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Sample records for v-notch absorbed energy

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

    Zhou, W.; Loh, N.L.

    1996-01-01

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

  3. 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.

  4. 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

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Mirco Peron

    2018-04-01

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

  8. 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.

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

    Science.gov (United States)

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

    2010-02-01

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

  10. 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.

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

    Science.gov (United States)

    McCormack, Jordan; Stover, Susan M; Gibeling, Jeffery C; Fyhrie, David P

    2012-06-01

    We recently developed a method to measure cortical bone fracture initiation toughness using a double-notched beam in four-point bending. This method was used to test the hypothesis that mineralization around the two notch roots is correlated with fracture toughness and crack extension (physical damage). Total energy absorbed to failure negatively correlated with average mineralization of the beam (r(2)=0.62), but not with notch root mineralization. Fracture initiation toughness was positively correlated to mineralization at the broken notch root (r(2)=0.34). Crack length extension at the unbroken notch was strongly negatively correlated with the average mineralization of the notch roots (r(2)=0.81) whereas crack length extension at the broken notch did not correlate with any of the mineralization measurements. Mineralization at the notch roots and the average mineralization contributed independently to the mechanical and damage properties. The data are consistent with a hypothesis that a) high notch root mineralization results in less stable crack length extension but high force to initiate unstable crack propagation while b) higher average mineralization leads to low post-yield (and total) energy absorption to failure. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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)

  13. Excellent solar energy absorbing and retaining fabric material. Chikunetsu hoon sen'i sozai

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, T. (Unitika Ltd., Osaka (Japan). Central Research Lab.)

    1993-11-10

    Carbides of group IV transition metals such as ZrC, which are used as solar energy selective absorption film for solar energy collectors, has characteristics of absorbing light with a high energy of 0.6eV or more and of converting it to heat when exposed to light, and of not absorbing but reflecting light with a low energy of less than 0.6eV. By using ZrC as fabric materials, therefore, portable and durable heat absorbing and retaining materials can be produced. The authors have developed a solar energy absorbing and retaining fabric material, 'Solar [alpha]' (registered trade mark), which absorbs visible and near infrared rays and converts them to heat, and reflects heat from a human body and confines it. The use of Solar [alpha] has been found in various fields such as clothing as a new material for winter-sportswear, slacks, coats, and swimming suits. In this report, the heat absorbing and retaining mechanisms, basic properties of Solar [alpha], and the results of wearing tests are described. 12 refs., 6 figs., 3 tabs.

  14. Absorbed dose in AgBr in direct film for photon energies (<150 keV): relation to optical density. Theoretical calculation and experimental evaluation

    International Nuclear Information System (INIS)

    Helmrot, E.; Alm Carlsson, G.

    1996-01-01

    Calculations of absorbed dose in the silver bromide were compared with measurements of optical densities in Ultra-speed and Ektaspeed films for a broad range (25-145 kV) of X-ray energy. The calculated absorbed dose values were appropriately averaged over the complete photon energy spectrum, which was determined experimentally using a Compton spectrometer. For the whole range of tube potentials used, the measured optical densities of the films were found to be proportional to the mean absorbed dose in the AgBr grains calculated according to GREENING's theory. They were also found to be proportional to the collision kerma in silver bromide (K c,AgBr ) indicating proportionality between K c,AgBr and the mean absorbed dose in silver bromide. While GREENING's theory shows that the quotient of the mean absorbed dose in silver bromide and K c,AgBr varies with photon energy, this is not apparent when averaged over the broad (diagnostic) X-ray energy spectra used here. Alternatively, proportionality between K c,AgBr and the mean absorbed dose in silver bromide can be interpreted as resulting from a combination of the SPIERS-CHARLTON theory, valid at low photon energies ( c,AgBr (at the position of the film) independent of photon energy. The importance of taking the complete X-ray energy spectrum into full account in deriving K c,AgBr is clearly demonstrated, showing that the concept of effective energy must be used with care. (orig./HP)

  15. On the absorbed dose determination method in high energy photon beams

    International Nuclear Information System (INIS)

    Scarlat, F.; Scarisoreanu, A.; Oane, M.; Mitru, E.; Avadanei, C.

    2008-01-01

    The absorbed dose determination method in water, based on standards of air kerma or exposure in high energy photon beams generated by electron with energies in the range of 1 MeV to 50 MeV is presented herein. The method is based on IAEA-398, AAPM TG-51, DIN 6800-2, IAEA-381, IAEA-277 and NACP-80 recommendations. The dosimetry equipment is composed of UNIDOS T 10005 electrometer and different ionization chambers calibrated in air kerma method in a Co 60 beam. Starting from the general formalism showed in IAEA-381, the determination of absorbed dose in water, under reference conditions in high energy photon beams, is given. This method was adopted for the secondary standard dosimetry laboratory (SSDL) in NILPRP-Bucharest

  16. Development of methodology for assessment of absorbed dose and stopping power for low energy conversion electrons

    International Nuclear Information System (INIS)

    Almeida, Ivan Pedro Salati de

    1995-08-01

    The evaluation of absorbed dose in the case of external and internal contamination due to radionuclides is sometimes hard, because of the difficulties in the assessment of the absorbed dose caused by electrons with energy less than 100 KeV in mucous membrane. In this work, a methodology for assessment of absorbed dose and stopping power in VYNS (co-polymer of polivinyl chloride - acetate) absorbers, for the 62.5 KeV and 84-88 KeV energy 109 Cd conversion electrons, working with a 4 π proportional pressurized detector, is presented. In order to assure the reproducibility of measurement conditions, one of the detector halves has been used to obtain a spectrum of a thin 109 Cd source, without absorber. The other half of the detector was used in concomitance to obtain spectra with different thicknesses if absorber. The absorbed energy was obtained subtracting each spectrum with absorber from the spectrum without absorber, which were stored in a microcomputer connected to signal processing systems by ACE type interface. The VYNS weight and thickness were evaluated using common radionuclide metrology procedures. As VYNS has characteristics similar to a tissue equivalent material, the results obtained are consistent with dosimetric concepts and have a good agreement with those of the literature. (author)

  17. Parabolic solar concentrators with fully illuminated inverted V absorber; Coletor concentrador parabolico composto (CPC) com absorvedor V invertido completamente iluminado

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Braulio Bezerra

    2004-10-01

    Although literature on parabolic solar concentrators is numerically considerable, there are no publications regarding CPC with fully illuminate, inverted V absorber, nothing is mentioned about optical and geometric properties or, collected thermal energy. This type of solar concentrator exists in the international market, but with little known divulgence of its properties, perhaps explained because of industrial protection. In the first part of this work, the equations that define the concentrator cavity curve and its optical and geometric properties were deduced and studied in detail, by a numeric simulation program, elaborated in Meatball language. Additionally, optimization studies about the viability of the construction of this collector were carried out, relative truncation effects (the elimination of the upper part of the cavity) on the optics and geometric properties and the annual energy generated by the equipment. For the CPC concentrator collectors with fully illuminated inverted V absorbers and ideal (without truncation) it was concluded that in the configuration in which the angle of angular acceptance of the CPC is equal to the apex angle of the absorber, there occurs a minimum perimeter of the reflector cavity, when the nominal concentration and the size of the absorber are constant. Regarding the CPC concentrator collectors fully illuminated with inverted V absorber and with optimized truncation, it is shown, for a concentrator of 1.2 concentration, a good related reflector surface length and opening, and a mean number of reflections and generated thermal energy that this occurs for concentrators arising from concentrators with acceptance angles among 33.75 up to 45.58 degrees. (author)

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

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

    DEFF Research Database (Denmark)

    Tvergaard, Viggo; Needleman, Allan

    2005-01-01

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

  20. 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.

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

    Science.gov (United States)

    Hill, Charles S.; Oliveras, Ovidio M.

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna Engler

    2018-01-01

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

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

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  4. On the absorbed dose determination method in high energy electrons beams

    International Nuclear Information System (INIS)

    Scarlat, F.; Scarisoreanu, A.; Oane, M.; Mitru, E.; Avadanei, C.

    2008-01-01

    The absorbed dose determination method in water for electron beams with energies in the range from 1 MeV to 50 MeV is presented herein. The dosimetry equipment for measurements is composed of an UNIDOS.PTW electrometer and different ionization chambers calibrated in air kerma in a Co 60 beam. Starting from the code of practice for high energy electron beams, this paper describes the method adopted by the secondary standard dosimetry laboratory (SSDL) in NILPRP - Bucharest

  5. TPX/TFTR Neutral Beam energy absorbers

    International Nuclear Information System (INIS)

    Dahlgren, F.; Wright, K.; Kamperschroer, J.; Grisham, L.; Lontai, L.; Peters, C.; VonHalle, A.

    1993-01-01

    The present beam energy absorbing surfaces on the TFTR Neutral Beams such as Ion Dumps, Calorimeters, beam defining apertures, and scrapers, are simple water cooled copper plates which wee designed to absorb (via their thermal inertia) the incident beam power for two seconds with a five minute coal down interval between pulses. These components are not capable of absorbing the anticipated beam power loading for 1000 second TPX pulses and will have to be replaced with an actively cooled design. While several actively cooled energy absorbing designs were considered,, the hypervapotron elements currently being used on the JET beamlines were chosen due to their lower cooling water demands and reliable performance on JET

  6. Energy Absorbing Effectiveness – Different Approaches

    Directory of Open Access Journals (Sweden)

    Kotełko Maria

    2018-03-01

    Full Text Available In the paper the study of different crashworthiness indicators used to evaluate energy absorbing effectiveness of thin-walled energy absorbers is presented. Several different indicators are used to assess an effectiveness of two types of absorbing structures, namely thin-walled prismatic column with flaws and thin-walled prismatic frustum (hollow or foam filled in both cases subjected to axial compressive impact load. The indicators are calculated for different materials and different geometrical parameters. The problem of selection of the most appropriate and general indicators is discussed.

  7. Experimental study on the ionizing radiation field in absorbers irradiated by the 0.8 GeV and 1.2 GeV electrons

    International Nuclear Information System (INIS)

    Ambrosimov, V.K.; Kalmykov, N.N.; Kovalenko, G.D.

    1987-01-01

    The measurement results of spatial distribution of aluminium detector energy release and radioactivity in absorbers irradiated by 0.8 and 1.2 GeV electrons are given. Absorbers are made of aluminium, iron and lead, 30x30 cm size across the thickness is about 18 radiation length units. Thermoluminescence dosimeters LiF and radiochromium film dosimeters have been used to measure energy release. Induced activity of 18 F and 24 Na nuclides is determined in aluminium detectors. The experimental data are compared with the results of calculation carried out by the Monte-Carlo method

  8. 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.

  9. Mechanical Design of a High Energy Beam Absorber for the Advanced Superconducting Test Accelerator (ASTA) at Fermilab

    Energy Technology Data Exchange (ETDEWEB)

    Baffes, C.; Church, M.; Leibfritz, J.; Oplt, S.; Rakhno, I.; /Fermilab

    2012-05-10

    A high energy beam absorber has been built for the Advanced Superconducting Test Accelerator (ASTA) at Fermilab. In the facility's initial configuration, an electron beam will be accelerated through 3 TTF-type or ILC-type SRF cryomodules to an energy of 750MeV. The electron beam will be directed to one of multiple downstream experimental and diagnostic beam lines and then deposited in one of two beam absorbers. The facility is designed to accommodate up to 6 cryomodules, which would produce a 75kW beam at 1.5GeV; this is the driving design condition for the beam absorbers. The beam absorbers consist of water-cooled graphite, aluminum and copper layers contained in a helium-filled enclosure. This paper describes the mechanical implementation of the beam absorbers, with a focus on thermal design and analysis. The potential for radiation-induced degradation of the graphite is discussed.

  10. The METAS absorbed dose to water calibration service for high energy photon and electron beam radiotherapy

    International Nuclear Information System (INIS)

    Stucki, G.; Muench, W.; Quintel, H.

    2002-01-01

    Full text: The Swiss Federal Office of Metrology and Accreditation (METAS) provides an absorbed dose to water calibration service for reference dosimeters using 60 Co γ radiation, ten X-ray beam qualities between TPR 20,10 =0.639 and 0.802 and ten electron beam qualities between R 50 =1.75 gcm -2 and 8.54 gcm -2 . A 22 MeV microtron accelerator with a conventional treatment head is used as radiation source for the high energy photon and electron beams. The treatment head produces clinical beams. The METAS absorbed dose calibration service for high energy photons is based on a primary standard sealed water calorimeter of the Domen type, that is used to calibrate several METAS transfer standards of type NE2611A and NE2571A in terms of absorbed dose to water in the energy range from 60 Co to TPR 20,10 = 0.802. User reference dosimeters are compared with the transfer standards to give calibration factors in absorbed dose to water with an uncertainty of 1.0% for 60 Co γ radiation and 1.4% for higher energies (coverage factor k=2). The calibration service was launched in 1997. The calibration factors measured by METAS have been compared with those derived from the Code of Practice of the International Atomic Energy Agency using the calculated k Q factors listed in table 14. The comparison showed a maximum difference of 0.8% for the NE25611A and NE 2571A chambers. At 60 Co γ radiation the METAS primary standard of absorbed dose to water was bilaterally compared with the primary standards of the Bureau International des Poids et Mesures BIPM (Sevres) as well as of the National Research Council NRC (Canada). In either case the standards were in agreement within the comparison uncertainties. The METAS absorbed dose calibration service for high energy electron beams is based on a primary standard chemical dosimeter. A monoenergetic electron beam of precisely known particle energy and beam charge is totally absorbed in Fricke solution (ferrous ammonium sulphate) of a given

  11. 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.

  12. Enhancing inhibition-induced plasticity in tinnitus--spectral energy contrasts in tailor-made notched music matter.

    Directory of Open Access Journals (Sweden)

    Alwina Stein

    Full Text Available Chronic tinnitus seems to be caused by reduced inhibition among frequency selective neurons in the auditory cortex. One possibility to reduce tinnitus perception is to induce inhibition onto over-activated neurons representing the tinnitus frequency via tailor-made notched music (TMNM. Since lateral inhibition is modifiable by spectral energy contrasts, the question arises if the effects of inhibition-induced plasticity can be enhanced by introducing increased spectral energy contrasts (ISEC in TMNM. Eighteen participants suffering from chronic tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC-TMNM group, listened to notched music for three hours on three consecutive days. The music was filtered for both groups by introducing a notch filter centered at the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth of 3/8 octaves on each side of the notch was amplified, additionally, by about 20 dB. Before and after each music exposure, participants rated their subjectively perceived tinnitus loudness on a visual analog scale. During the magnetoencephalographic recordings, participants were stimulated with either a reference tone of 500 Hz or a test tone with a carrier frequency representing the individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced after TMNM exposure, though TMNM type did not influence the loudness ratings. Tinnitus related neural activity in the N1m time window and in the so called tinnitus network comprising temporal, parietal and frontal regions was reduced after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition-induced plasticity in a temporal and a frontal cortical area. Overall, inhibition of tinnitus related neural activity could be strengthened in people affected with tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts of inhibition-induced plasticity via TMNM and spectral energy contrasts.

  13. Design and fabrication of an energy-harvesting device using vibration absorber

    Science.gov (United States)

    Heidari, Hamidreza; Afifi, Arash

    2017-05-01

    Energy-harvesting devices collect energy that is being wasted and convert to the electrical energy. For this reason, this type of devices is considered as a convenient alternative to traditional batteries. In this paper, experimental examinations were performed to investigate the application of harvesting device for the reduction of the vibration amplitude in a vibration system and also increase the efficiency of energy-harvesting device. This study focuses on the energy-harvesting device as both producing electrical device and a vibration disabled absorber. In this regard, a motion-based energy-harvesting device is designed to produce electrical energy and also eliminate vibrations of a two joint-end beam which is located under the harmonic excitation force. Then, the governing equations of the forced motion on the main beam are derived and energy-harvesting system are simulated. In addition, the system designed by MATLAB simulation is explained and its results are expressed. Finally, a prototype of the system was made and the ability of the energy-harvesting device to absorb the original system vibrations, as well as parameters impact on the efficiency of energy harvesting is investigated. Experimental results show that the energy-harvesting device, in addition to producing electric current with a maximum value of 1.5V, reduces 94% of the original system vibrations.

  14. Energy scavenging strain absorber: application to kinetic dielectric elastomer generator

    Science.gov (United States)

    Jean-Mistral, C.; Beaune, M.; Vu-Cong, T.; Sylvestre, A.

    2014-03-01

    Dielectric elastomer generators (DEGs) are light, compliant, silent energy scavengers. They can easily be incorporated into clothing where they could scavenge energy from the human kinetic movements for biomedical applications. Nevertheless, scavengers based on dielectric elastomers are soft electrostatic generators requiring a high voltage source to polarize them and high external strain, which constitutes the two major disadvantages of these transducers. We propose here a complete structure made up of a strain absorber, a DEG and a simple electronic power circuit. This new structure looks like a patch, can be attached on human's wear and located on the chest, knee, elbow… Our original strain absorber, inspired from a sailing boat winch, is able to heighten the external available strain with a minimal factor of 2. The DEG is made of silicone Danfoss Polypower and it has a total area of 6cm per 2.5cm sustaining a maximal strain of 50% at 1Hz. A complete electromechanical analytical model was developed for the DEG associated to this strain absorber. With a poling voltage of 800V, a scavenged energy of 0.57mJ per cycle is achieved with our complete structure. The performance of the DEG can further be improved by enhancing the imposed strain, by designing a stack structure, by using a dielectric elastomer with high dielectric permittivity.

  15. Attenuation and Emittance Growth of 450 GeV and 7 TeV Proton Beams in Low-Z Absorber Elements

    CERN Document Server

    Kadi, Y; Goddard, B; Schmidt, R

    2004-01-01

    The intensity of the LHC beams will be several orders of magnitude above the damage thresholds for equipment. Passive protection of accelerator equipment against failures during beam transfer, injection and dumping of the beam with diluters and collimators is foreseen. These protection devices must be robust in case of beam impact, and low-Z materials such as carbon are favored. In these diluters, the reduction of the energy density is determined both by the attenuation due to inelastic nuclear collisions and by the emittance growth of the surviving protons due to elastic scattering processes. The physics principles leading to attenuation and emittance growth for a hadron beam traversing matter are summarised, and FLUKA simulation results for 450 GeV and 7 TeV proton beams on low-Z absorbers are compared with these predictions. Design criteria for the LHC absorbers are derived from these results.

  16. Energy-donor phosphorescence quenching study of triplet–triplet energy transfer between UV absorbers

    International Nuclear Information System (INIS)

    Kikuchi, Azusa; Nakabai, Yuya; Oguchi-Fujiyama, Nozomi; Miyazawa, Kazuyuki; Yagi, Mikio

    2015-01-01

    The intermolecular triplet–triplet energy transfer from a photounstable UV-A absorber, 4-tert-butyl-4′-methoxydibenzoylmethane (BMDBM), to UV-B absorbers, 2-ethylhexyl 4-methoxycinnamate (octyl methoxycinnamate, OMC), octocrylene (OCR) and dioctyl 4-methoxybenzylidenemalonate (DOMBM) has been observed using a 355 nm laser excitation in rigid solutions at 77 K. The decay curves of the energy-donor phosphorescence in the presence of the UV-B absorbers deviate from the exponential decay at the initial stage of the decay. The Stern–Volmer formulation is not valid in rigid solutions because molecular diffusion is impossible. The experimental results indicate that the rate constant of triplet–triplet energy transfer from BMDBM to the UV-B absorbers, k T–T , decreases in the following order: k T–T (BMDBM–DOMBM)>k T–T (BMDBM–OMC)≥k T–T (BMDBM–OCR). The presence of DOMBM enhances the photostability of the widely used combination of UV-A and UV-B absorbers, BMDBM and OCR. The effects of the triplet–triplet energy transfer on the photostability of BMDBM are discussed. - Highlights: • The intermolecular triplet–triplet energy transfer between UV absorbers was observed. • The phosphorescence decay deviates from exponential at the initial stage of decay. • The effects of triplet–triplet energy transfer on the photostability are discussed

  17. Extension of the Commonwealth standard of absorbed dose from cobalt-60 energy to 25 MV

    International Nuclear Information System (INIS)

    Sherlock, S.L.

    1986-01-01

    With the introduction of high energy linear accelerators in hospitals, there is a need for direct measurement of absorbed dose for energies to 25 MV for photons and 20 MeV electrons. The present Australian standard for absorbed dose at cobalt-60 energy is a graphite micro-calorimeter maintained at the AAEC Lucas Heights Research Laboratories. A thorough theoretical analysis of calorimeter operation suggests that computer control and monitoring techniques are appropriate. Solution of Newton's law of cooling for a four-body calorimeter allows development of a computer simulation model. Different temperature control algorithms may then be run and assessed using this model. In particular, the application of a simple differencer is examined. Successful implementation of the calorimeter for energies up to 25 MV could lead to the introduction of an Australian absorbed dose protocol based on calorimetry, therby reducing the uncertainties associated with exposure-based protocols

  18. Absorbed energy for radiation crosslinking in stabilized PE systems

    International Nuclear Information System (INIS)

    Novakovic, Lj.; Gal, O.; Charlesby, A.

    1990-01-01

    A quantitative consideration on the absorbed energy consumption in various γ-irradiated polyethylene systems is given. On the base of the increased gel dose values for the PE systems containing antioxidant, relative to the gel doses for the pure polymers, the surplus of the absorbed energy due to the presence of the particular antioxidant is calculated. The increasing of the energy consumption in the stabilized systems depends on both the type and the content of the basic polymer. The surplus in the absorbed energy decreases with the radiation dose increasing, reflecting both the diminishing of the antioxidant concentration in the irradiating PE systems and the crosslinking level. The findings can be of interest in the estimation of the absorbed doses for the specific radiation crosslinking processes. (author)

  19. Absorbed energy for radiation crosslinking in stabilized PE systems

    Energy Technology Data Exchange (ETDEWEB)

    Novakovic, Lj; Gal, O [Institut za Nuklearne Nauke Boris Kidric, Belgrade (Yugoslavia); Charlesby, A

    1990-01-01

    A quantitative consideration on the absorbed energy consumption in various {gamma}-irradiated polyethylene systems is given. On the base of the increased gel dose values for the PE systems containing antioxidant, relative to the gel doses for the pure polymers, the surplus of the absorbed energy due to the presence of the particular antioxidant is calculated. The increasing of the energy consumption in the stabilized systems depends on both the type and the content of the basic polymer. The surplus in the absorbed energy decreases with the radiation dose increasing, reflecting both the diminishing of the antioxidant concentration in the irradiating PE systems and the crosslinking level. The findings can be of interest in the estimation of the absorbed doses for the specific radiation crosslinking processes. (author).

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Leticia Santos

    2006-04-01

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

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

    International Nuclear Information System (INIS)

    Rossoll, A.

    1998-12-01

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

  3. Absorbed Energy in Ship Collisions and Grounding

    DEFF Research Database (Denmark)

    Pedersen, Preben Terndrup; Zhang, Shengming

    1998-01-01

    is that the absorbed energy does not depend on the arrangement of the structure, the material properties, and the damage mode.The purpose of the present paper is to establish a new simple relation between the absorbed energy and the destroyed material volume, which can be used as a design tool for analysis of ship...... collisions and grounding. The developed expressions reflect the structural arrangement, the material properties and different damage patterns.The present method is validated against a large number of existing experimental results and detailed numerical simulation results. Applications to full-sale ship...

  4. A review on the performance of conventional and energy-absorbing rockbolts

    Directory of Open Access Journals (Sweden)

    Charlie C. Li

    2014-08-01

    Full Text Available This is a review paper on the performances of both conventional and energy-absorbing rockbolts manifested in laboratory tests. Characteristic parameters such as ultimate load, displacement and energy absorption are reported, in addition to load–displacement graphs for every type of rockbolt. Conventional rockbolts refer to mechanical rockbolts, fully-grouted rebars and frictional rockbolts. According to the test results, under static pull loading a mechanical rockbolt usually fails at the plate; a fully-grouted rebar bolt fails in the bolt shank at an ultimate load equal to the strength of the steel after a small amount of displacement; and a frictional rockbolt is subjected to large displacement at a low yield load. Under shear loading, all types of bolts fail in the shank. Energy-absorbing rockbolts are developed aiming to combat instability problems in burst-prone and squeezing rock conditions. They absorb deformation energy either through ploughing/slippage at predefined load levels or through stretching of the steel bolt. An energy-absorbing rockbolt can carry a high load and also accommodate significant rock displacement, and thus its energy-absorbing capacity is high. The test results show that the energy absorption of the energy-absorbing bolts is much larger than that of all conventional bolts. The dynamic load capacity is smaller than the static load capacity for the energy-absorbing bolts displacing based on ploughing/slippage while they are approximately the same for the D-Bolt that displaces based on steel stretching.

  5. Multi-Absorber Transition-Edge Sensors for X-Ray Astronomy Applications

    Science.gov (United States)

    Smith, S. J.; Adams, J. S.; Bandler, S. R.; Busch, S. E.; Chervenak, J. A.; Eckart, M. E.; Ewin, A. J.; Finkbeiner, F. M.; Kelley, R. L.; Kelly, D. P.; hide

    2012-01-01

    We are developing multi-absorber Transition-Edge Sensors (TESs) for applications in x-ray astronomy. These position-sensitive devices consist of multiple x-ray absorbers each with a different thermal coupling to a single readout TES. Heat diffusion between the absorbers and the TES gives rise to a characteristic pulse shape corresponding to each absorber element and enables position discrimination. The development of these detectors is motivated by a desire to maximize focal plane arrays with the fewest number of readout channels. In this contribution we report on the first results from devices consisting of nine) 65 X 65 sq. microns Au x-ray absorbers) 5 microns thick. These are coupled to a single 35 X 35 sq. microns Mo/Au bilayer TES. These devices have demonstrated full-width-half-maximum (FWHM) energy resolution of 2.1 eV at 1.5 keV) 2.5 eV at 5.9 keV and 3.3 eV at 8 keV. This is coupled with position discrimination from pulse shape over the same energy range. We use a finite-element model to reproduce the measured pulse shapes and investigate the detector non-linearity with energy) which impacts on the devices position sensitivity and energy resolution.

  6. Absorber Materials for Transition-Edge Sensor X-ray Microcalorimeters

    Science.gov (United States)

    Brown, Ari-David; Bandler, Simon; Brekosky, Regis; Chervenak, James; Figueroa-Feliciano, Enectali; Finkbeiner, Fred; Sadleir, Jack; Iyomoto, Naoko; Kelley, Richard; Kilbourne, Caroline; hide

    2007-01-01

    Arrays of superconducting transition-edge sensors (TES) can provide high spatial and energy resolution necessary for x-ray astronomy. High quantum efficiency and uniformity of response can be achieved with a suitable absorber material, in which absorber x-ray stopping power, heat capacity, and thermal conductivity are relevant parameters. Here we compare these parameters for bismuth and gold. We have fabricated electroplated gold, electroplated gold/electroplated bismuth, and evaporated gold/evaporated bismuth 8x8 absorber arrays and find that a correlation exists between the residual resistance ratio (RRR) and thin film microstructure. This finding indicates that we can tailor absorber material conductivity via microstructure alteration, so as to permit absorber thermalization on timescales suitable for high energy resolution x-ray microcalorimetry. We show that by incorporating absorbers possessing large grain size, including electroplated gold and electroplated gold/electroplated bismuth, into our current Mo/Au TES, devices with tunable heat capacity and energy resolution of 2.3 eV (gold) and 2.1 eV (gold/bismuth) FWHM at 6 keV have been fabricated.

  7. Energy absorbers as pipe supports

    International Nuclear Information System (INIS)

    Khlafallah, M.Z.; Lee, H.M.

    1985-01-01

    With the exception of springs, pipe supports currently in use are designed with the intent of maintaining their rigidity under load. Energy dissipation mechanisms in these pipe supports result in system damping on the order presented by Code Case N-411 of ASME Section III code. Examples of these energy dissipation mechanisms are fluids and gaps in snubbers, gaps in frame supports, and friction in springs and frame supports. If energy absorbing supports designed in accordance with Code Case N-420 are used, higher additional damping will result

  8. Triplet-triplet energy transfer from a UV-A absorber butylmethoxydibenzoylmethane to UV-B absorbers.

    Science.gov (United States)

    Kikuchi, Azusa; Oguchi-Fujiyama, Nozomi; Miyazawa, Kazuyuki; Yagi, Mikio

    2014-01-01

    The phosphorescence decay of a UV-A absorber, 4-tert-butyl-4'-methoxydibenzolymethane (BMDBM) has been observed following a 355 nm laser excitation in the absence and presence of UV-B absorbers, 2-ethylhexyl 4-methoxycinnamate (octyl methoxycinnamate, OMC) and octocrylene (OCR) in ethanol at 77 K. The lifetime of the lowest excited triplet (T1) state of BMDBM is significantly reduced in the presence of OMC and OCR. The observed quenching of BMDBM triplet by OMC and OCR suggests that the intermolecular triplet-triplet energy transfer occurs from BMDBM to OMC and OCR. The T1 state of OCR is nonphosphorescent or very weakly phosphorescent. However, we have shown that the energy level of the T1 state of OCR is lower than that of the enol form of BMDBM. Our methodology of energy-donor phosphorescence decay measurements can be applied to the study of the triplet-triplet energy transfer between UV absorbers even if the energy acceptor is nonphosphorescent. In addition, the delayed fluorescence of BMDBM due to triplet-triplet annihilation was observed in the BMDBM-OMC and BMDBM-OCR mixtures in ethanol at 77 K. Delayed fluorescence is one of the deactivation processes of the excited states of BMDBM under our experimental conditions. © 2013 The American Society of Photobiology.

  9. 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.

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

    DEFF Research Database (Denmark)

    Tvergaard, Viggo; Needleman, A.

    2000-01-01

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

  11. Reducing heat loss from the energy absorber of a solar collector

    Science.gov (United States)

    Chao, Bei Tse; Rabl, Ari

    1976-01-01

    A device is provided for reducing convective heat loss in a cylindrical radiant energy collector. It includes a curved reflective wall in the shape of the arc of a circle positioned on the opposite side of the exit aperture from the reflective side walls of the collector. Radiant energy exiting the exit aperture is directed by the curved wall onto an energy absorber such that the portion of the absorber upon which the energy is directed faces downward to reduce convective heat loss from the absorber.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  13. Kinetic energy absorbing pad

    International Nuclear Information System (INIS)

    Bricmont, R.J.; Hamilton, P.A.; Ming Long Ting, R.

    1981-01-01

    Reactors, fuel processing plants etc incorporate pipes and conduits for fluids under high pressure. Fractures, particularly adjacent to conduit elbows, produce a jet of liquid which whips the broken conduit at an extremely high velocity. An enormous impact load would be applied to any stationary object in the conduit's path. The design of cellular, corrugated metal impact pads to absorb the kinetic energy of the high velocity conduits is given. (U.K.)

  14. Innovative energy absorbing devices based on composite tubes

    Science.gov (United States)

    Tiwari, Chandrashekhar

    Analytical and experimental study of innovative load limiting and energy absorbing devices are presented here. The devices are based on composite tubes and can be categorized in to two groups based upon the energy absorbing mechanisms exhibited by them, namely: foam crushing and foam fracturing. The device based on foam crushing as the energy absorbing mechanism is composed of light weight elastic-plastic foam filling inside an angle ply composite tube. The tube is tailored to have a high Poisson’s ratio (>20). Upon being loaded the device experiences large transverse contraction resulting in rapid decrease in diameter. At a certain axial load the foam core begins to crush and energy is dissipated. This device is termed as crush tube device. The device based upon foam shear fracture as the energy absorbing mechanism involves an elastic-plastic core foam in annulus of two concentric extension-twist coupled composite tubes with opposite angles of fibers. The core foam is bonded to the inner and outer tube walls. Upon being loaded axially, the tubes twist in opposite directions and fracture the core foam in out of plane shear and thus dissipate the energy stored. The device is termed as sandwich core device (SCD). The devices exhibit variations in force-displacement characteristics with changes in design and material parameters, resulting in wide range of energy absorption capabilities. A flexible matrix composite system was selected, which was composed of high stiffness carbon fibers as reinforcements in relatively low stiffness polyurethane matrix, based upon large strain to failure capabilities and large beneficial elastic couplings. Linear and non-linear analytical models were developed encapsulating large deformation theory of the laminated composite shells (using non-linear strain energy formulation) to the fracture mechanics of core foam and elastic-plastic deformation theory of the foam filling. The non-linear model is capable of including material and

  15. Interactions of Particles with Momenta of 1–10 GeV in a Highly Granular Hadronic Calorimeter with Tungsten Absorbers

    CERN Document Server

    Lam, Ching Bon; van Eijk, Bob

    Linear electron-positron colliders are proposed to complement and extend the physics programme of the Large Hadron Collider at CERN. In order to satisfy the physics goal requirements at linear colliders, detector concepts based on the Particle Flow approach are developed. Central to this approach are a high resolution tracker and a highly granular calorimeter which provide excellent jet energy resolution and background separation. The Compact Linear Collider (CLIC) is an electron-positron collider under study, aiming at centre-of-mass energies up to 3TeV. For the barrel hadronic calorimeter of experiments at CLIC, a detector with tungsten absorber plates is considered, as it is able to contain shower jets while keeping the diameter of the surrounding solenoid magnet limited. A highly granular analogue hadron calorimeter with tungsten absorbers was built by the CALICE collaboration. This thesis presents the analysis of the low-momentum data (1 GeV $\\leq$ p $\\leq$ 10 GeV) recorded in 2010 at the CERN Proton Syn...

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

    Science.gov (United States)

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

    2014-09-01

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

  17. Energy Analysis of Solar Collector With perforated Absorber Plate

    Directory of Open Access Journals (Sweden)

    Ammar A. Farhan

    2017-09-01

    Full Text Available The thermal performance of three solar collectors with 3, 6 mm and without perforation absorber plate was assessed experimentally. The experimental tests were implemented in Baghdad during the January and February 2017. Five values of airflow rates range between 0.01 – 0.1 m3/s were used through the test with a constant airflow rate during the test day. The variation of the following parameters air temperature difference, useful energy, absorber plate temperature, and collector efficiency was recorded every 15 minutes. The experimental data reports that the increases the number of absorber plate perforations with a small diameter is more efficient rather than increasing the hole diameter of the absorber plate with decreasing the perforation numbers. Maximum air temperature difference throughout the solar collector with 3, 6 mm perforations and without perforations are 17, 15, and 12 oC, respectively. Also, it can be concluded that the energy gained from the solar collector with 3 mm perforation absorber plate is 28.2 % more than the energy gained from solar collector without holes per day for 0.1 m3/s airflow rate. The maximum values of the thermal performance curves are 0.67, 0.64, and 0.56 for the solar collector with 3, 6 mm, and without perforations, respectively.

  18. Energy dependence of the air kerma response of a liquid ionization chamber at photon energies between 8 keV and 1250 keV

    International Nuclear Information System (INIS)

    Hilgers, G.; Bahar-Gogani, J.; Wickman, G.

    2002-01-01

    Full text: In its recent reports on cardiovascular brachytherapy the DGMP recommends the source strength of brachytherapy sources being characterized in terms of absorbed dose to water at a distance of 2 mm from the central axis of the source. As a consequence, the response of a detector suitable for characterizing such sources with respect to absorbed dose to water should depend only to a small extent on radiation energy. Additionally, the detection volume of the detector has to be sufficiently small for the necessary spatial resolution to be obtained. The liquid ionization chamber as described in seems to be a promising means for this type of measurements. The two components of the ionization liquid (TMS and isooctane) can be mixed in a ratio which ensures that the mass-energy absorption coefficient of the resulting mixture deviates from that of water by less than ±15 % down to photon energies of 10 keV. Due to the high density of the ionization medium, the spacing between the two electrodes of the ionization chamber can be made as small as a few tenths of a millimeter and still the resulting ionization current is sufficiently large. The ionization chamber used in the present investigation is a plane parallel chamber 5 mm in diameter and of 0.3 mm electrode spacing. The ionization medium is a mixture of 40 % TMS and 60 % isooctane. The irradiations were carried out with the ISO wide spectra series with tube voltages between 10 kV and 300 kV and with 137 Cs and 60 Co γ-radiation. As a first step, the response of the liquid ionization chamber was investigated with respect to air kerma instead of absorbed dose to water. Although the mass-energy absorption coefficient of the liquid deviates from that of air by less than ±10 % over the photon energy range, the measured chamber response varies by a factor of about 3.5. Monte Carlo calculations carried out with EGSnrc show a variation of the chamber response smaller than ±20 %. Measurements of the ion yield of the

  19. Measurements of absorbed energy distributions in water from pulsed electron beams

    International Nuclear Information System (INIS)

    Devanney, J.A.

    1974-01-01

    An evaluation of the use of a holographic interferometer to measure the energy deposition as a function of depth in water from pulsed electron beams, together with a brief description of the interferometer and the technique of generating a hologram are presented. The holographic interferometer is used to measure the energy deposition as a function of depth in water from various pulsed beams of monoenergetic electrons in the energy range from 1.0 to 2.5 MeV. These results are compared to those computed by using a Monte Carlo radiation transport code, ETRAN-15, for the same electron energies. After the discrepancies between the measured and computed results are evaluated, reasonable agreement is found between the measured and computed absorbed energy distributions as a function of depth in water. An evalutation of the response of the interferometer as a function of electron intensities is performed. A comparison among four energy deposition curves that result from the irradiation of water with pulsed electron beams from a Febetron accelerator, model 705, is presented. These pulsed beams were produced by the same vacuum diode with the same charging voltage. The results indicate that the energy distribution of the electrons in the pulsed beam is not always constant. A comparison of the energy deposition curves that result from the irradiation of water with electron pulses from different vacuum diodes but the same charging voltage is presented. These results indicate again that the energy distribution of the electrons in the pulsed beam may vary between vacuum diodes. These differences would not be realized by using a totally absorbing metal calorimeter and Faraday Cup

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

    Science.gov (United States)

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

    2018-03-01

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

  1. Effective atomic numbers for photon energy absorption of essential amino acids in the energy range 1 keV to 20 MeV

    International Nuclear Information System (INIS)

    Manohara, S.R.; Hanagodimath, S.M.

    2007-01-01

    Effective atomic numbers for photon energy-absorption (Z PEAeff ) of essential amino acids histidine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine have been calculated by a direct method in the energy region of 1 keV to 20 MeV. The Z PEAeff values have been found to change with energy and composition of the amino acids. The variations of mass energy-absorption coefficient, effective atomic number for photon interaction (Z PIeff ) and Z PEAeff with energy are shown graphically. Significant differences exist between Z PIeff and the Z PEAeff in the energy region of 8-100 keV for histidine and threonine; 6-100 keV for leucine, lysine, tryptophan, phenylalanine and valine; 15-400 keV for methionine. The effect of absorption edge on effective atomic numbers and the possibility of defining two set values of these parameters at the K-absorption edge of high-Z element present in the amino acids are discussed. The reasons for using Z PEAeff rather than the commonly used Z PIeff in medical radiation dosimetry for the calculation of absorbed dose in radiation therapy are also discussed

  2. An experimental study of an energy absorbing restrainer for piping systems

    International Nuclear Information System (INIS)

    Sone, A.; Suzuki, K.

    1989-01-01

    Recently, in the seismic design methodology of the piping systems in nuclear power plants, new and improved design criteria and calculation techniques which will lead to more reliable and cost saving design products have been investigated. For instance, problems for reducing the snubbers in nuclear power plants which provide high costs for their inspections and maintenances and related flexible design problems for the dynamic piping systems have been investigated. Thus, in order to replace snubbers, various types of alternative supporting devices such as dynamic absorbers, gapped support and energy absorbing support devices have been proposed. A number of energy absorbing restrainers have been designed in Japan and United-States by allowing yield to occur during strong earthquakes. Advantages and disadvantages of these restrainers were examined analytically and experimentally. In order to overcome the disadvantages, the authors introduced new absorbing material LSPZ (laminated super plastic zinc) in which SPZ is expected to have reliable ductility and also efficient energy absorbability still under the normal temperature condition. This paper is devoted to an experimental works for this updated absorbing restrainer

  3. An Overview on Impact Behaviour and Energy Absorption of Collapsible Metallic and Non-Metallic Energy Absorbers used in Automotive Applications

    Science.gov (United States)

    Shinde, R. B.; Mali, K. D.

    2018-04-01

    Collapsible impact energy absorbers play an important role of protecting automotive components from damage during collision. Collision of the two objects results into the damage to one or both of them. Damage may be in the form of crack, fracture and scratch. Designers must know about how the material and object behave under impact event. Owing to above reasons different types of collapsible impact energy absorbers are developed. In the past different studies were undertaken to improve such collapsible impact energy absorbers. This article highlights such studies on common shapes of collapsible impact energy absorber and their impact behaviour under the axial compression. The literature based on studies and analyses of effects of different geometrical parameters on the crushing behaviour of impact energy absorbers is presented in detail. The energy absorber can be of different shape such as circular tube, square tube, and frustums of cone and pyramids. The crushing behaviour of energy absorbers includes studies on crushing mechanics, modes of deformation, energy absorbing capacity, effect on peak and mean crushing load. In this work efforts are made to cover major outcomes from past studies on such behavioural parameters. Even though the major literature reviewed is related to metallic energy absorbers, emphasis is also laid on covering literature on use of composite tube, fiber metal lamination (FML) member, honeycomb plate and functionally graded thickness (FGT) tube as a collapsible impact energy absorber.

  4. Energy-harvesting shock absorber with a mechanical motion rectifier

    Science.gov (United States)

    Li, Zhongjie; Zuo, Lei; Kuang, Jian; Luhrs, George

    2013-02-01

    Energy-harvesting shock absorbers are able to recover the energy otherwise dissipated in the suspension vibration while simultaneously suppressing the vibration induced by road roughness. They can work as a controllable damper as well as an energy generator. An innovative design of regenerative shock absorbers is proposed in this paper, with the advantage of significantly improving the energy harvesting efficiency and reducing the impact forces caused by oscillation. The key component is a unique motion mechanism, which we called ‘mechanical motion rectifier (MMR)’, to convert the oscillatory vibration into unidirectional rotation of the generator. An implementation of a MMR-based harvester with high compactness is introduced and prototyped. A dynamic model is created to analyze the general properties of the motion rectifier by making an analogy between mechanical systems and electrical circuits. The model is capable of analyzing electrical and mechanical components at the same time. Both simulation and experiments are carried out to verify the modeling and the advantages. The prototype achieved over 60% efficiency at high frequency, much better than conventional regenerative shock absorbers in oscillatory motion. Furthermore, road tests are done to demonstrate the feasibility of the MMR shock absorber, in which more than 15 Watts of electricity is harvested while driving at 15 mph on a smooth paved road. The MMR-based design can also be used for other applications of vibration energy harvesting, such as from tall buildings or long bridges.

  5. Energy-harvesting shock absorber with a mechanical motion rectifier

    International Nuclear Information System (INIS)

    Li, Zhongjie; Zuo, Lei; Kuang, Jian; Luhrs, George

    2013-01-01

    Energy-harvesting shock absorbers are able to recover the energy otherwise dissipated in the suspension vibration while simultaneously suppressing the vibration induced by road roughness. They can work as a controllable damper as well as an energy generator. An innovative design of regenerative shock absorbers is proposed in this paper, with the advantage of significantly improving the energy harvesting efficiency and reducing the impact forces caused by oscillation. The key component is a unique motion mechanism, which we called ‘mechanical motion rectifier (MMR)’, to convert the oscillatory vibration into unidirectional rotation of the generator. An implementation of a MMR-based harvester with high compactness is introduced and prototyped. A dynamic model is created to analyze the general properties of the motion rectifier by making an analogy between mechanical systems and electrical circuits. The model is capable of analyzing electrical and mechanical components at the same time. Both simulation and experiments are carried out to verify the modeling and the advantages. The prototype achieved over 60% efficiency at high frequency, much better than conventional regenerative shock absorbers in oscillatory motion. Furthermore, road tests are done to demonstrate the feasibility of the MMR shock absorber, in which more than 15 Watts of electricity is harvested while driving at 15 mph on a smooth paved road. The MMR-based design can also be used for other applications of vibration energy harvesting, such as from tall buildings or long bridges. (paper)

  6. Energy absorption coefficients for 662 keV gamma ray in some fatty acids

    International Nuclear Information System (INIS)

    Bhandal, G.S.; Singh, K.; Rama Rani; Vijay Kumar

    1993-01-01

    The mass energy absorption coefficient refers to the amount of energy dissipation by the secondary electron set in motion as a result of interactions between incident photons and matter. Under certain conditions, the energy dissipated by electrons in a given volume can be equated to the energy absorbed in that volume. The absorbed energy is of basic interest in radiation dosimetry because it represents the amount of energy made available for the production of chemical or biological effects. Sphere transmission is employed for the direct measurement of mass energy absorption coefficients at 662 keV in some fatty acids. Excellent agreement is obtained between the measured and theoretical values. (author). 6 refs., 1 fig., 1 tab

  7. Tritons at energies of 10 MeV to 1 TeV: Conversion coefficients for fluence-to-absorbed dose, equivalent dose, effective dose, and gray equivalent, calculated using Monte Carlo radiation transport code MCNPX 2.7.C

    International Nuclear Information System (INIS)

    Copeland, K.; Parker, D. E.; Friedberg, W.

    2010-01-01

    Conversion coefficients were calculated for fluence-to-absorbed dose, fluence-to-equivalent dose, fluence-to-effective dose and fluence-to-gray equivalent for isotropic exposure of an adult female and an adult male to tritons ( 3 H + ) in the energy range of 10 MeV to 1 TeV (0.01-1000 GeV). Coefficients were calculated using Monte Carlo transport code MCNPX 2.7.C and BodyBuilder TM 1.3 anthropomorphic phantoms. Phantoms were modified to allow calculation of effective dose to a Reference Person using tissues and tissue weighting factors from 1990 and 2007 recommendations of the International Commission on Radiological Protection (ICRP) and calculation of gray equivalent to selected tissues as recommended by the National Council on Radiation Protection and Measurements. At 15 of the 19 energies for which coefficients for effective dose were calculated, coefficients based on ICRP 2007 and 1990 recommendations differed by less than 3%. The greatest difference, 43%, occurred at 30 MeV. Published by Oxford Univ. Press on behalf of the US Government 2010. (authors)

  8. Helions at energies of 10 MeV to 1 TeV: Conversion coefficients for fluence-to-absorbed dose, equivalent dose, effective dose and gray equivalent, calculated using Monte Carlo radiation transport code MCNPX 2.7.C

    International Nuclear Information System (INIS)

    Copeland, K.; Parker, D. E.; Friedberg, W.

    2010-01-01

    Conversion coefficients were calculated for fluence-to-absorbed dose, fluence-to-equivalent dose, fluence-to-effective dose and fluence-to-gray equivalent, for isotropic exposure of an adult male and an adult female to helions ( 3 He 2+ ) in the energy range of 10 MeV to 1 TeV (0.01-1000 GeV). Calculations were performed using Monte Carlo transport code MCNPX 2.7.C and BodyBuilder TM 1.3 anthropomorphic phantoms modified to allow calculation of effective dose using tissues and tissue weighting factors from either the 1990 or 2007 recommendations of the International Commission on Radiological Protection (ICRP), and gray equivalent to selected tissues as recommended by the National Council on Radiation Protection and Measurements. At 15 of the 19 energies for which coefficients for effective dose were calculated, coefficients based on ICRP 2007 and 1990 recommendations differed by less than 2%. The greatest difference, 62%, occurred at 100 MeV. Published by Oxford Univ. Press on behalf of the U.S. Government 2010. (authors)

  9. Deuterons at energies of 10 MeV to 1 TeV: Conversion coefficients for fluence-to-absorbed dose, equivalent dose, effective dose and gray equivalent, calculated using Monte Carlo radiation transport code MCNPX 2.7.C

    International Nuclear Information System (INIS)

    Copeland, K.; Parker, D. E.; Friedberg, W.

    2011-01-01

    Conversion coefficients were calculated for fluence-to-absorbed dose, fluence-to-equivalent dose, fluence-to-effective dose and fluence-to-gray equivalent for isotropic exposure of an adult female and an adult male to deuterons ( 2 H + ) in the energy range 10 MeV -1 TeV (0.01-1000 GeV). Coefficients were calculated using the Monte Carlo transport code MCNPX 2.7.C and BodyBuilder TM 1.3 anthropomorphic phantoms. Phantoms were modified to allow calculation of the effective dose to a Reference Person using tissues and tissue weighting factors from 1990 and 2007 recommendations of the International Commission on Radiological Protection (ICRP) and gray equivalent to selected tissues as recommended by the National Council on Radiation Protection and Measurements. Coefficients for the equivalent and effective dose incorporated a radiation weighting factor of 2. At 15 of 19 energies for which coefficients for the effective dose were calculated, coefficients based on ICRP 1990 and 2007 recommendations differed by < 3 %. The greatest difference, 47 %, occurred at 30 MeV. (authors)

  10. 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.

  11. Moving core beam energy absorber and converter

    Science.gov (United States)

    Degtiarenko, Pavel V.

    2012-12-18

    A method and apparatus for the prevention of overheating of laser or particle beam impact zones through the use of a moving-in-the-coolant-flow arrangement for the energy absorbing core of the device. Moving of the core spreads the energy deposition in it in 1, 2, or 3 dimensions, thus increasing the effective cooling area of the device.

  12. Electron beam dosimetry for a thin-layer absorber irradiated by 300-keV electrons

    International Nuclear Information System (INIS)

    Kijima, Toshiyuki; Nakase, Yoshiaki

    1993-01-01

    Depth-dose distributions in thin-layer absorbers were measured for 300-keV electrons from a scanning-type irradiation system, the electrons having penetrated through a Ti-window and an air gap. Irradiations of stacks of cellulose triacetate(CTA) film were carried out using either a conveyor (i.e. dynamic irradiation) or fixed (i.e. static) irradiation. The sample was irradiated using various angles of incidence of electrons, in order to examine the effect of obliqueness of electron incidence at low-energy representative of routine radiation curing of thin polymeric or resin layers. Dynamic irradiation gives broader and shallower depth-dose distributions than static irradiation. Greater obliqueness of incident electrons gives results that can be explained in terms of broader and shallower depth-dose distributions. The back-scattering of incident electrons by a metal(Sn) backing material enhances the absorbed dose in a polymeric layer and changes the overall distribution. It is suggested that any theoretical estimations of the absorbed dose in thin layers irradiated in electron beam curing must be accomplished and supported by experimental data such as that provided by this investigation. (Author)

  13. Fracture Mechanics Assessment for Different Notch Sizes Using Finite Element Analysis Based on Ductile Failure Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Keun Hyung; Jeon, Jun Young; Han, Jae Jun; Nam, Hyun Suk; Lee, Dae Young; Kim, Yun Jae [Korea Univ., Seoul (Korea, Republic of)

    2016-08-15

    In this study, notch defects are evaluated using fracture mechanics. To understand the effects of notch defects, FE analysis is conducted to predict the limit load and J-integral for middle-cracked and single-edge cracked plates with various sizes of notch under tension and bending. As the radius of the notch increases, the energy release rate also increases, although the limit load remains constant. The values of fracture toughness(J{sub IC}) of SM490A are determined for various notch radii through FE simulation instead of conducting an experiment. As the radius of the notch increases, the energy release rate also increases, together with a more significant increase in fracture toughness. To conclude, as the notch radius increases, the resistance to crack propagation also increases.

  14. Energy deposition studies for the LBNE beam absorber

    International Nuclear Information System (INIS)

    Rakhno, Igor L.; Mokhov, Nikolai V.; Tropin, Igor S.

    2015-01-01

    Results of detailed Monte Carlo energy deposition studies performed for the LBNE absorber core and the surrounding shielding with the MARS15 code are described. The model of the entire facility that includes a pion-production target, focusing horns, target chase, decay channel, hadron absorber system - all with corresponding radiation shielding - was developed using the recently implemented ROOT-based geometry option in the MARS15 code. This option provides substantial flexibility and automation when developing complex geometry models. Both normal operation and accidental conditions were studied. Various design options were considered, in particular the following: (i) filling the decay pipe with air or helium; (ii) the absorber mask material and shape; (iii) the beam spoiler material and size. Results of detailed thermal calculations with the ANSYS code helped to select the most viable absorber design options. (authors)

  15. Multi-Level Experimental and Analytical Evaluation of Two Composite Energy Absorbers

    Science.gov (United States)

    Jackson, Karen E.; Littell, Justin D.; Fasanella, Edwin L.; Annett, Martin S.; Seal, Michael D., II

    2015-01-01

    Two composite energy absorbers were developed and evaluated at NASA Langley Research Center through multi-level testing and simulation performed under the Transport Rotorcraft Airframe Crash Testbed (TRACT) research program. A conical-shaped energy absorber, designated the conusoid, was evaluated that consisted of four layers of hybrid carbon-Kevlar plain weave fabric oriented at [+45 deg/-45 deg/-45 deg/+45 deg] with respect to the vertical, or crush, direction. A sinusoidal-shaped energy absorber, designated the sinusoid, was developed that consisted of hybrid carbon-Kevlar plain weave fabric face sheets, two layers for each face sheet oriented at +/-45deg with respect to the vertical direction and a closed-cell ELFOAM P200 polyisocyanurate (2.0-lb/cu ft) foam core. The design goal for the energy absorbers was to achieve average floor-level accelerations of between 25- and 40-g during the full-scale crash test of a retrofitted CH-46E helicopter airframe, designated TRACT 2. Variations in both designs were assessed through dynamic crush testing of component specimens. Once the designs were finalized, subfloor beams of each configuration were fabricated and retrofitted into a barrel section of a CH-46E helicopter. A vertical drop test of the barrel section was conducted onto concrete to evaluate the performance of the energy absorbers prior to retrofit into TRACT 2. The retrofitted airframe was crash tested under combined forward and vertical velocity conditions onto soil, which is characterized as a sand/clay mixture. Finite element models were developed of all test articles and simulations were performed using LS-DYNA, a commercial nonlinear explicit transient dynamic finite element code. Test-analysis results are presented for each energy absorber as comparisons of time-history responses, as well as predicted and experimental structural deformations and progressive damage under impact loading for each evaluation level.

  16. 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

  17. Synthesis of Numerical Methods for Modeling Wave Energy Converter-Point Absorbers: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Yu, Y. H.

    2012-05-01

    During the past few decades, wave energy has received significant attention among all ocean energy formats. Industry has proposed hundreds of prototypes such as an oscillating water column, a point absorber, an overtopping system, and a bottom-hinged system. In particular, many researchers have focused on modeling the floating-point absorber as the technology to extract wave energy. Several modeling methods have been used such as the analytical method, the boundary-integral equation method, the Navier-Stokes equations method, and the empirical method. However, no standardized method has been decided. To assist the development of wave energy conversion technologies, this report reviews the methods for modeling the floating-point absorber.

  18. Electron absorbed fractions of energy and S-values in an adult human skeleton based on {mu}CT images of trabecular bone

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R; Cassola, V F; Khoury, H J; De O Lira, C A B [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Professor Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Richardson, R B [Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, ON, K0J 1J0 (Canada); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); Brown, K Robson, E-mail: rkramer@uol.com.br [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)

    2011-03-21

    When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on {mu}CT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 {mu}m thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters {sup 14}C, {sup 59}Fe, {sup 131}I, {sup 89}Sr, {sup 32}P and {sup 90}Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 {mu}m endosteum and the previously recommended 10 {mu}m endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by {approx}20% when the beta emitters are in marrow.

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

    International Nuclear Information System (INIS)

    Zhang, Y.; Yang, J.L.

    2002-01-01

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

  20. 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.

  1. DETERMINATION OF ENERGY LOSSES BY SHOCK ABSORBER IN A FREIGHT CAR AT CRASH MODE

    Directory of Open Access Journals (Sweden)

    Ya. V. Bolzhelarskyi

    2016-08-01

    Full Text Available Purpose. The purpose of this work is to determine the energy losses in the shock absorber of the freight car whose wheel-set moves in the derailed state on the track panel depending on the axle load and structural parameters of spring suspension. Methodology. On the basis of spring suspension construction analysis and operating principle of the friction shock absorber of the freight car bogie the authors provide the method for determining the energy absorbed by it. The calculations take the maximum values of the absorber elements displacement and the regulatory values of spring suspension parameters. Findings. The authors obtained the calculated formula for determining the energy absorbed by shock absorber for regulation-set mounting schemes of elastic bogie elements depending on the axial load. The mentioned curves are parabolic. Originality. The work examines the crash mode of the wheel-set movement on the track panels after its derailment. It is shown that the energy dissipation in the shock absorbers is the reason for increase in resistance to rolling stock movement. The formulas for calculating the amount of energy dissipated in the shock absorber with a maximum displacement of its elements are derived. This energy depends on the axle load and structural parameters of spring suspension. Practical value. The proposed method allows setting the value of the additional resistance to motion that occurs in crash mode which makes it possible to increase the accuracy of traction calculations.

  2. Research on temperature characteristics of laser energy meter absorber irradiated by ms magnitude long pulse laser

    Science.gov (United States)

    Li, Nan; Qiao, Chunhong; Fan, Chengyu; Zhang, Jinghui; Yang, Gaochao

    2017-10-01

    The research on temperature characteristics for large-energy laser energy meter absorber is about continuous wave (CW) laser before. For the measuring requirements of millisecond magnitude long pulse laser energy, the temperature characteristics for absorber are numerically calculated and analyzed. In calculation, the temperature field distributions are described by heat conduction equations, and the metal cylinder cavity is used for absorber model. The results show that, the temperature of absorber inwall appears periodic oscillation with pulse structure, the oscillation period and amplitude respectively relate to the pulse repetition frequency and single pulse energy. With the wall deep increasing, the oscillation amplitude decreases rapidly. The temperature of absorber outerwall is without periodism, and rises gradually with time. The factors to affect the temperature rise of absorber are single pulse energy, pulse width and repetition frequency. When the laser irradiation stops, the temperature between absorber inwall and outerwall will reach agreement rapidly. After special technology processing to enhance the capacity of resisting laser damage for absorber inwall, the ms magnitude long pulse laser energy can be obtained with the method of measuring the temperature of absorber outerwall. Meanwhile, by optimization design of absorber structure, when the repetition frequency of ms magnitude pulse laser is less than 10Hz, the energy of every pulse for low repetition frequency pulse sequence can be measured. The work offers valuable references for the design of ms magnitude large-energy pulse laser energy meter.

  3. Impact Testing and Simulation of a Sinusoid Foam Sandwich Energy Absorber

    Science.gov (United States)

    Jackson, Karen E.; Fasanella, Edwin L; Littell, Justin D.

    2015-01-01

    A sinusoidal-shaped foam sandwich energy absorber was developed and evaluated at NASA Langley Research Center through multi-level testing and simulation performed under the Transport Rotorcraft Airframe Crash Testbed (TRACT) research project. The energy absorber, designated the "sinusoid," consisted of hybrid carbon- Kevlar® plain weave fabric face sheets, two layers for each face sheet oriented at +/-45deg with respect to the vertical or crush direction, and a closed-cell ELFOAM(TradeMark) P200 polyisocyanurate (2.0-lb/ft3) foam core. The design goal for the energy absorber was to achieve an average floor-level acceleration of between 25- and 40-g during the full-scale crash test of a retrofitted CH-46E helicopter airframe, designated TRACT 2. Variations in the design were assessed through quasi-static and dynamic crush testing of component specimens. Once the design was finalized, a 5-ft-long subfloor beam was fabricated and retrofitted into a barrel section of a CH-46E helicopter. A vertical drop test of the barrel section was conducted onto concrete to evaluate the performance of the energy absorber prior to retrofit into TRACT 2. Finite element models were developed of all test articles and simulations were performed using LSDYNA ®, a commercial nonlinear explicit transient dynamic finite element code. Test analysis results are presented for the sinusoid foam sandwich energy absorber as comparisons of load-displacement and acceleration-time-history responses, as well as predicted and experimental structural deformations and progressive damage for each evaluation level (component testing through barrel section drop testing).

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

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

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

  5. 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.

  6. 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)

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

    International Nuclear Information System (INIS)

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

    1996-06-01

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

  8. 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

  9. Absorbed dose rate meter for β-ray

    International Nuclear Information System (INIS)

    Bingo, K.

    1977-01-01

    The absorbed dose of β-ray depends on the energy of β-rays and the epidermal thickness of tissue in interest. In order to measure the absorbed dose rate at the interested tissue directly, the ratio of counting rate to absorbed dose should be constant independent of β-ray energy. In this purpose, a thin plastic scintillator was used as a detector with a single channel analyzer. The pulse height distribution, obtained using the scintillator whose thickness is less than the range of β-rays, shows a peak at a particular pulse height depending on the thickness of scintillator used. This means an increase of the number of pulses at lower pulse height. The lower level of discrimination and window width of the single channel analyzer are chosen according to the epidermal thickness of the tissue. In the experiment, scintillators of 0.5, 1, 2, 3, 5 and 10 mm thick were tested. It was found that desirable pulse height distribution, to obtain a constant dose sensitivity, could be obtained using the 2 mm thick scintillator. The sensitivity of the absorbed dose rate meter is constant within +-15% for β-ray with maximum energy from 0.4 to 3.5 MeV, when the absorbed dose rate for skin (epidermal thickness 7mg/cm 2 ) is measured. In order to measure the dose rate for a hand (epithermal thickness 40mg/cm 2 ) the lower level of discrimination is changed to be higher and at the same time the window width is also changed. Combining these techniques, one can get an absorbed dose rate meter for the tissue dose of various thickness, which has the constant dose sensitivity within +-15% for β-rays with maximum energy from 0.4 to 3.5 MeV

  10. Numerical Modeling of a Wave Energy Point Absorber

    DEFF Research Database (Denmark)

    Hernandez, Lorenzo Banos; Frigaard, Peter; Kirkegaard, Poul Henning

    2009-01-01

    The present study deals with numerical modelling of the Wave Star Energy WSE device. Hereby, linear potential theory is applied via a BEM code on the wave hydrodynamics exciting the floaters. Time and frequency domain solutions of the floater response are determined for regular and irregular seas....... Furthermore, these results are used to estimate the power and the energy absorbed by a single oscillating floater. Finally, a latching control strategy is analysed in open-loop configuration for energy maximization....

  11. Absorbed dose calculation of the energy deposition close to bone, lung and soft tissue interfaces in molecular radiotherapy

    International Nuclear Information System (INIS)

    Fernandez, M.; Lassman, M.

    2015-01-01

    Full text of publication follows. Aim: for voxel-based dosimetry in molecular radiotherapy (MRT) based on tabulated voxel S-values these values are usually obtained only for soft tissue. In order to study the changes in the dose deposition patterns at interfaces between different materials we have performed Monte Carlo simulations. Methods: the deposited energy patterns were obtained using the Monte-Carlo radiation code MCNPX v2.7 for Lu 177 (medium-energy) and Y 90 (high-energy). The following interfaces were studied: soft tissue-bone and soft tissue-lungs. For this purpose a volume of soft tissue homogeneously filled with Lu 177 or Y 90 was simulated at the interface to 3 different volumes containing no activity: soft tissue, lungs and bone. The emission was considered to be isotropic. The dimensions were chosen to ensure that the energy deposited by all generated particles was scored. The materials were defined as recommended by ICPR46; the decay schemes of Eckerman and Endo were used. With these data the absorbed dose patterns normalized to the maximum absorbed dose in the source region (soft tissue) were calculated. Results: the absorbed dose fractions in the boundary with soft tissue, bone and lungs are 50%, 47% and 57%, respectively, for Lu 177 and 50%, 47% and 51% for Y 90 . The distances to the interface at which the absorbed fractions are at 0.1% are 1.0, 0.6 and 3.0 mm for Lu 177 and 7.0, 4.0 and 24 mm for Y 90 , for soft tissue, bone and lungs respectively. Conclusions: in MRT, the changes in the absorbed doses at interfaces between soft tissue and bone/lungs need to be considered for isotopes emitting high energy particles. (authors)

  12. Initial electron energy spectra in water irradiated by photons with energies to 1 GeV

    International Nuclear Information System (INIS)

    Todo, A.S.; Hiromoto, G.; Turner, J.E.; Hamm, R.N.; Wright, H.A.

    1984-02-01

    This work was undertaken to provide basic physical data for use in the dosimetry of high-energy photons. Present and future sources of such photons are described, and the relevant literature is reviewed and summarized. Calculations were performed with a Monte Carlo computer code, PHOEL-3, which is also described. Tables of initial electron and positron energies are presented for monoenergetic photons undergoing single interactions in water. Photon energies to 1 GeV are treated. The code treats explicitly the production of electron-positron pairs, Compton scattering, photoelectric absorption, and the emission of Auger electrons following the occurrence of K-shell vacancies in oxygen. The tables give directly the information needed to specify the absolute single-collision kerma in water, which approximates tissue, at each photon energy. Results for continuous photon energy spectra can be obtained by using linear interpolation with the tables. (Continuous spectra can also be used directly in PHOEL-3.) The conditions under whch first-collision kerma approximate absorbed dose are discussed. A formula is given for estimating bremsstrahlung energy loss, one of the principal differences between kerma and absorbed dose in practical cases. 31 references, 4 figures, 18 tables

  13. 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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

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

    International Nuclear Information System (INIS)

    Rack, H.J.

    1975-01-01

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

  16. Crush Can Behaviour as an Energy Absorber in a Frontal Impact

    International Nuclear Information System (INIS)

    Bhuyan, Atanu; Ganilova, Olga

    2012-01-01

    The work presented is devoted to the investigation of a state-of-the-art technological solution for the design of a crush-can characterized by optimal energy absorbing properties. The work is focused on the theoretical background of the square tubes, circular tubes and inverbucktube performance under impact with the purpose of design of a novel optimized structure. The main system under consideration is based on the patent US 2008/0185851 A1 and includes a base flange with elongated crush boxes and back straps for stabilization of the crush boxes with the purpose of improvement of the energy-absorbing functionality. The modelling of this system is carried out applying both a theoretical approach and finite element analysis concentrating on the energy absorbing abilities of the crumple zones. The optimization process is validated under dynamic and quasi-static loading conditions whilst considering various modes of deformation and stress distribution along the tubular components. Energy absorbing behaviour of the crush-cans is studied concentrating on their geometrical properties and their diamond or concertina modes of deformation. Moreover, structures made of different materials, steel, aluminium and polymer composites are considered for the material effect analysis and optimization through their combination. Optimization of the crush-can behaviour is done within the limits of the frontal impact scenario with the purpose of improvement of the structural performance in the Euro NCAP tests.

  17. Crush Can Behaviour as an Energy Absorber in a Frontal Impact

    Science.gov (United States)

    Bhuyan, Atanu; Ganilova, Olga

    2012-08-01

    The work presented is devoted to the investigation of a state-of-the-art technological solution for the design of a crush-can characterized by optimal energy absorbing properties. The work is focused on the theoretical background of the square tubes, circular tubes and inverbucktube performance under impact with the purpose of design of a novel optimized structure. The main system under consideration is based on the patent US 2008/0185851 A1 and includes a base flange with elongated crush boxes and back straps for stabilization of the crush boxes with the purpose of improvement of the energy-absorbing functionality. The modelling of this system is carried out applying both a theoretical approach and finite element analysis concentrating on the energy absorbing abilities of the crumple zones. The optimization process is validated under dynamic and quasi-static loading conditions whilst considering various modes of deformation and stress distribution along the tubular components. Energy absorbing behaviour of the crush-cans is studied concentrating on their geometrical properties and their diamond or concertina modes of deformation. Moreover, structures made of different materials, steel, aluminium and polymer composites are considered for the material effect analysis and optimization through their combination. Optimization of the crush-can behaviour is done within the limits of the frontal impact scenario with the purpose of improvement of the structural performance in the Euro NCAP tests.

  18. 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

  19. A graphite calorimeter for absolute measurements of absorbed dose to water: application in medium-energy x-ray filtered beams.

    Science.gov (United States)

    Pinto, M; Pimpinella, M; Quini, M; D'Arienzo, M; Astefanoaei, I; Loreti, S; Guerra, A S

    2016-02-21

    The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) has designed and built a graphite calorimeter that, in a water phantom, has allowed the determination of the absorbed dose to water in medium-energy x-rays with generating voltages from 180 to 250 kV. The new standard is a miniaturized three-bodies calorimeter, with a disc-shaped core of 21 mm diameter and 2 mm thickness weighing 1.134 g, sealed in a PMMA waterproof envelope with air-evacuated gaps. The measured absorbed dose to graphite is converted into absorbed dose to water by means of an energy-dependent conversion factor obtained from Monte Carlo simulations. Heat-transfer correction factors were determined by FEM calculations. At a source-to-detector distance of 100 cm, a depth in water of 2 g cm(-2), and at a dose rate of about 0.15 Gy min(-1), results of calorimetric measurements of absorbed dose to water, D(w), were compared to experimental determinations, D wK, obtained via an ionization chamber calibrated in terms of air kerma, according to established dosimetry protocols. The combined standard uncertainty of D(w) and D(wK) were estimated as 1.9% and 1.7%, respectively. The two absorbed dose to water determinations were in agreement within 1%, well below the stated measurement uncertainties. Advancements are in progress to extend the measurement capability of the new in-water-phantom graphite calorimeter to other filtered medium-energy x-ray qualities and to reduce the D(w) uncertainty to around 1%. The new calorimeter represents the first implementation of in-water-phantom graphite calorimetry in the kilovoltage range and, allowing independent determinations of D(w), it will contribute to establish a robust system of absorbed dose to water primary standards for medium-energy x-ray beams.

  20. Development of methodology for assessment of absorbed dose and stopping power for low energy conversion electrons; Desenvolvimento de uma metodologia para estimativa da dose absorvida e do poder de freamento para eletrons de conversao de baixa energia

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Ivan Pedro Salati de

    1995-08-01

    The evaluation of absorbed dose in the case of external and internalcontamination due to radionuclides is sometimes hard, because of the difficulties in the assessment of the absorbed dose caused by electrons with energy less than 100 KeV in mucous membrane. In this work, a methodology for assessment of absorbed dose and stopping power in VYNS (co-polymer of polivinyl chloride - acetate) absorbers, for the 62.5 KeV and 84-88 KeV energy {sup 109} Cd conversion electrons, working with a 4 {pi} proportional pressurized detector, is presented. In order to assure the reproducibility of measurement conditions, one of the detector halves has been used to obtain a spectrum of a thin {sup 109} Cd source, without absorber. The other half of the detector was used in concomitance to obtain spectra with different thicknesses if absorber. The absorbed energy was obtained subtracting each spectrum with absorber from the spectrum without absorber, which were stored in a microcomputer connected to signal processing systems by ACE type interface. The VYNS weight and thickness were evaluated using common radionuclide metrology procedures. As VYNS has characteristics similar to a tissue equivalent material, the results obtained are consistent with dosimetric concepts and have a good agreement with those of the literature. (author)

  1. Thin absorbers for large-area soft X-ray microcalorimeters

    Energy Technology Data Exchange (ETDEWEB)

    Rocks, L. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States)]. E-mail: rocks@wisp.physics.wisc.edu; Anderson, M.B. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Bilgri, N. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Brekosky, R. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Gwynne Crowder, S. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Figueroa-Feliciano, E. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Kelley, R. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Kilbourne, C.A. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Lai, T. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Lindeman, M.A. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Man, J. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); McCammon, D. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Nelms, K.L. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Porter, F.S. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Sivananthan, S. [University of Illinois at Chicago, Chicago, IL 60607 (United States); Vidugiris, G. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Zhao, J. [University of Illinois at Chicago, Chicago, IL 60607 (United States)

    2006-04-15

    The X-ray Quantum Calorimeter (XQC) sounding rocket experiment utilizes a microcalorimeter array for observing the diffuse soft X-ray background. Observations of such low surface-brightness targets require a large-area detector. We will be using an array of large absorbers. Good absorbers must rapidly and completely thermalize photons, have small heat capacity for high stopping efficiency and have good lateral thermal transport. For observing the soft X-ray background (energies <1 keV), the volume and heat capacity of absorber material can be kept to a minimum by making the absorbers only as thick as needed for high quantum efficiency at these low energies. These thin, large-area absorbers are not self-supporting and have poor lateral heat transport. Depositing the absorber material on a Si substrate provides support and improves lateral thermal conduction. We present heat capacity results for thin HgTe and thin Bi, each on Si substrates. We also describe the HgTe absorber fabrication.

  2. Design and performance simulation of a segmented-absorber based muon detection system for high energy heavy ion collision experiments

    International Nuclear Information System (INIS)

    Ahmad, S.; Bhaduri, P.P.; Jahan, H.; Senger, A.; Adak, R.; Samanta, S.; Prakash, A.; Dey, K.; Lebedev, A.; Kryshen, E.; Chattopadhyay, S.; Senger, P.; Bhattacharjee, B.; Ghosh, S.K.; Raha, S.; Irfan, M.; Ahmad, N.; Farooq, M.; Singh, B.

    2015-01-01

    A muon detection system (MUCH) based on a novel concept using a segmented and instrumented absorber has been designed for high-energy heavy-ion collision experiments. The system consists of 6 hadron absorber blocks and 6 tracking detector triplets. Behind each absorber block a detector triplet is located which measures the tracks of charged particles traversing the absorber. The performance of such a system has been simulated for the CBM experiment at FAIR (Germany) that is scheduled to start taking data in heavy ion collisions in the beam energy range of 6–45 A GeV from 2019. The muon detection system is mounted downstream to a Silicon Tracking System (STS) that is located in a large aperture dipole magnet which provides momentum information of the charged particle tracks. The reconstructed tracks from the STS are to be matched to the hits measured by the muon detector triplets behind the absorber segments. This method allows the identification of muon tracks over a broad range of momenta including tracks of soft muons which do not pass through all the absorber layers. Pairs of oppositely charged muons identified by MUCH could therefore be combined to measure the invariant masses in a wide range starting from low mass vector mesons (LMVM) up to charmonia. The properties of the absorber (material, thickness, position) and of the tracking chambers (granularity, geometry) have been varied in simulations of heavy-ion collision events generated with the UrQMD generator and propagated through the setup using the GEANT3, the particle transport code. The tracks are reconstructed by a Cellular Automaton algorithm followed by a Kalman Filter. The simulations demonstrate that low mass vector mesons and charmonia can be clearly identified in central Au+Au collisions at beam energies provided by the international Facility for Antiproton and Ion Research (FAIR)

  3. Can polar bear hairs absorb environmental energy?

    Directory of Open Access Journals (Sweden)

    He Ji-Huan

    2011-01-01

    Full Text Available A polar bear (Ursus maritimus has superior ability to survive in harsh Arctic regions, why does the animal have such an excellent thermal protection? The present paper finds that the unique labyrinth cavity structure of the polar bear hair plays an important role. The hair can not only prevent body temperature loss but can also absorb energy from the environment.

  4. Gamma-ray energy absorption in absorbing homogeneous medium. Applications to Oceanography and Geophysics (Gamma-ray spectroscopy from 500 to 1500 keV)

    International Nuclear Information System (INIS)

    Lapicque, G.

    1980-01-01

    The aim of this study is to establish a general algebrical approach for the calculation, without any program, of the full energy peak efficiency of a detecting probe designed to measure the gamma activity of a radio-element in a (semi) infinite homogeneous absorbing medium such as the Sea. The radio-active source may be punctual or, most often, constitute an integral part of the medium. The proposed theory is valid for any purely absorptive process of particles moving along straight trajectories, diffusion effects being allowed for separately. The formulation assumes a spherical detector and calculations are made for models having the same volume as two standard phosphors (10 cm x8 cm and 5 cm x 4.5 cm) in the energy band 0.5 to 1.5 MeV. The parameters are the detector radius and, at energy E 0 , the absorption coefficients in the various media for gamma rays together with the 'peak/total' ratio in the detector. The fact that this latter factor, which varies with each trajectory, cannot be obtained with accuracy, constitutes the main limitation of the formulation. The comparison with experimental results obtained with a 10 cm x 8 cm phosphor at the C.F.R. (Centre des Faibles Radioactivites, Gif-sur-Yvette) and with various data indicates an error of about +-5% for a point source at contact and -30% for a homogeneously distributed source in an infinite medium. This latter value may be interpreted as a superiority of the spherical shape over the cylinder (used in practice), for detectors operating in infinite media. Calculations are made without allowing for the Compton effect, which is found to give an approximate correction of +5% in water for a band width of 10 keV in the MeV region. Finally, the shape of the detecting probe around the detector is shown to be indifferent in the assumption of a constant peak/total ratio [fr

  5. 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)

  6. Calculation of absorbed dose and biological effectiveness from photonuclear reactions in a bremsstrahlung beam of end point 50 MeV.

    Science.gov (United States)

    Gudowska, I; Brahme, A; Andreo, P; Gudowski, W; Kierkegaard, J

    1999-09-01

    The absorbed dose due to photonuclear reactions in soft tissue, lung, breast, adipose tissue and cortical bone has been evaluated for a scanned bremsstrahlung beam of end point 50 MeV from a racetrack accelerator. The Monte Carlo code MCNP4B was used to determine the photon source spectrum from the bremsstrahlung target and to simulate the transport of photons through the treatment head and the patient. Photonuclear particle production in tissue was calculated numerically using the energy distributions of photons derived from the Monte Carlo simulations. The transport of photoneutrons in the patient and the photoneutron absorbed dose to tissue were determined using MCNP4B; the absorbed dose due to charged photonuclear particles was calculated numerically assuming total energy absorption in tissue voxels of 1 cm3. The photonuclear absorbed dose to soft tissue, lung, breast and adipose tissue is about (0.11-0.12)+/-0.05% of the maximum photon dose at a depth of 5.5 cm. The absorbed dose to cortical bone is about 45% larger than that to soft tissue. If the contributions from all photoparticles (n, p, 3He and 4He particles and recoils of the residual nuclei) produced in the soft tissue and the accelerator, and from positron radiation and gammas due to induced radioactivity and excited states of the nuclei, are taken into account the total photonuclear absorbed dose delivered to soft tissue is about 0.15+/-0.08% of the maximum photon dose. It has been estimated that the RBE of the photon beam of 50 MV acceleration potential is approximately 2% higher than that of conventional 60Co radiation.

  7. Calculation of absorbed dose and biological effectiveness from photonuclear reactions in a bremsstrahlung beam of end point 50 MeV

    International Nuclear Information System (INIS)

    Gudowska, I.; Brahme, A.; Andreo, P.; Gudowski, W.; Kierkegaard, J.

    1999-01-01

    The absorbed dose due to photonuclear reactions in soft tissue, lung, breast, adipose tissue and cortical bone has been evaluated for a scanned bremsstrahlung beam of end point 50 MeV from a racetrack accelerator. The Monte Carlo code MCNP4B was used to determine the photon source spectrum from the bremsstrahlung target and to simulate the transport of photons through the treatment head and the patient. Photonuclear particle production in tissue was calculated numerically using the energy distributions of photons derived from the Monte Carlo simulations. The transport of photoneutrons in the patient and the photoneutron absorbed dose to tissue were determined using MCNP4B; the absorbed dose due to charged photonuclear particles was calculated numerically assuming total energy absorption in tissue voxels of 1 cm 3 . The photonuclear absorbed dose to soft tissue, lung, breast and adipose tissue is about (0.11-0.12)±0.05% of the maximum photon dose at a depth of 5.5 cm. The absorbed dose to cortical bone is about 45% larger than that to soft tissue. If the contributions from all photoparticles (n, p, 3 He and 4 He particles and recoils of the residual nuclei) produced in the soft tissue and the accelerator, and from positron radiation and gammas due to induced radioactivity and excited states of the nuclei, are taken into account the total photonuclear absorbed dose delivered to soft tissue is about 0.15±0.08% of the maximum photon dose. It has been estimated that the RBE of the photon beam of 50 MV acceleration potential is approximately 2% higher than that of conventional 60 Co radiation. (author)

  8. Methodology for calibration of ionization chambers for X-ray of low energy in absorbed dose to water

    International Nuclear Information System (INIS)

    Oliveira, C.T.; Vivolo, V.; Potiens, M.P.A.

    2015-01-01

    The beams of low energy X-ray (10 to 150 kV) are used in several places in the world to treat a wide variety of surface disorders, and between these malignancies. As in Brazil, at this moment, there is no calibration laboratory providing the control service or calibration of parallel plate ionization chambers, the aim of this project was to establish a methodology for calibration of this kind of ionization chambers at low energy X-ray beams in terms of absorbed dose to water using simulators in the LCI. (author)

  9. Development of a TPC for energy and fluence references in low energies neutronic fields (from 8 keV to 5 MeV)

    International Nuclear Information System (INIS)

    Maire, Donovan

    2015-01-01

    In order to judge the measurement reliability, metrology requires to measure quantities with their uncertainties, in relation to a reference through a documented and unbroken chain of calibrations. In neutron radiation field, instrument response has to be known as a function of the neutron energy. Then detector calibrations are required using reference neutron fields. In France, primary reference neutron fields are held by the LNE-IRSN, at the Laboratory for Neutron Metrology and Dosimetry (LMDN). In order to improve reference neutron field characterization, the LNE-IRSN MIMAC μTPC has been developed. This detector is a Time Projection Chamber (TPC), using a gas at low pressure (30 mbar abs. to 1 bar abs.). Nuclear recoils are generated by neutron elastic scattering onto gas atoms. By measuring the nuclear recoil energy and scattering angle, the μTPC detector is able to measure the energy distribution of the neutron fluence between 8 keV and 5 MeV. The main challenge was to perform accurate spectrometry of neutron fields in the keV range, following a primary procedure. First of all, a metrological approach was followed in order to master every physical process taking part in the neutron detection. This approach led to develop the direct and inverse models, representing the detector response function and its inverse function respectively. Using this detailed characterization, the energy distribution of the neutron fluence has been measured for a continuous neutron field of 27 keV. The reconstructed energy is 28,2 ± 4,5 keV, the difference between μTPC integral fluence measurement and other measurement methods is less than 6%. The LNE-IRSN MIMAC μTPC system becomes the only one system able to measure simultaneously energy and fluence at energies lower than 100 keV, following a primary procedure. The project goal is then reached. These measurements at energies lower than 100 keV shows also a non-linearity between the ionization charge and the ion kinetic energy

  10. 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

  11. Coastal dune dynamics in response to excavated foredune notches

    Science.gov (United States)

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

    2018-04-01

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

  12. Study on Ballistic Absorbing Energy Character of High Performance Polyethylene Needle Felt

    Science.gov (United States)

    Kailiang, Zhu; Jianqiao, Fu

    2017-11-01

    The ballistic performance of polyethylene needle felt is tested and the failure morphology after test is also observed. The results showed that when the non-dimensionally non-stressed fibers in polyethylene needles are subjected to high-speed projectile, secondary movement such as stretching and twisting occurs first. This secondary movement is very full, it is the main way of ballistic absorbing energy of the polyethylene needle felt which can avoid the polyethylene fiber short-term rapid heating-up and destroyed. Analysis results show that under normal temperature and humidity conditions, the V50 of 6-layer forded polyethylene needle felt sample is 250m/s. At (450 ± 50) m/s speed range of the target missile, the mean value of the penetrative specific energy absorption for 3-layer forded polyethylene needle felt anti-1.1g simulated projectiles (tapered column) reaches 24.1J·m2/kg.

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  14. 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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  16. Dynamic tuning of optical absorbers for accelerated solar-thermal energy storage.

    Science.gov (United States)

    Wang, Zhongyong; Tong, Zhen; Ye, Qinxian; Hu, Hang; Nie, Xiao; Yan, Chen; Shang, Wen; Song, Chengyi; Wu, Jianbo; Wang, Jun; Bao, Hua; Tao, Peng; Deng, Tao

    2017-11-14

    Currently, solar-thermal energy storage within phase-change materials relies on adding high thermal-conductivity fillers to improve the thermal-diffusion-based charging rate, which often leads to limited enhancement of charging speed and sacrificed energy storage capacity. Here we report the exploration of a magnetically enhanced photon-transport-based charging approach, which enables the dynamic tuning of the distribution of optical absorbers dispersed within phase-change materials, to simultaneously achieve fast charging rates, large phase-change enthalpy, and high solar-thermal energy conversion efficiency. Compared with conventional thermal charging, the optical charging strategy improves the charging rate by more than 270% and triples the amount of overall stored thermal energy. This superior performance results from the distinct step-by-step photon-transport charging mechanism and the increased latent heat storage through magnetic manipulation of the dynamic distribution of optical absorbers.

  17. Calibration of personnel monitors by exposure to gamma radiation with energies up to 9 MeV

    International Nuclear Information System (INIS)

    Leao, J.L.B.; Cunha, P.G. da; Diz, R.; Oberhofer, M.

    Occupational exposure with photons of high energy (higher than those from 60 Co) might occur from nuclear reactors and accelerators. Radiation monitors for absorbed dose determination, however, often do not have a wall thickness sufficient to establish electronical equilibrium in that energy range. Using calibration factors determined for lower energies (calibration factors for 60 Co radiation) might cause a significant underestimation of the soft tissue absorbed dose. The calibration factor of the personnel monitors of the Eberline Instrument Co.based on TL dosimeters of LiF is reported. This monitor was calibrated with 9 MeV photons produced by thermal neutrons capture in a Nitarget, at an absorbed dose rate of 125 rads/h at the C.E.N. in France. The results are compared with the corresponding calibration factors for different energies up to 60 Co radiation determined in the IRD (Instituto de Radioprotecao e Dosimetria Rio de Janeiro). (Author) [pt

  18. Experimental Study of an SWH System with V-Shaped Plate

    Directory of Open Access Journals (Sweden)

    Jalaluddin

    2016-05-01

    Full Text Available Solar energy is known as an environmentally friendly energy source with a wide range of applications. This energy can be utilized in various applications such as domestic and industrial water heating using solar water heating (SWH systems. The thermal performance of an SWH system using a V-shaped absorber plate is presented in this study. Two SWH systems with different absorber plates, i.e. a flat-plate and a V-shaped plate, have been investigated experimentally. First, the absorptivity of the absorber plates was calculated analytically. The optimum V-shaped configuration with angle at β = 21° (V-shaped dimensions t = 4 cm and l = 4 cm was determined from various V-shaped plate absorbers based on their absorptivity and applied in the experimental study. Two SWH systems were installed and tested at a low flowrate of 0.5 L/min and at a high flowrate of 2 L/min. The results showed that the SWH system with V-shaped plate absorber had a 3.6-4.4% better performance compared with that of the system with flat-plate absorber.

  19. System for determining absorbed dose and its distribution for high-energy electron radiation

    International Nuclear Information System (INIS)

    Hegewald, H.; Wulff, W.

    1977-01-01

    Taking into account the polarization effect, the dose determination for high-energy electron radiation from particle accelerators depends on the knowledge of the energy dependence of the mass stopping power. Results obtained with thermoluminescent dosemeters agree with theoretical values. For absorbed dose measurements the primary energy of electron radiation has been determined by nuclear photoreactions, and the calculation of the absorbed dose from charge measurements by means of the mass stopping power is described. Thus the calibration of ionization chambers for high-energy electron radiation by absolute measurements with the Faraday cage and chemical dosemeters has become possible. (author)

  20. 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.

  1. 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.

  2. Design considerations for application of metallic honeycomb as an energy absorber

    International Nuclear Information System (INIS)

    Lee, W.H.; Roemer, R.E.

    1980-01-01

    Design for postulated accidents in nuclear power plants often requires mitigation of impact to safety-related structures. Plastically designed, energy absorbing mechanisms are often used in the design of such mitigating structures. Metallic honeycomb is the most efficient, practical, energy-absorbing material currently in use. Recent tests indicate that its use in this application, however, presents some unique design and fabrication problems. The paper presents the results of static and dynamic crush tests concerned with the effect of impact velocity, material properties, cell density, loading configuration, and overall pad geometry. Specific design recommendations are made in each area, and suggestions are provided to improve fabrication techniques and minimize subsequent problems

  3. Absorbed fractions for alpha particles in ellipsoidal volumes

    International Nuclear Information System (INIS)

    Amato, Ernesto; Baldari, Sergio; Italiano, Antonio

    2013-01-01

    Internal dosimetry of alpha particles is gaining attention due to the increasing applications in cancer treatment and also for the assessment of environmental contamination from radionuclides. We developed a Monte Carlo simulation in GEANT4 in order to calculate the absorbed fractions for monoenergetic alpha particles in the energy interval between 0.1 and 10 MeV, uniformly distributed in ellipsoids made of soft tissue. For each volume, we simulated a spherical shape, three oblate and three prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a ‘generalized radius’ was found; and the dependence of the fit parameters on the alpha energy is discussed and fitted by parametric functions. With the proposed formulation, the absorbed fraction for alpha particles in the energy range explored can be calculated for volumes and for ellipsoidal shapes of practical interest. This method can be applied to the evaluation of absorbed fraction from alpha-emitting radionuclides. The contribution to the deposited energy coming from electron and photon emissions can be accounted for exploiting the specific formulations previously introduced. As an example of application, the dosimetry of 213 Bi and its decay chain in ellipsoids is reported. (paper)

  4. The influence of mammographic X-ray spectra on absorbed energy distribution in breast: Monte Carlo simulation studies

    International Nuclear Information System (INIS)

    Delis, H.; Spyrou, G.; Tzanakos, G.; Panayiotakis, G.

    2005-01-01

    A mathematical model, based on Monte Carlo simulation, is proposed for deriving absorbed energy and dose distribution in mammography utilizing a mathematical water-like phantom. The model was validated for its accuracy against experimental and published data. The main factor discriminating absorbed energy distribution characteristics among different mammographic techniques was considered the X-ray spectrum. The absorbed energy distribution inside the phantom was investigated via percentage depth dose and isodose curves. The influence of the factors affecting X-ray spectrum (tube voltage, anode material, filter material and thickness) on absorbed energy distribution was examined. The hardness of the beam, due to increase of tube voltage or filtration, was found to be the major factor affecting absorbed energy distribution inside the phantom. In general, Mo and W anode systems demonstrated superior dosimetric characteristics against those of W-Mo or Rh. The model presented can be used for estimating absolute and relative breast dose values and their spatial distributions

  5. Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5–18 eV) electron interactions with DNA

    Energy Technology Data Exchange (ETDEWEB)

    Rezaee, Mohammad, E-mail: Mohammad.Rezaee@USherbrooke.ca; Hunting, Darel J.; Sanche, Léon [Groupe en Sciences des Radiations, Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4 (Canada)

    2014-07-15

    Purpose: The present study introduces a new method to establish a direct correlation between biologically related physical parameters (i.e., stopping and damaging cross sections, respectively) for an Auger-electron emitting radionuclide decaying within a target molecule (e.g., DNA), so as to evaluate the efficacy of the radionuclide at the molecular level. These parameters can be applied to the dosimetry of Auger electrons and the quantification of their biological effects, which are the main criteria to assess the therapeutic efficacy of Auger-electron emitting radionuclides. Methods: Absorbed dose and stopping cross section for the Auger electrons of 5–18 eV emitted by{sup 125}I within DNA were determined by developing a nanodosimetric model. The molecular damages induced by these Auger electrons were investigated by measuring damaging cross section, including that for the formation of DNA single- and double-strand breaks. Nanoscale films of pure plasmid DNA were prepared via the freeze-drying technique and subsequently irradiated with low-energy electrons at various fluences. The damaging cross sections were determined by employing a molecular survival model to the measured exposure–response curves for induction of DNA strand breaks. Results: For a single decay of{sup 125}I within DNA, the Auger electrons of 5–18 eV deposit the energies of 12.1 and 9.1 eV within a 4.2-nm{sup 3} volume of a hydrated or dry DNA, which results in the absorbed doses of 270 and 210 kGy, respectively. DNA bases have a major contribution to the deposited energies. Ten-electronvolt and high linear energy transfer 100-eV electrons have a similar cross section for the formation of DNA double-strand break, while 100-eV electrons are twice as efficient as 10 eV in the induction of single-strand break. Conclusions: Ultra-low-energy electrons (<18 eV) substantially contribute to the absorbed dose and to the molecular damage from Auger-electron emitting radionuclides; hence, they should

  6. Influence of the electron energy and number of beams on the absorbed dose distributions in radiotherapy of deep seated targets.

    Science.gov (United States)

    Garnica-Garza, H M

    2014-12-01

    With the advent of compact laser-based electron accelerators, there has been some renewed interest on the use of such charged particles for radiotherapy purposes. Traditionally, electrons have been used for the treatment of fairly superficial lesions located at depths of no more than 4cm inside the patient, but lately it has been proposed that by using very high energy electrons, i.e. those with an energy in the order of 200-250MeV it should be possible to safely reach deeper targets. In this paper, we used a realistic patient model coupled with detailed Monte Carlo simulations of the electron transport in such a patient model to examine the characteristics of the resultant absorbed dose distributions as a function of both the electron beam energy as well as the number of beams for a particular type of treatment, namely, a prostate radiotherapy treatment. Each treatment is modeled as consisting of nine, five or three beam ports isocentrically distributed around the patient. An optimization algorithm is then applied to obtain the beam weights in each treatment plan. It is shown that for this particularly challenging case, both excellent target coverage and critical structure sparing can be obtained for energies in the order of 150MeV and for as few as three treatment ports, while significantly reducing the total energy absorbed by the patient with respect to a conventional megavoltage x-ray treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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 Australian Commonwealth standard of measurement for absorbed radiation dose

    International Nuclear Information System (INIS)

    Sherlock, S.L.

    1990-06-01

    This report documents the absorbed dose standard for photon beams in the range from 1 to 25 MeV. Measurements of absorbed dose in graphite irradiated by a beam of cobalt-60 gamma rays from an Atomic Energy of Canada Limited (AECL) E1 Dorado 6 teletherapy unit are reported. The measurements were performed using a graphite calorimeter, which is the primary standard for absorbed dose. The measurements are used to calibrate a working standard ion chamber in terms of absorbed dose in graphite. Details of the methods, results and correction factors applied are given in Appendices. 13 refs., 6 tabs., 6 figs

  9. 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

  10. Development of TES microcalorimeters with Sn absorber for hard x-ray detection

    International Nuclear Information System (INIS)

    Hatakeyama, Shuichi; Ohno, Masashi; Damayanthi, R.M. Thushara; Takahashi, Hiroyuki

    2013-01-01

    Superconducting transition edge sensors (TES) are used for high-resolution X-ray spectroscopy. In this study, we have designed a new TES detector using a superconducting tin (Sn) absorber to detect high energy photons over 100 keV. The Sn absorber is coupled to an Ir/Au super-conducting film which is deposited on an ultra-thin SiN membrane (500 nm thick) with a small amount of epoxy post (Stycast 2850FT) by handling with a flip-chip bonding machine. The 241 Am photoelectron peak, the Sn K α and K β X-ray escape peaks are clearly observed. The measured energy resolution is 320 eV FWHM at 59.5 keV and is better than that of HPGe detector. (author)

  11. 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

  12. 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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population

  14. Performance evaluation and parameter sensitivity of energy-harvesting shock absorbers on different vehicles

    Science.gov (United States)

    Guo, Sijing; Liu, Yilun; Xu, Lin; Guo, Xuexun; Zuo, Lei

    2016-07-01

    Traditional shock absorbers provide favourable ride comfort and road handling by dissipating the suspension vibration energy into heat waste. In order to harvest this dissipated energy and improve the vehicle fuel efficiency, many energy-harvesting shock absorbers (EHSAs) have been proposed in recent years. Among them, two types of EHSAs have attracted much attention. One is a traditional EHSA which converts the oscillatory vibration into bidirectional rotation using rack-pinion, ball-screw or other mechanisms. The other EHSA is equipped with a mechanical motion rectifier (MMR) that transforms the bidirectional vibration into unidirectional rotation. Hereinafter, they are referred to as NonMMR-EHSA and MMR-EHSA, respectively. This paper compares their performances with the corresponding traditional shock absorber by using closed-form analysis and numerical simulations on various types of vehicles, including passenger cars, buses and trucks. Results suggest that MMR-EHSA provides better ride performances than NonMMR-EHSA, and that MMR-EHSA is able to improve both the ride comfort and road handling simultaneously over the traditional shock absorber when installed on light-damped, heavy-duty vehicles. Additionally, the optimal parameters of MMR-EHSA are obtained for ride comfort. The optimal solutions ('Pareto-optimal solutions') are also obtained by considering the trade-off between ride comfort and road handling.

  15. Proton and photon absorbed-dose conversion coefficients for embryo and foetus from top-down irradiation geometry

    International Nuclear Information System (INIS)

    Chen, J.

    2007-01-01

    Absorbed-dose conversion coefficients are calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months when the mother's body is exposed to protons and photons from top-down (TOP) direction. It provides data sets in addition to other standard irradiation geometries published previously. The TOP-irradiation geometry is considered here, because high-energy particles are often peaked from the TOP direction onboard aircraft. The results show that absorbed-doses from high-energy particles could be underestimated significantly if isotropic (ISO) irradiation geometry is assumed. For protons of 100 GeV, absorbed-doses from TOP irradiation are ∼2.3-2.9 times higher than the doses from ISO irradiation for different foetal ages. For 10 GeV photons, foetal doses from TOP irradiation are ∼6.8-12 times higher than the doses from ISO irradiation. The coefficients from TOP-irradiation geometry are given in wide energy ranges, from 100 MeV to 100 GeV for protons and from 50 V to 10 GeV for photons. They can, therefore, be used in various applications whenever exposure from the TOP-irradiation direction is concerned. (authors)

  16. 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.

  17. Energy monitoring device for 1.5-2.4 MeV electron beams

    Energy Technology Data Exchange (ETDEWEB)

    Fuochi, P.G., E-mail: fuochi@isof.cnr.i [CNR-ISOF, Via P. Gobetti 101, I-40129 Bologna (Italy); Lavalle, M.; Martelli, A. [CNR-ISOF, Via P. Gobetti 101, I-40129 Bologna (Italy); Kovacs, A. [Institute of Isotopes, HAS, P.O.Box 77, H-1525 Budapest (Hungary); Mehta, K. [Arbeiterstrandbad Strasse 72, Vienna, A-1210 (Austria); Kuntz, F.; Plumeri, S. [Aerial, Parc d' Innovation Rue Laurent Fries F-67400 Illkirch (France)

    2010-03-11

    An easy-to-use and robust energy monitoring device has been developed for reliable detection of day-to-day small variations in the electron beam energy, a critical parameter for quality control and quality assurance in industrial radiation processing. It has potential for using on-line, thus providing real-time information. Its working principle is based on the measurement of currents, or charges, collected by two aluminium absorbers of specific thicknesses (dependent on the beam energy), insulated from each other and positioned within a faraday cup-style aluminium cage connected to the ground. The device has been extensively tested in the energy range of 4-12 MeV under standard laboratory conditions at Institute of Isotopes and CNR-ISOF using different types of electron accelerators; namely, a TESLA LPR-4 LINAC (3-6 MeV) and a L-band Vickers LINAC (7-12 MeV), respectively. This device has been also tested in high power electron beam radiation processing facilities, one equipped with a 7-MeV LUE-8 linear accelerator used for crosslinking of cables and medical device sterilization, and the other equipped with a 10 MeV Rhodotron TT100 recirculating accelerator used for in-house sterilization of medical devices. In the present work, we have extended the application of this method to still lower energy region, i.e. from 1.5 to 2.4 MeV. Also, we show that such a device is capable of detecting deviation in the beam energy as small as 40 keV.

  18. Energy monitoring device for 1.5-2.4 MeV electron beams

    Science.gov (United States)

    Fuochi, P. G.; Lavalle, M.; Martelli, A.; Kovács, A.; Mehta, K.; Kuntz, F.; Plumeri, S.

    2010-03-01

    An easy-to-use and robust energy monitoring device has been developed for reliable detection of day-to-day small variations in the electron beam energy, a critical parameter for quality control and quality assurance in industrial radiation processing. It has potential for using on-line, thus providing real-time information. Its working principle is based on the measurement of currents, or charges, collected by two aluminium absorbers of specific thicknesses (dependent on the beam energy), insulated from each other and positioned within a faraday cup-style aluminium cage connected to the ground. The device has been extensively tested in the energy range of 4-12 MeV under standard laboratory conditions at Institute of Isotopes and CNR-ISOF using different types of electron accelerators; namely, a TESLA LPR-4 LINAC (3-6 MeV) and a L-band Vickers LINAC (7-12 MeV), respectively. This device has been also tested in high power electron beam radiation processing facilities, one equipped with a 7-MeV LUE-8 linear accelerator used for crosslinking of cables and medical device sterilization, and the other equipped with a 10 MeV Rhodotron TT100 recirculating accelerator used for in-house sterilization of medical devices. In the present work, we have extended the application of this method to still lower energy region, i.e. from 1.5 to 2.4 MeV. Also, we show that such a device is capable of detecting deviation in the beam energy as small as 40 keV.

  19. Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

    Science.gov (United States)

    Takada, Masashi; Kosako, Kazuaki; Oishi, Koji; Nakamura, Takashi; Sato, Kouichi; Kamiyama, Takashi; Kiyanagi, Yoshiaki

    2013-03-01

    Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

  20. 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.

  1. High energy model for irregular absorbing particles

    International Nuclear Information System (INIS)

    Chiappetta, Pierre.

    1979-05-01

    In the framework of a high energy formulation of relativistic quantum scattering a model is presented which describes the scattering functions and polarization of irregular absorbing particles, whose dimensions are greater than the incident wavelength. More precisely in the forward direction an amplitude parametrization of eikonal type is defined which generalizes the usual diffraction theory, and in the backward direction a reflective model is used including a shadow function. The model predictions are in good agreement with the scattering measurements off irregular compact and fluffy particles performed by Zerull, Giese and Weiss (1977)

  2. Solar energy utilization by solar cells and superblack absorbers

    Energy Technology Data Exchange (ETDEWEB)

    Bonnet, D; Selders, M

    1975-10-31

    A review is presented of the physical principles responsible for the characteristics of solar cells, with particular reference to Si homojunction and CdS--Cu/sub 2/S thin film devices. Electric power generation from solar cells still appears uncompetitive economically except in special circumstances, but heating from solar energy using selective absorbers with low reemission is more promising.

  3. Evaluation of variation of voltage (kV) absorbed dose in chest CT scans

    International Nuclear Information System (INIS)

    Mendonca, Bruna G.A.; Mourao, Arnaldo P.

    2013-01-01

    Computed tomography (CT) is one of the most important diagnostic techniques images today. The increasing utilization of CT implies a significant increase of population exposure to ionizing radiation. Optimization of practice aims to reduce doses to patients because the image quality is directly related to the diagnosis. You can decrease the amount of dose to the patient, and maintain the quality of the image. There are several parameters that can be manipulated in a CT scan and these parameters can be used to reduce the energy deposited in the patient. Based on this, we analyzed the variation of dose deposited in the lungs, breasts and thyroid, by varying the supply voltage of the tube. Scans of the thorax were performed following the protocol of routine chest with constant and variable current for the same applied voltage. Moreover, a female phantom was used and thermoluminescent dosimeters (TLD-100), model bat, were used to record the specific organ doses. Scans were performed on a GE CT scanner, model 64 Discovery channels. Higher doses were recorded for the voltage of 120 kV with 200 mAs in the lungs (22.46 mGy) and thyroid (32.22 mGy). For scans with automatic mAs, variable between 100 and 440, this same tension contributed to the higher doses. The best examination in terms of the dose that was used with automatic 80 kV mAs, whose lungs and thyroid received lower dose. For the best breast exam was 100 kV. Since the increase in the 80 kV to 100 kV no impact so much the dose deposited in the lungs, it can be concluded that lowering the applied voltage to 100 kV resulted in a reduction in the dose absorbed by the patient. These results can contribute to optimizing scans of the chest computed tomography

  4. Heating nuclei with light ions at GeV incident energies

    International Nuclear Information System (INIS)

    Pollacco, E.C.; Brzychczyk, J.; Volant, C.; Legrain, R.; Nalpas, L.; Bracken, D.S.; Kwiatkowski, K.; Morley, K.B.; Foxford, E.R.; Viola, V.E.; Yoder, N.R.

    1996-03-01

    Hot nuclei are studied, where through an appropriate choice of incident channel and event selection, dynamical effects are attenuated and multifragmentation is limited. Three preparatory results are discussed, the 3 He(1.8 GeV) + nat Ag can be described using and intranuclear cascade, INC, model; through a suitable selection of events a limit of the excitation energy that a nucleus can absorb without breaking into large pieces is given, it is shown, that corresponding alpha decay is consistent with an, evaporative process. (K.A.)

  5. 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...

  6. Gyroscopic power take-off wave energy point absorber in irregular sea states

    DEFF Research Database (Denmark)

    Zhang, Zili; Chen, Bei; Nielsen, Søren R.K.

    2017-01-01

    Highlights •A GyroPTO wave energy point absorber with magnetic coupling mechanism is proposed. •A 4DOF nonlinear model of the GyroPTO absorber has been derived. •Rational approximations are performed on the radiation damping moments. •Synchronization of the device is more easily maintained...... in narrow-banded sea waves. •The generator gain and the magnetic coupling constant influence the performance of the device....

  7. Experimental and Numerical Analysis of Notched Composites Under Tension Loading

    Science.gov (United States)

    Aidi, Bilel; Case, Scott W.

    2015-12-01

    Experimental quasi-static tests were performed on center notched carbon fiber reinforced polymer (CFRP) composites having different stacking sequences made of G40-600/5245C prepreg. The three-dimensional Digital Image Correlation (DIC) technique was used during quasi-static tests conducted on quasi-isotropic notched samples to obtain the distribution of strains as a function of applied stress. A finite element model was built within Abaqus to predict the notched strength and the strain profiles for comparison with measured results. A user-material subroutine using the multi-continuum theory (MCT) as a failure initiation criterion and an energy-based damage evolution law as implemented by Autodesk Simulation Composite Analysis (ASCA) was used to conduct a quantitative comparison of strain components predicted by the analysis and obtained in the experiments. Good agreement between experimental data and numerical analyses results are observed. Modal analysis was carried out to investigate the effect of static damage on the dominant frequencies of the notched structure using the resulted degraded material elements. The first in-plane mode was found to be a good candidate for tracking the level of damage.

  8. Shock absorber

    International Nuclear Information System (INIS)

    Housman, J.J.

    1978-01-01

    A shock absorber is described for use in a hostile environment at the end of a blind passage for absorbing impact loads. The shock absorber includes at least one element which occupies the passage and which is comprised of a porous brittle material which is substantially non-degradable in the hostile environment. A void volume is provided in the element to enable the element to absorb a predetermined level of energy upon being crushed due to impact loading

  9. Genome-wide identification and characterization of Notch transcription complex-binding sequence paired sites in leukemia cells

    Science.gov (United States)

    Severson, Eric; Arnett, Kelly L.; Wang, Hongfang; Zang, Chongzhi; Taing, Len; Liu, Hudan; Pear, Warren S.; Liu, X. Shirley; Blacklow, Stephen C.; Aster, Jon C.

    2018-01-01

    Notch transcription complexes (NTCs) drive target gene expression by binding to two distinct types of genomic response elements, NTC monomer-binding sites and sequence-paired sites (SPSs) that bind NTC dimers. SPSs are conserved and are linked to the Notch-responsiveness of a few genes, but their overall contribution to Notch-dependent gene regulation is unknown. To address this issue, we determined the DNA sequence requirements for NTC dimerization using a fluorescence resonance energy transfer (FRET) assay, and applied insights from these in vitro studies to Notch-“addicted” leukemia cells. We find that SPSs contribute to the regulation of approximately a third of direct Notch target genes. While originally described in promoters, SPSs are present mainly in long-range enhancers, including an enhancer containing a newly described SPS that regulates HES5. Our work provides a general method for identifying sequence-paired sites in genome-wide data sets and highlights the widespread role of NTC dimerization in Notch-transformed leukemia cells. PMID:28465412

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

    Directory of Open Access Journals (Sweden)

    He Meng

    Full Text Available Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL is the best understood cause of dominantly inherited stroke and results from NOTCH3 mutations that lead to NOTCH3 protein accumulation and selective arterial smooth muscle degeneration. Previous studies show that NOTCH3 protein forms multimers. Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4. R90C and C49Y mutant NOTCH3 form complexes which are more resistant to detergents than wild type NOTCH3 complexes. Using quantitative NOTCH3-luciferase clearance assays, we found significant inhibition of mutant NOTCH3 clearance. In coculture assays of NOTCH function, overexpressed wild type and mutant NOTCH3 significantly repressed NOTCH-regulated smooth muscle transcripts and potently impaired the activity of three independent smooth muscle promoters. Wildtype and R90C recombinant NOTCH3 proteins applied to cell cultures also blocked canonical Notch fuction. We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells.

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

    Lifescience Database Archive (English)

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

  12. Evaluations of the criterion for lateral expansion of steels for nuclear components

    International Nuclear Information System (INIS)

    Susukida, H.; Satoh, M.; Fukuhara, A.

    1980-01-01

    The Charpy V notch impact tests were performed on Japanese made ferritic steels for nuclear components and their lateral expansions were investigated. The correlations of lateral expansion and absorbed energy with yield strength, and the correlation between lateral expansion and fracture toughness were also studied. The correlation at each lateral expansion level between absorbed energy and yield strength almost agreed with that published by the US PVRC. It was confirmed that lateral expansion could be used as a criterion for the toughness of the steels corresponding to changes in their yield strength, and that the lateral expansion criterion adopted in the ASME Code Section III was appropriate. Further, the correlation between fracture toughness and lateral expansion and that between fracture toughness and absorbed energy, were evaluated, and respective equations of correlation were proposed. (author)

  13. Diamond detector in absorbed dose measurements in high-energy linear accelerator photon and electron beams.

    Science.gov (United States)

    Ravichandran, Ramamoorthy; Binukumar, John Pichy; Al Amri, Iqbal; Davis, Cheriyathmanjiyil Antony

    2016-03-08

    Diamond detectors (DD) are preferred in small field dosimetry of radiation beams because of small dose profile penumbras, better spatial resolution, and tissue-equivalent properties. We investigated a commercially available 'microdiamond' detector in realizing absorbed dose from first principles. A microdiamond detector, type TM 60019 with tandem electrometer is used to measure absorbed doses in water, nylon, and PMMA phantoms. With sensitive volume 0.004 mm3, radius 1.1mm, thickness 1 x10(-3) mm, the nominal response is 1 nC/Gy. It is assumed that the diamond detector could collect total electric charge (nC) developed during irradiation at 0 V bias. We found that dose rate effect is less than 0.7% for changing dose rate by 500 MU/min. The reproducibility in obtaining readings with diamond detector is found to be ± 0.17% (1 SD) (n = 11). The measured absorbed doses for 6 MV and 15 MV photons arrived at using mass energy absorption coefficients and stop-ping power ratios compared well with Nd, water calibrated ion chamber measured absorbed doses within 3% in water, PMMA, and nylon media. The calibration factor obtained for diamond detector confirmed response variation is due to sensitivity due to difference in manufacturing process. For electron beams, we had to apply ratio of electron densities of water to carbon. Our results qualify diamond dosimeter as a transfer standard, based on long-term stability and reproducibility. Based on micro-dimensions, we recommend these detectors for pretreatment dose verifications in small field irradiations like stereotactic treatments with image guidance.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  15. Effect of low-Z absorber's thickness on gamma-ray shielding parameters

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Kulwinder Singh, E-mail: ksmann6268@gmail.com [Department of Applied Sciences, Punjab Technical University, Kapurthala 144601 (India); Department of Physics, D.A.V. College, Bathinda 151001, Punjab (India); Heer, Manmohan Singh [Department of Physics, Kanya Maha Vidyalaya, Jalandhar 144001 (India); Rani, Asha [Department of Applied Sciences, Ferozpur College of Engineering and Technology, Ferozshah, Ferozpur 142052 (India)

    2015-10-11

    Gamma ray shielding behaviour of any material can be studied by various interaction parameters such as total mass attenuation coefficient (μ{sub m}); half value layer (HVL); tenth value layer (TVL); effective atomic number (Z{sub eff}), electron density (N{sub el}), effective atomic weight (A{sub eff}) and buildup factor. For gamma rays, the accurate measurements of μ{sub m} (cm{sup 2} g{sup −1}) theoretically require perfect narrow beam irradiation geometry. However, the practical geometries used for the experimental investigations deviate from perfect-narrowness thereby the multiple scattered photons cause systematic errors in the measured values of μ{sub m}. Present investigation is an attempt to find the optimum value of absorber thickness (low-Z) for which these errors are insignificant and acceptable. Both experimental and theoretical calculations have been performed to investigate the effect of absorber's thickness on μ{sub m} of six low-Z (10energies 661.66 keV, 1173.24 keV and 1332.50 keV. A computer program (GRIC2-toolkit) was designed for theoretical evaluation of shielding parameters of any material. Good agreement of theoretical and measured values of μ{sub m} was observed for all absorbers with thickness ≤0.5 mean free paths, thus considered it as optimum thickness for low-Z materials in the selected energy range. White cement was found to possess maximum shielding effectiveness for the selected gamma rays. - Highlights: • Optimum thickness value is 0.5 mfp for low-Z absorbers in energy range 662–1332 keV. • For accurate measurement of μ{sub m} absorber's thickness should be ≤optimum thickness. • GRIC2-toolkit is useful for γ-ray shielding analysis of composite materials.

  16. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

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

    Science.gov (United States)

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

    2011-01-01

    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  19. Notch Signaling: Piercing a Harness of Simplicity

    NARCIS (Netherlands)

    Helbig, Christina; Amsen, Derk

    2015-01-01

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

  20. 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.

  1. Study of the yield of the Fricke dosimetry for electron energies from 2 to 90 MeV

    International Nuclear Information System (INIS)

    Berkvens, I.P.

    1988-01-01

    The chemical yield for the ferrous sulphate dosimeters was determined for 60 Co-γ radiation and for electron beams of mean energies in the points of measurements, between 2.7 and about 9 MeV. As references, absolute determinations of absorbed dose based on calorimetric measurements, were used. The irradiation geometry for the ferrous sulphate dosimeter differ always due to technical reasons somewhat from that for the absorber of the calorimeter. The investigators took this difference into account. Perturbation correction factors that correct for the difference in electron scattering in the air gaps around the absorber of the calorimeter and in the graphite, were computed with the Monte Carlo method. Also the ''reference volume method'' recently introduced by the ICRU (report No.35), was applied to correct for the introduction of a ferrous sulphate dosimeter in a graphite phantom. This correction is necessary as the electrons are stopped and scattered in a different way in graphite and water. The results indicated that there is no energy dependence of the chemical yield (G-value) of the dosimeter in the energy range 2.7 to about 9 MeV. A mean G-value of 1,584 (± 0.006) μ mol/J was obtained. For 60 Co-γ a G-value of 1.601 μ mol/J was determined. However, this difference might not be real but due to the present uncertainty in the stopping-power ratios graphite to water. These ratios are thus made use of to determine the G-value from measurements of the absorbed dose to graphite. Previous investigations, by the group from Gent, indicated a small increase of the G-value with the electron energy. These more accurate determinations thus instead indicate a constant G-value. Refs, figs, tabs

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

    Directory of Open Access Journals (Sweden)

    Thomas Donaldson

    2015-08-01

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

  3. Control of base-excited dynamical systems through piezoelectric energy harvesting absorber

    Science.gov (United States)

    Abdelmoula, H.; Dai, H. L.; Abdelkefi, A.; Wang, L.

    2017-09-01

    The spring-mass absorber usually offers a good control to dynamical systems under direct base excitations for a specific value of the excitation frequency. As the vibrational energy of a primary dynamical system is transferred to the absorber, it gets dissipated. In this study, this energy is no longer dissipated but converted to available electrical power by designing efficient energy harvesters. A novel design of a piezoelectric beam installed inside an elastically-mounted dynamical system undergoing base excitations is considered. A design is carried out in order to determine the properties and dimensions of the energy harvester with the constraint of simultaneously decreasing the oscillating amplitudes of the primary dynamical system and increasing the harvested power of the energy harvesting absorber. An analytical model for the coupled system is constructed using Euler-Lagrange principle and Galerkin discretization. Different strategies for controlling the primary structure displacement and enhancing the harvested power as functions of the electrical load resistance and thickness of the beam substrate are performed. The linear polynomial approximation of the system’s key parameters as a function of the beam’s substrate thickness is first carried out. Then, the gradient method is applied to determine the adequate values of the electrical load resistance and thickness of the substrate under the constraints of minimizing the amplitudes of the primary structure or maximizing the levels of the harvested power. After that, an iterative strategy is considered in order to simultaneously minimize the amplitudes of the primary structure and maximize the levels of the harvested power as functions of the thickness of the substrate and electrical load resistance. In addition to harmonic excitations, the coupled system subjected to a white noise is explored. Through this analysis, the load resistance and thickness of the substrate of the piezoelectric energy harvester

  4. Study of absorbed dose distribution to high energy electron beams

    International Nuclear Information System (INIS)

    Cecatti, E.R.

    1983-01-01

    The depth absorbed dose distribution by electron beams was studied. The influence of the beam energy, the energy spread, field size and design characteristics of the accelerator was relieved. Three accelerators with different scattering and collimation systems were studied leading todifferent depth dose distributions. A theoretical model was constructed in order to explain the increase in the depth dose in the build-up region with the increase of the energy. The model utilizes a three-dimensional formalism based on the Fermi-Eyges multiple scattering theory, with the introduction of modifications that takes into account the criation of secondary electrons. (Author) [pt

  5. Fluence-to-Absorbed Dose Conversion Coefficients for Use in Radiological Protection of Embryo and Foetus Against External Exposure to Muons from 20MeV to 50GeV

    International Nuclear Information System (INIS)

    Chen Jing

    2008-01-01

    This study used the Monte-Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to external muon fields. Monoenergetic muons ranging from 20 MeV to 50 GeV were considered. The irradiation geometries include anteroposterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT), isotropic (ISO), and top-down (TOP). At each of these irradiation geometries, absorbed doses to the foetal body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months, respectively. Muon fluence-to-absorbed-dose conversion coefficients were derived for the four prenatal ages. Since such conversion coefficients are yet unknown, the results presented here fill a data gap

  6. Absorbed Dose Distributions in Small Copper Wire Insulation due to Multiple-Sided Irradiations by 0.4 MeV Electrons

    DEFF Research Database (Denmark)

    Miller, Arne; McLaughlin, W. L.; Pedersen, Walther Batsberg

    1979-01-01

    When scanned electron beams are used to crosslink polymeric insulation of wire and cable, an important goal is to achieve optimum uniformity of absorbed dose distributions. Accurate measurements of dose distributions in a plastic dosimeter simulating a typical insulating material (polyethylene......) surrounding a copper wire core show that equal irradiations from as few as four sides give approximately isotropy and satisfactorily uniform energy depositions around the wire circumference. Electron beams of 0.4 MeV maximum energy were used to irradiate wires having a copper core of 1.0 mm dia....... and insulation thicknesses between 0.4 and 0.8 mm. The plastic dosimeter simulating polyethylene insulations was a thin radiochromic polyvinyl butyral film wrapped several times around the copper wire, such that when unwrapped and analyzed optically on a scanning microspectrophotometer, high-resolution radial...

  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. 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.

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

    Science.gov (United States)

    Lina, Ioan A; Lauer, Amanda M

    2013-04-01

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

  11. Absorbing phase transitions in deterministic fixed-energy sandpile models

    Science.gov (United States)

    Park, Su-Chan

    2018-03-01

    We investigate the origin of the difference, which was noticed by Fey et al. [Phys. Rev. Lett. 104, 145703 (2010), 10.1103/PhysRevLett.104.145703], between the steady state density of an Abelian sandpile model (ASM) and the transition point of its corresponding deterministic fixed-energy sandpile model (DFES). Being deterministic, the configuration space of a DFES can be divided into two disjoint classes such that every configuration in one class should evolve into one of absorbing states, whereas no configurations in the other class can reach an absorbing state. Since the two classes are separated in terms of toppling dynamics, the system can be made to exhibit an absorbing phase transition (APT) at various points that depend on the initial probability distribution of the configurations. Furthermore, we show that in general the transition point also depends on whether an infinite-size limit is taken before or after the infinite-time limit. To demonstrate, we numerically study the two-dimensional DFES with Bak-Tang-Wiesenfeld toppling rule (BTW-FES). We confirm that there are indeed many thresholds. Nonetheless, the critical phenomena at various transition points are found to be universal. We furthermore discuss a microscopic absorbing phase transition, or a so-called spreading dynamics, of the BTW-FES, to find that the phase transition in this setting is related to the dynamical isotropic percolation process rather than self-organized criticality. In particular, we argue that choosing recurrent configurations of the corresponding ASM as an initial configuration does not allow for a nontrivial APT in the DFES.

  12. 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.

  13. Absorbed-dose beam quality conversion factors for cylindrical chambers in high energy photon beams.

    Science.gov (United States)

    Seuntjens, J P; Ross, C K; Shortt, K R; Rogers, D W

    2000-12-01

    Recent working groups of the AAPM [Almond et al., Med. Phys. 26, 1847 (1999)] and the IAEA (Andreo et al., Draft V.7 of "An International Code of Practice for Dosimetry based on Standards of Absorbed Dose to Water," IAEA, 2000) have described guidelines to base reference dosimetry of high energy photon beams on absorbed dose to water standards. In these protocols use is made of the absorbed-dose beam quality conversion factor, kQ which scales an absorbed-dose calibration factor at the reference quality 60Co to a quality Q, and which is calculated based on state-of-the-art ion chamber theory and data. In this paper we present the measurement and analysis of beam quality conversion factors kQ for cylindrical chambers in high-energy photon beams. At least three chambers of six different types were calibrated against the Canadian primary standard for absorbed dose based on a sealed water calorimeter at 60Co [TPR10(20)=0.572, %dd(10)x=58.4], 10 MV [TPR10(20)=0.682, %dd(10)x=69.6), 20 MV (TPR10(20)=0.758, %dd(10)x= 80.5] and 30 MV [TPR10(20) = 0.794, %dd(10)x= 88.4]. The uncertainty on the calorimetric determination of kQ for a single chamber is typically 0.36% and the overall 1sigma uncertainty on a set of chambers of the same type is typically 0.45%. The maximum deviation between a measured kQ and the TG-51 protocol value is 0.8%. The overall rms deviation between measurement and the TG-51 values, based on 20 chambers at the three energies, is 0.41%. When the effect of a 1 mm PMMA waterproofing sleeve is taken into account in the calculations, the maximum deviation is 1.1% and the overall rms deviation between measurement and calculation 0.48%. When the beam is specified using TPR10(20), and measurements are compared with kQ values calculated using the version of TG-21 with corrected formalism and data, differences are up to 1.6% when no sleeve corrections are taken into account. For the NE2571 and the NE2611A chamber types, for which the most literature data are

  14. 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

  15. Radiation-absorbed doses and energy imparted from panoramic tomography, cephalometric radiography, and occlusal film radiography in children

    International Nuclear Information System (INIS)

    Bankvall, G.; Hakansson, H.A.

    1982-01-01

    The absorbed doses and energy imparted from radiographic examinations of children, using panoramic tomography (PTG), cephalometric radiography (CPR), and maxillary frontal occlusal overview (FOO), were examined. The absorbed dose at various sites of the head were measured with TL dosimeters in a phantom and in patients. The energy imparted was calculated from measurements of areal exposure using a planparallel ionization chamber. The maximum absorbed doses for panoramic tomography were located around the lateral rotation center, for cephalometric radiography in the left (tube side) parotid region, and for frontal occlusal radiography in the nose. The absorbed doses in the eyes, thyroid gland, and skin are discussed and compared with previous reports and, for the most part, are found to be in agreement. The mean energy imparted from all three examination methods is 5 mJ with about 57 percent from panoramic, 33 percent from cephalometric, and 10 percent from frontal occlusal examinations. The energy imparted from cephalometric radiography can be reduced to about 10 percent with the use of an improved examination technique, leaving panoramic tomography responsible for contributing about 80 percent of the total energy imparted

  16. Fluence-to-absorbed dose conversion coefficients for use in radiological protection of embryo and foetus against external exposure to protons from 100 MeV to 100 GeV

    International Nuclear Information System (INIS)

    Chen, J.

    2006-01-01

    In the literature, no conversion coefficients are available for use in radiological protection of embryo and foetus against external exposure to protons. This study used the Monte Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to proton fields. Monoenergetic protons ranging from 100 MeV to 100 GeV were considered. The irradiation geometries include antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT) and isotropic (ISO). At each of these standard irradiation geometries, absorbed doses to the foetal brain and body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Proton fluence-to-absorbed dose conversion coefficients were derived for the four prenatal ages. (authors)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-17

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  19. Optimized Latching Control of Floating Point Absorber Wave Energy Converter

    Science.gov (United States)

    Gadodia, Chaitanya; Shandilya, Shubham; Bansal, Hari Om

    2018-03-01

    There is an increasing demand for energy in today’s world. Currently main energy resources are fossil fuels, which will eventually drain out, also the emissions produced from them contribute to global warming. For a sustainable future, these fossil fuels should be replaced with renewable and green energy sources. Sea waves are a gigantic and undiscovered vitality asset. The potential for extricating energy from waves is extensive. To trap this energy, wave energy converters (WEC) are needed. There is a need for increasing the energy output and decreasing the cost requirement of these existing WECs. This paper presents a method which uses prediction as a part of the control scheme to increase the energy efficiency of the floating-point absorber WECs. Kalman Filter is used for estimation, coupled with latching control in regular as well as irregular sea waves. Modelling and Simulation results for the same are also included.

  20. 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

  1. Assessment criteria for assessing energy-absorbing front underrun protection on trucks

    NARCIS (Netherlands)

    Schram, R.; Leneman, F.J.W.; Zweep, C. van der; Wismans, J.S.H.M.; Witteman, W.J.

    2006-01-01

    The objective of this article is to investigate the possibilities to assess (energy-absorbing) front underrun protection (FUP) devices with respect to injuries of the car occupant without using a car and dummy in the test procedure. A large number of different crash configurations are simulated to

  2. Modeling and prediction of extraction profile for microwave-assisted extraction based on absorbed microwave energy.

    Science.gov (United States)

    Chan, Chung-Hung; Yusoff, Rozita; Ngoh, Gek-Cheng

    2013-09-01

    A modeling technique based on absorbed microwave energy was proposed to model microwave-assisted extraction (MAE) of antioxidant compounds from cocoa (Theobroma cacao L.) leaves. By adapting suitable extraction model at the basis of microwave energy absorbed during extraction, the model can be developed to predict extraction profile of MAE at various microwave irradiation power (100-600 W) and solvent loading (100-300 ml). Verification with experimental data confirmed that the prediction was accurate in capturing the extraction profile of MAE (R-square value greater than 0.87). Besides, the predicted yields from the model showed good agreement with the experimental results with less than 10% deviation observed. Furthermore, suitable extraction times to ensure high extraction yield at various MAE conditions can be estimated based on absorbed microwave energy. The estimation is feasible as more than 85% of active compounds can be extracted when compared with the conventional extraction technique. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Thermoluminescent dosemeters for determining the energy absorbed during X-ray radiography of the vertebral column

    International Nuclear Information System (INIS)

    Liebl, R.

    1983-01-01

    The dose and absorbed energy during normal diagnostic X-ray of various sections of the vertebral column were determined with LiF-dosemeters in a phantom. The paper describes a method to be used to determine integral doses from the dose measurements. The energy absorbed for one X-ray picture of the vertebral column is between 5 and 30 mJ. Compared to other diagnostical X-rays the quantity of the energy absorbed during X-ray of the vertebral column is rather high and is only reached by X-rays in the pelvic region. The speculations on the rate of incidence of malignent neoplasms on the basis of diagnostical X-ray of the vertebral column reveal a value of 50 per 60 x 10 6 persons. This value is likely to overestimate the risk, seems, however, to be low in comparison to other risks of every day life (traffic accident, mountainering, etc). (orig./HP) [de

  4. Advances in absorbed dose measurement standards at the australian radiation laboratory

    International Nuclear Information System (INIS)

    Boas, J.F.; Hargrave, N.J.; Huntley, R.B.; Kotler, L.H.; Webb, D.V.; Wise, K.N.

    1996-01-01

    The applications of ionising radiation in the medical and industrial fields require both an accurate knowledge of the amount of ionising radiation absorbed by the medium in question and the capability of relating this to National and International standards. The most useful measure of the amount of radiation is the absorbed dose which is defined as the energy absorbed per unit mass. For radiotherapy, the reference medium is water, even though the measurement of the absorbed dose to water is not straightforward. Two methods are commonly used to provide calibrations in absorbed dose to water. The first is the calibration of the chamber in terms of exposure in a Cobalt-60 beam, followed by the conversion by a protocol into dose to water in this and higher energy beams. The other route is via the use of a graphite calorimeter as a primary standard device, where the conversion from absorbed dose to graphite to absorbed dose in water is performed either by theoretical means making use of cavity ionisation theory, or by experiment where the graphite calorimeter and secondary standard ionisation chamber are placed at scaled distances from the source of the radiation beam (known as the Dose-Ratio method). Extensive measurements have been made at Cobalt-60 at ARL using both the exposure and absorbed dose to graphite routes. Agreement between the ARL measurements and those based on standards maintained by ANSTO and NPL is within ± 0.3%. Absorbed dose measurements have also been performed at ARL with photon beams of nominal energy 16 and 19 MeV obtained from the ARL linac. The validity of the protocols at high photon energies, the validity of the methods used to convert from absorbed dose in graphite to absorbed dose in water and the validity of the indices used to specify the beams are discussed. Brief mention will also be made of the establishment of a calibration facility for neutron monitors at ARL and of progress in the development of ERP dosimetry

  5. Advances in absorbed dose measurement standards at the australian radiation laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Boas, J.F.; Hargrave, N.J.; Huntley, R.B.; Kotler, L.H.; Webb, D.V.; Wise, K.N. [Australian Radiation Laboratory, Yallambie, VIC (Australia)

    1996-12-31

    The applications of ionising radiation in the medical and industrial fields require both an accurate knowledge of the amount of ionising radiation absorbed by the medium in question and the capability of relating this to National and International standards. The most useful measure of the amount of radiation is the absorbed dose which is defined as the energy absorbed per unit mass. For radiotherapy, the reference medium is water, even though the measurement of the absorbed dose to water is not straightforward. Two methods are commonly used to provide calibrations in absorbed dose to water. The first is the calibration of the chamber in terms of exposure in a Cobalt-60 beam, followed by the conversion by a protocol into dose to water in this and higher energy beams. The other route is via the use of a graphite calorimeter as a primary standard device, where the conversion from absorbed dose to graphite to absorbed dose in water is performed either by theoretical means making use of cavity ionisation theory, or by experiment where the graphite calorimeter and secondary standard ionisation chamber are placed at scaled distances from the source of the radiation beam (known as the Dose-Ratio method). Extensive measurements have been made at Cobalt-60 at ARL using both the exposure and absorbed dose to graphite routes. Agreement between the ARL measurements and those based on standards maintained by ANSTO and NPL is within {+-} 0.3%. Absorbed dose measurements have also been performed at ARL with photon beams of nominal energy 16 and 19 MeV obtained from the ARL linac. The validity of the protocols at high photon energies, the validity of the methods used to convert from absorbed dose in graphite to absorbed dose in water and the validity of the indices used to specify the beams are discussed. Brief mention will also be made of the establishment of a calibration facility for neutron monitors at ARL and of progress in the development of ERP dosimetry.

  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. Transition metal atoms absorbed on MoS2/h-BN heterostructure: stable geometries, band structures and magnetic properties.

    Science.gov (United States)

    Wu, Yanbing; Huang, Zongyu; Liu, Huating; He, Chaoyu; Xue, Lin; Qi, Xiang; Zhong, Jianxin

    2018-06-15

    We have studied the stable geometries, band structures and magnetic properties of transition-metal (V, Cr, Mn, Fe, Co and Ni) atoms absorbed on MoS2/h-BN heterostructure systems by first-principles calculations. By comparing the adsorption energies, we find that the adsorbed transition metal (TM) atoms prefer to stay on the top of Mo atoms. The results of the band structure without spin-orbit coupling (SOC) interaction indicate that the Cr-absorbed systems behave in a similar manner to metals, and the Co-absorbed system exhibits a half-metallic state. We also deduce that the V-, Mn-, Fe-absorbed systems are semiconductors with 100% spin polarization at the HOMO level. The Ni-absorbed system is a nonmagnetic semiconductor. In contrast, the Co-absorbed system exhibits metallic state, and the bandgap of V-absorbed system decreases slightly according to the SOC calculations. In addition, the magnetic moments of all the six TM atoms absorbed on the MoS2/h-BN heterostructure systems decrease when compared with those of their free-standing states.

  8. Comparison of iron and tungsten absorber structures for an analog hadron calorimeter

    International Nuclear Information System (INIS)

    Guenter, Clemens

    2015-05-01

    Future electron-positron-collider experiments will require unprecedented jet-energy resolution to complete their physics programs. This can only be achieved with novel approaches to calorimetry. One of these novel approaches is the Particle Flow Algorithm, which uses the best suited sub-detector to measure the energy of the particles produced by the electronpositron collision. The CALICE Collaboration evaluates different read-out technologies for Particle Flow Calorimeters. This thesis describes the comparison of two different absorber materials, iron and tungsten, for the CALICE Analog Hadron Calorimeter. It is described how test-beam data, that have been recorded in the range from 2 GeV to 10 GeV with the Analog Hadron Calorimeter are calibrated, and how samples are selected containing showers from just one particle type. The data are then compared to simulations, and the remaining disagreement between data and simulation is discussed. The validated simulations are then used to decompose the showers into different fractions. These fractions are compared for the two absorber materials to understand the impact of the absorber material choice on the calorimeter performance.

  9. Warm Absorber Diagnostics of AGN Dynamics

    Science.gov (United States)

    Kallman, Timothy

    Warm absorbers and related phenomena are observable manifestations of outflows or winds from active galactic nuclei (AGN) that have great potential value. Understanding AGN outflows is important for explaining the mass budgets of the central accreting black hole, and also for understanding feedback and the apparent co-evolution of black holes and their host galaxies. In the X-ray band warm absorbers are observed as photoelectric absorption and resonance line scattering features in the 0.5-10 keV energy band; the UV band also shows resonance line absorption. Warm absorbers are common in low luminosity AGN and they have been extensively studied observationally. They may play an important role in AGN feedback, regulating the net accretion onto the black hole and providing mechanical energy to the surroundings. However, fundamental properties of the warm absorbers are not known: What is the mechanism which drives the outflow?; what is the gas density in the flow and the geometrical distribution of the outflow?; what is the explanation for the apparent relation between warm absorbers and the surprising quasi-relativistic 'ultrafast outflows' (UFOs)? We propose a focused set of model calculations that are aimed at synthesizing observable properties of warm absorber flows and associated quantities. These will be used to explore various scenarios for warm absorber dynamics in order to answer the questions in the previous paragraph. The guiding principle will be to examine as wide a range as possible of warm absorber driving mechanisms, geometry and other properties, but with as careful consideration as possible to physical consistency. We will build on our previous work, which was a systematic campaign for testing important class of scenarios for driving the outflows. We have developed a set of tools that are unique and well suited for dynamical calculations including radiation in this context. We also have state-of-the-art tools for generating synthetic spectra, which are

  10. 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.)

  11. Estimated fluence-to-absorbed dose conversion coefficients for use in radiological protection of embryo and foetus against external exposure to photons from 50 keV to 10 GeV

    International Nuclear Information System (INIS)

    Chen, J.

    2006-01-01

    In the literature, no conversion coefficients are available for use in radiological protection of the embryo and foetus against external exposure to photons. This study used the Monte-Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to external photon fields. Monoenergetic photons ranging from 50 keV to 10 GeV were considered. The irradiation geometries included antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT), and isotropic (ISO). At each of these standard irradiation geometries, absorbed doses to the foetal brain and body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Photon fluence-to-absorbed-dose conversion coefficients were estimated for the four prenatal ages. (authors)

  12. Calibration of GafChromic EBT3 for absorbed dose measurements in 5 MeV proton beam and 60Co γ-rays

    International Nuclear Information System (INIS)

    Vadrucci, M.; Ronsivalle, C.; Marracino, F.; Montereali, R. M.; Picardi, L.; Piccinini, M.; Vincenti, M. A.; Esposito, G.; De Angelis, C.; Cherubini, R.; Pimpinella, M.

    2015-01-01

    Purpose: To study EBT3 GafChromic film in low-energy protons, and for comparison purposes, in a reference 60 Co beam in order to use it as a calibrated dosimetry system in the proton irradiation facility under construction within the framework of the Oncological Therapy with Protons (TOP)-Intensity Modulated Proton Linear Accelerator for RadioTherapy (IMPLART) Project at ENEA-Frascati, Italy. Methods: EBT3 film samples were irradiated at the Istituto Nazionale di Fisica Nucleare—Laboratori Nazionali di Legnaro, Italy, with a 5 MeV proton beam generated by a 7 MV Van de Graaff CN accelerator. The nominal dose rates used were 2.1 Gy/min and 40 Gy/min. The delivered dose was determined by measuring the particle fluence and the energy spectrum in air with silicon surface barrier detector monitors. A preliminary study of the EBT3 film beam quality dependence in low-energy protons was conducted by passively degrading the beam energy. EBT3 films were also irradiated at ENEA-National Institute of Ionizing Radiation Metrology with gamma radiation produced by a 60 Co source characterized by an absorbed dose to water rate of 0.26 Gy/min as measured by a calibrated Farmer type ionization chamber. EBT3 film calibration curves were determined by means of a set of 40 film pieces irradiated to various doses ranging from 0.5 Gy to 30 Gy absorbed dose to water. An EPSON Expression 11000XL color scanner in transmission mode was used for film analysis. Scanner response stability, intrafilm uniformity, and interfilm reproducibility were verified. Optical absorption spectra measurements were performed on unirradiated and irradiated EBT3 films to choose the most sensitive color channel to the dose range used. Results: EBT3 GafChromic films show an under response up to about 33% for low-energy protons with respect to 60 Co gamma radiation, which is consistent with the linear energy transfer dependence already observed with higher energy protons, and a negligible dose-rate dependence in

  13. SU-F-207-07: Dual-Energy Computed Tomography Detection Limit of Various Radiopaque Contrast Agents That Can Be Infused Within Absorbable Inferior Vena Cava Filters

    Energy Technology Data Exchange (ETDEWEB)

    Melancon, A; Jacobsen, M; Salatan, F; Jones, A; Cody, D; Nute, J; Melancon, M [U.T.M.D Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Absorbable IVC filters are shown to be safe and efficacious in preventing pulmonary embolism. These absorbable filters disappear from the body after their required duration, alleviating costly removal procedures and downstream complications. Monitoring the positioning and integrity of absorbable devices using dual-energy computed tomography (DECT) would improve treatment efficacy. The purpose of this study is to determine the limit of detection and the energy dependence of DECT for various contrast agents that may be infused within the IVC filters including gold nanoparticles (AuNP) having diameters of 2 and 4 nm. Methods: All imaging studies were performed on a GE Discovery CT750 system in Gemstone Spectral Imaging (GSI) mode. Plastic vials containing the contrast agent solutions of water and blood were placed in a water bath, and images were acquired with the GSI-5 preset. The images were reformatted into the coronal plane and 5mm diameter ROIs were placed within each solution on a GE Advantage Workstation. Monoenergetic reconstructions were generated from 40 – 140 keV. Results: Mass attenuation (contrast per unit density) for AuNPs was greater than iron, but less than barium and iodine. Contrast was 10.2 (± 3.6) HU for 4 nm AuNP at 0.72 mg/ml and 12.1 (± 4.2) for 2 nm AuNP at 0.31 mg/ml at 70 keV suggesting reasonable chance of visualization at these concentrations for 70 keV reconstruction. The contrast as a function of CT energy is similar in both water and blood. Iodine is most dependent, followed closely by barium and iron, and trailed by a large margin by the AuNP. This was unexpected given Au’s large atomic number and the predominance of photoelectric effect at low energy. Conclusion: Infusion of IVC filters with AuNP is feasible. Discrimination of AuNP-infused IVC filters from surrounding anatomy warrants further investigation.

  14. Erbium concentration dependent absorbance in tellurite glass

    Energy Technology Data Exchange (ETDEWEB)

    Sazali, E. S., E-mail: mdsupar@utm; Rohani, M. S., E-mail: mdsupar@utm; Sahar, M. R., E-mail: mdsupar@utm; Arifin, R., E-mail: mdsupar@utm; Ghoshal, S. K., E-mail: mdsupar@utm; Hamzah, K., E-mail: mdsupar@utm [Advanced Optical Material Research Group, Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310, Skudai, Johor Bahru, Johor (Malaysia)

    2014-09-25

    Enhancing the optical absorption cross-section in topically important rare earth doped tellurite glasses is challenging for photonic devices. Controlled synthesis and detailed characterizations of the optical properties of these glasses are important for the optimization. The influence of varying concentration of Er{sup 3+} ions on the absorbance characteristics of lead tellurite glasses synthesized via melt-quenching technique are investigated. The UV-Vis absorption spectra exhibits six prominent peaks centered at 490, 526, 652, 800, 982 and 1520 nm ascribed to the transitions in erbium ion from the ground state to the excited states {sup 4}F{sub 7/2}, {sup 2}H{sub 11/2}, {sup 4}F{sub 9/2}, {sup 4}I{sub 9/2}, {sup 2}H{sub 11/2} and {sup 4}I{sub 13/2}, respectively. The results are analyzed by means of optical band gap E{sub g} and Urbach energy E{sub u}. The values of the energy band gap are found decreased from 2.82 to 2.51 eV and the Urbach energy increased from 0.15 to 0.24 eV with the increase of the Er{sub 2}O{sub 3} concentration from 0 to 1.5 mol%. The excellent absorbance of the prepared tellurite glasses makes them suitable for fabricating solid state lasers.

  15. Simulation of a Local Collision of SC Wall Using High Energy Absorbing Steel

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, H. K.; Chung, C. H.; Park, J.; Lee, J. W. [Dankook University, Yongin (Korea, Republic of); Kim, S. Y. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2011-05-15

    Local damage evaluations for nuclear power plant(NPP) design are performed against turbine impact, tornado impact, airplane engine impact, etc., where turbine is a internal source of impact, whereas tornado and airplane engine are external sources of impact. The thickness of NPP wall structure is determined at initial design stage not to be penetrated by local impacts. This study investigated the local damage of NPP substructure against internal turbine impact. Simulation of local collisions of SC wall in NPP structure, which consists of two models: one using general steel and the other using high energy absorbing steel, were performed. The performance of SC wall using ductile high energy absorbing steel can be greatly improved on local collisions when compared with that of general steel

  16. Simulation of a Local Collision of SC Wall Using High Energy Absorbing Steel

    International Nuclear Information System (INIS)

    Yoo, H. K.; Chung, C. H.; Park, J.; Lee, J. W.; Kim, S. Y.

    2011-01-01

    Local damage evaluations for nuclear power plant(NPP) design are performed against turbine impact, tornado impact, airplane engine impact, etc., where turbine is a internal source of impact, whereas tornado and airplane engine are external sources of impact. The thickness of NPP wall structure is determined at initial design stage not to be penetrated by local impacts. This study investigated the local damage of NPP substructure against internal turbine impact. Simulation of local collisions of SC wall in NPP structure, which consists of two models: one using general steel and the other using high energy absorbing steel, were performed. The performance of SC wall using ductile high energy absorbing steel can be greatly improved on local collisions when compared with that of general steel

  17. Optimisation of energy absorbing liner for equestrian helmets. Part II: Functionally graded foam liner

    International Nuclear Information System (INIS)

    Cui, L.; Forero Rueda, M.A.; Gilchrist, M.D.

    2009-01-01

    The energy absorbing liner of safety helmets was optimised using finite element modelling. In this present paper, a functionally graded foam (FGF) liner was modelled, while keeping the average liner density the same as in a corresponding reference single uniform density liner model. Use of a functionally graded foam liner would eliminate issues regarding delamination and crack propagation between interfaces of different density layers which could arise in liners with discrete density variations. As in our companion Part I paper [Forero Rueda MA, Cui L, Gilchrist MD. Optimisation of energy absorbing liner for equestrian helmets. Part I: Layered foam liner. Mater Des [submitted for publication

  18. Wave energy extraction by coupled resonant absorbers.

    Science.gov (United States)

    Evans, D V; Porter, R

    2012-01-28

    In this article, a range of problems and theories will be introduced that will build towards a new wave energy converter (WEC) concept, with the acronym 'ROTA' standing for resonant over-topping absorber. First, classical results for wave power absorption for WECs constrained to operate in a single degree of freedom will be reviewed and the role of resonance in their operation highlighted. Emphasis will then be placed on how the introduction of further resonances can improve power take-off characteristics by extending the range of frequencies over which the efficiency is close to a theoretical maximum. Methods for doing this in different types of WECs will be demonstrated. Coupled resonant absorbers achieve this by connecting a WEC device equipped with its own resonance (determined from a hydrodynamic analysis) to a new system having separate mass/spring/damper characteristics. It is shown that a coupled resonant effect can be realized by inserting a water tank into a WEC, and this idea forms the basis of the ROTA device. In essence, the idea is to exploit the coupling between the natural sloshing frequencies of the water in the internal tank and the natural resonance of a submerged buoyant circular cylinder device that is tethered to the sea floor, allowing a rotary motion about its axis of attachment.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-25

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

  20. An Investigation into Power from Pitch-Surge Point-Absorber Wave Energy Converters.

    OpenAIRE

    Chaplin, R. V.; Aggidis, George A.

    2007-01-01

    There is a worldwide opportunity for clean renewable power. The results from the UK Government's "Marine Energy Challenge" showed that marine energy has the potential to become competitive with other forms of energy. The key to success in this lies in a low lifetime-cost of power as delivered to the user. Pitch-surge point-absorber WECs have the potential to do this with average annual powers of around 2 MW in North Atlantic conditions from relatively small devices that would be economically ...

  1. 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.

  2. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

    Directory of Open Access Journals (Sweden)

    Michael J Kluk

    Full Text Available Fixed, paraffin-embedded (FPE tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1 in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors, but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of

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

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

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

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

    Directory of Open Access Journals (Sweden)

    Pawel K Mazur

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

  5. 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,

  6. 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.

  7. 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.

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

    Science.gov (United States)

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

    2013-10-01

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

  9. Parameters Analysis of Hydraulic-Electrical Energy Regenerative Absorber on Suspension Performance

    Directory of Open Access Journals (Sweden)

    Han Zhang

    2014-05-01

    Full Text Available To recycle the vibration energy of vehicles over rough roads, a hydraulic-electricity energy regenerative suspension (HEERS was designed in the present work, and simulations were performed with focus on its performance. On the basis of the system principle, the mathematical model of hydraulic-electrical energy regenerative absorber (HEERA and two degrees of freedom (DOF suspension dynamic model were constructed. Using the model of HEERA, simulations on force-displacement and force-velocity characteristics were performed with a 1.67 Hz frequency and a sinusoidal input adopted. And then in combination with HEERA model and two DOF suspension models, simulations on the performance of HEERS also were carried out. Finally, the influences of charging pressure and volume of the accumulator, hydraulic motor displacement, orifice area of check valve, and inner diameter of hydraulic pipelines on the performance of HEERA and HEERS were investigated in depth. The simulation results indicated that (i the damping characteristic of HEERA was coincident with the damping characteristics of traditional absorber; (ii the most remarkable influencing factor on the performance of HEERS was the hydraulic motor displacement, followed by orifice area of check valve, inner diameter of pipelines, and charging pressure of accumulator, while the effects of charging volume of accumulator were quite limited.

  10. Absorbed dose optimization in the microplanar beam radiotherapy

    International Nuclear Information System (INIS)

    Company, F.Z.; Jaric, J.; Allen, B.J.

    1996-01-01

    Full text: Recent advances in synchrotron generated X-ray beams with high fluence rate, small divergence and sharply defined microbeam margins permit investigation of the application of an array of closely spaced, parallel or converging microbeams for radiotherapy. The proposed technique takes advantage of the repair mechanism hypothesis of capillary endothelial cells between alternate microbeam zones, which regenerates the lethally irradiated capillaries. Unlike a pencil beam, more accurate dose calculation, beam width and spacing are essential to minimise radiation damage to normal tissue cells outside the target. The absorbed dose between microbeam zones should be kept below the threshold for irreversible radiation damage. Thus the peak-to-valley ratio for the dose distribution should be optimized. The absorbed dose profile depends on the energy of the incident beam and the composition and density of the medium. Using Monte Carlo computations, the radial absorbed dose of single 24 x 24 μm 2 cross-section X-ray beams of different energies in a tissue/lung/tissue phantom was investigated. The results indicated that at 100 keV, closely spaced square cross-sectional microbeams can be applied to the lung. A bundle of parallel 24 μm-wide planar microbeams spaced at 200 μm intervals provides much more irradiation coverage of tissue than is provided by a bundle of parallel, square cross-sectional microbeam, although the former is associated with much smaller Peak (maximum absorbed dose on the beam axis) -to-Valley ( minimum interbeam absorbed dose ) ratios than the latter. In this study the lateral and depth dose of single and multiple microplanar beams with beam dimensions of width 24 μm and 48 μm and height 2-20 cm with energy of 100 keV in a tissue/lung/tissue phantom are investigated. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (2 x 2 cm 2 to 20 x 20 cm 2 square cross section) with a 150 μm 200 μm and

  11. Measurement of charge composition of electron flows with an energy above hundreds MeV in inner radiaion belt

    International Nuclear Information System (INIS)

    Gusev, A.A.; Pugacheva, G.I.

    1990-01-01

    A detector for studying the charge composition of a high-energy electron component of an internal radiation belt when measuring the precipitation of charged particles in the region of Brazil magnetic anomaly is suggested. The detector is a telescope consisting of two semiconductors and CsI crystal housed into a protection detector in the form of a cup made of plastic scintillator. An absorber of plastic scintillator is placed between semiconductive detections. The detector may record positrons with energy up to 5 MeV in the composition of precipitating particles from the belt in definite detector signal combination and specific energy release 511 keV in CsI crystal. 16 refs.; 3 figs

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

    Directory of Open Access Journals (Sweden)

    Galina Dvoriantchikova

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

  13. Dosimetry and LET spectrometry in C 290 MeV/n and Ne 400 MeV/n HIMAC ion beam by different TLD's, TED based LET spectrometers, and Si energy-deposition spectrometer

    International Nuclear Information System (INIS)

    Spurny, F.; Brabcova, K.; Jadrnickova, I.; Uchihori, Y.; Kitamura, H.; Yasuda, N.; Molokanov, A. G.

    2009-01-01

    The sets of track etched detectors based (TED) spectrometer's of the linear energy transfer (LET) have been, together with two types of thermoluminescent detectors (TLD)and MDU- Liulin energy deposition spectrometer exposed in the C 290 MeV/n and Ne 400 MeV/n ion beams at the HlMAC installation at NIRS, Chiba, Japan. The experiment has been performed in the frame of NPI project 20P241 agreed by HlMAC P AC at the beginning of 2008 year. Up to now, moxstle only results obtained in C-ion beam have been treated and analyzed. Sets of TED spectrometer's and TLD detectors have been exposed in 19 depths in the C-ion beam with expected LET values of primary particles from 13 keV/μm in water, through the Bragg peak area up to two depth behind the Bragg peak. The contribution of fragments to total number of events, and to the energy absorbed in Si has been determined, when possible separately for different fragments. In all cases also total contribution of fragments (and other secondary particles) to the total number of energy deposition events and to the absorbed dose has been estimated. LET and energy deposition spectra obtained will be compared together , a good agreement of data has bee stated. Some of results have been also compared with those obtained by calculation by means of PHITS code. (authors)

  14. 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

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    Daniel Mauricio Meza Lasso

    2016-01-01

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

  17. Semiconductor-based Multilayer Selective Solar Absorber for Unconcentrated Solar Thermal Energy Conversion.

    Science.gov (United States)

    Thomas, Nathan H; Chen, Zhen; Fan, Shanhui; Minnich, Austin J

    2017-07-13

    Solar thermal energy conversion has attracted substantial renewed interest due to its applications in industrial heating, air conditioning, and electricity generation. Achieving stagnation temperatures exceeding 200 °C, pertinent to these technologies, with unconcentrated sunlight requires spectrally selective absorbers with exceptionally low emissivity in the thermal wavelength range and high visible absorptivity for the solar spectrum. In this Communication, we report a semiconductor-based multilayer selective absorber that exploits the sharp drop in optical absorption at the bandgap energy to achieve a measured absorptance of 76% at solar wavelengths and a low emittance of approximately 5% at thermal wavelengths. In field tests, we obtain a peak temperature of 225 °C, comparable to that achieved with state-of-the-art selective surfaces. With straightforward optimization to improve solar absorption, our work shows the potential for unconcentrated solar thermal systems to reach stagnation temperatures exceeding 300 °C, thereby eliminating the need for solar concentrators for mid-temperature solar applications such as supplying process heat.

  18. 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.

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

    International Nuclear Information System (INIS)

    Al-Abduljabbar, Abdulhamid

    2003-01-01

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

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2018-02-20

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

  3. 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)

  4. Stability analysis of the Gyroscopic Power Take-Off wave energy point absorber

    DEFF Research Database (Denmark)

    Nielsen, Søren R. K.; Zhang, Zili; Kramer, Morten Mejlhede

    2015-01-01

    The Gyroscopic Power Take-Off (GyroPTO) wave energy point absorber consists of a float rigidly connected to a lever. The operational principle is somewhat similar to that of the so-called gyroscopic hand wrist exercisers, where the rotation of the float is brought forward by the rotational particle...

  5. Jet energy measurements with the ZEUS prototype calorimeter

    International Nuclear Information System (INIS)

    Kroeger, W.

    1993-01-01

    The uranium scintillator calorimeter of the ZEUS detector is designed to achieve an excellent energy calibration and the best possible energy resolution for jets. Therefore the response of the prototype calorimeter to jets has been measured using an interaction trigger. The mean response and energy resolution was measured for jets of 50 GeV - 100 GeV and compared to the one for pions. Within the ZEUS detector dead material is placed in front of the calorimeter. The influence of 4 cm and 10 cm thick aluminium absorbers in front of the calorimeter was measured. The charged multiplicity was measured in front and behind the aluminium absorber. With these multiplicities the energy loss in the absorber is corrected. The correction has been done so that the mean response with absorber is equal to the mean response without absorber. The improvement of the energy resolution is investigated. The measured results are compared with Monte Carlo simulations. (orig.) [de

  6. 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.

  7. 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.

  8. A robust method for determining the absorbed dose to water in a phantom for low-energy photon radiation

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, T, E-mail: thorsten.schneider@ptb.de [Physikalisch-Technische Bundesanstalt (PTB), 38116 Braunschweig (Germany)

    2011-06-07

    The application of more and more low-energy photon radiation in brachytherapy-either in the form of low-dose-rate radioactive seeds such as Pd-103 or I-125 or in the form of miniature x-ray tubes-has induced greater interest in determining the absorbed dose to water in water in this energy range. As it seems to be hardly feasible to measure the absorbed dose with calorimetric methods in this low energy range, ionometric methods are the preferred choice. However, the determination of the absorbed dose to water in water by ionometric methods is difficult in this energy range. With decreasing energy, the relative uncertainty of the photon cross sections increases and as the mass energy transfer coefficients show a steep gradient, the spectra of the radiation field must be known precisely. In this work two ionometric methods to determine the absorbed dose to water are evaluated with respect to their sensitivity to the uncertainties of the spectra and of the atomic database. The first is the measurement of the air kerma free in air and the application of an MC-based conversion factor to the absorbed dose to water. The second is the determination of the absorbed dose to water by means of an extrapolation chamber as an integral part of a phantom. In the complementing MC-calculations, two assortments of spectra each of which is based on a separate unfolding procedure were used as well as two kinds of databases: the standard PEGS and the recently implemented NIST database of EGSnrc. Experimental results were obtained by using a parallel-plate graphite extrapolation chamber and a free-air chamber. In the case when the water kerma in a phantom is determined from the measurements of air kerma free in air, differences in the order of 10% were found, according to which the database or the kind of spectrum is used. In contrast to this, for the second method, the differences found were about 0.5%.

  9. A novel energy absorber based on magnetorheological gel

    Science.gov (United States)

    Pang, Haoming; Xuan, Shouhu; Sun, Chuanlin; Gong, Xinglong

    2017-10-01

    In this work, a novel magnetorheological energy absorber (MREA) was designed by using magnetorheological gel (MRG) as the damping medium. The proposed MREA had tunable piston gap distances and variable inner magnetic flux density distribution. The piston gap distance could be varied from 7-2 mm and the magnetic flux density at the gap increased from 120-860 mT, respectively. Under both low velocity compression and high speed impact, the damping could be divided into three parts. In the impact test, the velocity of a drop hammer could be reduced from to 3.4-0 m s-1 within a very short time (13 ms) and distance (17 mm). The maximum damping force of the MREA reached to as high as 8 kN. The damping force could also be adjusted by changing the current input. Under a 2 A current, the energy absorption ratio increased about 23% (from 4.13-5.07 J mm-1).

  10. High-energy-beam welding of type 316LN stainless steel for cryogenic applications

    International Nuclear Information System (INIS)

    Siewert, T.A.; Gorni, D.; Kohn, G.

    1988-01-01

    Laser and electron beam welds in 25-mm-thick AISI 316LN specimens containing 0.16 wt.$% N were evaluated for fusion reactor applications and their mechanical properties were compared with those of welds generated by lower productivity processes such as shielded-metal-arc and gas-metal-arc welding. Tensile tests were performed on transverse tensile specimens at 4 K. For both welding processes the fractures occurred in the base metal at a strength level near 950 MPa. This indicated that the weld and heat affected zone had a strength similar to that of the base metal. The 4 K weld fracture toughness was only slightly less than that for the base metal and comparable to the best values achieved with conventional welding processes in 316Ln weld metal. The Charpy V-notch absorbed energies averaged near 70 J at 76 K. Metallographic analysis revealed cellular and fully austenitic solidification with little porosity and no evidence of hot cracking

  11. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1997-04-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-12-01

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

  16. The Effects on Absorbed Dose Distribution in Intraoral X-ray Imaging When Using Tube Voltages of 60 and 70 kV for Bitewing Imaging

    Directory of Open Access Journals (Sweden)

    Kristina Hellén-Halme

    2013-10-01

    Full Text Available Objectives: Efforts are made in radiographic examinations to obtain the best image quality with the lowest possible absorbed dose to the patient. In dental radiography, the absorbed dose to patients is very low, but exposures are relatively frequent. It has been suggested that frequent low-dose exposures can pose a risk for development of future cancer. It has previously been reported that there was no significant difference in the diagnostic accuracy of approximal carious lesions in radiographs obtained using tube voltages of 60 and 70 kV. The aim of this study was, therefore, to evaluate the patient dose resulting from exposures at these tube voltages to obtain intraoral bitewing radiographs.Material and Methods: The absorbed dose distributions resulting from two bitewing exposures were measured at tube voltages of 60 and 70 kV using Gafchromic® film and an anatomical head phantom. The dose was measured in the occlusal plane, and ± 50 mm cranially and caudally to evaluate the amount of scattered radiation. The same entrance dose to the phantom was used. The absorbed dose was expressed as the ratio of the maximal doses, the mean doses and the integral doses at tube voltages of 70 and 60 kV.Results: The patient receives approximately 40 - 50% higher (mean and integral absorbed dose when a tube voltage of 70 kV is used.Conclusions: The results of this study clearly indicate that 60 kV should be used for dental intraoral radiographic examinations for approximal caries detection.

  17. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

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

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    Mauro Di Ianni

    2018-04-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

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    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.

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

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    Matthew R. Broadus

    2016-05-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  3. Power maximization of a point absorber wave energy converter using improved model predictive control

    Science.gov (United States)

    Milani, Farideh; Moghaddam, Reihaneh Kardehi

    2017-08-01

    This paper considers controlling and maximizing the absorbed power of wave energy converters for irregular waves. With respect to physical constraints of the system, a model predictive control is applied. Irregular waves' behavior is predicted by Kalman filter method. Owing to the great influence of controller parameters on the absorbed power, these parameters are optimized by imperialist competitive algorithm. The results illustrate the method's efficiency in maximizing the extracted power in the presence of unknown excitation force which should be predicted by Kalman filter.

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

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    Robert J Lake

    2009-08-01

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

  5. Effect of absorption discontinuity on neutron spectra of water assemblies poisoned with non-1/V absorbers

    International Nuclear Information System (INIS)

    Gupta, I.J.; Trikha, S.K.

    1977-01-01

    Calculations are presented of the diffusion of thermal neutrons (2.5 x 10 -4 to 7 x 10 -1 eV) across an absorption discontinuity in a water assembly, consisting of pure water on one side and aqueous solutions of three different non-1/V absorbers on the other, which were obtained by solving the Boltzmann transport equation in the diffusion approximation using the multigroup formalism. The gradual appearance and disappearance of the depletion region in the neutron spectra (caused by the resonance absorption peaks at energies 0.096 and 0.179 eV for samarium and cadmium respectively), as one moves from the pure water assembly to the poisoned water assembly and vice versa, have also been studied. The minimum concentrations of Sm and Cd atoms in water for which the depletion region in the spectra just starts building up are found to be 60 x 10 18 Sm atom cm -3 and 125 x 10 18 Cd atom cm -3 respectively. However no such depletion region is observed in gadolinium-poisoned water assembly. At the boundary, the equilibrium neutron distribution gets disturbed and is re-established to the equilibrium distribution of the second medium at some distance from the interface. The diffusion lengths so calculated from the total neutron density curves are in good agreement with the experimental results of Goddard and Johnson (Nucl. Sci. Eng.; 37:127 (1969)) at various concentrations of Gd and Cd atoms in water. (author)

  6. 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...

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

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    Maria De Salvo

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

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

    Science.gov (United States)

    Dominguez, Maria

    2014-04-01

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

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

    Science.gov (United States)

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

    2015-06-06

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

  10. Can Plant-Based Natural Flax Replace Basalt and E-Glass for Fiber-Reinforced Polymer Tubular Energy Absorbers? A Comparative Study on Quasi-Static Axial Crushing

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    Libo Yan

    2017-12-01

    Full Text Available Using plant-based natural fibers to substitute glass fibers as reinforcement of composite materials is of particular interest due to their economic, technical, and environmental significance. One potential application of plant-based natural fiber reinforced polymer (FRP composites is in automotive engineering as crushable energy absorbers. Current study experimentally investigated and compared the energy absorption efficiency of plant-based natural flax, mineral-based basalt, and glass FRP (GFRP composite tubular energy absorbers subjected to quasi-static axial crushing. The effects of number of flax fabric layer, the use of foam filler and the type of fiber materials on the crashworthiness characteristics, and energy absorption capacities were discussed. In addition, the failure mechanisms of the hollow and foam-filled flax, basalt, and GFRP tubes in quasi-static axial crushing were analyzed and compared. The test results showed that the energy absorption capabilities of both hollow and foam-filled energy absorbers made of flax were superior to the corresponding energy absorbers made of basalt and were close to energy absorbers made of glass. This study, therefore, indicated that flax fiber has the great potential to be suitable replacement of basalt and glass fibers for crushable energy absorber application.

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

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    Zehua Wang

    2018-02-01

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

  12. A three-dimensional analysis of the sigmoid notch

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    Evan D. Collins

    2011-12-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  14. Mandibular Ramus Notching As a Tool for Sexual Dimorphism

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    Bibhuti Bhusana Panda

    2016-02-01

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

  15. Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

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    Robert Wunderlich

    Full Text Available Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and ¼-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.

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

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    Hong-Mei Zhang

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

  17. Modelling of TES X-ray Microcalorimeters with a Novel Absorber Design

    Science.gov (United States)

    Iyomoto, Naoko; Bandler, Simon; Brefosky, Regis; Brown, Ari; Chervenak, James; Figueroa-Feliciano, Enectali; Finkbeiner, Frederick; Kelley, Richard; Kilbourne, Caroline; Lindeman, Mark; hide

    2007-01-01

    Our development of a novel x-ray absorber design that has enabled the incorporation of high-conductivity electroplated gold into our absorbers has yielded devices that not only have achieved breakthrough performance at 6 keV, but also are extraordinarily well modelled. We have determined device parameters that reproduce complex impedance curves and noise spectra throughout transition. Observed pulse heights, decay time and baseline energy resolution were in good agreement with simulated results using the same parameters. In the presentation, we will show these results in detail and we will also show highlights of the characterization of our gold/bismuth-absorber devices. We will discuss possible improvement of our current devices and expected performance of future devices using the modelling results.

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

    Directory of Open Access Journals (Sweden)

    Floriane Auderset

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

  19. Calibration of film dosimeters by means of absorbed dose calorimeters

    International Nuclear Information System (INIS)

    Nikolaev, S.M.; Vanyushkin, B.M.; Kon'kov, N.G.

    1980-01-01

    Methods of graduating film dosimeters by means of calorimeters of absorbed doses, are considered. Graduating of film dosimeters at the energies of accelerated electrons from 4 to 10 MeV can be carried out by means of quasiadiabatic calorimeter of local absorption, the absorber thickness of which should not exceed 5-10% of Rsub(e) value, where Rsub(e) - free electron path of the given energy. In this case film is located inside the calorimeter. For graduating films with thickness not less than (0.1-0.2)Rsub(e) it is suggested to use calorimeter of full absorption; then the graduated dosimeters are located in front of the calorimeter. Graduation of films at small energies of electrons is exercised by means of a package of films, approximately Rsub(e) thick. A design of quasiadiabatic calorimeter, intended for graduating dosimeters within the energy range of electron beam from 4 to 10 MeV, is considered. The quasiadiabatic calorimeter is a thin graphite tablet with heater and thermocouple, surrounded by foam plastic thermostating case. Electricity quantity, accumulated during the radiation field pass, is measured in the case of using the quasiadiabatic calorimeter for film graduating. The results of graduating film dosimeters, obtained using film package with Rsub(e) thickness, are presented. The obtained results coincide within 5% limits with the data known beforehand [ru

  20. 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.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  2. DHCAL with Minimal Absorber: Measurements with Positrons

    CERN Document Server

    Freund, B; Repond, J.; Schlereth, J.; Xia, L.; Dotti, A.; Grefe, C.; Ivantchenko, V.; Antequera, J.Berenguer; Calvo Alamillo, E.; Fouz, M.C.; Marin, J.; Puerta-Pelayo, J.; Verdugo, A.; Brianne, E.; Ebrahimi, A.; Gadow, K.; Göttlicher, P.; Günter, C.; Hartbrich, O.; Hermberg, B.; Irles, A.; Krivan, F.; Krüger, K.; Kvasnicka, J.; Lu, S.; Lutz, B.; Morgunov, V.; Provenza, A.; Reinecke, M.; Sefkow, F.; Schuwalow, S.; Tran, H.L.; Garutti, E.; Laurien, S.; Matysek, M.; Ramilli, M.; Schroeder, S.; Bilki, B.; Norbeck, E.; Northacker, D.; Onel, Y.; Cvach, J.; Gallus, P.; Havranek, M.; Janata, M.; Kovalcuk, M.; Kvasnicka, J.; Lednicky, D.; Marcisovsky, M.; Polak, I.; Popule, J.; Tomasek, L.; Tomasek, M.; Sicho, P.; Smolik, J.; Vrba, V.; Zalesak, J.; van Doren, B.; Wilson, G.W.; Kawagoe, K.; Hirai, H.; Sudo, Y.; Suehara, T.; Sumida, H.; Takada, S.; Tomita, T.; Yoshioka, T.; Bilokin, S.; Bonis, J.; Cornebise, P.; Pöschl, R.; Richard, F.; Thiebault, A.; Zerwas, D.; Hostachy, J.Y.; Morin, L.; Besson, D.; Chadeeva, M.; Danilov, M.; Markin, O.; Popova, E.; Gabriel, M.; Goecke, P.; Kiesling, C.; Kolk, N.van der; Simon, F.; Szalay, M.; Corriveau, F.; Blazey, G.C.; Dyshkant, A.; Francis, K.; Zutshi, V.; Kotera, K.; Ono, H.; Takeshita, T.; Ieki, S.; Kamiya, Y.; Ootani, W.; Shibata, N.; Jeans, D.; Komamiya, S.; Nakanishi, H.

    2016-01-01

    In special tests, the active layers of the CALICE Digital Hadron Calorimeter prototype, the DHCAL, were exposed to low energy particle beams, without being interleaved by absorber plates. The thickness of each layer corresponded approximately to 0.29 radiation lengths or 0.034 nuclear interaction lengths, defined mostly by the copper and steel skins of the detector cassettes. This paper reports on measurements performed with this device in the Fermilab test beam with positrons in the energy range of 1 to 10 GeV. The measurements are compared to simulations based on GEANT4 and a standalone program to emulate the detailed response of the active elements.

  3. Design and testing of an energy-absorbing crewseat for the F/FB-111 aircraft. Volume 2: Data from seat testing

    Science.gov (United States)

    Shane, S. J.

    1985-01-01

    The unacceptably high injury rate during the escape sequence (including the ejection and ground impact) of the crew module for F/FB-111 aircraft is reviewed. A program to determine if the injury potential could be reduced by replacing the existing crewseats with energy absorbing crewseats is presented. An energy absorbing test seat is designed using much of the existing seat hardware. An extensive dynamic seat test series, designed to duplicate various crew module ground impact conditions is conducted at a sled test facility. Comparative tests with operational F-111 crewseats are also conducted. After successful dynamic testing of the seat, more testing is conducted with the seats mounted in an F-111 crew module. Both swing tests and vertical drop tests are conducted. The vertical drop tests are used to obtain comparative data between the energy absorbing and operational seats. Volume 1 describes the energy absorbing test seat and testing conducted, and evaluates the data from both test series. Volume 2 presents the data obtained during the seat test series, while Volume 3 presents the data from the crew module test series.

  4. Large flux change due to the intervening cold absorbers in NGC 3516

    International Nuclear Information System (INIS)

    Nogami, K.; Negoro, H.; Hong, S.; Mihara, T.

    2004-01-01

    NGC3516 in the low flux state shows a flat energy spectrum (photon index ∼1) and an intense narrow iron line. Such spectra are also observed in other Seyfert galaxies, and a broad bump structure around 6 keV above the 'flat' power-law spectrum has been interpreted as the gravitationally red-shifted iron line, disk reflection, or cold and/or warm absorbers. However, six years if BeppoSAX observations, including our latest three ones in 2001, clearly demonstrate that energy spectra above 20 keV always exhibit steep power-laws with photon indices ∼2, and the flux changes only by a factor of 2, while the soft X-ray flux by a factor of ∼10. From this fact, using BeppoSAX and ASCA data, we have concluded that the flat spectrum results from reprocessed, and partially covered power-laws with Γ∼1.8 by warm matter nearby the central source and a cold absorber moved in the line of sight, respectively, and that the broad iron line and disk reflection components are less significant than one ever thought. Thus, the long-term spectral variations can be considered by intervening absorbers rather than changes in the accretion rate

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

    Directory of Open Access Journals (Sweden)

    Xun Yuan

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

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

    Science.gov (United States)

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

    2017-08-01

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

  7. EV drivetrain inverter with V/HZ optimization

    Science.gov (United States)

    Gritter, David J.; O'Neil, Walter K.

    1986-01-01

    An inverter (34) which provides power to an A.C. machine (28) is controlled by a circuit (36) employing PWM control strategy whereby A.C. power is supplied to the machine at a preselectable frequency and preselectable voltage. This is accomplished by the technique of waveform notching in which the shapes of the notches are varied to determine the average energy content of the overall waveform. Through this arrangement, the operational efficiency of the A.C. machine is optimized. The control circuit includes a micro-computer which calculates optimized machine control data signals from various parametric inputs and during steady state load conditions, seeks a best V/HZ ratio to minimize battery current drawn (system losses) from a D.C. power source (32). In the preferred embodiment, the present invention is incorporated within an electric vehicle (10) employing a 144 VDC battery pack and a three-phase induction motor (18).

  8. 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.

  9. Absorbed dose determination in water in medium energy x-ray beam

    International Nuclear Information System (INIS)

    Nisevic, G.; Spasic-Jokic, V.

    1998-01-01

    Absorbed dose determination in water phantom in medium energy X-ray beam, according to IAEA recommendations is given. This method is applied on Radiotherapy department of Military Academy Hospital in Belgrade. Reference points of measurements are on depth of 5 cm and 2 cm as it recommended in ref. Experimental results are shown in aim to introduce new dosimetric concept based on air kerma calibration factor recommended for application in our radiotherapy centers (author)

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

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    2015-02-01

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

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

    International Nuclear Information System (INIS)

    Richard, H.A.; Theis, W.

    1982-01-01

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

  12. Calculation of absorbed dose at 0.07, 3.0 and 10.0 mm depths in a slab phantom for monoenergetic electrons

    International Nuclear Information System (INIS)

    Hirayama, H.

    1994-01-01

    The general-purpose electron gamma shower Monte Carlo code EGS4 has been used to calculate absorbed doses at 0.07, 3.0 and 10.0 mm depths per unit fluence for broad parallel beams of monoenergetic electrons impinging at an incident angle α on a slab phantom (30 cm x 30 cm x 15 cm) of polymethyl methacrylate (PMMA), water and ICRU 4-element tissue required by EURADOS WG4 for a revision of ICRP Publication 51. Absorbed doses at 7, 300 and 1000 mg.cm -2 were also calculated for PMMA. The electron kinetic energy range covered is 50 keV to 10 MeV. The incident angle (α) varies from 0 o to 75 o with an increment of 15 o . The calculated results are presented as tables. The depth against absorbed dose curves and dependence of the absorbed dose at each depth on the incident electron energy, incident angle and phantom material are also presented and discussed. (author)

  13. 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

  14. Notched K-wire for low thermal damage bone drilling.

    Science.gov (United States)

    Liu, Yao; Belmont, Barry; Wang, Yiwen; Tai, Bruce; Holmes, James; Shih, Albert

    2017-07-01

    The Kirschner wire (K-wire) is a common bone drilling tool in orthopedic surgery to affix fractured bone. Significant heat is produced due to both the cutting and the friction between the K-wire and the bone debris during drilling. Such heat can result in high temperatures, leading to osteonecrosis and other secondary injuries. To reduce thermal injury and other high-temperature associated complications, a new K-wire design with three notches along the three-plane trocar tip fabricated using a thin micro-saw tool is studied. These notches evacuate bone debris and reduce the clogging and heat generation during bone drilling. A set of four K-wires, one without notches and three notched, with depths of 0.5, 0.75, and 1mm, are evaluated. Bone drilling experiments conducted on bovine cortical bone show that notched K-wires could effectively decrease the temperature, thrust force, and torque during bone drilling. K-wires with notches 1mm deep reduced the thrust force and torque by approximately 30%, reduced peak temperatures by 43%, and eliminated blackened burn marks in bone. This study demonstrates that a simple modification of the tip of K-wires can effectively reduce bone temperatures during drilling. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  15. In-phantom measurement of absorbed dose to water in medium energy x-ray beams

    International Nuclear Information System (INIS)

    Hohlfeld, K.

    1996-01-01

    Absorbed dose values in a water phantom derived by the formalism of the IAEA Code of Practice of Absorbed Dose Determination in Photon and Electron Beams are a few per cent higher than those based on the procedure following e.g. ICRU Report 23. The maximum deviation exceeds 10% at 100 kV tube potential. The correction factor needed to take into account the differences at the calibration in terms of air kerma free in air and at the measurement in the water phantom can be determined in different ways: In comparing the result of the absorbed dose measurement by means of the ionization chambers with an other, preferably fundamental method of measurement of absorbed dose in the water phantom or by evaluating all component parts of the correction factor separately. The values of the perturbation correction factor in the IAEA Code were determined in the former way by comparing against a graphite extrapolation chamber. A review is given on a recent re-evaluation using former values of the extrapolation chamber measurements and on new determinations using an absorbed dose water calorimeter, a method based on calculated and measured air kerma values and a method of combining the component factors to the overall correction factor. Recent results achieved by the different methods are compared and a change of the data of the IAEA Code is recommended. (author). 31 refs, 14 figs, 3 tabs

  16. 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

  17. Performance evaluation of CFRP-rubber shock absorbers

    Science.gov (United States)

    Lamanna, Giuseppe; Sepe, Raffaele

    2014-05-01

    In the present work a numerical investigation on the energy absorbing capability of dedicated structural components made of a carbon fiber reinforced polymer and an emulsion polymerised styrene butadiene rubber is reported. The shock absorbers are devices designed to absorb large amounts of energy by sacrificing their own structural integrity. Their aim is to cushion the effects of an impact phenomenon with the intent to preserve other structures from global failure or local damaging. Another important role of shock absorbers is reducing the peak of the acceleration showed during an impact phenomenon. This effect is of considerable interest in the case of vehicles to preserve passengers' safety. Static and dynamic numerical results are compared with experimental ones in terms of mean crushing forces, energy and peak crushing. The global performance of the absorbers has been evaluated by referencing to a proposed quality index.

  18. Performance evaluation of CFRP-rubber shock absorbers

    Energy Technology Data Exchange (ETDEWEB)

    Lamanna, Giuseppe, E-mail: giuseppe.lamanna@unina2.it; Sepe, Raffaele, E-mail: giuseppe.lamanna@unina2.it [Department of Industrial and Information Engineering, Second University of Naples, via Roma, 29 - 81031 Aversa (Italy)

    2014-05-15

    In the present work a numerical investigation on the energy absorbing capability of dedicated structural components made of a carbon fiber reinforced polymer and an emulsion polymerised styrene butadiene rubber is reported. The shock absorbers are devices designed to absorb large amounts of energy by sacrificing their own structural integrity. Their aim is to cushion the effects of an impact phenomenon with the intent to preserve other structures from global failure or local damaging. Another important role of shock absorbers is reducing the peak of the acceleration showed during an impact phenomenon. This effect is of considerable interest in the case of vehicles to preserve passengers’ safety. Static and dynamic numerical results are compared with experimental ones in terms of mean crushing forces, energy and peak crushing. The global performance of the absorbers has been evaluated by referencing to a proposed quality index.

  19. Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2011-11-01

    Full Text Available Abstract Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites. Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (GCOT, their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4 and three ligands (Jagged1, Jagged2 and Delta1 was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0, mild (+, moderate (2+ and strong (3+. Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.

  20. In-situ tensile testing of notched poly- and oligocrystalline 316L wires

    Energy Technology Data Exchange (ETDEWEB)

    Mitevski, Bojan [Materials Science and Engineering (ITM), Duisburg (Germany); Weiss, Sabine [Brandenburg Technical Univ., Cottbus-Senftenberg (Germany). Chair of Physical Metallurgy and Materials Science.; Fischer, Alfons [Duisburg-Essen Univ. (Germany). Materials Science and Engineering; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Orthopedics

    2017-03-01

    In-situ testing inside a scanning electron microscope is a helpful tool for detailed analyses of small sized specimens with respect to their mechanical properties and the correlated microstructural alterations. Thus, this test method is used to analyze the tensional properties of thin 316L (1.4441) wires used for microscale components, e.g., like coronary artery stents. Tensile tests were conducted on unnotched and circularly notched 316L wires (oe 0.95 mm) with a special focus on the number of grains within the cross section as well as the notch geometry. Four combinations of notch width (2 and 4 mm) and notch depth (diameter at notch root: 0.5 and 0.75 mm) were chosen. Notch depth and notch shape were adjusted by means of electrochemical polishing. Previous investigations showed, that oligocrystalline structures exhibit a different mechanical behavior compared to polycrystalline ones or single crystals. There are only a few data available on mechanical testing of oligocrystalline structures with respect to varying notch geometries. Depending on the notch geometry, grain size and, therefore, the number of grains within the notch cross section widely scattering yield- and tensile strength as well as failure elongation values were measured. However, the transition criterion between poly- and oligocrystalline behavior could be quantified to be 6 to 7 grains within the cross section.

  1. Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study

    Science.gov (United States)

    Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

    2011-01-01

    Objectives The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. Methods We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. Results The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. Conclusions While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take

  2. Estimation of RF energy absorbed in the brain from mobile phones in the Interphone Study.

    Science.gov (United States)

    Cardis, E; Varsier, N; Bowman, J D; Deltour, I; Figuerola, J; Mann, S; Moissonnier, M; Taki, M; Vecchia, P; Villegas, R; Vrijheid, M; Wake, K; Wiart, J

    2011-09-01

    The objective of this study was to develop an estimate of a radio frequency (RF) dose as the amount of mobile phone RF energy absorbed at the location of a brain tumour, for use in the Interphone Epidemiological Study. We systematically evaluated and quantified all the main parameters thought to influence the amount of specific RF energy absorbed in the brain from mobile telephone use. For this, we identified the likely important determinants of RF specific energy absorption rate during protocol and questionnaire design, we collected information from study subjects, network operators and laboratories involved in specific energy absorption rate measurements and we studied potential modifiers of phone output through the use of software-modified phones. Data collected were analysed to assess the relative importance of the different factors, leading to the development of an algorithm to evaluate the total cumulative specific RF energy (in joules per kilogram), or dose, absorbed at a particular location in the brain. This algorithm was applied to Interphone Study subjects in five countries. The main determinants of total cumulative specific RF energy from mobile phones were communication system and frequency band, location in the brain and amount and duration of mobile phone use. Though there was substantial agreement between categorisation of subjects by cumulative specific RF energy and cumulative call time, misclassification was non-negligible, particularly at higher frequency bands. Factors such as adaptive power control (except in Code Division Multiple Access networks), discontinuous transmission and conditions of phone use were found to have a relatively minor influence on total cumulative specific RF energy. While amount and duration of use are important determinants of RF dose in the brain, their impact can be substantially modified by communication system, frequency band and location in the brain. It is important to take these into account in analyses of risk

  3. Absorbed dose to water determination with ionization chamber dosimetry and calorimetry in restricted neutron, photon, proton and heavy-ion radiation fields.

    Science.gov (United States)

    Brede, H J; Greif, K-D; Hecker, O; Heeg, P; Heese, J; Jones, D T L; Kluge, H; Schardt, D

    2006-08-07

    Absolute dose measurements with a transportable water calorimeter and ionization chambers were performed at a water depth of 20 mm in four different types of radiation fields, for a collimated (60)Co photon beam, for a collimated neutron beam with a fluence-averaged mean energy of 5.25 MeV, for collimated proton beams with mean energies of 36 MeV and 182 MeV at the measuring position, and for a (12)C ion beam in a scanned mode with an energy per atomic mass of 430 MeV u(-1). The ionization chambers actually used were calibrated in units of air kerma in the photon reference field of the PTB and in units of absorbed dose to water for a Farmer-type chamber at GSI. The absorbed dose to water inferred from calorimetry was compared with the dose derived from ionometry by applying the radiation-field-dependent parameters. For neutrons, the quantities of the ICRU Report 45, for protons the quantities of the ICRU Report 59 and for the (12)C ion beam, the recommended values of the International Atomic Energy Agency (IAEA) protocol (TRS 398) were applied. The mean values of the absolute absorbed dose to water obtained with these two independent methods agreed within the standard uncertainty (k = 1) of 1.8% for calorimetry and of 3.0% for ionometry for all types and energies of the radiation beams used in this comparison.

  4. Performance of compact TES arrays with integrated high-fill-fraction X-ray absorbers

    International Nuclear Information System (INIS)

    Lindeman, Mark A.; Bandler, Simon; Brekosky, Regis P.; Chervenak, James A.; Figueroa-Feliciano, Enectali; Finkbeiner, Fred M.; Kelley, Richard L.; Saab, Tarek; Stahle, Caroline K.; Talley, D.J.

    2004-01-01

    We have recently produced and tested two-dimensional arrays of Mo/Au transition-edge-sensor (TES) calorimeters with Bi/Cu absorbers. The arrays represent a significant step towards meeting the specifications of NASA's Constellation-X mission. The calorimeters are compactly spaced within 5x5 arrays of 250 μm square pixels necessary for an angular resolution of 5 arcsec. Lithographically produced absorbers hang over the substrate and wiring between the TESs for high filling fraction and high quantum efficiency. We designed the calorimeters with heat capacities and thermal couplings such that X-rays produce pulses with fall times of approximately 300 μs to allow relatively high count rates with low dead time. We read out up to four of the pixels simultaneously. The arrays demonstrated very good energy resolution (5 eV at 1.5 keV and 7 eV at 6 keV) and little crosstalk between neighboring pixels

  5. Beam test of ferrite absorber in TRISTAN MR

    International Nuclear Information System (INIS)

    Tajima, T.; Asano, K.; Furuya, T.; Ishi, Y.; Kijima, Y.; Mitsunobu, S.; Sennyu, K.; Takahashi, T.

    1996-06-01

    A study on the effect of beams on the ferrite absorber was performed using TRISTAN MR. The tested absorber consists of a 300 mm-diam. copper pipe with 4 mm-thick ferrite inner layer, which was fabricated with Hot Isostatic Press (HIP) technique. No spark, damage, or degradation were observed up to the highest available single bunch current of 4.4 mA, i.e. 2.8x10 11 electrons per bunch, which is 8.5 times higher than that of KEKB low energy ring. The loss factor showed significant increase with bunch shortening, e.g. 2.6 V/pC at 4 mm was about 40% higher than the value predicted by the calculation assuming Gaussian bunch and no incoming power from outside of the chamber. (author)

  6. Simulation of MeV electron energy deposition in CdS quantum dots absorbed in silicate glass for radiation dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Baharin, R; Hobson, P R; Smith, D R, E-mail: ruzalina.baharin@brunel.ac.u [Centre for Sensors and Instrumentation, School of Engineering and Design, Brunel University, Uxbridge UB8 3PH (United Kingdom)

    2010-09-01

    We are currently developing 2D dosimeters with optical readout based on CdS or CdS/CdSe core-shell quantum-dots using commercially available materials. In order to understand the limitations on the measurement of a 2D radiation profile the 3D deposited energy profile of MeV energy electrons in CdS quantum-dot-doped silica glass have been studied by Monte Carlo simulation using the CASINO and PENELOPE codes. Profiles for silica glass and CdS quantum-dot-doped silica glass were then compared.

  7. Simulation of MeV electron energy deposition in CdS quantum dots absorbed in silicate glass for radiation dosimetry

    International Nuclear Information System (INIS)

    Baharin, R; Hobson, P R; Smith, D R

    2010-01-01

    We are currently developing 2D dosimeters with optical readout based on CdS or CdS/CdSe core-shell quantum-dots using commercially available materials. In order to understand the limitations on the measurement of a 2D radiation profile the 3D deposited energy profile of MeV energy electrons in CdS quantum-dot-doped silica glass have been studied by Monte Carlo simulation using the CASINO and PENELOPE codes. Profiles for silica glass and CdS quantum-dot-doped silica glass were then compared.

  8. 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.

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

    Science.gov (United States)

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

    2018-05-16

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

  10. Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

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

    2010-01-01

    Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

  11. 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.

  12. Design and control of a point absorber wave energy converter with an open loop hydraulic transmission

    International Nuclear Information System (INIS)

    Fan, YaJun; Mu, AnLe; Ma, Tao

    2016-01-01

    Highlights: • Point absorber wave energy converter is presented. • Piston pump module captures and converts wave energy. • Hydraulic accumulator stores/releases the surplus energy. • Fuzzy controller adjusts the displacement of hydraulic motor. • Generator outputs meet the electricity demand precisely. - Abstract: In this paper, a point absorber wave energy converter combined with offshore wind turbine is proposed. In the system, the wave energy is captured and converted into hydraulic energy by a piston pump module, which is combined with a wind turbine floating platform, and then the hydraulic energy is converted into electricity energy by a variable displacement hydraulic motor and induction generator. In order to smooth and stabilize the captured wave energy, a hydraulic accumulator is applied to store and release the excess energy. In order to meet the demand power a fuzzy controller is designed to adjust the displacement of hydraulic motor and controlled the output power. Simulation under irregular wave condition has been carried out to verify the validity of the mathematical model and the effectiveness of the controller strategy. The results show that the wave energy converter system could deliver the required electricity power precisely as the motor output torque is controlled. The accumulator could damp out all the fluctuations in output power, so the wave energy would become a dispatchable power source.

  13. Cluster ion-surface interactions: from meV to MeV energies

    Energy Technology Data Exchange (ETDEWEB)

    Nordlund, Kai; Meinander, Kristoffer; Jaervi, Tommi T.; Peltola, Jarkko; Samela, Juha [Accelerator Laboratory, University of Helsinki (Finland)

    2008-07-01

    The nature of cluster ion-surface interactions changes dramatically with the kinetic energy of the incoming cluster species. In this talk I review some of our recent work on the nature of cluster-surface interactions spanning an energy range from a few MeV/cluster to about 1 MeV/cluster and cluster sizes in the range of 10 - 1000 atoms/cluster. In the energy range of a few MeV/cluster ion, the kinetic energy of the incoming ion is insignificant compared to the energy gained when the surface potential energy at the cluster-surface interface is released and partly translated into kinetic energy. Even in this energy regime I show that surprisingly drastic effects can occur. When the energy of the incoming cluster is raised to a few eV/atom, the kinetic energy of the incoming cluster starts to affect the deposition. It will cause the cluster to entirely reform on impact. When the energy is raised to the range of keV's/cluster, the clusters start to penetrate the sample, fairly similar to conventional ion implantation. However, in dense targets the cluster ions may stick close to each other long enough to cause a significant enhancement of the heat spike in the material. Finally, I show that at kinetic energies around 1 MeV/cluster the cluster enhancement of the heat spike may lead to dramatic surface effects.

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

    Science.gov (United States)

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

    2017-03-13

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

  15. Development of a Continuum Damage Mechanics Material Model of a Graphite-Kevlar(Registered Trademark) Hybrid Fabric for Simulating the Impact Response of Energy Absorbing Kevlar(Registered Trademark) Hybrid Fabric for Simulating the Impact Response of Energy Absorbing

    Science.gov (United States)

    Jackson, Karen E.; Fasanella, Edwin L.; Littell, Justin D.

    2017-01-01

    This paper describes the development of input properties for a continuum damage mechanics based material model, Mat 58, within LS-DYNA(Registered Trademark) to simulate the response of a graphite-Kevlar(Registered Trademark) hybrid plain weave fabric. A limited set of material characterization tests were performed on the hybrid graphite-Kevlar(Registered Trademark) fabric. Simple finite element models were executed in LS-DYNA(Registered Trademark) to simulate the material characterization tests and to verify the Mat 58 material model. Once verified, the Mat 58 model was used in finite element models of two composite energy absorbers: a conical-shaped design, designated the "conusoid," fabricated of four layers of hybrid graphite-Kevlar(Registered Trademark) fabric; and, a sinusoidal-shaped foam sandwich design, designated the "sinusoid," fabricated of the same hybrid fabric face sheets with a foam core. Dynamic crush tests were performed on components of the two energy absorbers, which were designed to limit average vertical accelerations to 25- to 40-g, to minimize peak crush loads, and to generate relatively long crush stroke values under dynamic loading conditions. Finite element models of the two energy absorbers utilized the Mat 58 model that had been verified through material characterization testing. Excellent predictions of the dynamic crushing response were obtained.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  17. The Australian Commonwealth standard of measurement for absorbed radiation dose. Part 1

    International Nuclear Information System (INIS)

    Sherlock, S.L.

    1989-08-01

    As an agent for the Commonwealth Scientific and Industrial Research Organisation, the Australian Nuclear Science and Technology Organisation is responsible for maintenance of the Australian Commonwealth standard of absorbed dose. This standard of measurement has application in radiation therapy dosimetry, which is required for the treatment of cancer patients. This report is the first in a series of reports documenting the absorbed dose standard for photon beams in the range from 1 to 25 MeV. The Urquhart graphite micro-calorimeters, which is used for the determination of absorbed dose under high energy photon beams, has been now placed under computer control. Accordingly, a complete upgrade of the calorimeter systems was performed to allow operation in the hospital. In this report, control and monitoring techniques have been described, with an assessment of the performance achieved being given for 6 and 18 MeV bremsstrahlung beams. Random errors have been reduced to near negligible proportions, while systematic errors have been minimized by achieving true quasi-adiabatic operation. 16 refs., 9 tabs., 11 figs

  18. 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.

  19. A closed-form formulation for the build-up factor and absorbed energy for photons and electrons in the Compton energy range in Cartesian geometry

    International Nuclear Information System (INIS)

    Borges, Volnei; Vilhena, Marco Tullio; Fernandes, Julio Cesar Lombaldo

    2011-01-01

    In this work, we report on a closed-form formulation for the build-up factor and absorbed energy, in one and two dimensional Cartesian geometry for photons and electrons, in the Compton energy range. For the one-dimensional case we use the LTS N method, assuming the Klein-Nishina scattering kernel for the determination of the angular radiation intensity for photons. We apply the two-dimensional LTS N nodal solution for the averaged angular radiation evaluation for the two-dimensional case, using the Klein-Nishina kernel for photons and the Compton kernel for electrons. From the angular radiation intensity we construct a closed-form solution for the build-up factor and evaluate the absorbed energy. We present numerical simulations and comparisons against results from the literature. (author)

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Specific absorbed fractions of energy at various ages from internal photon sources: 7, Adult male

    International Nuclear Information System (INIS)

    Cristy, M.; Eckerman, K.F.

    1987-04-01

    Specific absorbed fractions (PHI's) in various organs of the body (target organs) from sources of monoenergetic photons in various other organs (source organs) are tabulated. In this volume PHI-values are tabulated for an adult male (70-kg Reference Man). These PHI-values can be used in calculating the photon component of the dose-equivalent rate in a given target organ from a given radionuclide that is present in a given source organ. The International Commission on Radiological Protection recognizes that the endosteal, or bone surface, cells are the tissue at risk for bone cancer. We have applied the dosimetry methods developed for beta-emitting radionuclides deposited in bone to follow the transport of secondary electrons that were freed by photon interactions through the microscopic structure of the skeleton. With these methods we can estimate PHI in the endosteal cells and can better estimate PHI in the active marrow; the latter is overestimated with other methods at photon energies below 200 keV. 12 refs., 2 tabs

  2. hCLP46 regulates U937 cell proliferation via Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-29

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

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

    Science.gov (United States)

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

    2014-09-25

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

  4. Why does necking ignore notches in dynamic tension?

    Directory of Open Access Journals (Sweden)

    Rotbaum Y.

    2015-01-01

    Full Text Available Recent experimental work has revealed that necking of tensile specimens, subjected to dynamic loading, is a deterministic phenomenon, governed by the applied boundary conditions. Furthermore it was shown that the potential sited, dictated by the boundary conditions, may prevail even in the presence of a notch, thus necking may occur away of the notched region. The present paper combines experimental and numerical work to address this issue. Specifically, it is shown that the dynamic tensile failure locus is dictated by both the applied velocity boundary condition and the material mechanical properties, specifically strain-rate sensitivity and strain-rate hardening. It is shown that at sufficiently high impact velocities, the flows stress in the notch vicinity becomes quite higher than in the rest of the specimen, so that while the former resists deformation, it transfers the load to the latter, resulting in the formation of a local neck and failure away from the notch. Small local perturbations in the material properties are shown to be sufficient to stabilize the structure under local failure until a neck forms elsewhere. While the physical observations are quite counterintuitive with respect to the engineering views of stress concentrator's effect, the present work rationalizes those observations and also provides information for the designers of dynamically tensioned structures that may contain notches or similar flaws.

  5. Measurement of absorbed dose for high energy electron using CaSO4: Tm-PTFE TLD

    International Nuclear Information System (INIS)

    Park, Myeong Hwan; Kim, Do Sung

    2000-01-01

    In this study, the highly sensitive CaSO 4 : Tm-PTFE TLDs has been fabricated for the purpose of measurement of high energy electron. CaSO 4 : Tm phosphor powder was mixed with polytetrafluoroethylene(PTFE) powder and moulded in a disk type(diameter 8.5mm, thickness 90mg/cm 2 ) by cold pressing. The absorbed dose distribution and ranges for high energy electron were measured by using the CaSO 4 : Tm-PTFE TLDs. The ranges determined were R 100 =3D14.5mm, R 50 =3D24.1mm and R p =3D31.8mm, respectively and the beam flatness, the variation of relative dose in 80% of the field size, was 4.5%. The fabricated CaSO 4 : Tm-PTFE TLDs may be utilized in radiation dosimetry for personal, absorbed dose and environmental monitoring.=20

  6. Emitter/absorber interface of CdTe solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Tao, E-mail: tsong241@gmail.com; Sites, James R. [Physics Department, Colorado State University, Fort Collins, Colorado 80523 (United States); Kanevce, Ana [National Renewable Energy Laboratory, Golden, Colorado 80401 (United States)

    2016-06-21

    The performance of CdTe solar cells can be very sensitive to the emitter/absorber interface, especially for high-efficiency cells with high bulk lifetime. Performance losses from acceptor-type interface defects can be significant when interface defect states are located near mid-gap energies. Numerical simulations show that the emitter/absorber band alignment, the emitter doping and thickness, and the defect properties of the interface (i.e., defect density, defect type, and defect energy) can all play significant roles in the interface recombination. In particular, a type I heterojunction with small conduction-band offset (0.1 eV ≤ ΔE{sub C} ≤ 0.3 eV) can help maintain good cell efficiency in spite of high interface defect density, much like with Cu(In,Ga)Se{sub 2} (CIGS) cells. The basic principle is that positive ΔE{sub C}, often referred to as a “spike,” creates an absorber inversion and hence a large hole barrier adjacent to the interface. As a result, the electron-hole recombination is suppressed due to an insufficient hole supply at the interface. A large spike (ΔE{sub C} ≥ 0.4 eV), however, can impede electron transport and lead to a reduction of photocurrent and fill-factor. In contrast to the spike, a “cliff” (ΔE{sub C} < 0 eV) allows high hole concentration in the vicinity of the interface, which will assist interface recombination and result in a reduced open-circuit voltage. Another way to mitigate performance losses due to interface defects is to use a thin and highly doped emitter, which can invert the absorber and form a large hole barrier at the interface. CdS is the most common emitter material used in CdTe solar cells, but the CdS/CdTe interface is in the cliff category and is not favorable from the band-offset perspective. The ΔE{sub C} of other n-type emitter choices, such as (Mg,Zn)O, Cd(S,O), or (Cd,Mg)Te, can be tuned by varying the elemental ratio for an optimal positive value of ΔE{sub C}. These

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

    Directory of Open Access Journals (Sweden)

    Lee Norman H

    2010-07-01

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

  8. 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

  9. Design of a nonlinear torsional vibration absorber

    Science.gov (United States)

    Tahir, Ammaar Bin

    Tuned mass dampers (TMD) utilizing linear spring mechanisms to mitigate destructive vibrations are commonly used in practice. A TMD is usually tuned for a specific resonant frequency or an operating frequency of a system. Recently, nonlinear vibration absorbers attracted attention of researchers due to some potential advantages they possess over the TMDs. The nonlinear vibration absorber, or the nonlinear energy sink (NES), has an advantage of being effective over a broad range of excitation frequencies, which makes it more suitable for systems with several resonant frequencies, or for a system with varying excitation frequency. Vibration dissipation mechanism in an NES is passive and ensures that there is no energy backflow to the primary system. In this study, an experimental setup of a rotational system has been designed for validation of the concept of nonlinear torsional vibration absorber with geometrically induced cubic stiffness nonlinearity. Dimensions of the primary system have been optimized so as to get the first natural frequency of the system to be fairly low. This was done in order to excite the dynamic system for torsional vibration response by the available motor. Experiments have been performed to obtain the modal parameters of the system. Based on the obtained modal parameters, the design optimization of the nonlinear torsional vibration absorber was carried out using an equivalent 2-DOF modal model. The optimality criterion was chosen to be maximization of energy dissipation in the nonlinear absorber attached to the equivalent 2-DOF system. The optimized design parameters of the nonlinear absorber were tested on the original 5-DOF system numerically. A comparison was made between the performance of linear and nonlinear absorbers using the numerical models. The comparison showed the superiority of the nonlinear absorber over its linear counterpart for the given set of primary system parameters as the vibration energy dissipation in the former is

  10. Energy deposition at the bone-tissue interface from nuclear fragments produced by high-energy nucleons

    Science.gov (United States)

    Cucinotta, Francis A.; Hajnal, Ferenc; Wilson, John W.

    1990-01-01

    The transport of nuclear fragmentation recoils produced by high-energy nucleons in the region of the bone-tissue interface is considered. Results for the different flux and absorbed dose for recoils produced by 1 GeV protons are presented in a bidirectional transport model. The energy deposition in marrow cavities is seen to be enhanced by recoils produced in bone. Approximate analytic formulae for absorbed dose near the interface region are also presented for a simplified range-energy model.

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

    Directory of Open Access Journals (Sweden)

    Gabriel Olmos

    2013-05-01

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

  12. On the definition of absorbed dose

    International Nuclear Information System (INIS)

    Grusell, Erik

    2015-01-01

    Purpose: The quantity absorbed dose is used extensively in all areas concerning the interaction of ionizing radiation with biological organisms, as well as with matter in general. The most recent and authoritative definition of absorbed dose is given by the International Commission on Radiation Units and Measurements (ICRU) in ICRU Report 85. However, that definition is incomplete. The purpose of the present work is to give a rigorous definition of absorbed dose. Methods: Absorbed dose is defined in terms of the random variable specific energy imparted. A random variable is a mathematical function, and it cannot be defined without specifying its domain of definition which is a probability space. This is not done in report 85 by the ICRU, mentioned above. Results: In the present work a definition of a suitable probability space is given, so that a rigorous definition of absorbed dose is possible. This necessarily includes the specification of the experiment which the probability space describes. In this case this is an irradiation, which is specified by the initial particles released and by the material objects which can interact with the radiation. Some consequences are discussed. Specific energy imparted is defined for a volume, and the definition of absorbed dose as a point function involves the specific energy imparted for a small mass contained in a volume surrounding the point. A possible more precise definition of this volume is suggested and discussed. Conclusions: The importance of absorbed dose motivates a proper definition, and one is given in the present work. No rigorous definition has been presented before. - Highlights: • A stringent definition of absorbed dose is given. • This requires the definition of an irradiation and a suitable probability space. • A stringent definition is important for an understanding of the concept absorbed dose

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

    African Journals Online (AJOL)

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

  14. Specific absorbed fractions of energy at various ages from internal photon sources: 1, Methods

    International Nuclear Information System (INIS)

    Cristy, M.; Eckerman, K.F.

    1987-04-01

    Specific absorbed fractions (PHI's) in various organs of the body (target organs) from sources of monoenergetic photons in various other organs (source organs) are tabulated. This volume outlines various methods used to compute the PHI-values and describes how the ''best'' estimates recommended by us are chosen. These PHI-values can be used in calculating the photon component of the dose-equivalent rate in a given target organ from a given radionuclide that is present in a given source organ. The International Commission on Radiological Protection recognizes that the endosteal, or bone surface, cells are the tissue at risk for bone cancer. We have applied the dosimetry methods that Spiers and co-workers developed for beta-emitting radionuclides deposited in bone to follow the transport of secondary electrons that were freed by photon interactions through the microscopic structure of the skeleton. With these methods we can estimate PHI in the endosteal cells and can better estimate PHI in the active marrow; the latter is overestimated with the methods at photon energies below 200 keV. 41 refs., 25 figs., 23 tabs

  15. 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

  16. The Development of Two Composite Energy Absorbers for Use in a Transport Rotorcraft Airframe Crash Testbed (TRACT 2) Full-Scale Crash Test

    Science.gov (United States)

    Littell, Justin D.; Jackson, Karen E.; Annett, Martin S.; Seal, Michael D.; Fasanella, Edwin L.

    2015-01-01

    Two composite energy absorbers were developed and evaluated at NASA Langley Research Center through multi-level testing and simulation performed under the Transport Rotorcraft Airframe Crash Testbed (TRACT) research program. A conical-shaped energy absorber, designated the conusoid, was evaluated that consisted of four layers of hybrid carbon-Kevlar plain weave fabric oriented at [+45deg/-45deg/-45deg/+45deg] with respect to the vertical direction. A sinusoidal-shaped energy absorber, designated the sinusoid, was developed that consisted of hybrid carbon-Kevlar plain weave fabric face sheets, two layers for each face sheet oriented at +/-45deg with respect to the vertical direction, and a closed-cell ELFOAM P200 polyisocyanurate (2.0-lb/cu ft) foam core. The design goal for the energy absorbers was to achieve average floor-level accelerations of between 25- and 40-g during the full-scale crash test of a retrofitted CH-46E helicopter airframe, designated TRACT 2. Variations in both designs were assessed through dynamic crush testing of component specimens. Once the designs were finalized, subfloor beams of each configuration were fabricated and retrofitted into a barrel section of a CH-46E helicopter. A vertical drop test of the barrel section was conducted onto concrete to evaluate the performance of the energy absorbers prior to retrofit into TRACT 2. The retrofitted airframe was crash tested under combined forward and vertical velocity conditions onto soft soil. Finite element models were developed of all test articles and simulations were performed using LS-DYNA, a commercial nonlinear explicit transient dynamic finite element code. Test-analysis results are presented for each energy absorber as comparisons of time-history responses, as well as predicted and experimental structural deformations and progressive damage under impact loading for each evaluation level.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  19. Selective solar absorbers: A cost effective solution for access to clean energy in rural Africa

    CSIR Research Space (South Africa)

    Katumba, G

    2008-11-01

    Full Text Available by inadequate grid electricity infrastructure. This state of affairs has culminated in massive deforestation and desertification of some parts of Africa. One technology solution is to harness the energy from the sun through solar absorbers. This has applications...

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  1. 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.

  2. 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.

  3. 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....

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

    Science.gov (United States)

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

    2012-03-13

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

  5. Passive notch circuit for pulsed-off compression fields

    International Nuclear Information System (INIS)

    Nunnally, W.C.

    1976-06-01

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

  6. A closed-form formulation for the build-up factor and absorbed energy for photons and electrons in the Compton energy range in Cartesian geometry

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Volnei; Vilhena, Marco Tullio, E-mail: borges@ufrgs.b, E-mail: vilhena@pq.cnpq.b [Universidade Federal do Rio Grande do Sul (PROMEC/UFRGS), Porto Alegre, RS (Brazil). Programa de Pos-Graduacao em Engenharia Mecanica; Fernandes, Julio Cesar Lombaldo, E-mail: julio.lombaldo@ufrgs.b [Universidade Federal do Rio Grande do Sul (DMPA/UFRGS), Porto Alegre, RS (Brazil). Dept. de Matematica Pura e Aplicada. Programa de Pos Graduacao em Matematica Aplicada

    2011-07-01

    In this work, we report on a closed-form formulation for the build-up factor and absorbed energy, in one and two dimensional Cartesian geometry for photons and electrons, in the Compton energy range. For the one-dimensional case we use the LTS{sub N} method, assuming the Klein-Nishina scattering kernel for the determination of the angular radiation intensity for photons. We apply the two-dimensional LTS{sub N} nodal solution for the averaged angular radiation evaluation for the two-dimensional case, using the Klein-Nishina kernel for photons and the Compton kernel for electrons. From the angular radiation intensity we construct a closed-form solution for the build-up factor and evaluate the absorbed energy. We present numerical simulations and comparisons against results from the literature. (author)

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

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

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

  8. Measurements of a prototype synchrotron radiation pumped absorber for future light sources

    International Nuclear Information System (INIS)

    Chou, T.S.; Foerster, C.L.; Halama, H.; Lanni, C.

    1988-01-01

    In the new generation of advanced synchrotron light sources, the conventional concept of distributed pumping is no longer suitable for removing the gas load caused by photon stimulated desorption (PSD). A new concept using a combination of photon absorber and pumping station has been designed, constructed, and installed in the U1OB beam line at the VUV ring of the National Synchrotron Light Source. The system consists of an electrically insulated water cooled copper block, a titanium sublimation pump, calibrated BA gauges, a calibrated RGA, and a known conductance. A photon beam 10 milliradian wide and 3.26 milliradian high, having critical energy of 500 eV, is directed on the absorber. PSD yield is studied as a function of total beam dose and absorber surface preparation. The results from this experiment, pump characteristics, design of an absorber pump for future light sources, and the pressure improvement factors will be presented. 5 refs., 7 figs., 1 tab

  9. Comparison of GEANT4 Simulations with Experimental Data for Thick Al Absorbers

    International Nuclear Information System (INIS)

    Yevseyeva, Olga; Assis, Joaquim de; Evseev, Ivan; Schelin, Hugo; Paschuk, Sergei; Milhoretto, Edney; Setti, Joao; Diaz, Katherin; Lopes, Ricardo; Hormaza, Joel

    2009-01-01

    Proton beams in medical applications deal with relatively thick targets like the human head or trunk. Therefore, relatively small differences in the total proton stopping power given, for example, by the different models provided by GEANT4 can lead to significant disagreements in the final proton energy spectra when integrated along lengthy proton trajectories. This work presents proton energy spectra obtained by GEANT4.8.2 simulations using ICRU49, Ziegler1985 and Ziegler2000 models for 19.68 MeV protons passing through a number of Al absorbers with various thicknesses. The spectra were compared with the experimental data, with TRIM/SRIM2008 and MCNPX2.4.0 simulations, and with the Payne analytical solution for the transport equation in the Fokker-Plank approximation. It is shown that the MCNPX simulations reasonably reproduce well all experimental spectra. For the relatively thin targets all the methods give practically identical results but this is not the same for the thick absorbers. It should be noted that all the spectra were measured at the proton energies significantly above 2 MeV, i.e., in the so-called 'Bethe-Bloch region'. Therefore the observed disagreements in GEANT4 results, simulated with different models, are somewhat unexpected. Further studies are necessary for better understanding and definitive conclusions.

  10. Towards limits of excitation energy in the reaction 3He(1.8 GeV) + natAg

    International Nuclear Information System (INIS)

    Pollacco, E.C.; Brzychczyk, J.; Volant, C.; Legrain, R.; Nalpas, L.; Bracken, D.S.; Kwiatkowski, K.; Morley, K.B.; Foxford, E.R.; Viola, V.E.; Yoder, N.R.

    1996-03-01

    Hot nuclei are studied, where through an appropriate choice of incident channel and event selection, dynamical effects are attenuated and multifragmentation is limited. Three preparatory results are given, the 3 He(1.8 GeV) + nat Ag can be described using an intranuclear cascade, INC, model; through a suitable selection of events a limit of the excitation energy that a nucleus can absorb without breaking into large pieces is given, it is shown that corresponding alpha decay is consistent with an evaporative process. (K.A.)

  11. Design Considerations for an MEBT Chopper Absorber of 2.1 MeV H- at the Project X Injector Experiment at Fermilab

    Energy Technology Data Exchange (ETDEWEB)

    Baffes, C.; Awida, M.; Chen, A.; Eidelman, Y.; Lebedev, V.; Prost, L.; Shemyakin, A.; Solyak, N.; Yakovlev, V.; /Fermilab

    2012-05-14

    The Project X Injector Experiment (PIXIE) will be a prototype of the Project X front end that will be used to validate the design concept and decrease technical risks. One of the most challenging components of PIXIE is the wide-band chopping system of the Medium Energy Beam Transport (MEBT) section, which will form an arbitrary bunch pattern from the initially CW 162.5 MHz 5mA beam. The present scenario assumes diverting 80% of the beam to an absorber to provide a beam with the average current of 1mA to SRF linac. This absorber must withstand a high level of energy deposition and high ion fluence, while being positioned in proximity of the superconductive cavities. This paper discusses design considerations for the absorber. Thermal and mechanical analyses of a conceptual design are presented, and future plans for the fabrication and testing of a prototype are described.

  12. Visible light broadband perfect absorbers

    Energy Technology Data Exchange (ETDEWEB)

    Jia, X. L.; Meng, Q. X.; Yuan, C. X.; Zhou, Z. X.; Wang, X. O., E-mail: wxo@hit.edu.cn [School of Science, Harbin Institute of Technology, Harbin 150001 (China)

    2016-03-15

    The visible light broadband perfect absorbers based on the silver (Ag) nano elliptical disks and holes array are studied using finite difference time domain simulations. The semiconducting indium silicon dioxide thin film is introduced as the space layer in this sandwiched structure. Utilizing the asymmetrical geometry of the structures, polarization sensitivity for transverse electric wave (TE)/transverse magnetic wave (TM) and left circular polarization wave (LCP)/right circular polarization wave (RCP) of the broadband absorption are gained. The absorbers with Ag nano disks and holes array show several peaks absorbance of 100% by numerical simulation. These simple and flexible perfect absorbers are particularly desirable for various potential applications including the solar energy absorber.

  13. Sound Absorbers

    Science.gov (United States)

    Fuchs, H. V.; Möser, M.

    Sound absorption indicates the transformation of sound energy into heat. It is, for instance, employed to design the acoustics in rooms. The noise emitted by machinery and plants shall be reduced before arriving at a workplace; auditoria such as lecture rooms or concert halls require a certain reverberation time. Such design goals are realised by installing absorbing components at the walls with well-defined absorption characteristics, which are adjusted for corresponding demands. Sound absorbers also play an important role in acoustic capsules, ducts and screens to avoid sound immission from noise intensive environments into the neighbourhood.

  14. Regularities in the Changes of Absorber Material Properties as a Function of Absorber Concentration; Regularite des Variations des Proprietes des Substances Absorbantes en Fonction de la Concentration de l'Absorbant; Zakonomernosti izmeneniya svojstv poglashchayushchikh materialov v zavisimosti ot kontsentratsii poglotitelya; Leyes de Variacion de las Propiedades de los Materiales Absorbentes en Funcion de la Concentracion del Absorbente

    Energy Technology Data Exchange (ETDEWEB)

    Portnoj, K. I.

    1964-06-15

    pouvoir absorbant, en tant que fonction de la concentration de l'absorbant, varie d'apres une courbe caracteristique d'un phenomene de saturation et depend du spectre de neutrons. L'auteur formule une hypothese sur l'obtention du pouvoir absorbant maximum grace a la combinaison de plusieurs absorbants. Cette hypothese a ete largement confirmee par des experiences effectuees, dans des reacteurs a neutrons thermiques et intermediaires, sur de nombreuses combinaisons d'absorbants metalliques ou non. (author) [Spanish] En esta memoria se exponen las leyes que rigen las variaciones de las propiedades mecanicas y termofisicas y del poder de absorcion, en funcion de la concentracion del absorbente, en aleaciones destinadas a los reactores de neutrones termicos e intermedios. La conductividad y el coeficiente de dilatacion termica de las aleaciones absorbentes a base de boro y oxidos de las tierras raras se reducen al aumentar dicha concentracion. En el caso de las aleaciones con oxidos de las tierras raras, la variacion del coeficiente de dilatacion es lineal, mientras que para las alea,- ciones de boro esa caracteristica aditiva se altera. Ello se debe a que a temperaturas elevadas se forman fases de boruro con distintas redes cristalinas. En cuanto al poder absorbente, varia segun una curva de saturacion y depende tambien del espectro neutronico. El autor propone una hipotesis para explicar la aparicion de un maximo en la curva del poder absorbente, que atribuye a un fenomeno de interaleacion de los absorbentes. Esta hipotesis ha sido confirmada ampliamente por los resultados de experimentos efectuados con muchos sistemas absorbentes metalicos y no metalicos, de variada composicion, en reactores de neutrones termicos e intermedios. (author) [Russian] Doklad stavit cel'ju izlozhit' poluchennye zakonomernosti izmenenija mehanicheskih i teplofizicheskih svojstv, a takzhe pogloshhajushhej sposobnosti v zavisimosti ot koncentracii poglotitelej v sp lav a h , prednaznachennyh dlja

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  16. Prompt-gamma detection towards absorbed energy monitoring during hadrontherapy

    Energy Technology Data Exchange (ETDEWEB)

    Krimmer, J.; Balleyguier, L.; Dauvergne, D.; Mathez, H.; Pinto, M.; Testa, E.; Zoccarato, Y. [Institut de Physique Nucleaire de Lyon, Universite de Lyon, Universite de Lyon 1, IN2P3/CNRS, UMR 5822, F-69622 Villeurbanne cedex (France); Krimmer, J.; Freud, N.; L' etang, J.M. [Universite de Lyon, CREATIS, CNRS UMR 5220, Inserm U1044, INSA - Lyon, Universite Lyon 1, Centre Leon Berard (France); Herault, J.; Amblard, R.; Angellier, G. [Centre Antoine Lacassagne, Cyclotron Biomedical, 227 Avenue de la Lanterne, 06200 Nice (France)

    2015-07-01

    Hadrontherapy is an emerging technique which exploits the fact that a large quantity of the energy of the incident particles is deposited at the end of their flight path. This allows a conformation of the applied dose to the tumor volume and a simultaneous sparing of surrounding healthy tissue. A real-time control of the ion range during the treatment is possible via the detection of prompt secondary radiation (gamma rays or charged particles). Besides a monitoring of the ion range, the knowledge of the total energy absorbed inside the patient is also of importance for an improvement of the treatment quality. It has been shown that the ambient dose in a treatment room is correlated to the monitoring units, i.e. the number of protons of the beam delivery system. The present study consists in applying time-of-flight (TOF) information to identify prompt gamma-rays generated by interactions inside the patient which provides a direct information on the energy imparted. Results from test measurements will be given, which show that events generated in the nozzle and the target phantom can be discriminated. Furthermore, a standalone detection system is being developed which will be read out by a standard PC. The status of the developments for the corresponding electronics will be presented. (authors)

  17. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Science.gov (United States)

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  18. Methods for applying microchannels to separate methane using liquid absorbents, especially ionic liquid absorbents from a mixture comprising methane and nitrogen

    Science.gov (United States)

    Tonkovich, Anna Lee Y [Dublin, OH; Litt, Robert D [Westerville, OH; Dongming, Qiu [Dublin, OH; Silva, Laura J [Plain City, OH; Lamont, Micheal Jay [Plain City, OH; Fanelli, Maddalena [Plain City, OH; Simmons, Wayne W [Plain city, OH; Perry, Steven [Galloway, OH

    2011-10-04

    Methods of using microchannel separation systems including absorbents to improve thermal efficiency and reduce parasitic power loss. Energy is typically added to desorb methane and then energy or heat is removed to absorb methane using a working solution. The working solution or absorbent may comprise an ionic liquid, or other fluids that demonstrate a difference in affinity between methane and nitrogen in a solution.

  19. Collision cross sections of N2 by H+ impact at keV energies within time-dependent density-functional theory

    Science.gov (United States)

    Yu, W.; Gao, C.-Z.; Zhang, Y.; Zhang, F. S.; Hutton, R.; Zou, Y.; Wei, B.

    2018-03-01

    We calculate electron capture and ionization cross sections of N2 impacted by the H+ projectile at keV energies. To this end, we employ the time-dependent density-functional theory coupled nonadiabatically to molecular dynamics. To avoid the explicit treatment of the complex density matrix in the calculation of cross sections, we propose an approximate method based on the assumption of constant ionization rate over the period of the projectile passing the absorbing boundary. Our results agree reasonably well with experimental data and semi-empirical results within the measurement uncertainties in the considered energy range. The discrepancies are mainly attributed to the inadequate description of exchange-correlation functional and the crude approximation for constant ionization rate. Although the present approach does not predict the experiments quantitatively for collision energies below 10 keV, it is still helpful to calculate total cross sections of ion-molecule collisions within a certain energy range.

  20. 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.

  1. 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...

  2. Direct determination of k Q factors for cylindrical and plane-parallel ionization chambers in high-energy electron beams from 6 MeV to 20 MeV

    Science.gov (United States)

    Krauss, A.; Kapsch, R.-P.

    2018-02-01

    For the ionometric determination of the absorbed dose to water, D w, in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q, are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm  ×  10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

  3. Direct determination of k Q factors for cylindrical and plane-parallel ionization chambers in high-energy electron beams from 6 MeV to 20 MeV.

    Science.gov (United States)

    Krauss, A; Kapsch, R-P

    2018-02-06

    For the ionometric determination of the absorbed dose to water, D w , in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q , are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm  ×  10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

  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. Dangerous Liaisons: Deviant Endothelium NOTCHes toward Tumor Metastasis.

    Science.gov (United States)

    Guo, Peipei; Rafii, Shahin

    2017-03-13

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

  6. Designing a point-absorber wave energy converter for the Mediterranean Sea

    International Nuclear Information System (INIS)

    Archetti, Renata; Moreno Miquel, Adria; Antonini, Alessandro; Passoni, Giuseppe; Bozzi, Silvia; Gruosso, Giambattista; Scarpa, Francesca; Bizzozero, Federica; Giassi, Marianna

    2015-01-01

    This work aims to assess the potential for wave energy production in the Italian seas by the deployment of arrays of heaving point absorbers, specifically optimized for mild climates. We model a single-body WEC, consisting of a cylindrical heaving buoy, attached to a linear electric generator placed on the seabed. The model includes both hydrodynamic and electromechanical forces. The results show that the best buoy-generator configuration at the selected sites (Alghero and Mazara del Vallo) is given by a 6 to 10 kW device and with a buoy with diameter between 4 and 5 m. This device can be brought to resonance, increasing the performances, by adding a submerged sphere. These results are encouraging and enlarge the perspective on wave energy production in the Italian seas. [it

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  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. 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

  10. Update on the Code Intercomparison and Benchmark for Muon Fluence and Absorbed Dose Induced by an 18 GeV Electron Beam After Massive Iron Shielding

    Energy Technology Data Exchange (ETDEWEB)

    Fasso, A. [SLAC; Ferrari, A. [CERN; Ferrari, A. [HZDR, Dresden; Mokhov, N. V. [Fermilab; Mueller, S. E. [HZDR, Dresden; Nelson, W. R. [SLAC; Roesler, S. [CERN; Sanami, t.; Striganov, S. I. [Fermilab; Versaci, R. [Unlisted, CZ

    2016-12-01

    In 1974, Nelson, Kase and Svensson published an experimental investigation on muon shielding around SLAC high-energy electron accelerators [1]. They measured muon fluence and absorbed dose induced by 14 and 18 GeV electron beams hitting a copper/water beamdump and attenuated in a thick steel shielding. In their paper, they compared the results with the theoretical models available at that time. In order to compare their experimental results with present model calculations, we use the modern transport Monte Carlo codes MARS15, FLUKA2011 and GEANT4 to model the experimental setup and run simulations. The results are then compared between the codes, and with the SLAC data.

  11. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. 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.

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

    Science.gov (United States)

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

    2018-02-12

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

  15. 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.

  16. Charpy Impact Test on Polymeric Molded Parts

    Directory of Open Access Journals (Sweden)

    Alexandra Raicu

    2012-09-01

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

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

    OpenAIRE

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

    2016-01-01

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

  18. AMS of 93Zr: Passive absorber versus gas-filled magnet

    Science.gov (United States)

    Hain, Karin; Deneva, Boyana; Faestermann, Thomas; Fimiani, Leticia; Gómez-Guzmán, José Manuel; Koll, Dominik; Korschinek, Gunther; Ludwig, Peter; Sergeyeva, Victoria; Thiollay, Nicolas

    2018-05-01

    Two different isobar separation techniques were tested for the detection of the long-lived fission product 93Zr (T1/2 = 1.64 · 106 a) using Accelerator Mass Spectrometry (AMS), i.e. a passive absorber and a gas-filled magnet, respectively. Both techniques were used in combination with a Time-of-Flight path for the identification of the stable neighboring isotopes 92Zr and 94Zr. The passive absorber was represented by a stack of silicon nitride foils for high flexibility regarding the thickness for optimal isobar separation. Ion beams with a large variety of energies, between 80 and 180 MeV, were provided for this experiment by the tandem accelerator at the Maier-Leibnitz Laboratory in Garching, Germany. With these beams, the stopping powers of 93Zr and 93Nb as a function of energy were determined experimentally and compared to the results obtained with the simulation program SRIM. Considerable discrepancies regarding the energy dependence of the two stopping power curves relative to each other were found. The lowest detection limit for 93Zr achieved with the passive absorber setup was 93Zr/Zr = 1 · 10-10. In comparison, by optimizing the gas-filled magnet set-up, 93Nb was suppressed by around six orders of magnitude and a detection limit of 93Zr/Zr = 5 · 10-11 was obtained. To our knowledge, these results represent the lowest detection limit achieved for 93Zr until now.

  19. 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 ...

  20. 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)

  1. 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...

  2. 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.

  3. 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.

  4. A new energy-absorbing bolt for rock support in high stress rock masses

    Energy Technology Data Exchange (ETDEWEB)

    Charlie Chunlin Li [Norwegian University of Science and Technology (NTNU) (Norway)

    2010-04-15

    An energy-absorbing rock support device, called a D bolt, has been recently developed to counteract both burst-prone and squeezing rock conditions that occur during underground excavation. The bolt is a smooth steel bar with a number of anchors along its length. The anchors are firmly fixed within a borehole using either cement grout or resin, while the smooth sections of the bolt between the anchors may freely deform in response to rock dilation. Failure of one section does not affect the reinforcement performance of the other sections. The bolt is designed to fully use both the strength and the deformation capacity of the bolt material along the entire length. The bolt has large load-bearing and deformation capacities. Static pull tests and dynamic drop tests show that the bolt length elongates by 14-20% at a load level equal to the strength of the bolt material, thereby absorbing a large amount of energy. The impact average load of a 20 mm D bolt is 200-230 kN, with only a small portion of the load transferred to the bolt plate. The cumulative dynamic energy absorption of the bolt is measured to be 47 kJ/m. D bolts were tested in three deep mines. Filed measurements show that D bolts are loaded less than rebar bolts. This paper presents the layout and principle of the D bolt, and corresponding results from static, dynamic, and field tests.

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

    Directory of Open Access Journals (Sweden)

    Jerry S Chen

    2014-06-01

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

  6. Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2010-10-01

    Full Text Available Abstract Background Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. Method Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1 expression. Results Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I. Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Conclusions Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

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

    Directory of Open Access Journals (Sweden)

    Mozhgan Farshbaf

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

  8. 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.

  9. 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.

  10. Design and testing of an energy-absorbing crewseat for the F/FB-111 aircraft. Volume 3: Data from crew module testing

    Science.gov (United States)

    Shane, S. J.

    1985-01-01

    Over the past years, several papers and reports have documented the unacceptably high injury rate during the escape sequence (including the ejection and ground impact) of the crew module for F/FB-111 aircraft. This report documents a program to determine if the injury potential could be reduced by replacing the existing crewseats with energy absorbing crewseats. An energy absorbing test seat was designed using much of the existing seat hardware. An extensive dynamic seat test series, designed to duplicate various crew module ground impact conditions, was conducted at a sled test facility. Comparative tests with operational F-111 crewseats were also conducted. After successful dynamic testing of the seat, more testing was conducted with the seats mounted in an F-111 crew module. Both swing tests and vertical drop tests werre conducted. The vertical drop tests were used to obtain comparative data between the energy absorbing and operational seats.

  11. Microwave energy harvesting based on metamaterial absorbers with multi-layered square split rings for wireless communications

    Science.gov (United States)

    Karaaslan, Muharrem; Bağmancı, Mehmet; Ünal, Emin; Akgol, Oguzhan; Sabah, Cumali

    2017-06-01

    We propose the design of a multiband absorber based on multi-layered square split ring (MSSR) structure. The multi-layered metamaterial structure is designed to be used in the frequency bands such as WIMAX, WLAN and satellite communication region. The absorption levels of the proposed structure are higher than 90% for all resonance frequencies. In addition, the incident angle and polarization dependence of the multi-layered metamaterial absorber and harvester is also investigated and it is observed that the structure has polarization angle independent frequency response with good absorption characteristics in the entire working frequency band. The energy harvesting ratios of the structure is investigated especially for the resonance frequencies at which the maximum absorption occurs. The energy harvesting potential of the proposed MSSRs is as good as those of the structures given in the literature. Therefore, the suggested design having good absorption, polarization and angle independent characteristics with a wide bandwidth is a potential candidate for future energy harvesting applications in commonly used wireless communication bands, namely WIMAX, WLAN and satellite communication bands.

  12. 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.

  13. Comparison of measurements of absorbed dose to water using a water calorimeter and ionization chambers for clinical radiotherapy photon and electron beams

    International Nuclear Information System (INIS)

    Marles, A.E.M.

    1981-01-01

    With the development of the water calorimeter direct measurement of absorbed dose in water becomes possible. This could lead to the establishment of an absorbed dose rather than an exposure related standard for ionization chambers for high energy electrons and photons. In changing to an absorbed dose standard it is necessary to investigate the effect of different parameters, among which are the energy dependence, the air volume, wall thickness and material of the chamber. The effect of these parameters is experimentally studied and presented for several commercially available chambers and one experimental chamber, for photons up to 25 MV and electrons up to 20 MeV, using a water calorimeter as the absorbed dose standard and the most recent formalism to calculate the absorbed dose with ion chambers. For electron beams, the dose measured with the calorimeter was 1% lower than the dose calculated with the chambers, independent of beam energy and chamber. For photon beams, the absorbed dose measured with the calorimeter was 3.8% higher than the absorbed dose calculated from the chamber readings. Such differences were found to be chamber and energy independent. The results for the photons were found to be statistically different from the results with the electron beams. Such difference could not be attributed to a difference in the calorimeter response

  14. Alpha Beam Energy Determination Using a Range Measuring Device for Radioisotope Production

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jun Yong; Kim, Byeon Gil; Hong, Seung Pyo; Kim, Ran Young; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-05-15

    The threshold energy of the {sup 209}Bi(α,3n){sup 210} At reaction is at about 30MeV. Our laboratory suggested an energy measurement method to confirm the proton-beam's energy by using a range measurement device. The experiment was performed energy measurement of alpha beam. The alpha beam of energy 29 MeV has been extracted from the cyclotron for the production of {sup 211}At. This device was composed of four parts: an absorber, a drive shaft, and a servo motor and a Faraday cup. The drive shaft was mounted on the absorber and connects with the axis of the servo motor and rotates linearly and circularly by this servo motor. A Faraday cup is for measuring the beam flux. As this drive shaft rotates, the thickness of the absorber varies depending on the rotation angle of the absorber. The energy of the alpha particle accelerated and extracted from MC-50 cyclotron was calculated with the measurement of the particle range in Al foil and using ASTAR, SRIM, MCNPX software. There were a little discrepancy between the expected energy and the calculated energy within the 0.5MeV error range. We have a plan to make an experiment with various alpha particle energies and another methodology, for example, the cross section measurement of the nuclear reaction.

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

    Directory of Open Access Journals (Sweden)

    Murni Tio

    Full Text Available In Drosophila, dopaminergic (DA neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development. Furthermore, we show that loss of function (l-o-f mutations of genes of the apical complex proteins in the asymmetric cell division (ACD machinery, such as inscuteable and bazooka result in supernumerary DA neurons, whereas l-o-f mutations of genes of the basal complex proteins such as numb result in loss or reduction of DA neurons. In addition, when Notch signaling is reduced or abolished, additional DA neurons are formed and conversely, when Notch signaling is activated, less DA neurons are generated. Our data demonstrate that both ACD and Notch signaling are crucial mechanisms for DA neuronal specification. We propose a model in which ACD results in differential Notch activation in direct siblings and in this context Notch acts as a repressor for DA neuronal specification in the sibling that receives active Notch signaling. Our study provides the first link of ACD and Notch signaling in the specification of a neurotransmitter phenotype in Drosophila. Given the high degree of conservation between Drosophila and vertebrate systems, this study could be of significance to mechanisms of DA neuronal differentiation not limited to flies.

  16. 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

  17. BRIGITTE, Dose Rate and Heat Source and Energy Flux for Self-Absorbing Rods

    International Nuclear Information System (INIS)

    Jegu, M.; Clement, M.

    1978-01-01

    1 - Nature of physical problem solved: Calculation of dose rate, heat sources or energy flux. The sources are self-absorbing radioactive rods. The shielding consists of blocks of which the cross section can be defined. 2 - Method of solution: Exponential attenuation and build-up factor between source points and detector points. Source integration with error estimate. Automatic or controlled build-up with monitor print-out. 3 - Restrictions on the complexity of the problem: Number of energy points, regions, detector points, abscissa points of the rod, vertical position of the rod, are all limited to ten. The maximum total number of vertical steps is 124

  18. Experimental and Analytical Evaluation of a Composite Honeycomb Deployable Energy Absorber

    Science.gov (United States)

    Jackson, Karen E.; Kellas, Sotiris; Horta, Lucas G.; Annett, Martin S.; Polanco, Michael A.; Littell, Justin D.; Fasanella, Edwin L.

    2011-01-01

    In 2006, the NASA Subsonic Rotary Wing Aeronautics Program sponsored the experimental and analytical evaluation of an externally deployable composite honeycomb structure that is designed to attenuate impact energy during helicopter crashes. The concept, which is designated the Deployable Energy Absorber (DEA), utilizes an expandable Kevlar honeycomb structure to dissipate kinetic energy through crushing. The DEA incorporates a unique flexible hinge design that allows the honeycomb to be packaged and stowed flat until needed for deployment. A variety of deployment options such as linear, radial, and/or hybrid methods can be used. Experimental evaluation of the DEA utilized a building block approach that included material characterization testing of its constituent, Kevlar -129 fabric/epoxy, and flexural testing of single hexagonal cells. In addition, the energy attenuation capabilities of the DEA were demonstrated through multi-cell component dynamic crush tests, and vertical drop tests of a composite fuselage section, retrofitted with DEA blocks, onto concrete, water, and soft soil. During each stage of the DEA evaluation process, finite element models of the test articles were developed and simulations were performed using the explicit, nonlinear transient dynamic finite element code, LS-DYNA. This report documents the results of the experimental evaluation that was conducted to assess the energy absorption capabilities of the DEA.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Morphometric study of suprascapular notch in Indian dry scapulae with specific reference to the incidence of completely ossified superior transverse scapular ligament.

    Science.gov (United States)

    Kannan, Usha; Kannan, N S; Anbalagan, J; Rao, Sudha

    2014-03-01

    The suprascapular notch, a depression on the lateral part of the superior border of the scapula, medial to the coracoid process, is bridged by the superior transverse scapular ligament, which is sometimes ossified and the foramen which is thus completed, transmits the suprascapular nerve to the supraspinatus fossa. Variations in the morphology of suprascapular notch have been identified as one of the causes of suprascapular nerve entrapment. Rengachary et al. classified this notch into six types, based on its shape. To study morphological variations of suprascapular notch in Indian dry scapulae and to analyze the incidence of completely ossified superior transverse scapular ligament with other ethnic populations which have been cited earlier. A total of 400 human dry scapulae which were obtained from the Department of Anatomy of selected eight medical colleges were analyzed. The type of suprascapular notch was noted and it was recorded as per the description given by Rengachary et al. The results of the present study were compared with the results of previous authors in different populations. In our study, out of 400 scapulae, 40 (10%), were identified to have completely ossified superior transverse scapular ligaments. The frequencies of various types of suprascapular notches were: Type I -20%, Type II -10%, Type III -52%, Type IV -4%, Type V -4%, Type VI -10%. Since the suprascapular nerve entrapment syndrome might be caused by complete ossification of superior transverse scapular ligament with formation of suprascapular foramen and other morphometric variations of suprascapular notch, the knowledge on such variations is essential for clinicians, for making a proper diagnosis and for planning the most suitable surgical intervention.

  1. Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature

    DEFF Research Database (Denmark)

    Kristoffersen, Karina; Nedergaard, Mette Kjølhede; Villingshøj, Mette

    2014-01-01

    BACKGROUND: Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in the devastating brain tumor glioblastoma multiforme (GBM). bCSC are proposed a central role in tumor initiation, progression, treatment resistance and relapse and as such present...... a promising target in GBM research. The Notch signaling pathway is often deregulated in GBM and we have previously characterized GBM-derived bCSC cultures based on their expression of the Notch-1 receptor and found that it could be used as predictive marker for the effect of Notch inhibition. The aim...... of the present project was therefore to further elucidate the significance of Notch pathway activity for the tumorigenic properties of GBM-derived bCSC. METHODS: Human-derived GBM xenograft cells previously established as NSC-like neurosphere cultures were used. Notch inhibition was accomplished by exposing...

  2. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Directory of Open Access Journals (Sweden)

    Richa Tripathi

    Full Text Available Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis.This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting.80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively.These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Neeta Bala Tannan

    2018-01-01

    Full Text Available AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

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

    Science.gov (United States)

    Bala Tannan, Neeta; Collu, Giovanna; Humphries, Ashley C; Serysheva, Ekatherina; Weber, Ursula; Mlodzik, Marek

    2018-01-01

    AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

  5. Fluence-to-absorbed-dose conversion coefficients for neutron beams from 0.001 eV to 100 GeV calculated for a set of pregnant female and fetus models

    International Nuclear Information System (INIS)

    Taranenko, Valery; Xu, X George

    2008-01-01

    Protection of fetuses against external neutron exposure is an important task. This paper reports a set of absorbed dose conversion coefficients for fetal and maternal organs for external neutron beams using the RPI-P pregnant female models and the MCNPX code. The newly developed pregnant female models represent an adult female with a fetus including its brain and skeleton at the end of each trimester. The organ masses were adjusted to match the reference values within 1%. For the 3 mm cubic voxel size, the models consist of 10-15 million voxels for 35 organs. External monoenergetic neutron beams of six standard configurations (AP, PA, LLAT, RLAT, ROT and ISO) and source energies 0.001 eV-100 GeV were considered. The results are compared with previous data that are based on simplified anatomical models. The differences in dose depend on source geometry, energy and gestation periods: from 20% up to 140% for the whole fetus, and up to 100% for the fetal brain. Anatomical differences are primarily responsible for the discrepancies in the organ doses. For the first time, the dependence of mother organ doses upon anatomical changes during pregnancy was studied. A maximum of 220% increase in dose was observed for the placenta in the nine months model compared to three months, whereas dose to the pancreas, small and large intestines decreases by 60% for the AP source for the same models. Tabulated dose conversion coefficients for the fetus and 27 maternal organs are provided

  6. Application and validation of the notch master curve in medium and high strength structural steels

    Energy Technology Data Exchange (ETDEWEB)

    Cicero, Sergio; Garcia, Tiberio [Universidad de Cantabria, Santander (Spain); Madrazo, Virginia [PCTCAN, Santander (Spain)

    2015-10-15

    This paper applies and validates the Notch master curve in two ferritic steels with medium (steel S460M) and high (steel S690Q) strength. The Notch master curve is an engineering tool that allows the fracture resistance of notched ferritic steels operating within their corresponding ductile-to-brittle transition zone to be estimated. It combines the Master curve and the Theory of critical distances in order to take into account the temperature and the notch effect respectively, assuming that both effects are independent. The results, derived from 168 fracture tests on notched specimens, demonstrate the capability of the Notch master curve for the prediction of the fracture resistance of medium and high strength ferritic steels operating within their ductile-to-brittle transition zone and containing notches.

  7. Theoretical and experimental study of Chen chaotic system with notch filter feedback control

    International Nuclear Information System (INIS)

    Ming, Zhang Xiao; Jian-Hua, Peng; Ju-Fang, Chen

    2010-01-01

    Since the past two decades, the time delay feedback control method has attracted more and more attention in chaos control studies because of its simplicity and efficiency compared with other chaos control schemes. Recently, it has been proposed to suppress low-dimensional chaos with the notch filter feedback control method, which can be implemented in a laser system. In this work, we have analytically determined the controllable conditions for notch filter feedback controlling of Chen chaotic system in terms of the Hopf bifurcation theory. The conditions for notch filter feedback controlled Chen chaoitc system having a stable limit cycle solution are given. Meanwhile, we also analysed the Hopf bifurcation direction, which is very important for parameter settings in notch filter feedback control applications. Finally, we apply the notch filter feedback control methods to the electronic circuit experiments and numerical simulations based on the theoretical analysis. The controlling results of notch filter feedback control method well prove the feasibility and reliability of the theoretical analysis. (general)

  8. Mutations in the estrogen receptor alpha hormone binding domain promote stem cell phenotype through notch activation in breast cancer cell lines.

    Science.gov (United States)

    Gelsomino, L; Panza, S; Giordano, C; Barone, I; Gu, G; Spina, E; Catalano, S; Fuqua, S; Andò, S

    2018-04-24

    The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behavior of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44 + /CD24 - ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities. Mutant clones exhibited high expression of NOTCH receptors/ligands/target genes and blockade of NOTCH signaling reduced MFE and migratory potential. Mutant BCSC activity was dependent on ERα phosphorylation at serine 118, since its inhibition decreased MFE and NOTCH4 activation only in mutant cells. Collectively, we demonstrate that the expression of HBD-ESR1 mutations may drive BC cells to acquire stem cell traits through ER/NOTCH4 interplay. We propose the early detection of HBD-ESR1 mutations as a challenge in precision medicine strategy, suggesting the development of tailored-approaches (i.e. NOTCH inhibitors) to prevent disease development and metastatic spread in BC mutant-positive patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Genetic screens to identify new Notch pathway mutants in Drosophila.

    Science.gov (United States)

    Giagtzoglou, Nikolaos

    2014-01-01

    Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

  10. 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.

  11. A comparison of MCNP4C electron transport with ITS 3.0 and experiment at incident energies between 100 keV and 20 MeV: influence of voxel size, substeps and energy indexing algorithm

    International Nuclear Information System (INIS)

    Schaart, Dennis R.; Jansen, Jan Th.M.; Zoetelief, Johannes; Leege, Piet F.A. de

    2002-01-01

    The condensed-history electron transport algorithms in the Monte Carlo code MCNP4C are derived from ITS 3.0, which is a well-validated code for coupled electron-photon simulations. This, combined with its user-friendliness and versatility, makes MCNP4C a promising code for medical physics applications. Such applications, however, require a high degree of accuracy. In this work, MCNP4C electron depth-dose distributions in water are compared with published ITS 3.0 results. The influences of voxel size, substeps and choice of electron energy indexing algorithm are investigated at incident energies between 100 keV and 20 MeV. Furthermore, previously published dose measurements for seven beta emitters are simulated. Since MCNP4C does not allow tally segmentation with the *F8 energy deposition tally, even a homogeneous phantom must be subdivided in cells to calculate the distribution of dose. The repeated interruption of the electron tracks at the cell boundaries significantly affects the electron transport. An electron track length estimator of absorbed dose is described which allows tally segmentation. In combination with the ITS electron energy indexing algorithm, this estimator appears to reproduce ITS 3.0 and experimental results well. If, however, cell boundaries are used instead of segments, or if the MCNP indexing algorithm is applied, the agreement is considerably worse. (author)

  12. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    Science.gov (United States)

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

  13. Energy loss of muons in the energy range 1-10000 GeV

    International Nuclear Information System (INIS)

    Lohmann, W.; Kopp, R.; Voss, R.

    1985-01-01

    A summary is given of the most recent formulae for the cross-sections contributing to the energy loss of muons in matter, notably due to electro-magnetic interactions (ionization, bremsstrahlung and electron-pair production) and nuclear interactions. Computed energy losses dE/dx are tabulated for muons with energy between 1 GeV and 10,000 GeV in a number of materials commonly used in high-energy physics experiments. In comparison with earlier tables, these show deviations that grow with energy and amount to several per cent at 200 GeV muon energy. (orig.)

  14. Development of Lead Free Energy Absorber for Space Shuttle Blast Container

    Science.gov (United States)

    Balles, Donald; Ingram, Thomas; Novak, Howard; Schricker, Albert

    1999-01-01

    The Space Shuttle is connected to the mobile launch platform (MLP) by four aft skirt hold down studs on each solid rocket booster (SRB). Prior to lift-off, the frangible nuts inside the aft skirt blast containers are severed into two nut halves by two pyrotechnic booster cartridges. This action releases the Space Shuttle and allows the hold down studs to eject through the aft skirt bore and then down into the MLP. USBI has been tasked to upgrade the blast container for two specific reasons: (1) To eliminate lead for environmental concerns, and (2) To reduce the chance of nut recontact with the holddown stud. Nut recontact with the stud has been identified as a likely contributor to stud hang-ups. This upgrade will replace the lead liner with a unique open cell aluminum foam material, that has commercial and military uses. The aluminum foam used as an energy absorber is a proven design in many other aerospace/defense applications. Additional benefits of using the open cell, energy absorbent aluminum foam in place of the solid lead liner are: (1) Lead handling / exposure and possible contamination, along with hazardous waste disposal, will be eliminated; (2) Approximately 200 lbs. weight savings will be contributed to each Space Shuttle flight by using aluminum foam instead of lead; (3) The new aluminum liner is designed to catch all shrapnel from frangible nuts, thus virtually eliminating chance of debris exiting the HDP and causing potential damage to the vehicle; (4) Using the lighter aluminum liner instead of lead, allows for easier assembly and disassembly of blast container elements, which also improves safety, operator handling, and the efficiency of operations.

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

    Directory of Open Access Journals (Sweden)

    Yeh Hsiao-Fong

    2011-06-01

    Full Text Available Abstract Background The conserved Notch signaling pathway regulates cell fate decisions and maintains stem cells in multicellular organisms. Up-regulation of Notch signaling is observed in several types of cancer and is causally involved in proliferation and survival of cancer cells. Thus, it is of great interest to look for anti-Notch reagents for therapeutic purposes. In model animal Drosophila, Notch signaling restricts selection of sensory organ precursors (SOPs during external sensory (ES organ development. To look for novel genes that can suppress Notch signaling, we performed a gain-of-function modifier screen to look for genes that enhance the phenotype of ectopic ES organs induced by overexpression of phyllopod, a gene required for SOP specification. Results From the gain-of-function screen, we discovered that overexpression of polished rice/tarsal-less (pri/tal increases the numbers of ES organs as well as SOPs. pri/tal is a polycistronic gene that contains four short open reading frames encoding three 11-amino acid and one 32-amino acid peptides. Ectopic expression of the 11 amino-acid peptides recapitulates the pri/tal misexpression phenotype in ectopic ES organ formation. In situ hybridization experiment reveals that pri/tal mRNA is expressed in the SOPs of the chemosensory organs and the stretch-sensing chordotonal organs. In Drosophila wing development, the Notch signaling pathway mediates the formation of the dorsal-ventral (DV compartmental boundary and the restriction of the vein width from the primordial veins, the proveins. We also found that pri/tal mRNA is expressed in the DV boundary and the longitudinal proveins, and overexpression of Pri/Tal peptides disrupts the DV boundary formation and helps to expand the width of the wing vein. Genetic analyses further show that a Notch loss-of-function allele strongly enhances these two phenotypes. Cut and E(splmβ are target genes of the Notch pathway in DV boundary formation and

  16. Tensile behavior of unnotched and notched tungsten--copper laminar composites

    International Nuclear Information System (INIS)

    Hoffman, C.A.

    1976-06-01

    Relations were studied between the tensile strengths of unnotched and of notched, and elastic moduli of unnotched laminar sheet or foil composites and the amounts of reinforcement. Tungsten was used as the reinforcement and copper as the matrix, and the tests were run at room temperature. Three thicknesses of tungsten (i.e., 0.00254, 0.0127, and 0.0254 cm (0.001, 0.005, and 0.010 in) were used, and the nominal volume fraction of tungsten was varied from about 0.05 to 0.95. It was found that the tensile strength of the unnotched specimens could be related to the amount of reinforcement, as could the elastic moduli, and that these values could be predicted by use of the rule of mixtures. The tensile strengths of the notched laminar composites could be predicted by use of the rule of mixtures using strengths for notched constituents, provided notch effects did not predominate. (Author)

  17. Some observations on the nature of the audiometric 4000 hz notch: data from 3430 veterans.

    Science.gov (United States)

    Wilson, Richard H

    2011-01-01

    Pure-tone, air-conduction audiograms notched at 4000 Hz have long been considered the signature configuration for noise-induced hearing loss even though there is an extensive literature that does not mesh with this simple explanation. There are many reports of notched audiograms from individuals with no history of noise exposure and, conversely, reports of audiograms with no notches from individuals with a history of noise exposure. Recent reports increasingly suggest that unilateral 4000 Hz notches are common. The prevalence of notched audiograms at 4000 Hz is dependent on the definition of the notch and the population under study. To examine the prevalence and characteristics of audiograms that are notched at 4000 Hz. Retrospective, descriptive. The participants were 3430 veterans evaluated in the Audiology Clinic at the VA Medical Center, Mountain Home, Tennessee. The mean age was 62.3 yr. Data Collection and Analyses: The data were collected in the course of a 60 min, routine audiological evaluation. In addition to pure-tone audiometry, a history, otoscopy, speech audiometry in quiet and in noise, and aural-acoustic immittance measures were included in the clinic protocol but were not evaluated in this report. A notch was defined when the 4000 Hz threshold minus the 2000 Hz threshold and the 4000 Hz threshold minus the 8000 Hz threshold both were ≥10 dB. Overall the mean LE (left ear) thresholds at 2000, 3000, and 4000 Hz were at hearing levels 2-3 dB higher than the hearing levels for the corresponding mean RE (right ear) thresholds; the differences were significant. A notched audiogram was observed in 40.6% of the participants in at least one ear with 15.4% having bilateral notches, 28.8% LE notches, and 27.1% RE notches. Unilateral 4000 Hz notches were almost twice as prevalent as bilateral 4000 Hz notches. Viewed as a function of age, notched audiograms were most common (∼35% of the participants) in the 40 and 50 yr groups with a diminishing prevalence

  18. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    Science.gov (United States)

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  19. Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

    Directory of Open Access Journals (Sweden)

    Drasko Draskovic

    2013-01-01

    Full Text Available A design of a planar microstrip-fed ultrawideband (UWB printed circular monopole antenna with optically controlled notched bands is presented. The proposed antenna is composed of a circular ultrawideband patch, with an etched T-shaped slot controlled by an integrated silicon switch. The slot modifies the frequency response of the antenna suppressing 3.5–5 GHz band when the switch is in open state. The optical switch is controlled by a low-power near-infrared (808 nm laser diode, which causes the change in the frequency response of the antenna generating a frequency notch. This solution could be expanded to include several notches in the antenna frequency response achieving a fully reconfigurable UWB antenna. The antenna could be remotely controlled at large distances using optical fiber. The prototype antenna has been fully characterized to verify these design concepts.

  20. 2 TeV HEB beam abort at the SSCL

    International Nuclear Information System (INIS)

    Schailey, R.; Bull, J.; Clayton, T.; Kocur, P.; Mokhov, N.

    1993-05-01

    The High Energy Booster (HEB) of the Superconducting Super Collider Laboratory (SSCL) will require a full aperture beam abort over a dynamic energy range of 200 GeV to 2 TeV. Since the HEB is a bi-polar machine, both clockwise (CW) and the counter-clockwise (CCW) beam aborts are required. Also, the stored beam energy of 6.55 MJ in the superconducting HEB imposes upon the full aperture requirement. In this report, we describe the abort channels in the HEB utility straight sections, aperture restrictions, mechanical interferences and solutions, kicker misfires, and a 1 TeV beam absorber

  1. 2 TeV HEB beam abort at the SSCL

    International Nuclear Information System (INIS)

    Schailey, R.; Bull, J.; Clayton, T.; Kocur, P.; Mokhov, N.V.

    1993-01-01

    The High Energy Booster (HEB) of the Superconducting Super Collider Laboratory (SSCL) will require a full aperture beam abort over a dynamic energy range of 200 GeV to 2 TeV. Since the HEB is a bi-polar machine, both clockwise (CW) and counter-clockwise (CCW) beam aborts are required. Also, the stored beam energy of 6.55 MJ in the superconducting HEB imposes the full aperture requirement. In this report, the authors describe the abort channels in the HEB utility straight sections, aperture restrictions, mechanical interferences and solutions, kicker misfires, and a 2 TeV beam absorber

  2. Conceptual basis for calculations of absorbed-dose distributions

    International Nuclear Information System (INIS)

    Sinclair, W.K.; Rossi, H.H.; Alsmiller, R.G.; Berger, M.J.; Kellerer, A.M.; Roesch, W.C.; Spencer, L.V.; Zaider, M.A.

    1991-01-01

    The effects of radiation on matter are initiated by processes in which atoms and molecules of the medium are ionized or excited. Over a wide range of conditions, it is an excellent approximation to assume that the average number of ionizations and excitations is proportional to the amount of energy imparted to the medium by ionizing radiation in the volume of interest. The absorbed dose, that is, the average amount of energy imparted to the medium per unit mass, is therefore of central importance for the production of radiation effects, and the calculation of absorbed-dose distributions in irradiated media is the focus of interest of the present report. It should be pointed out, however, that even though absorbed dose is useful as an index relating absorbed energy to radiation effects, it is almost never sufficient; it may have to be supplemented by other information, such as the distributions of the amounts of energy imparted to small sites, the correlation of the amounts of energy imparted to adjacent sites, and so on. Such quantities are termed stochastic quantities. Unless otherwise stated, all quantities considered in this report are non-stochastic. 266 refs., 11 figs., 2 tabs

  3. TeV. The dream energy scale

    International Nuclear Information System (INIS)

    Murayama, Hitoshi

    2006-01-01

    In this talk, I'd like to explain why the TeV, 1,000,000,000,00 electron volt, is a particularly interesting energy scale in physics. I being recapitulating what particle physics is all about, citing two big questions: what the Universe is made of, and Einstein's dream of unification. TeV energy appears to be relevant to both questions, suggesting rich and complex physics at this energy. I outline how two facilities, LHC and ILC, will work together with reveal what is going on at this exciting energy scale. (author)

  4. Corundum-based transparent infrared absorbers

    KAUST Repository

    Schwingenschlögl, Udo

    2009-10-01

    Hypothetical corundum-based compounds are studied by electronic structure calculations. One quarter of the Al atoms in Al2O3 is replaced by a 3d transition metal from the M = Ti, ..., Zn (d1, ..., d9) series. Structure optimisations are performed for all the M-Al2O3 compounds and the electronic states are evaluated. Due to the M substitutes, narrow partially filled bands are formed at the Fermi energy. Beyond, for M = Ni and M = Cu the optical properties of Al2O3 in the visible range are conserved, while for M = Ti, ..., Co the systems form high accuracy optical filters. Since the compounds absorb the infrared radiation, the M = Ni and M = Cu systems are good candidates for heat-protective coatings. © 2009 Elsevier B.V. All rights reserved.

  5. Notching of samples for fracture toughness' measurements via SEVNB Method of brittle ceramics

    International Nuclear Information System (INIS)

    Ribeiro, S.; Atilio, I.; Oliveira, M.R.; Garcia, G.C.R.; Rodrigues, J.A.

    2012-01-01

    The goal of this work is to present a notching machine to produce notches in ceramic bodies as well the choice and how to make the notches, using SiC produced by liquid phase sintering as experimental material. For the liquid sintering a mixture of Al 2 O 3 and Yb 2 O 3 as additive was applied. It was developed and built by an enterprise sited in Sao Carlos-SP an equipment, which permits to obtain polished notches in ceramic specimens to be fractured afterwards. That is to facilitate the measurement of K IC via the SEVNB method. Specimens of 10% of (Al 2 O 3 +Yb 2 O 3 ) containing SiC were sintered at 1950 deg C. Those specimens were machined and notched using razor blades and diamond pastes of 15, 9, 6, 3, 1 and 0.25 μm of particle size. The built machine to notch specimens is installed at DEMAR-EEL-USP, and it is said to be the first of that type in Brazil. The results showed that depending on the thickness of the razor blade and the size of the diamond particles, it can be curried out notches with distinct tip radius and notch depth values. (author)

  6. 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.

  7. 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

  8. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  9. 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

  10. Performance of an absorbing concentrating solar collectors

    International Nuclear Information System (INIS)

    Imadojemu, H.

    1990-01-01

    This paper reports on a comparison of the efficiency of an absorbing fluid parabolic trough concentrating solar collector and a traditional concentrating collector that was made. In the absorbing fluid collector, black liquid flows through a glass tube absorber while the same black liquid flows through a selective black coated copper tube absorber while the same black fluid flows through a selective black coated copper tube absorber in the traditional collector. After a careful study of the properties of available black liquids, a mixture of water and black ink was chosen as the black absorbing medium or transfer fluid. In the black liquid glass collector there is a slightly improved efficiency based on beam radiation as a result of the direct absorption process and an increase in the effective transmittance absorptance. At worst the efficiency of this collector equals that of the traditional concentrating collector when the efficiency is based on total radiation. The collector's reflecting surfaces were made of aluminum sheet, parabolic line focus and with cylindrical receivers. The ease of manufacture and reduced cost per unit energy collected, in addition to the clean and pollution free mode of energy conversion, makes it very attractive

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

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.

    2008-08-15

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

  12. Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

    Directory of Open Access Journals (Sweden)

    Silvia Fre

    Full Text Available The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

  13. 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....

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  16. The series elastic shock absorber: tendon elasticity modulates energy dissipation by muscle during burst deceleration.

    Science.gov (United States)

    Konow, Nicolai; Roberts, Thomas J

    2015-04-07

    During downhill running, manoeuvring, negotiation of obstacles and landings from a jump, mechanical energy is dissipated via active lengthening of limb muscles. Tendon compliance provides a 'shock-absorber' mechanism that rapidly absorbs mechanical energy and releases it more slowly as the recoil of the tendon does work to stretch muscle fascicles. By lowering the rate of muscular energy dissipation, tendon compliance likely reduces the risk of muscle injury that can result from rapid and forceful muscle lengthening. Here, we examine how muscle-tendon mechanics are modulated in response to changes in demand for energy dissipation. We measured lateral gastrocnemius (LG) muscle activity, force and fascicle length, as well as leg joint kinematics and ground-reaction force, as turkeys performed drop-landings from three heights (0.5-1.5 m centre-of-mass elevation). Negative work by the LG muscle-tendon unit during landing increased with drop height, mainly owing to greater muscle recruitment and force as drop height increased. Although muscle strain did not increase with landing height, ankle flexion increased owing to increased tendon strain at higher muscle forces. Measurements of the length-tension relationship of the muscle indicated that the muscle reached peak force at shorter and likely safer operating lengths as drop height increased. Our results indicate that tendon compliance is important to the modulation of energy dissipation by active muscle with changes in demand and may provide a mechanism for rapid adjustment of function during deceleration tasks of unpredictable intensity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  17. Graphene Based Terahertz Absorber Designed With Effective Surface Conductivity Approach

    DEFF Research Database (Denmark)

    Andryieuski, Andrei; Pizzocchero, Filippo; Booth, Tim

    Young field of terahertz (THz) science and technology demands new materials and devices, such as filters, modulators, polarization converters and absorbers. Graphene, a recently discovered single-atom-thick material, provides exciting properties for functional terahertz applications. Graphene...... conductivity and how to use it in optical design. We demonstrate a tunable THz perfect absorber, which consists of continuous graphene various structured graphene metamaterials above a metal mirror. Changing the Fermi level from 0 eV to 0.5 eV allows for drastic changes in absorbance from less than 0.1 to 1...

  18. Damage Study in Notched Particulate Composie Specimens Under Nonuniform Strain Loading

    National Research Council Canada - National Science Library

    Kwon, Y

    1999-01-01

    .... The numerical specimen considered had a semi-circular notch with a linearly varying length. The initial crack size occurring at the notch tip was modeled and predicted using a micro/macro-approach along with a damage model...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN and satel...... and satellite communication signals. Due to planar structures proposed here, it is easy to integrate in the microwave integrated systems, which can play an important role in the microwave communication circuit and system.......Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN...

  20. Limit load and fully plastic stress analysis for circular notched plates and bars using fully plastic analysis

    International Nuclear Information System (INIS)

    Oh, Chang Kyun; Myung, Man Sik; Kim, Yun Jae; Park, Jin Moo

    2005-01-01

    For the last four decades, tension test of notched bars has been performed to investigate the effect of stress triaxiality on ductile fracture. To quantify the effect of the notch radius on stress triaxiality, the Bridgman equation is typically used. However, recent works based on detailed finite element analysis have shown that the Bridgman equation is not correct, possibly due to his assumption that strain is constant in the necked ligament. Up to present, no systematic work has been performed on fully plastic stress fields for notched bars in tension. This paper presents fully plastic results for tension of notched bars and plates in plane strain, via finite element limit analysis. The notch radius is systematically varied, covering both un-cracked and cracked cases. Comparison of plastic limit loads with existing solutions shows that existing solutions are accurate for notched plates, but not for notched bars. Accordingly new limit load solutions are given for notched bars. Variations of stress triaxiality with the notch radius and depth are also given, which again indicates that the Bridgman solution for notched bars is not correct and inaccuracy depends on the notch radius and depth

  1. 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.

  2. Self Absorbed Fraction for Electrons and Beta Particles in Small Spherical Volumes

    International Nuclear Information System (INIS)

    Grosev, D.

    2003-01-01

    Absorbed fraction and target organ mass are important parameters of internal dosimetry calculations that define the geometry of the system. Standard MIRD (Medical Internal Radiation Dosimetry) formalism assumes that the absorbed fraction for non-penetrating radiations (e.g., electrons, beta particles) is 1. This may not be correct in cases where dimensions of organs/tissues are comparable with the ranges of electrons/beta particles. Such is the case for example in radiodine ablation of thyroid remnant tissue. In this work the self-absorbed fraction (source and target volumes are the same) for monoenergetic electrons and beta particles is calculated for small spherical volumes of various sizes and unit density. Absorbed fraction can be expressed as an integral of the product of two quantities: (a) Scaled beta dose point kernel (mean absorbed dose rate per activity of the point source in infinite homogenous medium), F β ; (b) special geometrical reduction factor (GRF). F β is calculated using EGS4 Monte Carlo (MC) code for transport of electrons and photons. MC source code calculates the deposition of energy inside concentric spherical shells around the isotropic point source of electrons/beta particles in infinite medium (water). Shell thickness was δr=0.02·X 90 , where X 90 represents the radius of the sphere inside which 90% of the source energy is absorbed. Number of concentric spherical shells was 100, 10000 electron histories were started in each program run, and 10 runs were repeated for statistical reason. Numerical integration of the product of F β , calculated by MC program, and GRF for sphere was done using Simpson method. Absorbed fractions were calculated for spheres with mass from 0.01-20 g (r = 0.13 - 1.68 cm). Results are given for monoenergetic electrons with kinetic energy T=0.2, 0.4, 1.0 MeV, and for three beta emitters 1 31I , 3 2P , 9 0Y . For quantitative dosimetric protocols in radioiodine ablation therapy, results for 1 31I are of

  3. Role of Notch signalling pathway in cancer and its association with ...

    Indian Academy of Sciences (India)

    The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organ- ... Abnormal Notch signalling is seen in many cancers like T-cell acute ...... Morgan T. H. 1917 The theory of the gene.

  4. Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Tognon, Emiliana; Kobia, Francis; Busi, Ilaria

    2016-01-01

    16-1 expression follows differentiation of proneural regions of the disc. These regions, that will form sensory organs in the adult, appear to possess a distinctive endo-lysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endo-lysosomal function...

  5. Laboratory testing of a long expansion rock bolt support for energy-absorbing applications

    Directory of Open Access Journals (Sweden)

    Skrzypkowski Krzysztof

    2018-01-01

    Full Text Available The main purpose of rock support and reinforcement in underground mining is to maintain excavations safe and open for their intended lifespan. The basic type of rock mass reinforcement method both in ore and hard coal mining is rock bolt support. Very often, existing bolt support systems are not always capable of providing a reliable controlled performance. Therefore, in recent years energy-absorbing bolts which are exposed to dynamic loading, for example from rock burst caused by high rock stresses, earthquakes, or blasting have appeared. In this article particular attention was paid to short and long expansion bolts. Quasi-static tests of expansion bolts were carried out at the laboratory test facility in simulated mining conditions, especially for the KGHM Polska Miedź S.A. mines. In the underground mines of the Legnica-Głogów Copper District (LGOM the main way to protect the room excavation is rock bolt support with a length from 1.2 m to 2.6 m. Rock bolt support longer than 2.6 m is considered as additional support of excavations and is increasingly being used to reinforce the roofs. The comparisons of energy-absorbing short and long expansion bolts with a length of 1.8m, 3.6m and 5.2m were presented. In addition, for elastic and plastic range of each bolts were determined.

  6. Laboratory testing of a long expansion rock bolt support for energy-absorbing applications

    Science.gov (United States)

    Skrzypkowski, Krzysztof

    2018-01-01

    The main purpose of rock support and reinforcement in underground mining is to maintain excavations safe and open for their intended lifespan. The basic type of rock mass reinforcement method both in ore and hard coal mining is rock bolt support. Very often, existing bolt support systems are not always capable of providing a reliable controlled performance. Therefore, in recent years energy-absorbing bolts which are exposed to dynamic loading, for example from rock burst caused by high rock stresses, earthquakes, or blasting have appeared. In this article particular attention was paid to short and long expansion bolts. Quasi-static tests of expansion bolts were carried out at the laboratory test facility in simulated mining conditions, especially for the KGHM Polska Miedź S.A. mines. In the underground mines of the Legnica-Głogów Copper District (LGOM) the main way to protect the room excavation is rock bolt support with a length from 1.2 m to 2.6 m. Rock bolt support longer than 2.6 m is considered as additional support of excavations and is increasingly being used to reinforce the roofs. The comparisons of energy-absorbing short and long expansion bolts with a length of 1.8m, 3.6m and 5.2m were presented. In addition, for elastic and plastic range of each bolts were determined.

  7. Generation of single failures in memory devices irradiated by 1 GeV protons; Generatsiya edinichnykh sboev v ustrojstvakh pamyati, obluchaemykh protonami s ehnergiej 1 GehV

    Energy Technology Data Exchange (ETDEWEB)

    Ageev, S V [and others

    1994-12-31

    Cross sections of single reversible failures in the logic state of memory cells irradiated with 1 GeV energy protons are measured. It is found that the failure cross section does not depend on the beam intensity on the absorbed dose and on the source logic state of the memory cells.

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

    Science.gov (United States)

    Palaga, Tanapat; Ratanabunyong, Siriluk; Pattarakankul, Thitiporn; Sangphech, Naunpun; Wongchana, Wipawee; Hadae, Yukihiro; Kueanjinda, Patipark

    2013-09-01

    Macrophages are cellular targets for infection by bacteria and viruses. The fate of infected macrophages plays a key role in determining the outcome of the host immune response. Apoptotic cell death of macrophages is considered to be a protective host defense that eliminates pathogens and infected cells. In this study, we investigated the involvement of Notch signaling in regulating apoptosis in macrophages treated with tuberculin purified protein derivative (PPD). Murine bone marrow-derived macrophages (BMMs) treated with PPD or infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) induced upregulation of Notch1. This upregulation correlated well with the upregulation of the anti-apoptotic gene mcl-1 both at the transcriptional and translational levels. Decreased levels of Notch1 and Mcl-1 were observed in BMM treated with PPD when a gamma secretase inhibitor (GSI), which inhibits the processing of Notch receptors, was used. Moreover, silencing Notch1 in the macrophage-like cell line RAW264.7 decreased Mcl-1 protein expression, suggesting that Notch1 is critical for Mcl-1 expression in macrophages. A significant increase in apoptotic cells was observed upon treatment of BMM with PPD in the presence of GSI compared to the vehicle-control treated cells. Finally, analysis of the mcl-1 promoter in humans and mice revealed a conserved potential CSL/RBP-Jκ binding site. The association of Notch1 with the mcl-1 promoter was confirmed by chromatin immunoprecipitation. Taken together, these results indicate that Notch1 inhibits apoptosis of macrophages stimulated with PPD by directly controlling the mcl-1 promoter.

  9. Specific absorbed fractions of energy at various ages from internal photon sources: 3, Five-year-old

    International Nuclear Information System (INIS)

    Cristy, M.; Eckerman, K.F.

    1987-04-01

    Specific absorbed fractions (PHI's) in various organs of the body (target organs) from sources of monoenergetic photons in various other organs (source organs) are tabulated. In this volume PHI-values are tabulated for a five-year-old or 19-kg person. These PHI-values can be used in calculating the photon component of the dose-equivalent rate in a given target organ from a given radionuclide that is present in a given source organ. The International Commission on Radiological Protection recognizes that the endosteal, or bone surface, cells are the tissue at risk for bone cancer. We have applied the dosimetry methods developed for beta-emitting radionuclides deposited in bone to follow the transport of secondary electrons that were freed by photon interactions through the microscopic structure of the skeleton. With these methods we can estimate PHI in the endosteal cells and can better estimate PHI in the active marrow; the latter is overestimated with other methods at photon energies below 200 keV. 12 refs., 2 tabs

  10. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Science.gov (United States)

    Tripathi, Richa; Rath, Gayatri; Jawanjal, Poonam; Sharma, Shweta; Singhal, Pallavi; Bhambhani, Suresh; Hussain, Showket; Bharadwaj, Mausumi

    2014-01-01

    Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98), precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. 80% (24/30) were found to be positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001) and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001) obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; pcervix tissue (0.95±0.20, 0.70±0.20; pcancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

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

    Science.gov (United States)

    Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

    2012-09-21

    The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

  12. Study of thermal effects and optical properties of an innovative absorber in integrated collector storage solar water heater

    Science.gov (United States)

    Taheri, Yaser; Alimardani, Kazem; Ziapour, Behrooz M.

    2015-10-01

    Solar passive water heaters are potential candidates for enhanced heat transfer. Solar water heaters with an integrated water tank and with the low temperature energy resource are used as the simplest and cheapest recipient devices of the solar energy for heating and supplying hot water in the buildings. The solar thermal performances of one primitive absorber were determined by using both the experimental and the simulation model of it. All materials applied for absorber such as the cover glass, the black colored sands and the V shaped galvanized plate were submerged into the water. The water storage tank was manufactured from galvanized sheet of 0.0015 m in thickness and the effective area of the collector was 0.67 m2. The absorber was installed on a compact solar water heater. The constructed flat-plate collectors were tested outdoors. However the simulation results showed that the absorbers operated near to the gray materials and all experimental results showed that the thermal efficiencies of the collector are over than 70 %.

  13. 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.

  14. LINEAR MODEL FOR NON ISOSCELES ABSORBERS.

    Energy Technology Data Exchange (ETDEWEB)

    BERG,J.S.

    2003-05-12

    Previous analyses have assumed that wedge absorbers are triangularly shaped with equal angles for the two faces. In this case, to linear order, the energy loss depends only on the position in the direction of the face tilt, and is independent of the incoming angle. One can instead construct an absorber with entrance and exit faces facing rather general directions. In this case, the energy loss can depend on both the position and the angle of the particle in question. This paper demonstrates that and computes the effect to linear order.

  15. Ultra-Wideband Notched Characteristic Fed by Coplanar Waveguide

    Directory of Open Access Journals (Sweden)

    Rastanto Hadinegoro

    2015-02-01

    Full Text Available In this paper, a novel Ultra-Wide Band (UWB notch patch antenna with co-planar waveguide (CPW fed is presented. This antenna only used one layer and the patch antenna is constructed on the first layer and back to back with CPW fed and bottom part is ground plane. The width notch is used to achieve the UWB characteristic. The results shown that the impedance bandwidth is 1130 MHz (1.662–2.792 GHz or about 50.7% for VSWR <2.

  16. Numerical simulations of energy deposition caused by 50 MeV—50 TeV proton beams in copper and graphite targets

    CERN Document Server

    Nie, Y; Chetvertkova, V; Rosell-Tarrago, G; Burkart, F; Wollmann, D

    2017-01-01

    The conceptual design of the Future Circular Collider (FCC) is being carried out actively in an international collaboration hosted by CERN, for the post–Large Hadron Collider (LHC) era. The target center-of-mass energy of proton-proton collisions for the FCC is 100 TeV, nearly an order of magnitude higher than for LHC. The existing CERN accelerators will be used to prepare the beams for FCC. Concerning beam-related machine protection of the whole accelerator chain, it is critical to assess the consequences of beam impact on various accelerator components in the cases of controlled and uncontrolled beam losses. In this paper, we study the energy deposition of protons in solid copper and graphite targets, since the two materials are widely used in magnets, beam screens, collimators, and beam absorbers. Nominal injection and extraction energies in the hadron accelerator complex at CERN were selected in the range of 50 MeV–50 TeV. Three beam sizes were studied for each energy, corresponding to typical values ...

  17. Estimations of creep behavior and failure life for a circumferentially notched specimen

    International Nuclear Information System (INIS)

    Kobayashi, Ken-ichi; Yokobori, Toshimitsu; Kikuchi, Kenji.

    1997-01-01

    No method with which to characterize and/or illustrate total creep behavior for specimens with notches, holes or cracks has been proposed. In this paper it is proposed that most creep curves can be drawn with a master curve for each creep test whenever test conditions and failure modes are similar to each other, and the lifetime ratio normalized by the rupture time is introduced. Using smooth and circumferentially notched specimens of 2.25 Cr-1 Mo steel, creep tests were performed at 600degC for examination of this concept. Furthermore, a θ projection method was used to describe creep curves for notched specimens and to extrapolate longer creep lives. Then, the whole creep curve shape for notched specimens could be easily drawn, except for that in the vicinity of the rupture point. However, longer creep lives of notched specimens were underestimated in comparison with a simple extrapolation of the experimental data. This resulted from the negative dependence of the parameter of θ 3 on the applied stress. (author)

  18. Flow injection spectrophotometric determination of Fe(III) and V(v)

    International Nuclear Information System (INIS)

    Elrahman, Azza Mohamed

    2000-01-01

    Phenylflourone was synthesized with the objective of developing a method for determining Fe(III) and V(V) in the pressence of micelles using flow injectoin technique. Phenylflourone showed a wavelength of maximum absorption at 412 nm which was not affected by the presence of miccelles i.e. n-hexadodecylpyridinum bromide and sodium n-dodecylsulphate, but they have different effects on the absorbance of PHF. The example of PHF-Fe(III) and PHF-V(V) showed the wavelength of the maximum absorption at 4428 nm and 412 nm, respectively. Presence of micelles shifted the wavelength of the two complexes to a lower one. Generally the addition of micelles increased the absorbance of phenylflourone metal ions complexes except for PHF-V(V) with hexadodecylpyridinum bromide. With flow injection technique two approaches were practiced the use of micelle as a carrier or water as a carrier. Sodium n-dodecylsulphate increased the absorbance of the two complexes when it was used as a carrier or added to the metal ions using water as carrier. On the other hand, the use of n-hexadodecylpyridinum bromide as carrieer increased the absorbance of the complexes but it decreased the absorbance when it was used in conjunction with metal ions and water as a carrier. After establishing the optimum FI conditions for PHF-Fe(III) and PHF-V(V) complexes, the calibration curves were construction and produced semiliner response in the concentration range studied. Ti(IV) III, Mo(VI) showed a positive interference in PHF-Fe(III) and PHF-V(V) complexes, respectively.(Author)

  19. 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...

  20. Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros.

    Science.gov (United States)

    Naylor, Richard W; Jones, Elizabeth A

    2009-11-01

    Previous studies have highlighted a role for the Notch signalling pathway during pronephrogenesis in the amphibian Xenopus laevis, and in nephron development in the mammalian metanephros, yet a mechanism for this function remains elusive. Here, we further the understanding of how Notch signalling patterns the early X. laevis pronephros anlagen, a function that might be conserved in mammalian nephron segmentation. Our results indicate that early phase pronephric Notch signalling patterns the medio-lateral axis of the dorso-anterior pronephros anlagen, permitting the glomus and tubules to develop in isolation. We show that this novel function acts through the Notch effector gene hrt1 by upregulating expression of wnt4. Wnt-4 then patterns the proximal pronephric anlagen to establish the specific compartments that span the medio-lateral axis. We also identified pronephric expression of lunatic fringe and radical fringe that is temporally and spatially appropriate for a role in regulating Notch signalling in the dorso-anterior region of the pronephros anlagen. On the basis of these results, along with data from previous publications, we propose a mechanism by which the Notch signalling pathway regulates a Wnt-4 function that patterns the proximal pronephric anlagen.

  1. Reconstructing the energy band electronic structure of pulsed laser deposited CZTS thin films intended for solar cell absorber applications

    Science.gov (United States)

    Pandiyan, Rajesh; Oulad Elhmaidi, Zakaria; Sekkat, Zouheir; Abd-lefdil, Mohammed; El Khakani, My Ali

    2017-02-01

    We report here on the use of pulsed KrF-laser deposition (PLD) technique for the growth of high-quality Cu2ZnSnS4 (CZTS) thin films onto Si, and glass substrates without resorting to any post sulfurization process. The PLD-CZTS films were deposited at room temperature (RT) and then subjected to post annealing at different temperatures ranging from 200 to 500 °C in Argon atmosphere. The X-ray diffraction and Raman spectroscopy confirmed that the PLD films crystallize in the characteristic kesterite CZTS structure regardless of their annealing temperature (Ta), but their crystallinity is much improved for Ta ≥ 400 °C. The PLD-CZTS films were found to exhibit a relatively dense morphology with a surface roughness (RMS) that increases with Ta (from ∼14 nm at RT to 70 nm at Ta = 500 °C with a value around 40 nm for Ta = 300-400 °C). The optical bandgap of the PLD-CZTS films, was derived from UV-vis transmission spectra analysis, and found to decrease from 1.73 eV for non-annealed films to ∼1.58 eV for those annealed at Ta = 300 °C. These band gap values are very close to the optimum value needed for an ideal solar cell absorber. In order to achieve a complete reconstruction of the one-dimensional energy band structure of these PLD-CZTS absorbers, we have combined both XPS and UPS spectroscopies to determine their chemical bondings, the position of their valence band maximum (relative to Fermi level), and their work function values. This enabled us to sketch out, as accurately as possible, the band alignment of the heterojunction interface formed between CZTS and both CdS and ZnS buffer layer materials.

  2. Digital notch filter based active damping for LCL filters

    DEFF Research Database (Denmark)

    Yao, Wenli; Yang, Yongheng; Zhang, Xiaobin

    2015-01-01

    . In contrast, the active damping does not require any dissipation elements, and thus has become of increasing interest. As a result, a vast of active damping solutions have been reported, among which multi-loop control systems and additional sensors are necessary, leading to increased cost and complexity....... In this paper, a notch filter based active damping without the requirement of additional sensors is proposed, where the inverter current is employed as the feedback variable. Firstly, a design method of the notch filter for active damping is presented. The entire system stability has then been investigated...... in the z-domain. Simulations and experiments are carried out to verify the proposed active damping method. Both results have confirmed that the notch filter based active damping can ensure the entire system stability in the case of resonances with a good system performance....

  3. Notch and hydrogen effects on sensitized 21-6-9 stainless steel

    International Nuclear Information System (INIS)

    Caskey, C.R. Jr.

    1979-01-01

    Type 21-6-9 stainless steel alloy is slightly notch sensitive in the solution annealed condition, a behavior that is aggravated by sensitization anneal at 920 0 K. The lower toughness of the sensitized alloy is a measure of microstructural embrittlement associated with carbide precipitation in grain boundaries. The tendency toward grain boundary fracture in the sensitized alloy is accentuated by stress concentration at the notch. Also, there is an increase in notch sensitivity when the alloy is tested in a high pressure (69 MPa) hydrogen environment, due to susceptibility of the grain boundaries to hydrogen embrittlement

  4. 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

  5. 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.

  6. Mechano sorptive behaviour of notched beams in bending

    DEFF Research Database (Denmark)

    Jensen, Signe Kamp; Hoffmeyer, Preben

    1996-01-01

    Short term bending tests with end-notched beams at constant or varying moisture content have shown an apparent contradictory dependency between moisture content and strength. The higher the moisture content the higher the strength. Varying moisture results in particularly significant differences...... and by neglecting deformation due to shear. Compression stresses perpendicular to grain in excess of 6 MPa were found in the vicinity of the notch following a period of adsorption. Similarly, small tension stresses of the order 1 MPa were registered in this area when the specimens were at their most dry condition...

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-29

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

  9. 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

  10. The “Carpet-3” air shower array to search for diffuse gamma rays with energy Eγ>100TeV

    Science.gov (United States)

    Dzhappuev, D. D.; I, V. B. Petkov V.; Kudzhaev, A. U.; Lidvansky, A. S.; Volchenko, V. I.; Volchenko, G. V.; Gorbacheva, E. A.; Dzaparova, I. M.; Klimenko, N. F.; Kurenya, A. N.; Mikhilova, O. I.; Khadzhiev, M. M.; Yanin, A. F.

    2017-12-01

    At present an experiment for measuring the flux of cosmic diffuse gamma rays with energy higher than 100 TeV (experiment “Carpet-3”) is being prepared at the Baksan Neutrino Observatory of the Institute for Nuclear Research, Russian Academy of Sciences. The preparation of the experiment implies considerable enlargement of the area of both muon detector and surface part of the shower array. At the moment the plastic scintillation counters with a total continuous area of 410 m2 are installed in the muon detector (MD) underground tunnels, and they are totally equipped with electronics. Adjusting of the counters and their electronic circuits is in progress. Six modules of shower detectors (out of twenty planned to be installed) have already been placed on the surface of the MD absorber. A new liquid scintillation detector is developed for modules of the ground -surface part of the array, whose characteristics are presented. It is shown that the “Carpet-3” air shower array will have the best sensitivity to the flux of primary gamma rays with energies in the range 100TeV - 1PeV, being quite competitive in gamma-ray astronomy at such energies.

  11. 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.

  12. Acoustic emission during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches

    International Nuclear Information System (INIS)

    Mukhopadhyay, C.K.; Jayakumar, T.; Baldev Raj

    1996-01-01

    Acoustic emission generated during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches has been studied. The extent of acoustic activity generated depends on notch tip severity, notch tip blunting and tearing of the notches. The equation N=AK m applied to the acoustic emission data of the notched specimens has shown good correlation. Acoustic emission technique can be used to estimate the size of an unknown notch. (author)

  13. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  14. Development of decay energy spectroscopy using low temperature detectors.

    Science.gov (United States)

    Jang, Y S; Kim, G B; Kim, K J; Kim, M S; Lee, H J; Lee, J S; Lee, K B; Lee, M K; Lee, S J; Ri, H C; Yoon, W S; Yuryev, Y N; Kim, Y H

    2012-09-01

    We have developed a high-resolution detection technique for measuring the energy and activity of alpha decay events using low-temperature detectors. A small amount of source material containing alpha-emitting radionuclides was enclosed in a 4π metal absorber. The energy of the alpha particles as well as that of the recoiled nuclides, low-energy electrons, and low-energy x-rays and γ-rays was converted into thermal energy of the gold absorber. A metallic magnetic calorimeter serving as a fast and sensitive thermometer was thermally attached to the metal absorber. In the present report, experimental demonstrations of Q spectroscopy were made with a new meander-type magnetic calorimeter. The thermal connection between the temperature sensor and the absorber was established with annealed gold wires. Each alpha decay event in the absorber resulted in a temperature increase of the absorber and the temperature sensor. Using the spectrum measured for a drop of (226)Ra solution in a 4π gold absorber, all of the alpha emitters in the sample were identified with a demonstration of good detector linearity. The resolution of the (226)Ra spectrum showed a 3.3 keV FWHM at its Q value together with an expected gamma escape peak at the energy shifted by its γ-ray energy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Fibre Optic Notch Filter For The Antiproton Decelerator Stochastic Cooling System

    CERN Document Server

    Simmonds, Max Vincent John

    2016-01-01

    The project scope included reverse engineering, upgrading, and recovering the operational conditions of an existing fibre optic notch filter. Once operational, tests were to be preformed to confirm the performance of the temperature stabilisation. The end goal is to use said notch filter in the Antiproton Decelerator (AD) facility at CERN to help aid antimatter research. The notch filter was successfully reverse engineered and then documented. Changes were made in order to increase performance and reliability, and also allow easy integration into the AD. An additional phase was added whereby the notch filter was to be controller via a touchscreen computer, situated next to the filter, allowing engineers to set-up each of the electronic devices used. While one of the devices (Motorised Delay Line) can be controlled by the touchscreen computer, the other two cannot.Due to time constraints and difficulties with the Beckhoff TwincatII programming language, the USB devices were not able to be controlled via the To...

  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. 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.

  18. 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

  19. On the notch ductility of a magnesium-rare earth alloy

    Energy Technology Data Exchange (ETDEWEB)

    Kondori, B., E-mail: bkondori.13034@tamu.edu [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Benzerga, A.A. [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Department of Aerospace Engineering, Texas A& M University, College Station, TX 77843 (United States)

    2015-10-28

    The room-temperature notch ductility of magnesium-rare earth alloy WE43 is investigated for two loading orientations. This material is endowed with quasi-isotropic plastic flow properties, higher strength and similar uniaxial ductility in comparison with other commercially available Mg alloys. The authors have recently shown that the notch ductility of a Mg–Al–Zn alloy is greater than its uniaxial ductility over a wide range of notch geometries. This paper investigates whether the same trends hold for WE43, discusses the orientation dependence of ductility and the propensity for intergranular fracture at high levels of hydrostatic tension. The latter mode of fracture is analyzed by means of detailed fractography in order to elucidate the role of grain-boundary particles and precipitates in the fracture process.

  20. GEANT 4.8.2, 9.2 and 9.4 simulations versus experimental proton energy loss in thick absorbers

    Energy Technology Data Exchange (ETDEWEB)

    Evseev, Ivan; Schelin, Hugo R.; Ahmann, Francielle; Milhoretto, Edney; Paschuk, Sergei A., E-mail: evseev@utfpr.edu.b, E-mail: schelin@utfpr.edu.b, E-mail: sergei@utfpr.edu.b [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Yevseyeva, Olga; Assis, Joaquim T. de; Ievsieieva, Ievgeniia, E-mail: yevseveva@iprj.uerj.b, E-mail: joaquim@iprj.uerj.b [Instituto Politecnico do Rio de Janeiro (IPRJ/UERJ), Nova Friburgo, RJ (Brazil). Dept. de Modelagem Computacional; Hormaza, Joel M., E-mail: jmesa@ibb.unesp.b [Universidade Estadual Paulista (IBB/UNESP), Botucatu, SP (Brazil). Inst. de Biociencias; Diaz, Katherin S. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear, Havana (Cuba); Lopes, Ricardo T. [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LIN/COPPE/UFRJ), RJ (Brazil). Lab. de Instrumentacao Nuclear

    2011-07-01

    Monte Carlo simulations are a powerful tool to estimate the proton energy loss and straggling in medical applications. The physics of proton interaction with matter for thick absorbers (like a human body) has a well-established theory for the so-called Bethe-Bloch domain, and the basic principles of Monte Carlo simulation for such processes are well known since the middle of the past century. However, in spite of GEANT4 has been validated against proton stopping powers from the NIST PSTAR, the evolution of the code leads to some result instability within the various code releases. In this work, we present the recent results for the comparison of our GEANT4 simulations against experimental proton energy loss for some thick absorbers. All the simulations were performed using the GEANT4 Hadrontherapy Advanced Example. The GEANT4 versions 4.8.2, 4.9.2, and 4.9.4 were tested with different simulation parameters, such as varied cut values. In addition to the Standard model, some other models for the electromagnetic processes from the GEANT4 Low Energy Extension Pack were tested as well. Experimental data were taken from for polyethylene, and from for aluminum and gold absorbers. The theoretical predictions for the spectra were calculated using the self-consistent Gaussian solution of the Boltzmann kinetic equation in the Fokker-Plank form. In order to compare the GEANT4 simulations with other popular codes, the same spectra were simulated by TRIM/SRIM2011 and MCNPX2.4.0. The simultaneous comparison of the results obtained for different materials at various initial proton energies were done using the reduced calibration curve approach. (author)

  1. Seasonal Evolution and Interannual Variability of the Local Solar Energy Absorbed by the Arctic Sea Ice-Ocean System

    Science.gov (United States)

    Perovich, Donald K.; Nghiem, Son V.; Markus, Thorsten; Schwieger, Axel

    2007-01-01

    The melt season of the Arctic sea ice cover is greatly affected by the partitioning of the incident solar radiation between reflection to the atmosphere and absorption in the ice and ocean. This partitioning exhibits a strong seasonal cycle and significant interannual variability. Data in the period 1998, 2000-2004 were analyzed in this study. Observations made during the 1997-1998 SHEBA (Surface HEat Budget of the Arctic Ocean) field experiment showed a strong seasonal dependence of the partitioning, dominated by a five-phase albedo evolution. QuikSCAT scatterometer data from the SHEBA region in 1999-2004 were used to further investigate solar partitioning in summer. The time series of scatterometer data were used to determine the onset of melt and the beginning of freezeup. This information was combined with SSM/I-derived ice concentration, TOVS-based estimates of incident solar irradiance, and SHEBA results to estimate the amount of solar energy absorbed in the ice-ocean system for these years. The average total solar energy absorbed in the ice-ocean system from April through September was 900 MJ m(sup -2). There was considerable interannual variability, with a range of 826 to 1044 MJ m(sup -2). The total amount of solar energy absorbed by the ice and ocean was strongly related to the date of melt onset, but only weakly related to the total duration of the melt season or the onset of freezeup. The timing of melt onset is significant because the incident solar energy is large and a change at this time propagates through the entire melt season, affecting the albedo every day throughout melt and freezeup.

  2. 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

  3. Notch root strain measurement of WE43-T6 magnesium alloy using electronic speckle pattern interferometry

    International Nuclear Information System (INIS)

    Liew, H.L.; Ahmad, A.; Ramesh, S.; Purbolaksono, J.

    2013-01-01

    Highlights: • The use of ESPI for measuring total strains at the notch root of specimens. • Fine meshing in micron scale at the notch root regions. • The maximum elastic strain is shifted to be further away from the notch root tip. - Abstract: The notch root elasto-plastic strains of circumferentially grooved round specimen of cast magnesium WE43-T6 were experimentally measured using the electronic speckle pattern interferometry (ESPI) and numerically evaluated using the finite element analysis (FEA). The specimens have notch radii of 1.6 mm and 0.8 mm and an opening angle of 60°. The technique of ESPI showed its accuracy in measuring three-dimensional surface deformations on large negatively curved manifolds. The measured nominal stress for rupture is well beyond the ultimate strength, suggesting the existence of significant biaxial stress at the notch root region. The ESPI-based strains on the notch tips were shown to be in agreement with those evaluated by the FEA. The FEA also showed that the maximum elastic strain is shifted away from the notch root surface as the plastic strain is predominant

  4. The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

    Science.gov (United States)

    Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

    2001-01-01

    An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. Without definitions or examples of optic disc rim notching, the glaucoma

  5. 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

  6. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Science.gov (United States)

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

    Directory of Open Access Journals (Sweden)

    Chen-Yuan Tseng

    2014-12-01

    Full Text Available Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs, and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  8. The dynamics analysis of a ferrofluid shock absorber

    International Nuclear Information System (INIS)

    Yao, Jie; Chang, Jianjun; Li, Decai; Yang, Xiaolong

    2016-01-01

    The paper presents a shock absorber using three magnets as the inertial mass. Movement of the inertial mass inside a cylindrical body filled with ferrofluid will lead to a viscous dissipation of the oscillating system energy. The influence of a dumbbell-like ferrofluid structure on the energy dissipation is considered and the magnetic restoring force is investigated by experiment and theoretical calculation. A theoretical model of the hydrodynamics and energy dissipation processes is developed, which includes the geometrical characteristics of the body, the fluid viscosity, and the external magnetic field. The theory predicts the experimental results well under some condition. The shock absorber can be used in spacecraft technology. - Highlights: • We study a ferrofluid shock absorber. • The mechanical model of the flow of the ferrofluid has been built. • The theoretical model of the energy dissipation processes is developed. • The magnetic restoring force between the body and the magnets has been measured.

  9. The dynamics analysis of a ferrofluid shock absorber

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jie; Chang, Jianjun [School of Mechanical, Electronic and Control Engineering, Beijing Jiaotong University, Beijing 100044 (China); Li, Decai, E-mail: dcli@bjtu.edu.cn [School of Mechanical, Electronic and Control Engineering, Beijing Jiaotong University, Beijing 100044 (China); Yang, Xiaolong [School of Mechanical Engineering, Guangxi University of Science and Technology, Liuzhou, Guangxi 545006 (China)

    2016-03-15

    The paper presents a shock absorber using three magnets as the inertial mass. Movement of the inertial mass inside a cylindrical body filled with ferrofluid will lead to a viscous dissipation of the oscillating system energy. The influence of a dumbbell-like ferrofluid structure on the energy dissipation is considered and the magnetic restoring force is investigated by experiment and theoretical calculation. A theoretical model of the hydrodynamics and energy dissipation processes is developed, which includes the geometrical characteristics of the body, the fluid viscosity, and the external magnetic field. The theory predicts the experimental results well under some condition. The shock absorber can be used in spacecraft technology. - Highlights: • We study a ferrofluid shock absorber. • The mechanical model of the flow of the ferrofluid has been built. • The theoretical model of the energy dissipation processes is developed. • The magnetic restoring force between the body and the magnets has been measured.

  10. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  11. 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.

  12. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  13. 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

  14. 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.

  15. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  16. 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)

  17. 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.

  18. Chemical modifications of polymer films induced by high energy heavy ions

    International Nuclear Information System (INIS)

    Zhu Zhiyong; Sun Youmei; Liu Changlong; Liu Jie; Jin Yunfan

    2002-01-01

    Polymer films including polyethylene terephthalate (PET), polystyrene (PS) and polycarbonate (PC) were irradiated at room temperature with ions of 35 MeV/u 40 Ar, 25 MeV/u 84 Kr, 15.1 MeV/u 136 Xe and 11.4 MeV/u 238 U to fluences ranging from 9x10 9 to 5.5x10 12 ions/cm 2 . The radiation-induced chemical changes of the materials were investigated by Fourier-transform infrared (FTIR) and ultraviolet/visible spectroscopies. It is found that the absorbance in the ultraviolet and visible range induced by all irradiations follows a linear relationship with fluence. The radiation-induced absorbance normalized to one particle increases slowly with increasing of electronic energy loss below about 8 keV/nm followed by a sharp increase up to about 15 keV/nm above which saturation is reached. FTIR measurements reveal that the materials suffer serious degradation through bond breaking. The absorbance of the typical infrared bands decays exponentially with increase of ion fluence and the bond-disruption cross-section shows a sigmoid variation with electronic energy loss. In PET loss of crystallinity is attributed to the configuration transformation of the ethylene glycol residue from trans into the gauche. Alkyne end groups are induced in all the materials above certain electronic energy loss threshold, which is found to be about 0.8 keV/nm for PS and 0.4 keV/nm for PC. The production cross-section of alkyne end group increases with increasing of electronic energy loss and shows saturation at high electronic energy loss values. It is concluded that not only the physical processes but also the chemical processes of the energy deposition determine the modification of polymer

  19. Application of FIB technique to introduction of a notch into a carbon fiber for direct measurement of fracture toughness

    International Nuclear Information System (INIS)

    Ogihara, S; Imafuku, Y; Yamamoto, R; Kogo, Y

    2009-01-01

    For the direct measurement of the fracture toughness of the carbon fiber, a new technique was proposed and examined its applicability. At first, machining condition of the notch was examined. The notch was introduced using focused ion beam (FIB). The ion beam can be electronically scanned to introduce a sharp notch on the carbon fiber. Notches with various notch width and length were introduced by changing beam and scanning conditions. Tensile tests on notched carbon fibers were carried out following the test method for carbon fiber monofilaments. Fractured specimens were successfully corrected without secondary damage using protection films. SEM observations revealed that a crack propagated from a notch-tip, and notch size was able to be determined successfully. Effect of notch root radius was also examined to investigate the validity of the fracture toughness obtained by this method.

  20. Ferrite HOM Absorber for the RHIC ERL

    Energy Technology Data Exchange (ETDEWEB)

    Hahn,H.; Choi, E.M.; Hammons, L.

    2008-10-01

    A superconducting Energy Recovery Linac is under construction at Brookhaven National Laboratory to serve as test bed for RHIC upgrades. The damping of higher-order modes in the superconducting five-cell cavity for the Energy-Recovery linac at RHIC is performed exclusively by two ferrite absorbers. The ferrite properties have been measured in ferrite-loaded pill box cavities resulting in the permeability values given by a first-order Debye model for the tiled absorber structure and an equivalent permeability value for computer simulations with solid ring dampers. Measured and simulated results for the higher-order modes in the prototype copper cavity are discussed. First room-temperature measurements of the finished niobium cavity are presented which confirm the effective damping of higher-order modes in the ERL. by the ferrite absorbers.

  1. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    NARCIS (Netherlands)

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal.

  2. Adaptive inertial shock-absorber

    International Nuclear Information System (INIS)

    Faraj, Rami; Holnicki-Szulc, Jan; Knap, Lech; Seńko, Jarosław

    2016-01-01

    This paper introduces and discusses a new concept of impact absorption by means of impact energy management and storage in dedicated rotating inertial discs. The effectiveness of the concept is demonstrated in a selected case-study involving spinning management, a recently developed novel impact-absorber. A specific control technique performed on this device is demonstrated to be the main source of significant improvement in the overall efficiency of impact damping process. The influence of various parameters on the performance of the shock-absorber is investigated. Design and manufacturing challenges and directions of further research are formulated. (paper)

  3. 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.)

  4. 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.

  5. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.

    Science.gov (United States)

    Goh, Gerald; Walradt, Trent; Markarov, Vladimir; Blom, Astrid; Riaz, Nadeem; Doumani, Ryan; Stafstrom, Krista; Moshiri, Ata; Yelistratova, Lola; Levinsohn, Jonathan; Chan, Timothy A; Nghiem, Paul; Lifton, Richard P; Choi, Jaehyuk

    2016-01-19

    Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. To define the genetic basis of MCCs, we performed exome sequencing of 49 MCCs. We show that MCPyV-negative MCCs have a high mutation burden (median of 1121 somatic single nucleotide variants (SSNVs) per-exome with frequent mutations in RB1 and TP53 and additional damaging mutations in genes in the chromatin modification (ASXL1, MLL2, and MLL3), JNK (MAP3K1 and TRAF7), and DNA-damage pathways (ATM, MSH2, and BRCA1). In contrast, MCPyV-positive MCCs harbor few SSNVs (median of 12.5 SSNVs/tumor) with none in the genes listed above. In both subgroups, there are rare cancer-promoting mutations predicted to activate the PI3K pathway (HRAS, KRAS, PIK3CA, PTEN, and TSC1) and to inactivate the Notch pathway (Notch1 and Notch2). TP53 mutations appear to be clinically relevant in virus-negative MCCs as 37% of these tumors harbor potentially targetable gain-of-function mutations in TP53 at p.R248 and p.P278. Moreover, TP53 mutational status predicts death in early stage MCC (5-year survival in TP53 mutant vs wild-type stage I and II MCCs is 20% vs. 92%, respectively; P = 0.0036). Lastly, we identified the tumor neoantigens in MCPyV-negative and MCPyV-positive MCCs. We found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantigens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses. Collectively, these data support the use of immunotherapies for virus-negative MCCs.

  6. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Jian Liu

    Full Text Available Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

  7. ADAM10 regulates Notch function in intestinal stem cells of mice.

    Science.gov (United States)

    Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

    2014-10-01

    A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Determination of the absorbed dose and dose-distribution in water for low- and medium-energetic photons

    International Nuclear Information System (INIS)

    Bultman, J.H.

    1990-05-01

    The methods to determine the absorbed dose to water for low and medium energy photons were studied. Large differences between the results of these methods exists. So, a research proposition has been made to explain these differences. The goal of this research will be the development of a method to determine the absorbed dose below approximately 400 keV with an ionization chamber calibrated at 60 Co gamma radiation. To explain the differences between the set of methods, some causes were proposed, like the influence of the ionisation chamber on the measurement in water. Also, some methods to determine the factors are proposed. (author). 29 refs

  10. 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

  11. An obligatory role of mind bomb-1 in notch signaling of mammalian development.

    Directory of Open Access Journals (Sweden)

    Bon-Kyoung Koo

    2007-11-01

    Full Text Available The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood.Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2(-/- mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants.Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.

  12. Notch Filter Analysis and Its Application in Passive Coherent Location Radar (in English

    Directory of Open Access Journals (Sweden)

    Li Ji-chuan

    2015-01-01

    Full Text Available The Normalized Least-Mean-Squares (NLMS algorithm is widely used to cancel the direct and multiple path interferences in Passive Coherent Location (PCL radar systems. This study proposes that the interference cancelation using the NLMS algorithm and the calculation of the radar Cross Ambiguity Function (CAF can be modeled as a notch filter, with the notch located at zero Doppler frequency in the surface of the radar CAF. The analysis shows that the notch’s width and depth are closely related to the step size of the NLMS algorithm. Subsequently, the effect of the notch in PCL radar target detection is analyzed. The results suggest that the detection performance of the PCL radar deteriorates because of the wide notch. Furthermore, the Nonuniform NLMS (NNLMS algorithm is proposed for removing the clutter with the Doppler frequency by using notch filtering. A step-size matrix is adopted to mitigate the low Doppler frequency clutter and lower the floor of the radar CAF. With the step-size matrix, can be obtained notches of different depths and widths in different range units of the CAF, which can filter the low Doppler frequency clutter. In addition, the convergence rate of the NNLMS algorithm is better than that of the traditional NLMS algorithm. The validity of the NNLMS algorithm is verified by experimental results.

  13. Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    Science.gov (United States)

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-07-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  14. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Science.gov (United States)

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Kuang, Shao-Qing; Fang, Zhihong; Zweidler-McKay, Patrick A; Yang, Hui; Wei, Yue; Gonzalez-Cervantes, Emilio A; Boumber, Yanis; Garcia-Manero, Guillermo

    2013-01-01

    The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA)/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL). We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2'-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

  16. Simulated mixed absorbers and effective atomic numbers for γ ...

    Indian Academy of Sciences (India)

    The total -ray interaction crosss-sections on mixed absorbers were determined at 662 keV with a view to study the effective atomic numbers for -ray absorption under narrow beam good geometry set-up. The measurements were taken for the combination of metallic absorbers like aluminium, copper, lead and mercury ...

  17. Fluence to absorbed foetal dose conversion coefficients for photons in 50 keV-10 GeV calculated using RPI-P models

    International Nuclear Information System (INIS)

    Taranenko, V.; Xu, X.G.

    2008-01-01

    Radiation protection of pregnant females and the foetus against ionising radiation is of particular importance to radiation protection due to high foetal radiosensitivity. The only available set of foetal conversion coefficients for photons is based on stylised models of simplified anatomy. Using the RPI-P series of pregnant female and foetus models representing 3-, 6- and 9-month gestation, a set of new fluence to absorbed foetal dose conversion coefficients has been calculated. The RPI-P anatomical models were developed using novel 3D geometry modelling techniques. Organ masses were adjusted to agree within 1% with the ICRP reference data for a pregnant female. Monte Carlo dose calculations were carried out using the MCNPX and Penelope codes for external 50 keV-10 GeV photon beams of six standard configurations. The models were voxelised at 3-mm voxel resolution. Conversion coefficients were tabulated for the three gestational periods for the whole foetus and brain. Comparison with previously published data showed deviations up to 120% for the foetal doses at 50 keV. The discrepancy can be primarily ascribed to anatomical differences. Comparison with published data for five major mother organs is also provided for the 3-month model. Since the RPI-P models exhibit a high degree of anatomical realism, the reported dataset is recommended as a reference for radiation protection of the foetus against external photon exposure. (authors)

  18. Factors affecting sound energy absorbance in acute otitis media model of chinchilla.

    Science.gov (United States)

    Guan, Xiying; Seale, Thomas W; Gan, Rong Z

    2017-07-01

    Acute otitis media (AOM) is a rapid-onset infection of the middle ear which results in middle ear pressure (MEP), middle ear effusion (MEE), and structural changes in middle ear tissues. Previous studies from our laboratory have identified that MEP, MEE, and middle ear structural changes are three factors affecting tympanic membrane (TM) mobility and hearing levels (Guan et al., 2014, 2013). Sound energy reflectance or absorbance (EA) is a diagnostic tool increasingly used in clinical settings for the identification of middle ear diseases. However, it is unclear whether EA can differentiate these three factors in an AOM ear. Here we report wideband EA measurements in the AOM model of chinchilla at three experimental stages: unopened, pressure released, and effusion removed. These correspond to the combined and individual effects of the three factors on sound energy transmission. AOM was produced by transbullar injection of Haemophilus influenzae in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent the relatively early and later phase of AOM. In each group of chinchillas, EA at 250-8000 Hz was measured using a wideband tympanometer at three experimental stages. Results show that the effects of MEP, MEE, and tissue structural changes over the frequency range varied with the disease time course. MEP was the primary contributor to reduction of EA in 4D AOM ears and had a smaller effect in 8D ears. MEE reduced the EA at 6-8 kHz in 4D ears and 2-8 kHz in 8D ears and was responsible for the EA peak in both 4D and 8D ears. The residual EA loss due to structural changes was observed over the frequency range in 8D ears and only at high frequencies in 4D ears. The EA measurements were also compared with the published TM mobility loss in chinchilla AOM ears. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Reconstructing the energy band electronic structure of pulsed laser deposited CZTS thin films intended for solar cell absorber applications

    Energy Technology Data Exchange (ETDEWEB)

    Pandiyan, Rajesh [Institut National de la Recherche Scientifique, Centre-Énergie, Matériaux et Télécommunications, 1650 Blvd. Lionel–Boulet, C.P. 1020, Varennes, QC J3X-1S2 (Canada); Oulad Elhmaidi, Zakaria [Institut National de la Recherche Scientifique, Centre-Énergie, Matériaux et Télécommunications, 1650 Blvd. Lionel–Boulet, C.P. 1020, Varennes, QC J3X-1S2 (Canada); University of Mohammed V, Faculty of Sciences, Materials Physics Laboratory, B.P. 1014 Rabat (Morocco); Sekkat, Zouheir [Optics & Photonics Center, Moroccan Foundation for Advanced Science, Innovation and Research, Rabat (Morocco); Abd-lefdil, Mohammed [University of Mohammed V, Faculty of Sciences, Materials Physics Laboratory, B.P. 1014 Rabat (Morocco); El Khakani, My Ali, E-mail: elkhakani@emt.inrs.ca [Institut National de la Recherche Scientifique, Centre-Énergie, Matériaux et Télécommunications, 1650 Blvd. Lionel–Boulet, C.P. 1020, Varennes, QC J3X-1S2 (Canada)

    2017-02-28

    Highlights: • High quality CZTS thin films grown by means of PLD technique without resorting to any post sulfurization process. • Effect of thermal annealing treatments (in the 200–500 °C range) on the structural, morphological and optoelectronic properties of PLD-CZTS films. • Experimental determination of key optoelectronic parameters (i.e.; E{sub g}, VBM, ϕ, I{sub p}, and χ) enabling the reconstruction of energy band electronic structure of the PLD-CZTS films. • Investigation on the energy band alignments of the heterojunction interface formed between CZTS and both CdS and ZnS buffer layer materials. - Abstract: We report here on the use of pulsed KrF-laser deposition (PLD) technique for the growth of high-quality Cu{sub 2}ZnSnS{sub 4} (CZTS) thin films onto Si, and glass substrates without resorting to any post sulfurization process. The PLD-CZTS films were deposited at room temperature (RT) and then subjected to post annealing at different temperatures ranging from 200 to 500 °C in Argon atmosphere. The X-ray diffraction and Raman spectroscopy confirmed that the PLD films crystallize in the characteristic kesterite CZTS structure regardless of their annealing temperature (T{sub a}), but their crystallinity is much improved for T{sub a} ≥ 400 °C. The PLD-CZTS films were found to exhibit a relatively dense morphology with a surface roughness (RMS) that increases with T{sub a} (from ∼14 nm at RT to 70 nm at T{sub a} = 500 °C with a value around 40 nm for T{sub a} = 300–400 °C). The optical bandgap of the PLD-CZTS films, was derived from UV–vis transmission spectra analysis, and found to decrease from 1.73 eV for non-annealed films to ∼1.58 eV for those annealed at T{sub a} = 300 °C. These band gap values are very close to the optimum value needed for an ideal solar cell absorber. In order to achieve a complete reconstruction of the one-dimensional energy band structure of these PLD-CZTS absorbers, we have combined both XPS and UPS

  20. Calorimetry for absorbed dose measurement at 1-4 MeV electron accelerators

    International Nuclear Information System (INIS)

    Miller, A.

    2000-01-01

    Calorimeters are used for dose measurement, calibration and intercomparisons at industrial electron accelerators, and their use at 10 MeV electron accelerators is well documented. The work under this research agreement concerns development of calorimeters for use at electron accelerators with energies in the range of 2-4 MeV. The dose range of the calorimeters is 3-40 kGy, and their temperature stability after irradiation was found to be sufficient for practical use in an industrial environment. Measurement uncertainties were determined to be 5% at k = 2. (author)