A study on the notch effect on the low cycle fatigue of metals in creep-fatigue interacting conditions at elevated temperature

International Nuclear Information System (INIS)

Sakane, M.; Oknami, M.

1983-01-01

Frequency and hold-time effects on fatigue lives of cylindrical notched specimens of SUS 316 stainless steel were studied at 600 0 C in air. From the tests, the following conclusions were obtained: Neuber's rule, as used in the ASME N-47 Code, predicts very conservatively the life of notched specimens in tests without a hold-time. But it gives a nonconservative estimate for the reduction in the life of the material by the introduction of a hold-time. An empirical formula of a ''frequency-elastic stress concentration factor modified equation'' was obtained by analysing the experimental data. It predicts accurately the life of the notched specimen tested at different frequencies

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

Dwell Notch Low Cycle Fatigue Behavior of a Powder Metallurgy Nickel Disk Alloy

Science.gov (United States)

Telesman, J.; Gabb, T. P.; Yamada, Y.; Ghosn, L. J.; Jayaraman, N.

2012-01-01

A study was conducted to determine the processes which govern dwell notch low cycle fatigue (NLCF) behavior of a powder metallurgy (P/M) ME3 disk superalloy. The emphasis was placed on the environmentally driven mechanisms which may embrittle the highly stressed notch surface regions and reduce NLCF life. In conjunction with the environmentally driven notch surface degradation processes, the visco-plastic driven mechanisms which can significantly change the notch root stresses were also considered. Dwell notch low cycle fatigue testing was performed in air and vacuum on a ME3 P/M disk alloy specimens heat treated using either a fast or a slow cooling rate from the solutioning treatment. It was shown that dwells at the minimum stress typically produced a greater life debit than the dwells applied at the maximum stress, especially for the slow cooled heat treatment. Two different environmentally driven failure mechanisms were identified as the root cause of early crack initiation in the min dwell tests. Both of these failure mechanisms produced mostly a transgranular crack initiation failure mode and yet still resulted in low NLCF fatigue lives. The lack of stress relaxation during the min dwell tests produced higher notch root stresses which caused early crack initiation and premature failure when combined with the environmentally driven surface degradation mechanisms. The importance of environmental degradation mechanisms was further highlighted by vacuum dwell NLCF tests which resulted in considerably longer NLCF lives, especially for the min dwell tests.

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.

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.

Thermally induced high frequency random amplitude fatigue damage at sharp notches

International Nuclear Information System (INIS)

Lewis, M.W.J.

1992-01-01

Experiments have been performed using the SUPERSOMITE facility to investigate the initiation and growth of fatigue cracks at the tips of sharp surface notches subjected to random thermally-induced stress. The experimental situation is complex involving plasticity, random amplitude loading and heat transfer medium/surface coupling. Crack initiation and growth prediction have been considered using the Creager and Neuber methods to compute the strain ranges in the vicinity of the notch root. Good agreement has been obtained between the experimental results and theoretical predictions. The paper reports the results of the analysis of the notch behavior

Multiaxial fatigue assessment of welded joints using the notch stress approach

DEFF Research Database (Denmark)

Pedersen, Mikkel Melters

2016-01-01

This paper presents an evaluation of the safety involved when performing fatigue assessment of multiaxially loaded welded joints. The notch stress approach according to the IIW is used together with 8 different multiaxial criteria, including equivalent stress-, interaction equation- and critical...... plane approaches. The investigation is carried out by testing the criteria on a large amount of fatigue test results collected from the literature (351 specimens total). Subsequently, the probability of achieving a non-conservative fatigue assessment is calculated in order to evaluate the different...

Fatigue assessment of laserbeam welded PM steel components by the notch stress approach

Energy Technology Data Exchange (ETDEWEB)

Waterkotte, R. [Schaeffler Technologies GmbH and Co. KG, Herzogenaurach (Germany); Sonsino, C.M. [Fraunhofer Institute for Structural Durability and System Reliability LBF, Darmstadt (Germany); Baumgartner, J.

2011-10-15

The local fatigue strength of a laserbeam weld of a complex engine component, which joins a PM with a formed sheet component, was assessed by the notch stress concept with the fictitious reference radius of r{sub ref}= 0.05 mm. First, simplified specimens, following the main geometric dimensions of the parts, were manufactured. On these specimens the fatigue strength was identified by tests and the notch stresses calculated by finite element analysis. Based on these results a design SN-curve was derived to assess the fatigue strength of the engine component. The numerical assessment of the welded joint was verified by proof tests with the component. The assessment could be improved by considering statistical and stress gradient dependent size effects according to the concept of the highly stressed volume. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

The effect of shot peening on notched low cycle fatigue

International Nuclear Information System (INIS)

Soady, K.A.; Mellor, B.G.; Shackleton, J.; Morris, A.; Reed, P.A.S.

2011-01-01

Highlights: → Shot peening improves notched component three point bend low cycle fatigue life. → Notch shape does not affect the efficacy of the peening process. → Strain hardening and residual stress effects need separate consideration. → Loading direction residual stresses do not relax under bend load. - Abstract: The improvement in low cycle fatigue life created by shot peening ferritic heat resistant steel was investigated in components of varying geometries based on those found in conventional power station steam turbine blades. It was found that the shape of the component did not affect the efficacy of the shot peening process, which was found to be beneficial even under the high stress amplitude three point bend loads applied. Furthermore, by varying the shot peening process parameters and considering fatigue life it has been shown that the three surface effects of shot peening; roughening, strain hardening and the generation of a compressive residual stress field must be included in remnant life models as physically separate entities. The compressive residual stress field during plane bending low cycle fatigue has been experimentally determined using X-ray diffraction at varying life fractions and found to be retained in a direction parallel to that of loading and to only relax to 80% of its original magnitude in a direction orthogonal to loading. This result, which contributes to the retention of fatigue life improvement in low cycle fatigue conditions, has been discussed in light of the specific stress distribution applied to the components. The ultimate aim of the research is to apply these results in a life assessment methodology which can be used to justify a reduction in the length of scheduled plant overhauls. This will result in significant cost savings for the generating utility.

Fatigue strength evaluation of friction stir welded aluminium joints using the nominal and notch stress concepts

International Nuclear Information System (INIS)

Barsoum, Z.; Khurshid, M.; Barsoum, I.

2012-01-01

Highlights: ► Fatigue testing and evaluation of friction stir welded butt and overlap joints. ► Evaluation based on nominal and effective notch stress concept. ► Comparison with different design recommendations and codes. ► Higher fatigue strength and SN-slopes is observed. ► New fatigue design recommendations proposed for FSW joints. -- Abstract: In this study the fatigue strength is investigated for Friction Stir Welded (FSW) overlap and butt welded joints in different thicknesses based on nominal and effective notch stress concepts. The fatigue test results are compared with fatigue strength recommendations according to EN 1999-1-3 and International Institute of Welding (IIW). The results are also compared with available published data and Finite Element Analysis (FEA) is carried out to investigate the effect of plate thickness and nugget size on the fatigue strength of overlap joints. 3–3 mm butt welded joints shows the highest fatigue strength in comparison with 3–5 mm butt welded and overlap joints. Slopes of the SN-curves for two different joint types differ from the slope recommended by IIW. A specific failure trend is observed in overlap FSW joints. However, the slopes of the SN-curves are in close agreement with slopes found in EN 1999-1-3. The slopes of various published results and test results presented in this study are in good agreement with each other. The suggested fatigue design curves for the nominal and effective notch stress concept have a higher slope than given for fusion welds by IIW.

Simulation of Fatigue Crack Initiation at Corrosion Pits With EDM Notches

Science.gov (United States)

Smith, Stephen W.; Newman, John A.; Piascik, Robert S.

2003-01-01

Uniaxial fatigue tests were conducted to compare the fatigue life of laboratory produced corrosion pits, similar to those observed in the shuttle main landing gear wheel bolt-hole, and an electro-discharged-machined (EDM) flaw. EDM Jaws are used to simulate corrosion pits during shuttle wheel (dynamometer) testing. The aluminum alloy, (AA 7050) laboratory fatigue tests were conducted to simulate the local stress level contained in the wheel bolt-hole. Under this high local stress condition, the EDM notch produced a fatigue life similar to test specimens containing corrosion pits of similar size. Based on the laboratory fatigue test results, the EDM Jaw (semi-circular disc shaped) produces a local stress state similar to corrosion pits and can be used to simulate a corrosion pit during the shuttle wheel dynamometer tests.

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

Detection and closure measurement of short fatigue crack initiated at notch root

International Nuclear Information System (INIS)

Lee, Jong-Hyung; Kobayashi, Hideo

1985-01-01

Short fatigue cracks initiated at the notch root were successfully detected at a fairly high accuracy by the ultrasonic amplitude calibration method for the notched compact specimens of an A508-3 steel. Crack closure measurements by the ultrasonic and back-face strain compliance methods were also performed. Crack growth characteristics at the notch root are similar to those of delyed retardation caused by a single peak overload. Also, transitional behavior from short cracks to long cracks was interpreted in terms of effective stress intensity ΔKsub(eff). The relation between crack growth rate da/dN and ΔKsub(eff) for short cracks shows a fairly good agreement with those for long cracks. (author)

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)

Potential fatigue strength improvement of AA 5083-H111 notched parts by wire brush hammering: Experimental analysis and numerical simulation

International Nuclear Information System (INIS)

Sidhom, Naziha; Moussa, Naoufel Ben; Janeb, Sameh; Braham, Chedly; Sidhom, Habib

2014-01-01

Highlights: • Wire brush hammering increases by 20% the AA 5083-H111 notched parts fatigue limit. • Improvement of fatigue strength is related to the fatigue cracks nucleation. • Fatigue strength prediction accounts for wire brush hammering effects. - Abstract: The effects of milling as machining process and a post-machining treatment by wire-brush hammering, on the near surface layer characteristics of AA 5083-H111 were investigated. Surface texture, work-hardening and residual stress profiles were determined by roughness measurement, scanning electron microscope (SEM) examinations, microhardness and X-ray diffraction (XRD) measurements. The effects of surface preparation on the fatigue strength were assessed by bending fatigue tests performed on notched samples for two loading stress ratios R 0.1 and R 0.5 . It is found that the bending fatigue limit at R 0.1 and 10 7 cycles is 20% increased, with respect to the machined surface, by wire-brush hammering. This improvement was discussed on the basis of the role of surface topography, stabilized residual stress and work-hardening on the fatigue-crack network nucleation and growth. The effects biaxial residual stress field and surface work-hardening were taken into account in the finite element model. A multi-axial fatigue criterion was proposed to predict the fatigue strength of aluminum alloy notched parts for both machined and treated states

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.

Fatigue Assessment of High Strength Steel Welded Joints Under Bending Loading

International Nuclear Information System (INIS)

Lee, Myeong-Woo; Kim, Yun-Jae; Park, Jun-Hyub

2014-01-01

In this study, a fatigue assessment method for vehicle suspension systems having welded geometries was established under a bending loading condition. For the fatigue life estimation of the actual product s welded joints made of different steels, bending fatigue tests were performed on welded specimens with a simplified shape for obtaining the moment-fatigue-life plot. Further, geometry modeling of the simplified welded specimens was conducted. Results of finite element analysis were used to obtain the stress-fatigue-life plot. The analysis results were also used to calculate the stress concentration factors for notch-factor-based fatigue life estimation. The test results were compared with results of the general notch-factor-based fatigue life estimation for improving fatigue assessment. As a result, it was concluded that both the welded fatigue tests and the notch-factor-based fatigue life estimation are necessary for accurate fatigue assessment

Fatigue life evaluation based on welding residual stress relaxation and notch strain approach for cruciform welded joint

International Nuclear Information System (INIS)

Han, Jeong Woo; Han, Seung Ho; Shin, Byung Chun; Kim, Jae Hoon

2003-01-01

The fatigue strength of welded joint is influenced by the welding residual stress which is relaxed depending on local stress distributed in vicinity of stress raisers, eg. under cut, overlap and blow hole. To evaluate its fatigue life the geometry of the stress raisers and the welding residual stress should be taken into account. The several methods based on notch strain approach have been proposed in order to consider the two factors above mentioned. These methods, however, have shown considerable differences between analytical and experimental results. It is due to the fact that the amount of the relaxed welding residual stress evaluated by the cyclic stress-strain relationship do not correspond with that occurred in reality. In this paper the residual stress relaxation model based on experimental results was used in order to reduce the discrepancy of the estimated amount of the relaxed welding residual stress. Under an assumption of the superimposition of the relaxed welding residual stress and the local stress, a modified notch strain approach was proposed and verified to the cruciform welded joint

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

Directory of Open Access Journals (Sweden)

José Alexander Araújo

2010-10-01

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

Study on deformation behavior and life evaluation method for SUS304 notched plate under bending creep fatigue loading

International Nuclear Information System (INIS)

Fukuda, Yoshio; Satoh, Yoshimi; Nakamura, Kazuhiro; Takahashi, Yukio; Kuwabara, Kazuo.

1990-01-01

Creep-fatigue tests were carried out on notched plates under cyclic bending loads out of plane at 550degC, and the local strain at the notch-root and micro crack propagation behavior were measured. Then, inelastic analysis was performed for the experiment by using three kinds of constitutive models, such as kinematic hardening, ORNL and Ohno models. From the comparison of the experiment with the results of analysis, the following conclusions were obtained. (1) Creep strain caused at the notch-root during load holding was negligibly small compared with plastic strain, so that the neighborhood of the notch-root is subjected to constrained strain type damage. (2) The strain range at the notch-root can be calculated from the results of elastic-plastic analysis for monotonic loading independent of the constitutive models used, where the cyclic stress-strain relationship was used as the material monotonic deformation property. (3) The mean strain calculated was consistent with the experimental value in case of kinematic hardening or ORNL model, while not in case of Ohno model. (4) A method for predicting the crack initiation life of a notched plate has been proposed on the basis of micro-crack propagation behavior obtained by a fundamental creep-fatigue test. (author)

Influence of specimen thickness on the fatigue behavior of notched steel plates subjected to laser shock peening

Science.gov (United States)

Granados-Alejo, V.; Rubio-González, C.; Vázquez-Jiménez, C. A.; Banderas, J. A.; Gómez-Rosas, G.

2018-05-01

The influence of specimen thickness on the fatigue crack initiation of 2205 duplex stainless steel notched specimens subjected to laser shock peening (LSP) was investigated. The purpose was to examine the effectiveness of LSP on flat components with different thicknesses. For the LSP treatment a Nd:YAG pulsed laser operating at 10 Hz with 1064 nm of wavelength was used; pulse density was 2500 pulses/cm2. The LSP setup was the waterjet arrangement without sample coating. Residual stress distribution as a function of depth was determined by the hole drilling method. Notched specimens 2, 3 and 4 mm thick were LSP treated on both faces and then fatigue loading was applied with R = 0.1. Experimental fatigue lives were compared with life predictions from finite element simulation. A good comparison of the predicted and experimental fatigue lives was observed. LSP finite element simulation helps in explaining the influence of thickness on fatigue lives in terms of equivalent plastic strain distribution variations associated with the change in thickness. It is demonstrated that specimen size effect is an important issue in applying LSP on real components. Reducing the specimen thickness, the fatigue life improvement induced by LSP is significantly increased. Fatigue life extension up to 300% is observed on thin specimens with LSP.

Fatigue Strength of Weathering Steel

Czech Academy of Sciences Publication Activity Database

Kunz, Ludvík; Lukáš, Petr; Klusák, Jan

2012-01-01

Roč. 18, č. 1 (2012), s. 18-22 ISSN 1392-1320 Grant - others:GA MPO(CZ) FT/TA5/076 Institutional support: RVO:68081723 Keywords : fatigue of weathering steel * corrosion pits * fatigue notch factor Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.522, year: 2012

Fatigue of coated and laser hardened steels

International Nuclear Information System (INIS)

La Cruz, P. de.

1990-01-01

In the present work the effect of ion nitriding, laser hardening and hot dip galvanizing upon the fatigue limit and notch sensitivity of a B-Mn Swedish steel SS 2131 have been investigated. The fatigue tests were performed in plane reverse bending fatigue (R=1). The quenched and tempered condition was taken as the reference condition. The microstructure, microhardness, fracture surface and coating appearance of the fatigue surface treated specimens were studied. Residual stress and retained austenite measurements were also carried out. It was found that ion nitriding improves the fatigue limit by 53 % for smooth specimens and by 115 % for notched specimens. Laser hardening improves the fatigue limit by 18 % and 56 % for smooth and notched specimen respectively. Hot dip galvanizing gives a slight deterioration of the fatigue limit (9 % and 10 % for smooth and notched specimen respectively). Ion nitriding and laser hardening decrease the value of the notch sensitivity factor q by 78 % and 65 % respectively. Hot dip galvanizing does not modify it. A simple schematic model based on a residual stress distribution, has been used to explain the different effects. It seems that the presence of the higher compressive residual stresses and the higher uniformity of the microstructure may be the causes of the better fatigue performance of ion nitrided specimens. (119 refs.) (author)

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

Directory of Open Access Journals (Sweden)

Reza H Oskouei

2016-02-01

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

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

A comparison of conventional local approach and the short crack approach to fatigue crack initiation at a notch

Energy Technology Data Exchange (ETDEWEB)

Ranganathan, Narayanaswami; Leroy, Rene; Tougui, Abdellah [Laboratoire de Mecanique et Rheologie, Universite Francois Rabelais de Tours, Polytech Tours, Departement Mecanique et Conception de Systemes, Tours (France)

2009-09-15

Methods to estimate fatigue crack initiation life at a notch tip are compared. The methods used determine the strain amplitudes at the notch tip using Neuber's or Glinka's approximation. In conventional approaches, equivalent-damage levels are determined, using appropriate strain-life relationships coupled with damage-summation models. In the short-crack approach, a crack-like defect is assumed to exist at the notch tip. It is shown that the short-crack concept can be successfully applied to predict crack-initiation behavior at a notch. Model predictions are compared with carefully designed experiments. It is shown that model predictions are very close to experimentally measured lives under an aircraft-wing loading spectrum. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

Advanced methods of fatigue assessment

CERN Document Server

Radaj, Dieter

2013-01-01

The book in hand presents advanced methods of brittle fracture and fatigue assessment. The Neuber concept of fictitious notch rounding is enhanced with regard to theory and application. The stress intensity factor concept for cracks is extended to pointed and rounded corner notches as well as to locally elastic-plastic material behaviour. The averaged strain energy density within a circular sector volume around the notch tip is shown to be suitable for strength-assessments. Finally, the various implications of cyclic plasticity on fatigue crack growth are explained with emphasis being laid on the DJ-integral approach.   This book continues the expositions of the authors’ well known reference work in German language ‘Ermüdungsfestigkeit – Grundlagen für Ingenieure’ (Fatigue strength – fundamentals for engineers).

Simplified elastoplastic methods of analysing fatigue in notches

International Nuclear Information System (INIS)

Autrusson, B.

1993-01-01

The aim of this study is to show the state of the art concerning methods of mechanical analysis available in the literature for evaluating notch root elastoplastic strain. The components of fast breeder reactors are subjected to numerous thermal transients, which can cause fatigue failure. To prevent this from happening, it is necessary to know the local strain range and to use it to estimate the number of cycles to crack initiation. Practical methods have been developed for the calculation of the local strain range, and have led to the drafting of design rules. Direct methods of determining the local strain range of the 'inelastic analysis' type have also been described. In conclusion a series of recommendations is made on the applicability and the conservatism of these methods

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

Fatigue-creep life prediction for a notched specimen of 2[1]/[4]Cr-1Mo steel at 600 C

International Nuclear Information System (INIS)

Inoue, Tatsuo; Sakane, Masao; Fukuda, Yoshio; Igari, Toshihide; Miyahara, Mitsuo; Okazaki, Masakazu

1994-01-01

This paper presents the life prediction of 2[1]/[4]Cr-1Mo notched specimens subjected to fast-fast, slow-slow and hold-time loadings at 600 C. The crack initiation lives of notched specimens were estimated based on the local stress-strain calculated by inelastic finite element analyses. For the life prediction, combinations of seven different constitutive models and five fatigue-creep damage laws were used. The applicability of the constitutive model and damage law is discussed. The constitutive models predict similar stress-strain relations at the notch root, leading to similar predicted lives. The damage model, however, has a much larger influence on the life prediction. ((orig.))

Re-analysis of fatigue data for welded joints using the notch stress approach

DEFF Research Database (Denmark)

Pedersen, Mikkel Melters; Mouritsen, Ole Ø.; Hansen, Michael Rygaard

2010-01-01

Experimental fatigue data for welded joints have been collected and subjected to re-analysis using the notch stress approach according to IIW recommendations. This leads to an overview regarding the reliability of the approach, based on a large number of results (767 specimens). Evidently......-welded joints agree quite well with the FAT 225 curve; however a reduction to FAT 200 is suggested in order to achieve approximately the same safety as observed in the nominal stress approach....

Fatigue behaviour of friction welded medium carbon steel and austenitic stainless steel dissimilar joints

International Nuclear Information System (INIS)

Paventhan, R.; Lakshminarayanan, P.R.; Balasubramanian, V.

2011-01-01

Research highlights: → Fusion welding of dissimilar metals is a problem due to difference in properties. → Solid state welding process such as friction welding is a solution for the above problem. → Fatigue life of friction welded carbon steel and stainless steel joints are evaluated. → Effect of notch on the fatigue life of friction welded dissimilar joints is reported. → Formation of intermetallic is responsible for reduction in fatigue life of dissimilar joints. -- Abstract: This paper reports the fatigue behaviour of friction welded medium carbon steel-austenitic stainless steel (MCS-ASS) dissimilar joints. Commercial grade medium carbon steel rods of 12 mm diameter and AISI 304 grade austenitic stainless steel rods of 12 mm diameter were used to fabricate the joints. A constant speed, continuous drive friction welding machine was used to fabricate the joints. Fatigue life of the joints was evaluated conducting the experiments using rotary bending fatigue testing machine (R = -1). Applied stress vs. number of cycles to failure (S-N) curve was plotted for unnotched and notched specimens. Basquin constants, fatigue strength, fatigue notch factor and notch sensitivity factor were evaluated for the dissimilar joints. Fatigue strength of the joints is correlated with microstructure, microhardness and tensile properties of the joints.

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.

Fatigue damage mechanics of notched graphite-epoxy laminates

Science.gov (United States)

Spearing, Mark; Beaumont, Peter W. R.; Ashby, Michael F.

A modeling approach is presented that recognizes that the residual properties of composite laminates after any form of loading depend on the damage state. Therefore, in the case of cyclic loading, it is necessary to first derive a damage growth law and then relate the residual properties to the accumulated damage. The propagation of fatigue damage in notched laminates is investigated. A power law relationship between damage growth and the strain energy release rate is developed. The material constants used in the model have been determined in independent experiments and are invariant for all the layups investigated. The strain energy release rates are calculated using a simple finite element representation of the damaged specimen. The model is used to predict the effect of tension-tension cyclic loading on laminates of the T300/914C carbon-fiber epoxy system. The extent of damage propagation is successfully predicted in a number of cross-ply laminates.

Comparison of Fatigue Properties and Fatigue Crack Growth Rates of Various Implantable Metals

Science.gov (United States)

Okazaki, Yoshimitsu

2012-01-01

The fatigue strength, effects of a notch on the fatigue strength, and fatigue crack growth rate of Ti-15Zr-4Nb-4Ta alloy were compared with those of other implantable metals. Zr, Nb, and Ta are important alloying elements for Ti alloys for attaining superior long-term corrosion resistance and biocompatibility. The highly biocompatible Ti-15Zr-4Nb-4Ta alloy exhibited an excellent balance between strength and ductility. Its notched tensile strength was much higher than that of a smooth specimen. The strength of 20% cold-worked commercially pure (C.P.) grade 4 Ti was close to that of Ti alloy. The tension-to-tension fatigue strength of an annealed Ti-15Zr-4Nb-4Ta rod at 107 cycles was approximately 740 MPa. The fatigue strength of this alloy was much improved by aging treatment after solution treatment. The fatigue strengths of C.P. grade 4 Ti and stainless steel were markedly improved by 20% cold working. The fatigue strength of Co-Cr-Mo alloy was markedly increased by hot forging. The notch fatigue strengths of 20% cold-worked C.P. grade 4 Ti, and annealed and aged Ti-15Zr-4Nb-4Ta, and annealed Ti-6Al-4V alloys were less than those of the smooth specimens. The fatigue crack growth rate of Ti-15Zr-4Nb-4Ta was the same as that of Ti-6Al-4V. The fatigue crack growth rate in 0.9% NaCl was the same as that in air. Stainless steel and Co-Cr-Mo-Ni-Fe alloy had a larger stress-intensity factor range (ΔK) than Ti alloy.

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

Stress Concentration Factor and Stress Intensity Factor with U-notch and Crack in the Beam

Energy Technology Data Exchange (ETDEWEB)

Seo, Bo Seong; Lee, Kwang Ho [Kyungpook National Univ., Daegu (Korea, Republic of)

2016-05-15

The stress concentration factors and stress intensity factors for a simple beam and a cantilever are analyzed by using finite element method and photoelasticity. Using the analyzed results, the estimated graphs on stress concentration factors and stress intensity factors are obtained. To analyze stress concentration factors of notch, the dimensionless notch length H(height of specimen)/h=1.1-2 and dimensionless gap space r(radius at the notch tip)/h=0.1~0.5 are used, where h=H-c and c is the notch length. As the notch gap length increases and the gap decreases, the stress concentration factors increase. Stress concentration factors of a simple beam are greater than those of a cantilever beam. However, actually, the maximum stress values under a load, a notch length and a gap occur more greatly in the cantilever beam than in the simple beam. To analyze stress intensity factors, the normalized crack length α(crack length)/H=0.2~0.5 is used. As the length of the crack increases, the normalized stress intensity factors increase. The stress intensity factors under a constant load and a crack length occur more greatly in the cantilever beam than in the simple beam.

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.

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.

Oxidation and the Effects of High Temperature Exposures on Notched Fatigue Life of an Advanced Powder Metallurgy Disk Superalloy

Science.gov (United States)

Sudbrack, Chantal K.; Draper, Susan L.; Gorman, Timothy T.; Telesman, Jack; Gab, Timothy P.; Hull, David R.

2012-01-01

Oxidation and the effects of high temperature exposures on notched fatigue life were considered for a powder metallurgy processed supersolvus heat-treated ME3 disk superalloy. The isothermal static oxidation response at 704 C, 760 C, and 815 C was consistent with other chromia forming nickel-based superalloys: a TiO2-Cr2O3 external oxide formed with a branched Al2O3 internal subscale that extended into a recrystallized - dissolution layer. These surface changes can potentially impact disk durability, making layer growth rates important. Growth of the external scales and dissolution layers followed a cubic rate law, while Al2O3 subscales followed a parabolic rate law. Cr- rich M23C6 carbides at the grain boundaries dissolved to help sustain Cr2O3 growth to depths about 12 times thicker than the scale. The effect of prior exposures was examined through notched low cycle fatigue tests performed to failure in air at 704 C. Prior exposures led to pronounced debits of up to 99 % in fatigue life, where fatigue life decreased inversely with exposure time. Exposures that produced roughly equivalent 1 m thick external scales at the various isotherms showed statistically equivalent fatigue lives, establishing that surface damage drives fatigue debit, not exposure temperature. Fractographic evaluation indicated the failure mode for the pre-exposed specimens involved surface crack initiations that shifted with exposure from predominately single intergranular initiations with transgranular propagation to multi-initiations from the cracked external oxide with intergranular propagation. Weakened grain boundaries at the surface resulting from the M23C6 carbide dissolution are partially responsible for the intergranular cracking. Removing the scale and subscale while leaving a layer where M23C6 carbides were dissolved did not lead to a significant fatigue life improvement, however, also removing the M23C6 carbide dissolution layer led to nearly full recovery of life, with a

Mechanical factors affecting reliability of pressure components (fatigue, cracking)

International Nuclear Information System (INIS)

Lebey, J.; Garnier, C.; Roche, R.; Barrachin, B.

1978-01-01

The reliability of a pressure component can be seriously affected by the formation and development of cracks. The experimental studies presented in this paper are devoted to three different aspects of crack propagation phenomena which have been relatively little described. In close connection with safety analyses of PWR, the authors study the influence of the environment by carrying out fatigue tests with samples bathed in hot pressurized water. Ferritic, austenitic and Incolloy 800 steels were used and the results are presented in the form of fatigue curves in the oligocyclic region. The second part of the paper relates to crack initiation cirteria in ductile steels weakened by notches. The CT samples used make it possible to study almost all types of fracture (ductile, intermediate and brittle). The use of two criteria based on the load limit and on the toughness of the material constitutes a practical way of evaluating crack propagation conditions. A series of tests carried out on notched spherical vessels of different size shows that large vessels are relatively brittle; fast unstable fracture is observed as size increases. Crack growth rate in PWR primary circuits (3/6 steel) is studied on piping elements (0.25 scale) subjected to cyclic stress variations (285 0 C and with pressure varying between 1 and 160 bar in each cycle). By calculating the stress intensity factor, correlation with results obtained in the laboratory on CT samples is possible. (author)

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

Study on Fatigue Characteristics of High-Strength Steel Welds

Energy Technology Data Exchange (ETDEWEB)

Chang, Hong Suk; Yoo, Seung Won; Park, Jong Chan [Hyundai Motor Group, Seoul (Korea, Republic of)

2015-03-15

High-strength steel has replaced mild steel as the material of choice for truck decks or frames, owing to the growing demand for lightweight vehicles. Although studies on the weld fatigue characteristics of mild steel are available, studies on high-strength steels have been seldom conducted. In this study, firstly, we surveyed a chosen number of approaches and selected the Radaj method, which uses the notch factor approach, as the one suitable for evaluating the fatigue life of commercial vehicles. Secondly, we obtained the S-N curves of HARDOX and ATOS60 steel welds, and the F-N curves of the T-weld and overlapped-weld structures. Thirdly, we acquired a general S-N curve of welded structures made of high-strength steel from the F-N curve, using the notch factor approach. Fourthly, we extracted the weld fatigue characteristics of high-strength steel and incorporated the results in the database of a commercial fatigue program. Finally, we compared the results of the fatigue test and the CAE prediction of the example case, which demonstrated sufficiently good agreement.

Fatigue crack growth in austenitic stainless steel piping

International Nuclear Information System (INIS)

Bethmont, M.; Cheissoux, J.L.; Lebey, J.

1981-04-01

The study presented in this paper is being carried out with a view to substantiating the calculations of the fatigue crack growth in pipes made of 316 L stainless steel. The results obtained may be applied to P.W.R. primary piping. It is divided into two parts. First, fatigue tests (cyclic pressure) are carried out under hot and cold conditions with straight pipes machined with notches of various dimensions. The crack propagation and the fatigue crack growth rate are measured here. Second, calculations are made in order to interpret experimental results. From elastic calculations the stress intensity factor is assessed to predict the crack growth rate. The results obtained until now and presented in this paper relate to longitudinal notches

Investigating the effect of clamping force on the fatigue life of bolted plates using volumetric approach

International Nuclear Information System (INIS)

Esmaeili, F.; Chakherlou, T. N.; Zehsaz, M.; Hasanifard, S.

2013-01-01

In this paper, the effects of bolt clamping force on the fatigue life for bolted plates made from Al7075-T6 have been studied on the values of notch strength reduction factor obtained by volumetric approach. To attain stress distribution around the notch (hole) which is required for volumetric approach, nonlinear finite element simulations were carried out. To estimate the fatigue life, the available smooth S-N curve of Al7075-T6 and the notch strength reduction factor obtained from volumetric method were used. The estimated fatigue life was compared with the available experimental test results. The investigation shows that there is a good agreement between the life predicted by the volumetric approach and the experimental results for various specimens with different amount of clamping forces. Volumetric approach and experimental results showed that the fatigue life of bolted plates improves because of the compressive stresses created around the plate hole due to clamping force.

The effect of a free surface on fatigue crack behaviour

Czech Academy of Sciences Publication Activity Database

Hutař, Pavel; Náhlík, Luboš; Knésl, Zdeněk

2010-01-01

Roč. 32, č. 8 (2010), s. 1265-1269 ISSN 0142-1123 R&D Projects: GA ČR GA106/09/1954; GA ČR GA101/09/0867 Institutional research plan: CEZ:AV0Z20410507 Keywords : Vertex singularity * Generalized stress intenzity factor * Stress singularity * Fatigue crack * V- notch Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 1.799, year: 2010

Nanoscale and submicron fatigue crack growth in nickel microbeams

International Nuclear Information System (INIS)

Yang, Y.; Yao, N.; Imasogie, B.; Soboyejo, W.O.

2007-01-01

This paper presents a novel edge-notched microbeam technique for the study of short fatigue crack growth. The technique is used to study submicron and nanoscale fatigue in LIGA Ni thin films with columnar microstructures. The edge-notched microbeams were fabricated within LIGA Ni thin films, using focused ion beam (FIB) techniques. The microbeams were then cyclically deformed to failure at a stress ratio of 0.1. Different slip-band structures were observed below the nanoscale notches. Cyclic deformation resulted in the formation of primary slip bands below the notch. Subsequent crack growth then occurred by the unzipping of fatigue cracks along intersecting slip bands. The effects of the primary slip bands were idealized using dislocation-based models. These were used to estimate the intrinsic fatigue threshold and the fatigue endurance limit. The estimates from the model are shown to be consistent with experimental data from prior stress-life experiments and current/prior fatigue threshold estimates

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.

Fatigue damage mechanism and strength of woven laminates

International Nuclear Information System (INIS)

Xiao, J.; Bathias, C.

1993-01-01

The apparent secant stiffness changes with the cyclic number for both unnotched and notched woven laminated specimens (two orthotropic and one quasi-isotropic) during tensile fatigue test at a fixed ratio of maximum fatigue load to UTS were observed. The observable damage initiation and evolution as a function of the cyclic number were directly measured at the notched specimen surface with a video-camera system. The fatigue strengths of the unnotched and notched specimens were determined. The results show that the normalized apparent secant stiffness change curves as a function of cyclic numbers can be divided into three stages. For the first and the second stages in notched specimens and for total life of unnotched specimens, the damage has not been evidently observed and certainly verified with the traditional experimental methods such as radiography and microscopy although many acoustic emission signals can be obtained. The last stage for the notched specimens (N/Nf>0.4, the secant stiffness decreases fast) corresponds to the initiation and evolution of the observable damages. The fatigue strength of these woven composite laminates is dominated by the third stage during which the observable damage develops along the specimen ligament until fracture. During the third stage, a critical dimension at the specimen ligament and a life threshold can be found beyond which a final catastrophic fracture will immediately occur. The quasi-isotropic laminate is of a fatigue strength lower than the two orthotropic laminates of which the fatigue strengths are approaching to each other. The fatigue life is also influenced by the stacking sequences. (orig.)

Fatigue of non-welded pressure vessels made of high strength steel

International Nuclear Information System (INIS)

Rauscher, F.

2003-01-01

When using high strength steels for pressure vessels, cyclic fatigue requirements may become decisive for the design. Within a European research project, two typical non-welded types of vessels--gas cylinders as used for gas transportation and hydraulic accumulators with screwed in ends--were investigated. The results of the fatigue analyses and of the testing of these vessels are described here. Special attention is drawn to the evaluation of the stresses in the threads used for threaded in flat ends and rings, because the usual formulae for bolted connections cannot be used. In the case of sharp notches and of threads, the experiments showed that the fatigue calculation gave conservative results. The unexpected failure of the gas cylinders in the cylindrical part and at the onset of the end showed that the fatigue analyses according to prEN13445-3 clause 18 is non-conservative for these surfaces without mechanical preparation, and need special consideration. Based on the investigations, a stress concentration factor for small fabrication notches and a new surface finish factor is proposed

Fatigue of non-welded pressure vessels made of high strength steel

Energy Technology Data Exchange (ETDEWEB)

Rauscher, F

2003-03-01

When using high strength steels for pressure vessels, cyclic fatigue requirements may become decisive for the design. Within a European research project, two typical non-welded types of vessels--gas cylinders as used for gas transportation and hydraulic accumulators with screwed in ends--were investigated. The results of the fatigue analyses and of the testing of these vessels are described here. Special attention is drawn to the evaluation of the stresses in the threads used for threaded in flat ends and rings, because the usual formulae for bolted connections cannot be used. In the case of sharp notches and of threads, the experiments showed that the fatigue calculation gave conservative results. The unexpected failure of the gas cylinders in the cylindrical part and at the onset of the end showed that the fatigue analyses according to prEN13445-3 clause 18 is non-conservative for these surfaces without mechanical preparation, and need special consideration. Based on the investigations, a stress concentration factor for small fabrication notches and a new surface finish factor is proposed.

Quantitative x-ray fractographic analysis of fatigue fractures

International Nuclear Information System (INIS)

Saprykin, Yu.V.

1983-01-01

The study deals with quantitative X-ray fractographic investigation of fatigue fractures of samples with sharp notches tested at various stresses and temperatures with the purpose of establishing a connection between material crack resistance parameters and local plastic instability zones restraining and controlling the crack growth. At fatigue fractures of notched Kh18N9T steel samples tested at +20 and -196 deg C a zone of sharp ring notch effect being analogous to the zone in which crack growth rate is controlled by the microshifting mechanisms is singled out. The size of the notched effect zone in the investigate steel is unambiguosly bound to to the stress amplitude. This provides the possibility to determine the stress value by the results of quantitative fractographic analysis of notched sample fractures. A possibility of determining one of the threshold values of cyclic material fracture toughness by the results of fatigue testing and fractography of notched sample fractures is shown. Correlation between the size of the hsub(s) crack effect zone in the notched sample, delta material yield limit and characteristic of cyclic Ksub(s) fracture toughness has been found. Such correlation widens the possibilities of quantitative diagnostics of fractures by the methods of X-ray fractography

Corrosion fatigue of steels

International Nuclear Information System (INIS)

Spaehn, H.; Wagner, G.H.

1976-01-01

Corrosion fatigue phenomena can be classified into two main groups according to the electrochemical state of the metal surface in the presence of electrolytes: the active and the passive state with an important sub-group of corrosion fatigue in the unstable passive state. The allowable stress for structures exposed to the conjoint action of corrosion and fatigue is influenced by many factors: kind of media, number of cycles, frequency, mean stress, size, notches, loading mode, alloy composition and mechanical strength. A critical literature review shows contradictory results if a classification by the electrochemical surface state is not applied. Case histories and counter measures illustrate the practical importance of corrosion fatigue in many branches of industry as well as the urgent need for a better knowledge about the mutual influence of the phenomena to get rules by which the engineer can appraise the risk of corrosion fatigue. (orig.) [de

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

Effects of stress concentrations on the fatigue life of a gamma based titanium aluminide

International Nuclear Information System (INIS)

Trail, S.J.; Bowen, P.

1995-01-01

S-N curves for a gamma based titanium aluminide alloy of composition Ti-47.2Al-2.1Mn-1.9Nb(at.%)+2TiB 2 (wt.%) have been used to define fatigue life. Effects of residual stress, stressed volume, loading ratio, loading mode, elevated temperature and surface roughness have been considered. Residual tensile stresses and micro-cracking are introduced by Electro Discharge Machining and the fatigue life is reduced slightly compared with polished samples. Notched fatigue tests show a significant notch strengthening effect which increases with increasing stress concentration factor. The fracture surfaces of specimens tested at room temperature reveal fully brittle failure mechanisms and no evidence of stable crack growth is observed. The fatigue life appears, therefore, to be determined predominantly by the number of cycles to crack initiation. At the elevated temperature of 830 C, evidence for some stable fatigue crack growth has been found. Probable sites for crack initiation are addressed

Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

NARCIS (Netherlands)

Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

2008-01-01

Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

Response of notched AS4/PEEK laminates to tension/compression loading

Science.gov (United States)

Simonds, Robert A.; Stinchcomb, Wayne W.

1989-01-01

Fatigue life, damage-initiation and propagation, and residual strength data are presently examined to ascertain the response of notched AS4/PEEK specimens to fully reversed tension/compression loading. Stiffness measurements made during the low-level fatigue history show that compression stiffness and tension stiffness degrade throughout the fatigue life. Damage to specimens fatigued at higher cyclic stresses developed primarily in the direction perpendicular to the loading. As in the case of specimens fatigued at lower stress levels, residual compressive stress decreased with damage development.

The interaction between non-metallic inclusions and surface roughness in fatigue failure and their influence on fatigue strength

International Nuclear Information System (INIS)

Saberifar, S.; Mashreghi, A.R.; Mosalaeepur, M.; Ghasemi, S.S.

2012-01-01

Highlights: ► The fatigue strength of a tested steel was affected by inclusions and surface notches. ► Inclusions were the main fatigue crack sources even in rough specimens. ► The stress intensity factor represented the behavior of inclusions properly. ► In rough steels the effect of inclusions was intensified by surface roughness. ► The critical inclusion size increased when surface roughness was removed. -- Abstract: In this study, the influence of non-metallic inclusions on the fatigue behavior of 30MnVS6 steel containing different inclusion sizes and surface roughness has been investigated. Scanning electron microscope (SEM) was used to examine fatigue fracture origins. It was concluded that the non-metallic inclusions were dominant fatigue crack initiation sites in both smooth and rough specimens. This was justified by the calculation of stress intensity factor generated by both surface roughness and non-metallic inclusions, based on Murakami’s model. In addition, it was found that for a given stress, the critical inclusion size could be increased by eliminating the surface roughness.

In situ observation of fatigue crack initiation and propagation behavior of a high-Nb TiAl alloy at 750 °C

Energy Technology Data Exchange (ETDEWEB)

Min, Zhang [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Xi-ping, Song, E-mail: xpsong@skl.ustb.edu.cn [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Long, Yu; Hong-liang, Li [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Ze-hui, Jiao; Hui-chen, Yu [National Key Laboratory of Science and Technology on Advanced High Temperature Structural Materials, Beijing Institute of Aeronautical Materials, Beijing 100095 (China)

2015-01-12

In this paper, the fatigue crack initiation and propagation behavior of a high-Nb TiAl alloy with nearly lamellar microstructure was studied by in situ scanning electron microscope observation at 750 °C. Dog-bone shaped specimens with a single-edge notch were used in the test. The results showed that the fatigue crack initiated first at the central portion of the notch, and then shifted to the edge portion. As the cycle numbers went on increasing, these cracks joined together and formed a main fatigue crack, which could propagate along the surface of the specimen. During the fatigue crack propagation two or three propagation stages were found depending on the microstructure of the crack tip. When the fatigue crack was parallel to the lamellar laths, it exhibited the rapid, steady and accelerated propagation stages successively, while when the fatigue crack was perpendicular to the lamellar laths, it exhibited only the steady and accelerated propagation stages, with no rapid propagation stage being found. In these different propagation stages the fatigue crack propagation rates were different and depended intensively on the lamellar laths orientation, lamellar colony size, equiaxed gamma grains and peak stress intensity factor K{sub max}. Based on the experimental data it was concluded that the fatigue crack initiation lifetime was much longer than the propagation lifetime for the single-edge notched specimens at 750 °C.

In situ observation of fatigue crack initiation and propagation behavior of a high-Nb TiAl alloy at 750 °C

International Nuclear Information System (INIS)

Min, Zhang; Xi-ping, Song; Long, Yu; Hong-liang, Li; Ze-hui, Jiao; Hui-chen, Yu

2015-01-01

In this paper, the fatigue crack initiation and propagation behavior of a high-Nb TiAl alloy with nearly lamellar microstructure was studied by in situ scanning electron microscope observation at 750 °C. Dog-bone shaped specimens with a single-edge notch were used in the test. The results showed that the fatigue crack initiated first at the central portion of the notch, and then shifted to the edge portion. As the cycle numbers went on increasing, these cracks joined together and formed a main fatigue crack, which could propagate along the surface of the specimen. During the fatigue crack propagation two or three propagation stages were found depending on the microstructure of the crack tip. When the fatigue crack was parallel to the lamellar laths, it exhibited the rapid, steady and accelerated propagation stages successively, while when the fatigue crack was perpendicular to the lamellar laths, it exhibited only the steady and accelerated propagation stages, with no rapid propagation stage being found. In these different propagation stages the fatigue crack propagation rates were different and depended intensively on the lamellar laths orientation, lamellar colony size, equiaxed gamma grains and peak stress intensity factor K max . Based on the experimental data it was concluded that the fatigue crack initiation lifetime was much longer than the propagation lifetime for the single-edge notched specimens at 750 °C

Design rule for fatigue of welded joints in elevated-temperature nuclear components

International Nuclear Information System (INIS)

O'Connor, D.G.; Corum, J.M.

1986-01-01

Elevated-temperature weldment fatigue failures have occurred in several operating liquid-metal reactor plants. Yet, ASME Code Case N-47, which governs the design of such plants in the United States, does not currently address the Code Subgroup on Elevated Temperature Design recently proposed a fatigue strength reduction factor for austenitic and ferritic steel weldments. The factor is based on a variety of weld metal and weldment fatigue data generated in the United States, Europe, and Japan. This paper describes the factor and its bases, and it presents the results of confirmatory fatigue tests conducted at Oak Ridge National Laboratory on 316 stainless steel tubes with axial and circumferential welds of 16-8-2 filler metal. These test results confirm the suitability of the design factor, and they support the premise that the metallurgical notch effect produced by yield strength variations across a weldment is largely responsible for the observed elevated-temperature fatigue strength reduction

Determination of the threshold values of orthotropic bi-material notches

Czech Academy of Sciences Publication Activity Database

Klusák, Jan; Profant, T.; Kotoul, M.

2010-01-01

Roč. 2, č. 1 (2010), s. 1635-1642 E-ISSN 1877-7058. [Fatigue 2010. Praha, 06.06.2010-11.06.2010] R&D Projects: GA ČR GA101/08/0994; GA ČR GAP108/10/2049 Institutional research plan: CEZ:AV0Z20410507 Keywords : Bi-material notch es * Generalized singular stress concentrators * Stability criterion * Orthotropic materials Subject RIV: JL - Materials Fatigue, Friction Mechanics

The effect of electric discharge machined notches on the fracture toughness of several structural alloys

International Nuclear Information System (INIS)

Joyce, J.A.; Link, R.E.

1993-09-01

Recent computational studies of the stress and strain fields at the tip of very sharp notches have shown that the stress and strain fields are very weakly dependent on the initial geometry of the notch once the notch has been blunted to a radius that is 6 to 10 times the initial root radius. It follows that if the fracture toughness of a material is sufficiently high so that fracture initiation does not occur in a specimen until the crack-tip opening displacement (CTOD) reaches a value from 6 to 10 times the size of the initial notch tip diameter, then the fracture toughness will be independent of whether a fatigue crack or a machined notch served as the initial crack. In this experimental program the fracture toughness (J Ic and J resistance (J-R) curve, and CTOD) for several structure alloys was measured using specimens with conventional fatigue cracks and with EDM machined notches. The results of this program have shown, in fact, that most structural materials do not achieve initiation CTOD values on the order of 6 to 10 times the radius of even the smallest EDM notch tip presently achievable. It is found furthermore that tougher materials do not seem to be less dependent on the type of notch tip present. Some materials are shown to be much more dependent on the type of notch tip used, but no simple pattern is found that relates this observed dependence to the material strength toughness, or strain hardening rate

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.

Fatigue Reliability and Calibration of Fatigue Design Factors for Offshore Wind Turbines

Directory of Open Access Journals (Sweden)

Sergio Márquez-Domínguez

2012-06-01

Full Text Available Consequences of failure of offshore wind turbines (OWTs is in general lower than consequences of failure of, e.g., oil & gas platforms. It is reasonable that lower fatigue design factors can be applied for fatigue design of OWTs when compared to other fixed offshore structures. Calibration of appropriate partial safety factors/Fatigue Design Factors (FDF for steel substructures for OWTs is the scope of this paper. A reliability-based approach is used and a probabilistic model has been developed, where design and limit state equations are established for fatigue failure. The strength and load uncertainties are described by stochastic variables. SN and fracture mechanics approaches are considered for to model the fatigue life. Further, both linear and bi-linear SN-curves are formulated and various approximations are investigated. The acceptable reliability level for fatigue failure of OWTs is discussed and results are presented for calibrated optimal fatigue design factors. Further, the influence of inspections is considered in order to extend and maintain a given target safety level.

Restraint of fatigue crack growth by wedge effects of fine particles

CERN Document Server

Takahashi, I; Kotani, N

2000-01-01

Presents some experimental results which demonstrate restraint of fatigue crack growth in an Al-Mg alloy by wedge effects of fine particles. Fatigue test specimens were machined from a JIS A5083P-O Al-Mg alloy plate of 5 mm thickness and an EDM starter notch was introduced to each specimen. Three kinds of fine particles were prepared as the materials to be wedged into the fatigue cracks, i.e. magnetic particles and two kinds of alumina particles having different mean particle sizes of 47.3 mu m and 15.2 mu m. Particles of each kind were suspended in an oil to form a paste, which was applied on the specimen surface covering the notch zone prior to the fatigue tests. In order to make some fracture mechanics approaches, in situ observations of fatigue cracks were performed for the two cases using a CCD microscope, with a magnification of *1000. The crack length and the crack opening displacement (COD) at the notch root, delta , were measured. The crack retardation effect continues almost through the entire lifet...

The effect of microstructure and geometry on the fatigue behaviour of bundle assembly welds

International Nuclear Information System (INIS)

Surette, B.A.; Gabbani, M.

1997-01-01

Cracking of end plates, in the Darlington NGS, was attributed to high-cycle fatigue resulting from flow-induced vibrations. Because the cracks were predominantly associated with the bundle assembly welds and with certain element positions, a program was initiated to study whether the microstructure and geometry of the weld zone affected the fatigue behaviour of the assembly welds. Assembly weld samples were subjected to different heat treatments, resulting in different microstructures of the weld zone. Results of fatigue testing suggest that heat treatment of the welds (i.e., microstructure) had little effect on the fatigue life. Assembly welds were also produced with different weld notch geometries, and compared with samples having notches produced by machining (instead of welding). The results of these tests showed that geometry of the weld had a significant effect on fatigue life. However, the geometry of the weld notch required to significantly improve fatigue life is not achievable using the current assembly welding process. A small improvement in fatigue life of welded samples appears possible by increasing the weld diameter. (author)

The Static and Fatigue Behavior of AlSiMg Alloy Plain, Notched, and Diamond Lattice Specimens Fabricated by Laser Powder Bed Fusion

Directory of Open Access Journals (Sweden)

Hugo Soul

2018-04-01

Full Text Available The fabrication of engineered lattice structures has recently gained momentum due to the development of novel additive manufacturing techniques. Interest in lattice structures resides not only in the possibility of obtaining efficient lightweight materials, but also in the functionality of pre-designed architectured structures for specific applications, such as biomimetic implants, chemical catalyzers, and heat transfer devices. The mechanical behaviour of lattice structures depends not only the composition of the base material, but also on the type and size of the unit cells, as well as on the material microstructure resulting from a specific fabrication procedure. The present work focuses on the static and fatigue behavior of diamond cell lattice structures fabricated from an AlSiMg alloy by laser powder bed fusion technology. In particular, the specimens were fabricated with three different orientations of lattice cells—[001], [011], [111]—and subjected to static tensile testing and force-controlled pull–pull fatigue testing up to 1 × 107 cycles. In parallel, the mechanical behavior of dense tensile plain and notched specimens was also studied and compared to that of their lattice counterparts. Results showed a significant effect of the cell orientation on the fatigue lives: specimens oriented at [001] were ~30% more fatigue-resistant than specimens oriented at [011] and [111].

Thermographic Inspection of Fatigue Crack by Using Contact Thermal Resistance

Energy Technology Data Exchange (ETDEWEB)

Yang, Seung Yong; Kim, No Hyu [Korean University of Technology and Education, Cheonan (Korea, Republic of)

2013-04-15

Fatigue crack was detected from a temperature change around surface crack using the thermographic technique. Thermal gradient across the crack decreased very much due to thermal resistance of contact surface in the crack. Heat diffusion flow passing through the discontinuity was visualized in temperature by infrared camera to find and locate the crack. A fatigue crack specimen(SM-45C), which was prepared according to KS specification and notched in its center to initiate fatigue crack from the notch tip, was heated by halogen lamp at the end of one side to generate a heat diffusion flow in lateral direction. A abrupt jump in temperature across the fatigue crack was observed in thermographic image, by which the crack could be located and sized from temperature distribution.

Thermographic Inspection of Fatigue Crack by Using Contact Thermal Resistance

International Nuclear Information System (INIS)

Yang, Seung Yong; Kim, No Hyu

2013-01-01

Fatigue crack was detected from a temperature change around surface crack using the thermographic technique. Thermal gradient across the crack decreased very much due to thermal resistance of contact surface in the crack. Heat diffusion flow passing through the discontinuity was visualized in temperature by infrared camera to find and locate the crack. A fatigue crack specimen(SM-45C), which was prepared according to KS specification and notched in its center to initiate fatigue crack from the notch tip, was heated by halogen lamp at the end of one side to generate a heat diffusion flow in lateral direction. A abrupt jump in temperature across the fatigue crack was observed in thermographic image, by which the crack could be located and sized from temperature distribution.

Aspartyl-(asparaginyl β-Hydroxylase, Hypoxia-Inducible Factor-1α and Notch Cross-Talk in Regulating Neuronal Motility

Directory of Open Access Journals (Sweden)

Margot Lawton

2010-01-01

Full Text Available Aspartyl-(Asparaginyl-β-Hydroxylase (AAH promotes cell motility by hydroxylating Notch. Insulin and insulin-like growth factor, type 1 (IGF-I stimulate AAH through Erk MAP K and phosphoinositol-3-kinase-Akt (PI3K-Akt. However, hypoxia/oxidative stress may also regulate AAH . Hypoxia-inducible factor-1alpha (HIF-1α regulates cell migration, signals through Notch, and is regulated by hypoxia/oxidative stress, insulin/IGF signaling and factor inhibiting HIF-1α (FIH hydroxylation. To examine cross-talk between HIF-1α and AAH , we measured AAH , Notch-1, Jagged-1, FIH, HIF-1α, HIF-1β and the hairy and enhancer of split 1 (HE S-1 transcription factor expression and directional motility in primitive neuroectodermal tumor 2 (PNET2 human neuronal cells that were exposed to H2O2 or transfected with short interfering RNA duplexes (siRNA targeting AAH , Notch-1 or HIF-1α. We found that: (1 AAH , HIF-1α and neuronal migration were stimulated by H2O2; (2 si-HIF-1α reduced AAH expression and cell motility; (3 si-AAH inhibited Notch and cell migration, but not HIF-1α and (4 si-Notch-1 increased FIH and inhibited HIF-1α. These findings suggest that AAH and HIF-1α crosstalk within a hydroxylation-regulated signaling pathway that may be transiently driven by oxidative stress and chronically regulated by insulin/IGF signaling.

Fracture probability properties of pure and cantilever bending fatigue of STS304 steel

International Nuclear Information System (INIS)

Roh, Sung Kuk; Park, Dae Hyun; Jeong, Soon Uk

2001-01-01

Big accidents of flyings, vessel, subways, gas equipments, buildings and bridge happens frequently. Therefore many people are suffering harm of property. The destruction cause of marcaine components is almost accused by fatigue. This study is test for STS304 specimen using pure and cantilever bending state. Rounded and notched specimen including fracture surface investigation was comparatively experimented, fatigue life according to degree of surface finishing was examined. Fatigue fracture probability of notched canilever specimens were predicted by P-S-N curve, median rank and Weibull distribution. And at the relation with the rotational speed and stress, the fatigue life of the test specimen was higher at high speed than low speed

A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis.

Directory of Open Access Journals (Sweden)

Hidenobu Okuda

Full Text Available Spermatogenesis is an elaborately regulated system dedicated to the continuous production of spermatozoa via the genesis of spermatogonia. In this process, a variety of genes are expressed that are relevant to the differentiation of germ cells at each stage. Although Notch signaling plays a critical role in germ cell development in Drosophila and Caenorhabditis elegans, its function and importance for spermatogenesis in mammals is controversial. We report that Nkapl is a novel germ cell-specific transcriptional suppressor in Notch signaling. It is also associated with several molecules of the Notch corepressor complex such as CIR, HDAC3, and CSL. It was expressed robustly in spermatogonia and early spermatocytes after the age of 3 weeks. Nkapl-deleted mice showed complete arrest at the level of pachytene spermatocytes. In addition, apoptosis was observed in this cell type. Overexpression of NKAPL in germline stem cells demonstrated that Nkapl induced changes in spermatogonial stem cell (SSC markers and the reduction of differentiation factors through the Notch signaling pathway, whereas testes with Nkapl deleted showed inverse changes in those markers and factors. Therefore, Nkapl is indispensable because aberrantly elevated Notch signaling has negative effects on spermatogenesis, affecting SSC maintenance and differentiation factors. Notch signaling should be properly regulated through the transcriptional factor Nkapl.

Short fatigue cracks growth and closure behavior in an austenitic stainless steel at 600 C and 650 C

International Nuclear Information System (INIS)

Polvora, J.P.; Laiarinandrasana, L.; Drubay, B.; Piques, R.; Martelet, B.

1995-01-01

In this work, following fatigue crack growth tests carried out at the CEN-SACLAY (AMORFIS program) by Laiarinandrasana (1994) on 316 L(N) CT specimens at 650 0 C and 600 0 C, short crack behavior of cracks emanating from machined notches is investigated. Experimental results are presented and discussions are directed to notch plasticity effect in relation with variations in crack opening stress intensity factor, K op , with crack lenght (author). 12 refs., 5 figs., 2 tab

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.

Suppression of Fatigue Crack Propagation of Duralumin by Cavitation Peening

Directory of Open Access Journals (Sweden)

Hitoshi Soyama

2015-08-01

Full Text Available It was demonstrated in the present paper that cavitation peening which is one of the mechanical surface modification technique can suppress fatigue crack propagation in duralumin. The impacts produced when cavitation bubble collapses can be utilised for the mechanical surface modification technique in the same way as laser peening and shot peening, which is called “cavitation peening”. Cavitation peening employing a cavitating jet in water was used to treat the specimen made of duralumin Japanese Industrial Standards JIS A2017-T3. After introducing a notch, fatigue test was conducted by a load-controlled plate bending fatigue tester, which has been originally developed. The fatigue crack propagation behavior was evaluated and the relationship between the fatigue crack propagation rate versus stress intensity factor range was obtained. From the results, the fatigue crack propagation rate was drastically reduced by cavitation peening and the fatigue life of duralumin plate was extended 4.2 times by cavitation peening. In addition, the fatigue crack propagation can be suppressed by 88% in the stable crack propagation stage by cavitation peening.

Incorporating mesh-insensitive structural stress into the fatigue assessment procedure of common structural rules for bulk carriers

Directory of Open Access Journals (Sweden)

Seong-Min Kim

2015-01-01

Full Text Available This study introduces a fatigue assessment procedure using mesh-insensitive structural stress method based on the Common Structural Rules for Bulk Carriers by considering important factors, such as mean stress and thickness effects. The fatigue assessment result of mesh-insensitive structural stress method have been compared with CSR procedure based on equivalent notch stress at major hot spot points in the area near the ballast hold for a 180 K bulk carrier. The possibility of implementing mesh-insensitive structural stress method in the fatigue assessment procedure for ship structures is discussed.

Cancer-related fatigue--mechanisms, risk factors, and treatments.

Science.gov (United States)

Bower, Julienne E

2014-10-01

Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.

Cancer-related fatigue: Mechanisms, risk factors, and treatments

Science.gov (United States)

Bower, Julienne E.

2015-01-01

Fatigue is one of the most common and distressing side effects of cancer and its treatment, and may persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and may be a risk factor for reduced survival. The prevalence and course of fatigue in cancer patients has been well characterized, and there is growing understanding of underlying biological mechanisms. Inflammation has emerged as a key biological pathway for cancer-related fatigue, with studies documenting links between markers of inflammation and fatigue before, during, and particularly after treatment. There is considerable variability in the experience of cancer-related fatigue that is not explained by disease- or treatment-related characteristics, suggesting that host factors may play an important role in the development and persistence of this symptom. Indeed, longitudinal studies have begun to identify genetic, biological, psychosocial, and behavioral risk factors for cancer-related fatigue. Given the multi-factorial nature of cancer-related fatigue, a variety of intervention approaches have been examined in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. Although there is currently no gold standard for treating fatigue, several of these approaches have shown beneficial effects and can be recommended to patients. This report provides a state of the science review of mechanisms, risk factors, and interventions for cancer-related fatigue, with a focus on recent longitudinal studies and randomized trials that have targeted fatigued patients. PMID:25113839

Short fatigue cracks growth and closure behavior in an austenitic stainless steel at 600 C and 650 C

Energy Technology Data Exchange (ETDEWEB)

Polvora, J.P.; Laiarinandrasana, L.; Drubay, B.; Piques, R.; Martelet, B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

1995-12-31

In this work, following fatigue crack growth tests carried out at the CEN-SACLAY (AMORFIS program) by Laiarinandrasana (1994) on 316 L(N) CT specimens at 650{sup 0}C and 600{sup 0}C, short crack behavior of cracks emanating from machined notches is investigated. Experimental results are presented and discussions are directed to notch plasticity effect in relation with variations in crack opening stress intensity factor, K{sub op}, with crack lenght (author). 12 refs., 5 figs., 2 tab.

Micro-computed tomography of fatigue microdamage in cortical bone using a barium sulfate contrast agent.

Science.gov (United States)

Leng, Huijie; Wang, Xiang; Ross, Ryan D; Niebur, Glen L; Roeder, Ryan K

2008-01-01

Accumulation of microdamage during fatigue can lead to increased fracture susceptibility in bone. Current techniques for imaging microdamage in bone are inherently destructive and two-dimensional. Therefore, the objective of this study was to image the accumulation of fatigue microdamage in cortical bone using micro-computed tomography (micro-CT) with a barium sulfate (BaSO(4)) contrast agent. Two symmetric notches were machined on the tensile surface of bovine cortical bone beams in order to generate damage ahead of the stress concentrations during four-point bending fatigue. Specimens were loaded to a specified number of cycles or until one notch fractured, such that the other notch exhibited the accumulation of microdamage prior to fracture. Microdamage ahead of the notch was stained in vitro by precipitation of BaSO(4) and imaged using micro-CT. Reconstructed images showed a distinct region of bright voxels around the notch tip or along propagating cracks due to the presence of BaSO(4), which was verified by backscattered electron imaging and energy dispersive spectroscopy. The shape of the stained region ahead of the notch tip was consistent with principal strain contours calculated by finite element analysis. The relative volume of the stained region was correlated with the number of loading cycles by non-linear regression using a power-law. This study demonstrates new methods for the non-destructive and three-dimensional detection of fatigue microdamage accumulation in cortical bone in vitro, which may be useful to gain further understanding into the role of microdamage in bone fragility.

Improved Fatigue Performance of Threaded Drillstring Connections by Cold Rolling

Energy Technology Data Exchange (ETDEWEB)

Kristoffersen, Steinar

2002-01-01

The research work presented in this thesis is concerned with analytical, numerical and experimental studies of the effect of cold rolling on the fatigue behaviour of threaded drillstring connections. A comprehensive literature study is made of the various effects on the fatigue behaviour of residual stresses introduced by mechanical deformation of notched components. Some of the effects studied are cyclic hardening behaviour after prestraining, cyclic creep, fatigue initiation in prestrained materials, short cracks and crack growth models including crack closure. Residual stresses were introduced in the surface of a smooth pipe by a rolling device to simulate a cold rolling process and verify the calculated residual stresses by measurements. Strain hardening and contact algorithm of the two bodies were incorporated in the FE analyses. Two significant errors were found in the commercial software package for residual stress evaluation, Restran v. 3.3.2a also called SINT, when using the Schajer method. The Schajer algorithm is the only hole-drilling algorithm without theoretical shortcomings, and is recommended when measuring large residual stress gradients in the depth direction. Using the Schajer method solved by in-house Matlab-routines good agreement between measured residual stress gradients and residual stress gradients from FE analyses was found. Full scale fatigue tests were performed on pipes cut from used drillstrings with notches of similar geometry as threads used in drillstring connections. The simulated threads consisted of four full depth helix notches with runouts at the surface. The pipe threads were cold rolled and fatigue tested in a full-scale four-point rotating bending fatigue testing rig. The test results showed that cold rolling had an effect on the crack initiation period. A major part of the fatigue life was with cracks observed at the notch root, but due to the increased fatigue crack propagation resistance the final fracture initiated at

The influence of the shape of a saw-cut notch in quasi-brittle 3PB specimens on the critical applied force

Czech Academy of Sciences Publication Activity Database

Seitl, Stanislav; Řoutil, L.; Klusák, Jan; Veselý, V.

2008-01-01

Roč. 2, č. 1 (2008), s. 123-132 ISSN 1802-680X Institutional research plan: CEZ:AV0Z20410507 Keywords : three point bending specimens * cement based composites * fracture parameters * notch geometry * notch width Subject RIV: JL - Materials Fatigue, Friction Mechanics

Effect of the Machining Processes on Low Cycle Fatigue Behavior of a Powder Metallurgy Disk

Science.gov (United States)

Telesman, J.; Kantzos, P.; Gabb, T. P.; Ghosn, L. J.

2010-01-01

A study has been performed to investigate the effect of various machining processes on fatigue life of configured low cycle fatigue specimens machined out of a NASA developed LSHR P/M nickel based disk alloy. Two types of configured specimen geometries were employed in the study. To evaluate a broach machining processes a double notch geometry was used with both notches machined using broach tooling. EDM machined notched specimens of the same configuration were tested for comparison purposes. Honing finishing process was evaluated by using a center hole specimen geometry. Comparison testing was again done using EDM machined specimens of the same geometry. The effect of these machining processes on the resulting surface roughness, residual stress distribution and microstructural damage were characterized and used in attempt to explain the low cycle fatigue results.

Risk factors of fatigue status among Chinese adolescents.

Science.gov (United States)

Jin, Yuelong; Peng, Baozhen; Li, Yijun; Song, Lei; He, Lianping; Fu, Rui; Wu, Qianqian; Fan, Qingxiu; Yao, Yingshui

2015-01-01

In recent years, fatigue is common among adolescents. The aim of this study is to evaluate fatigue status and find related factors of fatigue among students ranged from 13-26 years from Wuhu, China. This is a case-control, cross-sectional observational study. The students from six middle schools (high school? 26 years old?) in Wuhu city were recruited, Self-Rating Fatigue Scale (SFS) was used to measure the fatigue status among students ranged from 13-26 years, and some demographic characteristics of students also was determined. A total of 726 students are included in our study. A significant difference was observed between fatigue status and grade, a balanced diet, the partial eclipse, picky for food, lack of sleep, excessive fatigue, drinking (P sleep, drinking; grade while a balanced diet is the protective factor of fatigue. Therefore, the school should pay more attention to the fatigue among students in middle school in China, and take some properly measures to reduce the fatigue.

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)

Effects of hydrogen on fatigue of vanadium and niobium. Annual report

International Nuclear Information System (INIS)

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

1977-01-01

The fatigue behavior of unalloyed vanadium and niobium as well as their alloys with hydrogen is described. The response of vanadium-hydrogen alloys to cyclic loading is shown to depend markedly upon the presence or absence of notches, the hydrogen level, method of test, and frequency. In general, hydrides improve high cycle life of unnotched alloys, but are detrimental in the presence of a notch. Low test frequencies also lead to reduced fatigue lives. Stress-assisted hydride growth in previously hydrided alloys has been noted both in fatigue and in delayed failure experiments. Unalloyed vanadium and solid solution vanadium-hydrogen alloys do not undergo delayed failure. Preliminary tests on unalloyed niobium and several niobium-vanadium alloys reveal improvements in stress-controlled fatigue life and decreased low cycle life, in agreement with previous observations on vanadium-hydrogen alloys

Notch sensitivity of cast AZ31 magnesium alloy

Czech Academy of Sciences Publication Activity Database

Kunz, Ludvík; Lukáš, Petr; Estrin, Y.; Zúberová, Z.

2005-01-01

Roč. 12, č. 3 (2005), s. 88-91 ISSN 1335-0803. [Degradácia konštrukčných materiálov 2005. Terchová - Biely Potok, 05.09.2005-07.09.2005] R&D Projects: GA MŠk(CZ) 1P05ME804 Institutional research plan: CEZ:AV0Z20410507 Keywords : notch sensitivity * magnesium alloy * fatigue lifetime Subject RIV: JG - Metallurgy

On the direction of a crack initiated from an orthotropic bi-material notch composed of materials with non-uniform fracture mechanics properties

Czech Academy of Sciences Publication Activity Database

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

525-526, č. 1 (2013), s. 545-548 ISSN 1013-9826. [Fracture and Damage Mechanics /11./. Xi'an, 18.09.2012-21.09.2012] R&D Projects: GA ČR GA101/09/1821; GA ČR GAP108/10/2049 Institutional support: RVO:68081723 Keywords : Orthotropic bi-material notch * generalized stress intensity factor * complex potentials Subject RIV: JL - Materials Fatigue, Friction Mechanics

Fatigue in Intensive Care Nurses and Related Factors.

Science.gov (United States)

Çelik, Sevim; Taşdemir, Nurten; Kurt, Aylin; İlgezdi, Ebru; Kubalas, Özge

2017-10-01

Fatigue negatively affects the performance of intensive care nurses. Factors contributing to the fatigue experienced by nurses include lifestyle, psychological status, work organization and sleep problems. To determine the level of fatigue among nurses working in intensive care units and the related factors. This descriptive study was conducted with 102 nurses working in intensive care units in the West Black Sea Region of Turkey. Data were collected between February and May 2014 using a personal information form, the Visual Analogue Scale for Fatigue (VAS-F), the Hospital Anxiety and Depression Scale and the Pittsburg Sleep Quality Index. The intensive care nurses in the study were found to be experiencing fatigue. Significant correlations were observed between scores on the VAS-F Fatigue and anxiety (p=0.01), depression (p=0.002), and sleep quality (pnurses' levels of fatigue. These results can be of benefit in taking measures which may be used to reduce fatigue in nurses, especially the fatigue related to work organization and social life.

Various methods of numerical estimation of generalized stress intensity factors of bi-material notches

Directory of Open Access Journals (Sweden)

Klusák J.

2009-12-01

Full Text Available The study of bi-material notches becomes a topical problem as they can model efficiently geometrical or material discontinuities. When assessing crack initiation conditions in the bi-material notches, the generalized stress intensity factors H have to be calculated. Contrary to the determination of the K-factor for a crack in an isotropic homogeneous medium, for the ascertainment of the H-factor there is no procedure incorporated in the calculation systems. The calculation of these fracture parameters requires experience. Direct methods of estimation of H-factors need choosing usually length parameter entering into calculation. On the other hand the method combining the application of the reciprocal theorem (Ψ-integral and FEM does not require entering any length parameter and is capable to extract the near-tip information directly from the far-field deformation.

Case Study of Crack Initiation from Bi-material Notches

Czech Academy of Sciences Publication Activity Database

Klusák, Jan; Knésl, Zdeněk

2011-01-01

Roč. 452-453, - (2011), s. 449-452 ISSN 1013-9826. [Fracture and Damage Mechanics /9./. Nagasaki, 20.09.2010-22.09.2010] R&D Projects: GA ČR GAP108/10/2049; GA ČR GA101/08/0994 Institutional research plan: CEZ:AV0Z20410507 Keywords : Crack initiation * bi-material notch * fracture mechanics Subject RIV: JL - Materials Fatigue, Friction Mechanics

Some considerations about improvement for fatigue strength of structures; Shatai kozobutsu no hiro kyodo kojo ni kansuru ichikosatsu

Energy Technology Data Exchange (ETDEWEB)

Kimoto, H; Toyama, K; Maruyama, H; Magara, S [Press Kogyo Co. Ltd., Kanagawa (Japan)

1997-10-01

To reduce weight, higher tensile strength and/or thinner plate are used or considered in vehicle structures. In general, welded or notch sections, fatigue strength decreases because of increasing concentrated stress or effect of notch sensitivity and so on. In this paper, some methods are studied to improve fatigue strength and obtain a long life. 2 refs., 11 figs., 5 tabs.

Fretting fatigue life estimation using fatigue damage gradient correction factor in various contact configurations

Energy Technology Data Exchange (ETDEWEB)

Hwang, Dong Hyeon; Cho, Sung-San [Hongik University, Seoul (Korea, Republic of)

2017-03-15

A fretting fatigue life estimation method that takes into account the stress gradient effect was developed by the authors [Journal of Mechanical Science and Technology, 28 (2014) 2153-2159]. In the developed method, fatigue damage value at the cracking location is corrected with fatigue damage gradient and the corrected value is compared directly with the plain fatigue data for life estimation. In other words, the correction factor is the ratio of plain fatigue damage to fretting fatigue damage at the same life and a function of fatigue damage gradient. Since reliability of the method was verified only for cylinder-on-flat contact configuration in the previous study, the present study extends application of the method to flat-on-flat contact configurations by developing the correction factor for both the contact configuration. Fretting fatigue experiments were conducted to obtain fatigue life data for various fretting pads. Finite element analyses were conducted to evaluate the Smith-Watson-Topper (SWT) fatigue damage parameter in the cracking region. It is revealed that the SWT parameter in fat-on-flat contact configuration decreases exponentially away from the surface as in cylinder-on-flat contact configuration, and thus the SWT gradient at the surface can be evaluated reliably. Moreover, it is found that decrease in the SWT parameter around the cracking location can be expressed by piecewise exponential curves. If the gradient of SWT at the surface is used as a representative value of SWT gradient, it is impossible to establish functional relationship between the SWT gradient and the correction factor for both the contact configurations although it was possible for cylinder-on-flat contact configuration. However, if weighted average of the SWT gradient values obtained from each exponential curve in the piecewise exponential curve is used as a representative value, the correction factor for both the contact configurations becomes a function of the SWT gradient

Effects of Specimen Diameters on the Distribution of Corrosion Fatigue Cracks

OpenAIRE

石原, 外美; 塩澤, 和章; 宮尾, 嘉寿

1988-01-01

The distribution of corrosion fatigue cracks observed on the un-notched round specimen surface differs with specimen diameter, especially in the low stress amplitude region. At a constant fatigue life ratio, many long cracks are initiated on the larger specimen, 12 mm (diameter), in comparison with the smaller specimen, 6 mm (diameter). On the other hand, in the high stress amplitude region of corrosion fatigue and fatigue in laboratory air, the distribution of cracks during the fatigue proce...

High Load Ratio Fatigue Strength and Mean Stress Evolution of Quenched and Tempered 42CrMo4 Steel

Science.gov (United States)

Bertini, Leonardo; Le Bone, Luca; Santus, Ciro; Chiesi, Francesco; Tognarelli, Leonardo

2017-08-01

The fatigue strength at a high number of cycles with initial elastic-plastic behavior was experimentally investigated on quenched and tempered 42CrMo4 steel. Fatigue tests on unnotched specimens were performed both under load and strain controls, by imposing various levels of amplitude and with several high load ratios. Different ratcheting and relaxation trends, with significant effects on fatigue, are observed and discussed, and then reported in the Haigh diagram, highlighting a clear correlation with the Smith-Watson-Topper model. High load ratio tests were also conducted on notched specimens with C (blunt) and V (sharp) geometries. A Chaboche model with three parameter couples was proposed by fitting plain specimen cyclic and relaxation tests, and then finite element analyses were performed to simulate the notched specimen test results. A significant stress relaxation at the notch root became clearly evident by reporting the numerical results in the Haigh diagram, thus explaining the low mean stress sensitivity of the notched specimens.

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.

Joined application of a multiaxial critical plane criterion and a strain energy density criterion in low-cycle fatigue

Directory of Open Access Journals (Sweden)

Andrea Carpinteri

2017-07-01

Full Text Available In the present paper, the multiaxial fatigue life assessment of notched structural components is performed by employing a strain-based multiaxial fatigue criterion. Such a criterion, depending on the critical plane concept, is extended by implementing the control volume concept reated to the Strain Energy Density (SED approach: a material point located at a certain distance from the notch tip is assumed to be the verification point where to perform the above assessment. Such a distance, measured along the notch bisector, is a function of both the biaxiality ratio (defined as the ratio between the applied shear stress amplitude and the normal stress amplitude and the control volume radii under Mode I and Mode III. Once the position of the verification point is determined, the fatigue lifetime is assessed through an equivalent strain amplitude, acting on the critical plane, together with a unique material reference curve (i.e. the Manson-Coffin curve. Some uniaxial and multiaxial fatigue data related to V-notched round bars made of titanium grade 5 alloy (Ti-6Al-4V are examined to validate the present criterion.

Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Wei-Ming Wang

Full Text Available Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC. The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

Prediction of fatigue life under service loading using the relative method

International Nuclear Information System (INIS)

Buch, A.

1982-01-01

Fatigue life estimates obtained with the local strain approach (LSA) and with the conventional nominal stress approach (NSA) were compared with experimental results obtained on notched AlCuMg2 aircraft material specimens with flight simulation random tensile loading. The effect of change of the reference stress, of the loading program and of some changes in the loading frequency distribution, on the ratio Nsub(exp)/Nsub(pred) was investigated. A material strain-life curve, a cyclic stress-strain curve. The Neuber-Topper rule Ksub(sigma) x Ksub(epsilon) = K 2 = const. and a K value estimated with an exact two-parameter notch factor formula for the case R = 0, N = 10 7 were used for life predictions. (orig./RW) [de

On the Crack Initiated From the Bi-material Notch Tip

Czech Academy of Sciences Publication Activity Database

Profant, T.; Klusák, Jan; Kotoul, M.

452-453, - (2011), s. 441-444 ISSN 1013-9826. [Fracture and Damage Mechanics. Nagasaki, 20.09.2010-22.09.2010] R&D Projects: GA ČR GAP108/10/2049; GA ČR GA101/08/0994 Institutional research plan: CEZ:AV0Z20410507 Keywords : orthotropic bi-material notch * crack initiation * Matched asymptotic procedure Subject RIV: JL - Materials Fatigue, Friction Mechanics

Small fatigue cracks; Proceedings of the Second International Conference/Workshop, Santa Barbara, CA, Jan. 5-10, 1986

Energy Technology Data Exchange (ETDEWEB)

Ritchie, R.O.; Lankford, J.

1986-01-01

Topics discussed in this volume include crack initiation and stage I growth, microstructure effects, crack closure, environment effects, the role of notches, analytical modeling, fracture mechanics characterization, experimental techniques, and engineering applications. Papers are presented on fatigue crack initiation along slip bands, the effect of microplastic surface deformation on the growth of small cracks, short fatigue crack behavior in relation to three-dimensional aspects and the crack closure effect, the influence of crack depth on crack electrochemistry and fatigue crack growth, and nondamaging notches in fatigue. Consideration is also given to models of small fatigue cracks, short crack theory, assessment of the growth of small flaws from residual strength data, the relevance of short crack behavior to the integrity of major rotating aero engine components, and the relevance of short fatigue crack growth data to the durability and damage tolerance analyses of aircraft.

Fatigue Reliability and Calibration of Fatigue Design Factors for Offshore Wind Turbines

DEFF Research Database (Denmark)

Dominguez, Sergio Marquez; Sørensen, John Dalsgaard

2012-01-01

Consequences of failure of offshore wind turbines (OWTs) are in general lower than consequences of failure of, e.g., oil & gas platforms. It is reasonable that lower fatigue design factors can be applied for fatigue design of OWTs when compared to other fixed offshore structures. Calibration...

A study on damage and fatigue characteristics of plain woven carbon fiber reinforced composite material(I)

International Nuclear Information System (INIS)

Kim, Kwang Soo; Kim, Sang Tae

1993-01-01

The characteristics of damage and fatigue subjected to tensile fatigue loading in plain woven carbon fiber reinforced composite material were studied. Constant amplitude load of 90% stress of notch strength was applied to each specimen, which had different initial notch length, and crack dectectvie compliance curve was determined form load-displacement data. The effective crack length(a eff ) was obtained form this compliance curve and the effective crack growth could be divided to three-steps and explained separately. After cycling the shape of fatigue crack was observed by S.E.M.. Change of elastic modulus(E N ) during fatigue cycle was explained by repeated sudden-death medel. The material constant determined by Jen-Hsu model was more useful to evaluate damage than Wang-Chim model. (Author)

Risk factors of fatigue status among Chinese adolescents

OpenAIRE

Jin, Yuelong; Peng, Baozhen; Li, Yijun; Song, Lei; He, Lianping; Fu, Rui; Wu, Qianqian; Fan, Qingxiu; Yao, Yingshui

2015-01-01

In recent years, fatigue is common among adolescents. The aim of this study is to evaluate fatigue status and find related factors of fatigue among students ranged from 13-26 years from Wuhu, China. This is a case-control, cross-sectional observational study. The students from six middle schools (high school? 26 years old?) in Wuhu city were recruited, Self-Rating Fatigue Scale (SFS) was used to measure the fatigue status among students ranged from 13-26 years, and some demographic characteri...

Spot weld arrangement effects on the fatigue behavior of multi-spot welded joints

International Nuclear Information System (INIS)

Hassanifard, Soran; Zehsaz, Mohammad; Esmaeili, Firooz

2011-01-01

In the present study, the effects of spot weld arrangements in multi-spot welded joints on the fatigue behavior of the joints are studied. Three different four-spot welded joints are considered: one-row four-spot parallel to the loading direction, one-row four-spot perpendicular to the loading direction and two-row four-spot weld specimens. The experimental fatigue test results reveal that the differences between the fatigue lives of three spot welded types in the low cycle regime are more considerable than those in the high cycle regime. However, all kinds of spot weld specimens have similar fatigue strength when approaching a million cycles. A non-linear finite element analysis is performed to obtain the relative stress gradients, effective distances and notch strength reduction factors based on the volumetric approach. The work here shows that the volumetric approach does a very good job in predicting the fatigue life of the multi-spot welded joints

Three-point bending fatigue behavior of WC–Co cemented carbides

International Nuclear Information System (INIS)

Li, Anhai; Zhao, Jun; Wang, Dong; Gao, Xinliang; Tang, Hongwei

2013-01-01

Highlights: ► Mechanical fatigue tests were conducted on a specific designed jig. ► Three-point bending fatigue behavior of WC–Co cemented carbides was studied. ► Fatigue mechanisms of WC–Co cemented carbides with different WC grain sizes and Co binder contents were revealed. -- Abstract: WC–Co cemented carbides with different WC grain sizes and Co binder contents were sintered and fabricated. The three-point bending specimens with a single edge notch were prepared for tests. In the experiments, the mechanical properties of materials were investigated under static and cyclic loads (20 Hz) in air at room temperature. The fatigue behaviors of the materials under the same applied loading conditions are presented and discussed. Optical microscope and scanning electron microscopy were used to investigate the micro-mechanisms of damage during fatigue, and the results were used to correlate with the mechanical fatigue behavior of WC–Co cemented carbides. Experimental results indicated that the fatigue fracture surfaces exhibited more fracture origins and diversification of crack propagation paths than the static strength fracture surfaces. The fatigue fracture typically originates from inhomogeneities or defects such as micropores or aggregates of WC grains near the notch tip. Moreover, due to the diversity and complexity of the fatigue mechanisms, together with the evolution of the crack tip and the ductile deformation zone, the fatigue properties of WC–Co cemented carbides were largely relevant with the combination of transverse rupture strength and fracture toughness, rather than only one of them. Transverse rupture strength dominated the fatigue behavior of carbides with low Co content, whilst the fatigue behavior of carbides with high Co content was determined by fracture toughness.

Meta-analysis of the predictive factors of postpartum fatigue.

Science.gov (United States)

Badr, Hanan A; Zauszniewski, Jaclene A

2017-08-01

Nearly 64% of new mothers are affected by fatigue during the postpartum period, making it the most common problem that a woman faces as she adapts to motherhood. Postpartum fatigue can lead to serious negative effects on the mother's health and the newborn's development and interfere with mother-infant interaction. The aim of this meta-analysis was to identify predictive factors of postpartum fatigue and to document the magnitude of their effects using effect sizes. We used two search engines, PubMed and Google Scholar, to identify studies that met three inclusion criteria: (a) the article was written in English, (b) the article studied the predictive factors of postpartum fatigue, and (c) the article included information about the validity and reliability of the instruments used in the research. Nine articles met these inclusion criteria. The direction and strength of correlation coefficients between predictive factors and postpartum fatigue were examined across the studies to determine their effect sizes. Measurement of predictor variables occurred from 3days to 6months postpartum. Correlations reported between predictive factors and postpartum fatigue were as follows: small effect size (r range =0.10 to 0.29) for education level, age, postpartum hemorrhage, infection, and child care difficulties; medium effect size (r range =0.30 to 0.49) for physiological illness, low ferritin level, low hemoglobin level, sleeping problems, stress and anxiety, and breastfeeding problems; and large effect size (r range =0.50+) for depression. Postpartum fatigue is a common condition that can lead to serious health problems for a new mother and her newborn. Therefore, increased knowledge concerning factors that influence the onset of postpartum fatigue is needed for early identification of new mothers who may be at risk. Appropriate treatments, interventions, information, and support can then be initiated to prevent or minimize the postpartum fatigue. Copyright © 2017 Elsevier

Experimental verification of different parameters influencing the fatigue S/N-curve

International Nuclear Information System (INIS)

Roos, E.; Maile, K.; Herter, K.-H.; Schuler, X.

2005-01-01

For the construction, design and operation of nuclear components the appropriate technical codes and standards provide detailed stress analysis procedures, material data and a design philosophy which guarantees a reliable behavior throughout the specified lifetime. Especially for cyclic stress evaluation the different codes and standards provide different fatigue analyses procedures to be performed considering the various (specified or measured) loading histories which are of mechanical and/or thermal origin and the geometric complexities of the components. In order to fully understand the background of the fatigue analysis included in the codes and standards as well as of the fatigue design curves used as a limiting criteria (to determine the fatigue life usage factor), it is important to understand the history, background as well as the methodologies which are important for the design engineers to get reliable results. The design rules according to the technical codes and standards provide for explicit consideration of cyclic operation, using design fatigue curves of allowable alternating loads (allowable stress or strain amplitudes) vs. number of loading cycles (S/N-curves), specific rules for assessing the cumulative fatigue damage (cumulative fatigue life usage factor) caused by different specified or monitored load cycles. The influence of different factors like welds, environment, surface finish, temperature, mean stress and size must be taken into consideration. In the paper parameters influencing the S/N-curves used within a fatigue analysis, like different type of material, the surface finish, the temperature, the difference between unwelded and welded areas, the strain rate as well as the influences of notches are verified on the basis of experimental results obtained by specimens testing in the LCF regime for high strain amplitudes. Thus safety margins relevant for the assessment of fatigue life depending on the different influencing parameters are

Case Criterion of Crack Onset in Orthotropic Bi-material Notches

Czech Academy of Sciences Publication Activity Database

Profant, T.; Klusák, Jan; Kotoul, M.

2011-01-01

Roč. 465, - (2011), s. 157-160 ISSN 1013-9826. [Materials Structure and Micromechanics of Fracture. Brno, 28.06.2010-30.06.2010] R&D Projects: GA ČR GA101/08/0994; GA ČR GAP108/10/2049 Institutional research plan: CEZ:AV0Z20410507 Keywords : orthotropic bi-material notch * crack initiation * matched asymptotic procedure Subject RIV: JL - Materials Fatigue, Friction Mechanics

Crack propagation from bi-material notches – matched asymptotic procedure

Czech Academy of Sciences Publication Activity Database

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

488-489, - (2012), s. 416-419 ISSN 1013-9826. [International Conference on Fracture and Damage Mechanics - FDM 2011 /10./. Dubrovník, 19.09.2011-21.09.2011] R&D Projects: GA ČR GAP108/10/2049 Institutional research plan: CEZ:AV0Z20410507 Keywords : Orthotropic bi-material notch * two-state integral * matched asymptotic expansion Subject RIV: JL - Materials Fatigue, Friction Mechanics

Risk factors for fatigue among airline pilots.

Science.gov (United States)

van Drongelen, Alwin; Boot, Cécile R L; Hlobil, Hynek; Smid, Tjabe; van der Beek, Allard J

2017-01-01

The objective of this study is to determine risk factors for fatigue among airline pilots, taking into account person-, work-, health-, sleep-, and lifestyle-related characteristics. The study population consisted of 502 pilots who participated in the MORE Energy study. Included risk factors were either measured through an online questionnaire or provided by the company. The outcome of this study, fatigue, was assessed using the Checklist Individual Strength (CIS), and was defined as scoring more than 76 points on this questionnaire. The association of the risk factors with fatigue was determined using univariate and multivariate logistic regression analyses. Of the participating pilots, 29.5 % scored more than 76 points on the CIS and were classified as being fatigued. The fully adjusted regression model showed that person-, work-, health-, and lifestyle-related characteristics were associated with fatigue. Pilots who were aged 31 to 40 (OR 3.36, 95 % CI 1.32-8.53) or 41 to 50 (OR 4.19, 95 % CI 1.40-12.47), an evening type (OR 2.40, 95 % CI 1.38-4.16), scored higher on work-life balance disturbance (OR 1.22, 95 % CI 1.10-1.36), scored higher on need for recovery (OR 1.02, 95 % CI 1.01-1.04), scored lower on general health perception (OR 0.31, 95 % CI 0.20-0.47), were less physically active (OR 0.77, 95 % CI 0.66-0.89), and had a moderate alcohol consumption (OR 3.88, 95 % CI 1.21-12.43), were at higher risk for fatigue. Higher age, being an evening type, disturbance of the work-life balance, more need for recovery, a lower perceived health, less physical activity, and moderate alcohol consumption were shown to be risk factors for fatigue. Further longitudinal research is needed to elucidate the direction of the associations found and to evaluate the effects of possible countermeasures in airline pilots.

Corrosion fatigue initiation and short crack growth behaviour of austenitic stainless steels under light water reactor conditions

International Nuclear Information System (INIS)

Seifert, H.P.; Ritter, S.; Leber, H.J.

2012-01-01

Highlights: ► Corrosion fatigue in austenitic stainless steels under light water reactor conditions. ► Identification of major parameters of influence on initiation and short crack growth. ► Critical system conditions for environmental reduction of fatigue initiation life. ► Comparison with the environmental factor (F env ) approach. - Abstract: The corrosion fatigue initiation and short crack growth behaviour of different wrought low-carbon and stabilised austenitic stainless steels was characterised under simulated boiling water reactor and pressurised water reactor primary water conditions by cyclic fatigue tests with sharply notched fracture mechanics specimens. The special emphasis was placed to the behaviour at low corrosion potentials and, in particular, to hydrogen water chemistry conditions. The major parameter effects and critical conjoint threshold conditions, which result in relevant environmental reduction and acceleration of fatigue initiation life and subsequent short crack growth, respectively, are discussed and summarised. The observed corrosion fatigue behaviour is compared with the fatigue evaluation procedures in codes and regulatory guidelines.

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

Directory of Open Access Journals (Sweden)

Marcin eTeodorczyk

2015-01-01

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

Fatigue life prediction of oil ducts under service loads

Energy Technology Data Exchange (ETDEWEB)

Meggiolaro, Marco A.; Castro, Jaime T.P. [Pontificia Univ. Catolica do Rio de Janeiro, RJ (Brazil)

2003-07-01

A methodology to calculate the residual initiation and propagation lives of fatigue cracks in oil pipelines with corrosion-like defects is proposed and applied to predict the residual life of an old duct made of API 5L Gr. B steel, in service for more than 40 years. Since its inauguration, this pipeline has carried several heated products under variable temperatures and pressures. The calculated (nominal) service stresses are very high, due to thermal loads that induce significant bending in curved parts of the duct, with peaks close to the yield strength of the steel. The elastic- plastic fatigue damage at a notch or a corrosion pit root is calculated using the {epsilon}N method, and the effects of surface semi-elliptical cracks in its internal (or external) wall is studied considering appropriate stress intensity factor expressions and the actual service loads. In the presence of surface flaws associated to stress concentration factors of the order of three, a fatigue crack likely will initiate in the pipeline. However, if these surface cracks are small compared to the duct wall thickness, their predicted propagation rates are very low. (author)

Flexural fracture and fatigue behavior of steel-fiber-reinforced concrete structures

International Nuclear Information System (INIS)

Chang, D.I.

1995-01-01

Fracture and fatigue tests were performed in order to investigate the fracture and fatigue behavior of steel-fibre-reinforced concrete (SFRC) structures. 33 SFRC beams were used in the fracture and fatigue tests. The relationship between loading, strain and midspan deflection of the beams was observed under the three-point loading system.From the test results, the effects of the fiber content, fiber aspect ratio and notch-to-depth ratio on the concrete fracture and fatigue behavior were studied, and the fatigue strengths of SFRC beams were calculated. According to the regression technique, some empirical formulae for predicting the fatigue strength of SFRC beams were also suggested. (orig.)

A study into psychosocial factors as predictors of work-related fatigue.

Science.gov (United States)

Rahman, Hanif Abdul; Abdul-Mumin, Khadizah; Naing, Lin

2016-07-14

To explore and determine relationship between psychosocial factors and work-related fatigue among emergency and critical care nurses in Brunei. Cross-sectional study conducted on all emergency and critical care nurses across Brunei public hospitals from February to April 2016. 201 nurses participated in the study (82% response rate). A total of 36% of the variance of chronic fatigue was explained by stress, trust in management, decision latitude, self-rated health, and work-family conflict. Burnout, self-rated health, commitment to workplace, and trust in management explained 30% of the variance of acute fatigue. Stress, work-family conflict and reward explained 28% of the variance of intershift recovery after controlling for significant sociodemographic variables. Smoking was identified as an important sociodemographic factor for work-related fatigue. Psychosocial factors were good predictors of work-related fatigue. A range of psychosocial factors were established, however more research is required to determine all possible causation factors of nurses' work-related fatigue.

Damage and fatigue crack growth of Eurofer steel first wall mock-up under cyclic heat flux loads. Part 1: Electron beam irradiation tests

Energy Technology Data Exchange (ETDEWEB)

You, J.H., E-mail: you@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Euratom Association, Boltzmannstr. 2, 85748 Garching (Germany); Höschen, T. [Max-Planck-Institut für Plasmaphysik, Euratom Association, Boltzmannstr. 2, 85748 Garching (Germany); Pintsuk, G. [Forschungszentrum Jülich GmbH, IEK2, Euratom Association, 52425 Jülich (Germany)

2014-04-15

Highlights: • Clear evidence of microscopic damage and crack formation at the notch root in the early stage of the fatigue loading (50–100 load cycles). • Propagation of fatigue crack at the notch root in the course of subsequent cyclic heat-flux loading followed by saturation after roughly 600 load cycles. • No sign of damage on the notch-free surface up to 800 load cycles. • No obvious effect of the pulse time duration on the crack extension. • Slight change in the grain microstructure due to the formation of sub-grain boundaries by plastic deformation. - Abstract: Recently, the idea of bare steel first wall (FW) is drawing attention, where the surface of the steel is to be directly exposed to high heat flux loads. Hence, the thermo-mechanical impacts on the bare steel FW will be different from those of the tungsten-coated one. There are several previous works on the thermal fatigue tests of bare steel FW made of austenitic steel with regard to the ITER application. In the case of reduced-activation steel Eurofer97, a candidate structural material for the DEMO FW, there is no report on high heat flux tests yet. The aim of the present study is to investigate the thermal fatigue behavior of the Eurofer-based bare steel FW under cyclic heat flux loads relevant to DEMO operation. To this end, we conducted a series of electron beam irradiation tests with heat flux load of 3.5 MW/m{sup 2} on water-cooled mock-ups with an engraved thin notch on the surface. It was found that the notch root region exhibited a marked development of damage and fatigue cracks whereas the notch-free surface manifested no sign of crack formation up to 800 load cycles. Results of extensive microscopic investigation are reported.

A fatigue initiation parameter for gas pipe steel submitted to hydrogen absorption

Energy Technology Data Exchange (ETDEWEB)

Capelle, J; Gilgert, J; Pluvinage, G [LaBPS - Ecole Nationale d' Ingenieurs de Metz et Universite Paul Verlaine Metz, Ile du Saulcy, 57045 Metz (France)

2010-01-15

Fatigue initiation resistance has been determined on API 5L X52 gas pipe steel. Tests have been performed on Roman Tile (RT) specimen and fatigue initiation was detected by acoustic emission. A comparison between specimens electrolytically charged with hydrogen and specimens without hydrogen absorption were made and it has been noted that fatigue initiation time is reduced of about 3 times when hydrogen embrittlement occurs. It has been proposed to use the concept of Notch Stress Intensity Factor as parameter to describe the fatigue initiation process. Due to the fact that hydrogen is localised in area with high hydrostatic pressure, definitions of local effective stress and distance have been modified when hydrogen is absorbed. This modification can be explained by existence of a ductile-brittle transition with hydrogen concentration. The fatigue initiation resistance curve allows that to determine a threshold for large number of cycles of fatigue non initiation. This parameter introduced in a Failure Assessment Diagram (FAD) provides supplementary information about defect nocivity in gas pipes: a non-critical defect can be detected as dormant or not dormant defect i.e., as non propagating defect. (author)

Low cycle fatigue of irradiated LMFBR materials

International Nuclear Information System (INIS)

Blackburn, L.D.

1976-01-01

A review of low cycle fatigue data on irradiated LMFBR materials was conducted and extensive graphical representations of available data are presented. Representative postirradiation tensile properties of annealed 304 and 316 SS are selected and employed in several predictive methods to estimate irradiated material fatigue curves. Experimental fatigue data confirm the use of predictive methods for establishing conservative design curves over the range of service conditions relevant to such CRBRP components as core former, fixed radial shielding, core barrel, lower inlet module and upper internals structures. New experimental data on fatigue curves and creep-fatigue interaction in irradiated 20 percent cold worked (CW) 316 SS and Alloy 718 would support the design of removable radial shielding and upper internals in CRBRP. New experimental information on notched fatigue behavior and cyclic stress-strain curves of all these materials in the irradiated condition could provide significant design data

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

Risk factors for fatigue in patients with epilepsy.

Science.gov (United States)

Yan, Song; Wu, Yuanbin; Deng, Yanchun; Liu, Yonghong; Zhao, Jingjing; Ma, Lei

2016-11-01

Fatigue is highly prevalent in patients with epilepsy and has a major impact on quality of life, but little data is available on its effects and management in epilepsy. To identify the incidence and risk factors of fatigue in patients with epilepsy, 105 epilepsy patients (45 women and 60 men) were enrolled in our study. Demographic and clinical data were collected and psychological variables including fatigue, sleep quality, excess daytime sleepiness, anxiety, and depression were measured by Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale, respectively. Of 105 patients, 29.5% exhibited fatigue (FSS score ⩾4). We found no correlation between the occurrence of fatigue and any of our demographic or clinical variables. Fatigue is correlated with low sleep quality, anxiety, and depression, but not with excess daytime sleepiness. Thus, we concluded that fatigue is highly prevalent in patients with epilepsy, and that low sleep quality, anxiety, and depression are significantly correlated with fatigue in epileptics, while excess daytime sleepiness not. Copyright © 2016. Published by Elsevier Ltd.

Crack initiation life analysis in notched pipe under cyclic bending loads

International Nuclear Information System (INIS)

Goak, S. R.; Kim, Y. J.; Lee, J. S.; Park, Y. W.

2000-01-01

In order to improve LBB(Leak-Before-Break) methodology, more precisely the crack growth evaluation, a benchmark problem was proposed by the CEA Saclay. The aim of this benchmark analysis was to evaluate the crack growth in a notched pipe under cyclic bending loads. The proposed benchmark analysis is composed of three main topic; fatigue crack initiation, crack propagation and crack penetration. This paper deals with the first topic, crack initiation in a notched pipe under four point bending. Both elastic-plastic finite element analysis and Neuber's rule were used to estimate the crack initiation life and the finite element models were verified by mesh-refinement, stress distribution and global deflection. In elastic-plastic finite element analysis, crack initiation life was determined by strain amplitude at the notch tip and strain-life curve of the material. In the analytical method, Neuber's rule with the consideration of load history and mean stress effect, was used for the life estimation. The effect of notch tip radius, strain range, cyclic hardening rule were examined in this study. When these results were compared with the experimental ones, the global deformation was a good agreement but the crack initiation cycle was higher than the experimental result

Fatigue life response of ASME SA 106-B steel in pressurized water reactor environments

International Nuclear Information System (INIS)

Terrell, J.B.

1989-01-01

Fatigue strain-life tests were conducted on ASMESA 106-B piping steel base metal and weld metal specimens in 288 0 C (550 0 F) pressurized water reactor (PWR) environments as a function of strain amplitude, strain ratio, notch acuity, and cyclic frequency. Notched base metal specimens tested at 0.017 Hz in 0.001 part per million (ppm) dissolved oxygen environments nearly completely used up the margins of safety of 2 on stress and 20 on cycles incorporated into the ASMA Section III design curve for carbon steels. Tests conducted with smooth base metal and weld metal specimens at 1.0 Hz showed virtually no degradation in cycles to failure when compared to 288 0 C air test results. In all cases, however, the effect of temperature alone reduced the margin of safety offered by the design curve in the low cycle regime for the test specimens. Comparison between the fatigue life results of smooth and notched specimens suggests that fatigue crack initiation is not significantly affected by 0.001 ppm dissolved oxygen, and that most of the observed degradation may be attributed to crack growth acceleration. These results suggest that the ASMA Section III methodology should be reviewed, taking into account the PWR environment variables which degrade the fatigue life of pressure-retaining components. (author)

Fatigue life response of ASME SA 106-B steel in pressurized water reactor environments

Energy Technology Data Exchange (ETDEWEB)

Terrell, J B [Materials Engineering Associates, Inc., Lanham, MD (USA)

1989-01-01

Fatigue strain-life tests were conducted on ASMESA 106-B piping steel base metal and weld metal specimens in 288{sup 0}C (550{sup 0}F) pressurized water reactor (PWR) environments as a function of strain amplitude, strain ratio, notch acuity, and cyclic frequency. Notched base metal specimens tested at 0.017 Hz in 0.001 part per million (ppm) dissolved oxygen environments nearly completely used up the margins of safety of 2 on stress and 20 on cycles incorporated into the ASMA Section III design curve for carbon steels. Tests conducted with smooth base metal and weld metal specimens at 1.0 Hz showed virtually no degradation in cycles to failure when compared to 288{sup 0}C air test results. In all cases, however, the effect of temperature alone reduced the margin of safety offered by the design curve in the low cycle regime for the test specimens. Comparison between the fatigue life results of smooth and notched specimens suggests that fatigue crack initiation is not significantly affected by 0.001 ppm dissolved oxygen, and that most of the observed degradation may be attributed to crack growth acceleration. These results suggest that the ASMA Section III methodology should be reviewed, taking into account the PWR environment variables which degrade the fatigue life of pressure-retaining components. (author).

Evaluation of fatigue crack growth and fracture resistance of SA350 LF2 material

International Nuclear Information System (INIS)

Singh, P.K.; Dubey, J.S.; Chakrabarty, J.K.; Vaze, K.K.; Kushwaha, H.S.

2003-01-01

The aim of the present paper is to evaluate the tensile and fracture mechanics properties of the SA350 LF2 carbon steel material used as the Header material in the primary heat transport (PHT) system piping of the Indian pressurized heavy water reactors (PHWR). Tensile, fatigue crack growth rate and fracture toughness tests have been carried out on specimens machined from the Header of the actual PHT pipes. The effect of temperature on tensile properties has been discussed. The effect of temperature and notch orientation on fracture resistance behavior of the material and fatigue crack growth rate dependence on the notch orientation and stress ratio has also been discussed. (author)

Crack growth and fracture in fiber reinforced concrete beams under static and fatigue loading

International Nuclear Information System (INIS)

Jeanfreau, J.; Arockiasamy, M.; Reddy, D.V.

1987-01-01

The paper presents the results of a two-phase experimental investigation on the fatigue and fracture of six different types of concrete: plain, 0.5%, 1.0%, 1.5%, and 2.0% steel fibers and 0.5% kevlar fibers. In the first phase the J-integral was evaluated for different types of concrete from load-displacement curves. The value shows a marked increase in the energy required to fracture concrete when fibers are added. The values did not vary substantially for different notch depths. In the second phase concrete beams were subjected to fatigue by applying a pure bending on the notch. The effect of fiber addition was examined with emphasis on the crack propagation and the increase in the fatigue strength. The crack pattern was mainly influenced by the presence, amount, and the distribution of the fibers in the concrete. (orig./HP)

Effect of Crack Tip Stress Concentration Factor on Fracture Resistance in Vacuum Environment

Science.gov (United States)

2015-01-20

indicate: (1) in all alloys, the fracture resistance is highest for blunt-notches (smaller Kt), and is lowest for fatigue -sharpened precracked...paths are transgranular and the fracture mode is ductile void coalescence in all cases, irrespective of the stress concentration factor. 20-01-2015...because of corrosion and/or various loading conditions such as fatigue , fretting, abrasion, etc. Also, the geometry of the structure may cause an

Evaluation of Variation in Residual Strength of Carbon Fiber Reinforced Plastic Plate with a Hole Subjected to Fatigue Load

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Young; Kang, Min Sung; Koo, Jae Mean; Seok, Chang Sung [Sungkyunkwan University, Seoul (Korea, Republic of)

2010-10-15

CFRP (Carbon Fiber Reinforced Plastic) has received considerable attention in various fields as a structural material, because of its high specific strength, high specific stiffness, excellent design flexibility, favorable chemical properties, etc. Most products consisting of several parts are generally assembled by mechanical joining methods (using rivets, bolts, pins, etc.). Holes must be drilled in the parts to be joined, and the strength of the components subjected to static and fatigue loads caused by stress concentration must be decreased. In this study, we experimentally evaluated the variation in the residual strength of a holenotched CFRP plate subjected to fatigue load. We repeatedly subjected the hole-notched specimen to fatigue load for a certain number of cycles, and then we investigated the residual strength of the hole-notched specimen by performing the fracture test. From the results of the test, we can observe the initiation of a directional crack caused by the applied fatigue load. Further, we observed that the residual strength increases with a decrease in the notch effect due to this crack. It was evaluated that the residual strength increases to a certain level and subsequently decreases. This variation in the residual strength was represented by a simple equation by using a model of the decrease in residual strength for plain plate, which was developed by Reifsnider and a stress redistribution model for hole-notched plate, which was developed by Yip.

Partial Safety Factors for Fatigue Design of Wind Turbine Blades

DEFF Research Database (Denmark)

Toft, Henrik Stensgaard; Sørensen, John Dalsgaard

2010-01-01

In the present paper calibration of partial safety factors for fatigue design of wind turbine blades is considered. The stochastic models for the physical uncertainties on the material properties are based on constant amplitude fatigue tests and the uncertainty on Miners rule for linear damage...... accumulation is determined from variable amplitude fatigue tests with the Wisper and Wisperx spectra. The statistical uncertainty for the assessment of the fatigue loads is also investigated. The partial safety factors are calibrated for design load case 1.2 in IEC 61400-1. The fatigue loads are determined...... from rainflow-counting of simulated time series for a 5MW reference wind turbine [1]. A possible influence of a complex stress state in the blade is not taken into account and only longitudinal stresses are considered....

Fatigue - determination of a more realistic usage factor

International Nuclear Information System (INIS)

Lang, H.

2001-01-01

The ability to use a suitable counting method for determining the stress range spectrum in elastic and simplified elastic-plastic fatigue analyses is of crucial importance for enabling determination of a realistic usage factor. Determination of elastic-plastic strain range using the K e factor from fictitious elastically calculated loads is also important in the event of elastic behaviour being exceeded. This paper thus examines both points in detail. A fatigue module with additional options, which functions on this basis is presented. The much more realistic determination of usage factor presented here offers various economic benefits depending on the application

Study of the stress distribution around an orthotropic bi-material notch tip

Czech Academy of Sciences Publication Activity Database

Klusák, Jan; Profant, T.; Kotoul, M.

417-418, - (2010), s. 385-388 ISSN 1013-9826. [International Conference on Fracture and Damage Mechanics /8./. Malta, 08.09.2009-10.09.2009] R&D Projects: GA ČR GA101/08/0994; GA AV ČR 1QS200410502 Institutional research plan: CEZ:AV0Z20410507 Keywords : Generalized fracture mechanics * Singular stress distribution * Orthotropic bimaterial notch Subject RIV: JL - Materials Fatigue, Friction Mechanics www.scientific.net

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.

Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study).

Science.gov (United States)

Meliou, E; Kerezoudis, Np; Tosios, Ki; Kiaris, H

2010-07-27

Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion.

Strength gradient enhances fatigue resistance of steels

Science.gov (United States)

Ma, Zhiwei; Liu, Jiabin; Wang, Gang; Wang, Hongtao; Wei, Yujie; Gao, Huajian

2016-02-01

Steels are heavily used in infrastructure and the transportation industry, and enhancing their fatigue resistance is a major challenge in materials engineering. In this study, by introducing a gradient microstructure into 304 austenitic steel, which is one of the most widely used types of stainless steel, we show that a strength gradient substantially enhances the fatigue life of the material. Pre-notched samples with negative strength gradients in front of the notch’s tip endure many more fatigue cycles than do samples with positive strength gradients during the crack initiation stage, and samples with either type of gradient perform better than do gradient-free samples with the same average yield strength. However, as a crack grows, samples with positive strength gradients exhibit better resistance to fatigue crack propagation than do samples with negative gradients or no gradient. This study demonstrates a simple and promising strategy for using gradient structures to enhance the fatigue resistance of materials and complements related studies of strength and ductility.

Thermomechanical fatigue life prediction of high temperature components

Energy Technology Data Exchange (ETDEWEB)

Seifert, Thomas; Hartrott, Philipp von; Riedel, Hermann; Siegele, Dieter [Fraunhofer-Inst. fuer Werkstoffmechanik (IWM), Freiburg (Germany)

2009-07-01

The aim of the work described in this paper is to provide a computational method for fatigue life prediction of high temperature components, in which the time and temperature dependent fatigue crack growth is a relevant damage mechanism. The fatigue life prediction is based on a law for microcrack growth and a fracture mechanics estimate of the cyclic crack tip opening displacement. In addition, a powerful model for nonisothermal cyclic plasticity is employed, and an efficient laboratory test procedure is proposed for the determination of the model parameters. The models are efficiently implemented into finite element programs and are used to predict the fatigue life of a cast iron exhaust manifold and a notch in the perimeter of a turbine rotor made of a ferritic/martensitic 10%-chromium steel. (orig.)

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

Fatigue behaviour of 304L steel welded structures: influence of residual stresses and surface mechanical finishing

International Nuclear Information System (INIS)

Magnier-Monin, L.

2007-12-01

This study focuses on the influence of residual stresses and surface mechanical finishing on lifetime of stainless steel 304L welded structures. Residual stresses are determined on specific specimens of three types: base-metal, as-welded and ground-welded specimens. Each type is submitted to fatigue tests in order to assess the influence of these parameters on the lifetime, and to determine their evolution. The experiments show that an important surface stress concentration is located in the weld root of as-welded structures, which has a negative effect on the fatigue life. The grinding operation generates high-level surface residual stresses but the lifetime is higher thanks to the reduction of the notch effect. The fatigue test results are compared to the nuclear industry best-fit S-N curves. This enables the determination of correction factors related to fatigue test results of polished specimens, and to assess the lifetime of structures. (author)

Factors related to fatigue; priority of interventions to reduce or eliminate fatigue and the exploration of a multidisciplinary research model for further study of fatigue

NARCIS (Netherlands)

Tiesinga, LJ; Dassen, TWN; Halfens, RJG; van den Heuvel, WJA

A growing interest in the health problem presented by fatigue, both in clinical practice and research, coupled with a decreasing number of reported studies on fatigue in the last decade, make an updated and systematic review of factors related to fatigue necessary. A search of the literature,

Fatigue life evaluation of 42CrMo4 nitrided steel by local approach: Equivalent strain-life-time

International Nuclear Information System (INIS)

Terres, Mohamed Ali; Sidhom, Habib

2012-01-01

Highlights: → Ion nitriding treatment of 42CrMo4 steel improves their fatigue strength by 32% as compared with the untreated state. → This improvement is the result of the beneficial effects of the superficial work- hardening and of the stabilized compressive residual stress. → The notch region is found to be the fatigue crack nucleation site resulting from a stress concentration (Kt = 1.6). → The local equivalent strain-fatigue life method was found to be an interesting predictive fatigue life method for nitrided parts. -- Abstract: In this paper, the fatigue resistance of 42CrMo4 steel in his untreated and nitrided state was evaluated, using both experimental and numerical approaches. The experimental assessment was conducted using three points fatigue flexion tests on notched specimens at R = 0.1. Microstructure analysis, micro-Vickers hardness test, and scanning electron microscope observation were carried out for evaluating experiments. In results, the fatigue cracks of nitrided specimens were initiated at the surface. The fatigue life of nitrided specimens was prolonged compared to that of the untreated. The numerical method used in this study to predict the nucleation fatigue life was developed on the basis of a local approach, which took into account the applied stresses and stabilized residual stresses during the cyclic loading and the low cyclic fatigue characteristics. The propagation fatigue life was calculated using fracture mechanics concepts. It was found that the numerical results were well correlated with the experimental ones.

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.

What paramedics think about when they think about fatigue: contributing factors.

Science.gov (United States)

Paterson, Jessica L; Sofianopoulos, Sarah; Williams, Brett

2014-04-01

Paramedic fatigue is associated with burnout, attrition, sick leave, work disability, physical and mental health complaints and impaired performance. However, no studies have addressed how fatigue is understood by paramedics. The present study addresses this shortcoming by exploring factors paramedics recognise as contributors to fatigue. Forty-nine (12F; 38 years ± 9.7 years) Australian paramedics completed a survey on perceived causes of performance impairing fatigue. A total of 107 responses were systematically coded following principles common to qualitative data analysis: data immersion, coding, categorisation and theme generation. Six themes emerged: working time, sleep, workload, health and well-being, work-life balance and environment. Consistent with a scientific understanding of fatigue, prior sleep and wake, time of day and task-related factors were often identified as contributing to fatigue. In other cases, paramedics' attributions deviated from a scientific understanding of direct causes of fatigue. These findings demonstrate that paramedics have a broad understanding of fatigue. It is critical to take this into account when discussing fatigue with paramedics, particularly in the case of fatigue education or wellness programmes. These data highlight areas for intervention and education to minimise the experience of paramedic fatigue and the negative health and safety outcomes for paramedics and patients as a result. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Effects of applied stress ratio on the fatigue behavior of additively manufactured porous biomaterials under compressive loading.

Science.gov (United States)

de Krijger, Joep; Rans, Calvin; Van Hooreweder, Brecht; Lietaert, Karel; Pouran, Behdad; Zadpoor, Amir A

2017-06-01

Additively manufactured (AM) porous metallic biomaterials are considered promising candidates for bone substitution. In particular, AM porous titanium can be designed to exhibit mechanical properties similar to bone. There is some experimental data available in the literature regarding the fatigue behavior of AM porous titanium, but the effect of stress ratio on the fatigue behavior of those materials has not been studied before. In this paper, we study the effect of applied stress ratio on the compression-compression fatigue behavior of selective laser melted porous titanium (Ti-6Al-4V) based on the diamond unit cell. The porous titanium biomaterial is treated as a meta-material in the context of this work, meaning that R-ratios are calculated based on the applied stresses acting on a homogenized volume. After morphological characterization using micro computed tomography and quasi-static mechanical testing, the porous structures were tested under cyclic loading using five different stress ratios, i.e. R = 0.1, 0.3, 0.5, 0.7 and 0.8, to determine their S-N curves. Feature tracking algorithms were used for full-field deformation measurements during the fatigue tests. It was observed that the S-N curves of the porous structures shift upwards as the stress ratio increases. The stress amplitude was the most important factor determining the fatigue life. Constant fatigue life diagrams were constructed and compared with similar diagrams for bulk Ti-6Al-4V. Contrary to the bulk material, there was limited dependency of the constant life diagrams to mean stress. The notches present in the AM biomaterials were the sites of crack initiation. This observation and other evidence suggest that the notches created by the AM process cause the insensitivity of the fatigue life diagrams to mean stress. Feature tracking algorithms visualized the deformation during fatigue tests and demonstrated the root cause of inclined (45°) planes of specimen failure. In conclusion, the R

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

Directory of Open Access Journals (Sweden)

L. Náhlík

2014-10-01

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

Complete Absence of Suprascapular Notch: A Case Report

Directory of Open Access Journals (Sweden)

Rohini Mohan Pawar

2015-10-01

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

Fatigue crack propagation under elastic plastic medium at elevated temperature

International Nuclear Information System (INIS)

Asada, Y.; Yuuki, R.; Sakon, T.; Sunamoto, D.; Tokimasa, K.; Makino, Y.; Kitagawa, M; Shingai, K.

1980-01-01

The purposes of the present study are to establish the testing method to obtain compatible data on the low cycle fatigue crack propagation at elevated temperature, and to investigate the parameter controlling the crack propagation rate. In the present study, the preliminary experiments have been carried out on low cycle fatigue crack propagation behaviour in type 304 stainless steel in air at 550 0 C, using two types of specimen with a through thickness notch. Both strain controlled and stress controlled fatigue tests have been done under a fully reversed strain or stress cycling. The data obtained are correlated with some fracture mechanics parameters and are discussed with the appropriate parameter for evaluating the low cycle fatigue crack propagation behaviour at elevated temperature. (author)

Factors Affecting Quality of Life and Fatigue in Gynaecologic Cancer Patients

Directory of Open Access Journals (Sweden)

Güngör İ

2017-06-01

Full Text Available Background: Cancer-related fatigue (CRF is the most commonly reported and most distressing symptom in cancer patients. Health-related quality of life (QOL is an important outcome in cancer management, the authors sought to better understand its determinants. Aim: This study aims to identify quality of life and fatigue levels and the affecting factors in gynaecologic cancer patients. Method: This descriptive and cross-sectional study was conducted with 154 volunteer women with gynaecologic cancer. The data were collected through the interview form, functional assessment of cancer therapy-general (FACT-G Quality of Life Scale, and Piper Fatigue Scale. Results: The mean score of total quality of life in gynaecologic cancer patients was low, 53.4 ± 15.4. Physical and emotional states were found to be the mostly affected states in the quality of life. According to the Piper Fatigue Scale, the total fatigue score was mild, 3.5 ± 2.4. Total fatigue scores were found to be high in metastatic cancers. Multivariate analyses indicate that the most important factor affecting the quality of life is economic condition, and the most important variables affecting fatigue are the level of activity and use of medicine. Conclusion: This study found that quality of life dimensions in women with gynaecologic cancer was affected by factors such as cancer type, time of diagnosis, and stage and spread of the cancer.

Notch signaling protects retina from nuclear factor-kB- and poly-ADP-ribosepolymerase-mediated apoptosis under high-glucose stimulation

Institute of Scientific and Technical Information of China (English)

Xiuhong Qin1; Zhenzhen Zhang2; Haitao Xu1; and Yazhen Wu1

2011-01-01

Proliferative diabetic retinopathy,the primary cause of vision loss in adults,is one of serious microvascular complications caused by diabetes.Both poly-ADP-ribosepolymerase (PARP) and nuclear factor (NF)-kB signaling are involved in the injury process.Injury activates PARP,which in turn potentiates NF-kB activation and causes cell apoptosis.Like the NF-kB pathway,Notch1 signaling plays a key role in the regulation of cell proliferation,differentiation,and apoptosis.However,the connections between these signaling pathways are not well understood.In this study,we used both streptozotocin (STZ)-induced diabetic mice and human retinal vascular endothelial cells (HRVECs) cultured in high glucose to detect these relationships.We found that apoptosis was increased in both STZinduced diabetic mice and high-glucose-treated HRVECs,which was due to increased activation of PARP,cleaved caspase3,and reduced expression of Notch1 and p-Akt.The results of Notch1 overexpression and knockdown indicated that Notch1 signaling participated in the interaction of PARP and p50,and inhibited PARP- and p50-mediated apoptosis directly.These phenomena could be blocked by pretreatment with the PI3K inhibitor wortmannin via reducing p-Akt levels.Thus,our study demonstrated that Notch1 signaling protects cells from PARP- and NF-kB-induced apoptosis under high glucose through the activation of Akt.

Depressive symptoms and inflammation are independent risk factors of fatigue in breast cancer survivors.

Science.gov (United States)

Xiao, C; Miller, A H; Felger, J; Mister, D; Liu, T; Torres, M A

2017-07-01

Psychosocial and inflammatory factors have been associated with fatigue in breast cancer survivors. Nevertheless, the relative contribution and/or interaction of these factors with cancer-related fatigue have not been well documented. This cross-sectional study enrolled 111 stage 0-III breast cancer patients treated with breast surgery followed by whole breast radiotherapy. Fatigue was measured by the total score of the Multidimensional Fatigue Inventory-20. Potential risk factors included inflammatory markers (plasma cytokines and their receptors and C-reactive protein; CRP), depressive symptoms (as assessed by the Inventory of Depressive Symptomatology-Self Reported), sleep (as assessed by the Pittsburgh Sleep Quality Index) and perceived stress (as assessed by the Perceived Stress Scale) as well as age, race, marital status, smoking history, menopause status, endocrine treatment, chemotherapy and cancer stage. Linear regression modeling was employed to examine risk factors of fatigue. Only risk factors with a significance level fatigue. At 1 year post-radiotherapy, depressive symptoms (pfatigue. Mediation analysis showed that depressive symptoms also mediated the associations of fatigue with sleep and stress. Depressive symptoms and inflammation were independent risk factors for cancer-related fatigue at 1 year post-radiotherapy, and thus represent independent treatment targets for this debilitating symptom.

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.

Fatigue in cold-forging dies: Tool life analysis

DEFF Research Database (Denmark)

Skov-Hansen, P.; Bay, Niels; Grønbæk, J.

1999-01-01

In the present investigation it is shown how the tool life of heavily loaded cold-forging dies can be predicted. Low-cycle fatigue and fatigue crack growth testing of the tool materials are used in combination with finite element modelling to obtain predictions of tool lives. In the models...... the number of forming cycles is calculated first to crack initiation and then during crack growth to fatal failure. An investigation of a critical die insert in an industrial cold-forging tool as regards the influence of notch radius, the amount and method of pre-stressing and the selected tool material...

Crack initiation life analysis in notched pipe under cyclic bending loads

International Nuclear Information System (INIS)

Lee, Joon Seong; Kwak, Sang Log; Kim, Young Jin; Park, Youn Won

2001-01-01

In order to improve leak-before-break methodology, more precisely the crack growth evaluation, a round robin analysis was proposed by the CEA Saclay. The aim of this analysis was to evaluate the crack initiation life, penetration life and shape of through wall crack under cyclic bending loads. The proposed round robin analysis is composed of three main topic; fatigue crack initiation, crack propagation and crack penetration. This paper deals with the first topic, crack initiation in a notched pipe under four point bending. Both elastic-plastic finite element analysis and Neuber's rule were used to estimate the crack initiation life and the finite element models were verified by mesh-refinement, stress distribution and global deflection. In elastic-plastic finite element analysis, crack initiation life was determined by strain amplitude at the notch tip and strain-life curve of the material. In the analytical method, Neuber's rule with the consideration of load history and mean stress effect, was used for the life estimation. The effect of notch tip radius, strain range, cyclic hardening rule were examined in this study. When these results were compared with the experimental ones, the global deformation was a good agreement but crack initiation cycle was higher than the experimental result

[Factors related to subjective fatigue symptoms of adolescent girls].

Science.gov (United States)

Ikeda, Junko; Fukuda, Sayuri; Murakami, Toshio; Kawamoto, Naoki

2011-09-01

To assess changes in subjective fatigue symptoms of adolescent girls over a 15-year period and investigate factors related to these symptoms. A total of 86 items on physical health (including subjective fatigue symptoms), dietary life, and daily living were investigated and five items on physical activity were measured for approximately 100 female first-year dietetic students at a junior college each October over the 15-year period from 1994 to 2008. A total of 1,547 students (mean age, 19.2 +/- 0.3 years) were studied. Subjects were first divided into two groups using the median subjective fatigue score as the cutoff point, and annual changes in the proportion of students in the high subjective fatigue group were investigated by simple regression analysis. In addition, relationships between the two subjective fatigue groups and each item were investigated. 1) The proportion of students with many subjective fatigue symptoms showed a significantly increasing trend over the 15-year period. 2) Investigation of relationships between subjective fatigue symptoms and each factor revealed significance for many items, including dietary habits, life satisfaction, amount of sleep, and desire for a positive body image. 3) In order to determine which of the items were most strongly related to subjective fatigue symptoms, multiple logistic regression analysis was performed for the 15-year period as well as three 5-year periods into which it was divided. The results showed that the dietary habits score (an indicator of dietary habits) and life satisfaction were related to subjective fatigue symptoms during all four periods. As for other items, relationships were observed for amount of sleep in three, diet and salt intake score in two, and liking for coffee/tea, juice drinks, and oily food, bedtime snack, desire for body image, self-assessment of body type, and health consciousness in one. These findings indicate that perspectives in education for promoting the health of

Prediction of fretting fatigue behavior under elastic-plastic conditions

International Nuclear Information System (INIS)

Shin, Ki Su

2009-01-01

Fretting fatigue generally leads to the degradation of the fatigue strength of a material due to cyclic micro-slip between two contacting materials. Fretting fatigue is regarded as an important issue in designing aerospace structures. While many studies have evaluated fretting fatigue behavior under elastic deformation conditions, few have focused on fretting fatigue behavior under elastic-plastic deformation conditions, especially the crack orientation and fatigue life prediction for Ti-6Al-4V. The primary goal of this study was to characterize the fretting fatigue crack initiation behavior in the presence of plasticity. Experimental tests were performed using pad configurations involving elastic-plastic deformations. To calculate stress distributions under elastic-plastic fretting fatigue conditions, FEA was also performed. Several parametric approaches were used to predict fretting fatigue life along with stress distribution resulting from FEA. However, those parameters using surface stresses were unable to establish an equivalence between elastic fretting fatigue data and elastic-plastic fretting fatigue data. Based on this observation, the critical distance methods, which are commonly used in notch analysis, were applied to the fretting fatigue problem. In conclusion, the effective strain range method when used in conjunction with the SMSSR parameter showed a good correlation of data points between the pad configurations involving elastic and elastic plastic deformations

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

Directory of Open Access Journals (Sweden)

Matthew R. Broadus

2016-05-01

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

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

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

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.

Fatigue behavior of niobium--hydrogen alloys

International Nuclear Information System (INIS)

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

1978-01-01

The effects of hydrogen on room temperature fatigue behavior of niobium were investigated under both high frequency stress control and low frequency strain control conditions, in air. Hydrogen markedly improved the fatigue life in high frequency tests, while low frequency tests resulted in decreased fatigue life with increasing hydrogen content. Notches in hydrogen-charged alloys reduced high cycle life significantly but had little effect on low cycle tests. Fracture surfaces of annealed niobium mainly exhibited striations, with numerous cracks originating at troughs of striated bands in both stress and strain control tests. The fracture mode for alloys with hydrogen in solution was mixed, with striations interspersed with cleavage facets at high frequencies but generally cleavage steps at low frequencies. For the hydrided alloys, distinctive steps of mixed ductile-brittle appearance were revealed under high frequency conditions, but large cleavage facets only were observed for low frequency tests. The results are discussed in terms of the effects of hydrogen on the cyclic strain hardening rate, as well as on fatigue strength and ductility of niobium

Environmental-assisted fatigue in austenitic stainless steels under light water reactor conditions

International Nuclear Information System (INIS)

Seifert, H.P.; Ritter, S.; Spaetig, P.

2015-01-01

The environmental-assisted fatigue (EAF) initiation and subsequent short crack growth behaviour of different austenitic stainless steels were characterised under simulated BWR/HWC and primary PWR conditions by cyclic fatigue tests with sharply notched fracture mechanics specimens. After a brief summary overview on the previous PSI observations, an update with new and preliminary results about the effect of pH, dissolved hydrogen, load ratio/mean stress, long static load hold times and load sequences is given in this paper. At low electrochemical corrosion potentials (ECP), the physical EAF initiation life moderately decreases with increasing dissolved hydrogen content and decreasing pH. Both parameters have little effect on the subsequent short EAF crack growth within the investigated range. Notch strain amplitude thresholds for environmental effects on physical EAF crack initiation decrease with increasing load ratio and mean stress. At small notch strain amplitudes, the effect of mean stress is more pronounced in BWR/HWC environment than in air and predicted by typical fatigue life mean stress corrections. Under certain loading conditions, long static load hold times result in an increase of the physical EAF initiation life, which saturates for very long hold times. On the other hand, little effect of hold times on subsequent stationary short EAF crack growth rates is observed. The physical EAF initiation life under load sequence loading in high-temperature water may be moderately shorter or significantly longer than predicted by a linear damage accumulation rule and corresponding constant load amplitude tests depending on the load history. (authors)

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 ...

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.

The Effect of Numerical 2D and 3D Fem Element Modelling on Strain and Stress Distributions at Laser Weld Notches in Steel Sandwich Type Panels

Directory of Open Access Journals (Sweden)

Niklas Karol

2018-03-01

Full Text Available Like other means of transport, merchant ships face the problem of increasing requirements concerning the environment protection, which, among other issues, implies the reduction of fuel consumption by the ship. Here, the conventional approach which consists in making use of higher strength steels to decrease the mass of the ship hull can be complemented by the use of new steel structures of sandwich panel type. However, the lack of knowledge and experience concerning, among other issues, fatigue strength assessment of thin-walled sandwich structures makes their use limited. Untypical welds imply the need for individual approach to the fatigue analysis. The article presents the effect of numerical FEM modelling with the aid of two-dimensional (2D and three-dimensional (3D elements on the results of strain and stress distributions in the areas of toe and root notches of the analysed laser weld. The presented results of computer simulation reveal that modelling of strain and stress states in 2D (instead of full 3D affects only the results in close vicinity of the notch, and the observed differences rapidly disappear at a distance of 0.05 mm from the bottom of the notch. The obtained results confirm the possibility of use of numerically effective 2D strain and stress state models for analysing the fatigue strength of laser weld according to local approach.

Biopsychosocial risk factors of persistent fatigue after acute infection: A systematic review to inform interventions.

Science.gov (United States)

Hulme, Katrin; Hudson, Joanna L; Rojczyk, Philine; Little, Paul; Moss-Morris, Rona

2017-08-01

Fatigue is a prevalent and debilitating symptom, preceded by an acute infectious episode in some patients. This systematic review aimed to identify risk factors for the development of persistent fatigue after an acute infection, to develop an evidence-based working model of post-infectious fatigue. Electronic databases (Medline, PsycINFO and EMBASE) were searched, from inception to March 2016, for studies which investigated biopsychosocial risk factors of on-going fatigue after an acute infection. Inclusion criteria were: prospective design; biological, psychological or social risk factors; standardised measure of post-infectious fatigue (self-report scales or clinical diagnosis). Studies were excluded if the sample had a pre-existing medical condition, infection was conceptualised as 'vaccination' or they were intervention trials. A narrative synthesis was performed. Eighty-one full texts were screened, of which seventeen were included in the review. Over half included glandular fever populations. Other infections included dengue fever, 'general'/'viral' and Q-fever. Risk factors were summarised under biological, social, behavioural, cognitive and emotional subthemes. Patients' cognitive and behavioural responses to the acute illness, and pre-infection or baseline distress and fatigue were the most consistent risk factors for post-infectious fatigue. An empirical summary model is provided, highlighting the risk factors most consistently associated with persistent fatigue. The components of the model, the possible interaction of risk factors and implications for understanding the fatigue trajectory and informing preventative treatments are discussed. Copyright © 2017. Published by Elsevier Inc.

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

The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma

International Nuclear Information System (INIS)

Revet, Ingrid; Huizenga, Gerda; Chan, Alvin; Koster, Jan; Volckmann, Richard; Sluis, Peter van; Ora, Ingrid; Versteeg, Rogier; Geerts, Dirk

2008-01-01

Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro-array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated. Western blot analysis showed that MSX1 induction caused cleavage of the NOTCH3 protein to its activated form, further confirming activation of the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology. Affymetrix micro-array analysis of a neuroblastic tumour series consisting of neuroblastomas and the more benign ganglioneuromas showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas. This suggests a block in differentiation of these tumours at distinct developmental stages or lineages

Analysis on the factors affecting seafarers fatigue based on European Navigation Inc

DEFF Research Database (Denmark)

Zhao, Zhi Wei; Zhu, Yun Qi; Zheng, En Xi

2017-01-01

In order to analyze the main factors associated with fatigue and analyze the main factors which contribute to fatigue of different types of seafarers. SPSS software was used to carry out optimal scale multiple regression and variance analysis based on the questionnaire surveys of 454 employees...

The Factors and Features of Museum Fatigue in Science Centres Felt by Korean Students

Science.gov (United States)

Kim, Minchul; Dillon, Justin; Song, Jinwoong

2018-03-01

One of the objectives of science education in science centres has been the enhancement of interest in science. However, museum fatigue has a negative impact on interest. Museum fatigue has been described as physical tiredness or a decrease in visitors' interest in a museum. The learning experience of students in science centres is also influenced by museum fatigue. The purpose of this study is to identify the phenomena of museum fatigue in science centres and to identity how it is manifested. First, we identified the factors causing museum fatigue in science centres using the data from an open-ended questionnaire which was given to 597 primary, middle and high school students in South Korea. From the responses to the questionnaire, 50 factors causing museum fatigue in science centres were identified. A second Likert-type questionnaire with the 50 factors of museum fatigue in science centres was administered to 610 primary, middle and high school students in South Korea. Using reliability and factor analyses, we developed a framework of the factors causing museum fatigue in science centres, which consists of three contexts, 12 categories and 50 factors. Secondly, through statistical analyses including T test and ANOVA analysis, the features of students' museum fatigue in science centres were analysed and compared regarding student gender, school level, interest in science, grade of school science, the number of visits, and type of visit. The results, which were found to be statistically significant, are reported and discussed. The findings of this study are intended to serve for a deeper understanding and practical improvement of science learning in science centres.

Proinflammatory cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) suppresses satellite cell self-renewal through inversely modulating Notch and NF-κB signaling pathways.

Science.gov (United States)

Ogura, Yuji; Mishra, Vivek; Hindi, Sajedah M; Kuang, Shihuan; Kumar, Ashok

2013-12-06

Satellite cell self-renewal is an essential process to maintaining the robustness of skeletal muscle regenerative capacity. However, extrinsic factors that regulate self-renewal of satellite cells are not well understood. Here, we demonstrate that TWEAK cytokine reduces the proportion of Pax7(+)/MyoD(-) cells (an index of self-renewal) on myofiber explants and represses multiple components of Notch signaling in satellite cell cultures. The number of Pax7(+) cells is significantly increased in skeletal muscle of TWEAK knock-out (KO) mice compared with wild-type in response to injury. Furthermore, Notch signaling is significantly elevated in cultured satellite cells and in regenerating myofibers of TWEAK-KO mice. Forced activation of Notch signaling through overexpression of the Notch1 intracellular domain (N1ICD) rescued the TWEAK-mediated inhibition of satellite cell self-renewal. TWEAK also activates the NF-κB transcription factor in satellite cells and inhibition of NF-κB significantly improved the number of Pax7(+) cells in TWEAK-treated cultures. Furthermore, our results demonstrate that a reciprocal interaction between NF-κB and Notch signaling governs the inhibitory effect of TWEAK on satellite cell self-renewal. Collectively, our study demonstrates that TWEAK suppresses satellite cell self-renewal through activating NF-κB and repressing Notch signaling.

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

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.)

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

Self-Reported Fatigue and Associated Factors Six Years after Stroke.

Directory of Open Access Journals (Sweden)

Marie Elf

Full Text Available Several studies have found that fatigue is one of the most commonly reported symptoms after stroke and the most difficult to cope with. The present study aimed to investigate the presence and severity of self-reported fatigue six years after stroke onset and associated factors. The cohort "Life After Stroke Phase I" (n = 349 persons was invited at six years to report fatigue (Fatigue Severity Scale 7-item version, perceived impact of stroke and global recovery after stroke (Stroke Impact Scale, anxiety and depression (Hospital Anxiety and Depression Scale, life satisfaction (Life Satisfaction Checklist and participation in everyday social activities (Frenchay Activities Index. At six years 37% of the 102 participants in this cross-sectional study reported fatigue. The results showed that in nearly all SIS domains the odds for post-stroke fatigue were higher in persons with a higher perceived impact. Furthermore, the odds for post-stroke fatigue were higher in those who had experienced a moderate/severe stroke and had signs of depression and anxiety. Fatigue is still present in one-third of persons as long as six years after stroke onset and is perceived to hinder many aspects of functioning in everyday life. There is an urgent need to develop and evaluate interventions to reduce fatigue.

Fatigue strength of Al2O3 and Si3N4 ceramics

International Nuclear Information System (INIS)

Sonsino, C.M.

1992-01-01

Various Al 2 O 3 ceramics and random samples of two Si 3 N 4 ceramics were examined, with all specimens differing in terms of material and manufacturing parameters. Of the Al 2 O 3 ceramics, randomly selected specimens were tested for their banding strength at room temperature, and three specifically selected specimens were tested for their compressive strength at room temperature, at 800 C and at 1200 C. A number of specimen variants were examined by cyclic fatigue tests at room temperature and 800 C, and at 1200 C in one case, the specimens used being slightly notched specimens (α n = 1,02 and 1,08), or more heavily notched speciments (α n = 1.77, 1.90 and 2.24), with bending loads being either cyclic or growing. The Si 3 N 4 specimens were randomly chosen for bending tests and cyclic fatigue tests, at room temperature. (orig./MM) [de

Damage and fatigue crack growth of Eurofer steel first wall mock-up under cyclic heat flux loads. Part 2: Finite element analysis of damage evolution

International Nuclear Information System (INIS)

You, Jeong-Ha

2014-01-01

Highlights: • The surface heat flux load of 3.5 MW/m 2 produced substantial stresses and inelastic strains in the heat-loaded surface region, especially at the notch root. • The notch root exhibited a typical notch effect such as stress concentration and localized inelastic yield leading to a preferred damage development. • The predicted damage evolution feature agrees well with the experimental observation. • The smooth surface also experiences considerable stresses and inelastic strains. However, the stress intensity and the amount of inelastic deformation are not high enough to cause any serious damage. • The level of maximum inelastic strain is higher at the notch root than at the smooth surface. On the other hand, the amplitude of inelastic strain variation is comparable at both positions. • The amount of inelastic deformation is significantly affected by the length of pulse duration time indicating the important role of creep. - Abstract: In the preceding companion article (part 1), the experimental results of the high-heat-flux (3.5 MW/m 2 ) fatigue tests of a Eurofer bare steel first wall mock-up was presented. The aim was to investigate the damage evolution and crack initiation feature. The mock-up used there was a simplified model having only basic and generic structural feature of an actively cooled steel FW component for DEMO reactor. In that study, it was found that microscopic damage was formed at the notch root already in the early stage of the fatigue loading. On the contrary, the heat-loaded smooth surface exhibited no damage up to 800 load cycles. In this paper, the high-heat-flux fatigue behavior is investigated with a finite element analysis to provide a theoretical interpretation. The thermal fatigue test was simulated using the coupled damage-viscoplastic constitutive model developed by Aktaa. The stresses, inelastic deformation and damage evolution at the notch groove and at the smooth surface are compared. The different damage

Influence of laser hardening with weld penetration onto mechanical and fatigue properties of 40H steel

International Nuclear Information System (INIS)

Napadlek, W.; Przetakiewicz, W.

2003-01-01

In the article were described investigations results of mechanical properties (hardness, R 0.2 , R m , A 5 , Z) and fatigue properties (rotary bending) of the 40H steel samples, being quenched and tempered, induction and laser hardened. In the laser hardened samples with weld penetration of top layer cracking process in fatigue strength is started mainly in weld penetration area as structural notch. (author)

Concentration of stresses and strains in a notched cyclinder of a viscoplastic material under harmonic loading

Science.gov (United States)

Zhuk, Ya A.; Senchenkov, I. K.

1999-02-01

Certain aspects of the correct definitions of stress and strain concentration factors for elastic-viscoplastic solids under cyclic loading are discussed. Problems concerning the harmonic kinematic excitation of cylindrical specimens with a lateral V-notch are examined. The behavior of the material of a cylinder is modeled using generalized flow theory. An approximate model based on the concept of complex moduli is used for comparison. Invariant characteristics such as stress and strain intensities and maximum principal stress and strain are chosen as constitutive quantities for concentration-factor definitions. The behavior of time-varying factors is investigated. Concentration factors calculated in terms of the amplitudes of the constitutive quantities are used as representative characteristics over the cycle of vibration. The dependences of the concentration factors on the loads are also studied. The accuracy of Nueber's and Birger's formulas is evaluated. The solution of the problem in the approximate formulation agrees with its solution in the exact formulation. The possibilities of the approximate model for estimating low-cycle fatigue are evaluated.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan.

Directory of Open Access Journals (Sweden)

Feng-Cheng Tang

Full Text Available Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1 to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2 to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled.A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine, psychological condition (perceived mental health and psychological distress, job-related psychosocial factors (job demand, job control, and workplace social support, and prolonged fatigue.A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue.Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers' prolonged fatigue. However, more research is required to verify the causation among all the variables.

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.

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.

Estimation of Fatigue Crack Growth Behavior of Cracked Specimen Under Mixed-mode Loads

International Nuclear Information System (INIS)

Han, Jeong Woo; Woo, Eun Taek; Han, Seung Ho

2015-01-01

To estimate the fatigue crack propagation behavior of compact tension shear (CTS) specimen under mixed-mode loads, crack path prediction theories and Tanaka’s equation were applied. The stress intensity factor at a newly created crack tip was calculated using a finite element method via ANSYS, and the crack path and crack increment were then obtained from the crack path prediction theories, Tanaka’s equation, and the Paris’ equation, which were preprogrammed in Microsoft Excel. A new method called the finite element crack tip updating method (FECTUM) was developed. In this method, the finite element method and Microsoft Excel are used to calculate the stress intensity factors and the crack path, respectively, at the crack tip per each crack increment. The developed FECTUM was applied to simulate the fatigue crack propagation of a single-edge notched bending (SENB) specimen under eccentric three-point bending loads. The results showed that the number of cycles to failure of the specimen obtained experimentally and numerically were in good agreement within an error range of less than 3%

Estimation of Fatigue Crack Growth Behavior of Cracked Specimen Under Mixed-mode Loads

Energy Technology Data Exchange (ETDEWEB)

Han, Jeong Woo [KIMM, Daejeon (Korea, Republic of); Woo, Eun Taek; Han, Seung Ho [Dong-A University, Busan (Korea, Republic of)

2015-07-15

To estimate the fatigue crack propagation behavior of compact tension shear (CTS) specimen under mixed-mode loads, crack path prediction theories and Tanaka’s equation were applied. The stress intensity factor at a newly created crack tip was calculated using a finite element method via ANSYS, and the crack path and crack increment were then obtained from the crack path prediction theories, Tanaka’s equation, and the Paris’ equation, which were preprogrammed in Microsoft Excel. A new method called the finite element crack tip updating method (FECTUM) was developed. In this method, the finite element method and Microsoft Excel are used to calculate the stress intensity factors and the crack path, respectively, at the crack tip per each crack increment. The developed FECTUM was applied to simulate the fatigue crack propagation of a single-edge notched bending (SENB) specimen under eccentric three-point bending loads. The results showed that the number of cycles to failure of the specimen obtained experimentally and numerically were in good agreement within an error range of less than 3%.

An evaluation on fatigue crack growth in a fine-grained isotropic graphite

International Nuclear Information System (INIS)

Wang Hongtao; Sun Libin; Li Chenfeng; Shi Li; Wang Haitao

2012-01-01

Highlights: ► The propagation of micro- and macro-fatigue cracks in IG-11 graphite was studied. ► The curves of the fatigue crack growth rate versus the SIF range show three stages. ► The fatigue microcrack propagation is very sensitive to graphite's microstructures. ► Graphite's microstructures have no significant impact on fatigue macrocrack growth. ► The fatigue fracture surface indicates the fracture mechanism of the IG-11 graphite. - Abstract: The aim of this paper is to investigate the mechanism of fatigue crack propagation in IG-11 graphite, and determine the crack growth rate in relation to the stress level. Experimental studies were performed at both micro and macro scales. For fatigue microcrack propagation, single-edge-notch specimens were chosen for testing and the fatigue crack growth was measured in situ with a scanning electron microscope. For fatigue macrocrack propagation, CT specimens were used and the fatigue crack growth was measured with a high-accuracy optic microscope. Combining the two groups of experimental results, the following conclusions are derived: (1) The heterogeneous microstructures of the graphite material have significant impact on the fatigue microcrack growth, while their influence on fatigue macrocrack growth is very limited. (2) The relationship between the fatigue crack growth rate and the crack-tip stress intensity factor range can be expressed in the form of Paris formulae, which contains three stages: an initial rising part with a small slope, an abrupt rise with a very large acceleration, and a short final part with a small slope. (3) The fatigue fracture surface of the graphite material contains considerable sliding of leaf-shape graphite flakes combined with small cotton-shape plastic deformations. These sliding traces are approximately aligned at 45°, showing the main cause of the fatigue fracture is the shear stress. There are also a large amount of secondary cracks inside unit cells and on cell walls

Fatigue crack growth in fiber-metal laminates

Science.gov (United States)

Ma, YuE; Xia, ZhongChun; Xiong, XiaoFeng

2014-01-01

Fiber-metal laminates (FMLs) consist of three layers of aluminum alloy 2024-T3 and two layers of glass/epoxy prepreg, and it (it means FMLs) is laminated by Al alloy and fiber alternatively. Fatigue crack growth rates in notched fiber-metal laminates under constant amplitude fatigue loading were studied experimentally and numerically and were compared with them in monolithic 2024-T3 Al alloy plates. It is shown that the fatigue life of FMLs is about 17 times longer than monolithic 2024-T3 Al alloy plate; and crack growth rates in FMLs panels remain constant mostly even when the crack is long, unlike in the monolithic 2024-T3 Al alloy plates. The formula to calculate bridge stress profiles of FMLs was derived based on the fracture theory. A program by Matlab was developed to calculate the distribution of bridge stress in FMLs, and then fatigue growth lives were obtained. Finite element models of FMLs were built and meshed finely to analyze the stress distributions. Both results were compared with the experimental results. They agree well with each other.

FATIGUE AS A HAZARDOUS FACTOR FOR FLIGHT SAFETY

Directory of Open Access Journals (Sweden)

M. Lushkin Alexander

2017-01-01

Full Text Available The main priority of any air company activity and the main condition for its development is the achievement of the highest flight safety level. Significant positive results in this area have been recently achieved, hence, the relative stagna- tion of indexes, reflecting the flight safety as a condition of air transport system, has been revealed. It has become evident that the present accident prevention philosophy seems to be exhausted, and at the current stage of development it doesn’t allow to make a breakthrough in the solution of all the problems, which air companies face in this respect. In the perspec- tive to find new ways to solve the existing tasks, in 2011, International Civil Aviation Organization Council adopted fatigue risk management international standards as an alternative for the traditional approach to managing crewmember fatigue by prescribing limits on maximum daily, monthly and yearly flight and duty hours. It’s a well-known fact that state of fatigue has a special place among the functional states, which are professionally significant for airmen work and which are the key link in “man-aircraft-environment” system.In this article, fatigue is considered to be a risk factor that contributes to the formation and development of crew violations and errors in the process of piloting the aircraft. We have analyzed the characteristics and reasons leading to in- flight fatigue and estimated its influence on crew performance, considering the interrelation between them. The article specifies the methods and techniques to measure pilots fatigue; besides it has been substantiated the necessity of fatigue risk management system development in airlines to effectively ensure the flight safety.

Risk factors and visual fatigue of baggage X-ray security screeners: a structural equation modelling analysis.

Science.gov (United States)

Yu, Rui-Feng; Yang, Lin-Dong; Wu, Xin

2017-05-01

This study identified the risk factors influencing visual fatigue in baggage X-ray security screeners and estimated the strength of correlations between those factors and visual fatigue using structural equation modelling approach. Two hundred and five X-ray security screeners participated in a questionnaire survey. The result showed that satisfaction with the VDT's physical features and the work environment conditions were negatively correlated with the intensity of visual fatigue, whereas job stress and job burnout had direct positive influences. The path coefficient between the image quality of VDT and visual fatigue was not significant. The total effects of job burnout, job stress, the VDT's physical features and the work environment conditions on visual fatigue were 0.471, 0.469, -0.268 and -0.251 respectively. These findings indicated that both extrinsic factors relating to VDT and workplace environment and psychological factors including job burnout and job stress should be considered in the workplace design and work organisation of security screening tasks to reduce screeners' visual fatigue. Practitioner Summary: This study identified the risk factors influencing visual fatigue in baggage X-ray security screeners and estimated the strength of correlations between those factors and visual fatigue. The findings were of great importance to the workplace design and the work organisation of security screening tasks to reduce screeners' visual fatigue.

Fatigue in out-patients with inflammatory bowel disease: Prevalence and predictive factors.

Science.gov (United States)

Villoria, Albert; García, Víctor; Dosal, Angelina; Moreno, Laura; Montserrat, Antònia; Figuerola, Ariadna; Horta, Diana; Calvet, Xavier; Ramírez-Lázaro, María José

2017-01-01

Fatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue. Consecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores. Biological parameters were assessed, including levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients. We prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn's disease) for the study. Fatigue measured by FACIT-F score was prevalent in the studied population (54%, 96/177) and higher than in the general population. In the univariate analysis no relation was found between IL levels or micronutrient deficiencies and fatigue. Fatigue was significantly related to female sex, Crohn's disease, joint disorders, body mass index (BMI), psychological tests, thiopurine use, and anti-TNF treatment. All these variables were included in the multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score (OR: 0.82) was significantly related to lower degrees of fatigue. Fatigue was prevalent in quiescent IBD patients with moderate-to-severe disease. It was associated with high levels of depression, low quality of life, and female sex. No association was found with the other biological and psychological factors evaluated.

Fatigue of Chinese railway employees and its influential factors: Structural equation modelling.

Science.gov (United States)

Tsao, Liuxing; Chang, Jing; Ma, Liang

2017-07-01

Fatigue is an identifiable and preventable cause of accidents in transport operations. Regarding the railway sector, incident logs and simulation studies show that employee fatigue leads to lack of alertness, impaired performance, and occurrence of incidents. China has one of the largest rail systems in the world, and Chinese railway employees work under high fatigue risks; therefore, it is important to assess their fatigue level and find the major factors leading to fatigue. We designed a questionnaire that uses Multidimensional Fatigue Instrument (MFI-20), NASA-TLX and subjective rating of work overtime feelings to assess employee fatigue. The contribution of each influential factor of fatigue was analysed using structural equation modelling. In total, 297 employees from the rail maintenance department and 227 employees from the locomotive department returned valid responses. The average scores and standard deviations for the five subscales of MFI-20, namely General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue, were 2.9 (0.8), 2.8 (0.8), 2.5 (0.8), 2.5 (0.7), and 2.4 (0.8) among the rail maintenance employees and 3.5 (0.8), 3.5 (0.7), 3.3 (0.7), 3.0 (0.6), and 3.1 (0.7), respectively, among the locomotive employees. The fatigue of the locomotive employees was influenced by feelings related to working overtime (standardized r = 0.22) and workload (standardized r = 0.27). The work overtime control and physical working environment significantly influenced subjective feelings (standardized r = -0.25 and 0.47, respectively), while improper work/rest rhythms and an adverse physical working environment significantly increased the workload (standardized r = 0.48 and 0.33, respectively). Copyright © 2017 Elsevier Ltd. All rights reserved.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan

Science.gov (United States)

Tang, Feng-Cheng; Li, Ren-Hau; Huang, Shu-Ling

2016-01-01

Background and Objectives Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1) to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2) to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled. Methods A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine), psychological condition (perceived mental health and psychological distress), job-related psychosocial factors (job demand, job control, and workplace social support), and prolonged fatigue. Results A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue. Conclusion Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers’ prolonged fatigue. However, more research is required to verify the causation among all the variables. PMID:26930064

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.

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

Fatigue of weld ends under combined in- and out-of-phase multiaxial loading

Directory of Open Access Journals (Sweden)

E. Shams

2016-10-01

Full Text Available Weld start and end points are fatigue failure sensitive locations. Their fatigue behaviour especially in thin sheet structures under multiaxial load conditions is not sufficiently explored so far. Therefore, a research project was initiated to increase the knowledge concerning this topic, which is of special interest in the automotive industry. In the present study, fatigue tests on welded joints were conducted. In the numerical part of the study, notch stresses were calculated with an idealised weld end model. A numerical method which combines the geometrical and statistical size effect to an integrated approach was used, in order to consider the size effects

IIW guidelines on weld quality in relationship to fatigue strength

CERN Document Server

Jonsson, Bertil; Hobbacher, A F; Kassner, M; Marquis, G

2016-01-01

This book presents guidelines on quantitative and qualitative measures of the geometric features and imperfections of welds to ensure that it meets the fatigue strength requirements laid out in the recommendations of the IIW (International Institute of Welding). Welds that satisfy these quality criteria can be assessed in accordance with existing IIW recommendations based on nominal stress, structural stress, notch stress or linear fracture mechanics. Further, the book defines more restrictive acceptance criteria based on weld geometry features and imperfections with increased fatigue strength. Fatigue strength for these welds is defined as S-N curves expressed in terms of nominal applied stress or hot spot stress. Where appropriate, reference is made to existing quality systems for welds.In addition to the acceptance criteria and fatigue assessment curves, the book also provides guidance on their inspection and quality control. The successful implementation of these methods depends on adequate training for o...

Fatigue Analysis of Tubesheet/Shell Juncture Applying the Mitigation Factor for Over-conservatism

International Nuclear Information System (INIS)

Kang, Deog Ji; Kim, Kyu Hyoung; Lee, Jae Gon

2009-01-01

If the environmental fatigue requirements are applied to the primary components of a nuclear power plant, to which the present ASME Code fatigue curves are applied, some locations with high level CUF (Cumulative Usage Factor) are anticipated not to meet the code criteria. The application of environmental fatigue damage is still particularly controversial for plants with 60-year design lives. Therefore, it is need to develop a detailed fatigue analysis procedure to identify the conservatisms in the procedure and to lower the cumulative usage factor. Several factors are being considered to mitigate the conservatism such as three-dimensional finite element modeling. In the present analysis, actual pressure transient data instead of conservative maximum and minimum pressure data was applied as one of mitigation factors. Unlike in the general method, individual transient events were considered instead of the grouped transient events. The tubesheet/shell juncture in the steam generator assembly is the one of the weak locations and was, therefore, selected as a target to evaluate the mitigation factor in the present analysis

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

Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

Science.gov (United States)

Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

2011-01-01

Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

Science.gov (United States)

Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

2011-04-01

Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Influence of surface finish on fatigue properties of metallic materials: a bibliographic study

International Nuclear Information System (INIS)

Akamatsu, M.

1997-01-01

The investigation of a fatigue failed component very often shows that cracks initiated at the surface. It is actually well known that the surface finish notably influences the fatigue strength of a component. We have carried out a bibliographic study in order to clarify the influence of the different surface parameters. The analysis of the literature has shown that most of the data concerns high cycle fatigue. Three aspects of the surface finish have been examined: geometry (roughness), residual stresses and microstructure. In a general way, the influence of geometrical surface finish is tackled either empirically, with a factor assessing the fatigue limit decrease when the roughness and the tensile strength increase, or theoretically, with approaches modelling geometrical irregularities as notches or cracks. In all cases, the effect of roughness on fatigue strength depends on the material, through mechanical properties or microstructural features. The theoretical approaches seem particularly interesting, but their use is not straightforward and requires further development. The creation of residual stresses at the surface of a component can just as well reduce as improve its fatigue strength. In a first approach, these stresses can be regarded as a mean service stress. In fact, mechanical and metallurgical gradients near the surface have to be taken into account, which affect the relaxation of residual stresses during fatigue cycling. Actually, the effect of residual stresses can hardly be isolated, because these stresses are associated with geometrical and microstructural modifications. Microstructural features (metallurgical structure, grain size, inclusions, strain hardening) have an undoubted influence on fatigue strength, but the quantification of the effects remains tricky. The influence of the microstructure of surface layers on fatigue strength generally depends on the mechanical properties of materials. In short, fatigue strength predictions through a

Small Crack Growth and Fatigue Life Predictions for High-Strength Aluminium Alloys. Part 1; Experimental and Fracture Mechanics Analysis

Science.gov (United States)

Wu, X. R.; Newman, J. C.; Zhao, W.; Swain, M. H.; Ding, C. F.; Phillips, E. P.

1998-01-01

The small crack effect was investigated in two high-strength aluminium alloys: 7075-T6 bare and LC9cs clad alloy. Both experimental and analytical investigations were conducted to study crack initiation and growth of small cracks. In the experimental program, fatigue tests, small crack and large crack tests A,ere conducted under constant amplitude and Mini-TWIST spectrum loading conditions. A pronounced small crack effect was observed in both materials, especially for the negative stress ratios. For all loading conditions, most of the fatigue life of the SENT specimens was shown to be crack propagation from initial material defects or from the cladding layer. In the analysis program, three-dimensional finite element and A weight function methods were used to determine stress intensity factors and to develop SIF equations for surface and corner cracks at the notch in the SENT specimens. A plastisity-induced crack-closure model was used to correlate small and large crack data, and to make fatigue life predictions, Predicted crack-growth rates and fatigue lives agreed well with experiments. A total fatigue life prediction method for the aluminum alloys was developed and demonstrated using the crack-closure model.

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Directory of Open Access Journals (Sweden)

Angelo Sparaneo

2016-01-01

Full Text Available The transcription factor Nrf2 (NF-E2 related factor 2 is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

Work factors as predictors of persistent fatigue: a prospective study of nurses' aides.

Science.gov (United States)

Eriksen, W

2006-06-01

To identify work factors that predict persistent fatigue in nurses' aides. The sample comprised 5547 Norwegian nurses' aides, not on leave when they completed a mailed questionnaire in 1999. Of these, 4645 (83.7%) completed a second questionnaire 15 months later. The outcome measure was the occurrence of persistent fatigue, defined as having felt "usually fatigued" or "always fatigued" in daytime during the previous 14 days. In respondents without persistent fatigue at baseline, medium and high work demands, heavy smoking, being single, and having long term health problems were associated with increased risk of persistent fatigue at follow up. Medium and high rewards for well done work, medium levels of leadership fairness, and regular physical exercise were associated with reduced risk of persistent fatigue at follow up. In respondents with persistent fatigue at baseline, medium and high levels of positive challenges at work, high support from immediate superior, medium feedback about quality of one's work, and changes of work or work tasks that resulted in less heavy work or lower work pace were associated with increased odds of recovery (no persistent fatigue at follow up). Working in a nursing home and being intensely bothered by long term health problems were associated with reduced odds of recovery. High demands and lack of rewards at work may cause persistent fatigue in nurses' aides. Reduction of demands, adequate feedback, and mental stimulation in the form of support and positive challenges may facilitate recovery in those who have persistent fatigue. Leaders in the health services may be in a position to regulate factors that influence the level of fatigue in nurses' aides.

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.

Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity

International Nuclear Information System (INIS)

Liu, Baohui; Lin, Xi; Yang, Xiangsheng; Dong, Huimin; Yue, Xiaojing; Andrade, Kelsey C; Guo, Zhentao; Yang, Jian; Wu, Liquan; Zhu, Xiaonan; Zhang, Shenqi; Tian, Daofeng; Wang, Junmin; Cai, Qiang; Chen, Qizuan; Mao, Shanping; Chen, Qianxue; Chang, Jiang

2015-01-01

Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency-mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis

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.

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.

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.

[Analysis of work-related fatigue characteristics and its influencing factors in scientific and technical personnel].

Science.gov (United States)

Yang, Ting; Zhou, Dinglun; Song, Mingying; Lan, Yajia

2015-02-01

To investigate the current status and characteristics of work-related fatigue among scientific and technical personnel and its associated factors, and to provide a scientific basis for further interventions. A cross-sectional survey was conducted in the staff from a single scientific institution, using a self-administered questionnaire. Basic information of participants, Fatigue Scale-14, and Job Content Questionnaire were collected. The prevalence of work-related fatigue among the scientific and technical personnel was 54.6%; work-related fatigue was positively correlated with occupational stress (rs = 0.384, P work-related fatigue included occupational stress profiles, social support, and educational status. A higher risk of work-related fatigue was found in the staff under high stress, compared with those under low stress (OR = 8.5, 95%CI = 3.9∼18.7). Social support served as a protective factor for work-related fatigue, while a higher level of education was correlated with more severe work-related fatigue. Work-related fatigue is common and serious among scientific and technical personnel, especially in those under high stress. Effective interventions according to occupational stress are of great importance to reduce work-related fatigue.

An evaluation on fatigue crack growth in a fine-grained isotropic graphite

Energy Technology Data Exchange (ETDEWEB)

Wang Hongtao; Sun Libin [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084 (China); Li Chenfeng [College of Engineering, Swansea University, Singleton Park, Swansea SA2 8PP (United Kingdom); Shi Li [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084 (China); Wang Haitao, E-mail: wanght@tsinghua.edu.cn [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084 (China)

2012-09-15

Highlights: Black-Right-Pointing-Pointer The propagation of micro- and macro-fatigue cracks in IG-11 graphite was studied. Black-Right-Pointing-Pointer The curves of the fatigue crack growth rate versus the SIF range show three stages. Black-Right-Pointing-Pointer The fatigue microcrack propagation is very sensitive to graphite's microstructures. Black-Right-Pointing-Pointer Graphite's microstructures have no significant impact on fatigue macrocrack growth. Black-Right-Pointing-Pointer The fatigue fracture surface indicates the fracture mechanism of the IG-11 graphite. - Abstract: The aim of this paper is to investigate the mechanism of fatigue crack propagation in IG-11 graphite, and determine the crack growth rate in relation to the stress level. Experimental studies were performed at both micro and macro scales. For fatigue microcrack propagation, single-edge-notch specimens were chosen for testing and the fatigue crack growth was measured in situ with a scanning electron microscope. For fatigue macrocrack propagation, CT specimens were used and the fatigue crack growth was measured with a high-accuracy optic microscope. Combining the two groups of experimental results, the following conclusions are derived: (1) The heterogeneous microstructures of the graphite material have significant impact on the fatigue microcrack growth, while their influence on fatigue macrocrack growth is very limited. (2) The relationship between the fatigue crack growth rate and the crack-tip stress intensity factor range can be expressed in the form of Paris formulae, which contains three stages: an initial rising part with a small slope, an abrupt rise with a very large acceleration, and a short final part with a small slope. (3) The fatigue fracture surface of the graphite material contains considerable sliding of leaf-shape graphite flakes combined with small cotton-shape plastic deformations. These sliding traces are approximately aligned at 45 Degree-Sign , showing the

Effect of laser shock peening on residual stress and fatigue life of clad 2024 aluminium sheet containing scribe defects

International Nuclear Information System (INIS)

Dorman, M.; Toparli, M.B.; Smyth, N.; Cini, A.; Fitzpatrick, M.E.; Irving, P.E.

2012-01-01

Highlights: ► Effect of laser peen intensity on local residual stress fields in 2024 aluminium. ► Peening induces significant changes in surface topography and local hardness. ► Residual stress at peen spot centre in tension, spot overlap in compression. ► Notched fatigue lives increased; crack morphology correlated to residual stress field. ► Large peening power densities can cause fatigue life reduction in notched samples. - Abstract: Laser peening at a range of power densities has been applied to 2 mm-thick sheets of 2024 T351 aluminium. The induced residual stress field was measured using incremental hole drilling and synchrotron X-ray diffraction techniques. Fatigue samples were subjected to identical laser peening treatments followed by scribing at the peen location to introduce stress concentrations, after which they were fatigue tested. The residual stresses were found to be non-biaxial: orthogonal to the peen line they were tensile at the surface, moving into the desired compression with increased depth. Regions of peen spot overlap were associated with large compression strains; the centre of the peen spot remaining tensile. Fatigue lives showed moderate improvement over the life of unpeened samples for 50 μm deep scribes, and slight improvement for samples with 150 μm scribes. Use of the residual stress intensity K resid approach to calculate fatigue life improvement arising from peening was unsuccessful at predicting the relative effects of the different peening treatments. Possible reasons for this are explored.

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

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.

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

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

On the influence of the environment on modeling the fatigue crack growth process

International Nuclear Information System (INIS)

Mc Evily, A.J.

1987-01-01

The effect of the environment at room and elevated temperature were considered with respect to the influence exerted on the basic mechanical aspects of the fatigue crack growth process. An experimental assessment of this influence was obtained by conducting fatigue crack growth tests both in air and vacuum and the results of such experiments are given. Topics considered include crack closure, short crack growth in notched and unnotched specimens, Mode II crack growth, and the effects of oxidation at elevated temperatures. It is shown that the basic mechanisms of fatigue crack growth can be greatly altered by the presence of oxide films at the fatigue crack tip. Modeling the mechanical aspects of the crack growth process is by itself a challenging task. In addition, the environmental considerations adds to the complexity of the modeling process. (Author)

Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

Science.gov (United States)

Saligan, L N; Lukkahatai, N; Holder, G; Walitt, B; Machado-Vieira, R

2016-12-01

Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P fatigue. SNAPIN levels were associated with fatigue scores (r s = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

Fracture Toughness and Fatigue Crack Growth Behavior of As-Cast High-Entropy Alloys

Science.gov (United States)

Seifi, Mohsen; Li, Dongyue; Yong, Zhang; Liaw, Peter K.; Lewandowski, John J.

2015-08-01

The fracture toughness and fatigue crack growth behavior of two as-vacuum arc cast high-entropy alloys (HEAs) (Al0.2CrFeNiTi0.2 and AlCrFeNi2Cu) were determined. A microstructure examination of both HEA alloys revealed a two-phase structure consisting of body-centered cubic (bcc) and face-centered cubic (fcc) phases. The notched and fatigue precracked toughness values were in the range of those reported in the literature for two-phase alloys but significantly less than recent reports on a single phase fcc-HEA that was deformation processed. Fatigue crack growth experiments revealed high fatigue thresholds that decreased significantly with an increase in load ratio, while Paris law slopes exhibited metallic-like behavior at low R with significant increases at high R. Fracture surface examinations revealed combinations of brittle and ductile/dimpled regions at overload, with some evidence of fatigue striations in the Paris law regime.

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

Standard test method for plane-strain (Chevron-Notch) fracture toughness of metallic materials

CERN Document Server

American Society for Testing and Materials. Philadelphia

1997-01-01

1.1 This test method covers the determination of plane-strain (chevron-notch) fracture toughnesses, KIv or KIvM, of metallic materials. Fracture toughness by this method is relative to a slowly advancing steady state crack initiated at a chevron-shaped notch, and propagating in a chevron-shaped ligament (Fig. 1). Some metallic materials, when tested by this method, exhibit a sporadic crack growth in which the crack front remains nearly stationary until a critical load is reached. The crack then becomes unstable and suddenly advances at high speed to the next arrest point. For these materials, this test method covers the determination of the plane-strain fracture toughness, KIvj or KIvM, relative to the crack at the points of instability. Note 1—One difference between this test method and Test Method E 399 (which measures KIc) is that Test Method E 399 centers attention on the start of crack extension from a fatigue precrack. This test method makes use of either a steady state slowly propagating crack, or a...

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

Transitional behaviour of thickness effects in shipbuilding materials (MS plate)

Science.gov (United States)

Mahmud, S. M. Ikhtiar; Razib, Amirul Hasan; Rahman, Md. Rabab Raiyatur

2017-12-01

Majority of the crack propagation in ships and offshore structures are caused due to fatigue. Previously, it was known that fatigue strength of notched specimen is dependent on size, but recently it came to light that fatigue strength of some welded joints depends on the thickness. Much investigation is done on the fatigue growth of welded joints. Fatigue often results in fracture accidents, which starts from the sites of structural discontinuities because of the reason that they may induce local stress concentrations. Structural discontinuities include notches, holes, sharp corners, and weld defects. Weld defects include undercut, porosity, lack of fusion, slag inclusion, incomplete weld root penetration, and misalignments. In order to investigate the effects of plate thickness on fatigue strength, semi-elliptical side notches (U and V shaped) in plates are studied in the present research. First consider a simple problem of crack emanating from notches in plates where the solution of stress intensity factor is given by an empirical formula so that the thickness effect on fatigue strength can easily be investigated for a variety of geometrical parameters. The present study aims to investigate the transitional behaviour of thickness effect in plates on fatigue strength. In order to calculate the stress, finite element analysis is carried by using ANSYS.

Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions.

Science.gov (United States)

Heitzler, P; Simpson, P

1993-03-01

In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

Effect of hot dip galvanization on the fatigue strength of steel bolted connections

Directory of Open Access Journals (Sweden)

S.M.J. Razavi

2017-07-01

Full Text Available Hot dip galvanized steel bolted joints has been tested under fatigue loading to evaluate the effect of galvanizing coating on the fatigue strength of S355 structural steel. The experimental results showed that the decrease of the fatigue life of coated specimens in comparison with that of uncoated joints is very limited and the results are in good agreement with Eurocode detail category, without substantial reductions. The procedure for coating and preparation of the bolted joints is described in detail in this paper providing a useful tool for engineers involved in similar practical applications. The experimental results are compared with the previously published data on central hole notched galvanized and not treated specimens characterized by the same geometry.

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

Sequestration of latent TGF-β binding protein 1 into CADASIL-related Notch3-ECD deposits.

Science.gov (United States)

Kast, Jessica; Hanecker, Patrizia; Beaufort, Nathalie; Giese, Armin; Joutel, Anne; Dichgans, Martin; Opherk, Christian; Haffner, Christof

2014-08-13

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents the most common hereditary form of cerebral small vessel disease characterized by early-onset stroke and premature dementia. It is caused by mutations in the transmembrane receptor Notch3, which promote the aggregation and accumulation of the Notch3 extracellular domain (Notch3-ECD) within blood vessel walls. This process is believed to mediate the abnormal recruitment and dysregulation of additional factors including extracellular matrix (ECM) proteins resulting in brain vessel dysfunction. Based on recent evidence indicating a role for the transforming growth factor-β (TGF-β) pathway in sporadic and familial small vessel disease we studied fibronectin, fibrillin-1 and latent TGF-β binding protein 1 (LTBP-1), three ECM constituents involved in the regulation of TGF-β bioavailability, in post-mortem brain tissue from CADASIL patients and control subjects. Fibronectin and fibrillin-1 were found to be enriched in CADASIL vessels without co-localizing with Notch3-ECD deposits, likely as a result of fibrotic processes secondary to aggregate formation. In contrast, LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates. We also detected increased levels of the TGF-β prodomain (also known as latency-associated peptide, LAP) indicating dysregulation of the TGF-β pathway in CADASIL development. In vitro analyses revealed a direct interaction between LTBP-1 and Notch3-ECD and demonstrated a specific co-aggregation of LTBP-1 with mutant Notch3. We propose LTBP-1 as a novel component of Notch3-ECD deposits and suggest its involvement in pathological processes triggered by Notch3-ECD aggregation.

Lifestyle Risk Factors Associated with Fatigue in Graduate Students

Directory of Open Access Journals (Sweden)

Yi-Chin Lee

2007-01-01

Conclusion: A high prevalence rate of fatigue among the graduate students was demonstrated. The risk factors among young adults are not only related to current chronic disease and insomnia but are also attributed to the lack of physical activity.

Designing aluminium friction stir welded joints against multiaxial fatigue

Directory of Open Access Journals (Sweden)

L. Susmel

2016-07-01

Full Text Available The present paper investigates the accuracy of the Modified Wöhler Curve Method (MWCM in estimating multiaxial fatigue strength of aluminium friction stir (FS welded joints. Having developed a bespoke joining technology, circumferentially FS welded tubular specimens of Al 6082-T6 were tested under proportional and non-proportional tension and torsion, the effect of non-zero mean stresses being also investigated. The validation exercise carried out using the experimental results have demonstrated that the MWCM applied in terms of nominal stresses, notch stresses, and also the Point Method is accurate in predicting the fatigue lifetime of the tested FS welded joints, with its use resulting in life estimates that fall within the uniaxial and torsional calibration scatter bands.

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.

Probabilistic Calibration of Fatigue Design Factors for Offshore Wind Turbine Support Structures

DEFF Research Database (Denmark)

Ramirez, José Rangel; Sørensen, John Dalsgaard

2010-01-01

for the considered offshore wind turbines in such a way that the specific uncertainties for the fatigue life are accounted in a rational manner. Similar approaches have been used for offshore oil & gas sub-structures, but the required reliability level for offshore wind turbines is generally lower and the fatigue......This paper describes a reliability-based approach to determine fatigue design factors (FDF) for offshore wind turbine support structures made of steel. The FDF values are calibrated to a specific reliability level and linked to a specific inspection and maintenance (I&M) strategy used...

Areva fatigue concept. Fast fatigue evaluation, a new method for fatigue analysis

International Nuclear Information System (INIS)

Heinz, Benedikt; Bergholz, Steffen; Rudolph, Juergen

2011-01-01

Within the discussions on the long term operation (LTO) of nuclear power plants the ageing management is on the focus of that analysis. The knowledge of the operational thermal cyclic load data on components of the power plants and their evaluation in the fatigue analysis is a central concern. The changes in fatigue requirements (e.g. the consideration of environmentally assisted fatigue - EAF) recently discussed and LTO efforts are a strong motivation for the identification of margins in the existing fatigue analysis approaches. These margins should be considered within new approaches in order to obtain realistic (or more accurate) analysis results. Of course, these new analysis approaches have to be manageable and efficient. The Areva Fatigue Concept (AFC) offers the comprehensive conceptual basis for the consideration of fatigue on different levels and depths. The combination of data logging and automated fatigue evaluation are important modules of the AFC. Besides the established simplified stress based fatigue estimation Areva develops a further automated fatigue analysis method called Fast Fatigue Evaluation (FFE). This method comprises highly automated stress analyses at the fatigue relevant locations of the component. Hence, a component specific course of stress as a function of time is determined based on FAMOS or similar temperature measurement systems. The subsequent application of the rain flow cycle counting algorithm allows for the determination of the usage factor following the rules of the design code requirements. The new FFE approach constitutes a cycle counting method based on the real stresses in the component, and determined as result a rule-conformity cumulative usage factor. (orig.)

Assessment of the sulfide corrosion fatigue strength for a multi-pass welded A106 Gr B steel pipe below the low SSCC limit

International Nuclear Information System (INIS)

Lee, Gyu Young; Bae, Dong Ho

2009-01-01

In the area of heavy construction, welding processes are vital in the production and maintenance of pipelines and power plants. Welding processes happen to produce residual stresses and change the metal structure as a result of the large nonlinear thermal loading that is created by a moving heat source. The fusion welding process generates formidable welding residual stresses and metallurgical change, which increase the crack driving force and reduce the resistance to the brittle fracture as well as the environmental fracture. This is a serious problem with many alloys as well as the A106 Gr B steel pipe. This pipe that is used in petrochemical and heavy chemical plants either degrades due to corrosive environments, e.g., chlorides and sulfides, and/or become damaged during service due to the various corrosion damage mechanisms. Thus, in this study, after numerically and experimentally analyzing the welding residual stress of a multi-pass welded A106 Gr B steel pipe, the sulfide stress corrosion cracking (SSCC) characteristics were assessed in a 3.5 wt.% NaCl solution that was saturated with H 2 S gas at room temperature on the basis of NACE TM 0177-90. The specimens used are of two kinds: un-notched and notched. Then, the sulfide corrosion fatigue (SCF) strength for the un-notched specimen was assessed below the low SSCC limit that was previously obtained from the SSCC tests for the notched specimen. From the results, in terms of the SSCC and SCF, all the specimens failed at the heat-affected zone, where a high welding residual stress is distributed. It was found that the low SSCC limit of un-notched specimens (σSSCCun-notched) was 46% (230 MPa) of the ultimate tensile strength (σU=502 MPa) of a multi-pass welded A106 Gr B steel pipe, and the notched specimens (σSSCCnotched) had 40% (200 MPa) of the ultimate tensile strength. Thus, it was determined that σSSCCun-notched was 13% lower than σSSCCnotched. Further, the sulfide corrosion fatigue limit (σSCFun-notched

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...

Seafarer fatigue

DEFF Research Database (Denmark)

Jepsen, Jørgen Riis; Zhao, Zhiwei; van Leeuwen, Wessel M. A.

2015-01-01

Background: The consequences of fatigue for the health and safety of seafarers has caused concern in the industry and among academics, and indicates the importance of further research into risk factors and preventive interventions at sea. This review gives an overview of the key issues relating...... to seafarer fatigue. Materials and methods: A literature study was conducted aiming to collect publications that address risk factors for fatigue, short-term and long-term consequences for health and safety, and options for fatigue mitigation at sea. Due to the limited number of publications that deals...... with seafarers, experiences from other populations sharing the same exposures (e.g. shift work) were also included when appropriate. Results: Work at sea involves multiple risk factors for fatigue, which in addition to acute effects (e.g., impaired cognition, accidents) contributes through autonomic, immunologic...

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.

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

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 ...

Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer.

Science.gov (United States)

Cuneo, Michaela G; Schrepf, Andrew; Slavich, George M; Thaker, Premal H; Goodheart, Michael; Bender, David; Cole, Steve W; Sood, Anil K; Lutgendorf, Susan K

2017-10-01

Fatigue is a challenge in ovarian cancer survivorship and greatly impacts quality of life. In other cancer populations, fatigue has been associated with abnormal diurnal cortisol patterns. However, little is known about biological and behavioral factors in 5+-year ovarian cancer survivors and potential mechanisms underlying persistent fatigue have not been investigated in this population. Moreover, relationships between neuroendocrine and psychosocial factors in 5+-year ovarian cancer survivors have not been studied. We addressed these issues by examining relationships between diurnal cortisol rhythms, fatigue, life stress, and social support in 30 survivors of ovarian cancer who were assessed at least 5 years (mean=6.20years) following their primary diagnosis. Flatter diurnal cortisol slopes were associated with higher levels of fatigue, suggesting a role for HPA-axis dysregulation in sustained fatigue experienced by survivors. Moreover, greater cumulative lifetime stressor exposure (p=0.023) and stressor severity (p=0.004) were associated with flatter diurnal cortisol slopes, while higher social attachment (p=0.001) was associated with steeper diurnal cortisol slopes. These findings suggest that ovarian cancer survivors with greater lifetime stress exposure or lower social attachment may be at increased risk for circadian rhythm disruption, which in turn is associated with fatigue. Future research should examine relationships of clinical stage and inflammatory cytokines to cortisol rhythms and fatigue in long-term ovarian cancer survivors, as well as investigating the clinical significance of abnormal diurnal cortisol profiles in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors influencing healthcare provider respondent fatigue answering a globally administered in-app survey

Directory of Open Access Journals (Sweden)

Vikas N. O’Reilly-Shah

2017-09-01

Full Text Available Background Respondent fatigue, also known as survey fatigue, is a common problem in the collection of survey data. Factors that are known to influence respondent fatigue include survey length, survey topic, question complexity, and open-ended question type. There is a great deal of interest in understanding the drivers of physician survey responsiveness due to the value of information received from these practitioners. With the recent explosion of mobile smartphone technology, it has been possible to obtain survey data from users of mobile applications (apps on a question-by-question basis. The author obtained basic demographic survey data as well as survey data related to an anesthesiology-specific drug called sugammadex and leveraged nonresponse rates to examine factors that influenced respondent fatigue. Methods Primary data were collected between December 2015 and February 2017. Surveys and in-app analytics were collected from global users of a mobile anesthesia calculator app. Key independent variables were user country, healthcare provider role, rating of importance of the app to personal practice, length of time in practice, and frequency of app use. Key dependent variable was the metric of respondent fatigue. Results Provider role and World Bank country income level were predictive of the rate of respondent fatigue for this in-app survey. Importance of the app to the provider and length of time in practice were moderately associated with fatigue. Frequency of app use was not associated. This study focused on a survey with a topic closely related to the subject area of the app. Respondent fatigue rates will likely change dramatically if the topic does not align closely. Discussion Although apps may serve as powerful platforms for data collection, responses rates to in-app surveys may differ on the basis of important respondent characteristics. Studies should be carefully designed to mitigate fatigue as well as powered with the

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

Directory of Open Access Journals (Sweden)

Sara N. Koenig

2015-03-01

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

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.

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.

Surface Irregularity Factor as a Parameter to Evaluate the Fatigue Damage State of CFRP

Directory of Open Access Journals (Sweden)

Pablo Zuluaga-Ramírez

2015-11-01

Full Text Available This work presents an optical non-contact technique to evaluate the fatigue damage state of CFRP structures measuring the irregularity factor of the surface. This factor includes information about surface topology and can be measured easily on field, by techniques such as optical perfilometers. The surface irregularity factor has been correlated with stiffness degradation, which is a well-accepted parameter for the evaluation of the fatigue damage state of composite materials. Constant amplitude fatigue loads (CAL and realistic variable amplitude loads (VAL, representative of real in- flight conditions, have been applied to “dog bone” shaped tensile specimens. It has been shown that the measurement of the surface irregularity parameters can be applied to evaluate the damage state of a structure, and that it is independent of the type of fatigue load that has caused the damage. As a result, this measurement technique is applicable for a wide range of inspections of composite material structures, from pressurized tanks with constant amplitude loads, to variable amplitude loaded aeronautical structures such as wings and empennages, up to automotive and other industrial applications.

Surface Irregularity Factor as a Parameter to Evaluate the Fatigue Damage State of CFRP

Science.gov (United States)

Zuluaga-Ramírez, Pablo; Frövel, Malte; Belenguer, Tomás; Salazar, Félix

2015-01-01

This work presents an optical non-contact technique to evaluate the fatigue damage state of CFRP structures measuring the irregularity factor of the surface. This factor includes information about surface topology and can be measured easily on field, by techniques such as optical perfilometers. The surface irregularity factor has been correlated with stiffness degradation, which is a well-accepted parameter for the evaluation of the fatigue damage state of composite materials. Constant amplitude fatigue loads (CAL) and realistic variable amplitude loads (VAL), representative of real in- flight conditions, have been applied to “dog bone” shaped tensile specimens. It has been shown that the measurement of the surface irregularity parameters can be applied to evaluate the damage state of a structure, and that it is independent of the type of fatigue load that has caused the damage. As a result, this measurement technique is applicable for a wide range of inspections of composite material structures, from pressurized tanks with constant amplitude loads, to variable amplitude loaded aeronautical structures such as wings and empennages, up to automotive and other industrial applications. PMID:28793655

Effects of pulse current stimulation on the thermal fatigue crack propagation behavior of CHWD steel

International Nuclear Information System (INIS)

Lin, H.Q.; Zhao, Y.G.; Gao, Z.M.; Han, L.G.

2008-01-01

The fatigue crack propagating behaviors of cast hot working die (CHWD) steel untreated and treated by an electric current in the intermediate stage of thermal fatigue were investigated in the present study. The circle/elliptical heating affected zone (HAZ) was formed ahead of the notch tip on the fatigued specimens after pulse electric current stimulation. Both SEM observation and X-ray diffraction analysis revealed that pulse electric current stimulation refined grains/subgrains in the HAZs. With the prolonging of discharging duration, the grains/subgrains decreased in size and the dislocation density and microhardness increased gradually. The grain refinement and dislocation density increase played an important role in the material strengthening, which inevitably enhanced the propagation resistance and delayed the propagation of thermal fatigue cracks. Therefore, the pulse electric current stimulation was an effective method to improve the service lifetime of die material

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

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

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.

Risk factors for fatigue in shipping, the consequences for seafarers’ health and options for preventive intervention

DEFF Research Database (Denmark)

Jepsen, Jørgen Riis; Zhao, Zhiwei; Pekcan, Claire

2017-01-01

fatigue. A literature study was conducted aimed at collecting publications that address risk factors for fatigue, short-term and long-term consequences for health and safety, and options for fatigue mitigation at sea. Due to the limited number of publications that deal with seafarers, experiences from...

All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

Science.gov (United States)

Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

2015-07-17

All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Surface-finish effects on the high-cycle fatigue of Alloy 718

International Nuclear Information System (INIS)

Korth, G.E.

1981-06-01

Alloy 718 us a precipitation-hardening nickel-base superalloy that is being specified for various components for liquid-meal fast breeder reactors (LMFBRs). This alloy maintains high strength at elevated temperatures making it a desirable structural material. But the property that justifies most LMFBR applications is the alloy's resistance to thermal striping damage due to its high fatigue endurance strength. Thermal striping is a high-cycle fatigue phenomenon caused by thermal stresses from the fluctuating mixing action of sodium streams of differing temperatures impinging on the metal surfaces. Most of the design data is generated from laboratory fatigue specimens with carefully controlled surface finishes prepared with a low-stress grind and buffed to a surface finish 8--12 in. Since Alloy 718 has been shown to be quite notch sensitive under cyclic loading, the detrimental effect on the high-cycle fatigue properties caused by shop surface finishes of actual components has been questioned. This report examines some of the surface finishes that could be produced in a commercial shop on an actual component

Effects Of Welding On The Fatigue Behaviour Of Commercial Aluminum AA-1100 Joints

Science.gov (United States)

Uthayakumar, M.; Balasubramanian, V.; Rani, Ahmad Majdi Abdul; Hadzima, Branislav

2018-04-01

Friction Stir Welding (FSW) is an budding solid state welding process, which is frequently used for joining aluminum alloys where materials can be joined without melt and recast. Therefore, when welding alloys through FSW the phase transformations occurs will be in the solid state form. The present work is aimed in evaluating the fatigue life of friction stir welded commercial grade aluminum alloy joints. The commercial grade AA1100 aluminum alloy of 12mm thickness plate is welded and the specimens are tested using a rotary beam fatigue testing machine at different stress levels. The stress versus number of cycles (S-N) curves was plotted using the data points. The Fatigue life of tungsten inert gas (TIG) and metal inert gas (MIG) welded joints was compared. The fatigue life of the weld joints was interrelated with the tensile properties, microstructure and micro hardness properties. The effects of the notches and welding processes are evaluated and reported.

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.

FOXP3 expression is modulated by TGF-β1/NOTCH1 pathway in human melanoma

Science.gov (United States)

Skarmoutsou, Eva; Bevelacqua, Valentina; D'Amico, Fabio; Russo, Angela; Spandidos, Demetrios A.; Scalisi, Aurora

2018-01-01

Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor-β (TGF-β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF-β-induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used. FOXP3 subcellular distribution was evaluated by immuno cytochemical analysis. Gene expression levels were assessed by reverse transcription-quantitative polymerase chain reaction. Protein levels were assessed by western blot analysis. The γ-secretase inhibitor (GSI) was used for NOTCH1 inhibition and recombinant human (rh)TGF-β was used for melanoma cell stimulation. Cell proliferation and viability were respectively assessed by MTT and Trypan blue dye assays. FOXP3 mRNA and protein levels were progressively higher in WM35, A375 and A2058 cell lines compared to NHEM and their levels were further increased after stimulation with rh-TGF-β. TGF-β-mediated FOXP3 expression was mediated by NOTCH1 signaling. Inhibition of NOTCH1 with concomitant rh-TGF-β stimulation determined the reduction in gene expression and protein level of FOXP3. Finally, melanoma cell line proliferation and viability were reduced by NOTCH1 inhibition. The results show that nn increase in FOXP3 expression in metastatic melanoma cell lines is a potential marker of tumor aggressiveness and metastasis. NOTCH1 is a central mediator of TGF-β-mediated FOXP3 expression and NOTCH1 inhibition produces a significant reduction of melanoma cell proliferation and viability. PMID:29620159

The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development

Directory of Open Access Journals (Sweden)

Bryan W. Heck

2011-12-01

SMRTER (SMRT-related and ecdysone receptor interacting factor is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicated them in a wide range of transcriptional regulatory pathways. However, little is currently known about how this conserved class of transcriptional corepressors regulates the development of particular tissues via specific pathways. In this study, through our characterization of multiple Smrter (Smr mutant lines, mosaic analysis of a loss-of-function Smr allele, and studies of two independent Smr RNAi fly lines, we report that SMRTER is required for the development of both ovarian follicle cells and the wing. In these two tissues, SMRTER inhibits not only the ecdysone pathway, but also the Notch pathway. We differentiate SMRTER's influence on these two signaling pathways by showing that SMRTER inhibits the Notch pathway, but not the ecdysone pathway, in a spatiotemporally restricted manner. We further confirm the likely involvement of SMRTER in the Notch pathway by demonstrating a direct interaction between SMRTER and Suppressor of Hairless [Su(H], a DNA-binding transcription factor pivotal in the Notch pathway, and the colocalization of both proteins at many chromosomal regions in salivary glands. Based on our results, we propose that SMRTER regulates the Notch pathway through its association with Su(H, and that overcoming a SMRTER-mediated transcriptional repression barrier may represent a key mechanism used by the Notch pathway to control the precise timing of events and the formation of sharp boundaries between cells in multiple tissues during development.

On residual stresses and fatigue of laser hardened steels

International Nuclear Information System (INIS)

Lin, Ru.

1992-01-01

This thesis deals with studies on residual stresses and fatigue properties of laser-transformation hardened steels. Two types of specimens, cylinders and fatigue specimens were used in the studies. The cylinders, made of Swedish steels SS 2244 and SS 2258 which correspond to AISI 4140 and AISI 52100 respectively, were locally hardened by a single scan of laser beam in the longitudinal direction, with various laser parameters. Residual stress distributions across the hardened tracks were measured by means of X-ray diffraction. The origins of residual stresses were investigated and discussed. For the fatigue specimens, including smooth and notched types made of Swedish steels SS 2244, SS 2225 and SS 1572 (similar to AISI 4140, AISI 4130 and AISI 1035, respectively), laser hardening was carried out in the gauge section. The residual stress field induced by the hardening process and the fatigue properties by plane bending fatigue test were studied. In order to investigate the stability of the residual stress field, stress measurements were also made on specimens being loaded near the fatigue limits for over 10 7 cycles. Further the concept of local fatigue strength was employed to correlate quantitatively the effect of hardness and residual stress field on the fatigue limits. In addition a group of smooth specimens of SS 2244 was induction hardened and the hardening results were compared with the corresponding laser hardened ones in terms of residual stress and fatigue behaviour. It has been found that compressive stresses exist in the hardened zone of all the specimens studied. The laser hardening condition, the specimen and how the hardening is carried out can significantly affect the residual stress field. Laser hardening can greatly improve the fatigue properties by inducing a hardened and compressed surface layer. (112 refs.)(au)

On residual stresses and fatigue of laser hardened steels

Energy Technology Data Exchange (ETDEWEB)

Lin, Ru.

1992-01-01

This thesis deals with studies on residual stresses and fatigue properties of laser-transformation hardened steels. Two types of specimens, cylinders and fatigue specimens were used in the studies. The cylinders, made of Swedish steels SS 2244 and SS 2258 which correspond to AISI 4140 and AISI 52100 respectively, were locally hardened by a single scan of laser beam in the longitudinal direction, with various laser parameters. Residual stress distributions across the hardened tracks were measured by means of X-ray diffraction. The origins of residual stresses were investigated and discussed. For the fatigue specimens, including smooth and notched types made of Swedish steels SS 2244, SS 2225 and SS 1572 (similar to AISI 4140, AISI 4130 and AISI 1035, respectively), laser hardening was carried out in the gauge section. The residual stress field induced by the hardening process and the fatigue properties by plane bending fatigue test were studied. In order to investigate the stability of the residual stress field, stress measurements were also made on specimens being loaded near the fatigue limits for over 10[sup 7] cycles. Further the concept of local fatigue strength was employed to correlate quantitatively the effect of hardness and residual stress field on the fatigue limits. In addition a group of smooth specimens of SS 2244 was induction hardened and the hardening results were compared with the corresponding laser hardened ones in terms of residual stress and fatigue behaviour. It has been found that compressive stresses exist in the hardened zone of all the specimens studied. The laser hardening condition, the specimen and how the hardening is carried out can significantly affect the residual stress field. Laser hardening can greatly improve the fatigue properties by inducing a hardened and compressed surface layer. (112 refs.)(au).

Fatigue approach for addressing environmental effects in fatigue usage calculation

Energy Technology Data Exchange (ETDEWEB)

Wilhelm, Paul; Rudolph, Juergen [AREVA GmbH, Erlangen (Germany); Steinmann, Paul [Erlangen-Nuremberg Univ., erlangen (Germany). Chair of Applied Mechanics

2015-04-15

Laboratory tests consider simple trapezoidal, triangle, and sinusoidal signals. However, actual plant components are characterized by complex loading patterns and periods of holds. Fatigue tests in water environment show, that the damage from a realistic strain variation or the presence of hold-times within cyclic loading results in an environmental reduction factor (Fen) only half that of a simple waveform. This study proposes a new fatigue approach for addressing environmental effects in fatigue usage calculation for class 1 boiler and pressure vessel reactor components. The currently accepted method of fatigue assessment has been used as a base model and all cycles, which have been comparable with realistic fatigue tests, have been excluded from the code-based fatigue calculation and evaluated directly with the test data. The results presented show that the engineering approach can successfully be integrated in the code-based fatigue assessment. The cumulative usage factor can be reduced considerably.

Fatigue approach for addressing environmental effects in fatigue usage calculation

International Nuclear Information System (INIS)

Wilhelm, Paul; Rudolph, Juergen; Steinmann, Paul

2015-01-01

Laboratory tests consider simple trapezoidal, triangle, and sinusoidal signals. However, actual plant components are characterized by complex loading patterns and periods of holds. Fatigue tests in water environment show, that the damage from a realistic strain variation or the presence of hold-times within cyclic loading results in an environmental reduction factor (Fen) only half that of a simple waveform. This study proposes a new fatigue approach for addressing environmental effects in fatigue usage calculation for class 1 boiler and pressure vessel reactor components. The currently accepted method of fatigue assessment has been used as a base model and all cycles, which have been comparable with realistic fatigue tests, have been excluded from the code-based fatigue calculation and evaluated directly with the test data. The results presented show that the engineering approach can successfully be integrated in the code-based fatigue assessment. The cumulative usage factor can be reduced considerably.

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.

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.

Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

International Nuclear Information System (INIS)

Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

2005-01-01

Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

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.

The theory of critical distances applied to problems in fracture and fatigue of bone

Directory of Open Access Journals (Sweden)

Emma Brazel

2009-10-01

Full Text Available The theory of critical distances (TCD has been applied to predict notch-based fracture and fatigue in a wide range of materials and components. The present paper describes a series of projects in which we applied this approach to human bone. Using experimental data from the literature, combined with finite element analysis, we showed that the TCD was able to predict the effect of notches and holes on the strength of bone failing in brittle fracture due to monotonic loading, in different loading regimes. Bone also displays short crack effects, leading to R-curve data for both fracture toughness and fatigue crack propagation thresholds; we showed that the TCD could predict this data. This analysis raised a number of questions for discussion, such as the significance of the L value itself in this and other materials. Finally, we applied the TCD to a practical problem in orthopaedic surgery: the management of bone defects, showing that predictions could be made which would enable surgeons to decide on whether a bone graft material would be needed to repair a defect, and to specify what mechanical properties this material should have.

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.

An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

Directory of Open Access Journals (Sweden)

Masaya Koshizaka

2012-01-01

Full Text Available Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1 is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway.

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)

Some aspects of thermal fatigue in stainless steel

International Nuclear Information System (INIS)

Iorio, A.F.; Crespi, J.C.

1987-01-01

This paper is concerned with the analysis of failures in a moderator circuit branch piping of the ATUCHA-I pressurized heavy water reactor (PHWR), made of austenitic steel to DIN 1.4550 specification (similar to AISI 347). These failures are considered to result from a thermal fatigue processes induced by fluctuations in a zone where stratified temperature layers occurred -the fluctuations being associated with variations in the heavy water flow. The first section evaluates the possibility of cracking due to thermal fatigue phenomena and concludes that under service conditions a crack may be initiated and growth through 7 mm of the wall thickness of the pipe. Laboratory thermal fatigue tests that simulated the thermomechanical conditions for such a component, showed that the number of cycles required to initiate a thermal fatigue crack in a notched modified standard fatigue specimen was about 10 3 . This value may be used to give a conservative prediction of the number of thermal cycles for crack initiation in actual station piping, including those who suffered a cold plug condition which is produced in some emergency shut-down and valve testing situations. It was also demonstrated that beyond a crack depth of 7 mm stress corrosion cracking has the main process in further crack propagation. The relevance of this prediction has been confirmed by microfractographic observations, since the brittle nature of the fracture surfaces under service conditions appears very different from the transgranular ductile striations found in both thermal and mechanical fatigue test specimens as a result of environmental effects. (Author)

Psychosocial factors, musculoskeletal disorders and work-related fatigue amongst nurses in Brunei: structural equation model approach.

Science.gov (United States)

Abdul Rahman, Hanif; Abdul-Mumin, Khadizah; Naing, Lin

2017-09-01

Psychosocial factors, musculoskeletal disorders and work-related fatigue have adverse effects on individual nurses and place a substantial financial burden on health care. Evidence of an association has been reported in the literature, but no theoretical explanation has been published to date. To explore and develop a structural model to provide a theoretical explanation for this relationship. A cross-sectional study using data from 201 valid samples of emergency and critical care nurses across public hospitals in Brunei was performed via self-administered questionnaire. The structural equation model was assessed using partial least squares analysis. A valid and robust structural model was constructed. This revealed that 61.5% of the variance in chronic fatigue could be explained by psychosocial factors and musculoskeletal disorders pathways. Among the psychosocial factors, work-family conflict was identified as a key mediator for progression of musculoskeletal problems and subsequent fatigue through stress and burnout. This report provides a novel theoretical contribution to understanding the relationship between psychosocial factors, musculoskeletal disorders and work-related fatigue. These preliminary results may be useful for future studies on the development of work-related fatigue and musculoskeletal disorders, particularly the central role of work-family conflict. Copyright © 2017 Elsevier Ltd. All rights reserved.

RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

Science.gov (United States)

Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

2011-01-05

The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

Predictors and Trajectories of Morning Fatigue Are Distinct from Evening Fatigue

Science.gov (United States)

Wright, Fay; Melkus, Gail D’Eramo; Hammer, Marilyn; Schmidt, Brian L.; Knobf, M. Tish; Paul, Steven M.; Cartwright, Frances; Mastick, Judy; Cooper, Bruce A.; Chen, Lee-May; Melisko, Michelle; Levine, Jon D.; Kober, Kord; Aouizerat, Bradley E.; Miaskowski, Christine

2015-01-01

Context Fatigue is the most common symptom in oncology patients during chemotherapy (CTX). Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients. Objectives An evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue. Methods A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N=586) completed demographic and symptom questionnaires a total of six times over two cycles of CTX. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling (HLM) was used to answer the study objectives. Results A large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index (BMI), who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance and depressive symptoms, reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients’ ethnicity and younger age. Conclusion The modifiable risk factors that were associated with only morning fatigue were BMI, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors. PMID:25828559

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

International Nuclear Information System (INIS)

Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-04-29

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

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-09-17

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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 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

The significance of the neurovascular structures passing through the spinoglenoid notch

International Nuclear Information System (INIS)

Atekin, Mustafa; Demiryiirek, Deniz; Bayramoglu, Alp; Tuccar, Eray

2003-01-01

To define the detailed anatomy of the neurovascular bundle at the spinoglenoid notch and to report the dimensions of these structures in cadavers. In the present study, the external diameters of suprascapular artery, vein and nerve were measured at the spinoglenoid region in 18 formalin fixed cadavers (36 soulders) by using a caliper. The study was carried out in the dissection laboratory of Anatomy Department of Hacettepe University ,Ankara University, Ankara and Mersin University ,Mersin,Turkey, between2002 and 2003.The average external diameter for suprascapular vein was 2.6 mmand nerve was 2.2 mm. The spinoglenoid notch was roofed by the spinoglenoid ligament and appeared as a fibroosseous foramen in all cadavers. We found that vascular structures (suprascapular artery and vein )occupied 68.5% and the suprascapular nerve occupied 31.5% of this foramen. Although the diameters of the vascular structures at the spinoglenoid notch measured by magnetic resonance imaging have been reported,to our knowledge, external diameters of these structures at the spinoglenoid notch have not been described in cadavers. We believe that detailed anatomy of suprascapular neurovascular bundle at the spinoglenoid notch should be appreciated for better understanding of risk factors possibly causing the sprascapular nerve entrapment syndrome specially for those who are involved in voilent ovehead sports activities such as volleyball and baseball. (author)

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

International Nuclear Information System (INIS)

Gao, Rundi; Chen, Ruilin; Cao, Yu; Wang, Yuan; Song, Kang; Zhang, Ya; Yang, Junchao

2017-01-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Gao, Rundi; Chen, Ruilin; Cao, Yu [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Wang, Yuan [Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Song, Kang [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Zhang, Ya [Zhejiang Chinese Medicine University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province 310006 (China); Yang, Junchao, E-mail: yangjunchaozj@zcmu.edu.cn [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China)

2017-03-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

An experimental study on the effects of compressive stress on the fatigue crack growth of low-alloy steel

International Nuclear Information System (INIS)

Jones, D.P.; Hoppe, R.G.; James, B.A.

1993-01-01

A series of fatigue crack growth rate tests was conducted in order to study effects of negative stress ratio on fatigue crack growth rate of low-alloy steel in air. Four-point bend specimens were used to simulate linear stress distributions typical of pressure vessel applications. This type of testing adds to knowledge on negative stress ratio effects for low-alloy steels obtained in the past from uniform tension-compression tests. Applied bending stress range was varied over twice the yield strength. Load control was used for tests for which the stress range was less than twice the yield strength and deflection control was used for the higher stress range tests. Crack geometries were both short and long fatigue cracks started at notches and tight fatigue cracks for which crack closure could occur over the full crack face. Results are presented in terms of the stress intensity factor ratio R = K MIN /K MAX . The negative R-ratio test results were correlated to an equation of the form da/dN = C[ΔK/(A-R)] n , where A, C, and n are curve fitting parameters. It was found that effects of negative R-ratio on fatigue crack growth rates for even the high stress range tests could be bounded by correlating the above equation to only positive R-ratio test results and extending the resulting equation into the negative R-ratio regime

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 ...

Studies on the fatigue of branched connections related to the shakedown pressure

International Nuclear Information System (INIS)

Cook, T.R.

1977-01-01

The concept of shakedown is that regions which plastically deform during initial loading subsequently adopt an elastic mode of deformation. High strain fatigue, i.e. up to 10,000 cycles, will be eliminated. Two branches of different thickness were welded to a common cylindrical vessel and hydraulically tested, simultaneously. The test pressure was the shakedown limit for the stronger branch and about 1.5 x shakedown for the weaker branch. The thinner branch failed by penetration through the weld near the crotch corner at 3,543 cycles. The thicker branch was given 10,000 cycles when, since no cracks were apparent, a starter notch was made in the crotch corner. Leakage occurred after another 10,678 cycles. This crack was also influenced by weld defects. Using fracture mechanics and a reported relationship between crack rate and stress intensity factors, some predictions of endurance at design pressure are derived for these branches. These lives are compared with the British Standard 1515 formula for fatigue avoidance and with the curves given in Section III of the ASME Boiler and Pressure Vessel Code. The former is considered conservative, while the ASME Code curve requires an additional safety factor as suggested by Jettam; A multiplication factor of 2 on the nominal stress concentration factor for welds is then considered satisfactory. It is tentatively considered that such junctions manufactured to Class 1 standard are satisfactory for daily cycling for 30 years, but are marginal for twice daily cycling for that time. This conclusion is tentative, since it depends critically on the size of weld defects present

Correlation of Stress Concentration Factors for T-Welded Connections – Finite Element Simulations and Fatigue Behavior

Directory of Open Access Journals (Sweden)

Gerardo Terán Méndez

Full Text Available Abstract The stress concentration factors (SCFs in welded connections usually occur at zones with high stress levels. Stress concentrations reduce the fatigue behavior of welded connections in offshore structures and cracking can develop. By using the grinding technique, cracking can be eliminated. Stress concentration factors are defined as a ratio of maximum stress at the intersection to nominal stress on the brace. Defining the stress concentration factor is an important stage in the fatigue behavior of welded connections. Several approaches have evolved for designing structures with the classical S-N approach for estimating total life. This work correlates to the stress concentration factors of T-welded connections and the fatigue behavior. Stress concentration factors were computed with the finite element employing 3D T-welded connections with intact and grinding depth conditions. Then, T-welded connections were constructed with A36 plate steel and welded with E6013 electrodes to obtain the stress-life (S-N approach. The methodology from previous works was used to compute the SCF and fabricate the T-welded connections. The results indicated that the grinding process could restore the fatigue life of the T-welded connections for SCFs values in the range of 1.29. This value can be considered to be a low SCF value in T-welded connection. However, for higher SCF values, the fatigue life decreased, compromising and reducing the structural integrity of the T-welded connections.

Analysis of the Mechanical Behavior, Creep Resistance and Uniaxial Fatigue Strength of Martensitic Steel X46Cr13

Science.gov (United States)

Brnic, Josip; Krscanski, Sanjin; Lanc, Domagoj; Brcic, Marino; Turkalj, Goran; Canadija, Marko; Niu, Jitai

2017-01-01

The article deals with the analysis of the mechanical behavior at different temperatures, uniaxial creep and uniaxial fatigue of martensitic steel X46Cr13 (1.4034, AISI 420). For the purpose of considering the aforementioned mechanical behavior, as well as determining the appropriate resistance to creep and fatigue strength levels, numerous uniaxial tests were carried out. Tests related to mechanical properties performed at different temperatures are presented in the form of engineering stress-strain diagrams. Short-time creep tests performed at different temperatures and different stress levels are presented in the form of creep curves. Fatigue tests carried out at stress ratios R=0.25 and R=−1 are shown in the form of S–N (fatigue) diagrams. The finite fatigue regime for each of the mentioned stress ratios is modeled by an inclined log line, while the infinite fatigue regime is modeled by a horizontal line, which represents the fatigue limit of the material and previously was calculated by the modified staircase method. Finally, the fracture toughness has been calculated based on the Charpy V-notch impact energy. PMID:28772749

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.

Effect of some types of machining processes on beryllium fatigue strength properties

International Nuclear Information System (INIS)

Armbruster, M.

1977-01-01

The aim of this work, which is sponsored by the French D.G.R.S.T., is to determine a machining process giving both the highest tensile strength and the highest fatigue limit to beryllium parts. A comparison is made of the effects of : mechanical machining, electro discharge machining, electro-chemical machining, electrolytical and chemical polishing, glass shot peening, on the mechanical strength and fatigue limits of samples taken from hot pressed and extruded rods and from cast ingot sheets, either notched or not as required. Complementary examinations are performed principally by fractographic study. The results show that for beryllium, electrochemical machining followed by glass shot peening gives the best results; however mechanical machining with electrolytical polishing followed by glass shot peening are also satisfactory. (author)

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.)

Fatigue crack propagation in additively manufactured porous biomaterials.

Science.gov (United States)

Hedayati, R; Amin Yavari, S; Zadpoor, A A

2017-07-01

Additively manufactured porous titanium implants, in addition to preserving the excellent biocompatible properties of titanium, have very small stiffness values comparable to those of natural bones. Although usually loaded in compression, biomedical implants can also be under tensional, shear, and bending loads which leads to crack initiation and propagation in their critical points. In this study, the static and fatigue crack propagation in additively manufactured porous biomaterials with porosities between 66% and 84% is investigated using compact-tension (CT) samples. The samples were made using selective laser melting from Ti-6Al-4V and were loaded in tension (in static study) and tension-tension (in fatigue study) loadings. The results showed that displacement accumulation diagram obtained for different CT samples under cyclic loading had several similarities with the corresponding diagrams obtained for cylindrical samples under compression-compression cyclic loadings (in particular, it showed a two-stage behavior). For a load level equaling 50% of the yield load, both the CT specimens studied here and the cylindrical samples we had tested under compression-compression cyclic loading elsewhere exhibited similar fatigue lives of around 10 4 cycles. The test results also showed that for the same load level of 0.5F y , the lower density porous structures demonstrate relatively longer lives than the higher-density ones. This is because the high bending stresses in high-density porous structures gives rise to local Mode-I crack opening in the rough external surface of the struts which leads to quicker formation and propagation of the cracks. Under both the static and cyclic loading, all the samples showed crack pathways which were not parallel to but made 45 ° angles with respect to the notch direction. This is due to the fact that in the rhombic dodecahedron unit cell, the weakest struts are located in 45 ° direction with respect to the notch direction

Experiences of Fatigue at Sea

DEFF Research Database (Denmark)

Zhao, Zhiwei; Jepsen, Jørgen Riis; Chen, Zhonglong

2016-01-01

Fatigue has negative impacts on the general working population as well as on seafarers. In order to study seafarers’ fatigue, a questionnaire-base survey was conducted to gain information about potential risk factors for fatigue and construct indexes indicating fatigue. The study applies T-test t......-test to compare strata of seafarers to analyse work and sleep patterns in global seafaring. Qualitative analysis are also employed to explore the impacts of fatigue on seafarer’s occupational health and safety.......Fatigue has negative impacts on the general working population as well as on seafarers. In order to study seafarers’ fatigue, a questionnaire-base survey was conducted to gain information about potential risk factors for fatigue and construct indexes indicating fatigue. The study applies T...

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

Directory of Open Access Journals (Sweden)

Zou Jie

2013-01-01

Full Text Available Abstract Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL. Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1 transfected with HIF-1α or Notch1 small interference RNA (siRNA were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2 and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation

Fatigue after Stroke: The Patient's Perspective

Directory of Open Access Journals (Sweden)

Victoria Louise Barbour

2012-01-01

Full Text Available Background. Fatigue after stroke is common and distressing to patients. Aims. Our aims were to explore patients' perceptions of post-stroke fatigue, including the causes of fatigue and the factors that alleviate fatigue, in a mixed methods study. Results. We interviewed 15 patients who had had a stroke and were inpatients on stroke rehabilitation wards. A substantial proportion of patients reported that their fatigue started at the time of their stroke. Various different factors were reported to improve fatigue, including exercise, good sleep, rehabilitation and rest. Fatigue influences patients' sense of “control” after their stroke. Conclusion. Our results are consistent with the possibility that poststroke fatigue might be triggered by factors that occur at the time of the stroke (e.g., the stroke lesion itself, or admission to hospital and then exacerbated by poor sleep and boredom. These factors should be considered when developing complex interventions to improve post-stroke fatigue.

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.

Corrosion Fatigue Crack Growth Behavior at Notched Hole in 7075 T6 Under Different Biaxial Stress Ratios

Science.gov (United States)

2016-08-18

Subjected to Biaxial Cyclic Loads.” Engineering Fracture Mechanics , 78:1516- 1528, 2011. [37] Sih, G.C.. “A Special Theory of Crack Propagation...of Aeronautics and Astronautics Graduate School of Engineering and Management Air Force Institute of Technology Air University Air Education and...environments from pre- cracked notched circular hole in a 7075-T6 cruciform specimen using a fracture mechanics approach. With stress ratio of R

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.

Directory of Open Access Journals (Sweden)

Pawel K Mazur

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

Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation.

Science.gov (United States)

Di Tullio, Alessandro; Passaro, Diana; Rouault-Pierre, Kevin; Purewal, Sukhveer; Bonnet, Dominique

2017-07-11

Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated) and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation

Directory of Open Access Journals (Sweden)

Alessandro Di Tullio

2017-07-01

Full Text Available Nuclear factor erythroid-derived 2 (NF-E2 has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation.

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,

Magnetoresistance effect in permalloy nanowires with various types of notches

Directory of Open Access Journals (Sweden)

Y. Gao

2018-05-01

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

Experimental verification of the statistical theories of scaling factor effect in fatigue fracture of steel

International Nuclear Information System (INIS)

Svistun, R.P.; Babej, Yu.I.; Tkachenko, N.N.

1976-01-01

Statistical theories of the scale effect in the fatigue failure of 40KH18N9T, 10 and 20 steels have been verified. The theories are shown to be not invariably suitable for a satisfactory exlanation of the fatigue strength of the samples with respect to their dimensions. One of the main reasons for displaying the scale effect in the process of steel fatigue is the sample self-heating, i.e. a temperature factor which in many cases overlaps a statistical one

Experimental verification of the statistical theories of scaling factor effect in fatigue fracture of steel

Energy Technology Data Exchange (ETDEWEB)

Svistun, R P; Babei, Yu I; Tkachenko, N N [AN Ukrainskoj SSR, Lvov. Fiziko-Mekhanicheskij Inst.; L' vovskij Lesotekhnicheskij Inst. (Ukrainian SSR))

1976-01-01

Statistical theories of the scale effect in the fatigue failure of 40KH18N9T, 10 and 20 steels have been verified. The theories are shown to be not invariably suitable for a satisfactory exlanation of the fatigue strength of the samples with respect to their dimensions. One of the main reasons for displaying the scale effect in the process of steel fatigue is the sample self-heating, i.e. a temperature factor which in many cases overlaps a statistical one.

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.

Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

Directory of Open Access Journals (Sweden)

Taslima T. Lina

2016-07-01

Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

Simplified elastoplastic fatigue analysis

International Nuclear Information System (INIS)

Autrusson, B.; Acker, D.; Hoffmann, A.

1987-01-01

Oligocyclic fatigue behaviour is a function of the local strain range. The design codes ASME section III, RCC-M, Code Case N47, RCC-MR, and the Guide issued by PNC propose simplified methods to evaluate the local strain range. After having briefly described these simplified methods, we tested them by comparing the results of experimental strains with those predicted by these rules. The experiments conducted for this study involved perforated plates under tensile stress, notched or reinforced beams under four-point bending stress, grooved specimens under tensile-compressive stress, and embedded grooved beams under bending stress. They display a relative conservatism depending on each case. The evaluation of the strains of rather inaccurate and sometimes lacks conservatism. So far, the proposal is to use the finite element codes with a simple model. The isotropic model with the cyclic consolidation curve offers a good representation of the real equivalent strain. There is obviously no question of representing the cycles and the entire loading history, but merely of calculating the maximum variation in elastoplastic equivalent deformations with a constant-rate loading. The results presented testify to the good prediction of the strains with this model. The maximum equivalent strain will be employed to evaluate fatigue damage

Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

Science.gov (United States)

Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

2014-12-01

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

Epithelial–stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues

Science.gov (United States)

Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

2014-01-01

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj—a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. Subject Categories Development & Differentiation; Immunology; Signal Transduction PMID:25378482

SCC and Corrosion Fatigue characterization of a Ti-6Al-4V alloy in a corrosive environment – experiments and numerical models

Directory of Open Access Journals (Sweden)

S. Baragetti

2014-10-01

Full Text Available In the present article, a review of the complete characterization in different aggressive media of a Ti-6Al-4V titanium alloy, performed by the Structural Mechanics Laboratory of the University of Bergamo, is presented. The light alloy has been investigated in terms of corrosion fatigue, by axial fatigue testing (R = 0.1 of smooth and notched flat dogbone specimens in laboratory air, 3.5% wt. NaCl–water mixture and methanol–water mixture at different concentrations. The first corrosive medium reproduced a marine environment, while the latter was used as a reference aggressive environment. Results showed that a certain corrosion fatigue resistance is found in a salt water medium, while the methanol environment caused a significant drop – from 23% to 55% in terms of limiting stress reduction – of the fatigue resistance of the Ti-6Al-4V alloy, even for a solution containing 5% of methanol. A Stress Corrosion Cracking (SCC experimental campaign at different methanol concentrations has been conducted over slightly notched dog-bone specimens (Kt = 1.18, to characterize the corrosion resistance of the alloy under quasi-static load conditions. Finally, crack propagation models have been implemented to predict the crack propagation rates for smooth specimens, by using Paris, Walker and Kato-Deng-Inoue-Takatsu propagation formulae. The different outcomes from the forecasting numerical models were compared with experimental results, proposing modeling procedures for the numerical simulation of fatigue behavior of a Ti-6Al-4V alloy.

Prevalence of Fatigue and Associated Factors in a Spinal Cord Injury Population: Data from an Internet-Based and Face-to-Face Surveys.

Science.gov (United States)

Cudeiro-Blanco, Javier; Onate-Figuérez, Ana; Soto-León, Vanesa; Avendaño-Coy, Juan; Mordillo-Mateos, Laura; Brocalero-Camacho, Angela; Esclarin-Ruz, Ana; Rotondi, Mario; Aguilar, Juan; Arias, Pablo; Oliviero, Antonio

2017-08-01

Fatigue has a profound impact on patients with spinal cord injury (SCI), but only limited treatments are available. The aim of this study was to determine the prevalence of fatigue in SCI and its association with clinical and demographic factors. We used an internet-based survey and a face-to-face interview to estimate the prevalence of fatigue in a SCI population. Fatigue was measured using the Fatigue Severity Scale (FSS). Clinically significant fatigue was defined as FSS scores greater than or equal to four. A total of 253 participants with SCI were included in the study. Clinically significant fatigue was present in one third of our sample. There was no relationship between fatigue and injury level or completeness. We found significant correlations between depression, pain, and level of injury. The relation of fatigue with completeness of injury and spasticity is less clear. Moreover, the online survey and the standard face-to-face interview showed similar results concerning fatigue evaluation. Several factors may contribute to fatigue, however. Future studies should be conducted to clarify which are the most relevant ones and, if possible, to determine which factors are modifiable.

Clinically significant fatigue: prevalence and associated factors in an international sample of adults with multiple sclerosis recruited via the internet.

Directory of Open Access Journals (Sweden)

Tracey J Weiland

Full Text Available Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS. Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors.To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate and modifiable lifestyle, disease-modifying drugs (DMD and supplement use in a large international sample of PwMS.PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate.Of 2469 participants with confirmed MS, 2138 (86.6% completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7-67.7 screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil.This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this sample may help clarify the contribution

IIW recommendations for the HFMI treatment for improving the fatigue strength of welded joints

CERN Document Server

Marquis, Gary B

2016-01-01

This book of recommendations presents an overview of High Frequency Mechanical Impact (HFMI) techniques existing today in the market and their proper procedures, quality assurance measures and documentation. Due to differences in HFMI tools and the wide variety of potential applications, certain details of proper treatments and quantitative quality control measures are presented generally. An example of procedure specification as a quality assurance measure is given in the Appendix. Moreover, the book presents procedures for the fatigue life assessment of HFMI-improved welded joints based on nominal stress, structural hot spot stress and effective notch stress. It also considers the extra benefit that has been experimentally observed for HFMI-treated high-strength steels. The recommendations offer proposals on the effect of loading conditions like high mean stress fatigue cycles, variable amplitude loading and large amplitude/low cycle fatigue cycles. Special considerations for low stress concentration welded...

Evaluation of weldment creep and fatigue strength-reduction factors for elevated-temperature design

International Nuclear Information System (INIS)

Corum, J.M.

1989-01-01

New explicit weldment strength criteria in the form of creep and fatigue strength-reduction factors were recently introduced into the American Society of Mechanical Engineers Code Case N-47, which governs the design of elevated-temperature nuclear plants components in the United States. This paper provides some of the background and logic for these factors and their use, and it describes the results of a series of long-term, confirmatory, creep-rupture and fatigue tests of simple welded structures. The structures (welded plates and tubes) were made of 316 stainless steel base metal and 16-8-2 weld filler metal. Overall, the results provide further substantiation of the validity of the strength-reduction factor approach for ensuring adequate life in elevated-temperature nuclear component weldments. 16 refs., 7 figs

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

Evaluation of the effect of corrosion defects on the structural integrity of X52 gas pipelines using the SINTAP procedure and notch theory

International Nuclear Information System (INIS)

Adib, H.; Jallouf, S.; Schmitt, C.; Carmasol, A.; Pluvinage, G.

2007-01-01

The notch stress intensity factor concept and the structural integrity assessment procedure for European industry (SINTAP) structural integrity procedure are used to assess gas pipeline integrity using deterministic and probabilistic methods. These pipes have external longitudinal semi-elliptical corrosion defects. Stress concentration at a defect tip is investigated via elastic-plastic finite element method analysis. The notch stress intensity concept is implemented into the SINTAP procedure and a notch-based failure assessment diagram is proposed. The safety factor and security factor are calculated through the SINTAP basic level

Evaluation of the effect of corrosion defects on the structural integrity of X52 gas pipelines using the SINTAP procedure and notch theory

Energy Technology Data Exchange (ETDEWEB)

Adib, H. [ENIM, Laboratoire de Fiabilite Mecanique (LFM) Ile du Saulcy, 57045 Metz Cedex (France); Jallouf, S. [ENIM, Laboratoire de Fiabilite Mecanique (LFM) Ile du Saulcy, 57045 Metz Cedex (France); Schmitt, C. [ENIM, Laboratoire de Fiabilite Mecanique (LFM) Ile du Saulcy, 57045 Metz Cedex (France)]. E-mail: schmitt@enim.fr; Carmasol, A. [ENIM, Laboratoire de Fiabilite Mecanique (LFM) Ile du Saulcy, 57045 Metz Cedex (France); Pluvinage, G. [ENIM, Laboratoire de Fiabilite Mecanique (LFM) Ile du Saulcy, 57045 Metz Cedex (France)

2007-03-15

The notch stress intensity factor concept and the structural integrity assessment procedure for European industry (SINTAP) structural integrity procedure are used to assess gas pipeline integrity using deterministic and probabilistic methods. These pipes have external longitudinal semi-elliptical corrosion defects. Stress concentration at a defect tip is investigated via elastic-plastic finite element method analysis. The notch stress intensity concept is implemented into the SINTAP procedure and a notch-based failure assessment diagram is proposed. The safety factor and security factor are calculated through the SINTAP basic level.

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.

Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.

LENUS (Irish Health Repository)

Pradeep, C-R

2012-02-16

A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor lesion of invasive breast cancer, overexpresses the HER2\\/neu oncogene. The ducts of DCIS are abnormally filled with cells that evade apoptosis, but the underlying mechanisms remain incompletely understood. We overexpressed HER2 in mammary epithelial cells and observed growth factor-independent proliferation. When grown in extracellular matrix as three-dimensional spheroids, control cells developed a hollow lumen, but HER2-overexpressing cells populated the lumen by evading apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS drives transcriptional upregulation of multiple components of the Notch survival pathway. Importantly, luminal filling required upregulation of a signaling pathway comprising Notch3, its cleaved intracellular domain and the transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin D1. In line with HER2-Notch3 collaboration, drugs intercepting either arm reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3 in hyperplastic lesions of HER2 transgenic animals, as well as an association between HER2 levels and expression levels of components of the Notch pathway in tumor specimens of breast cancer patients. Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS.

Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation.

Directory of Open Access Journals (Sweden)

Laura Asnaghi

Full Text Available The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2 further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

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...

[Valsartan inhibits angiotensin II-Notch signaling of mesangial cells induced by high glucose].

Science.gov (United States)

Yuan, Qin; Lyu, Chuan; Wu, Can; Lei, Sha; Shao, Ying; Wang, Qiuyue

2016-01-01

To explore the role of angiotensin II (Ang II)-Notch signaling in high glucose-induced secretion of extracellular matrix of rat mesangial cells (RMCs) and to further investigate the protective effect of valsartan (one of Ang II receptor blockers) on kidney. Subcultured RMCs were divided into groups as follows: normal glucose group (5.5 mmol/L glucose); high glucose group (30 mmol/L glucose); high concentration of mannitol as osmotic control group (5.5 mmol/L glucose and 24.5 mmol/L mannitol); normal glucose plus 1 μmol/L N-[N-(3, 5-difluorophenacetyl)-L-alanyl ]-S-phenylglycine t-butyl ester (DAPT) group; normal glucose plus (1, 5, 10) μmol/L valsartan group; high glucose plus 1 μmol/L DAPT group; high glucose plus (1, 5, 10) μmol/L valsartan group. Cells and supernatants were harvested after 12, 24 and 48 hours. Notch1 expression was examined by Western blotting. Secretion of transforming growth factor (TGF-β) and fibronectin (FN) were detected by ELISA. Compared to the normal glucose group, Notch1 expression was elevated in the high glucose group after 12 hours, and peaked at 24 hours. Besides, secretion of TGF-β and FN were much higher in the high glucose group than in the normal glucose group in a time-dependent manner. Compared to the untreated group, Notch1 expression decreased in a dose-dependent manner in the valsartan or DAPT treated group under high glucose after 24 hours. After pre-treatment by either valsartan or DAPT in the high glucose group, secretion of TGF-β and FN obviously decreased as compared to the untreated group. Hyperglycemia could stimulate activation of Notch signaling in cultured RMCs, which may increase secretion of downstream fibrotic factors such as TGF-β and FN. Valsartan may decrease the secretion of downstream FN in a dose-dependent manner via inhibiting AngII-Notch signaling.

Random non-proportional fatigue tests with planar tri-axial fatigue testing machine

Directory of Open Access Journals (Sweden)

T. Inoue

2016-10-01

Full Text Available Complex stresses, which occur on the mechanical surfaces of transport machinery in service, bring a drastic degradation in fatigue life. However, it is hard to reproduce such complex stress states for evaluating the fatigue life with conventional multiaxial fatigue machines. We have developed a fatigue testing machine that enables reproduction of such complex stresses. The testing machine can reproduce arbitrary in-plane stress states by applying three independent loads to the test specimen using actuators which apply loads in the 0, 45, and 90 degree directions. The reproduction was tested with complex stress data obtained from the actual operation of transport machinery. As a result, it was found that the reproduced stress corresponded to the measured stress with an error range of less than 10 %. Then, we made a comparison between measured fatigue lives under random non-proportional loading conditions and predicted fatigue lives. It was found that predicted fatigue lives with cr, stress on critical plane, were over a factor of 10 against measured fatigue lives. On the other hand, predicted fatigue lives with ma, stress in consideration of a non-proportional level evaluated by using amplitude and direction of principal stress, were within a factor of 3 against measured fatigue lives

Reduction factors for creep strength and fatigue life of modified 9 Cr-1 Mo steel weldments

International Nuclear Information System (INIS)

Blass, J.J.; Battiste, R.L.; O'Connor, D.G.

1991-01-01

The provisions of ASME B ampersand PV Code Case N-47 currently include reduction factors for creep strength and fatigue life of weldments. To provide experimental confirmation of such factors for modified 9 Cr-1 Mo steel, tests of tubular specimens were conducted at 538 degree C (1000 degree F). Three creep-rupture specimens with longitudinal welds were tested in tension; and, of three with circumferential welds, two were tested in tension and one in torsion. In each specimen with a circumferential weld, a nonuniform axial distribution of strain was easily visible. The test results were compared to an existing empirical model of creep-rupture life. For the torsion test, the comparison was based on a definition of equivalent normal stress recently adopted in Code Case N-47. Some 27 fatigue specimens, with longitudinal, circumferential, or no welds, were tested under axial or torsional strain control. In specimens with welds, fatigue cracking initiated at fusion lines. In axial tests cracks grew in the circumferential direction, and in torsional tests cracks grew along fusion lines. The test results were compared to empirical models of fatigue life based on two definition of equivalent normal strain range. The results have provided some needed confirmation of the reduction factors for creep strength and fatigue life of modified 9 Cr-1 Mo steel weldments currently under consideration by ASME Code committees. 8 refs., 5 figs

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.

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)

Prevalence and factors associated with fatigue in female patients with systemic lupus erythematosus.

Science.gov (United States)

Carrión-Barberà, Irene; Salman-Monte, Tarek Carlos; Castell, Sonia; Castro, Francisco; Ojeda, Fabiola; Carbonell, Jordi

2018-02-10

To determine the prevalence of fatigue in our cohort as well as the factors to which it is associated, its relationship with demographic variables, vitamin D levels, treatment, systemic lupus erythematosus (SLE) symptoms and disease activity. A cross-sectional study was carried out including 102 consecutive female patients with SLE (American College of Rheumatology 1997 criteria) who attended the Parc de Salut Mar between January 2012 and May 2014. Variables collected were: sociodemographic data, vitamin D supplementation, fatigue VAS, pharmacological treatment, main serological markers of SLE, and plasma levels of 25(OH)-vitD. The association between fatigue and the different variables was evaluated by the Spearman's Rho correlation coefficient for the continuous variables, the Mann-Whitney U test for the categorical and the Kruskal-Wallis test for the seasons of the year. The fatigue variable was evaluated through a fatigue VAS with a mean score of 52.84 (range 0-100), a median of 59 and a standard deviation of 29.86. A statistically significant relationship was found between fatigue and age, MHAQ, SLICC, summer and photosensitivity. As for the relationship between fatigue and vitamin D insufficiency (defined as 25-(OH)-vitD≤30 levels), the sample was divided into patients receiving vitamin D supplements (n=60) and patients without supplements (n=40), finding a significant relationship in that last group. A statistically significant association was found between the presence of fatigue and age, MHAQ, SLICC, photosensitivity, fibromyalgia and summer, and with vitamin D insufficiency in the group of patients without supplements (n=40). Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Eye movements discriminate fatigue due to chronotypical factors and time spent on task--a double dissociation.

Directory of Open Access Journals (Sweden)

Dario Cazzoli

Full Text Available Systematic differences in circadian rhythmicity are thought to be a substantial factor determining inter-individual differences in fatigue and cognitive performance. The synchronicity effect (when time of testing coincides with the respective circadian peak period seems to play an important role. Eye movements have been shown to be a reliable indicator of fatigue due to sleep deprivation or time spent on cognitive tasks. However, eye movements have not been used so far to investigate the circadian synchronicity effect and the resulting differences in fatigue. The aim of the present study was to assess how different oculomotor parameters in a free visual exploration task are influenced by: a fatigue due to chronotypical factors (being a 'morning type' or an 'evening type'; b fatigue due to the time spent on task. Eighteen healthy participants performed a free visual exploration task of naturalistic pictures while their eye movements were recorded. The task was performed twice, once at their optimal and once at their non-optimal time of the day. Moreover, participants rated their subjective fatigue. The non-optimal time of the day triggered a significant and stable increase in the mean visual fixation duration during the free visual exploration task for both chronotypes. The increase in the mean visual fixation duration correlated with the difference in subjectively perceived fatigue at optimal and non-optimal times of the day. Conversely, the mean saccadic speed significantly and progressively decreased throughout the duration of the task, but was not influenced by the optimal or non-optimal time of the day for both chronotypes. The results suggest that different oculomotor parameters are discriminative for fatigue due to different sources. A decrease in saccadic speed seems to reflect fatigue due to time spent on task, whereas an increase in mean fixation duration a lack of synchronicity between chronotype and time of the day.

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.

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)

Local strain energy density for the fatigue assessment of hot dip galvanized welded joints: some recent outcomes

Directory of Open Access Journals (Sweden)

M. Peron

2017-10-01

Full Text Available Since in literature only data about the effect of the hot-dip galvanizing coating on fatigue behavior of unnotched specimens are available, whereas very few for notched components and none for welded joints, the aim of this paper is to partially fill this lack of knowledge comparing fatigue strength of uncoated and hot-dip galvanized fillet welded cruciform joints made of structural steel S355 welded joints, subjected to a load cycle R = 0. 34. The results are shown in terms of stress range ?s and of the averaged strain energy density range DW in a control volume of radius R0 = 0.28 mm

Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors

Science.gov (United States)

Rad, Ehsan Bonyadi; Hammerlindl, Heinz; Wels, Christian; Popper, Ulrich; Menon, Dinoop Ravindran; Breiteneder, Heimo; Kitzwoegerer, Melitta; Hafner, Christine; Herlyn, Meenhard; Bergler, Helmut; Schaider, Helmut

2016-01-01

The effects of Notch signaling are context-dependent and both oncogenic and tumor-suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial-like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial–mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the reexpression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo. Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E-cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting. PMID:26801977

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.

Environmental factor approach to account for water effects in pressure vessel and piping fatigue evaluations

International Nuclear Information System (INIS)

Mehta, H.S.; Gosselin, S.R.

1998-01-01

This paper summarizes past and current studies of the environmental fatigue effects in light water reactor (LWR) applications. Current Argonne and Japanese research efforts are reviewed and an approach to calculate an environmental correction factor is described. A description of how the proposed approach can be implemented in section III, NB-3600 and NB-3200-type fatigue evaluations is presented along with examples of applying the approach to piping (NB-3600) and safe end fatigue evaluations. These procedures were applied to several BWR and pressurized water reactor (PWR) example cases. The results of these case studies indicated that there is a modest increase in calculated fatigue usage, which is considerably less than the results obtained when the NUREG/CR-5999 curves are applied directly. (orig.)

Experimental and numerical determination of critical stress intensity factor of aluminum curved thin sheets under tensile stress

Energy Technology Data Exchange (ETDEWEB)

Heidarvand, Majid; Soltani, Naser; Hajializadeh, Farshid [University of Tehran, Tehran (Iran, Islamic Republic of)

2017-05-15

We determined the fracture toughness of aluminum curved thin sheets using tensile stress tests and finite element method. We applied Linear elastic fracture mechanics (LEFM) and Feddersen procedure to evaluate stress intensity factor of the samples with central wire-cut cracks and fatigue cracks with different lengths to investigate the notch radius effect. Special fixture design was utilized to establish uniform stress distribution at the crack zone. Less than 9 % difference was found between the wire-cut and the fatigue cracked samples. Since generating central fatigue crack with different lengths required so much effort, wire-cut cracked samples were used to determine critical stress intensity factor. Finite element analysis was also performed on one-quarter of the specimen using both the singular Borsum elements and the regular isoparametric elements to further investigate fracture toughness of the samples. It was observed that the singular elements presented better results than the isoparametric ones. A slight difference was also found between the results obtained from finite element method using singular elements and the experimental results.

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

The influence of discontinuity and orthotropy of fracture toughness on conditions of fracture initiation in singular stress concentrators

Czech Academy of Sciences Publication Activity Database

Klusák, Jan; Profant, T.; Knésl, Zdeněk; Kotoul, M.

2013-01-01

Roč. 110, SEP (2013), s. 438-447 ISSN 0013-7944 R&D Projects: GA ČR GAP108/10/2049 Institutional support: RVO:68081723 Keywords : Stability criterion of notch es * crack initiation * Singular stress concentrators * bi-material notch Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 1.662, year: 2013

Study of microstructure and fracture properties of blunt notched and sharp cracked high density polyethylene specimens.

Science.gov (United States)

Pan, Huanyu; Devasahayam, Sheila; Bandyopadhyay, Sri

2017-07-21

This paper examines the effect of a broad range of crosshead speed (0.05 to 100 mm/min) and a small range of temperature (25 °C and 45 °C) on the failure behaviour of high density polyethylene (HDPE) specimens containing a) standard size blunt notch and b) standard size blunt notch plus small sharp crack - all tested in air. It was observed that the yield stress properties showed linear increase with the natural logarithm of strain rate. The stress intensity factors under blunt notch and sharp crack conditions also increased linearly with natural logarithm of the crosshead speed. The results indicate that in the practical temperature range of 25 °C and 45 °C under normal atmosphere and increasing strain rates, HDPE specimens with both blunt notches and sharp cracks possess superior fracture properties. SEM microstructure studies of fracture surfaces showed craze initiation mechanisms at lower strain rate, whilst at higher strain rates there is evidence of dimple patterns absorbing the strain energy and creating plastic deformation. The stress intensity factor and the yield strength were higher at 25 °C compared to those at 45 °C.

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....

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

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

African Journals Online (AJOL)

ajl yemi

2011-11-30

Nov 30, 2011 ... Notch-1 signaling is crucial for stem cell maintenance and in a variety of tissues. Previous ... family of transcription factors (CBF-1/RBP-Jk, Su (h) and. LAG-1) .... prostate stem cell renew and cell differentiation (Chhipa,. 2011).

Acoustic Emission Signatures of Fatigue Damage in Idealized Bevel Gear Spline for Localized Sensing

Directory of Open Access Journals (Sweden)

Lu Zhang

2017-06-01

Full Text Available In many rotating machinery applications, such as helicopters, the splines of an externally-splined steel shaft that emerges from the gearbox engage with the reverse geometry of an internally splined driven shaft for the delivery of power. The splined section of the shaft is a critical and non-redundant element which is prone to cracking due to complex loading conditions. Thus, early detection of flaws is required to prevent catastrophic failures. The acoustic emission (AE method is a direct way of detecting such active flaws, but its application to detect flaws in a splined shaft in a gearbox is difficult due to the interference of background noise and uncertainty about the effects of the wave propagation path on the received AE signature. Here, to model how AE may detect fault propagation in a hollow cylindrical splined shaft, the splined section is essentially unrolled into a metal plate of the same thickness as the cylinder wall. Spline ridges are cut into this plate, a through-notch is cut perpendicular to the spline to model fatigue crack initiation, and tensile cyclic loading is applied parallel to the spline to propagate the crack. In this paper, the new piezoelectric sensor array is introduced with the purpose of placing them within the gearbox to minimize the wave propagation path. The fatigue crack growth of a notched and flattened gearbox spline component is monitored using a new piezoelectric sensor array and conventional sensors in a laboratory environment with the purpose of developing source models and testing the new sensor performance. The AE data is continuously collected together with strain gauges strategically positioned on the structure. A significant amount of continuous emission due to the plastic deformation accompanied with the crack growth is observed. The frequency spectra of continuous emissions and burst emissions are compared to understand the differences of plastic deformation and sudden crack jump. The

Notched audiograms and noise exposure history in older adults.

Science.gov (United States)

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

2009-12-01

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

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

Directory of Open Access Journals (Sweden)

Lijun Zhang

2014-01-01

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

Technical report on the fatigue crack Growth Benchmark based on CEA pipe bending tests

International Nuclear Information System (INIS)

2001-07-01

In order to improve the estimation methods of surface crack propagation through the thickness of components, CEA has proposed a benchmark to members of the IAGE WG, sub-group on Integrity of metal components and structures. The subject is a simple configuration of a pipe containing an axisymmetric notch and submitted to a cyclic bending load. An experimental data-set form CEA was used to validate three issues in the topic of Leak Before Break. - Crack initiation, - Crack propagation through the thickness, - Crack penetration. All material and geometrical data which are necessary for the simulation were given in the proposal, including experimental results. Due to the peculiar complexity of the problem, it was decided to focus the work on methodologies comparison so as to allow participants to tune up parameters and adjust their models and tools. This report presents all estimations performed by the participants and collected by CEA. They are compared to the experimental results. An analysis of the used procedures is also proposed. This, associated with the study of the accuracy of different methodologies, leads to comments and recommendations on the analysis of fatigue crack growth. The participation in the first step was important: nine participants have proposed analyses, sometimes parametric analysis to estimate crack growth. Results sorted out three estimation methods groups that give results in accordance with experimental ones (these three groups are based on a strain range evaluation and the fatigue curve of the material): - The use of an elastic stress at the notch tip and a fatigue notch concentration factor to determine the strain range. - The use of a KI (or elastic F.E. calculation) and a Neuber rule for the estimation of the strain range at a characteristic distance from the crack tip. - The direct calculation of the strain range at the characteristic distance by an elastic plastic F.E. calculation. Only 4 participants have proposed an estimate of the

The role of psychological factors in oncology nurses' burnout and compassion fatigue symptoms.

Science.gov (United States)

Duarte, Joana; Pinto-Gouveia, José

2017-06-01

This study explored the role of several psychological factors in professional quality of life in nurses. Specifically, we tried to clarify the relationships between several dimensions of empathy, self-compassion, and psychological inflexibility, and positive (compassion satisfaction) and negative (burnout and compassion fatigue) domains of professional quality of life. Using a cross-sectional design, a convenience sample of 221 oncology nurses recruited from several public hospitals filling out a battery of self-report measures. Results suggested that nurses that benefit more from their work of helping and assisting others (compassion satisfaction) seem to have more empathic feelings and sensibility towards others in distress and make an effort to see things from others' perspective. Also, they are less disturbed by negative feelings associated with seeing others' suffering and are more self-compassionate. Nurses more prone to experience the negative consequences associated with care-providing (burnout and compassion fatigue) are more self-judgmental and have more psychological inflexibility. In addition, they experience more personal feelings of distress when seeing others in suffering and less feelings of empathy and sensibility to others' suffering. Psychological factors explained 26% of compassion satisfaction, 29% of burnout and 18% of compassion fatigue. We discuss the results in terms of the importance of taking into account the role of these psychological factors in oncology nurses' professional quality of life, and of designing nursing education training and interventions aimed at targeting such factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Crew Factors in Flight Operations. 8; A Survey of Fatigue Factors in Corporate/Executive A Viation Operations

Science.gov (United States)

Rosekind, Mark R.; Co, Elizabeth L.; Gregory, Kevin B.; Miller, Donna L.

2000-01-01

Corporate flight crews face unique challenges including unscheduled flights, quickly changing schedules, extended duty days, long waits, time zone changes, and peripheral tasks. Most corporate operations are regulated by Part 91 FARs which set no flight or duty time limits. The objective of this study was to identify operationally significant factors that may influence fatigue, alertness, and performance in corporate operations. In collaboration with the National Business Aircraft Association and the Flight Safety Foundation, NASA developed and distributed a retrospective survey comprising 107 questions addressing demographics, home sleep habits, flight experience, duty schedules, fatigue during operations, and work environment. Corporate crewmembers returned 1,488 surveys. Respondents averaged 45.2 years of age, had 14.9 years of corporate flying experience, and 9,750 total flight hours. The majority (89%) rated themselves as 'good' or 'very good' sleepers at home. Most (82%) indicated they are subject to call for duty and described an average duty day of 9.9 h. About two-thirds reported having a daily duty time limit and over half (57%) reported a daily flight time limit. Nearly three-quarters (71%) acknowledged having 'nodded off' during a flight. Only 21% reported that their flight departments offer training on fatigue issues. Almost three-quarters (74%) described fatigue as a 'moderate' or 'serious' concern, and a majority (61%) characterized it as a common occurrence. Most (85%) identified fatigue as a 'moderate' or 'serious' safety issue.

dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats

International Nuclear Information System (INIS)

Baladron, Victoriano; Ruiz-Hidalgo, Maria Jose; Nueda, Maria Luisa; Diaz-Guerra, Maria Jose M.; Garcia-Ramirez, Jose Javier; Bonvini, Ezio; Gubina, Elena; Laborda, Jorge

2005-01-01

The protein dlk, encoded by the Dlk1 gene, belongs to the Notch epidermal growth factor (EGF)-like family of receptors and ligands, which participate in cell fate decisions during development. The molecular mechanisms by which dlk regulates cell differentiation remain unknown. By using the yeast two-hybrid system, we found that dlk interacts with Notch1 in a specific manner. Moreover, by using luciferase as a reporter gene under the control of a CSL/RBP-Jk/CBF-1-dependent promoter in the dlk-negative, Notch1-positive Balb/c 14 cell line, we found that addition of synthetic dlk EGF-like peptides to the culture medium or forced expression of dlk decreases endogenous Notch activity. Furthermore, the expression of the gene Hes-1, a target for Notch1 activation, diminishes in confluent Balb/c14 cells transfected with an expression construct encoding for the extracellular EGF-like region of dlk. The expression of Dlk1 and Notch1 increases in 3T3-L1 cells maintained in a confluent state for several days, which is associated with a concomitant decrease in Hes-1 expression. On the other hand, the decrease of Dlk1 expression in 3T3-L1 cells by antisense cDNA transfection is associated with an increase in Hes-1 expression. These results suggest that dlk functionally interacts in vivo with Notch1, which may lead to the regulation of differentiation processes modulated by Notch1 activation and signaling, including adipogenesis

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Mauro Di Ianni

2018-04-01

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

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.

The role of uric acid in the pathogenesis of diabetic retinopathy based on notch pathway.

Science.gov (United States)

Zhu, Dan-Dan; Wang, Yun-Zhi; Zou, Chen; She, Xin-Ping; Zheng, Zhi

2018-06-19

Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown. We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively. In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly

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

Science.gov (United States)

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

2015-10-01

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

In vivo analysis of the Notch receptor S1 cleavage.

Directory of Open Access Journals (Sweden)

Robert J Lake

2009-08-01

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

Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling.

Science.gov (United States)

Altmann, Christine; Vasic, Verica; Hardt, Stefanie; Heidler, Juliana; Häussler, Annett; Wittig, Ilka; Schmidt, Mirko H H; Tegeder, Irmgard

2016-10-22

Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues. Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve. Oppositely, progranulin deficient mice have long-lasting deficits in motor function tests after nerve injury due to enhanced losses of motor neurons and stronger microglia activation in the ventral horn of the spinal cord. Deep proteome and gene ontology (GO) enrichment analysis revealed that the proteins upregulated in progranulin overexpressing mice were involved in 'regulation of transcription' and 'response to insulin' (GO terms). Transcription factor prediction pointed to activation of Notch signaling and indeed, co-immunoprecipitation studies revealed that progranulin bound to the extracellular domain of Notch receptors, and this was functionally associated with higher expression of Notch target genes in the dorsal root ganglia of transgenic mice with neuronal progranulin overexpression. Functionally, these transgenic mice recovered normal gait and running, which was not achieved by controls and was stronger impaired in progranulin deficient mice. We infer that progranulin activates Notch signaling pathways, enhancing thereby the regenerative capacity of partially injured neurons, which leads to improved motor function recovery.

Effect of Stress Ratio on Fatigue Crack Growth Rate at Notched Hole in 7075-T6 Aluminum Alloy Under Biaxial Fatigue

Science.gov (United States)

2016-08-18

Berezhnitski, L.T., and R.S. Gromyak. “Evaluation of Limiting State of Matrix in Vicinity of Sharp-Edge Rigid Inclusion.” Material Science, Volume 13...Effect of Surface Enhancement on the Corrosion Properties, Fatigue Strength, and Degradation Of Aircraft Aluminum.” Lambda Research, 2010. [38

Mechanism of electric fatigue crack growth in lead zirconate titanate

International Nuclear Information System (INIS)

Westram, Ilona; Oates, William S.; Lupascu, Doru C.; Roedel, Juergen; Lynch, Christopher S.

2007-01-01

A series of experiments was performed with through-thickness cracks in ferroelectric double cantilever beam (DCB) specimens. Cyclic electric fields of different amplitudes were applied which resulted in cyclic crack propagation perpendicular to the electric field direction. Crack propagation was observed optically and three regimes were identified: a pop-in from a notch, steady-state crack growth and a decrease of the crack growth rate with increasing cycle number. Crack growth only occurred if the applied field exceeded the coercive field strength of the material. Furthermore, the crack extended during each field reversal and the crack growth rate increased with increasing field. Based on the experimental observations, a mechanistic understanding was developed and contrasted with a nonlinear finite element analysis which quantified the stress intensity in the DCB specimens. The driving forces for crack formation at the notch and subsequent fatigue crack growth were computed based on the distribution of residual stresses due to ferroelectric switching. The finite element results are in good agreement with the experimental observations and support the proposed mechanism

Effects of Various Factors on the Viv-Induced Fatigue Damage In The Cable Of Submerged Floating Tunnel

Directory of Open Access Journals (Sweden)

Luoa Gang

2015-12-01

Full Text Available According to the modal superposition method, the vortex vibration procedure of submerged floating tunnel cable was compiled using Matlab, based on the calculated results, the fatigue damage was predicted. The effects of various factors, such as cable density, cable length, and pretension and velocity distribution on vortex induced fatigue damage in the cable were studied. The results show that velocity distribution has more effect on the cable fatigue damage than cable length, cable density and pre-tension. Secondly, cable length has also relatively effect on the cable damage fatigue, cable density and pretension has limited in a certain range.

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.

Directory of Open Access Journals (Sweden)

Maria De Salvo

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

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

Science.gov (United States)

Dominguez, Maria

2014-04-01

The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour-cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring 'organized crime'. Copyright © 2014 Elsevier Ltd. All rights reserved.

PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

Science.gov (United States)

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

2015-06-06

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

Fatigue and related factors among hotel workers: the effects of emotional labor and non-standard working hours.

Science.gov (United States)

Lee, Ju Jong; Moon, Hyun Jey; Lee, Kyung-Jae; Kim, Joo Ja

2014-01-01

This study assessed fatigue and its association with emotional labor and non-standard working hours among hotel workers. A structured self-administered questionnaire was distributed to 1,320 employees of five hotels located in Seoul. The questionnaire survey included questions concerning the participants' sociodemographics, health-related behaviors, job-related factors, emotional labor, and fatigue. Fatigue was assessed using the Multidimensional Fatigue Scale (MFS). Multiple logistic regression modeling was used to determine the associations between fatigue and emotional labor. Among male workers, there was a significant association between fatigue and both emotional disharmony (OR=5.52, 95% CI=2.35-12.97) and emotional effort (OR=3.48, 95% CI=1.54-7.86). These same associations were seen among the female workers (emotional disharmony: OR=6.91, 95% CI=2.93-16.33; emotional effort: OR=2.28, 95% CI=1.00-5.16). These results indicate that fatigue is associated with emotional labor and, especially, emotional disharmony among hotel workers. Therefore, emotional disharmony management would prove helpful for the prevention of fatigue.

Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

Directory of Open Access Journals (Sweden)

Sangbin Park

2011-08-01

Full Text Available Drosophila neuroendocrine cells comprising the corpora cardiaca (CC are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

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