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Sample records for fatigue notch factor

  1. Factors Influencing Dwell Fatigue Cracking in Notches of Powder Metallurgy Superalloys

    Science.gov (United States)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  3. Probabilistic fatigue life prediction methodology for notched components based on simple smooth fatigue tests

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Z. R.; Li, Z. X. [Dept.of Engineering Mechanics, Jiangsu Key Laboratory of Engineering Mechanics, Southeast University, Nanjing (China); Hu, X. T.; Xin, P. P.; Song, Y. D. [State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing (China)

    2017-01-15

    The methodology of probabilistic fatigue life prediction for notched components based on smooth specimens is presented. Weakestlink theory incorporating Walker strain model has been utilized in this approach. The effects of stress ratio and stress gradient have been considered. Weibull distribution and median rank estimator are used to describe fatigue statistics. Fatigue tests under different stress ratios were conducted on smooth and notched specimens of titanium alloy TC-1-1. The proposed procedures were checked against the test data of TC-1-1 notched specimens. Prediction results of 50 % survival rate are all within a factor of two scatter band of the test results.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

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

  5. Fatigue crack growth from blunt notches

    International Nuclear Information System (INIS)

    Rhodes, D.

    1982-01-01

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

  6. The effect of notches and pits on corrosion fatigue strength

    Science.gov (United States)

    Tatner, Ian

    calculation of the elastic stress intensity factor (K[t]) for the specimen geometry used. The experimental results together with numerical results of FEA were used to calculate of the notch strength reduction factor (K[f]) for the material. This has been used to derive the notch sensitivity factors (q) for both materials.The results of fatigue tests in air showed that although both materials have similar tensile strength their plain fatigue strengths are different. The sensitivity of the fatigue strength to notches was also found to be significantly different. The marageing steel showed a higher sensitivity to a notch than the FV520B.An empirical model has been proposed to quantify the notch sensitivity and the effects of various microstructural features on the fatigue strength. A model has been developed to predict the serviceable life of a peak hardened FV520B turbine blade subjected to aggressive low load conditions during start-up and non-aggressive high load conditions during continual running. The model is based on the conclusions suggested in the work of a threshold stress intensity factor being reached where a fatigue crack will grow from a corrosion pit at the root of a notch. The model is then used to highlight the life reduction caused to steam turbine blades due to increased numbers of start-up cycles.

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

    Directory of Open Access Journals (Sweden)

    Yafei Ma

    2017-05-01

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

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

    International Nuclear Information System (INIS)

    Ren Weiju; Nicholas, Theodore

    2003-01-01

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

  9. Estimation of Low Cycle Fatigue Response of 316 LN Stainless Steel in the Presence of Notch

    Science.gov (United States)

    Agrawal, Richa; Veerababu, J.; Goyal, Sunil; Sandhya, R.; Uddanwadiker, Rashmi; Padole, Pramod

    2018-02-01

    Notches introduced in the plain specimen result in the multiaxial state of stress that exists in the actual components due to the presence of flaws and defects. In the present work, low cycle fatigue life estimation of plain and notched specimens of 316 LN stainless steel is carried out at room temperature and 823 K. The plain and notched specimens with different notch radii were subjected to varying strain amplitudes ranging from ± 0.25 to ± 1.0% at a strain rate of 3 × 10-3 s-1. The fatigue life decreased in the presence of notch for all strain amplitudes at both the temperatures. The decrease in fatigue life was found to be more at room temperature than at 823 K. The fatigue life of the notched specimen decreased by approximately 94.2% compared to plain specimen at room temperature. However, at 823 K the decrease in fatigue life for notched specimen was approximately 84.6%. Low cycle fatigue life of the plain and notched specimens was estimated by Neuber's rule and finite element analysis approach. Neuber's rule overestimated the fatigue life by maximum factor of 2.6 for specimens at room temperature and by maximum factor of 5 for specimens at 823 K. However, it gives closer approximation at higher strain amplitudes at 823 K. Life estimation by finite element analysis at room temperature was within a factor of 1.5 as compared to experimental life, whereas it underestimated the fatigue life within a factor of 6 at high temperature.

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

    Science.gov (United States)

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

    2005-06-01

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

  11. Effect of vibration loading on the fatigue life of part-through notched pipe

    International Nuclear Information System (INIS)

    Mittal, Rahul; Singh, P.K.; Pukazhendi, D.M.; Bhasin, V.; Vaze, K.K.; Ghosh, A.K.

    2011-01-01

    A systematic experimental and analytical study has been carried out to investigate the effect of vibration loading on the fatigue life of the piping components. Three Point bend (TPB) specimens machined from the actual pipe have been used for the evaluation of Paris constants by carrying out the experiments under vibration + cyclic and cyclic loading as per the ASTM Standard E647. These constants have been used for the prediction of the fatigue life of the pipe having part-through notch of a/t = 0.25 and aspect ratio (2c/a) of 10. Predicted results have shown the reduction in fatigue life of the notched pipe subjected to vibration + cyclic loading by 50% compared to that of cyclic loading. Predicted results have been validated by carrying out the full-scale pipe (with part-through notch) tests. Notched pipes were subjected to loading conditions such that the initial stress-intensity factor remains same as that of TPB specimen. Experimental results of the full-scale pipe tests under vibration + cyclic loading has shown the reduction in fatigue life by 70% compared to that of cyclic loading. Fractographic examination of the fracture surface of the tested specimens subjected to vibration + cyclic loading have shown higher presence of brittle phases such as martensite (in the form of isolated planar facets) and secondary micro cracks. This could be the reason for the reduction of fatigue life in pipe subjected to vibration + cyclic loading. - Highlights: → Vibration loading affects fatigue crack growth rate. → Crack initiation life depends on crack tip radius. → Crack initiation life depends on the characteristic distance. → Characteristic distance depends on the loading conditions. → Vibration + cyclic load gives lower fatigue life.

  12. Experience with the Notch Stress Approach for Fatigue Assessment of Welded Joints

    DEFF Research Database (Denmark)

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

    2010-01-01

    In this paper, fatigue assessment using the notch stress approach is discussed based on re-analysis of many fatigue test results and experience from practical application. Three topics are treated; evaluation of the fatigue strength for as-welded details (FAT225) in the notch stress system......, problems regarding assessment of mild-SCF details and a novel proposal for extension of the notch stress approach for use with post-weld treated details....

  13. 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.

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

    Science.gov (United States)

    Kuhn, Paul; Hardrath, Herbert F

    1952-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Use of Neuber's rule to estimate the fatigue life of notched specimens of ASME SA 106-B steel piping in 2880C air

    International Nuclear Information System (INIS)

    Terrell, J.B.

    1989-01-01

    Fatigue strain-life tests were conducted on notched specimens of ADMESA 106-B piping steel at PWR operating temperatures (288 0 C (550 0 F)), under completely reversed loading. Fatigue limits at 10 7 cycles were estimated for smooth specimens to be 185 M Pa (26.8 ksi) at 24 0 C and 232 MPa (33.7 ksi) at 288 0 C. The higher fatigue strength observed at the PWR temperature is postulated to be caused by dynamic strain aging processes. However, a reduction in fatigue strength in the low cycle fatigue regime was observed in 288 0 C air environment tests, which may indicate that the current ASME Section III design curve for carbon steels is nonconservative in its positioning. Notch strain histories were estimated for the notched specimen tests using various interpretations of Neuber's rule. It was concluded that the use of the fatigue notch concentration factor (K f ) in the Neuber relation in conjunction with the uniaxial cyclic stress-strain curve provided the best correlation of notched specimen fatigue data with results obtained from smooth specimen tests. The notched specimen strain-life results derived from the application of Neuber's rule alone proved to be conservative when compared with smooth specimen test results to such an extent that Neuber-generated notch stresses and strain amplitudes cannot accurately be compared with the mean data curves derived from the ASME Section III fatigue curves for carbon steels which are based on net section stress measurements. (author)

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

    Directory of Open Access Journals (Sweden)

    Eriksson Robert

    2018-01-01

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

  18. 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.

  19. 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

  20. Notch fatigue crack propagation - A consistent concept for calculating flawed service life

    International Nuclear Information System (INIS)

    Dankert, M.

    1999-01-01

    The research report presents a consistent concept of elastic-plastic fatigue fracture mechanics, to be used for numerical description of crack initiation and propagation behaviour within and out of notched areas of circular notched specimens for Woehler tests, two-phase fatigue tests and tests under service conditions. It is shown that a fracture-mechanics approach yields results capable of describing the load history over the whole service life of a structural member. A J-integral-related crack propagation model is derived that takes into account the crack opening and closure behaviour. The model is based on specially developed formulas, algorithms and approximation formulas required for description of crack opening and closure behaviour as well as calculation of the stress intensity factor K and the J-integral of cracks at notches. The values relating to crack opening were compared with experimental data, and those describing the stress intensity factor K and the J-integrals with 2D and 3D elastic-plastic FE calculations. Good and very good agreement of results was achieved. (orig./CB) [de

  1. Theoretical modeling and experimental study on fatigue initiation life of 16MnR notched components

    International Nuclear Information System (INIS)

    Wang Xiaogui; Gao Zengliang; Qiu Baoxiang; Jiang Yanrao

    2010-01-01

    In order to investigate the effects of notch geometry and loading conditions on the fatigue initiation life and fatigue fracture life of 16MnR material, fatigue experiments were conducted for both smooth rod specimens and notched rod specimens. The detailed elastic-plastic stress and strain responses were computed by the finite element software (ABAQUS) incorporating a robust cyclic plasticity model via a user subroutine UMAT. The obtained stresses and strains were applied to the multiaxial fatigue damage criterion to compute the fatigue damage induced by a loading cycle on the critical material plane. The fatigue initiation life was then obtained by the proposed theoretical model. The well agreement between the predicted results and the experiment data indicated that the fatigue initiation of notched components in the multiaxial stress state related to all the nonzero stress and strain quantities. (authors)

  2. Averaged strain energy density-based synthesis of crack initiation life in notched steel bars under torsional fatigue

    Directory of Open Access Journals (Sweden)

    Filippo Berto

    2016-10-01

    Full Text Available The torsional fatigue behaviour of circumferentially notched specimens made of austenitic stainless steel, SUS316L, and carbon steel, SGV410, characterized by different notch root radii has been recently investigated by Tanaka. In that contribution, it was observed that the total fatigue life of the austenitic stainless steel increases with increasing stress concentration factor for a given applied nominal shear stress amplitude. By using the electrical potential drop method, Tanaka observed that the crack nucleation life was reduced with increasing stress concentration, on the other hand the crack propagation life increased. The experimental fatigue results, originally expressed in terms of nominal shear stress amplitude, have been reanalysed by means of the local strain energy density (SED averaged over a control volume having radius R0 surrounding the notch tip. To exclude all extrinsic effects acting during the fatigue crack propagation phase, such as sliding contact and/or friction between fracture surfaces, crack initiation life has been considered in the present work. In the original paper, initiation life was defined in correspondence of a 0.1÷0.4-mm-deep crack. The control radius R0 for fatigue strength assessment of notched components, thought of as a material property, has been estimated by imposing the constancy of the averaged SED for both smooth and cracked specimens at NA = 2 million loading cycles

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Correlation of eddy current responses between fatigue cracks and electrical-discharge-machining notches

    Science.gov (United States)

    Seo, Sukho; Choi, Gyudong; Eom, Tae Jhoun; Lee, Bokwon; Lee, Soo Yeol

    2017-07-01

    The eddy current responses of Electrical Discharge Machining (EDM) notches and fatigue cracks are directly compared to verify the reliability of eddy current inspection. The fatigue crack growth tests using a constant load range control mode were conducted to obtain a variety of edge crack sizes, ranging from 0.9 to 6.6 mm for Al alloy and from 0.1 to 3 mm for Ti alloy. EDM notch specimens of Al and Ti alloys were accordingly prepared in lengths similar to that of the fatigued specimen. The crack length was determined by optical microscope and scanning electron microscope. The eddy current responses between the EDM and fatigued specimens with varying notch/crack length were examined using probe sensors at (100-500) kHz and (1-2) MHz for Al and Ti alloys, respectively. The results show a significant difference in the eddy current signal between the two specimens, based on the correlation between the eddy current response and notch/crack length. This suggests that eddy current inspection using the EDM reference specimen is inaccurate in determining the precise crack size, unless the eddy current response data base is obtained from a fatigue-cracked specimen.

  8. 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.

  9. 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.

  10. 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...

  11. 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)

  12. 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

  13. 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.

  14. 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)

  15. 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....

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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)

  1. 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.)

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  12. 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)

  13. 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.

  14. 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.))

  15. 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

  16. 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.

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

    Science.gov (United States)

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

    2015-07-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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].

  3. 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

  4. 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)

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. 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

  10. 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).

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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....

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Fatigue

    Science.gov (United States)

    ... to help you find out what's causing your fatigue and recommend ways to relieve it. Fatigue itself is not a disease. Medical problems, treatments, and personal habits can add to fatigue. These include Taking certain medicines, such as antidepressants, ...

  2. 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,

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. [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

  9. 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.

  10. 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.

  11. Application of Weakest Link Probabilistic Framework for Fatigue Notch Factor to Aero Engine Materials

    Science.gov (United States)

    2014-08-25

    42 3.1.1 The Physical Metallurgy of Nickel and Its Alloys... metallurgy [88]. . 43 Figure 3.2. Procedural steps of producing turbine disc alloys by powder metallurgy techniques [88... weld fillets, holes for bolts, and rivets. Other forms of discontinuities are caused by the ingestion of foreign objects during operation causing

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Fatigue

    Science.gov (United States)

    ... sleep. Fatigue is a lack of energy and motivation. Drowsiness and apathy (a feeling of not caring ... Call your provider right away if you have any of the following: Confusion or dizziness Blurred vision Little or no urine, or recent ...

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. Fatigue strength reduction factors for welds based on nondestructive examination

    International Nuclear Information System (INIS)

    Hechmer, J.L.; Kuhn, E.J. III

    1999-01-01

    Based on the author's hypothesis that nondestructive examination (NDE) has a major role in predicting the fatigue life of pressure vessels, a project was initiated to develop a defined relationship between NDE and fatigue strength reduction factors (FSRF). Even though a relationship should apply to both base metal and weld metal, the project was limited to weld metal because NDE for base metal is reasonably well established, whereas NDE for weld metal is more variable, depending on application. A matrix of FSRF was developed based on weld type (full penetration, partial penetration, and fillet weld) versus the NDE that is applied. The NDE methods that are included are radiographic testing (RT), ultrasonic testing (UT), magnetic particle testing (MT), dye penetrant testing (PT), and visual testing (VT). The first two methods (RT and UT) are volumetric examinations, and the remaining three are surface examinations. Seven combinations of volumetric and surface examinations were defined; thus, seven levels of FSRF are defined. Following the initial development of the project, a PVRC (Pressure Vessel Research Council) grant was obtained for the purpose of having a broad review. The report (Hechmer, 1998) has been accepted by PVRC. This paper presents the final matrix, the basis for the FSRF, and key definitions for accurate application of the FSRF matrix. A substantial amount of additional information is presented in the PVRC report (Hechmer, 1998)

  6. 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.

  7. 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.

  8. 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...

  9. [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.

  10. Notch Sensitivity of Fatigue Behavior of a Hi-Nicalon/SiC Ceramic Composite with an Oxidation Inhibited Matrix at 1200 degree C in Air and in Steam

    Science.gov (United States)

    2011-03-24

    Stress Ratio and Frequency. AGARD - CP -569, NATO, AGARD , SMP, 7 Rue Ancelle, 92200 Neuilly sur Seine, France, March 1996. 5. Chawla, K.K. Ceramic Matrix...fatigue at 1.0 Hz in air at 1200°C. σmax = 120 MPa, Nf = 77,575, tf = 21.5 h ........................................................ 73 Figure 55: SEM...areas of oxidation. ............ 73 Figure 56: SEM micrographs of the fiber fracture surfaces of specimen 13 tested in fatigue at 1.0 Hz in steam at

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. 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.

  11. Creep-fatigue crack initiation assessment on thick circumferentially notched 316L tubes under cyclic thermal shocks and uniform tension with the σd approach

    International Nuclear Information System (INIS)

    Michel, B.; Poette, C.

    1997-01-01

    For crack initiation assessment under creep fatigue loading, in high temperature Fast Reactor's components, specific approaches based on fracture mechanics analysis had to be developed. In the present paper the crack initiation assessment method proposed in the A16 document is presented. The so called ''σ d method'' is also validated on experimental results for tubular specimens with internal axisymmetric surface cracks. Experimental data are extracted from the TERFIS program carried out on a sodium test device at the CEA Cadarache. Metallurgical examinations on TERFIS specimens confirm that the initiation assessment of the ''σ d '' approach is conservative even for a different geometry than the CT specimen on which the method was set up. However, the conservatism is reduced when the creep residual stress field is relaxed during the hold time. An investigation concerning this last point is needed in order to know if relaxing the stress, when using a lower bound of the mechanical properties, always keeps a safety margin. (author). 14 refs, 10 figs, 4 tabs

  12. Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells.

    Science.gov (United States)

    Panepucci, Rodrigo Alexandre; Oliveira, Lucila Habib B; Zanette, Dalila Luciola; Viu Carrara, Rita de Cassia; Araujo, Amélia Goes; Orellana, Maristela Delgado; Bonini de Palma, Patrícia Vianna; Menezes, Camila C B O; Covas, Dimas Tadeu; Zago, Marco Antonio

    2010-03-01

    As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.

  13. 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.)

  14. The role of cognitive, emotional and personality factors in the experience of fatigue in a university and community sample.

    Science.gov (United States)

    Kangas, Maria; Montgomery, Guy H

    2011-05-01

    The aim of this study was to investigate the contribution of cognitive, emotional and personality factors to the experience of fatigue severity in healthy adult individuals. Specifically, the study examined whether fatigue catastrophising and emotional distress mediated the relationships between neuroticism, general irrational and rational thoughts to fatigue severity. One hundred and eighty nine university students and community volunteers completed self-report questionnaires assessing fatigue catastrophising and symptom severity, neuroticism, general rational and irrational thoughts and emotional distress. A series of correlational and path analyses were conducted to test the study hypotheses. Neuroticism and more general negative, irrational cognitions were associated with elevated fatigue catastrophising and fatigue severity, whereas more adaptive, rational cognitions were related to lower fatigue catastrophising and fatigue severity. Both elevated fatigue catastrophising and emotional distress uniquely and simultaneously mediated the relationships between irrational and rational cognitions and neuroticism to fatigue severity. These findings demonstrate that cognitions play a role in fatigue severity. The results have implications in the assessment and treatment of fatigue disturbances in the general community.

  15. 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.

  16. Factors that influence the development of compassion fatigue, burnout, and compassion satisfaction in emergency department nurses.

    Science.gov (United States)

    Hunsaker, Stacie; Chen, Hsiu-Chin; Maughan, Dale; Heaston, Sondra

    2015-03-01

    The purpose of this study was twofold: (a) to determine the prevalence of compassion satisfaction, compassion fatigue, and burnout in emergency department nurses throughout the United States and (b) to examine which demographic and work-related components affect the development of compassion satisfaction, compassion fatigue, and burnout in this nursing specialty. This was a nonexperimental, descriptive, and predictive study using a self-administered survey. Survey packets including a demographic questionnaire and the Professional Quality of Life Scale version 5 (ProQOL 5) were mailed to 1,000 selected emergency nurses throughout the United States. The ProQOL 5 scale was used to measure the prevalence of compassion satisfaction, compassion fatigue, and burnout among emergency department nurses. Multiple regression using stepwise solution was employed to determine which variables of demographics and work-related characteristics predicted the prevalence of compassion satisfaction, compassion fatigue, and burnout. The α level was set at .05 for statistical significance. The results revealed overall low to average levels of compassion fatigue and burnout and generally average to high levels of compassion satisfaction among this group of emergency department nurses. The low level of manager support was a significant predictor of higher levels of burnout and compassion fatigue among emergency department nurses, while a high level of manager support contributed to a higher level of compassion satisfaction. The results may serve to help distinguish elements in emergency department nurses' work and life that are related to compassion satisfaction and may identify factors associated with higher levels of compassion fatigue and burnout. Improving recognition and awareness of compassion satisfaction, compassion fatigue, and burnout among emergency department nurses may prevent emotional exhaustion and help identify interventions that will help nurses remain empathetic and

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Fatigue reliability and calibration of fatigue design factors of wave energy converters

    DEFF Research Database (Denmark)

    Ambühl, Simon; Ferri, Francesco; Kofoed, Jens Peter

    2015-01-01

    Target reliability levels, which are chosen dependent on the consequences in case of structural collapse, are used in this paper to calibrate partial safety factors for structural details of wave energy converters (WECs). The consequences in case of structural failure are similar for WECs and off...

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. The factors associated with the burnout syndrome and fatigue in Cypriot nurses: a census report

    Directory of Open Access Journals (Sweden)

    Raftopoulos Vasilios

    2012-06-01

    Full Text Available Abstract Background Fatigue and burnout are two concepts often linked in the literature. However, regardless of their commonalities they should be approached as distinct concepts. The current and ever-growing reforms regarding the delivery of nursing care in Cyprus, stress for the development of ways to prevent burnout and effectively manage fatigue that can result from working in stressful clinical environments. Methods To explore the factors associated with the burnout syndrome in Cypriot nurses working in various clinical departments. A random sampling method taking into account geographical location, specialty and type of employment has been used. Results A total of 1,482 nurses (80.4% were females working both in the private and public sectors completed and returned an anonymous questionnaire that included several aspects related to burnout; the MBI scale, questions related to occupational stress, and questions pertaining to self reported fatigue. Two-thirds (65.1% of the nurses believed that their job is stressful with the majority reporting their job as stressful being female nurses (67.7%. Twelve point eight percent of the nurses met Maslach’s criteria for burnout. The prevalence of fatigue in nurses was found 91.9%. The prevalence of fatigue was higher in females (93% than in males (87.5% (p = 0.003. As opposed to the burnout prevalence, fatigue prevalence did not differ among the nursing departments (p = 0.166 and among nurses with a different marital status (p = 0.553. Burnout can be associated adequately knowing if nurses find their job stressful, their age, the level of emotional exhaustion and depersonalization. It has been shown that the fatigue may be thought of as a predictor of burnout, but its influence is already accounted by emotional exhaustion and depersonalization. Conclusion The clinical settings in Cyprus appear as stress generating environment for nurses. Nurses working both in the private and public

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. Factors Associated with Visual Fatigue from Curved Monitor Use: A Prospective Study of Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Haeng Jin Lee

    Full Text Available To investigate the factors associated with visual fatigue using monitors with various radii of curvature.Twenty normal healthy adults (8 men, 12 women; mean age, 26.2 ± 2.5 years prospectively watched five types of monitors including flat, 4000R, 3000R, 2000R, and 1000R curved monitors for 30 min. An experienced examiner measured the ophthalmological factors including near point of accommodation (NPA, near point of convergence (NPC, refraction, parameters during pupil response at light and saccadic movement just before and after the visual tasks. The questionnaires about subjective ocular symptoms were also investigated just before and after the visual tasks.The NPA increased after the visual tasks with a flat monitor compared with the curved monitors, with the 1000R curved monitor showing the smallest change (p = 0.020. The NPC increased for every monitor after the visual tasks; the largest increase occurred with the flat monitor (p = 0.001. There was no difference in refractive error, pupil response, or saccadic movement in the comparison of before and after the visual tasks. Among the nine factors in the questionnaire, the score of "eye pain" was significantly higher for the flat monitor versus the 1000R curved monitor after the visual tasks (p = 0.034.We identified NPA, NPC, and eye pain as factors associated with visual fatigue. Also, the curvature of the monitor was related to the visual fatigue.

  20. 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

  1. Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

    Science.gov (United States)

    Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

    2015-08-01

    Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. 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.

  3. 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

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

    OpenAIRE

    Meliou, E; Kerezoudis, NP; Tosios, KI; Kiaris, H

    2010-01-01

    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 exami...

  5. Fatigue in the Danish general population. Influence of sociodemographic factors and disease

    DEFF Research Database (Denmark)

    Watt, T; Groenvold, M; Bjorner, J B

    2000-01-01

    -77 with an equal gender distribution (response rate 67%). MAIN OUTCOME MEASURES: Five fatigue scales from the questionnaire Multidimensional Fatigue Inventory: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation and Mental Fatigue. RESULTS: Fatigue scores were skewed towards absence of fatigue....... The General Fatigue and Physical Fatigue scales showed the highest fatigue levels while the Reduced Motivation scale showed lowest levels. Gender differences in fatigue scores were small, but the variability among women was higher-that is, more women had high scores. A multiple linear regression analysis......, gender and/or whether the person was living alone. For example, General and Physical Fatigue decreased with age among healthy people, whereas scores on these scales increased with age among those with a somatic disease. CONCLUSIONS: Physical and mental diseases play essential parts for the level...

  6. 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 ...

  7. 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...

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

    International Nuclear Information System (INIS)

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

    1991-01-01

    This paper reports on the provisions of ASME B and 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 degrees C (1000 degrees 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

  9. 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.

  10. 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.

  11. The bHLH factors Dpn and members of the E(spl complex mediate the function of Notch signalling regulating cell proliferation during wing disc development

    Directory of Open Access Journals (Sweden)

    Beatriz P. San Juan

    2012-05-01

    The Notch signalling pathway plays an essential role in the intricate control of cell proliferation and pattern formation in many organs during animal development. In addition, mutations in most members of this pathway are well characterized and frequently lead to tumour formation. The Drosophila imaginal wing discs have provided a suitable model system for the genetic and molecular analysis of the different pathway functions. During disc development, Notch signalling at the presumptive wing margin is necessary for the restricted activation of genes required for pattern formation control and disc proliferation. Interestingly, in different cellular contexts within the wing disc, Notch can either promote cell proliferation or can block the G1-S transition by negatively regulating the expression of dmyc and bantam micro RNA. The target genes of Notch signalling that are required for these functions have not been identified. Here, we show that the Hes vertebrate homolog, deadpan (dpn, and the Enhancer-of-split complex (E(splC genes act redundantly and cooperatively to mediate the Notch signalling function regulating cell proliferation during wing disc development.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Fatigue damage estimation using irregularity factor. First report, irregularity factor calculations for narrow and broadband random time histories

    Science.gov (United States)

    Susuki, I.

    1981-11-01

    The results of an analysis of the irregularity factors of stationary and Gaussian random processes which are generated by filtering the output of a pure or a band-limited white noise are presented. An ideal band pass filter, a trapezoidal filter, and a Butterworth type band pass filter were examined. It was found that the values of the irregularity factors were approximately equal among these filters if only the end-slopes were the same rates. As the band width of filters increases, irregularity factors increase monotonically and approach the respective constant values depending on the end-slopes. This implies that the noise characteristics relevant to the fatigue damage such as statistical aspects of the height of the rise and fall or the distribution of the peak values are not changed for a broad band random time history. It was also found that the effect of band limitation of input white noise on irregularity factors is negligibly small.

  17. An environmental factor approach to account for reactor water effects in light water reactor pressure vessel and piping fatigue evaluations

    International Nuclear Information System (INIS)

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

    1996-01-01

    This paper summarizes past and current studies of the environmental fatigue effects in 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 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

  18. The Drosophila T-box transcription factor Midline functions within the Notch-Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc.

    Science.gov (United States)

    Das, Sudeshna; Chen, Q Brent; Saucier, Joseph D; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M

    2013-01-01

    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch-Delta signaling pathway essential for specifying the fates of sensory organ precursor (SOP) cells. These findings complement an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in unique neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch-Delta signaling hierarchy and is essential for maintaining cell viability by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. 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.

  20. 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)

  1. Predicting Performance during Chronic Sleep Loss: Identification of Factors Sensitive to Individual Fatigue Resistance

    Science.gov (United States)

    2015-03-18

    fatigue-related performance impairments for a given schedule. However, these models fail to account for individual differences in fatigue susceptibility...Tool, FAST ™ ), yet these models fail to take into account important individual differences in fatigue states and susceptibility to fatigue. However...Venkatraman et al., 2007) and confusion ( Drury et al., 2012). However, sustained or continuous operations in high tempo, wartime operations often

  2. 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.

  3. 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.

  4. 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

  5. Study of fatigue, depression, and associated factors in type 2 diabetes mellitus in industrial workers

    Directory of Open Access Journals (Sweden)

    Akhilesh Jain

    2015-01-01

    Full Text Available Introduction: Type 2 diabetes mellitus is a significant health problem and imposes great physical, financial and psychological burden among the affected population. Among people with diabetes, fatigue is a pervasive and distressing complaint, which is further accentuated by presence of depression. Objective: To assess the prevalence of fatigue and depression and associated clinical and socio demographic correlates in type 2diabetes. Materials and Methods: This cross sectional study included 100 patients of diabetes type 2 and equal number of healthy controls between the ages of 18 to 70 years . A detailed evaluation of socio demographic and clinical parameters was made. Participants were also assessed for presence of depression and fatigue using PHQ-9 and Fatigue Severity Scale(FSSrespectively. Results: Fatigue and depression was found in 68 % and 53 % of diabetic participants. Diabetic patients were 10.37 times and 4.80 times more likely to suffer from fatigue and depression respectively. Both fatigue and depression were found to be significantly associated with duration of illness, fasting and post prandial blood glucose level ,diabetic complications and Body Mass Index (BMI. Fatigue was also strongly correlated with depression in study sample. Conclusions: Fatigue and depression are reasonably correlated with type 2 diabetes. Various clinical parameters of diabetes are strongly associated with both fatigue and depression. Fatigue itself has significant correlation with depression in type 2 diabetes. Regular monitoring of biochemical parameters are paramount to predict the development of fatigue and depression in type 2 diabetes.

  6. 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.

  7. Fatigue in adults with Marfan syndrome, occurrence and associations to pain and other factors.

    Science.gov (United States)

    Bathen, Trine; Velvin, Gry; Rand-Hendriksen, Svend; Robinson, Hilde Stendal

    2014-08-01

    This study aims to investigate how fatigue affects adults with verified Marfan syndrome (MFS) in their daily lives, by examining fatigue levels and prevalence of severe fatigue compared to the general Norwegian population and individuals with other comparable chronic conditions. We investigated associations between socio-demographic characteristics, Marfan-related health problems, pain and fatigue. A cross-sectional study was conducted, using a postal questionnaire including the Fatigue Severity Scale (FSS) and questions on socio-demographic characteristics, Marfan-related health problems and pain. One hundred seventeen persons with MFS were invited to participate, 73 answered (62%). Participants reported significantly higher FSS scores and prevalence of severe fatigue compared to the general Norwegian population and patients with rheumatoid arthritis (RA), but lower than for other chronic conditions. Participants with chronic pain reported higher fatigue scores than those without chronic pain. Participants on disability benefits reported higher fatigue scores than participants who were working or enrolled in higher education. Marfan-related health problems like aortic dissection and use of blood pressure medication were not significantly associated with fatigue. In multivariable regression analyses chronic pain and employment status were significantly associated with fatigue. The final multivariable model explained 24% of the variance in fatigue scores. Our results show that fatigue is common in MFS patients and that it interferes with their daily lives. Chronic pain and employment status show significant associations to fatigue. This implies that fatigue is important to address when meeting MFS patients in clinical practice. There is need for more research on fatigue in Marfan syndrome. © 2014 Wiley Periodicals, Inc.

  8. 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

  9. 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

  10. 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

  11. Discerning Primary and Secondary Factors Responsible for Clinical Fatigue in Multisystem Diseases

    Directory of Open Access Journals (Sweden)

    David Maughan

    2014-09-01

    Full Text Available Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.

  12. 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

  13. Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Attree EA

    2014-02-01

    Full Text Available Elizabeth A Attree,1 Megan A Arroll,1 Christine P Dancey,1 Charlene Griffith,1 Amolak S Bansal1,2 1Chronic Illness Research Team, School of Psychology, University of East London, London, UK; 2Department of Immunology and the Sutton CFS Service, St Helier Hospital, Carshalton, UK Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures. Methods: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression to predict cognitive function (self-ratings on prospective and retrospective memory, and cognitive failures. Results: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective memory. Conclusion: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Stress intensity factors for fatigue loaded details between crossbeams and trapezoidal stringers

    NARCIS (Netherlands)

    Maljaars, J.; Pijpers, R.J.M.

    2013-01-01

    A number of orthotropic deck structures of existing bridges are suffering from fatigue cracks. Maintenance of these deck structures may consist of regular inspections and repair of detected cracks. The usual fatigue design life procedure for aswelded structures based on S-N curves is not feasible

  1. Fatigue associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis.

    Science.gov (United States)

    Li, Jing; Gu, Jian

    2017-10-01

    The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017. Thirteen randomized controlled trials and 4395 patients were included. The current analysis suggested that the use of five newly approved VEGFR-TKIs increased the risk of all-grade fatigue (1.43; 95% CI 1.23-1.66; p fatigue (1.97; 95% CI1.44-2.70; p fatigue varied significantly within drug type, but high-grade fatigue did not. The RR of all-grade and high-grade fatigue did not vary significantly according to cancer type, treatment line, and treatment duration. The risk of high-grade fatigue may vary with treatment duration, whereas all-grade fatigue may not. The available data suggest that the use of the five newly approved VEGFR-TKIs is associated with a significantly increased risk of fatigue in cancer patients. Physicians should be aware of this adverse effect and should monitor cancer patients receiving these drugs.

  2. 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

  3. Determinants of seafarers’ fatigue

    DEFF Research Database (Denmark)

    Bøggild Dohrmann, Solveig; Leppin, Anja

    2017-01-01

    in the review. The main reason for exclusion was fatigue not being the outcome variable. Results: Most evidence was available for work time-related factors suggesting that working nights was most fatiguing, that fatigue levels were higher toward the end of watch or shift, and that the 6-h on–6-h off watch...

  4. 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

  5. Fatigue and Relating Factors in High-Risk Breast Cancer Patients Treated With Adjuvant Standard or High-Dose Chemotherapy: A Longitudinal Study

    NARCIS (Netherlands)

    Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.; Mulder, N.H.; Graaf, W.T.A. van der; TenVergert, E.M.; Tinteren, H. van; Vries, E.G.E. de

    2005-01-01

    PURPOSE Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to posttreatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  6. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

    NARCIS (Netherlands)

    Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.S.G.J.; Mulder, N.H.; Graaf, W.T.A. van der; Vergert, E.M. ten; Tinteren, H.L.G. van; Vries, E.G.F. de

    2005-01-01

    PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  7. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study

    NARCIS (Netherlands)

    Nieboer, Peter; Buijs, Ciska; Rodenhuis, Sjoerd; Seynaeve, Caroline; Beex, Louk V. A. M.; van der Wall, Elsken; Richel, Dick J.; Nooij, Marianne A.; Voest, Emile E.; Hupperets, Pierre; Mulder, Nanno H.; van der Graaf, Winette T. A.; TenVergert, Els M.; van Tinteren, Harm; de Vries, Elisabeth G. E.

    2005-01-01

    PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  8. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy : A longitudinal study

    NARCIS (Netherlands)

    Nieboer, P; Buijs, C; Rodenhuis, S; Seynaeve, C; Beex, LVAM; van der Wall, E; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; Mulder, NH; van der Graaf, WTA; TenVergert, EM; van Tinteren, H; de Vries, EGE

    2005-01-01

    Purpose Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. Performance study of K{sub e} factors in simplified elastic plastic fatigue analyses with emphasis on thermal cyclic loading

    Energy Technology Data Exchange (ETDEWEB)

    Lang, Hermann, E-mail: hermann.lang@areva.com [AREVA NP GmbH, PEEA-G, Henri-Dunant-Strasse 50, 91058 Erlangen (Germany); Rudolph, Juergen; Ziegler, Rainer [AREVA NP GmbH, PEEA-G, Henri-Dunant-Strasse 50, 91058 Erlangen (Germany)

    2011-08-15

    As code-based fully elastic plastic code conforming fatigue analyses are still time consuming, simplified elastic plastic analysis is often applied. This procedure is known to be overly conservative for some conditions due to the applied plastification (penalty) factor K{sub e}. As a consequence, less conservative fully elastic plastic fatigue analyses based on non-linear finite element analyses (FEA) or simplified elastic plastic analysis based on more realistic K{sub e} factors have to be used for fatigue design. The demand for more realistic K{sub e} factors is covered as a requirement of practical fatigue analysis. Different code-based K{sub e} procedures are reviewed in this paper with special regard to performance under thermal cyclic loading conditions. Other approximation formulae such as those by Neuber, Seeger/Beste or Kuehnapfel are not evaluated in this context because of their applicability to mechanical loading excluding thermal cyclic loading conditions typical for power plant operation. Besides the current code-based K{sub e} corrections, the ASME Code Case N-779 (e.g. Adam's proposal) and its modification in ASME Section VIII is considered. Comparison of elastic plastic results and results from the Rules for Nuclear Facility Components and Rules for Pressure Vessels reveals a considerable overestimation of usage factor in the case of ASME III and KTA 3201.2 for the examined examples. Usage factors according to RCC-M, Adams (ASME Code Case N-779), ASME VIII (alternative) and EN 13445-3 are essentially comparable and less conservative for these examples. The K{sub v} correction as well as the applied yield criterion (Tresca or von Mises) essentially influence the quality of the more advanced plasticity corrections (e.g. ASME Code Case N-779 and RCC-M). Hence, new proposals are based on a refined K{sub v} correction.

  15. Performance study of Ke factors in simplified elastic plastic fatigue analyses with emphasis on thermal cyclic loading

    International Nuclear Information System (INIS)

    Lang, Hermann; Rudolph, Juergen; Ziegler, Rainer

    2011-01-01

    As code-based fully elastic plastic code conforming fatigue analyses are still time consuming, simplified elastic plastic analysis is often applied. This procedure is known to be overly conservative for some conditions due to the applied plastification (penalty) factor K e . As a consequence, less conservative fully elastic plastic fatigue analyses based on non-linear finite element analyses (FEA) or simplified elastic plastic analysis based on more realistic K e factors have to be used for fatigue design. The demand for more realistic K e factors is covered as a requirement of practical fatigue analysis. Different code-based K e procedures are reviewed in this paper with special regard to performance under thermal cyclic loading conditions. Other approximation formulae such as those by Neuber, Seeger/Beste or Kuehnapfel are not evaluated in this context because of their applicability to mechanical loading excluding thermal cyclic loading conditions typical for power plant operation. Besides the current code-based K e corrections, the ASME Code Case N-779 (e.g. Adam's proposal) and its modification in ASME Section VIII is considered. Comparison of elastic plastic results and results from the Rules for Nuclear Facility Components and Rules for Pressure Vessels reveals a considerable overestimation of usage factor in the case of ASME III and KTA 3201.2 for the examined examples. Usage factors according to RCC-M, Adams (ASME Code Case N-779), ASME VIII (alternative) and EN 13445-3 are essentially comparable and less conservative for these examples. The K v correction as well as the applied yield criterion (Tresca or von Mises) essentially influence the quality of the more advanced plasticity corrections (e.g. ASME Code Case N-779 and RCC-M). Hence, new proposals are based on a refined K v correction.

  16. Chemotherapy-induced Fatigue among Jordanian Cancer Patients: What are the Contributing Factors?

    Directory of Open Access Journals (Sweden)

    Kholoud Abu Obead

    2014-03-01

    Full Text Available Background: The purposes of this study were to examine the impact of chemotherapy treatment on Jordanian cancer patients’ fatigue and to correlate their fatigue with selected sociodemographic variables at the beginning of treatment and after four weeks of treatment. Methods: This was a single group quasi-experimental correlational design study that enrolled 43 patients diagnosed with cancer who required chemotherapy treatment. Fatigue was measured according to the Piper Fatigue Scale (PFS before starting chemotherapy treatment and after four weeks of receiving the first dose of chemotherapy. Data were collected over a period of four weeks and analyzed with descriptive statistics, the paired-sample t-test, and Pearson product-moment correlation. Results: The study included 17 (39.5% males and 26 (60.5% females with a mean age of 45.98 years. Most (n=17 were diagnosed with breast cancer. Obesity was present in about 64.4% of patients. The majority (46% received an anthracycline-based regimen. There were statistically significant differences between respondents’ total mean scores of fatigue pre-treatment and four weeks following chemotherapy treatment (t= -2.31, df=42, P<0.05. In addition, significant differences were found in the scores for behavioral, affective, sensory, and cognitive dimensions subscales (t= -2.24, -2.19, - 2.4, -2.4, df=42, P<0.05 between pre-treatment and four weeks after receiving the first dose of chemotherapy treatment. We observed a significant negative relationship between fatigue scores and hemoglobin levels (r= -0.04, P<0.01. Conclusion: Cancer-related fatigue is common among cancer patients who received chemotherapy and result in substantial adverse physical, behavioral, cognitive and affective consequences for patient. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.

  17. The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.

    Science.gov (United States)

    Mills, K C; Spruill, S E; Kanne, R W; Parkman, K M; Zhang, Y

    2001-01-01

    A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.

  18. The number of sectors and other risk factors related to fatigue among shorthaul commercial pilots in Indonesia

    Directory of Open Access Journals (Sweden)

    Inne Yuliawati

    2016-03-01

     AbstractBackground: Fatigue could impair cognitive function in pilots which may lead to accidents in short-haul flight. Theaim of this study was to identify the risk factors related to fatigue among short-haul commercial pilots in Indonesia.Methods: A cross-sectional study with purposive sampling was conducted among Boeing 737 seriestyped-rating pilots taking medical examination at the Civil Aviation Medical Center, Jakarta from May5-26, 2014. Fatigue was measured with Self-Reporting Questionnaire, Fatigue Severity Scale (FSS. Datawere collected using anonymous self-reporting questionnaire on demographics, workload, sleep restriction(Epworth Sleepiness Scale-ESS, personal factors, and managerial support. Linear regression was used toidentify dominant risk factors related to fatigue.Results: During data collection, 785 pilots were taking medical examination, 382 pilots were willing toparticipate, and 239 pilots met the criteria. The FSS mean was 4.66 ± 1.202. The number of sectors in 24hours, flight times of unplanned flights in 30 days, and sleep restriction were dominant factors of fatigue.Each additional sector increased FSS by 0.371 points [regression coefficient (β = 0.371; P = 0.000].Furthermore, each additional ESS, increased FSS by 0.043 points (β = 0.043; P = 0.008, while eachadditional unplanned flights increased FSS by 0.033 points (β = 0.033; P = 0.000.Conclusions: Additional number of sectors in 24 hours, additional unplanned flight times within 30 days,and sleep restriction increased the risk of fatigue among short-haul commercial pilots in Indonesia. (HealthScience Journal of Indonesia 2015;6:69-75Keyword: Fatigue, number of sectors, pilots, Indonesia

  19. Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture.

    Science.gov (United States)

    Zonana-Nacach, A; Roseman, J M; McGwin, G; Friedman, A W; Baethge, B A; Reveille, J D; Alarcón, G S

    2000-01-01

    To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.

  20. Development and Application of a Clinical Microsystem Simulation Methodology for Human Factors-Based Research of Alarm Fatigue.

    Science.gov (United States)

    Kobayashi, Leo; Gosbee, John W; Merck, Derek L

    2017-07-01

    (1) To develop a clinical microsystem simulation methodology for alarm fatigue research with a human factors engineering (HFE) assessment framework and (2) to explore its application to the comparative examination of different approaches to patient monitoring and provider notification. Problems with the design, implementation, and real-world use of patient monitoring systems result in alarm fatigue. A multidisciplinary team is developing an open-source tool kit to promote bedside informatics research and mitigate alarm fatigue. Simulation, HFE, and computer science experts created a novel simulation methodology to study alarm fatigue. Featuring multiple interconnected simulated patient scenarios with scripted timeline, "distractor" patient care tasks, and triggered true and false alarms, the methodology incorporated objective metrics to assess provider and system performance. Developed materials were implemented during institutional review board-approved study sessions that assessed and compared an experimental multiparametric alerting system with a standard monitor telemetry system for subject response, use characteristics, and end-user feedback. A four-patient simulation setup featuring objective metrics for participant task-related performance and response to alarms was developed along with accompanying structured HFE assessment (questionnaire and interview) for monitor systems use testing. Two pilot and four study sessions with individual nurse subjects elicited true alarm and false alarm responses (including diversion from assigned tasks) as well as nonresponses to true alarms. In-simulation observation and subject questionnaires were used to test the experimental system's approach to suppressing false alarms and alerting providers. A novel investigative methodology applied simulation and HFE techniques to replicate and study alarm fatigue in controlled settings for systems assessment and experimental research purposes.

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

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2016-01-01

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

  2. 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

  3. 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

  4. 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

  5. Fatigue analysis - computation of the actual strain range using elastic calculations (factor Ke)

    International Nuclear Information System (INIS)

    Roche, R.L.

    1987-01-01

    Pressure vessels are not eternal, their life is not endless, but must be long enough for profitable use. Fatigue is the most important damage limiting life time. It is due to variable loading and especially to deformation-controlled loading like thermal dilatation (thermal stress). Hence, it is of prime importance to perform an fatigue analysis in the design phase in order to be sure the pressure vessel life meet requirement of the design specification. It is also useful to perform such an analysis for assessing the remaining life. To compute the fatigue damage, knowledge of the strain range is needed. As calculation taking into account non linear behavior of the material are very expensive and not always reliable, the current practice is using elastic computation. The aim of this paper is to discuss the methods for correcting the elastically calculated strain range and to propose a sound and practical method

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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)

  14. Precracking of round notched bars. Progress Report

    International Nuclear Information System (INIS)

    Scibetta, M.

    1996-02-01

    Precracking round notched bars is the first step before fracture mechanics testing. This report gives an overview of the different techniques described in the literature. Difficulties generally encountered are linked to the crack length determination and the creation of eccentric cracks. As the compliance technique is often used, a detailed study of the stress intensity factor and the compliance of the precracked bar under bending and tension is presented. Comparison with finite element calculations is made to validate the proposed analytical formulation. Finally a practical way for precracking is described

  15. 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

  16. 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.

  17. 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

  18. Predictive factors of postpartum fatigue: a prospective cohort study among working women

    NARCIS (Netherlands)

    Bakker, M.; Beek, A.J. van der; Hendriksen, I.J.M.; Bruinvels, D.J.; Poppel, M.N. van

    2014-01-01

    Objectives The aim of this study was to investigate which prepartum determinants contribute to the development of postpartum (PP) fatigue among working women in the Netherlands. Methods A prospective cohort study in 15 Dutch companies was conducted to measure different potential predictors using

  19. The low cycle fatigue factor in the construction of sodium-cooled fast reactors

    International Nuclear Information System (INIS)

    Petrequin, Pierre; Mottot, Michel; Valibus, Louis; Grattier, Georges

    1976-01-01

    The working conditions of fast neutron reactors are such that it is essential to know the resistance of the component steels to low cycle fatigue. The behavior of Z2CND17-13 type austenitic stainless steels and of welds was studied in three laboratories. The steels offer an excellent resistance to low cycle fatigue, in keeping with their good ductility and very strong aptitude for cyclic strain hardening. Increasing the testing temperature from 20 to 600 deg C reduces the resistance to some extent (about an order of magnitude on the number of cycles to failure). Steels possessing improved mechanical properties without loss of ductility show greater fatigue resistance. Welds characterized by an austenitic ferritic structure and a slightly cold-hardened state are less ductile than laminated steels. Their resistance to low cycle fatigue is lower at strong deformations. At high temperature (600 deg C) a reduced test frequency or a pause at each cycle leads to a considerable drop in the number of cycles to failure and the appearance of intergranular cracking [fr

  20. 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

  1. 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

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. 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.

  8. 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

  9. 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...

  10. Effect of Water Vapor Pressure on Fatigue Crack Growth in Al-Zn-Cu-Mg Alloy Over Wide-Range Stress Intensity Factor Loading

    Science.gov (United States)

    2014-05-07

    pressure and frequency on fatigue behaviour in 7017-T651 aluminium alloy plate, Acta Mater, 45 (1997) 281-293. [30) N.J.H. Holroyd, D. Hardie, Factors... aluminium alloys , Acta Mater, 45 (1997) 3855-3870. [33) S. Lynch, Hydrogen embrittlement phenomena and mechanisms, Corros Rev, 30 (2012) 105-123. [34...role of environmental exposure in the fatigue behaviour of an aluminium alloy , Corros Sci, 39 (1997) 2117-2141. [39) R.S. Piascik, R.P. Gangloff

  11. 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.

  12. False Alarms and Overmonitoring: Major Factors in Alarm Fatigue Among Labor Nurses.

    Science.gov (United States)

    Simpson, Kathleen Rice; Lyndon, Audrey

    2018-06-08

    Nurses can be exposed to hundreds of alarms during their shift, contributing to alarm fatigue. The purposes were to explore similarities and differences in perceptions of clinical alarms by labor nurses caring for generally healthy women compared with perceptions of adult intensive care unit (ICU) and neonatal ICU nurses caring for critically ill patients and to seek nurses' suggestions for potential improvements. Nurses were asked via focus groups about the utility of clinical alarms from medical devices. There was consensus that false alarms and too many devices generating alarms contributed to alarm fatigue, and most alarms lacked clinical relevance. Nurses identified certain types of alarms that they responded to immediately, but the vast majority of the alarms did not contribute to their clinical assessment or planned nursing care. Monitoring only those patients who need it and only those physiologic values that are warranted, based on patient condition, may decrease alarm burden.

  13. 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.

  14. Compassion Fatigue Among Palliative Care Clinicians: Findings on Personality Factors and Years of Service.

    Science.gov (United States)

    O'Mahony, Sean; Ziadni, Maisa; Hoerger, Michael; Levine, Stacie; Baron, Aliza; Gerhart, James

    2018-02-01

    Palliative medicine is a rewarding field, but providers encounter patient trauma on a routine basis. Compassion fatigue, marked by burnout, secondary traumatic stress, and low satisfaction may result. However, professionals differ markedly in how they respond to patient trauma. The objective of the current study was to determine whether personality traits of neuroticism and agreeableness relate to aspects of compassion fatigue, after accounting for time spent working in the field. Sixty-six palliative medicine physicians, nurses, social workers, and chaplains completed validated measures of personality traits, compassion fatigue, and work background. Providers who had worked longer reported higher levels of satisfaction and lower levels of burnout. Neuroticism demonstrated strong significant associations with secondary traumatic stress and burnout ( Ps accounting for years spent working in the field. Personality traits of neuroticism and agreeableness may convey risk and resilience, respectively, for palliative care professionals. More research is needed to determine if assessing personality traits can help identify providers at risk for adverse reactions to patient trauma.

  15. The time of day differently influences fatigue and locomotor activity: is body temperature a key factor?

    Science.gov (United States)

    Machado, Frederico Sander Mansur; Rodovalho, Gisele Vieira; Coimbra, Cândido Celso

    2015-03-01

    The aim of this study was to verify the possible interactions between exercise capacity and spontaneous locomotor activity (SLA) during the oscillation of core body temperature (Tb) that occurs during the light/dark cycle. Wistar rats (n=11) were kept at an animal facility under a light/dark cycle of 14/10h at an ambient temperature of 23°C and water and food ad libitum. Initially, in order to characterize the daily oscillation in SLA and Tb of the rats, these parameters were continuously recorded for 24h using an implantable telemetric sensor (G2 E-Mitter). The animals were randomly assigned to two progressive exercise test protocols until fatigue during the beginning of light and dark-phases. Fatigue was defined as the moment rats could not keep pace with the treadmill. We assessed the time to fatigue, workload and Tb changes induced by exercise. Each test was separated by 3days. Our results showed that exercise capacity and heat storage were higher during the light-phase (plocomotor physical activity have an important inherent component (r=0.864 and r=0.784, respectively, plocomotor activity are not directly associated, both are strongly influenced by daily cycles of light and dark. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 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.

  17. Factors impacting the illness trajectory of post-infectious fatigue syndrome: a qualitative study of adults' experiences.

    Science.gov (United States)

    Stormorken, Eva; Jason, Leonard A; Kirkevold, Marit

    2017-12-13

    Post-infectious fatigue syndrome (PIFS), also known as post-viral fatigue syndrome, is a complex condition resulting in physical, cognitive, emotional, neurological, vocational and/or role performance disabilities in varying degrees that changes over time. The needs for health care resources are high, and costly, as is the economic burden on the affected individuals. Many factors may impact the trajectory, and frequently PIFS develops into a chronic condition. Health professionals lack understanding and knowledge, which results in delayed diagnosis, lack of recognition, appropriate treatment, support and practical help. The aim of our study was to explore, from the perspective of persons who had lived with PIFS for four years following an outbreak of Giardia l. induced enteritis, factors that may have impacted their illness trajectory and how these factors had played a role during different phases. In this retrospective exploratory qualitative study a group of 26 affected adults between 26 and 59 years old were selected for in-depth interviews. A maximum variation sample was recruited from a physician-diagnosed cohort of persons with PIFS enrolled at a tertiary outpatient fatigue clinic. The interviews were audio-recorded, transcribed verbatim and subjected to qualitative content analysis. Unhelpful and helpful factors were associated with the healthcare system, health professionals and the affected persons were experienced as having an impact on the trajectory. External impacting factors which are related to the health care system, providers and the social security system are misdiagnosis, trivialization of symptoms, unhelpful advice, delayed diagnosis and lack of appropriate help. Internal impacting factors related to the affected individuals were lack of knowledge, overestimating functional capacity, assuming the condition will pass, ignoring body signals and denial. A model of impacting factors in each phase of the trajectory is presented. Unmet needs may

  18. 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.

  19. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Xu

    2010-08-01

    Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

  20. 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)

  1. 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

  2. Physical activity and physical activity cognitions are potential factors maintaining fatigue in patients with primary Sjogren's syndrome

    NARCIS (Netherlands)

    Wouters, Eveline J. M.; van Leeuwen, Ninke; Bossema, Ercolie R.; Kruize, Aike A.; Bootsma, Hendrika; Bijlsma, Johannes W. J.; Geenen, Rinie

    Background Fatigue is a prevalent and debilitating problem in Sjogren's syndrome. It has been suggested that physical activity and cognitions about physical activity can influence fatigue. Objective The aim of this study was to examine fatigue and physical activity levels in patients with Sjogren's

  3. Physical activity and physical activity cognitions are potential factors maintaining fatigue in patients with primary Sjögren's syndrome

    NARCIS (Netherlands)

    Van Leeuwen; Bossema; Kruize; Geenen; Bijlsma; Bootsma; MD E.J.M. Wouters

    2012-01-01

    Background Fatigue is a prevalent and debilitating problem in Sjögren's syndrome. It has been suggested that physical activity and cognitions about physical activity can influence fatigue. Objective The aim of this study was to examine fatigue and physical activity levels in patients with Sjögren's

  4. 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

  5. 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.

  6. 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.)

  7. 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

  8. 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 ...

  9. 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.)

  10. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    LENUS (Irish Health Repository)

    Minnock, Patricia

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood\\/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0-33); 6.9 ± 8.9 (0-33)), more recent and current pain intensity (41.4 ± 26.6 (0-80) 24.4 ± 26.6 (0-100) and depression (11.8 ± 7.5 (1-35); 8.2 ± 6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Pain in People with Multiple Sclerosis: Associations with Modifiable Lifestyle Factors, Fatigue, Depression, Anxiety, and Mental Health Quality of Life

    Directory of Open Access Journals (Sweden)

    Claudia H. Marck

    2017-09-01

    Full Text Available BackgroundPeople with multiple sclerosis (MS often experience pain, which can interfere with mobility, employment, and quality of life (QOL.MethodsThis cross-sectional study explored associations between pain, demographic, disease, and modifiable lifestyle factors in an international sample of people with MS recruited online.ResultsSubstantial pain, of moderate/severe intensity and interfering at least moderately with work/household or enjoyment of life in the past 4 weeks, was reported by 682/2,362 (28.9%. Substantial pain was associated with fatigue (odds ratio (OR: 6.7, 95% confidence interval (CI: 4.9,9.3, depression (OR:4.0, 95% CI:3.2,5.1, anxiety (OR:2.4, 95% CI:1.9,2.9, and lower mental health QOL (Mean Difference: −14.7, 95% CI:−16.6,−12.8. Regression analyses showed that smoking (OR: 2.0, 95% CI:1.35,2.87 and obesity (OR:2.1, 95% CI: 1.5,2.8, moderate alcohol use (OR: 0.7, 95% CI:0.5,0.9, moderate (OR 0.7, 95% CI: 0.55,0.98 or high (OR 0.6, 95% CI: 0.4,0.8 physical activity level, and healthy diet (OR 0.8, 95% CI: 0.75,0.95, per 10 points were associated with substantial pain.ConclusionOur results show clear associations with modifiable lifestyle factors and substantial pain in MS. These factors are already considered in the prevention and management of pain in other populations but have not previously been considered in MS. Conversely, pain and associated common MS comorbidities, such as depression, anxiety, and fatigue, may hamper efforts to start or maintain healthy behaviors. Strategies to overcome these barriers need to be considered. Further research should clarify the direction of these associations.

  17. 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

  18. Fatigue Reliability of Offshore Wind Turbine Systems

    DEFF Research Database (Denmark)

    Marquez-Dominguez, Sergio; Sørensen, John Dalsgaard

    2012-01-01

    of appropriate partial safety factors / fatigue design factors (FDF) for steel substructures of offshore wind turbines (OWTs). The fatigue life is modeled by the SN approach. Design and limit state equations are established based on the accumulated fatigue damage. The acceptable reliability level for optimal...... fatigue design of OWTs is discussed and results for reliability assessment of typical fatigue critical design of offshore steel support structures are presented....

  19. 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.

  20. 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.

  1. Adrenal Fatigue

    Science.gov (United States)

    ... Search Featured Resource New Mobile App DOWNLOAD Adrenal Fatigue October 2017 Download PDFs English Editors Irina Bancos, MD Additional Resources Mayo Clinic What is adrenal fatigue? The term “adrenal fatigue” has been used to ...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Survival Analysis of Factors Influencing Cyclic Fatigue of Nickel-Titanium Endodontic Instruments

    Directory of Open Access Journals (Sweden)

    Eva Fišerová

    2015-01-01

    Full Text Available Objective. The aim of this study was to validate a survival analysis assessing the effect of type of rotary system, canal curvature, and instrument size on cyclic resistance. Materials and Methods. Cyclic fatigue testing was carried out in stainless steel artificial canals with radii of curvature of 3 or 5 mm and the angle of curvature of 60 degrees. All the instruments were new and 25 mm in working length, and ISO colour coding indicated the instrument size (yellow for size 20; red for size 25. Wizard Navigator instruments, Mtwo instruments, ProTaper instruments, and Revo-S instruments were passively rotated at 250 rotations per minute, and the time fracture was being recorded. Subsequently, fractographic analysis of broken tips was performed by scanning electron microscope. The data were then analysed by the Kaplan-Meier estimator of the survival function, the Cox proportional hazards model, the Wald test for regression covariates, and the Wald test for significance of regression model. Conclusion. The lifespan registered for the tested instruments was Mtwo > Wizard Navigator > Revo-S > ProTaper; 5 mm radius > 3 mm radius; and yellow > red in ISO colour coding system.

  9. Chronobiological factors for compassion satisfaction and fatigue among ambulatory oncology caregivers.

    Science.gov (United States)

    Bellicoso, Daniela; Trudeau, Maureen; Fitch, Margaret I; Ralph, Martin R

    2017-01-01

    Primary caregivers for victims of chronic illness and or trauma experience both positive and negative emotional consequences. These are broadly classified as compassion satisfaction (CS) and compassion fatigue (CF). Because one of the components of CF, burnout, varies with chronotype and sleep quality, we assessed the influence of chronobiological features on the broader constructs of CS and CF. Responses from primary ambulatory care oncology staff working dayshifts were assessed for potential relationships of chronotype and sleep quality with CS and CF using the professional quality of life scale. These were analyzed further in a multivariate model that included personality and job satisfaction as cofactors. We found that sleep quality was a key contributor to CS development and CF reduction. Morningness was positively linked to CS, but the univariate association was masked in the multivariate model. Job satisfaction (contingent rewards, nature of work and operating procedures) heavily influenced CS and CF development. Agreeableness and openness showed positive correlations with CS and negative with burnout, while emotional stability was linked to reduced CF. While job satisfaction and personality predictably played roles in the development of CS and CF, sleep quality and chronotype contributed significantly to benefits and negative consequences of providing care.

  10. The effect of aroma stimulation during isotonic exercise on the rating of perceived exertion and blood fatigue factors of athletes with patellofemoral pain syndrome.

    Science.gov (United States)

    Kim, Sangsoo; Choo, JongHoo; Ju, Sungbum

    2018-02-01

    [Purpose] The purpose of this study is to examine the effect of aroma stimulation during isotonic exercise on the rating of perceived exertion (RPE) and the blood fatigue factors of athletes who have patellofemoral pain syndrome (PFPS). [Subjects and Methods] The research subjects were seven athletes in their twenties who suffer from PFPS. They were divided into a control group and an aroma stimulation group and performed isotonic exercises repeatedly. After exercising, the RPE and blood fatigue factors, including creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and ammonia, were measured through blood sampling. [Results] The aroma stimulus group showed significantly lower RPE than the control group immediately after exercising, which included leg presses, leg curls, bicep curls, and leg extensions. Among the blood fatigue factors, the change in LDH indicated the effect of aroma stimulation. [Conclusion] We confirmed that aroma stimulation during isotonic exercise has the positive effect of reducing the RPE and blood fatigue factors, such as blood LDH, of the athletes with PFPS.

  11. 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...

  12. Suppression of p53 by Notch3 is mediated by Cyclin G1 and sustained by MDM2 and miR-221 axis in hepatocellular carcinoma

    Science.gov (United States)

    Baglioni, Michele; Fornari, Francesca; Giannone, Ferdinando; Ravaioli, Matteo; Cescon, Matteo; Chieco, Pasquale; Bolondi, Luigi; Gramantieri, Laura

    2014-01-01

    To successfully target Notch receptors as part of a multidrug anticancer strategy, it will be essential to fully characterize the factors that are modulated by Notch signaling. We recently reported that Notch3 silencing in HCC results in p53 up-regulation in vitro and, therefore, we focused on the mechanisms that associate Notch3 to p53 protein expression. We explored the regulation of p53 by Notch3 signalling in three HCC cell lines HepG2, SNU398 and Hep3B.We found that Notch3 regulates p53 at post-transcriptional level controlling both Cyclin G1 expression and the feed-forward circuit involving p53, miR-221 and MDM2. Moreover, our results were validated in human HCCs and in a rat model of HCC treated with Notch3 siRNAs. Our findings are becoming an exciting area for further in-depth research toward targeted inactivation of Notch3 receptor as a novel therapeutic approach for increasing the drug-sensitivity, and thereby improving the treatment outcome of patients affected by HCC. Indeed, we proved that Notch3 silencing strongly increases the effects of Nutilin-3. With regard to therapeutic implications, Notch3-specific drugs could represent a valuable strategy to limit Notch signaling in the context of hepatocellular carcinoma over-expressing this receptor. PMID:25431954

  13. 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.

  14. 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.

  15. Muscle Deoxygenation Causes Muscle Fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  16. Fatigue Crack Growth Rate and Stress-Intensity Factor Corrections for Out-of-Plane Crack Growth

    Science.gov (United States)

    Forth, Scott C.; Herman, Dave J.; James, Mark A.

    2003-01-01

    Fatigue crack growth rate testing is performed by automated data collection systems that assume straight crack growth in the plane of symmetry and use standard polynomial solutions to compute crack length and stress-intensity factors from compliance or potential drop measurements. Visual measurements used to correct the collected data typically include only the horizontal crack length, which for cracks that propagate out-of-plane, under-estimates the crack growth rates and over-estimates the stress-intensity factors. The authors have devised an approach for correcting both the crack growth rates and stress-intensity factors based on two-dimensional mixed mode-I/II finite element analysis (FEA). The approach is used to correct out-of-plane data for 7050-T7451 and 2025-T6 aluminum alloys. Results indicate the correction process works well for high DeltaK levels but fails to capture the mixed-mode effects at DeltaK levels approaching threshold (da/dN approximately 10(exp -10) meter/cycle).

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Work stress, fatigue and risk behaviors at the wheel: Data to assess the association between psychosocial work factors and risky driving on Bus Rapid Transit drivers

    Directory of Open Access Journals (Sweden)

    Sergio Useche

    2017-12-01

    Full Text Available This Data in Brief (DiB article presents a hierarchical multiple linear regression model that examine the associations between psychosocial work factors and risk behaviors at the wheel in Bus Rapid Transit (BRT drivers (n=524. The data were collected using a structured self-administrable questionnaire made of measurements of wok stress (job strain and effort- reward imbalance, fatigue (need for recovery and chronic fatigue, psychological distress and demographics (professional driving experience, hours driven per day and days working per week. The data contains 4 parts: descriptive statistics, bivariate correlations between the study variables and a regression model predicting risk behaviors at the wheel and the entire study dataset. For further information, it is convenient to read the full article entitled “Stress-related Psychosocial Factors at Work, Fatigue, and Risky Driving Behavior in Bus Rapid Transport (BRT Drivers”, published in Accident Analysis & Prevention. Keywords: Professional drivers, Work stress, Fatigue, Psychological distress, Risk behaviors, Bus Rapid Transport, BRT

  4. 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

  5. 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

  6. Patient and surgery related factors associated with fatigue type polyethylene wear on 49 PCA and DURACON retrievals at autopsy and revision

    Directory of Open Access Journals (Sweden)

    Ochsner Peter E

    2008-02-01

    Full Text Available Abstract Background Polyethylene wear is an important factor for longevity of total knee arthroplasty. Proven and suspicious factors causing wear can be grouped as material, patient and surgery related. There are more studies correlating design and/or biomaterial factors to in vivo wear than those to patient and surgery related factors. Many retrieval studies just include revision implants and therefore may not be representative. This study is aimed to correlate patient- and surgery- related factors to visual wear score by minimizing design influence and include both autopsy and revision implants. Comparison between the groups was expected to unmask patient and surgery-related factors responsible for wear. Methods The amount of joint side wear on polyethylene retrievals was measured using a modification of an established visual wear score. Fatigue type wear was defined as summation of the most severe wear modes of delamination, pitting and cracks. Analysis of patient and surgery related variables suspicious to cause wear included prospectively sampled patient activity which was measured by self reported walking capacity. Statistical analysis was done by univariate analysis of variance. Activity level and implantation time were merged to an index of use and correlated to the wear score. Results Wear score after comparable implantation time was significantly less in the autopsy group. Even so, fatigue type wear accounted for 84 and 93 % of total wear score on autopsy and revision implants respectively. A highly significant influence on wear score was found in time of implantation (p = 0.002, level of activity (p = 0.025 and inserts belonging to revision group (p = 0.006. No influence was found for the kind of patella replacement (p = 0.483. Body mass index and accuracy of component alignment had no significant influence on visual wear score. Fatigue-type wear in the medial compartment was closely correlated to the index of use in the autopsy (R2

  7. 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.

  8. 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

  9. 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

  10. Main factors for fatigue failure probability of pipes subjected to fluid thermal fluctuation

    International Nuclear Information System (INIS)

    Machida, Hideo; Suzuki, Masaaki; Kasahara, Naoto

    2015-01-01

    It is very important to grasp failure probability and failure mode appropriately to carry out risk reduction measures of nuclear power plants. To clarify the important factors for failure probability and failure mode of pipes subjected to fluid thermal fluctuation, failure probability analyses were performed by changing the values of a stress range, stress ratio, stress components and threshold of stress intensity factor range. The important factors for the failure probability are range, stress ratio (mean stress condition) and threshold of stress intensity factor range. The important factor for the failure mode is a circumferential angle range of fluid thermal fluctuation. When a large fluid thermal fluctuation acts on the entire circumferential surface of the pipe, the probability of pipe breakage increases, calling for measures to prevent such a failure and reduce the risk to the plant. When the circumferential angle subjected to fluid thermal fluctuation is small, the failure mode of piping is leakage and the corrective maintenance might be applicable from the viewpoint of risk to the plant. (author)

  11. 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

  12. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  13. 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

  14. Satisfaction with life in adults with Marfan syndrome (MFS): associations with health-related consequences of MFS, pain, fatigue, and demographic factors.

    Science.gov (United States)

    Velvin, Gry; Bathen, Trine; Rand-Hendriksen, Svend; Geirdal, Amy Østertun

    2016-07-01

    The objective with this study was to explore satisfaction with life (SWL) among adults with Marfan syndrome (MFS) compared to the general Norwegian population and other patient groups and further to examine the associations between SWL and demographic factors, contact with social and health services, MFS-related health problems, chronic pain, and fatigue. This is a cross-sectional study with postal questionnaire, including the Satisfaction with Life Scale (SWLS), questions on demographic factors, health-related aspects of MFS, and validated instruments measuring chronic pain (Standardized Nordic Questionnaire) and fatigue (Fatigue Severity Scale). One hundred and seventeen adults with MFS were invited to participate, and 73 (62 %) participated. The SWLS mean score in adults with MFS was significantly lower than that reported for the general Norwegian population, but similar to or higher than that reported for other patient groups. Only fatigue, aortic dissection, and having regular contact with psychologist showed significant unique contribution to the SWLS score in the hierarchical multiple linear analyses. The total variance explained by the model was 45.2 % p ≤ 0.000, confirming that the combination of independent variables significantly predicted SWLS. The results reflect that MFS influences people's SWL and that particularly severe fatigue, aortic dissection, and psychological aspects are associated with lower SWL. This is important to take into account in the clinical work with people with MFS. Further investigation is needed, especially on larger sample groups. Studies with combination of qualitative and quantitative approaches are recommended to obtain more comprehensive and accurate knowledge about the consequences of MFS on satisfaction with life.

  15. Notch and VEGF Interactions in Breast Cancer

    National Research Council Canada - National Science Library

    Shawber, Carrie J

    2006-01-01

    The proposal objective is to define Notch and VEGFR-3 in breast cancer. We investigated this relationship in primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts...

  16. Notch signaling in embryology and cancer

    National Research Council Canada - National Science Library

    Reichrath, J; Reichrath, Sandra

    2012-01-01

    "The goal of this volume is to comprehensively cover a highly readable overview on our present knowledge of the role of Notch signalling for embryology and cancer, with a focus on new findings in molecular biology...

  17. 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

  18. Aeromedical Factors in Aviator Fatigue, Crew Work/Rest Schedules and Extended Flight Operations: An Annotated Bibliography.

    Science.gov (United States)

    1981-01-01

    medicina aeronatica). Revisti de Aoronautica y Astronautica. 37:109-118. (In Spanish.) English translation NASA TM-75165, October 1977. Literature on...treatment of flight fatigue. Rxi.t,, 9. Medicina Aeronautica E Spaziale. 32:231-268. (In Italian.) The author frames nosologically flight fatigue syndrome... China Lake, CA 93555 (1) Warminster, PA 18974 (1) US Navy US Navy Naval Aerospace Medical Institute Naval Research Laboratory Library Library Shock

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Influence of overelastic loading on the stress intensity factor under thermal fatigue conditions

    International Nuclear Information System (INIS)

    Stamm, H.; Munz, D.

    1983-10-01

    Thermal shock loading often creates high thermal stresses which may exceed yield strength of the material in a surface layer. In this report the application of the linear elastic ΔK-concept in the case of cyclic thermal loading within the shakedown region is discussed. To this K-factors for an edge crack in a linear elastic - perfectly plastic plate are calculated using the weight function method and are compared with results obtained with the Finite Element Method. It is shown, that rearrangement stresses during plastic flow in the first cycle must be taken into account developing conservative approximation procedures. (orig.) [de

  4. 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.

  5. Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Mirjana Lapčević

    Full Text Available Abstract Introduction: Fatigue, anxiety and depression are very frequent symptoms in patients with rheumatoid arthritis (RA. Goals: In this study we evaluated the influence of socioeconomic characteristics, therapy and comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA. Method: Multicenter cross-sectional study was performed in 22 health institutions in Serbia during the period from April-August 2014 in population of older RA patients. Self-reported patients health status was measured by: Fatigue Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined as: (1 non-steroidal anti-inflammatory drugs (NSAIDs and/or analgesics and/or corticosteroids; (2 synthetic disease-modifying antirheumatic drugs (DMARDs alone or in combination with corticosteroids and/or NSAIDs and (3 any RA treatment which includes biologic DMARDs. Results: There were significant predictors of high depression: synthetic DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent taxi use, alternative treatment and employment status. The need for another person's assistance, supplemental calcium therapy and professional qualifications were the predictors of a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection with proton-pump inhibitors and patient occupation. Conclusion Socioeconomic predictors of self-reported high depression, anxiety or fatigue are different for each of the mentioned outcomes, while accompanied with the basic RA treatment they exclusively explain a high depression. The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients.

  6. 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

  7. Trastuzumab Resistance: Role for Notch Signaling

    Directory of Open Access Journals (Sweden)

    Kinnari Mehta

    2009-01-01

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

  8. The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial.

    Science.gov (United States)

    Prinsen, Hetty; van Dijk, Johannes P; Zwarts, Machiel J; Leer, Jan Willem H; Bleijenberg, Gijs; van Laarhoven, Hanneke W M

    2015-02-01

    Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue. The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial. Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle. Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group. Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  9. Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

    Science.gov (United States)

    Sprauten, M; Haugnes, H S; Brydøy, M; Kiserud, C; Tandstad, T; Bjøro, T; Bjerner, J; Cvancarova, M; Fosså, S D; Oldenburg, J

    2015-10-01

    Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. 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.

  11. 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.

  12. 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.

  13. Fatigue analysis of aluminum drill pipes

    Directory of Open Access Journals (Sweden)

    João Carlos Ribeiro Plácido

    2005-12-01

    Full Text Available An experimental program was performed to investigate the fundamental fatigue mechanisms of aluminum drill pipes. Initially, the fatigue properties were determined through small-scale tests performed in an optic-mechanical fatigue apparatus. Additionally, full-scale fatigue tests were carried out with three aluminum drill pipe specimens under combined loading of cyclic bending and constant axial tension. Finally, a finite element model was developed to simulate the stress field along the aluminum drill pipe during the fatigue tests and to estimate the stress concentration factors inside the tool joints. By this way, it was possible to estimate the stress values in regions not monitored during the fatigue tests.

  14. 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.

  15. 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.

  16. Stress-related psychosocial factors at work, fatigue, and risky driving behavior in bus rapid transport (BRT) drivers.

    Science.gov (United States)

    Useche, Sergio A; Ortiz, Viviola Gómez; Cendales, Boris E

    2017-07-01

    There is consistent scientific evidence that professional drivers constitute an occupational group that is highly exposed to work related stressors. Furthermore, several recent studies associate work stress and fatigue with unsafe and counterproductive work behaviors. This study examines the association between stress-related work conditions of Bus Rapid Transport (BRT) drivers and risky driving behaviors; and examines whether fatigue is a mechanism that mediates the association between the two. A sample of 524 male Bus Rapid Transit (BRT) operators were drawn from four transport companies in Bogotá, Colombia. The participants answered a survey which included an adapted version of the Driver Behavior Questionnaire (DBQ) for BRT operators, as well as the Effort-Reward Imbalance and Job Content Questionnaires, the Subjective Fatigue subscale of the Checklist Individual Strength (CIS) and the Need for Recovery after Work Scale (NFR). Utilizing Structural Equation Models (SEM) it was found that risky driving behaviors in BRT operators could be predicted through job strain, effort-reward imbalance and social support at work. It was also found that fatigue and need for recovery fully mediate the associations between job strain and risky driving, and between social support and risky driving, but not the association between effort/reward imbalance (ERI) and risky driving. The results of this study suggest that a) stress related working conditions (Job Strain, Social Support and ERI) are relevant predictors of risky driving in BRT operators, and b) that fatigue is the mechanism which links another kind of stress related to working conditions (job strain and low social support) with risky driving. The mechanism by which ERI increases risky driving in BRT operators remains unexplained. This research suggests that in addition to the individual centered stress-reduction occupational programs, fatigue management interventions aimed to changing some working conditions may reduce

  17. 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)

  18. 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.

  19. Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy.

    Science.gov (United States)

    Jiao, Jiao; Tian, Weihua; Qiu, Ping; Norton, Elizabeth L; Wang, Michael M; Chen, Y Eugene; Yang, Bo

    2018-03-12

    The NOTCH1 gene mutation has been identified in bicuspid aortic valve patients. We developed an in vitro model with human induced pluripotent stem cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial cell (EC) differentiation. The iPSCs were derived from a patient with a normal tricuspid aortic valve and aorta. The NOTCH1 gene was targeted in iPSCs with the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 nuclease (Cas9) system. The NOTCH1 -/- (NOTCH1 homozygous knockout) and isogenic control iPSCs (wild type) were differentiated into neural crest stem cells (NCSCs) and into cardiovascular progenitor cells (CVPCs). The NCSCs were differentiated into smooth muscle cells (SMCs). The CVPCs were differentiated into ECs. The differentiations of SMCs and ECs were compared between NOTCH1 -/- and wild type cells. The expression of NCSC markers (SRY-related HMG-box 10 and transcription factor AP-2 alpha) was significantly lower in NOTCH1 -/- NCSCs than in wild type NCSCs. The SMCs derived from NOTCH1 -/- NCSCs showed immature morphology with smaller size and decreased expression of all SMC-specific contractile proteins. In NOTCH1 -/- CVPCs, the expression of ISL1, NKX2.5, and MYOCD was significantly lower than that in isogenic control CVPCs, indicating impaired differentiation from iPSCs to CVPCs. The NOTCH1 -/- ECs derived from CVPCs showed significantly lower expression of cluster of differentiation 105 and cluster of differentiation 31 mRNA and protein, indicating a defective differentiation process. NOTCH1 is critical in SMC and EC differentiation of iPSCs through NCSCs and CVPCs, respectively. NOTCH1 gene mutations might potentially contribute to the development of thoracic aortic aneurysms by affecting SMC differentiation in some patients with bicuspid aortic valve. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  20. Fatigue (PDQ)

    Science.gov (United States)

    ... Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Problems getting enough sleep. Being less active. Other medical conditions. Fatigue is common in people with advanced ...

  1. The putative Notch ligand HyJagged is a transmembrane protein present in all cell types of adult Hydra and upregulated at the boundary between bud and parent

    Directory of Open Access Journals (Sweden)

    Tischer Susanne

    2011-09-01

    Full Text Available Abstract Background The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet. Results We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures. Conclusions The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.

  2. 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.

  3. Is impact of fatigue an independent factor associated with physical activity in patients with idiopathic Parkinson's disease?

    NARCIS (Netherlands)

    Elbers, R.; Wegen, van E.E.H.; Rochester, L.; Hetherington, V.; Nieuwboer, A.; Willems, A.M.; Jones, D.; Kwakkel, G.

    2009-01-01

    To investigate the longitudinal association between fatigue and physical activity in Parkinson's disease (PD) and determine whether this association is distorted by potential confounders. Data from baseline, 3, 6, and 12 week assessments in a single blind randomized clinical trial with cross-over

  4. Fatigue in U.S. Astronauts Onboard the International Space Station: Environmental factors, Operational Impacts, and Implementation of Countermeasures

    Science.gov (United States)

    Scheuring, R. A.; Moomaw, R. C.; Johnston, S. L.

    2015-01-01

    Crewmembers have experienced fatigue for reasons similar to military deployments. Astronauts experience psychological stressors such as: heavy workloads, extended duty periods, circadian misalignment, inadequate/ineffective sleep, distracting background noise, unexpected and variable mission schedules, unfavorable thermal control, unusual sleep environment with schedules that impinge on pre-sleep periods.

  5. Compact microstrip bandpass filter with tunable notch

    DEFF Research Database (Denmark)

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

    2014-01-01

    Two different designs combining a bandpass and a notch filter are developed to operate in the receiving band from 350–470 MHz. The bandpass filter is designed from a simple structure, by use of only four short circuited stubs and a half wavelength transmission line connecting the stubs. The tunable...... notch filter ensures an attenuation level of 19.3 dB to 27.3 dB in the frequency range from 360–480 MHz. The measured passband ripple of the combined filter is less than 0.5 dB, while the insertion loss for the simplest design is less than 1.7 dB only 10 MHz from the notch frequency. Even though...... the wavelength on the selected substrate (εr = 3.55) is approximately 45 cm, the outer dimensions of the final filter only measure 10×10 cm2....

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. 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.

  12. Fatigue, insomnia and nervousness: gender disparities and roles of individual characteristics and lifestyle factors among economically active people.

    Science.gov (United States)

    Peretti-Watel, Patrick; Legleye, Stéphane; Baumann, Michèle; Choquet, Marie; Falissard, Bruno; Chau, Nearkasen

    2009-09-01

    Individuals with certain personal, family and job characteristics are at elevated risk of poor mental health. Yet, the respective role of obesity, smoking, alcohol abuse, low education, income, living and family conditions, and socio-occupational category in fatigue/insomnia (FI), nervousness (N) and frequent drug use for those disorders (DFI and DN) among men and women and in gender disparities are not well known. We studied gender differences in FI, N, DFI, DN, and in their correlated, and whether the gender differences were mediated by individual and lifestyle factors among 3,450 active subjects aged 18-64, randomly selected from North-eastern France. Subjects completed a post-mailed questionnaire. Data were analyzed via adjusted odds ratio (ORa) computed with the logistic regression model. Women were more affected than men for FI (21.3 vs. 13.1%, OR adjusted for age ORa 1.80, 95% CI 1.50-2.16), DFI (11.6 vs. 7.1%, ORa 1.74, 1.38-2.21), N (14.7 vs. 9.9%, ORa 1.58, 1.28-1.94), and for DN (12.1 vs. 5.7%, ORa 2.29, 1.79-2.94). These differences were not mediated by the individual characteristics studied. Multivariate analysis showed that the risk patterns varied between the two sexes. Smoking was related to N in men as well as in women; alcohol abuse to DFI in men only; lack of family support to all outcome variables in men and women; low educational level to DFI in men only; low income to FI, N and DN in men and to FI and DN in women; being unmarried to DN in men; being divorced/separated to N and DN in women; being a manual worker to FI and being a farmer to DFI in men; and being a manual worker to DN and being an employee to FI in women (1.50 roles among men and women but they did not explain the gender disparities.

  13. 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

  14. 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

  15. 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)

  16. Lipid Replacement Therapy Functional Food Formulation with NT Factor for Reducing Weight, Girth, Body Mass, Appetite and Fatigue While Improving Blood Lipid Profiles

    Directory of Open Access Journals (Sweden)

    Rita R. Ellithorpe

    2012-01-01

    Full Text Available Background: Lipid Replacement Therapy using NT Factor® plus kidney bean alpha-amylase inhibitor (Healthy Curb® was used in a two month weight loss clinical trial to reduce weight and improve fatigue without changing easting or exercise patterns and without use of drugs, stimulants or herbs. Objectives: To determine the effects of an all-natural functional food, NT Factor® plus alpha-amylase inhibitor (Healthy Curb®, on weight loss, body girth, body mass and index, basal metabolic rate, appetite, carvings for sweets and fatigue as well as blood lipid profiles during a 2-month open label clinical trial without food restrictions or increases in physical activity.Methods: Thirty subjects (Mean Age = 56.8 ± 1.8; 24 females and 6 males used the functional food containing NT Factor® (500 mg and alpha-amylase inhibitor (500 mg 30 min before each meal in tablet form. Participants were told to eat and exercise normally. Weight, waist and hip measurements were taken weekly. Appetite and sweet cravings were assessed weekly by standard methods. Fatigue was determined using the Piper Fatigue Scale. Blood samples were taken prior to and at the end of the trial for lipid and chemical analyses. Results: Sixty-three percent of the participants lost an average of 6.11 ± 0.28 pounds (2.77 ± 0.12 Kg (p<0.001 along with average reductions of 2.51 ± 0.05 inches (6.4 ± 0.13 cm (p<0.0001 and 1.5 ± 0.04 inches (3.8 ± 0.10 cm (p<0.0001 from waist and hip circumferences, respectively. The entire Functional Foods in Health and Disease 2012, 2(1:11-24 group lost an average of 3.63 ± 0.13 pounds (1.65 ± 0.11 Kg (p<0.001 with average reductions of 1.59 ± 0.03 inches (4.04 ± 0.06 cm (p<0.0001 and 1.13 ± 0.02 inch (2.87 ± 0.05 cm (p<0.0001 from waist and hip circumferences, respectively. Weight loss and body measurement decreases were gradual, consistent and significant, along with reductions in body mass index (BMI and basal metabolic rate (BMR measurements

  17. Effects of Supplementation with BCAA and L-glutamine on Blood Fatigue Factors and Cytokines in Juvenile Athletes Submitted to Maximal Intensity Rowing Performance.

    Science.gov (United States)

    Koo, Ga Hee; Woo, Jinhee; Kang, Sungwhun; Shin, Ki Ok

    2014-08-01

    [Purpose] This study was conducted to understand the impacts of BCAA (branched-chain amino acid) and glutamine supplementation on the degree of blood fatigue factor stimulation and cytokines along with performance of exercise at the maximal intensity. [Subjects] Five male juvenile elite rowing athletes participated in this study as the subjects; they took 3 tests and received placebo supplementation (PS), BCAA supplementation (BS), and glutamine supplementation (GS). [Methods] The exercise applied in the tests was 2,000 m of rowing at the maximal intensity using an indoor rowing machine, and blood samples were collected 3 times, while resting, at the end of exercise, and after 30 min of recovery, to analyze the blood fatigue factors (lactate, phosphorous, ammonia, creatine kinase (CK)) and blood cytokines (IL (interleukin)-6, 8, 15). [Results] The results of the analysis showed that the levels of blood phosphorous in the BS and GS groups at the recovery stage were decreased significantly compared with at the end of exercise, and the level of CK appeared lower in the GS group alone at recovery stage than at the end of exercise. The level of blood IL-15 in the PS and BS groups appeared higher at the end of exercise compared with the resting stage. [Conclusion] It seemed that glutamine supplementation had a positive effect on the decrease in fatigue factor stimulation at the recovery stage after maximal intensity exercise compared with supplementation with the placebo or BCAA. Besides, pre-exercise glutamine supplementation seemed to help enhance immune function and the defensive inflammatory reaction.

  18. 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.

  19. 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)

  20. Calibration of partial safety factors for wind turbine rotor blades against fatigue failure; Kalibrering af partielle sikkerhedsfaktorer for udmattelse af vindmoellerotorer

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, C.J.; Ronold, K.O.; Thoegersen, M.L.

    2000-08-01

    The report describes a calibration of partial safety factors for wind turbine rotor blades subjected to fatigue loading in flapwise and edgewise bending. While earlier models - developed by the authors - dealt with such calibrations for site-specific individual turbines only, the calibration model applied herein covers an integrated analysis with different turbines on different sites and with different blade materials. The result is an optimized set of partial safety factors, i.e. a set of safety factors that lead to minimum deviation from the target reliability of the achieved reliabilities over the selected scope of turbines, sites and materials. The turbines included in the study cover rated powers of 450-600 kW. The result from the calibration are discussed in relation to the partial safety factors that are given in the Danish codes for design of glass fibre reinforced rotor blades (DS472 and DS456). (au)

  1. 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.)

  2. An experimental study on the factors that affect fatigue crack growth retardation behavior in SM45C steel

    International Nuclear Information System (INIS)

    Kim, Seon Jin; Kim, Jong Hoon; Ahn, Seok Hwan

    2000-01-01

    Constant ΔK fatigue crack growth tests were performed applying an intermediate multiple overload for SM45C steel. The purpose of the present study is to investigate the effects of specimen thickness at various baseline stress intensity levels(ΔK b ), overload application position(a/W) and overload application frequency(OL Hz ) on fatigue crack growth retardation behavior. The principal results are summarized as follows. The amount of retardation for a given ΔK b level is increased with increasing the baseline stress intensity level in all specimen thickness. The normalized minimum crack growth rate is increased with increasing the specimen thickness, except for ΔK=45MPa√m. The retardation cycle is decreased with increasing the overload application position and increased with the overload application frequency

  3. 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

  4. The nature of self-regulatory fatigue and “ego depletion”: Lessons from physical fatigue

    Science.gov (United States)

    Evans, Daniel R.; Boggero, Ian A.; Segerstrom, Suzanne C.

    2016-01-01

    Self-regulation requires overriding a dominant response, and leads to temporary self-regulatory fatigue. Existing theories of the nature and causes of self-regulatory fatigue highlight physiological substrates such as glucose or psychological processes such as motivation, but these explanations are incomplete on their own. Historically, theories of physical fatigue demonstrate a similar pattern of useful but incomplete explanations, as recent views of physical fatigue emphasize the roles of both physiological and psychological factors. In addition to accounting for multiple inputs, these newer views also explain how fatigue can occur even in the presence of sufficient resources. Examining these newer theories of physical fatigue can serve as a foundation on which to build a more comprehensive understanding of self-regulatory fatigue that integrates possible neurobiological underpinnings of physical and self-regulatory fatigue, and suggests the possible function of self-regulatory fatigue. PMID:26228914

  5. The Nature of Self-Regulatory Fatigue and "Ego Depletion": Lessons From Physical Fatigue.

    Science.gov (United States)

    Evans, Daniel R; Boggero, Ian A; Segerstrom, Suzanne C

    2015-07-30

    Self-regulation requires overriding a dominant response and leads to temporary self-regulatory fatigue. Existing theories of the nature and causes of self-regulatory fatigue highlight physiological substrates such as glucose, or psychological processes such as motivation, but these explanations are incomplete on their own. Historically, theories of physical fatigue demonstrate a similar pattern of useful but incomplete explanations, as recent views of physical fatigue emphasize the roles of both physiological and psychological factors. In addition to accounting for multiple inputs, these newer views also explain how fatigue can occur even in the presence of sufficient resources. Examining these newer theories of physical fatigue can serve as a foundation on which to build a more comprehensive understanding of self-regulatory fatigue that integrates possible neurobiological underpinnings of physical and self-regulatory fatigue, and suggests the possible function of self-regulatory fatigue. © 2015 by the Society for Personality and Social Psychology, Inc.

  6. 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

  7. [Epidemiology of fatigue in general practice].

    Science.gov (United States)

    Fuhrer, R

    1994-11-01

    The epidemiology of fatigue is not well known in France, and this study reports on factors associated with fatigue in a sample of 3,784 general practice patients. Prevalence rates according to several definitions of fatigue are presented and factors are examined that have been reported to be associated with fatigue. Although 41.2% of the sample report having experienced symptoms of fatigue for at least three days, only 7.6% declare fatigue as a reason for consulting a doctor. Women report more symptoms of fatigue, but they do not consult more often than men for this reason. Age is strongly correlated with fatigue, but this is found only for men. Socioprofessional category bears no relationship to fatigue as a reason for consultation, however, the diagnosis of fatigue is more often attributed to professionals and upper management than it is to office staff or skilled and unskilled workers. We do find a strong relationship between depressive symptomatology as measured by the Center for Epidemiologic Studies (CES-D) and fatigue; nonetheless, fatigue is neither sensitive nor specific to the diagnosis of depression.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Calibration of partial safety factors for wind turbine rotor blades against fatigue; Kalibrering af partielle sikkerhedsfaktorer for udmattelse af vindmoellerotorer. Bilagsrapport

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, C.J.; Ronold, K.O.; Thoegersen, M.L.

    2000-08-01

    The report describes a calibration of partial safety factors for wind turbine rotor blades subjected to fatigue loading in flapwise and edgewise bending. While earlier models - developed by the authors - dealt with such calibrations for site-specific individual turbines only, the calibration model applied herein covers an integrated analysis with different turbines on different sites and with different blade materials. The result is an optimized set of partial safety factors, i.e. a set of safety factors that lead to minimum deviation from the target reliability of the achieved reliabilities over the selected scope of turbines, sites and materials. The turbines included in the study cover rated powers of 450-600 kW. (au)

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  1. 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).

  2. Role of Notch-1 signaling in ethanol induced PC12 apoptosis | Li ...

    African Journals Online (AJOL)

    Chronic alcoholic dementia has crucial role in progress of neurodegenerative disease and affects a large portion of our aging population. Neuronal cell apoptosis may be a contributing factor of neurodegenerative disease (ND) and Alzheimer's disease (AD). Previous researches have indicated that Notch-1 signaling ...

  3. 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.

  4. 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...

  5. The Notch ligand delta-like 3 promotes tumor growth and inhibits Notch signaling in lung cancer cells in mice

    International Nuclear Information System (INIS)

    Deng, San-Ming; Yan, Xian-Chun; Liang, Liang; Wang, Li; Liu, Yuan; Duan, Juan-Li; Yang, Zi-Yan; Chang, Tian-Fang; Ruan, Bai; Zheng, Qi-Jun; Han, Hua

    2017-01-01

    Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues. Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro, and enhanced tumor growth when inoculated in vivo in mice. The Dll3-mediated proliferation could be due to increased Akt phosphorylation in LLC cells, because an Akt inhibitor counteracted Dll3-induced proliferation. Moreover, Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling. - Highlights: • The level of Dll3 in Lewis lung carcinoma changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with TNF-α. • The Dll3 was rarely detectable in the para-carcinoma tissues, but positive in 82.1% of NSCLC tissues from 84 patients. • Overexpression of Dll3 in LLC cells promoted tumor growth but did not remarkably alter TME after inoculated in mice. • Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro in an Akt-dependent way. • Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling.

  6. 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...

  7. 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.)

  8. 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)

  9. Interactions of Notch1 and TLR4 signaling pathways in DRG neurons of in vivo and in vitro models of diabetic neuropathy.

    Science.gov (United States)

    Chen, Tianhua; Li, Hao; Yin, Yiting; Zhang, Yuanpin; Liu, Zhen; Liu, Huaxiang

    2017-11-02

    Understanding the interactions between Notch1 and toll-like receptor 4 (TLR4) signaling pathways in the development of diabetic peripheral neuropathy may lead to interpretation of the mechanisms and novel approaches for preventing diabetic neuropathic pain. In the present study, the interactions between Notch1 and TLR4 signaling pathways were investigated by using dorsal root ganglion (DRG) from diabetic neuropathic pain rats and cultured DRG neurons under high glucose challenge. The results showed that high glucose induced not only Notch1 mRNA, HES1 mRNA, and TLR4 mRNA expression, but also Notch1 intracellular domain (NICD1) and TLR4 protein expression in DRG neurons. The proportion of NICD1-immunoreactive (IR) and TLR4-IR neurons in DRG cultures was also increased after high glucose challenge. The above alterations could be partially reversed by inhibition of either Notch1 or TLR4 signaling pathway. Inhibition of either Notch1 or TLR4 signaling pathway could improve mechanical allodynia and thermal hyperalgesia thresholds. Inhibition of Notch1 or TLR4 signaling also decreased tumor necrosis factor-α (TNF-α) levels in DRG from diabetic neuropathic rats. These data imply that the interaction between Notch1 and TLR4 signaling pathways is one of the important mechanisms in the development or progression of diabetic neuropathy.

  10. 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.

  11. Thermo-elastic-plastic analysis for elastic component under high temperature fatigue crack growth rate

    Science.gov (United States)

    Ali, Mohammed Ali Nasser

    The research project presents a fundamental understanding of the fatigue crack growth mechanisms of AISI 420 martensitic stainless steel, based on the comparison analysis between the theoretical and numerical modelling, incorporating research findings under isothermal fatigue loading for solid cylindrical specimen and the theoretical modelling with the numerical simulation for tubular specimen when subjected to cyclic mechanical loading superimposed by cyclic thermal shock.The experimental part of this research programme studied the fatigue stress-life data for three types of surface conditions specimen and the isothermal stress-controlled fatigue testing at 300 °C - 600 °C temperature range. It is observed that the highest strength is obtained for the polished specimen, while the machined specimen shows lower strength, and the lowest strength is the notched specimen due to the high effect of the stress concentration. The material behaviour at room and high temperatures shows an initial hardening, followed by slow extension until fully plastic saturation then followed by crack initiation and growth eventually reaching the failure of the specimen, resulting from the dynamic strain ageing occurred from the transformation of austenitic microstructure to martensite and also, the nucleation of precipitation at grain boundaries and the incremental temperature increase the fatigue crack growth rate with stress intensity factor however, the crack growth rate at 600 °C test temperature is less than 500 °C because of the creep-fatigue taking place.The theoretical modelling presents the crack growth analysis and stress and strain intensity factor approaches analysed in two case studies based on the addition of thermo-elastic-plastic stresses to the experimental fatigue applied loading. Case study one estimates the thermal stresses superimposed sinusoidal cyclic mechanical stress results in solid cylinder under isothermal fatigue simulation. Case study two estimates the

  12. 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

  13. Design of UWB Filter with WLAN Notch

    Directory of Open Access Journals (Sweden)

    Harish Kumar

    2012-01-01

    Full Text Available UWB technology- (operating in broad frequency range of 3.1–10.6 GHz based filter with WLAN notch has shown great achievement for high-speed wireless communications. To satisfy the UWB system requirements, a band pass filter with a broad pass band width, low insertion loss, and high stop-band suppression are needed. UWB filter with wireless local area network (WLAN notch at 5.6 GHz and 3 dB fractional bandwidth of 109.5% using a microstrip structure is presented. Initially a two-transmission-pole UWB band pass filter in the frequency range 3.1–10.6 GHz is achieved by designing a parallel-coupled microstrip line with defective ground plane structure using GML 1000 substrate with specifications: dielectric constant 3.2 and thickness 0.762 mm at centre frequency 6.85 GHz. In this structure a λ/4 open-circuited stub is introduced to achieve the notch at 5.6 GHz to avoid the interference with WLAN frequency which lies in the desired UWB band. The design structure was simulated on electromagnetic circuit simulation software and fabricated by microwave integrated circuit technique. The measured VNA results show the close agreement with simulated results.

  14. Hormone levels in radiotherapy treatment related fatigue

    International Nuclear Information System (INIS)

    Biswal, B.M.; Mallik, G.S.

    2003-01-01

    Radiotherapy is known to cause debilitating treatment related fatigue. Fatigue in general is a conglomeration of psychological, physical, hematological and unknown factors influencing the internal milieu of the cancer patient. Radiotherapy can add stress at the cellular and somatic level to aggravate further fatigue in cancer patients undergoing radiotherapy. Stress related hormones might be mediating in the development of fatigue. This is an ongoing prospective study to evaluate if the hormonal profile related to stress is influenced by radiotherapy treatment related fatigue. The study was conducted from September 2002 onwards in the division of Radiotherapy and Oncology of our Medical School. Previously untreated patients with histopathology proof of malignancy requiring external beam radiotherapy were considered for this study. Selection criteria were applied to exclude other causes of fatigue. Initial fatigue score was obtained using Pipers Fatigue Score questionnaire containing 23 questions, subsequently final fatigue score was obtained at the end of radiotherapy. Blood samples were obtained to estimate the levels of ACTH, TSH, HGH, and cortisol on the final assessment. The hormone levels were compared with resultant post radiotherapy fatigue score. At the time of reporting 50 patients were evaluable for the study. The total significant fatigue score was observed among 12 (24%) patients. The individual debilitating fatigue score were behavioral severity 14 (28%), affective meaning 14(28%), Sensory 13 (26%) and cognitive mood 10 (20%) respectively. From the analysis of hormonal profile, growth hormone level > 1 ng/mL and TSH <0.03 appears to be associated with high fatigue score (though statistically not significant); whereas there was no correlation with ACTH and serum cortisol level. In our prospective study severe radiotherapy treatment related fatigue was found among our patient population. Low levels of TSH and high levels of GH appear to be associated

  15. 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.

  16. 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%

  17. 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%.

  18. Influence of Fretting on Flexural Fatigue of 304 Stainless Steel and Mild Steel

    National Research Council Canada - National Science Library

    Bill, Robert

    1978-01-01

    Fretting fatigue experiments conducted on 304 stainless steel using a flexural-fatigue test arrangement with bolted-on fretting pads have demonstrated that fatigue life is reduced by at least a factor...

  19. An overview of fatigue

    International Nuclear Information System (INIS)

    Mc Evily, A.J.

    1987-01-01

    Four topics are briefly discussed in this paper: fatigue crack initiation and growth in a nickel-base superalloy single crystal, the environment effect on near-threshold fatigue crack growth behaviour, the role of crack closure in load-interaction effects in fatigue crack growth, and the nature of creep-fatigue interactions, if any, during fatigue crack growth. (Author)

  20. Fatigue 󈨛. Volume 1,

    Science.gov (United States)

    1987-06-01

    277 FATIGUE 87 da/dn (m/ ciclo ) 10 - 07 10 - 08 10 - 0 9 R=0.5 S* • -Long Crack 10-10 e Smax = 195 MPa *Smax = 205 MPa 1Smax = 225 MPa 0.5 1 5 10 AK...MPa/m) Figure 1 Crack growth rate vs stress intensity factor range 10 . da/dn (m/ ciclo ) i0 - ° 09 i0-o -Long crack 10 . ° Smax = 10 Pa 10 Smax...120 NPa Smax = 145 NlPa 0.5 I 10 AKN~~)50 Figure 2 Crack growth rate vs stress intensity factor range 278 FATIGUE 87 da/dn (m/ ciclo ) 10- 10- 0 7 % 10

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

    Directory of Open Access Journals (Sweden)

    Hong-Mei Zhang

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

  2. 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

  3. Shift work with and without night work as a risk factor for fatigue and changes in sleep length: A cohort study with linkage to records on daily working hours.

    Science.gov (United States)

    Härmä, Mikko; Karhula, Kati; Puttonen, Sampsa; Ropponen, Annina; Koskinen, Aki; Ojajärvi, Anneli; Kivimäki, Mika

    2018-01-31

    We examined shift work with or without night work as a risk factor for fatigue and short or long sleep. In a prospective cohort study with 4- and 6-year follow-ups (the Finnish Public Sector study), we linked survey responses of 3,679 full-time hospital employees on sleep duration and fatigue to records on daily working hours in 2008 (baseline), 2012 and 2014. We used logistic regression to estimate risk ratios and their confidence intervals to examine whether continuous exposure to shift work or changes between shift work and day work were associated with short (≤6.5 hr) or long (≥9.0 hr) sleep over 24 hr and fatigue at work and during free days. Compared with continuous day work and adjusting for age, gender, education and fatigue/sleep duration at baseline, continuous shift work with night shifts was associated with increased fatigue during free days (risk ratio = 1.38, 95% confidence interval 1.17-1.63) and long sleep (risk ratio = 8.04, 95% confidence interval 2.88-22.5, without adjustment for education) after 6-year follow-up. Exposure to shift work without night shifts increased only long sleep after 6 years (risk ratio = 5.87, 95% confidence interval 1.94-17.8). A change from day work to shift work with or without night shifts was associated with an increased risk for long sleep, and a change from shift work to day work with a decreased risk for long sleep and fatigue. This study suggests that irregular shift work is a modifiable risk factor for long sleep and increased fatigue, probably reflecting a higher need for recovery. © 2018 European Sleep Research Society.

  4. 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.

  5. Role of Notch Signaling in Human Breast Cancer Pathogenesis

    Science.gov (United States)

    2006-11-01

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

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

    Science.gov (United States)

    2005-07-01

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

  7. 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 ...

  8. 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...

  9. 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

  10. 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

  11. EFFECT OF STRAIN HARDENING ON FATIGUE CRACK CLOSURE IN ALUMINUM ALLOY UNDER CONSTANT AMPLITUDE WITH SINGLE OVERLOAD

    Directory of Open Access Journals (Sweden)

    Nirpesh Vikram

    2015-12-01

    Full Text Available In this study effect of strain hardening on crack closure has been examined with the help of experiments and finite element method on the side edge notched specimen of five different Aluminum alloy (3003 Al, 5052 Al, 6061 T6, 6063 T6, 6351 in mode I under constant amplitude fatigue loading with single overload using Abaqus® 6.10 which is very well accepted FEM application in research. Extended Finite Element Method Module has been used to determine effective stress intensity factor at the crack tip while propagation takes place. FEM results have given good agreement with experimental results. Regression analysis has also been done with SPSS® 16 and dependency of strain hardening coefficient on crack closure has analyzed. A generalized empirical formula has been developed based on strain hardening to calculate effective stress intensity range ratio and a modified Paris law has also been formulated for these aluminum alloy.

  12. 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...

  13. Side Effects: Fatigue

    Science.gov (United States)

    Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

  14. 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)

  15. Probabilistic modeling of crack networks in thermal fatigue

    International Nuclear Information System (INIS)

    Malesys, N.

    2007-11-01

    Thermal superficial crack networks have been detected in mixing zone of cooling system in nuclear power plants. Numerous experimental works have already been led to characterize initiation and propagation of these cracks. The random aspect of initiation led to propose a probabilistic model for the formation and propagation of crack networks in thermal fatigue. In a first part, uniaxial mechanical test were performed on smooth and slightly notched specimens in order to characterize the initiation of multiple cracks, their arrest due to obscuration and the coalescence phenomenon by recovery of amplification stress zones. In a second time, the probabilistic model was established under two assumptions: the continuous cracks initiation on surface, described by a Poisson point process law with threshold, and the shielding phenomenon which prohibits the initiation or the propagation of a crack if this one is in the relaxation stress zone of another existing crack. The crack propagation is assumed to follow a Paris' law based on the computation of stress intensity factors at the top and the bottom of crack. The evolution of multiaxial cracks on the surface can be followed thanks to three quantities: the shielding probability, comparable to a damage variable of the structure, the initiated crack density, representing the total number of cracks per unit surface which can be compared to experimental observations, and the propagating crack density, representing the number per unit surface of active cracks in the network. The crack sizes distribution is also computed by the model allowing an easier comparison with experimental results. (author)

  16. 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)

  17. 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.

  18. 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.

  19. The Notch ligand Delta-like 1 integrates inputs from TGFbeta/Activin and Wnt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org; Tewari, Shruti, E-mail: stewari@tcmedc.org; Atamna, Wafa, E-mail: watamna@tcmedc.org; Lazarova, Darina L., E-mail: dlazarova@tcmedc.org

    2011-06-10

    Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promoter sequences containing a Smad binding element. The indirect upregulation of CTGF expression by Dll1 is likely due to the ability of Dll1icd to increase Wnt signaling, a pathway that targets CTGF. CTGF expression is induced in butyrate-treated CC cells and results from clonal growth assays support a role for CTGF in the cell growth-suppressive role of butyrate. In conclusion, integration of the Notch, Wnt, and TGFbeta/Activin signaling pathways is in part mediated by the interactions of Dll1 with Smad2/3 and Tcf4.

  20. 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.)

  1. 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.

  2. 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.

  3. [Research Progress on the Interaction Effects and Its Neural Mechanisms between Physical Fatigue and Mental Fatigue].

    Science.gov (United States)

    Zhang, Lixin; Zhang, Chuncui; He, Feng; Zhao, Xin; Qi, Hongzhi; Wan, Baikun; Ming, Dong

    2015-10-01

    Fatigue is an exhaustion state caused by prolonged physical work and mental work, which can reduce working efficiency and even cause industrial accidents. Fatigue is a complex concept involving both physiological and psychological factors. Fatigue can cause a decline of concentration and work performance and induce chronic diseases. Prolonged fatigue may endanger life safety. In most of the scenarios, physical and mental workloads co-lead operator into fatigue state. Thus, it is very important to study the interaction influence and its neural mechanisms between physical and mental fatigues. This paper introduces recent progresses on the interaction effects and discusses some research challenges and future development directions. It is believed that mutual influence between physical fatigue and mental fatigue may occur in the central nervous system. Revealing the basal ganglia function and dopamine release may be important to explore the neural mechanisms between physical fatigue and mental fatigue. Future effort is to optimize fatigue models, to evaluate parameters and to explore the neural mechanisms so as to provide scientific basis and theoretical guidance for complex task designs and fatigue monitoring.

  4. Assessing Fatigue in Late-Midlife

    DEFF Research Database (Denmark)

    Fieo, Robert A; Mortensen, Erik Lykke; Lund, Rikke

    2014-01-01

    Previous methods examining the Multiple Fatigue Inventory-20 (MFI-20) fatigue questionnaire have been limited to classical test theory, for example, factor analytic approaches. We employed modern test theory to further strengthen the construct validity of the MFI-20 fatigue in a sample of healthy...... the interpretive power of the MFI-20, allowing for the identification of the most optimal scales. Poorly performing items were more easily identified, and person ability was assessed more accurately....

  5. Fatigue lifetime estimation of railway axles

    Czech Academy of Sciences Publication Activity Database

    Náhlík, Luboš; Pokorný, Pavel; Ševčík, Martin; Fajkoš, R.; Matušek, P.; Hutař, Pavel

    2017-01-01

    Roč. 73, MAR (2017), s. 139-157 ISSN 1350-6307 R&D Projects: GA MŠk LM2015069; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : Residual fatigue lifetime * Railway axle * Variable amplitude loading * Fatigue crack propagation * Damage tolerance methodology Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis Impact factor: 1.676, year: 2016

  6. Progress Report on Alloy 617 Notched Specimen Testing

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-01

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

  7. 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.

  8. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two "fatigue" syndromes with overlapping symptoms and possibly related aetiologies.

    Science.gov (United States)

    Rovigatti, Ugo

    2012-12-01

    In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit. Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors. All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Construction Worker Fatigue Prediction Model Based on System Dynamic

    OpenAIRE

    Wahyu Adi Tri Joko; Ayu Ratnawinanda Lila

    2017-01-01

    Construction accident can be caused by internal and external factors such as worker fatigue and unsafe project environment. Tight schedule of construction project forcing construction worker to work overtime in long period. This situation leads to worker fatigue. This paper proposes a model to predict construction worker fatigue based on system dynamic (SD). System dynamic is used to represent correlation among internal and external factors and to simulate level of worker fatigue. To validate...

  10. 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)

  11. SI:FatiguePro 4 Advanced Approach for Fatigue Monitoring

    International Nuclear Information System (INIS)

    Evon, Keith; Gilman, Tim; Carney, Curt

    2012-01-01

    Many nuclear plants are making commitments to implement fatigue monitoring systems in support of license renewal. Current fatigue monitoring systems use the methodology of ASME Code Subarticle NB-3200, which is a design code intended to compute a bounding cumulative usage factor (CUF). The first generation of fatigue monitoring software utilized a simplified, single stress term assumption and classical stress cycle-counting methods that take order into account such as Rainflow or Ordered Overall Range counting. Recently, the NRC has indicated in Regulatory Issue Summary 2008-30 that any fatigue analyses in support of License Renewal should use ASME Code Section III methodologies considering all six stress components. In addition, fatigue calculations for the license renewal term are required to consider the effects of environment. The implementation of a six stress term NB-3200 fatigue calculation to a Boiling Water Reactor (BWR) feedwater nozzle, including environmental effects, is the topic of this paper. Differences in results between the advanced methodology and the simplified methodology are discussed. (author)

  12. 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

  13. 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.

  14. 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)

  15. 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).

  16. A Preliminary Review of Fatigue Among Rail Staff

    Directory of Open Access Journals (Sweden)

    Jialin Fan

    2018-05-01

    Full Text Available Background: Fatigue is a severe problem in the rail industry, which may jeopardize train crew's health and safety. Nonetheless, a preliminary review of all empirical evidence for train crew fatigue is still lacking. The aim of the present paper is, therefore, to provide a preliminary description of occupational fatigue in the rail industry. This paper reviews the literature with the research question examining the risk factors associated with train crew fatigue, covering both papers published in refereed journals and reports from trade organizations and regulators. It assesses the progress of research on railway fatigue, including research on the main risk factors for railway fatigue, the association between fatigue and railway incidents, and how to better manage fatigue in the railway industry.Methods: Systematic searches were performed in both science and industry databases. The searches considered studies published before August 2017. The main exclusion criterion was fatigue not being directly measured through subjective or objective methods.Results: A total of 31 studies were included in the main review. The causes of fatigue included long working hours, heavy workload, early morning or night shifts, and insufficient sleep. Poor working environment, particular job roles, and individual differences also contributed to fatigue.Conclusion: Fatigue in the rail industry includes most of the features of occupational fatigue, and it is also subject to industry-specific factors. The effect of fatigue on well-being and the fatigued population in the railway industry are still not clear. Future studies can consider associations between occupational risk factors and perceived fatigue by examining the prevalence of fatigue and identifying the potential risk factors in staff within the railway industry.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    African Journals Online (AJOL)

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

  19. Failure of a porous solid from a deep notch

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  20. 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.

  1. The incidence of burnout or compassion fatigue in medical dosimetrists as a function of various stress and psychologic factors

    International Nuclear Information System (INIS)

    Howard, Michelle

    2013-01-01

    ABSTRACT: Burnout and compassion fatigue (CF) adversely affect medical professionals, including those employed in radiation oncology. Previously conducted research acknowledged the presence of burnout in populations of radiation therapists, radiation oncologists, and oncology nursing staff. The aim of the following research was to measure the incidence of burnout or CF in the specific population of medical dosimetrists surveyed. As professional members of the radiation oncology team, this group had not been included in published research data to date. The hypothesis of the subsequent study stated that a comparable incidence of burnout would be observed among medical dosimetrists as had been reported by earlier researchers for a population of radiation therapists. A survey tool based on the Maslach Burnout Inventory (MBI) and distributed to full members of the American Association of Medical Dosimetrists (AAMD) was utilized as the research measurement method. Results obtained indicated an incidence rates of burnout or CF for medical dosimetrists were less than the rates previously measured for radiation therapists (53% vs 11% for emotional exhaustion [EE] and 45% vs 27% for depersonalization [DP]). The incidence of burnout was based on the Burnout Inventory (BI) developed for the research project. Each of the subscales, EE, DP, and decreased personal accomplishment (PA), was considered and analyzed independently. Although not as prevalent among medical dosimetrists as a variety of additional radiation oncology professionals, a significant portion of the population demonstrated signs of burnout or CF. Future concerns abound for the population of medical dosimetrists as a large number of members scored positive for intermediate risk of burnout and CF. Additionally, a large portion of the population was found to be rapidly approaching retirement

  2. The incidence of burnout or compassion fatigue in medical dosimetrists as a function of various stress and psychologic factors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, Michelle, E-mail: Mhoward24601@yahoo.com [University of Wisconsin—La Crosse, WI 54601 (United States)

    2013-04-01

    ABSTRACT: Burnout and compassion fatigue (CF) adversely affect medical professionals, including those employed in radiation oncology. Previously conducted research acknowledged the presence of burnout in populations of radiation therapists, radiation oncologists, and oncology nursing staff. The aim of the following research was to measure the incidence of burnout or CF in the specific population of medical dosimetrists surveyed. As professional members of the radiation oncology team, this group had not been included in published research data to date. The hypothesis of the subsequent study stated that a comparable incidence of burnout would be observed among medical dosimetrists as had been reported by earlier researchers for a population of radiation therapists. A survey tool based on the Maslach Burnout Inventory (MBI) and distributed to full members of the American Association of Medical Dosimetrists (AAMD) was utilized as the research measurement method. Results obtained indicated an incidence rates of burnout or CF for medical dosimetrists were less than the rates previously measured for radiation therapists (53% vs 11% for emotional exhaustion [EE] and 45% vs 27% for depersonalization [DP]). The incidence of burnout was based on the Burnout Inventory (BI) developed for the research project. Each of the subscales, EE, DP, and decreased personal accomplishment (PA), was considered and analyzed independently. Although not as prevalent among medical dosimetrists as a variety of additional radiation oncology professionals, a significant portion of the population demonstrated signs of burnout or CF. Future concerns abound for the population of medical dosimetrists as a large number of members scored positive for intermediate risk of burnout and CF. Additionally, a large portion of the population was found to be rapidly approaching retirement.

  3. Measurement of fatigue in industries.

    Science.gov (United States)

    Saito, K

    1999-04-01

    Fatigue of workers is a complex phenomenon resulting from various factors in technically innovated modern industries, and it appears as a feeling of exhaustion, lowering of physiological functions, breakdown of autonomic nervous balance, and decrease in work efficiency. On the other hand industrial fatigue is caused by excessive workload, remarkable alteration in working posture and diurnal and nocturnal rhythms in daily life. Working modes in modern industries have changed from work with the whole body into that with the hands, arms, legs and/or eyes which are parts of the body, and from physical work to mental work. Visual display terminal (VDT) work is one of the most characteristic jobs in the various kinds of workplaces. A large number of fatigue tests have already been adopted, but it is still hard to draw a generalized conclusion as to the method of selecting the most appropriate test battery for a given work load. As apparatus for fatigue measurement of VDT work we have developed VRT (Visual Reaction Test) and the Portable Fatigue Meter. Furthermore, we have presented immune parameters of peripheral blood and splenic T cells for physical fatigue.

  4. Scalable Notch Antenna System for Multiport Applications

    Directory of Open Access Journals (Sweden)

    Abdurrahim Toktas

    2016-01-01

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

  5. Fatigue Strength of Titanium Risers - Defect Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Babalola, Olusegun Tunde

    2001-07-01

    This study is centred on assessment of the fatigue strength of titanium fusion welds for deep-water riser's applications. Deep-water risers are subjected to significant fatigue loading. Relevant fatigue data for titanium fusion welds are very scarce. Hence there is a need for fatigue data and life prediction models for such weldments. The study has covered three topics: Fatigue testing, Fractography and defect assessment, and Fracture Mechanics modelling of fatigue crack growth. Two series of welded grade of titanium consisting of 14 specimens in each series were fatigue tested under constant amplitude loading. Prior to fatigue testing, strain gauge measurements of some specimens was conducted to enable the definition of stress range in the fatigue assessment procedure. The results were compared with finite solid element analysis and related to fatigue stresses in a riser pipe wall. Distribution and geometry of internal and surface defects both in the as-welded and in the post-weld machined conditions were assessed using fractography. This served as a tool to determine the fatigue initiation point in the welds. Fracture mechanics was applied to model fatigue strength of titanium welds with initiation from weld defects. Two different stress intensity factor formulations for embedded eccentrically placed cracks were used for analysis of elliptical cracks with the major axis parallel and close to one of the free surfaces. The methods were combined to give a satisfactory model for crack growth analysis. The model analyses crack growth of elliptical and semi-elliptical cracks in two directions, with updating of the crack geometry. Fatigue strength assessment was conducted using two crack growth models, the Paris-Erdogan relation with no threshold and the Donahue et al. relation with an implied threshold. The model was validated against experimental data, with a discussion on the choice of crack growth model. (author)

  6. 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.

  7. 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.

  8. 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

  9. Fiber Bragg grating based notch filter for bit-rate-transparent NRZ to PRZ format conversion with two-degree-of-freedom optimization

    International Nuclear Information System (INIS)

    Cao, Hui; Zuo, Jun; Xiong, Bangyun; Cheng, Jianqun; Shu, Xuewen; Shen, Fangcheng; Liu, Xin; Atai, Javid

    2015-01-01

    We propose a novel notch-filtering scheme for bit-rate transparent all-optical NRZ-to-PRZ format conversion. The scheme is based on a two-degree-of-freedom optimally designed fiber Bragg grating. It is shown that a notch filter optimized for any specific operating bit rate can be used to realize high-Q-factor format conversion over a wide bit rate range without requiring any tuning. (paper)

  10. 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...

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

    Science.gov (United States)

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

    2013-10-01

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

  12. Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity.

    Science.gov (United States)

    Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M

    2011-08-01

    Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.

  13. Main factors of thermal fatigue failure induced by thermal striping and total simulation of thermal hydraulic and structural behaviors (research report)

    International Nuclear Information System (INIS)

    Kasahara, Naoto; Muramatsu, Toshiharu

    1999-01-01

    At incomplete mixing area of high temperature and low temperature fluids near the surface of structures, temperature fluctuation of fluid gives thermal fatigue damage to wall structures. This phenomenon is called thermal striping, which becomes sometimes a critical problem in LMFR plants. Since thermal striping phenomenon is characterized by the complex thermohydraulic and thermomechanical coupled problem, conventional evaluation procedures require mock-up experiments. In order to replace them by simulation-base methods, the authors have developed numerical simulation codes and applied them to analyze a tee junction of the PHENIX secondary circuit due to thermal striping phenomenon, in the framework of the IAEA coordinated research program (CRP). Through this analysis, thermohydraulic and thermomechanical mechanism of thermal striping phenomenon was clarified, and main factors on structural integrity was extracted in each stage of thermal striping phenomenon. Furthermore, simulation base evaluation methods were proposed taking above factors of structural integrity into account. Finally, R and D problems were investigated for future development of design evaluation methods. (author)

  14. 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

  15. 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.

  16. 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).

  17. 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)

  18. Microstructure degradation in high temperature fatigue of TiAl

    Czech Academy of Sciences Publication Activity Database

    Kruml, Tomáš; Obrtlík, Karel

    2014-01-01

    Roč. 65, AUG (2014), s. 28-32 ISSN 0142-1123 R&D Projects: GA ČR(CZ) GAP107/11/0704 Institutional support: RVO:68081723 Keywords : Low cycle fatigue * lamellar TiAl alloy * high temperature fatigue * dislocations Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.275, year: 2014

  19. 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

  20. The MAPK-dependent regulation of the Jagged/Notch gene expression by VEGF, bFGF or PPAR gamma mediated angiogenesis in HUVEC

    DEFF Research Database (Denmark)

    Kiec-Wilk, B; Grzybowska-Galuszka, J; Polus, A

    2010-01-01

    The Jagged-Notch signalling, plays a crucial role in cell differentiation. Angiogenesis, is regulated by VEGF, bFGF as well as by the free fatty acid metabolites , which are regulators of transcription factors such as peroxisome proliferation activating receptors (PPARs). The study analyzed...... the signalling pathways involved in the regulation of Jagged-1/Notch-4 expression in endothelial cells (HUVECs) in response to VEGF, bFGF and PPAR-gamma exogenous activator - ciglitazone. HUVECs were incubated with investigated substances for 24 hours, with or without the presence of the MAP-kinases inhibitors...... were used. Jagged-1 and Notch-4 gene expression was determined using quantitative Real-Time PCR. The Jagged-1/Notch-4 protein expression was compared by flow cytometry, when the phosphorylation-dependent activation of kinases was estimated by Western-blot method. The opposite effect of VEGF, b...

  1. Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

    Directory of Open Access Journals (Sweden)

    Jin Wan

    2017-04-01

    Full Text Available The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Muller glia (or, Muller glial cells; MGs, which produce progenitors for retinal growth and repair. We report that Fgf8a may be an MG niche factor that acts through Notch signaling to regulate spontaneous and injury-dependent MG proliferation. Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG proliferation in young tissue but increases Notch signaling and suppresses MG proliferation in older tissue. Furthermore, cessation of Fgf8a signaling enhances MG proliferation in both young and old retinal tissue. Our study suggests that multiple MG populations contribute to retinal growth and regeneration, and it reveals a previously unappreciated role for Fgf8a and Notch signaling in regulating MG quiescence, activation, and proliferation.

  2. Mandibular Ramus Notching As a Tool for Sexual Dimorphism

    Directory of Open Access Journals (Sweden)

    Bibhuti Bhusana Panda

    2016-02-01

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

  3. 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.

  4. [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.

  5. Construction Worker Fatigue Prediction Model Based on System Dynamic

    Directory of Open Access Journals (Sweden)

    Wahyu Adi Tri Joko

    2017-01-01

    Full Text Available Construction accident can be caused by internal and external factors such as worker fatigue and unsafe project environment. Tight schedule of construction project forcing construction worker to work overtime in long period. This situation leads to worker fatigue. This paper proposes a model to predict construction worker fatigue based on system dynamic (SD. System dynamic is used to represent correlation among internal and external factors and to simulate level of worker fatigue. To validate the model, 93 construction workers whom worked in a high rise building construction projects, were used as case study. The result shows that excessive workload, working elevation and age, are the main factors lead to construction worker fatigue. Simulation result also shows that these factors can increase worker fatigue level to 21.2% times compared to normal condition. Beside predicting worker fatigue level this model can also be used as early warning system to prevent construction worker accident

  6. A Preliminary Review of Fatigue Among Rail Staff

    OpenAIRE

    Jialin Fan; Andrew P. Smith

    2018-01-01

    Background: Fatigue is a severe problem in the rail industry, which may jeopardize train crew's health and safety. Nonetheless, a preliminary review of all empirical evidence for train crew fatigue is still lacking. The aim of the present paper is, therefore, to provide a preliminary description of occupational fatigue in the rail industry. This paper reviews the literature with the research question examining the risk factors associated with train crew fatigue, covering both papers published...

  7. Population based study of fatigue and psychological distress.

    OpenAIRE

    Pawlikowska, T.; Chalder, T.; Hirsch, S. R.; Wallace, P.; Wright, D. J.; Wessely, S. C.

    1994-01-01

    OBJECTIVES--To determine the prevalence of fatigue in the general population and the factors associated with fatigue. DESIGN--Postal survey. SETTING--Six general practices in southern England. SUBJECTS--31,651 men and women aged 18-45 years registered with the practices. MAIN OUTCOME MEASURES--Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue. RESULTS--15,283 valid questionnaires...

  8. Basic Mechanisms Leading to Fatigue Failure of Structural Materials

    Czech Academy of Sciences Publication Activity Database

    Polák, Jaroslav; Petráš, Roman; Mazánová, Veronika

    2016-01-01

    Roč. 69, č. 2 (2016), s. 289-294 ISSN 0972-2815. [International Conference on CREEP , FATIGUE and CREEP -FATIGUE INTERACTION /7./. Kalpakkam, 19.01.2016-22.01.2016] R&D Projects: GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : Damage mechanism * Fatigue crack initiation * Austenitic steel * Oxide cracking Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.533, year: 2016

  9. Effects of friction and high torque on fatigue crack propagation in mode III

    International Nuclear Information System (INIS)

    Nayeb-Hashemi, H.; McClintock, F.A.; Ritchie, R.O.

    1982-01-01

    Turbo-generator and automotive shafts are often subjected to complex histories of high torques. To provide a basis for fatigue life estimation in such components, a study of fatigue crack propagation in Mode III (anti-plane shear) for a mill-annealed AISI 4140 steel (R /SUB B/ 88, 590 MN/m 2 tensile strength) has been undertaken, using torsionally-loaded, circumferentially-notched cylindrical specimens. As demonstrated previously for higher strength AISI 4340 steel, Mode III cyclic crack growth rates (dc/dN) /SUB III/ can be related to the alternating stress intensity factor ΔK /SUB III/ for conditions of small-scale yielding. However, to describe crack propagation behavior over an extended range of crack growth rates (about 10 -6 to 10 -2 mm per cycle), where crack growth proceeds under elastic-plastic and full plastic conditions, no correlation between (dc/dN) /SUB III/ and ΔK /SUB III/ is possible. Accordingly, a new parameter for torsional crack growth, termed the plastic strain intensity GAMMA /SUB III/, is introduced and is shown to provide a unique description of Mode III crack growth behavior for a wide range of testing conditions, provided a mean load reduces friction, abrasion, and interlocking between mating fracture surfaces A micro-mechanical model for the main radial Mode III growth is extended to high nominal stress levels, and predicts that Mode III fatigue crack propagation rates should be proportional to the range of plastic strain intensity (ΔGAMMA /SUB III/) if local Mode II growth rates are proportional to the displacements. Such predictions are shown to be in agreement with measured growth rates in AISI 4140 steel from 10 -6 to 10 -2 mm per cycle

  10. Research progress of exercise-induced fatigue

    Directory of Open Access Journals (Sweden)

    Peng-yi DAI

    2016-12-01

    Full Text Available Exercise-induced fatigue is a comprehensive response to a variety of physiological and biochemical changes in the body, and can affect people's quality of life to different extents. If no timely recovery after occurrence of fatigue, accumulated gradually, it can lead to "burnout", a "overtraining syndrome", "chronic fatigue syndrome", etc., which will cause endocrine disturbance, immune suppression, even physical illness. Exercise-induced fatigue becomes an important factor endangering human health. In recent years, many experts and scholars at home and abroad are committed to the research of exercise-induced fatigue, and have put forward a variety of hypothesis to explain the cause of exercise-induced fatigue. They expect to find out the methods for preventing and eliminating exercise-induced fatigue. This article discusses mainly the pathogenesis, model building, elimination/ relief, etc. of exercise-induced fatigue to point out the research achievements of exercise-induced fatigue and its existing problems. DOI: 10.11855/j.issn.0577-7402.2016.11.14

  11. Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

    International Nuclear Information System (INIS)

    Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

    2015-01-01

    The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

  12. 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,

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

    DEFF Research Database (Denmark)

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank

    2010-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  15. 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.)

  16. 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.

  17. Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.

    Science.gov (United States)

    Fan, Hong; Paiboonrungruan, Chorlada; Zhang, Xinyan; Prigge, Justin R; Schmidt, Edward E; Sun, Zheng; Chen, Xiaoxin

    2017-11-04

    Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC. We established the Nrf2-overexpressing and Nrf2-knockdown OSCC cell lines, and examined the function of Nrf2 in regulating cell proliferation, migration, invasion, cell cycle and colony formation. Our data showed that Nrf2 overexpression promoted cancer phenotypes in OSCC cells, whereas Nrf2 silencing inhibited these phenotypes. In addition, Nrf2 positively regulated Notch signaling pathway in OSCC cells in vitro. Consistent with this observation, Nrf2 activation in Keap1 -/- mice resulted in not only hyperproliferation of squamous epithelial cells in mouse tongue as evidenced by increased expression of PCNA, but also activation of Notch signaling in these cells as evidenced by increased expression of NICD1 and Hes1. In conclusion, Nrf2 regulates cancer behaviors and Notch signaling in OSCC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Fatigue crack initiation and propagation in steels exposed to inert and corrosive environments. Final report, May 1, 1977--December 31, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Youseffi, K.; Finnie, I.

    1978-02-01

    The fatigue crack initiation life of AISI 1018 steel was investigated using compact tension specimens having sharp notch root radii. The data were analyzed using two methods for predicting initiation in strain cycling experiments. Also, another approach in which initiation is related to the stress intensity factor was developed. The next phase, that of propagation, was studied using AISI 1018 steel and a new high strength steel HY-180. The crack propagation data obtained for both steels tested in air can be described accurately by the power law first suggested by Paris, da/dN = C(..delta..K)/sup n/, where a is the crack length, N the number of cycles, and C and n are material constants. However, the exponent n was found to be two times larger for AISI 1018 steel than HY-180 steel.

  19. Fatigue crack initiation and propagation in steels exposed to inert and corrosive environments. Final report, May 1, 1977--December 31, 1977

    International Nuclear Information System (INIS)

    Youseffi, K.; Finnie, I.

    1978-02-01

    The fatigue crack initiation life of AISI 1018 steel was investigated using compact tension specimens having sharp notch root radii. The data were analyzed using two methods for predicting initiation in strain cycling experiments. Also, another approach in which initiation is related to the stress intensity factor was developed. The next phase, that of propagation, was studied using AISI 1018 steel and a new high strength steel HY-180. The crack propagation data obtained for both steels tested in air can be described accurately by the power law first suggested by Paris, da/dN = C(ΔK)/sup n/, where a is the crack length, N the number of cycles, and C and n are material constants. However, the exponent n was found to be two times larger for AISI 1018 steel than HY-180 steel

  20. NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells

    International Nuclear Information System (INIS)

    Nagel, Stefan; Scherr, Michaela; MacLeod, Roderick AF; Venturini, Letizia; Przybylski, Grzegorz K; Grabarczyk, Piotr; Meyer, Corinna; Kaufmann, Maren; Battmer, Karin; Schmidt, Christian A; Drexler, Hans G

    2009-01-01

    Homeodomain proteins control fundamental cellular processes in development and in cancer if deregulated. Three members of the NK-like subfamily of homeobox genes (NKLs), TLX1, TLX3 and NKX2-5, are implicated in T-cell acute lymphoblastic leukemia (T-ALL). They are activated by particular chromosomal aberrations. However, their precise function in leukemogenesis is still unclear. Here we screened further NKLs in 24 T-ALL cell lines and identified the common expression of MSX2. The subsequent aim of this study was to analyze the role of MSX2 in T-cell differentiation which may be disturbed by oncogenic NKLs. Specific gene activity was examined by quantitative real-time PCR, and globally by expression profiling. Proteins were analyzed by western blot, immuno-cytology and immuno-precipitation. For overexpression studies cell lines were transduced by lentiviruses. Quantification of MSX2 mRNA in primary hematopoietic cells demonstrated higher levels in CD34+ stem cells as compared to peripheral blood cells and mature CD3+ T-cells. Furthermore, analysis of MSX2 expression levels in T-cell lines after treatment with core thymic factors confirmed their involvement in regulation. These results indicated that MSX2 represents an hematopoietic NKL family member which is downregulated during T-cell development and may functionally substituted by oncogenic NKLs. For functional analysis JURKAT cells were lentivirally transduced, overexpressing either MSX2 or oncogenic TLX1 and NKX2-5, respectively. These cells displayed transcriptional activation of NOTCH3-signaling, including NOTCH3 and HEY1 as analyzed by gene expression profiling and quantitative RT-PCR, and consistently attenuated sensitivity to gamma-secretase inhibitor as analyzed by MTT-assays. Furthermore, in addition to MSX2, both TLX1 and NKX2-5 proteins interacted with NOTCH-pathway repressors, SPEN/MINT/SHARP and TLE1/GRG1, representing a potential mechanism for (de)regulation. Finally, elevated expression of NOTCH3

  1. 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

  2. Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

    Science.gov (United States)

    Lattie, Emily G; Antoni, Michael H; Fletcher, Mary Ann; Penedo, Frank; Czaja, Sara; Lopez, Corina; Perdomo, Dolores; Sala, Andreina; Nair, Sankaran; Fu, Shih Hua; Klimas, Nancy

    2012-08-01

    Stressors and emotional distress responses impact chronic fatigue syndrome (CFS) symptoms, including fatigue. Having better stress management skills might mitigate fatigue by decreasing emotional distress. Because CFS patients comprise a heterogeneous population, we hypothesized that the role of stress management skills in decreasing fatigue may be most pronounced in the subgroup manifesting the greatest neuroimmune dysfunction. In total, 117 individuals with CFS provided blood and saliva samples, and self-report measures of emotional distress, perceived stress management skills (PSMS), and fatigue. Plasma interleukin-1-beta (IL-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α), and diurnal salivary cortisol were analyzed. We examined relations among PSMS, emotional distress, and fatigue in CFS patients who did and did not evidence neuroimmune abnormalities. Having greater PSMS related to less fatigue (p=.019) and emotional distress (pfatigue levels most strongly in CFS patients in the top tercile of IL-6, and emotional distress mediated the relationship between PSMS and fatigue most strongly in patients with the greatest circulating levels of IL-6 and a greater inflammatory (IL-6):anti-inflammatory (IL-10) cytokine ratio. CFS patients having greater PSMS show less emotional distress and fatigue, and the influence of stress management skills on distress and fatigue appear greatest among patients who have elevated IL-6 levels. These findings support the need for research examining the impact of stress management interventions in subgroups of CFS patients showing neuroimmune dysfunction. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Best estimate procedures for fatigue evaluation in the framework of German KTA code

    Energy Technology Data Exchange (ETDEWEB)

    Seichter, Johannes [Siempelkamp Pruef- und Gutachter-Gesellschaft mbH, Dresden (Germany); Reese, Sven H.; Klucke, Dietmar [E.ON Kernkraft GmbH, Hannover (Germany)

    2013-07-01

    By decreasing the level of conservatism in fatigue analyses it is possible to reduce as well fatigue usage factors calculated for EOL (end of life) as 'actual CUF' (cumulative fatigue usage factor) of NPP components considerably. It is the opinion of the authors, that the mentioned best estimate procedures should be used in the course of fatigue assessment to fulfill e.g. the demands of the KTA code with regard to environmental assisted fatigue. (orig.)

  4. Fatigue with HIV/AIDS

    Science.gov (United States)

    ... 21, 2014 Select a Language: Fact Sheet 551 Fatigue WHAT IS FATIGUE? IS FATIGUE IMPORTANT? HOW DO ... It can be physical or psychological. With physical fatigue , your muscles cannot do things as easily as ...

  5. miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages

    Directory of Open Access Journals (Sweden)

    Fei Huang

    2017-10-01

    Full Text Available The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs. In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF. Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS. Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.

  6. Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Chung Hyung-Min

    2009-08-01

    Full Text Available Abstract Background Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs which are derived from human embryonic stem cell (hESC and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs. Results From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons. Conclusion Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.

  7. O-fucosylation of the notch ligand mDLL1 by POFUT1 is dispensable for ligand function.

    Directory of Open Access Journals (Sweden)

    Julia Müller

    Full Text Available Fucosylation of Epidermal Growth Factor-like (EGF repeats by protein O-fucosyltransferase 1 (POFUT1 in vertebrates, OFUT1 in Drosophila is pivotal for NOTCH function. In Drosophila OFUT1 also acts as chaperone for Notch independent from its enzymatic activity. NOTCH ligands are also substrates for POFUT1, but in Drosophila OFUT1 is not essential for ligand function. In vertebrates the significance of POFUT1 for ligand function and subcellular localization is unclear. Here, we analyze the importance of O-fucosylation and POFUT1 for the mouse NOTCH ligand Delta-like 1 (DLL1. We show by mass spectral glycoproteomic analyses that DLL1 is O-fucosylated at the consensus motif C²XXXX(S/TC³ (where C² and C³ are the second and third conserved cysteines within the EGF repeats found in EGF repeats 3, 4, 7 and 8. A putative site with only three amino acids between the second cysteine and the hydroxy amino acid within EGF repeat 2 is not modified. DLL1 proteins with mutated O-fucosylation sites reach the cell surface and accumulate intracellularly. Likewise, in presomitic mesoderm cells of POFUT1 deficient embryos DLL1 is present on the cell surface, and in mouse embryonic fibroblasts lacking POFUT1 the same relative amount of overexpressed wild type DLL1 reaches the cell surface as in wild type embryonic fibroblasts. DLL1 expressed in POFUT1 mutant cells can activate NOTCH, indicating that POFUT1 is not required for DLL1 function as a Notch ligand.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.

    1977-01-01

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

  10. A Compact Printed Quadruple Band-Notched UWB Antenna

    Directory of Open Access Journals (Sweden)

    Xiaoyin Li

    2013-01-01

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

  11. Evaluation of micro fatigue crack growth under equi-biaxial stress by membranous pressure fatigue test

    International Nuclear Information System (INIS)

    Iida, Satoshi; Abe, Shigeki; Nakamura, Takao; Kamaya, Masayuki

    2014-01-01

    For preventing nuclear power plant (NPP) accidents, NPPs are required to ensure system safety in long term safe operation under aging degradation. Now, fatigue accumulation is one of major ageing phenomena and are evaluated to ensure safety by design fatigue curve that are based on the results of uniaxial fatigue tests. On the other hand, thermal stress that occurs in piping of actual components is not uniaxial but equi-biaxial. For accurate evaluation, it is required to conform real circumstance. In this study, membranous pressure fatigue test was conducted to simulated equi-biaxial stress. Crack initiation and crack growth were examined by replica investigation. Calculation result of equivalent stress intensity factor shows crack growth under equi-biaxial stress is faster than under uniaxial stress. It is concluded that equi-biaxial fatigue behavior should be considered in the evaluation of fatigue crack initiation and crack growth. (author)

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

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