 12 CrMoV steels

International Nuclear Information System (INIS)

Oakes, G.; Orr, J.

1978-01-01

A collaborative project involving the Brown-Firth Research Laboratories, the Sheffield Laboratories of the British Steel Corporation and Tube Investments Limited has been carried out to assess the effect of a controlled tungsten addition (0.5%) on the tensile and rupture properties of 12 CrMoV steel. The results obtained indicate that 0.5% tungsten increases the tensile properties at room temperature by approximately 3% but this diminishes with increasing test temperature. The creep rupture properties of the tungsten-bearing material showed a marked short time (500-1000 hours) strength advantage over the tungsten-free material at temperatures up to 650 0 C. At longer times and higher temperatures this stress advantage was reduced considerably so that at times in the region of 10,000 to 15,000 hours it was approximately 5%. In view of the limited data generated, it was found impossible to extrapolate with confidence to longer times but there was, however, no indication that a significant strength advantage is to be anticipated at 100,000 hours for the tungsten-bearing material. (author)

Influence of sample geometry and microstructure on the hydrogen induced cracking characteristics under uniaxial load

Energy Technology Data Exchange (ETDEWEB)

Laureys, A., E-mail: aurelie.laureys@ugent.be [Department of Materials, Textiles and Chemical Engineering, Ghent University (UGent), Tech Lane Ghent Science Park - Campus A, Technologie park 903, B-9052 Gent (Belgium); Depover, T., E-mail: tom.depover@ugent.be [Department of Materials, Textiles and Chemical Engineering, Ghent University (UGent), Tech Lane Ghent Science Park - Campus A, Technologie park 903, B-9052 Gent (Belgium); Petrov, R., E-mail: roumen.petrov@ugent.be [Department of Materials, Textiles and Chemical Engineering, Ghent University (UGent), Tech Lane Ghent Science Park - Campus A, Technologie park 903, B-9052 Gent (Belgium); Department of Materials Science and Engineering, Delft University of Technology, Mekelweg 2, 2628 CD Delft (Netherlands); Verbeken, K., E-mail: kim.verbeken@ugent.be [Department of Materials, Textiles and Chemical Engineering, Ghent University (UGent), Tech Lane Ghent Science Park - Campus A, Technologie park 903, B-9052 Gent (Belgium)

2017-04-06

The present work evaluates hydrogen induced cracking in a TRIP (transformation induced plasticity) assisted steel and pure iron. The goal of this work is to understand the effect of the macroscopic stress distribution in the material on the hydrogen induced cracking phenomenon. Additionally, the effect of a complex multiphase microstructure on the characteristics of hydrogen induced cracking was investigated by comparing results for TRIP-assisted steel and pure iron as reference material. Tensile tests on notched and unnotched samples combined with in-situ electrochemical hydrogen charging were conducted. Tests were performed until the tensile strength was reached and until fracture. The resulting hydrogen induced cracks were studied by optical microscopy and scanning electron microscopy (SEM). Hydrogen induced cracks showed a typical S-shape and crack propagation was mainly transgranular, independently of the presence of a notch or the material's microstructure. This was also the case for the V-shaped secondary crack network and resulting stepped crack morphology characteristic for hydrogen induced damage. These observations indicate that the stress state surrounding the crack tip has a very large impact on the hydrogen induced cracking characteristics. The use of a notch or the presence of a different microstructure did not influence the overall hydrogen induced cracking features, but did change the kinetics of the hydrogen induced cracking process.

Influence of sample geometry and microstructure on the hydrogen induced cracking characteristics under uniaxial load

International Nuclear Information System (INIS)

Laureys, A.; Depover, T.; Petrov, R.; Verbeken, K.

2017-01-01

The present work evaluates hydrogen induced cracking in a TRIP (transformation induced plasticity) assisted steel and pure iron. The goal of this work is to understand the effect of the macroscopic stress distribution in the material on the hydrogen induced cracking phenomenon. Additionally, the effect of a complex multiphase microstructure on the characteristics of hydrogen induced cracking was investigated by comparing results for TRIP-assisted steel and pure iron as reference material. Tensile tests on notched and unnotched samples combined with in-situ electrochemical hydrogen charging were conducted. Tests were performed until the tensile strength was reached and until fracture. The resulting hydrogen induced cracks were studied by optical microscopy and scanning electron microscopy (SEM). Hydrogen induced cracks showed a typical S-shape and crack propagation was mainly transgranular, independently of the presence of a notch or the material's microstructure. This was also the case for the V-shaped secondary crack network and resulting stepped crack morphology characteristic for hydrogen induced damage. These observations indicate that the stress state surrounding the crack tip has a very large impact on the hydrogen induced cracking characteristics. The use of a notch or the presence of a different microstructure did not influence the overall hydrogen induced cracking features, but did change the kinetics of the hydrogen induced cracking process.

Effect of tensile stress on cavitation damage formation in mercury

Energy Technology Data Exchange (ETDEWEB)

Naoe, Takashi, E-mail: naoe.takashi@jaea.go.j [J-PARC Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Kogawa, Hiroyuki [J-PARC Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Yamaguchi, Yoshihito [Nuclear Safety Research Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Futakawa, Masatoshi [J-PARC Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan)

2010-03-15

Cavitation erosion or so called pitting damage was investigated under tensile stress conditions in mercury. In MW-class liquid metal spallation targets, pitting damage is a critical issue to satisfy required power and/or lifetime of the target vessel. Cavitation occurs by negative pressure which is induced through pressure wave propagation due to proton beam injection. Pitting damage is formed by microjet and/or shock wave during cavitation bubble collapse. A mercury target vessel suffers tensile stress due to thermal stress or welding. In order to investigate the effect of tensile stress on pitting damage formation, cavitation erosion tests were performed using stress imposed specimens in mercury. An ultrasonic vibratory horn and electro-Magnetic IMpact Testing Machine (MIMTM) were used to vary the cavitation intensity. In the incubation period of pitting damage, damaged area was slightly increased with increasing imposed tensile stress. In the steady state period, a mean depth of erosion was increased by the tensile stress. Additionally, in order to quantitatively evaluate the effect of tensile stress, an indentation test with Vickers indenter was carried out to quasi-statically simulate the impact load. From the measurement of the diagonal length of the indent aspect ratio and hardness, it is recognized that the threshold of the deformation, i.e. pitting damage formation, was decreased by the tensile stress.

High strain rate tensile behavior of Al-4.8Cu-1.2Mg alloy

International Nuclear Information System (INIS)

Bobbili, Ravindranadh; Paman, Ashish; Madhu, V.

2016-01-01

The purpose of the current study is to perform quasi static and high strain rate tensile tests on Al-4.8Cu-1.2Mg alloy under different strain rates ranging from 0.01–3500/s and also at temperatures of 25,100, 200 and 300 °C. The combined effect of strain rate, temperature and stress triaxiality on the material behavior is studied by testing both smooth and notched specimens. Johnson–Cook (J–C) constitutive and fracture models are established based on high strain rate tensile data obtained from Split hopkinson tension bar (SHTB) and quasi-static tests. By modifying the strain hardening and strain rate hardening terms in the Johnson–Cook (J–C) constitutive model, a new J–C constitutive model of Al-4.8Cu-1.2Mg alloy was obtained. The improved Johnson–Cook constitutive model matched the experiment results very well. With the Johnson–Cook constitutive and fracture models, numerical simulations of tensile tests at different conditions for Al-4.8Cu-1.2Mg alloy were conducted. Numerical simulations are performed using a non-linear explicit finite element code autodyn. Good agreement is obtained between the numerical simulation results and the experiment results. The fracture surfaces of specimens tested under various strain rates and temperatures were studied under scanning electron microscopy (SEM).

Effects of substrate preheating during direct energy deposition on microstructure, hardness, tensile strength, and notch toughness

Science.gov (United States)

Baek, Gyeong Yun; Lee, Ki Yong; Park, Sang Hu; Shim, Do Sik

2017-11-01

This study examined the effects of substrate preheating for the hardfacing of cold-press dies using the high-speed tool steel AISI M4. The preheating of the substrate is a widely used technique for reducing the degree of thermal deformation and preventing crack formation. We investigated the changes in the metallurgical and mechanical properties of the high-speed tool steel M4 deposited on an AISI D2 substrate with changes in the substrate preheating temperature. Five preheating temperatures (100-500 °C; interval of 100 °C) were selected, and the changes in the temperature of the substrate during deposition were observed. As the preheating temperature of the substrate was increased, the temperature gradient between the melting layer and the substrate decreased; this prevented the formation of internal cracks, owing to thermal stress relief. Field-emission scanning electron microscopy showed that a dendritic structure was formed at the interface between the deposited layer and the substrate while a cellular microstructure was formed in the deposited layer. As the preheating temperature was increased, the sizes of the cells and precipitated carbides also increased. Furthermore, the hardness increased slightly while the strength and toughness decreased. Moreover, the tensile and impact properties deteriorated rapidly at excessively high preheating temperatures (greater than 500 °C). The results of this study can be used as preheating criteria for achieving the desired mechanical properties during the hardfacing of dies and molds.

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.

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

Directory of Open Access Journals (Sweden)

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

Fatigue Behavior under Multiaxial Stress States Including Notch Effects and Variable Amplitude Loading

Science.gov (United States)

Gates, Nicholas R.

life predictions were found to improve for all loading conditions considered in this study. The quantification of multiaxial fatigue damage was identified as being a key area of improvement, where the shear-based Fatemi-Socie (FS) critical plane damage parameter was shown to correlate all fully-reversed constant amplitude fatigue data relatively well. Additionally, a proposed modification to the FS parameter was found to result in improved life predictions in the presence of high tensile mean stress and for different ratios of nominal shear to axial stress. For notched specimens, improvements were also gained through the use of more robust notch deformation and stress gradient models. Theory of Critical Distances (TCD) approaches, together with pseudo stress-based plasticity modeling techniques for local stress-strain estimation, resulted in better correlation of multiaxial fatigue data when compared to traditional approaches such as Neuber's rule with fatigue notch factor. Since damage parameters containing both stress and strain terms, such as the FS parameter, are able to reflect changes in fatigue damage due to transient material hardening behavior, this issue was also investigated with respect to its impact on variable amplitude life predictions. In order to ensure that material deformation behavior was properly accounted for, stress-strain predictions based on an Armstrong-Frederick-Chaboche style cyclic plasticity model were first compared to results from deformation tests performed under a variety of complex multiaxial loading conditions. The model was simplified based on the assumption of Masing material behavior, and a new transient hardening formulation was proposed so that all modeling parameters could be determined from a relatively limited amount of experimental data. Overall, model predictions were found to agree fairly well with experimental results for all loading histories considered. Finally, in order to evaluate life prediction procedures under

Development of India-specific RAFM steel through optimization of tungsten and tantalum contents for better combination of impact, tensile, low cycle fatigue and creep properties

Energy Technology Data Exchange (ETDEWEB)

Laha, K., E-mail: laha@igcar.gov.in [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102, TN (India); Saroja, S.; Moitra, A.; Sandhya, R.; Mathew, M.D.; Jayakumar, T. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102, TN (India); Rajendra Kumar, E. [Institute for Plasma Research, Bhat, Gandhinagar 382 428, Gujarat (India)

2013-08-15

Effects of tungsten and tantalum contents on impact, tensile, low cycle fatigue and creep properties of Reduced Activation Ferritic–Martensitic (RAFM) steel were studied to develop India-specific RAFM steel. Four heats of the steel have been melted with tungsten and tantalum contents in the ranges 1–2 wt.% and 0.06–0.14 wt.% respectively. Increase in tungsten content increased the ductile-to-brittle transition temperature (DBTT), low cycle fatigue and creep strength of the steel, whereas the tensile strength was not changed significantly. Increase in tantalum content increased the DBTT and low cycle fatigue strength of the steel whereas the tensile and creep strength decreased. Detailed TEM investigations revealed enhanced microstructural stability of the steel against creep exposure on tungsten addition. The RAFM steel having 1.4 wt.% tungsten with 0.06 wt.% tantalum was found to possess optimum combination of impact, tensile, low cycle fatigue and creep properties and is considered for Indian-specific RAFM steel.

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

Ultrasound transmission measurements for tensile strength evaluation of tablets.

Science.gov (United States)

Simonaho, Simo-Pekka; Takala, T Aleksi; Kuosmanen, Marko; Ketolainen, Jarkko

2011-05-16

Ultrasound transmission measurements were performed to evaluate the tensile strength of tablets. Tablets consisting of one ingredient were compressed from dibasic calcium phosphate dehydrate, two grades of microcrystalline cellulose and two grades of lactose monohydrate powders. From each powder, tablets with five different tensile strengths were directly compressed. Ultrasound transmission measurements were conducted on every tablet at frequencies of 2.25 MHz, 5 MHz and 10 MHz and the speed of sound was calculated from the acquired waveforms. The tensile strength of the tablets was determined using a diametrical mechanical testing machine and compared to the calculated speed of sound values. It was found that the speed of sound increased with the tensile strength for the tested excipients. There was a good correlation between the speed of sound and tensile strength. Moreover, based on the statistical tests, the groups with different tensile strengths can be differentiated from each other by measuring the speed of sound. Thus, the ultrasound transmission measurement technique is a potentially useful method for non-destructive and fast evaluation of the tensile strength of tablets. Copyright © 2011 Elsevier B.V. All rights reserved.

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...

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.

Impact Tensile Testing of Stainless Steels at Various Temperatures

Energy Technology Data Exchange (ETDEWEB)

D. K. Morton

2008-03-01

Stainless steels are used for the construction of numerous spent nuclear fuel or radioactive material containers that may be subjected to high strains and moderate strain rates during accidental drop events. Mechanical characteristics of these base materials and their welds under dynamic loads in the strain rate range of concern (1 to 300 per second) are not well documented. However, research is being performed at the Idaho National Laboratory to quantify these characteristics. The work presented herein discusses tensile impact testing of dual-marked 304/304L and 316/316L stainless steel material specimens. Both base material and welded material specimens were tested at -20 oF, room temperature, 300 oF, and 600 oF conditions. Utilizing a drop weight impact test machine and 1/4-inch and 1/2-inch thick dog bone-shaped test specimens, a strain rate range of approximately 4 to 40 per second (depending on initial temperature conditions) was achieved. Factors were determined that reflect the amount of increased strain energy the material can absorb due to strain rate effects. Using the factors, elevated true stress-strain curves for these materials at various strain rates and temperatures were generated. By incorporating the strain rate elevated true stress-strain material curves into an inelastic finite element computer program as the defined material input, significant improvement in the accuracy of the computer analyses was attained. However, additional impact testing is necessary to achieve higher strain rates (up to 300 per second) before complete definition of strain rate effects can be made for accidental drop events and other similar energy-limited impulsive loads. This research approach, using impact testing and a total energy analysis methodology to quantify strain rate effects, can be applied to many other materials used in government and industry.

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.

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

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)

Analysis of tensile and fracture toughness results on irradiated molybdenum alloys, TZM and Mo-5%Re. Analysis of results performed in the frame of the NET task PDS 1.4

Energy Technology Data Exchange (ETDEWEB)

Scibetta, M.; Chaouadi, R.; Puzzolante, J.L

1999-10-01

Due to their good resistance at high temperature, good thermal conductivity and swelling resistance, molybdenum alloys are considered amongst the candidates for divertor structural materials. However, little is known about their tensile and fracture toughness behaviour, in particular after irradiation. This report aims to investigate the tensile and fracture toughness properties of two molybdenum alloys, namely TZM and Mo-5%Re. Tensile and compact tension specimens were irradiated in the BR2 reactor at 40 and 450 degrees Celsius up to a fast neutron fluence of 3.5 1020 n/cm{sup 2} (0.2 dpa). Fracture toughness tests were performed on both precracked and notched specimens. Results show a drastic decrease of the ductility due to irradiation, but only a slight decrease of the fracture toughness in the lower shelf domain.

Analysis of tensile and fracture toughness results on irradiated molybdenum alloys, TZM and Mo-5%Re. Analysis of results performed in the frame of the NET task PDS 1.4

International Nuclear Information System (INIS)

Scibetta, M.; Chaouadi, R.; Puzzolante, J.L.

1999-10-01

Due to their good resistance at high temperature, good thermal conductivity and swelling resistance, molybdenum alloys are considered amongst the candidates for divertor structural materials. However, little is known about their tensile and fracture toughness behaviour, in particular after irradiation. This report aims to investigate the tensile and fracture toughness properties of two molybdenum alloys, namely TZM and Mo-5%Re. Tensile and compact tension specimens were irradiated in the BR2 reactor at 40 and 450 degrees Celsius up to a fast neutron fluence of 3.5 1020 n/cm 2 (0.2 dpa). Fracture toughness tests were performed on both precracked and notched specimens. Results show a drastic decrease of the ductility due to irradiation, but only a slight decrease of the fracture toughness in the lower shelf domain

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.

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.

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.

In situ room temperature tensile deformation of a 1% CrMoV bainitic steel using synchrotron and neutron diffraction

Energy Technology Data Exchange (ETDEWEB)

Weisser, M.A. [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Ecole Polytechnique Federale de Lausanne (EPFL), Institute of Materials (IMX), CH-1012 Lausanne (Switzerland); Evans, A.D.; Van Petegem, S. [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Holdsworth, S.R. [EMPA Materials Science and Technology, CH-8600 Duebendorf (Switzerland); Van Swygenhoven, H., E-mail: helena.vs@psi.ch [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Ecole Polytechnique Federale de Lausanne (EPFL), Institute of Materials (IMX), CH-1012 Lausanne (Switzerland)

2011-06-15

Neutron and synchrotron X-ray diffraction spectra have been acquired during room temperature tensile deformation of a creep-resistant bainitic 1% CrMoV steel, in order to study the evolution of internal microstresses and load-sharing mechanisms between the ferrite matrix and the various carbides. Cementite takes load from the plastifying matrix at the onset of macroscopic plasticity resulting in residual interphase stresses. Single peak fitting indicates an elastic anisotropic behaviour of cementite.

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)

High-rate tensile behavior of steel fiber-reinforced concrete for nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Jin; Park, Gi-Joon [Department of Civil and Environmental Engineering, Sejong University, 98 Gunja-Dong, Gwangjin-Gu, Seoul 143-747 (Korea, Republic of); Kim, Dong Joo, E-mail: djkim75@sejong.ac.kr [Department of Civil and Environmental Engineering, Sejong University, 98 Gunja-Dong, Gwangjin-Gu, Seoul 143-747 (Korea, Republic of); Moon, Jae Heum; Lee, Jang Hwa [Korea Institute of Construction Technology, 2311 Daewha-Dong, Ilsan-Gu, Goyang-Si, Gyeonggi-Do 411-712 (Korea, Republic of)

2014-01-15

Highlights: • The final goal is to develop a fiber reinforced concrete for containment buildings. • High rate tensile behavior of FRC was investigated. • Strain energy frame impact machine was used for tensile impact tests. • Different rate sensitivity of FRC was found according to the type fiber. • Adding more fibers by increasing S/a is positive for higher impact resistance of FRC. -- Abstract: The direct tensile behavior of fiber-reinforced concrete (FRC) at high strain rates were investigated for their potential to enhance the resistance of the containment building of nuclear power plants (NPPs) against aircraft impact. Two types of deformed steel, hooked (H) and twisted (T) fibers were employed. To improve the tensile resistance of FRCs even at higher rates by adding more fibers, the mixture of concrete was modified by either increasing the sand-to-coarse aggregate ratio or decreasing the maximum size of coarse aggregate. All FRC specimens produced two to six times greater tensile strength and one to five times higher toughness at high strain rates (4–53 s{sup −1}) than those at a static rate (0.000167 s{sup −1}). T-fiber generally produced higher tensile strength and toughness than H-fiber at both static and high rates. Although both fibers showed favorable rate sensitivity, T-fiber produced much greater enhancement, at higher strain rates, in tensile strength and slightly lower enhancement in toughness than H-fiber. As the maximum size of coarse aggregate decreased from 19 to 5 mm, the tensile strength and toughness of FRCs with T-fibers noticeably increased at both static and high strain rates.

The influences of impurity content, tensile strength, and grain size on in-service temper embrittlement of CrMoV steels

International Nuclear Information System (INIS)

Cheruvu, N.S.; Seth, B.B.

1989-01-01

The influences of impurity levels, grain size, and tensile strength on in-service temper embrittlement of CrMoV steels have been investigated. The samples for this study were taken from steam turbine CrMoV rotors which had operated for 15 to 26 years. The effects of grain size and tensile strength on embrittlement susceptibility were separated by evaluating the embrittlement behavior of two rotor forgings made from the same ingot after an extended step-cooling treatment. Among the residual elements in the steels, only P produces a significant embrittlement. The variation of P and tensile strength has no effect on in-service temper embrittlement susceptibility, as measured by the shift in fracture appearance transition temperature (FATT). However, the prior austenite grain size plays a major role in service embrittlement. The fine grain steels with a grain size of ASTM No. 9 or higher are virtually immune to in-service embrittlement. In steels having duplex grain sizes, embrittlement susceptibility is controlled by the size of coarser grains. For a given steel chemistry, the coarse grain steel is more susceptible to in-service embrittlement, and a decrease in ASTM grain size number from 4 to 0/1 increases the shift in FATT by 61 degrees C (10/10 degrees F). It is demonstrated that long-term service embrittlement can be simulated, except in very coarse grain steels, by using the extended step-cooling treatment. The results of step-cooling studies show that the coarse grain rotor steels take longer time during service to reach a fully embrittled state than the fine grain rotor steels

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

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.

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.

Effect of helium on tensile properties of vanadium alloys

Energy Technology Data Exchange (ETDEWEB)

Chung, H.M.; Billone, M.C.; Smith, D.L. [Argonne National Lab., IL (United States)

1997-08-01

Tensile properties of V-4Cr-4Ti (Heat BL-47), 3Ti-1Si (BL-45), and V-5Ti (BL-46) alloys after irradiation in a conventional irradiation experiment and in the Dynamic Helium Charging Experiment (DHCE) were reported previously. This paper presents revised tensile properties of these alloys, with a focus on the effects of dynamically generated helium of ductility and work-hardening capability at <500{degrees}C. After conventional irradiation (negligible helium generation) at {approx}427{degrees}C, a 30-kg heat of V-4Cr-4Ti (BL-47) exhibited very low uniform elongation, manifesting a strong susceptibility to loss of work-hardening capability. In contrast, a 15-kg heat of V-3Ti-1Si (BL -45) exhibited relatively high uniform elongation ({approx}4%) during conventional irradiation at {approx}427{degrees}C, showing that the heat is resistant to loss of work-hardening capability.

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....

Measuring the stress field around an evolving crack in tensile deformed Mg AZ31 using three-dimensional X-ray diffraction

International Nuclear Information System (INIS)

Oddershede, Jette; Camin, Bettina; Schmidt, Søren; Mikkelsen, Lars P.; Sørensen, Henning Osholm; Lienert, Ulrich; Poulsen, Henning Friis; Reimers, Walter

2012-01-01

The stress field around a notch in a coarse grained Mg AZ31 sample has been measured under tensile load using the individual grains as probes in an in situ high energy synchrotron diffraction experiment. The experimental set-up, a variant of three-dimensional X-ray diffraction microscopy, allows the position, orientation and full stress tensor of each illuminated grain to be determined and, hence, enables the study of evolving stress fields in coarse grained materials with a spatial resolution equal to the grain size. Grain resolved information like this is vital for understanding what happens when the traditional continuum mechanics approach breaks down and fracture is governed by local heterogeneities (e.g. phase or stress differences) between grains. As a first approximation the results obtained were averaged through the thickness of the sample and compared with an elastic–plastic continuum finite element simulation. It was found that a full three-dimensional simulation was required to account for the measured transition from the overall plane stress case away from the notch to the essentially plane strain case observed near the notch tip. The measured and simulated stress contours were shown to be in good agreement except at the highest applied load, at which stress relaxation at the notch tip was observed in the experimental data. This stress relaxation is attributed to the initiation and propagation of a crack. Finally, it was demonstrated that the measured lattice rotations could be used as a qualitative measure of the shape and extent of the plastic deformation zone.

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

Notched audiograms and noise exposure history in older adults.

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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.

Prediction of Tensile Behavior of UHSFRC Considering the Flow Field in the Placing Dominated by Shear Flow

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Joon-Shik Moon

2018-01-01

Full Text Available Considering the case of fabricating a UHSFRC (ultra-high strength fiber-reinforced concrete beam with the method of one end placing and self-flowing to the other end, it was intended to simulate the variation of the fiber orientation distribution according to the flow distance and the variation of the resultant tensile behaviors. Then the validity of the simulation approach was shown by comparing the simulated results with experimental ones. A three-point bending test with a notched beam was adopted for the experiment and a finite element analysis was performed to obtain the simulated results for the bending test considering the flow-dependent tensile behavior of the UHSFRC. From the simulation for the fiber orientation distribution according to the flow distance, it could be found that the major change in the fiber orientation distribution took place within a short flow distance and most of the fibers became nearly aligned to the flow direction. After some flow distance, there was a not-so-remarkable variation in the fiber orientation distribution that could influence the tensile behavior of the composite. For this flow region, the consistent flexural test results, regardless of flow distance, demonstrate the reliability of the simulation.

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.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

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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.

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.

Influence of hydrogen on high cycle fatigue of polycrystalline vanadium

International Nuclear Information System (INIS)

Chung, D.W.; Lee, K.S.; Stoloff, N.S.

1977-02-01

The room temperature fatigue behavior of several polycrystalline V-H 2 alloys is described. Hydrogen extends the life of unnotched vanadium but has a deleterious effect in notched materials. Crack propagation data are correlated with tensile yield stress and cyclic strain hardening data

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

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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.

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

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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.

In vivo analysis of the Notch receptor S1 cleavage.

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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.

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...

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

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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.

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

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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.

PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

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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.

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

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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.

A three-dimensional analysis of the sigmoid notch

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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.

Far infrared promotes wound healing through activation of Notch1 signaling.

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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.

Mandibular Ramus Notching As a Tool for Sexual Dimorphism

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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.

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

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.

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

Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.

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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.

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

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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.

Complete Absence of Suprascapular Notch: A Case Report

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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.

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

Effects of strain rate, test temperature and test environment on tensile properties of vandium alloys

International Nuclear Information System (INIS)

Gubbi, A.N.; Rowcliffe, A.F.; Eatherly, W.S.; Gibson, L.T.

1996-01-01

Tensile testing was carried out on SS-3 tensile specimens punched from 0.762-mm-thick sheets of the large heat of V-4Cr-4Ti and small heats of V-3Cr-3Ti and V-6Cr-6Ti. The tensile specimens were annealed at 1000 degrees for 2 h to obtain a fully recrystallized, fine grain microstructure with a grain size in the range of 10-19 μm. Room temperature tests at strain rates ranging from 10 -3 to 5 x 10 -1 /s were carried out in air; elevated temperature testing up to 700 degrees C was conducted in a vacuum better than 1 x 10 -5 torr ( -3 Pa). To study the effect of atomic hydrogen on ductility, tensile tests were conducted at room temperature in an ultra high vacuum chamber (UHV) with a hydrogen leak system

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.

Behaviour of eggshell membranes at tensile loading

Czech Academy of Sciences Publication Activity Database

Strnková, M.J.; Nedomová, Š.; Trnka, Jan; Buchar, J.; Kumbár, V.

46 B, December (2014), s. 44-48 ISSN 0324-1130 Institutional support: RVO:61388998 Keywords : eggshell membrane * tensile loading * loading rate * stress * strain strength Subject RIV: GM - Food Processing Impact factor: 0.201, year: 2014

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.

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.

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.

Effects of strain rate, test temperature and test environment on tensile properties of vandium alloys

Energy Technology Data Exchange (ETDEWEB)

Gubbi, A.N.; Rowcliffe, A.F.; Eatherly, W.S.; Gibson, L.T. [Oak Ridge National Lab., TN (United States)

1996-10-01

Tensile testing was carried out on SS-3 tensile specimens punched from 0.762-mm-thick sheets of the large heat of V-4Cr-4Ti and small heats of V-3Cr-3Ti and V-6Cr-6Ti. The tensile specimens were annealed at 1000{degrees} for 2 h to obtain a fully recrystallized, fine grain microstructure with a grain size in the range of 10-19 {mu}m. Room temperature tests at strain rates ranging from 10{sup {minus}3} to 5 x 10{sup {minus}1}/s were carried out in air; elevated temperature testing up to 700{degrees}C was conducted in a vacuum better than 1 x 10{sup {minus}5} torr (<10{sup {minus}3} Pa). To study the effect of atomic hydrogen on ductility, tensile tests were conducted at room temperature in an ultra high vacuum chamber (UHV) with a hydrogen leak system.

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

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.

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

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.

Impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin: an in vitro study.

Science.gov (United States)

Stawarczyk, Bogna; Hartmann, Leonie; Hartmann, Rahel; Roos, Malgorzata; Ender, Andreas; Ozcan, Mutlu; Sailer, Irena; Hämmerle, Christoph H F

2012-02-01

This study tested the impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin. Human teeth were prepared and randomly divided into six groups (N = 144, n = 24 per group). For each tooth, a zirconia crown was manufactured. The zirconia crowns were cemented with: (1) Panavia21 (PAN), (2) Panavia21 combined with Gluma Desensitizer (PAN-G), (3) RelyX Unicem (RXU), (4) RelyX Unicem combined with Gluma Desensitizer (RXU-G), (5) G-Cem (GCM) and (6) G-Cem combined with Gluma Desensitizer (GCM-G). The initial tensile strength was measured in half (n = 12) of each group and the other half (n = 12) subjected to a chewing machine (1.2 Mio, 49 N, 5°C/50°C). The cemented crowns were pulled in a Universal Testing Machine (1 mm/min, Zwick Z010) until failure occurred and tensile strength was calculated. Data were analyzed with one-way and two-way ANOVA followed by a post hoc Scheffé test, t test and Kaplan-Meier analysis with a Breslow-Gehan analysis test (α = 0.05). After the chewing simulation, the self-adhesive resin cements combined with Gluma Desensitizer showed significantly higher tensile strength (RXU-G, 12.8 ± 4.3 MPa; GCM-G, 13.4 ± 6.2 MPa) than PAN (7.3 ± 1.7 MPa) and PAN-G (0.9 ± 0.6). Within the groups, PAN, PAN-G and RXU resulted in significantly lower values when compared to the initial tensile strength; the values of all other test groups were stable. In this study, self-adhesive resin cements combined with Gluma Desensitizer reached better long-term stability compared to PAN and PAN-G after chewing simulation.

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.

Improvement in tensile properties of PVC–montmorillonite ...

Indian Academy of Sciences (India)

mechanical properties of PVC–montmorillonite materials are also currently of huge ... Its hard form can withstand a tensile stress in the order of 46–52 MPa before .... 2θ at 25 mA and 40 kV using Cu-Kα radiation. X-ray diffraction patterns of the ...

Stress analysis and optimization of Nd:YAG pulsed laser processing of notches for fracture splitting of a C70S6 connecting rod

International Nuclear Information System (INIS)

Kou, Shuqing; Gao, Yan; Zhao, Yong; Lin, Baojun

2017-01-01

The pulsed laser pre-processing of a notch as the fracture initiation source for the splitting process is the key mechanism of an advanced fracture splitting technology for C70S6 connecting rods. This study investigated the stress field of Nd:YAG pulsed laser grooving, which affects the rapid fracture initiation at the notch root and the controlled crack extension in the critical fracture splitting quality, to improve manufacturing quality. Thermal elastic-plastic incremental theory was applied to build the finite element analysis model of the stress field of pulsed laser grooving for fracture splitting based on the Rotary-Gauss body heat source. The corresponding numerical simulation of the stress field was conducted. The changes and distributions of the stress during pulsed laser grooving were examined, the influence rule of the primary technological parameters on the residual stress was analyzed, and the analysis results were validated by the corresponding cutting experiment. Results showed that the residual stress distribution was concentrated in the Heat-affected zone (HAZ) near the fracture splitting notch, which would cause micro-cracks in the HAZ. The stress state of the notch root in the fracture initiation direction was tensile stress, which was beneficial to the fracture initiation and the crack rapid extension in the subsequent fracture splitting process. However, the uneven distribution of the stress could lead to fracture splitting defects, and thus the residual stress should be lowered to a reasonable range. Decreasing the laser pulse power, increasing the processing speed, and lowering the pulse width can lower the residual stress. Along with the actual production, the reasonable main technological parameters were obtained.

Stress analysis and optimization of Nd:YAG pulsed laser processing of notches for fracture splitting of a C70S6 connecting rod

Energy Technology Data Exchange (ETDEWEB)

Kou, Shuqing; Gao, Yan; Zhao, Yong; Lin, Baojun [Jilin University, Changchun (China)

2017-05-15

The pulsed laser pre-processing of a notch as the fracture initiation source for the splitting process is the key mechanism of an advanced fracture splitting technology for C70S6 connecting rods. This study investigated the stress field of Nd:YAG pulsed laser grooving, which affects the rapid fracture initiation at the notch root and the controlled crack extension in the critical fracture splitting quality, to improve manufacturing quality. Thermal elastic-plastic incremental theory was applied to build the finite element analysis model of the stress field of pulsed laser grooving for fracture splitting based on the Rotary-Gauss body heat source. The corresponding numerical simulation of the stress field was conducted. The changes and distributions of the stress during pulsed laser grooving were examined, the influence rule of the primary technological parameters on the residual stress was analyzed, and the analysis results were validated by the corresponding cutting experiment. Results showed that the residual stress distribution was concentrated in the Heat-affected zone (HAZ) near the fracture splitting notch, which would cause micro-cracks in the HAZ. The stress state of the notch root in the fracture initiation direction was tensile stress, which was beneficial to the fracture initiation and the crack rapid extension in the subsequent fracture splitting process. However, the uneven distribution of the stress could lead to fracture splitting defects, and thus the residual stress should be lowered to a reasonable range. Decreasing the laser pulse power, increasing the processing speed, and lowering the pulse width can lower the residual stress. Along with the actual production, the reasonable main technological parameters were obtained.

Characterization of cracking in Strain-Hardening Cementitious Composites using the compact tension test

DEFF Research Database (Denmark)

Pereira, Eduardo B.; Fischer, Gregor; Barros, Joaquim A. O.

The characterization of the tensile behavior of strain hardening cementitious composites (SHCC) is of significant importance to the material design. In a previous work the tensile stress-crack opening response of different types of SHCC was characterized using notched specimens tested in direct...... tension, where a single crack was obtained and mechanically characterized by performing Single Crack Tension Test (SCTT). In this study the tensile behavior of SHCC materials is characterized under eccentric tensile load using the Compact Tension Test (CTT). The long edge notch placed in the rectangular...... plate specimens and the eccentrically applied tensile load create the local conditions necessary to the initiation of a single crack at the tip of the notch. Further propagation and opening of the crack in Mode I allow the assessment of the tensile load-displacement relationship. The experimental...

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.

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.

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...

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.

Elevated Temperature Tensile Tests on DU–10Mo Rolled Foils

Energy Technology Data Exchange (ETDEWEB)

Schulthess, Jason [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-09-01

Tensile mechanical properties for uranium-10 wt.% molybdenum (U–10Mo) foils are required to support modeling and qualification of new monolithic fuel plate designs. It is expected that depleted uranium-10 wt% Mo (DU–10Mo) mechanical behavior is representative of the low enriched U–10Mo to be used in the actual fuel plates, therefore DU-10Mo was studied to simplify material processing, handling, and testing requirements. In this report, tensile testing of DU-10Mo fuel foils prepared using four different thermomechanical processing treatments were conducted to assess the impact of foil fabrication history on resultant tensile properties.

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.

Relationship of microstructure and tensile properties for neutron-irradiated vanadium alloys

International Nuclear Information System (INIS)

Loomis, B.A.; Smith, D.L.

1990-01-01

The microstructures in V-15Cr-5Ti, V-10Cr-5RTi, V-3Ti-1Si, V-15Ti-7.5Cr, and V-20Ti alloys were examined by transmission electron microscopy after neutron irradiation at 600 degree C to 21--84 atom displacements per atom in the Materials Open Test Assembly of the Fast Flux Test Facility. The microstructures in these irradiated alloys were analyzed to determine the radiation-produced dislocation density, precipitate number density and size, and void number density and size. The results of these analyses were used to compute increases in yield stress and swelling of the irradiated alloys. The computed increase in yield stress was compared with the increase in yield stress determined from tensile tests on these irradiated alloys. This comparison made it possible to evaluate the influence of alloy composition on the evolution of radiation-damaged microstructures and the resulting tensile properties. 11 refs

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

Notch co-operates with Lozenge/Runx to lock hemocytes into a differentiation programme

Czech Academy of Sciences Publication Activity Database

Terriente-Felix, A.; Li, J.; Collins, S.; Mulligan, A.; Reekie, I.; Bernard, F.; Krejčí, Alena; Bray, S.

2013-01-01

Roč. 140, č. 4 (2013), s. 926-937 ISSN 0950-1991 R&D Projects: GA ČR(CZ) GAP305/11/0126 Grant - others:MRC programme(GB) G0800034 Institutional support: RVO:60077344 Keywords : Lozenge/Runx * Notch * chromatin immunoprecipitation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.273, year: 2013

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.

Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.

Science.gov (United States)

Abdou, Asmaa Gaber; El-Wahed, Moshira Mohammed Abd; Kandil, Mona Abd-Elhalim; Samaka, Rehab Monir; Elkady, Noha

2013-10-01

Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells. © 2013 APMIS Published by Blackwell Publishing Ltd.

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.

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.

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.

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

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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

Reliability assessment of a bi-material notch: Strain energy density factor approach

Czech Academy of Sciences Publication Activity Database

Klusák, Jan; Knésl, Zdeněk

2010-01-01

Roč. 53, č. 2 (2010), s. 89-93 ISSN 0167-8442 R&D Projects: GA ČR GAP108/10/2049; GA ČR GA101/08/0994 Institutional research plan: CEZ:AV0Z20410507 Keywords : crack initiation * bi-material notch * strain energy density factor Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 1.073, year: 2010

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

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.

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 ...

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

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.

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.

Exosomal lipids impact notch signaling and induce death of human pancreatic tumoral SOJ-6 cells.

Directory of Open Access Journals (Sweden)

Sadia Beloribi

Full Text Available Exosomes are of increasing interest as alternative mode of cell-to-cell communication. We previously reported that exosomes secreted by human SOJ-6 pancreatic tumor cells induce (glycoprotein ligand-independent cell death and inhibit Notch-1 pathway, this latter being particularly active during carcinogenesis and in cancer stem cells. Therefore, we asked whether exosomal lipids were key-elements for cell death and hypothesized that cholesterol-rich membrane microdomains were privileged sites of exosome interactions with tumor cells. To address these questions and based on the lipid composition of exosomes from SOJ-6 cells (Ristorcelli et al. (2008 FASEB J. 22; 3358-3369 enriched in cholesterol and sphingomyelin (lipids forming liquid-ordered phase, Lo and depleted in phospholipids (lipids forming liquid-disordered phase, Ld, we designed Synthetic Exosome-Like Nanoparticles (SELN with ratios Lo/Ld from 3.0 to 6.0 framing that of SOJ-6 cell exosomes. SELN decreased tumor cell survival, the higher the Lo/Ld ratio, the lower the cell survival. This decreased survival was due to activation of cell death with inhibition of Notch pathway. FRET analyses indicated fusions/exchanges of SELN with cell membranes. Fluorescent SELN co-localized with the ganglioside GM1 then with Rab5A, markers of lipid microdomains and of early endosomes, respectively. These interactions occurred at lipid microdomains of plasma and/or endosome membranes where the Notch-1 pathway matures. We thus demonstrated a major role for lipids in interactions between SELN and tumor cells, and in the ensued cell death. To our knowledge this is the first report on such effects of lipidic nanoparticles on tumor cell behavior. This may have implications in tumor progression.

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

The effect of residual thermal stresses on the fatigue crack growth of laser-surface-annealed AISI 304 stainless steel Part I: computer simulation

International Nuclear Information System (INIS)

Shiue, R.K.; Chang, C.T.; Young, M.C.; Tsay, L.W.

2004-01-01

The effect of residual thermal stresses on the fatigue crack growth of the laser-surface-annealed AISI 304 stainless steel, especially the effect of stress redistribution ahead of the crack tip was extensively evaluated in the study. Based on the finite element simulation, the longitudinal residual tensile stress field has a width of roughly 20 mm on the laser-irradiated surface and was symmetric with respect to the centerline of the laser-annealed zone (LAZ). Meanwhile, residual compressive stresses distributed over a wide region away from the LAZ. After introducing a notch perpendicular to the LAZ, the distribution of longitudinal residual stresses became unsymmetrical about the centerline of LAZ. High residual compressive stresses exist within a narrow range ahead of notch tip. The improved crack growth resistance of the laser-annealed specimen might be attributed to those induced compressive stresses. As the notch tip passed through the centerline of the LAZ, the residual stress ahead of the notch tip was completely reverted into residual tensile stresses. The existence of unanimous residual tensile stresses ahead of the notch tip was maintained, even if the notch tip extended deeply into the LAZ. Additionally, the presence of the residual tensile stress ahead of the notch tip did not accelerate the fatigue crack growth rate in the compact tension specimen

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.

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

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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.

Microstructure and tensile properties of neutron-irradiated (FE061Ni039)3V ordered alloy

International Nuclear Information System (INIS)

Braski, D.N.

1982-01-01

Small tensile specimens of the (Fe 0 61 Ni 0 39 ) 3 V long-range-ordered alloy were irradiated in the ORR to 4 dpa at 523, 623, and 823 K and subsequently tested at the same respective temperatueres. The alloy remained ordered after irradiation at all three temperatures. Irradiation at 523 and 623 K increased the yield strength of the material by producing Frank loops in the microstructure and reduced the total elongation. The low strain hardening observed was attributed to planar slip and the absence of cross slip. Irradiation at 823 K embrittled the alloy. Premature failure was apparently initiated by helium bubbles on sigma phase boundaries which grew rapidly during the test to form microcracks. Fracture occurred after a microcrack propagated across grain boundaries that were weakened by helium and possible sulfur. New LRO alloys without sigma phase should perform better under neutron irradiation

Optimization of tensile method and specimen geometry in modified ring tensile test

International Nuclear Information System (INIS)

Kitano, Koji; Fuketa, Toyoshi; Sasajima, Hideo; Uetsuka, Hiroshi

2001-03-01

Several techniques in ring tensile test are proposed in order to evaluate mechanical properties of cladding under hoop loading condition caused by pellet/cladding mechanical interaction (PCMI). In the modified techniques, variety of tensile methods and specimen geometry are being proposed in order to limit deformation within the gauge section. However, the tensile method and the specimen geometry were not determined in the modified techniques. In the present study, we have investigated the tensile method and the specimen geometry through finite element method (FEM) analysis of specimen deformation and tensile test on specimens with various gauge section geometries. In using two-piece tensile tooling, the mechanical properties under hoop loading condition can be correctly evaluated when deformation part (gauge section) is put on the top of a half-mandrel, and friction between the specimen and the half-mandrel is reduced with Teflon tape. In addition, we have shown the optimum specimen geometry for PWR 17 by 17 type cladding. (author)

Fatigue Analysis of Notched Laminates: A Time-Efficient Macro-Mechanical Approach

Science.gov (United States)

Naghipour, P.; Pineda, E. J.; Bednarcyk, B. A.; Arnold, S. M.; Waas, A. M.

2016-01-01

A coupled transversely isotropic deformation and damage fatigue model is implemented within the finite element method and was utilized along with a static progressive damage model to predict the fatigue life, stiffness degradation as a function of number of cycles, and post-fatigue tension and compression response of notched, multidirectional laminates. Initially, the material parameters for the fatigue model were obtained utilizing micromechanics simulations and the provided [0], [90] and [plus or minus 45] experimental composite laminate S-N (stress-cycle) data. Within the fatigue damage model, the transverse and shear properties of the plies were degraded with an isotropic scalar damage variable. The damage in the longitudinal (fiber) ply direction was suppressed, and only the strength of the fiber was degraded as a function of fatigue cycles. A maximum strain criterion was used to capture the failure in each element, and once this criterion was satisfied, the longitudinal stiffness of the element was decreased by a factor of 10 (sup 4). The resulting, degraded properties were then used to calculate the new stress state. This procedure was repeated until final failure of the composite laminate was achieved or a specified number of cycles reached. For post-fatigue tension and compression behavior, four internal state variables were used to control the damage and failure. The predictive capability of the above-mentioned approach was assessed by performing blind predictions of the notched multidirectional IM7/977-3 composite laminates response under fatigue and post-fatigue tensile and compressive loading, followed by a recalibration phase. Although three different multidirectional laminates were analyzed in the course of this study, only detailed results (i.e., stiffness degradation and post-fatigue stress-train curves as well as damage evolution states for a single laminate ([30/60/90/minus 30/minus 60] (sub 2s)) are discussed in detail here.

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....

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.

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

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

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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.

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...

Tensile properties of V-Cr-Ti alloys after exposure in oxygen-containing environments

International Nuclear Information System (INIS)

Natesan, K.; Soppet, W.K.

1998-01-01

A systematic study was conducted to evaluate the oxidation kinetics of V-4Cr-4Ti (44 alloy) and V-5Cr-5Ti alloys (55 alloy) and to establish the role of oxygen ingress on the tensile behavior of the alloys at room temperature and at 500 C. The oxidation rate of the 44 alloy is slightly higher than that of the 55 alloy. The oxidation process followed parabolic kinetics. Maximum engineering stress for 55 alloy increased with an increase in oxidation time at 500 C. The maximum stress values for 55 alloy were higher at room temperature than ta 500 C for the same oxidation treatment. Maximum engineering stresses for 44 alloy were substantially lower than those for 55 alloy in the same oxidation ∼500 h exposure in air at 500 C; the same values were 4.8 and 6.1%, respectively, at 500 C after ∼2060 h oxidation in air at 500 C. Maximum engineering stress for 44 alloy at room temperature was 421.6--440.6 MPa after ∼250 h exposure at 500 C in environments with a pO 2 range of 1 x 10 -6 to 760 torr. The corresponding uniform and total elongation values were 11--14.4% and 14.5--21.7%, respectively. Measurements of crack depths in various specimens showed that depth is independent of pO 2 in the preexposure environment and was of 70--95 microm after 250--275 h exposure at 500 C

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.

Deformation and fatigue of tough 3D printed elastomer scaffolds processed by fused deposition modeling and continuous liquid interface production.

Science.gov (United States)

Miller, Andrew T; Safranski, David L; Wood, Catherine; Guldberg, Robert E; Gall, Ken

2017-11-01

Polyurethane (PU) based elastomers continue to gain popularity in a variety of biomedical applications as compliant implant materials. In parallel, advancements in additive manufacturing continue to provide new opportunities for biomedical applications by enabling the creation of more complex architectures for tissue scaffolding and patient specific implants. The purpose of this study was to examine the effects of printed architecture on the monotonic and cyclic mechanical behavior of elastomeric PUs and to compare the structure-property relationship across two different printing approaches. We examined the tensile fatigue of notched specimens, 3D crosshatch scaffolds, and two 3D spherical pore architectures in a physically crosslinked polycarbonate urethane (PCU) printed via fused deposition modeling (FDM) as well as a photo-cured, chemically-crosslinked, elastomeric PU printed via continuous liquid interface production (CLIP). Both elastomers were relatively tolerant of 3D geometrical features as compared to stiffer synthetic implant materials such as PEEK and titanium. PCU and crosslinked PU samples with 3D porous structures demonstrated a reduced tensile failure stress as expected without a significant effect on tensile failure strain. PCU crosshatch samples demonstrated similar performance in strain-based tensile fatigue as solid controls; however, when plotted against stress amplitude and adjusted by porosity, it was clear that the architecture had an impact on performance. Square shaped notches or pores in crosslinked PU appeared to have a modest effect on strain-based tensile fatigue while circular shaped notches and pores had little impact relative to smooth samples. When plotted against stress amplitude, any differences in fatigue performance were small or not statistically significant for crosslinked PU samples. Despite the slight difference in local architecture and tolerances, crosslinked PU solid samples were found to perform on par with PCU solid

Tensile and shear methods for measuring strength of bilayer tablets.

Science.gov (United States)

Chang, Shao-Yu; Li, Jian-Xin; Sun, Changquan Calvin

2017-05-15

Both shear and tensile measurement methods have been used to quantify interfacial bonding strength of bilayer tablets. The shear method is more convenient to perform, but reproducible strength data requires careful control of the placement of tablet and contact point for shear force application. Moreover, data obtained from the shear method depend on the orientation of the bilayer tablet. Although more time-consuming to perform, the tensile method yields data that are straightforward to interpret. Thus, the tensile method is preferred in fundamental bilayer tableting research to minimize ambiguity in data interpretation. Using both shear and tensile methods, we measured the mechanical strength of bilayer tablets made of several different layer combinations of lactose and microcrystalline cellulose. We observed a good correlation between strength obtained by the tensile method and carefully conducted shear method. This suggests that the shear method may be used for routine quality test of bilayer tablets during manufacturing because of its speed and convenience, provided a protocol for careful control of the placement of the tablet interface, tablet orientation, and blade is implemented. Copyright © 2017 Elsevier B.V. All rights reserved.

Electron-microscopic investigation of a pressure vessel steel after neutron irradiation

International Nuclear Information System (INIS)

Klaar, H.J.

1975-01-01

As an introduction, changes in the mechanical properties of pressure vessel steels on neutron irradiation and the causes of radiation embrittlement are discussed. After this, the author describes his own experiments with steel of the composition 0.19% C; 3.88% Ni; 1.57% Cr; 0.51% Mo; 0.2% V. Samples of this material were irradiated in-pile at 300 0 C with various neutron doses. To study the influence of neutron dose, irradiation temperature, and heat treatment on the mechanical properties, tensile tests, notched bar impact bending tests, hardness tests and structural analyses were carried out. The findings are reported. (GSC) [de

The Effects of Fe-Particles on the Tensile Properties of Al-Si-Cu Alloys

Directory of Open Access Journals (Sweden)

Anton Bjurenstedt

2016-12-01

Full Text Available The effect of Fe-rich particles has been a topic for discussion in the aluminum casting industry because of the negative impact they exert on the mechanical properties. However, there are still contradictions on the effects of various morphologies of Fe-particles. In this study, microstructural characterization of tensile tested samples has been performed to reveal how unmodified and modified Fe-rich particles impact on the tensile behavior. Analysis of additions of Fe modifiers such as Mn and Cr, showed higher amounts of primary Fe-rich particles (sludge with increased porosity and, as result, degraded tensile properties. From the fracture analysis of tensile tested hot isostatic pressed (HIPed samples it could be concluded that the mechanical properties were mainly governed by the Fe-rich particles, which were fracturing through cleavage, not by the porosity.

High-Tensile Strength Tape Versus High-Tensile Strength Suture: A Biomechanical Study.

Science.gov (United States)

Gnandt, Ryan J; Smith, Jennifer L; Nguyen-Ta, Kim; McDonald, Lucas; LeClere, Lance E

2016-02-01

To determine which suture design, high-tensile strength tape or high-tensile strength suture, performed better at securing human tissue across 4 selected suture techniques commonly used in tendinous repair, by comparing the total load at failure measured during a fixed-rate longitudinal single load to failure using a biomechanical testing machine. Matched sets of tendon specimens with bony attachments were dissected from 15 human cadaveric lower extremities in a manner allowing for direct comparison testing. With the use of selected techniques (simple Mason-Allen in the patellar tendon specimens, whip stitch in the quadriceps tendon specimens, and Krackow stitch in the Achilles tendon specimens), 1 sample of each set was sutured with a 2-mm braided, nonabsorbable, high-tensile strength tape and the other with a No. 2 braided, nonabsorbable, high-tensile strength suture. A total of 120 specimens were tested. Each model was loaded to failure at a fixed longitudinal traction rate of 100 mm/min. The maximum load and failure method were recorded. In the whip stitch and the Krackow-stitch models, the high-tensile strength tape had a significantly greater mean load at failure with a difference of 181 N (P = .001) and 94 N (P = .015) respectively. No significant difference was found in the Mason-Allen and simple stitch models. Pull-through remained the most common method of failure at an overall rate of 56.7% (suture = 55%; tape = 58.3%). In biomechanical testing during a single load to failure, high-tensile strength tape performs more favorably than high-tensile strength suture, with a greater mean load to failure, in both the whip- and Krackow-stitch models. Although suture pull-through remains the most common method of failure, high-tensile strength tape requires a significantly greater load to pull-through in a whip-stitch and Krakow-stitch model. The biomechanical data obtained in the current study indicates that high-tensile strength tape may provide better repair

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.

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

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...

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.

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.

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

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

Tensile behavior of laser treated Fe-Si-B metallic glass

Energy Technology Data Exchange (ETDEWEB)

Joshi, Sameehan S.; Samimi, Peyman; Ghamarian, Iman; Katakam, Shravana; Collins, Peter C.; Dahotre, Narendra B., E-mail: narendra.dahotre@unt.edu [Department of Materials Science and Engineering, University of North Texas, 1150 Union Circle 305310, Denton, Texas 76203-5017 (United States)

2015-10-28

Fe-Si-B metallic glass foils were treated with a linear laser track using a continuous wave Nd-YAG laser and its effect on the overall tensile behavior was investigated. Microstructure and phase evolutions were evaluated using X-ray diffraction, resistivity measurements, and transmission electron microscopy. Crystallization fraction was estimated via the differential scanning calorimetry technique. Metallic glass foils treated with the lower laser fluences (<0.49 J/mm{sup 2}) experienced structural relaxation, whereas higher laser fluences led to crystallization within the laser treated region. The overall tensile behavior was least impacted by structural relaxation, whereas crystallization severely reduced the ultimate tensile strength of the laser treated metallic glass foils.

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

Characterization of high temperature tensile and creep–fatigue properties of Alloy 800H for intermediate heat exchanger components of (V)HTRs

Energy Technology Data Exchange (ETDEWEB)

Kolluri, M., E-mail: kolluri@nrg.eu; Pierick, P. ten, E-mail: tenpierick@nrg.eu; Bakker, T., E-mail: t.bakker@nrg.eu

2015-04-01

Highlights: • High temperature tensile, creep–fatigue (C–F) properties of Alloy 800H are studied. • Strength and uniform elongation properties at 800 °C are much lower than RT values. • Strong influence of hold time and Δε{sub tot} on low cycle fatigue life was observed. • The total allowable C–F damage (D) at 800 °C decreases with the decreasing Δε{sub tot}. • Synergetic effect of C–F interactions showed stronger effect at lower Δε{sub tot} values. - Abstract: Alloy 800H is considered as a candidate material for intermediate heat exchanger (IHX) components of (very) high temperature reactors (V)HTRs. Qualification of the this alloy for the aforementioned nuclear applications requires understanding of its high temperature tensile, low-cycle fatigue behavior and creep–fatigue interactions because the IHX components suffer from combined creep–fatigue loadings resulting from thermally induced strain cycles associated with start-up and shutdown cycles. To this end, in this paper, the tensile properties of the Alloy 800H base and tungsten inert gas (TIG) welded materials are studied at three different temperatures, room temperature 21, 700 and 800 °C. Low cycle fatigue (LCF) behavior of the base material is investigated at 800 °C with no-hold time (no-HT) and hold time (HT) to study creep–fatigue interactions. The tensile test results showed substantial differences between the strength and ductility properties of the base and weld materials at all 3 temperatures, however, the trends in temperature dependence of tensile properties are similar for both base and weld materials. LCF studies with no-HT and HT showed a strong influence of HT on the low cycle fatigue life of this alloy illustrating the substantial influence of creep mechanisms at 800 °C. Finally, cumulative values of creep versus fatigue damage fractions are plotted in a creep–fatigue interaction diagram and these results are discussed with respect to the existing bi

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...

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...

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.

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.

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.

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...

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 ...

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)

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...

EXPERIMENTAL INVESTIGATION ON TENSILE STRENGTH OF JACQUARD KNITTED FABRICS

Directory of Open Access Journals (Sweden)

BRAD Raluca

2015-05-01

Full Text Available An objective approach to select the best fabric for technical and home textiles consists in mechanical properties evaluation. The goal of this study is to analyze the behavior of knitted fabrics undergoing stretch stress. In this respect, three types of 2 colors Rib structure (backstripes jacquard, twillback jacquard and double-layered 3x3 rib fabric have been presented and tested for tensile strength and elongation on three directions. First, the elasticity and the behavior of knitted Rib fabrics were described The fabrics were knitted using 100% PAN yarns with Nm 1/15x2 on a E5 CMS 330 Stoll V-bed knitting machine, and have been tested using INSTROM 5587 Tensile Testing Machine in respect of standards conditions. After a relaxation period, 15 specimens were prepared, being disposed at 0°, 45 and 90 angles to the wale direction on the flat knitted panel. The tensile strength and the elongation values were recorded and mean values were computed. After strength and tensile elongation testing for 3 types of rib based knitted fabrics, one can see that the double layer knit presents the best mechanical behavior, followed by birds-eyebacking 2 colors Jacquard and then back striped Jacquard. For tensile stress in bias direction, the twillbacking Jacquard has a good breakage resistance value due to the higher number of rib sinker loops in structure that are positioned on the same direction with the tensile force. The twillbacking Jacquard structure could be considered as an alternative for the base material for decorative and home textile products.

Dynamic tensile response of alumina-Al composites

International Nuclear Information System (INIS)

Atisivan, R.; Bandyopadhyay, A.; Gupta, Y. M.

2002-01-01

Plate impact experiments were carried out to examine the high strain-rate tensile response of alumina-aluminum (Al) composites with tailored microstructures. A novel processing technique was used to fabricate interpenetrating phase alumina-aluminum composites with controlled microstructures. Fused deposition modeling (FDM), a commercially available rapid prototyping technique, was used to produce the controlled porosity mullite ceramic preforms. Alumina-Al composites were then processed via reactive metal infiltration of porous mullite ceramics. With this approach, both the micro as well as the macro structures can be designed via computer aided design (CAD) to tailor the properties of the composites. Two sets of dynamic tensile experiments were performed. In the first, the metal content was varied between 23 and 39 wt. percent. In the second, the microstructure was varied while holding the metal content nearly constant. Samples with higher metal content, as expected, displayed better spall resistance. For a given metal content, samples with finer metal diameter showed better spall resistance. Relationship of the microstructural parameters on the dynamic tensile response of the structured composites is discussed here

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.

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.

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.

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.

Developing mathematical models to predict tensile properties of pulsed current gas tungsten arc welded Ti-6Al-4V alloy

International Nuclear Information System (INIS)

Balasubramanian, M.; Jayabalan, V.; Balasubramanian, V.

2008-01-01

Titanium (Ti-6Al-4V) alloy has gathered wide acceptance in the fabrication of light weight structures requiring a high strength-to-weight ratio, such as transportable bridge girders, military vehicles, road tankers and railway transport systems. The preferred welding process of titanium alloy is frequently gas tungsten arc (GTA) welding due to its comparatively easier applicability and better economy. In the case of single pass GTA welding of thinner section of this alloy, the pulsed current has been found beneficial due to its advantages over the conventional continuous current process. Many considerations come into the picture and one need to carefully balance various pulse current parameters to arrive at an optimum combination. Hence, in this investigation an attempt has been made to develop mathematical models to predict tensile properties of pulsed current GTA welded titanium alloy weldments. Four factors, five level, central composite, rotatable design matrix is used to optimise the required number of experiments. The mathematical models have been developed by response surface method (RSM). The adequacy of the models has been checked by ANOVA technique. By using the developed mathematical models, the tensile properties of the joints can be predicted with 99% confidence level

Developing mathematical models to predict tensile properties of pulsed current gas tungsten arc welded Ti-6Al-4V alloy

Energy Technology Data Exchange (ETDEWEB)

Balasubramanian, M. [Department of Production Engineering, Sathyabama University, Old Mamallapuram Road, Chennai 600 119 (India)], E-mail: manianmb@rediffmail.com; Jayabalan, V. [Department of Manufacturing Engineering, Anna University, Guindy, Chennai 600 025 (India)], E-mail: jbalan@annauniv.edu; Balasubramanian, V. [Department of Manufacturing Engineering, Annamalai University, Annamalai Nagar 608 002 (India)], E-mail: visvabalu@yahoo.com

2008-07-01

Titanium (Ti-6Al-4V) alloy has gathered wide acceptance in the fabrication of light weight structures requiring a high strength-to-weight ratio, such as transportable bridge girders, military vehicles, road tankers and railway transport systems. The preferred welding process of titanium alloy is frequently gas tungsten arc (GTA) welding due to its comparatively easier applicability and better economy. In the case of single pass GTA welding of thinner section of this alloy, the pulsed current has been found beneficial due to its advantages over the conventional continuous current process. Many considerations come into the picture and one need to carefully balance various pulse current parameters to arrive at an optimum combination. Hence, in this investigation an attempt has been made to develop mathematical models to predict tensile properties of pulsed current GTA welded titanium alloy weldments. Four factors, five level, central composite, rotatable design matrix is used to optimise the required number of experiments. The mathematical models have been developed by response surface method (RSM). The adequacy of the models has been checked by ANOVA technique. By using the developed mathematical models, the tensile properties of the joints can be predicted with 99% confidence level.

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

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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.

Tensile strength and impact resistance properties of materials used in prosthetic check sockets, copolymer sockets, and definitive laminated sockets

OpenAIRE

Maria J. Gerschutz, PhD; Michael L. Haynes, MS; Derek M. Nixon, BS; James M. Colvin, MS

2011-01-01

Prosthetic sockets serve as the interface between people with amputations and their prostheses. Although most materials used to make prosthetic sockets have been used for many years, knowledge of these materials' properties is limited, especially after they are subjected to fabrication processes. This study evaluated tensile and impact properties of the current state-of-the-art materials used to fabricate prosthetic check sockets, copolymer sockets, and definitive laminated sockets. Thermolyn...

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.

Microstructure and mechanical behavior of Al-Li-Zr alloys

International Nuclear Information System (INIS)

Wang, Wego; Wells, M.G.H.

1991-01-01

The mechanical properties of two Al-Li-Zr alloys, A and B, are determined at various heat treatment conditions. Alloy B was found to have superior mechanical properties. It shows improvements in yield strength by 31.2-56.2 MPa and in ultimate tensile strength by 14.7-40.7 MPa, and yet still has a 20-25 percent better elongation value. The microstructure and fracture surface were studied by SEM and TEM. A fracture surface with mixed ductile samples and brittle facets was observed in both tensile and notch tensile samples. The fracture was more localized in alloy A than alloy B. Both alloys exhibited good notch toughness with a notch tensile strength to yield a strength ratio larger than one for all heat treatment conditions. 32 refs

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.

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.

Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.

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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.

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

Effect of niobium on tensile, impact and hardness mechanical properties in martensitic steels that could be strengthened

International Nuclear Information System (INIS)

Casteletti, L.C.

1986-01-01

Martensitic steels that could be strengthened by precipitation, based on traditional maraging steels were developed, aiming to total or partial substitution of the expensive elements. Niobium was used as the precipitation forming element and it was very effective in the strengthening of martensitic matrix. The Ni element was completely and partially substituted by Mn. Tensile and impact tests at room temperature and aging curves were obtained in the temperature range from 400 to 600 sup(0)C, for 20 alloys systems. Metallographic and fractographic analysis were done, and the results are presents. (M.C.K.)

Ductility and failure behaviour of both unirradiated and irradiated zircaloy-4 cladding using plane strain tensile specimens

International Nuclear Information System (INIS)

Carassou, S.; Le Saux, M.; Pizzanelli, J.P.; Rabouille, O.; Averty, X.; Poussard, C.; Cazalis, B.; Desquines, J.; Bernaudat, C.

2010-01-01

In this work, eight PST (Plan Strain Tensile) tests machined from a Zircaloy-4 (Zy-4) cladding irradiated up to 5 annual cycles have been performed at 280, 350 and 480 Celsius degrees. The specimen displacements during the tests were filmed and digitally recorded to allow the use of a Digital Image Correlation (DIC) analysis technique to experimentally determine the local strains on the outer surface of the specimens. The plane strain conditions have been verified and prevail over a wide area between the notches of the specimen, as expected from full 3D FE numerical analysis performed in support of the tests. For the first time, the location of the onset of fracture for this geometry on irradiated material has been experimentally observed: at 280 C.degrees, crack initiates in the vicinity of the notches, in an area where plane strain conditions are not fulfilled, and for a local circumferential strain value of about 5%. At 350 C. degrees and 480 C. degrees, cracks initiate at a location where plane strain conditions prevail, for circumferential strain values respectively close to 10% and greater than 50%. These results have been compared to results obtained previously by similar test on fresh and hydrided material, as well as tests performed as support to the study. At 350 C. degrees, the homogeneous 700 ppm hydrided Zy-4 and the Zy-4 irradiated during 5 annual cycles exhibit similar fracture behaviour, for both fracture hoop strain values (10%) and fracture mode (through-wall slant fracture). For the irradiated material, it has clearly been established that at 350 C. degrees, a brittle fracture occurs at the outer surface in the hydride rim. The crack propagates subsequently toward the inner surface and the notches, where final fracture occurs

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

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.

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...

AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster.

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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.

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.

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.

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)

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.

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.

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.

Temperature and heat effects on polyethylene behaviour in the presence of imperfections

Directory of Open Access Journals (Sweden)

Murariu Alin Constantin

2016-01-01

Full Text Available This paper highlights the changes of polyethylene behaviour during various loading rate as well as the influence of test temperature on the material characteristics. Passive infrared thermography (IRT method and a high speed infrared camera were used to observe the temperature changes of the sample surface during the tests. The experimental program was carried out on samples taken from PE80 polyethylene gas pipes with simulated imperfections with bilateral V-notch, U-notch and central hole. Samples have been tensile tested (TT and the results are correlated with the temperature distribution of the samples surface.

DYNAMIC TENSILE TESTING WITH A LARGE SCALE 33 MJ ROTATING DISK IMPACT MACHINE

OpenAIRE

Kussmaul , K.; Zimmermann , C.; Issler , W.

1985-01-01

A recently completed testing machine for dynamic tensile tests is described. The machine consists essentially of a pendulum which holds the specimen and a large steel disk with a double striking nose fixed to its circumference. Disk diameter measures 2000 mm, while its mass is 6400 kg. The specimens to be tested are tensile specimens with a diameter of up to 20 mm and 300 mm length or CT 15 specimens at various temperatures. Loading velocity ranges from 1 to 150 m/s. The process of specimen-n...

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.

Identification of 11-amino acid peptides that disrupt Notch-mediated processes in Drosophila

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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

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

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

Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

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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.

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)

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.

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

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.

The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila

Czech Academy of Sciences Publication Activity Database

Horváth, Matěj; Mihajlović, Zorana; Slaninová, Věra; Perez-Gomez, Raquel; Moshkin, Y.; Krejčí, Alena

2016-01-01

Roč. 473, č. 22 (2016), s. 4129-4143 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GA14-08583S Institutional support: RVO:60077344 Keywords : Drosophila * silent information regulator 1 * Notch pathway Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.797, year: 2016

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

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.

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....

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.

Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

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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

Tensile properties of orthodontic elastomeric ligatures.

Science.gov (United States)

Ahrari, F; Jalaly, T; Zebarjad, M

2010-01-01

Tensile properties of elastomeric ligatures become important when efficiency of orthodontic appliances is considered. The aim of this study was to compare tensile strength, extension to tensile strength, toughness and modulus of elasticity of elastomeric ligatures in both the as--received condition and after 28 days of immersion in the simulated oral environment. Furthermore, the changes that occurred in tensile properties of each brand of ligatures after 28 days were evaluated. Experimental-laboratory based. Elastomeric ligatures were obtained from different companies and their tensile properties were measured using Zwick testing machine in both the as-received condition and after 28 days of immersion in the simulated oral environment. The data were analyzed using independent sample t-tests, analysis of variance and Tukey tests. After 28 days, all the ligatures experienced a significant decrease in tensile strength, extension to tensile strength and toughness ( P tensile properties of different brands of ligatures in both conditions ( P tensile properties of different brands of ligatures, which should be considered during selection of these products.

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...

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...

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

Tensile properties and impact toughness of S30408 stainless steel and its welded joints at cryogenic temperatures

Science.gov (United States)

Ding, Huiming; Wu, Yingzhe; Lu, Qunjie; Xu, Ping; Zheng, Jinyang; Wei, Lijun

2018-06-01

Designing a cryogenic pressure vessel based on the mechanical properties of the austenitic stainless steel (ASS) at its cryogenic operating temperature fully utilizes the potential of the material at low temperatures, resulting in lightweight and compact products. A series of tensile tests and impact tests were carried out in a wide range of 77-293 K, to investigate the mechanical properties of S30408 base metal (BM) and welded joints (WJ) at cryogenic temperatures. As the temperature decreases, yield stress (Rp0.2) and ultimate tensile stress (Rm) increase significantly thanks to the low-temperature strengthening effects. To estimate strengths at cryogenic temperatures, quadratic polynomial model was used to accurately predict the variations of Rp0.2 and Rm from 77 K to 293 K. As an important phase in the WJ, ferrite presents a radial pattern and an inhomogeneity in the WJ's cross-section. Due to the formation of ferrite in the WJ, the WJ has higher Rp0.2 and lower Rm , Charpy absorbed energy and lateral expansion compared with the BM. Strain-induced martensite transformation is an important role influencing the deformation of ASS at low temperatures. In this study, less martensite amount was measured in the weldment zone with higher Nickel equivalents which stabilize the austenite phase at cryogenic temperatures. Additionally, due to higher ferrite content and more precipitates forming, the SAW joints has lower Rm and impact toughness than PAW + GTAW joints. To ensure the structural integrity and safety, the PAW + GTAW method should be chosen and ferrite content be controlled.

The Relationships Between Microstructure, Tensile Properties and Fatigue Life in Ti-5Al-5V-5Mo-3Cr-0.4Fe (Ti-5553)

Science.gov (United States)

Foltz, John W., IV

beta-titanium alloys are being increasingly used in airframes as a way to decrease the weight of the aircraft. As a result of this movement, Ti-5Al-5V-5Mo-3Cr-0.4Fe (Timetal 555), a high-strength beta titanium alloy, is being used on the current generation of landing gear. This alloy features good combinations of strength, ductility, toughness and fatigue life in alpha+beta processed conditions, but little is known about beta-processed conditions. Recent work by the Center for the Accelerated Maturation of Materials (CAMM) research group at The Ohio State University has improved the tensile property knowledge base for beta-processed conditions in this alloy, and this thesis augments the aforementioned development with description of how microstructure affects fatigue life. In this work, beta-processed microstructures have been produced in a Gleeble(TM) thermomechanical simulator and subsequently characterized with a combination of electron and optical microscopy techniques. Four-point bending fatigue tests have been carried out on the material to characterize fatigue life. All the microstructural conditions have been fatigue tested with the maximum test stress equal to 90% of the measured yield strength. The subsequent results from tensile tests, fatigue tests, and microstructural quantification have been analyzed using Bayesian neural networks in an attempt to predict fatigue life using microstructural and tensile inputs. Good correlation has been developed between lifetime predictions and experimental results using microstructure and tensile inputs. Trained Bayesian neural networks have also been used in a predictive fashion to explore functional dependencies between these inputs and fatigue life. In this work, one section discusses the thermal treatments that led to the observed microstructures, and the possible sequence of precipitation that led to these microstructures. The thesis then describes the implications of microstructure on fatigue life and

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.

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.

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.

Magnetic epoxy nanocomposites reinforced with hierarchical α-Fe2O3 nanoflowers: a study of mechanical properties

Science.gov (United States)

Balguri, Praveen Kumar; Harris Samuel, D. G.; Thumu, Udayabhaskararao

2017-09-01

In this work, we presented the potentiality of monodispersed 3D hierarchical α-Fe2O3 nanoflowers (α-Fe2O3) as reinforcement for epoxy polymer. α-Fe2O3 are synthesized through the thermal decomposition of iron alkoxide precursor in ethylene glycol. α-Fe2O3/epoxy nanocomposites (0.1 wt% of α-Fe2O3) show 109%, 59%, 13%, and 15% enhancement in impact (un-notched), impact (notched), flexural and tensile properties, respectively. The uniformly embedded α- Fe2O3 nanoflowers in epoxy polymer not only provide mechanical strength but also induced magnetic nature to the nanocomposite as observed from the Scanning electron microscopy and vibrating sample magnetometer.

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.

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...

A technique to remove the tensile instability in weakly compressible SPH

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Xu, Xiaoyang; Yu, Peng

2018-01-01

When smoothed particle hydrodynamics (SPH) is directly applied for the numerical simulations of transient viscoelastic free surface flows, a numerical problem called tensile instability arises. In this paper, we develop an optimized particle shifting technique to remove the tensile instability in SPH. The basic equations governing free surface flow of an Oldroyd-B fluid are considered, and approximated by an improved SPH scheme. This includes the implementations of the correction of kernel gradient and the introduction of Rusanov flux into the continuity equation. To verify the effectiveness of the optimized particle shifting technique in removing the tensile instability, the impacting drop, the injection molding of a C-shaped cavity, and the extrudate swell, are conducted. The numerical results obtained are compared with those simulated by other numerical methods. A comparison among different numerical techniques (e.g., the artificial stress) to remove the tensile instability is further performed. All numerical results agree well with the available data.

Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages.

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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.

Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway

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In Kyoung Mah

2015-11-01

Full Text Available The number of stem/progenitor cells available can profoundly impact tissue homeostasis and the response to injury or disease. Here, we propose that an atypical PKC, Prkci, is a key player in regulating the switch from an expansion to a differentiation/maintenance phase via regulation of Notch, thus linking the polarity pathway with the control of stem cell self-renewal. Prkci is known to influence symmetric cell division in invertebrates; however a definitive role in mammals has not yet emerged. Using a genetic approach, we find that loss of Prkci results in a marked increase in the number of various stem/progenitor cells. The mechanism used likely involves inactivation and symmetric localization of NUMB, leading to the activation of NOTCH1 and its downstream effectors. Inhibition of atypical PKCs may be useful for boosting the production of pluripotent stem cells, multipotent stem cells, or possibly even primordial germ cells by promoting the stem cell/progenitor fate.

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

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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.

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.

Effects of mineral content on the fracture properties of equine cortical bone in double-notched beams.