A 0.8V, 7μA, rail-to-rail input/output, constant Gm operational amplifier in standard digital 0.18μm CMOS

OpenAIRE

Citakovic, J; Nielsen, I. Riis; Nielsen, Jannik Hammel; Asbeck, P; Andreani, Pietro

2005-01-01

A two-stage amplifier, operational at 0.8V and drawing 7μA, has been integrated in a standard digital 0.18μm CMOS process. Rail-to-rail operations at the input are enabled by complementary transistor pairs with gm control. The efficient rail-to-rail output stage is biased in class AB. The measured DC gain of the amplifier is 75dB, and the unity-gain frequency is 870kHz with a 12pF, 100kΩload. Both input and output stage transistors are biased in weak inversion.

Plastic deformation and failure mechanisms in nano-scale notched metallic glass specimens under tensile loading

Science.gov (United States)

Dutta, Tanmay; Chauniyal, Ashish; Singh, I.; Narasimhan, R.; Thamburaja, P.; Ramamurty, U.

2018-02-01

In this work, numerical simulations using molecular dynamics and non-local plasticity based finite element analysis are carried out on tensile loading of nano-scale double edge notched metallic glass specimens. The effect of acuteness of notches as well as the metallic glass chemical composition or internal material length scale on the plastic deformation response of the specimens are studied. Both MD and FE simulations, in spite of the fundamental differences in their nature, indicate near-identical deformation features. Results show two distinct transitions in the notch tip deformation behavior as the acuity is increased, first from single shear band dominant plastic flow localization to ligament necking, and then to double shear banding in notches that are very sharp. Specimens with moderately blunt notches and composition showing wider shear bands or higher material length scale characterizing the interaction stress associated with flow defects display profuse plastic deformation and failure by ligament necking. These results are rationalized from the role of the interaction stress and development of the notch root plastic zones.

Experimental Investigation of Adiabatic Shear Banding at Different Impact Velocities

Science.gov (United States)

1993-01-01

plasticity and ASB’s is the Double-notch Shear specimen, it has been decided to use this concept in shear testing at medium and high strain rates...is the Double-notch Shear specimen. it has been decided to use this concept in shear testing at medium and high strain rates. Originally, Campbell...7] C. Fressengeas, Analyse dynamique 61asto-viscoplastique de l’h6tdrogdndit6 de la ddforma- tion plastique de cisalllement, Proc. Int. Conf. on

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....

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.

Experimental testing of hold down devices for timber frame shear walls

OpenAIRE

Caprolu, Giuseppe

2012-01-01

Källsner and Girhammar [1] have presented a new plastic design method for wood-framed shear walls at ultimate limit state. This method allows the designer to calculate the load-carrying capacity of partially anchored shear walls, where the leading stud is not anchored against uplift. The anchorage system of shear walls is provided by anchor bolts in the bottom rail and hold downs at the leading stud. Anchor bolts provide horizontal shear continuity between the bottom rail and the foundation. ...

Material Evaluation of an Elastomer, Epoxy and Lightweight Concrete Rail Attachment System for Direct Fixation Light Rail Applications

Science.gov (United States)

Swarner, Benjamin R.

Sound Transit plans to extend its current light rail system, which runs along the I-5 corridor in Seattle, Washington, across the I-90 Homer Hadley floating bridge as part of a project to connect the major city centers in the region. But, no light rail has ever crossed a floating bridge due to several unique engineering challenges. One of these challenges is attaching the rails to the existing bridge deck without drilling into the bridge pontoons. This research program was developed to test and analyze a direct fixation method that uses lightweight concrete plinths and an elastomer-epoxy system to attach the rails to the bridge deck. The elastomer used was a two-part, pourable elastomer with cork particles intermixed to alter the mechanical properties of the material. A lightweight concrete mixture was analyzed for use in the plinths, and system tests investigated the system response under tensile, compressive and shear loading. The shear response of the system was examined further under varying loading conditions including different surface preparations, elastomer thicknesses, strain-rates and after freeze-thaw conditioning. Experimental data was examined for trends based on these parameters to best characterize the system, and the elastomer was evaluated in the context of modern elastomer research.

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.

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

A Current-Mode Common-Mode Feedback Circuit (CMFB) with Rail-to-Rail Operation

Science.gov (United States)

Suadet, Apirak; Kasemsuwan, Varakorn

2011-03-01

This paper presents a current-mode common-mode feedback (CMFB) circuit with rail-to-rail operation. The CMFB is a stand-alone circuit, which can be connected to any low voltage transconductor without changing or upsetting the existing circuit. The proposed CMFB employs current mirrors, operating as common-mode detector and current amplifier to enhance the loop gain of the CMFB. The circuit employs positive feedback to enhance the output impedance and gain. The circuit has been designed using a 0.18 μm CMOS technology under 1V supply and analyzed using HSPICE with BSIM3V3 device models. A pseudo-differential amplifier using two common sources and the proposed CMFB shows rail to rail output swing (± 0.7 V) with low common-mode gain (-36 dB) and power dissipation of 390 μW.

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...

Characterization of deformed pearlitic rail steel

Science.gov (United States)

Nikas, Dimitrios; Meyer, Knut Andreas; Ahlström, Johan

2017-07-01

Pearlitic steels are commonly used for railway rails because they combine good strength and wear properties. During service, the passage of trains results in a large accumulation of shear strains in the surface layer of the rail, leading to crack initiation. Knowledge of the material properties in this region is therefore important for fatigue life prediction. As the strain is limited to a thin surface layer, very large strain gradients can be found. This makes it very difficult to quantify changes in material behavior. In this study hardness measurements were performed close to the surface using the Knoop hardness test method. The orientation of the pearlitic lamellas was measured to give an overview of the deformed microstructure in the surface of the rail. Microstructural characterization of the material was done by optical microscopy and scanning electron microscopy to evaluate the changes in the microstructure due to the large deformation. A strong gradient can be observed in the top 50 μm of the rail, while deeper into the rail the microstructure of the base material is preserved.

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.

Computation of wheel-rail contact force for non-mapping wheel-rail profile of Translohr tram

Science.gov (United States)

Ji, Yuanjin; Ren, Lihui; Zhou, Jinsong

2017-09-01

Translohr tram has steel wheels, in V-like arrangements, as guide wheels. These operate over the guide rails in inverted-V arrangements. However, the horizontal and vertical coordinates of the guide wheels and guide rails are not always mapped one-to-one. In this study, a simplified elastic method is proposed in order to calculate the contact points between the wheels and the rails. By transforming the coordinates, the non-mapping geometric relationship between wheel and rail is converted into a mapping relationship. Considering the Translohr tram's multi-point contact between the guide wheel and the guide rail, the elastic-contact hypothesis take into account the existence of contact patches between the bodies, and the location of the contact points is calculated using a simplified elastic method. In order to speed up the calculation, a multi-dimensional contact table is generated, enabling the use of simulation for Translohr tram running on curvatures with different radii.

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

Rail-to-rail low-power fully differential OTA utilizing adaptive biasing and partial feedback

DEFF Research Database (Denmark)

Tuan Vu, Cao; Wisland, Dag T.; Lande, Tor Sverre

A fully differential rail-to-rail Operational Transconductance Amplifier (OTA) with improved DC-gain and reduced power consumption is proposed in this paper. By using the adaptive biasing circuit and two differential inputs, a low stand-by current can be obtained together with reduced power...... consumption. The DC-gain of the proposed OTA is improved by adding a partial feedback loop. A Common-Mode Feedback (CMFB) circuit is required for fully differential rail-to-rail operation. Simulations show that the OTA topology has a low stand-by power consumption of 96μW and a high FoM of 3.84 [(V...

Tartu ihkab Rail Baltica kiirraudteed endale / Madis Aesma

Index Scriptorium Estoniae

Aesma, Madis

2005-01-01

2005. aasta sügisel alustatakse uuringuid, et välja selgitada, millisest Eesti linnast - Tartust, Pärnust või Viljandist - peaks tulevikus läbi minema kiirraudtee Rail Baltica, mis viib kuue tunniga Tallinnast Varssavisse. Kaart: Kiirraudtee Rail Baltica kolm võimalikku suunda. Kommenteerib Andrus Ansip

Use of notched beams to establish fracture criteria for beryllium

International Nuclear Information System (INIS)

Mayville, R.A.

1980-01-01

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

Rail-to-rail low-power fully differential OTA utilizing adaptive biasing and partial feedback

DEFF Research Database (Denmark)

Tuan Vu, Cao; Wisland, Dag T.; Lande, Tor Sverre

consumption. The DC-gain of the proposed OTA is improved by adding a partial feedback loop. A Common-Mode Feedback (CMFB) circuit is required for fully differential rail-to-rail operation. Simulations show that the OTA topology has a low stand-by power consumption of 96μW and a high FoM of 3.84 [(V...

An alternative to FASTSIM for tangential solution of the wheel-rail contact

Science.gov (United States)

Sichani, Matin Sh.; Enblom, Roger; Berg, Mats

2016-06-01

In most rail vehicle dynamics simulation packages, tangential solution of the wheel-rail contact is gained by means of Kalker's FASTSIM algorithm. While 5-25% error is expected for creep force estimation, the errors of shear stress distribution, needed for wheel-rail damage analysis, may rise above 30% due to the parabolic traction bound. Therefore, a novel algorithm named FaStrip is proposed as an alternative to FASTSIM. It is based on the strip theory which extends the two-dimensional rolling contact solution to three-dimensional contacts. To form FaStrip, the original strip theory is amended to obtain accurate estimations for any contact ellipse size and it is combined by a numerical algorithm to handle spin. The comparison between the two algorithms shows that using FaStrip improves the accuracy of the estimated shear stress distribution and the creep force estimation in all studied cases. In combined lateral creepage and spin cases, for instance, the error in force estimation reduces from 18% to less than 2%. The estimation of the slip velocities in the slip zone, needed for wear analysis, is also studied. Since FaStrip is as fast as FASTSIM, it can be an alternative for tangential solution of the wheel-rail contact in simulation packages.

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.

77 FR 17121 - RailAmerica, Inc., Palm Beach Rail Holding, Inc., RailAmerica Transportation Corp., RailTex, Inc...

Science.gov (United States)

2012-03-23

...% of the Class A Common Units of TransRail, giving RailTex a 70% ownership interest in TransRail and control of W&C through TransRail. The MG Principals will retain the Class B Common Units of TransRail... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35605] RailAmerica, Inc...

A low power and low distortion rail-to-rail input/output amplifier using constant current technique

International Nuclear Information System (INIS)

Liu Yan; Zhao Yiqiang; Zhang Shilin; Zhao Hongliang

2011-01-01

A rail-to-rail amplifier with constant transconductance, intended for audio processing, is presented. The constant transconductance is obtained by a constant current technique based on the input differential pairs operating in the weak inversion region. MOSFETs working in the weak inversion region have the advantages of low power and low distortion. The proposed rail-to-rail amplifier, fabricated in a standard 0.35 μm CMOS process, occupies a core die area of 75 x 183 μm 2 . Measured results show that the maximum power consumption is 85.37 μW with a supply voltage of 3.3 V and the total harmonic distortion level is 1.2% at 2 kHz. (semiconductor integrated circuits)

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

A CMOS rail-to-rail linear VI-converter

NARCIS (Netherlands)

Vervoort, P.P.; Vervoort, P.P.; Wassenaar, R.F.

1995-01-01

A linear CMOS VI-converter operating in strong inversion with a common-mode input range from the negative to the positive supply rail is presented. The circuit consists of three linear VI-converters based on the difference of squares principle. Two of these perform the actual V to I conversion,

Recent developments in multi-parametric three-dimensional stress field representation in plates weakened by cracks and notches

Directory of Open Access Journals (Sweden)

P. Lazzarin

2013-07-01

Full Text Available The paper deals with the three-dimensional nature and the multi-parametric representation of the stress field ahead of cracks and notches of different shape. Finite thickness plates are considered, under different loading conditions. Under certain hypotheses, the three-dimensional governing equations of elasticity can be reduced to a system where a bi-harmonic equation and a harmonic equation have to be simultaneously satisfied. The former provides the solution of the corresponding plane notch problem, the latter provides the solution of the corresponding out-of-plane shear notch problem. The analytical frame is applied to some notched and cracked geometries and its degree of accuracy is discussed comparing theoretical results and numerical data from 3D FE models.

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.

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...

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.

Rail electrodynamics in a plasma armature railgun

International Nuclear Information System (INIS)

Rolader, G.E.; Jamison, K.A.; Villecco, R.A.; Graham, F.R.

1991-01-01

A model is developed to investigate rail electrodynamics in a plasma armature railgun. This model describes the rail motion in response to the transitory Lorentz force and the compressive restoration force from the material which is between the rails and the containment structure. In this model the distance between the rails is found to oscillate with a frequency of β. The magnetic field and the dynamic behavior of the rails induce local electric fields. We investigate the significance of these electric fields in the laboratory frame and in the projectile frame. In the lab frame, rail electrodynamics induces local electric fields which have maximums spaced behind the projectile at locations where βt p is an odd multiple of π, where t p is the time since the projectile has passed an axial location on the rails. When the projectile is accelerating, rail dynamics induce electric fields in the projectile frame which have maximums where βt p is an even multiple of π. As the projectile velocity increases, the locations of the peak voltages move farther behind the projectile. For the CHECMATE railgun, calculations indicate that the rail displacement is on the order of 2 mm, the rail velocity is on the order of 50 m/s, and the voltages induced in the projectile frame are on the order of 20--40 V

Unistuste Rail Baltic - ilus ja kallis / Mikk Salu

Index Scriptorium Estoniae

Salu, Mikk, 1975-

2011-01-01

Rail Balticu puhul on tähtsaim küsimus, kas uut raudteeühendust on üldse vaja, mitte aga see, kas tee läheb läbi Tartu või Pärnu. Konsutatsioonifirma AECOM koostatud raportist Rail Balticu tasuvuse kohta

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

RailSiTe® (Rail Simulation and Testing

Directory of Open Access Journals (Sweden)

Martin Johne

2016-10-01

Full Text Available RailSiTe® (Rail Simulation and Testing is DLR’s rail simulation and testing laboratory (see Figure 1. It is the implementation of a fully modular concept for the simulation of on-board and trackside control and safety technology. The RailSiTe® laboratory additionally comprises the RailSET (Railway Simulation Environment for Train Drivers and Operators human-factors laboratory, a realistic environment containing a realistic train mockup including 3D simulation.

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.

Further study on the wheel-rail impact response induced by a single wheel flat: the coupling effect of strain rate and thermal stress

Science.gov (United States)

Jing, Lin; Han, Liangliang

2017-12-01

A comprehensive dynamic finite-element simulation method was proposed to study the wheel-rail impact response induced by a single wheel flat based on a 3-D rolling contact model, where the influences of the structural inertia, strain rate effect of wheel-rail materials and thermal stress due to the wheel-rail sliding friction were considered. Four different initial conditions (i.e. pure mechanical loading plus rate-independent, pure mechanical loading plus rate-dependent, thermo-mechanical loading plus rate-independent, and thermo-mechanical loading plus rate-dependent) were involved into explore the corresponding impact responses in term of the vertical impact force, von-Mises equivalent stress, equivalent plastic strain and shear stress. Influences of train speed, flat length and axle load on the flat-induced wheel-rail impact response were discussed, respectively. The results indicate that the maximum thermal stresses are occurred on the tread of the wheel and on the top surface of the middle rail; the strain rate hardening effect contributes to elevate the von-Mises equivalent stress and restrain the plastic deformation; and the initial thermal stress due to the sliding friction will aggravate the plastic deformation of wheel and rail. Besides, the wheel-rail impact responses (i.e. impact force, von-Mises equivalent stress, equivalent plastic strain, and XY shear stress) induced by a flat are sensitive to the train speed, flat length and axle load.

Dynamic Shear Deformation and Failure of Ti-6Al-4V and Ti-5Al-5Mo-5V-1Cr-1Fe Alloys.

Science.gov (United States)

Ran, Chun; Chen, Pengwan

2018-01-05

To study the dynamic shear deformation and failure properties of Ti-6Al-4V (Ti-64) alloy and Ti-5Al-5Mo-5V-1Cr-1Fe (Ti-55511) alloy, a series of forced shear tests on flat hat shaped (FHS) specimens for the two investigated materials was performed using a split Hopkinson pressure bar setup. The evolution of shear deformation was monitored by an ultra-high-speed camera (Kirana-05M). Localized shear band is induced in the two investigated materials under forced shear tests. Our results indicate that severe strain localization (adiabatic shear) is accompanied by a loss in the load carrying capacity, i.e., by a sudden drop in loading. Three distinct stages can be identified using a digital image correlation technique for accurate shear strain measurement. The microstructural analysis reveals that the dynamic failure mechanisms for Ti-64 and Ti-55511 alloys within the shear band are of a cohesive and adhesive nature, respectively.

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

DEFF Research Database (Denmark)

Jacobsen, Torben Krogsdal; Brøndsted, Povl

1997-01-01

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

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

Directory of Open Access Journals (Sweden)

Sung Hee Choi

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

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

Directory of Open Access Journals (Sweden)

Eileen M Redmond

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

Micromechanical and in situ shear testing of Al–SiC nanolaminate composites in a transmission electron microscope (TEM)

Energy Technology Data Exchange (ETDEWEB)

Mayer, C. [Materials Science and Engineering, Arizona State University, Tempe, AZ 85287-6106 (United States); Li, N.; Mara, N. [Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Albuquerque, NM (United States); Chawla, N., E-mail: nchawla@asu.edu [Materials Science and Engineering, Arizona State University, Tempe, AZ 85287-6106 (United States)

2015-01-05

Nanolaminate composites show promise as high strength and toughness materials. However, due to the limited volume of these materials, micron scale mechanical testing methods must be used to determine the properties of these films. To this end, a novel approach combining a double notch shear testing geometry and compression with a flat punch in a nanoindenter was developed to determine the mechanical properties of these films under shear loading. To further elucidate the failure mechanisms under shear loading, in situ TEM experiments were performed using a double notch geometry cut into the TEM foil. Aluminum layer thicknesses of 50 nm and 100 nm were used to show the effect of constraint on the deformation. Higher shear strength was observed in the 50 nm sample (690±54 MPa) compared to the 100 nm sample (423±28.7 MPa). Additionally, failure occurred close to the Al–SiC interface in the 50 nm sample as opposed to failure within the Al layer in the 100 nm sample.

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

Science.gov (United States)

Chan, Kwai S.

2015-12-01

Rectangular plates of Ti-6Al-4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti-6Al-4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%-75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm.

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

International Nuclear Information System (INIS)

Chan, Kwai S.

2015-01-01

Rectangular plates of Ti–6Al–4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti–6Al–4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%–75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm. (paper)

Rail Baltica tuleb : reisiterminalide arhitektuurivõistlused Tallinnas ja Pärnus = Rail Baltic is coming : Arhitecture competitions for passenger rail terminals in Tallinn and Pärnu / Andres Lindemann

Index Scriptorium Estoniae

Lindemann, Andres

2015-01-01

2014.a. lõpus lõppesid arhitektuurivõistlused Tallinnas Ülemistele ja Pärnus Papiniidu piirkonda plaanitavatele Rail Baltica reisiterminalidele. Artiklis on antud põgus ülevaade võitnud töödest

Taanlased pidasid Pärnut läbivat Rail Balticat kalleimaks / Raavo Raadik

Index Scriptorium Estoniae

Raadik, Raavo

2007-01-01

Taani konsultatsioonifirma COWI tutvustas uuringut, milles analüüsiti Balti riike Euroopaga ühendava raudtee Rail Baltica majanduslikku tasuvust ning selle loomiseks vajalike investeeringute mahtu. Kaart: Rail Baltica võimalik teekond Eestis

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

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 ...

IR thermographic observation and shear bands plasticity analysis in Fe-based metallic glass

International Nuclear Information System (INIS)

Bouzakher, B.; Benameur, T.; Sidhom, H.

2009-01-01

Infrared thermography observation and in situ atomic force microscopy characterization were carried out to investigate the mechanical damage processes at the edge-notch region of large ribbons of Fe 78 Si 10 B 12 metallic glass. An obvious thermoelastic and inelastic degradation phenomenon was observed ahead at the notched region of the specimens, which probably result from free volume accumulation process and shear band activity during plane stress solicitations. Moreover, AFM topographic and frictional analysis of changes in the crack path during stable crack propagation regime revealed a periodic morphology evolution, formation of nanoscale damage cavity in the range of 20-140 nm and a maximum temperature rise ahead of the pre-crack tip was found in the order of 1.5 deg. C. The nanometer scaled shear offset, discreteness and shear bands density were determined. While these key parameters play a role in observing a large plastic zone in front of the crack, however they are unable to explain the distinct intrinsic ductility of some monolithic metallic glasses. A general Mohr-Coulomb-type constitutive description was used to deduce analytic expressions for prediction of the variation of hydrostatic component of the applied stress to the shear stress ratio as function of Poisson's ratio.

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

A symmetrical rail accelerator

International Nuclear Information System (INIS)

Igenbergs, E.

1991-01-01

This paper reports on the symmetrical rail accelerator that has four rails, which are arranged symmetrically around the bore. The opposite rails have the same polarity and the adjacent rails the opposite polarity. In this configuration the radial force acting upon the individual rails is significantly smaller than in a conventional 2-rail configuration and a plasma armature is focussed towards the axis of the barrel. Experimental results indicate a higher efficiency compared to a conventional rail accelerator

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

International Nuclear Information System (INIS)

Rack, H.J.

1975-01-01

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

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

Directory of Open Access Journals (Sweden)

Miguel Aste-Amézaga

2010-02-01

Full Text Available Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target.Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library. Two classes of antibodies were found, one directed against the EGF-repeat region that encompasses the ligand-binding domain (LBD, and the second directed against the activation switch of the receptor, the Notch negative regulatory region (NRR. The antibodies are selective for Notch1, inhibiting Jag2-dependent signaling by Notch1 but not by Notch 2 and 3 in reporter gene assays, with EC(50 values as low as 5+/-3 nM and 0.13+/-0.09 nM for the LBD and NRR antibodies, respectively, and fail to recognize Notch4. While more potent, NRR antibodies are incomplete antagonists of Notch1 signaling. The antagonistic activity of LBD, but not NRR, antibodies is strongly dependent on the activating ligand. Both LBD and NRR antibodies bind to Notch1 on human tumor cell lines and inhibit the expression of sentinel Notch target genes, including HES1, HES5, and DTX1. NRR antibodies also strongly inhibit ligand-independent signaling in heterologous cells transiently expressing Notch1 receptors with diverse NRR "class I" point mutations, the most common type of mutation found in human T-cell acute lymphoblastic leukemia (T-ALL. In contrast, NRR antibodies failed to antagonize Notch1 receptors bearing rare "class II" or "class III" mutations, in which amino acid insertions generate a duplicated or constitutively sensitive metalloprotease cleavage site. Signaling in T-ALL cell lines bearing class I mutations is partially refractory to inhibitory antibodies as compared to cell

Rail Baltic trügib Nabalasse / Ulvar Käärt

Index Scriptorium Estoniae

Käärt, Ulvar, 1982-

2013-01-01

Majandusministeeriumi plaanitava kiirrongiühenduse Rail Balticu võimalikud kulgemisteed läbivad keskkonnaministeeriumis kavandatavat Nabala karstiala maastikukaitseala, samuti pole trassivariantide koostamisel arvesse võetud metsloomade liikumist

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)

Rails on Windows

CERN Document Server

Hibbs, Curt

2007-01-01

It's no secret that the entire Ruby onRails core team uses OS X as their preferreddevelopment environment. Becauseof this, it is very easy to findauthoritative information on the webabout using Rails on OS X. But the truthis that Windows developers using Railsprobably outnumber those using otherplatforms. A Windows development environmentcan be just as productive asany other platform. This is a guide to developing with Rubyon Rails under Windows. It won't teachyou how to write Ruby on Rails web applications,but it will show you what toolsto use and how to set them up to createa complete Rail

Personal interests hinder Rail Baltica

Index Scriptorium Estoniae

2011-01-01

Läti seimi liige Janis Reirs leiab, et Rail Baltica ehitus on Moskva ja Riia vahelise raudtee ehitusest prioriteetsem, kuna esimest võib potentsiaalselt finantseerida Euroopa Liit. Transpordiminister Uldis Augulis kohtub oma Venemaa kolleegi Igor Levitiniga 7. aprillil. Peaminister Valdis Dombrovskise sõnul vajavad mõlemad projektid majandusanalüüsi

Electrodynamic wear of rails in high current density rail gun discharges

International Nuclear Information System (INIS)

Edwards, W.T.; Caldwell, S.G.

1984-01-01

Significant advances in high current, high speed power sources, has in recent years allowed rail guns to produce very high velocity (> 10 km/sec) macroscopic particles (> 1/10 grams). A continuing problem is the structural integrity of the components under these loadings and in particular, the rail wear due to the high current density plasma contacts. In this investigation a small bore rail gun (6x5 mm) was used with a 10.6 kjoule capacitor energy source to examine the modes of rail damage. The rails were constructed of 110 copper base material. These rails were used in an uncoated condition and also with plasma sprayed coatings of W and W/WC. The resulting surface wear was characterized by standard metallurgical techniques and analyzed for the various coatings

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

Erastaja varjas osalusi Rail Estonias / Anneli Ammas

Index Scriptorium Estoniae

Ammas, Anneli, 1962-

2001-01-01

Eesti Päevalehe andmeil on Eesti Raudtee erastamiskonkursi võitnud Rail Estonia suurim aktsionär John Orrison. Vt. samas "Töötasid koos Bushi kabinetis". Väidetavalt salgab J. Orrison Tony Massei tundmise maha

Impact of the rail-pad multi-discrete model upon the prediction of the rail response

Science.gov (United States)

Mazilu, T.; Leu, M.

2017-08-01

Wheel/rail vibration has many technical effects such as wear of the rolling surfaces, rolling noise, settlement of the ballast and subgrade etc. This vibration is depending on the rail pad characteristic and subsequently, it is important to have an accurate overview on the relation between the rail pad characteristic and the level of the wheel/rail vibration. To this end, much theoretical and experimental research has been developed in the past, and for the theoretical approach the track model, in general, and, particularly, the rail pad model is of crucial importance. Usually, the rail pad model is discrete model one, neglecting the length of the rail pad. This fact is questionable because the sleepers span is only 4 times the rail pad length. Using the rail pad discrete model, the rail response is overestimated when the frequency of the excitation equals the pinned-pinned resonance frequency. In this paper, a multi-discrete model for the rail pad, consisting in many Kelvin-Voigt parallel systems, is inserted into an analytical model of the track. The track model is reduced to a rail taken as infinite Timoshenko beam, discretely supported via rail pad, sleeper and ballast. The influence of the number of Kelvin-Voigt systems of the rail pad model on the rail response is analysed.

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

Možnosti vstřikovacího systému common-rail

OpenAIRE

Smilek, Tomáš

2008-01-01

Tomáš Smilek Možnosti vstřikovacího systému common-rail BP, Ústav automobilního a dopravního inženýrství, 2008, str. 23, obr. 18, přílohy 0 Bakalářská práce se zabývá vstřikovacím systémem common-rail. Popisuje historii vývoje stejně jako jednotlivé části systému a jejich funkci. Také stanovuje výhody oproti starým způsobům vstřikování. Tomáš Smilek Possibilities of Common-rail Injection System BT, Institute of Automotive Engineering, 2008, p. 23, fig. 18, appendices 0 This study´s motivat...

Determination of the primary technical parameters of the test bench for controlling the temperature of rails and rail bars of continuous welded rail

Directory of Open Access Journals (Sweden)

Tertychnyi Vitalii

2017-01-01

Full Text Available One of the most important factors determining the reliability and safety of operation of the continuous welded rail track is the temperature of the rails. All conditions of laying, repair and maintenance of the track during the entire cycle of rails operation depend on it. The existing rail temperature monitoring method does not take into account a few significant factors and that leads to significant errors in determining the actual temperature of the rail bar. The authors propose a new rail temperature measurement method on a special test bench which maximally simulates possible environmental operating conditions for the rail bars, the profile of the roadway (embankment or cut, as well as the actual spatial latitude and meridian location of the rail slabs. At the bench, the studied rails are fastened with the help of rail braces on half ties, in the ballast bed, with sizes in accordance with the existing reference documents. At the first stage, the most common KB-65 intermediate fastener for the continuous welded rail in Ukraine will be used, while in subsequent stages KPP-5 fastening will be used.

Managing rail service life

Directory of Open Access Journals (Sweden)

Z. Popović

2014-10-01

Full Text Available The service life of rails depends especially on the operational loads and speeds on the railway lines, as well as on the rail maintenance policy. There are multiple aspects of rail maintenance optimization. The following article considers optimisation of rail maintenance activities relating to rail head surface condition in order to reduce corrective work on track geometry, as well as to minimize the overall costs for track maintenance. The objects of this research are issues and challenges related to rail and track maintenance in curves on modern conventional railway lines for mixed traffic.

Rail passengers rights

Directory of Open Access Journals (Sweden)

Đurđev Dušanka J.

2016-01-01

Full Text Available The legal framework of rail passengers rights is set out in a combination of international and European law: an international measure, the rather unwieldy Uniform Rules concerning the Contract for International Carriage of Passengers and Luggage by Rail, forming part of the Convention concerning International Carriage by Rail of 9 May 1980 (as amended by the Vilnius Protocol of 3 June 1999 ['CIV'], lays down a basic framework which is then fleshed out by more recent EU legislation, Regulation (EC No 1371/2007 on Rail Passengers ' Rights and Obligations. Regulation 1371/2007/EC on rail passenger rights and obligations sets out minimum quality standards that have to be guaranteed to all passengers on all lines. .

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

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.)

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

Some design aspects of a two-stage rail-to-rail CMOS op amp

NARCIS (Netherlands)

Gierkink, Sander L.J.; Holzmann, Peter J.; Wiegerink, Remco J.; Wassenaar, R.F.

1999-01-01

A two-stage low-voltage CMOS op amp with rail-to-rail input and output voltage ranges is presented. The circuit uses complementary differential input pairs to achieve the rail-to-rail common-mode input voltage range. The differential pairs operate in strong inversion, and the constant

Preliminary rail access study

International Nuclear Information System (INIS)

1990-01-01

The Yucca Mountain site, located on the southwestern edge of the Nevada Test Site, is an undeveloped area under investigation as a potential site for nuclear waste disposal by the US Department of Energy. The site currently lacks rail service and an existing rail right-of-way. If the site is suitable and selected for development as a disposal site, rail service is desirable to the Office of Civilian Radioactive Waste Management Program because of the potential of rail to reduce number of shipments and costs relative to highway transportation. This preliminary report is a summary of progress to date for activities to identify and evaluate potential rail options from major rail carriers in the region to the Yucca Mountain site. It is currently anticipated that the rail spur will be operational after the year 2000. 9 refs., 13 figs., 2 tabs

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

Science.gov (United States)

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

2018-01-17

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

Band-notched spiral antenna

Science.gov (United States)

Jeon, Jae; Chang, John

2018-03-13

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

Atomistic simulation study of the shear-band deformation mechanism in Mg-Cu metallic glasses

DEFF Research Database (Denmark)

Bailey, Nicholas; Schiøtz, Jakob; Jacobsen, Karsten Wedel

2006-01-01

We have simulated plastic deformation of a model Mg-Cu metallic glass in order to study shear banding. In uniaxial tension, we find a necking instability occurs rather than shear banding. We can force the latter to occur by deforming in plane strain, forbidding the change of length in one...... of the transverse directions. Furthermore, in most of the simulations a notch is used to initiate shear bands, which lie at a 45 degrees angle to the tensile loading direction. The shear bands are characterized by the Falk and Langer local measure of plastic deformation D-min(2), averaged here over volumes...... observe a slight decrease in density, up to 1%, within the shear band, which is consistent with notions of increased free volume or disorder within a plastically deforming amorphous material....

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

Science.gov (United States)

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

2016-01-01

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

Implications of rail electrodynamics

International Nuclear Information System (INIS)

Rolader, G.E.; Jamison, K.A.

1990-01-01

A model is developed to investigate possible effects of rail electrodynamics on the performance of railguns. This model describes the oscillatory nature of the rail motion in response to the Lorentz force and the compressive restoration force of material which is behind the rails. In this simple model the rails are found to oscillate with a frequency of β. The rail dynamic behavior induces local electric fields. The authors investigate the significance of these electric fields on stationary particles (lab frame) and on particles moving at the velocity of the plasma/projectile system (projectile frame)

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

75 FR 76520 - Tennessee Southern Railroad Company, Patriot Rail, LLC, Patriot Rail Holdings LLC, and Patriot...

Science.gov (United States)

2010-12-08

... family by converting two of its subsidiaries from corporations into limited liability companies: (1... Railroad Company, Patriot Rail, LLC, Patriot Rail Holdings LLC, and Patriot Rail Corp.--Corporate Family... Railroad Company (TSRR), Patriot Rail, LLC (PRL) and its subsidiaries, Patriot Rail Holdings LLC (PRH) and...

Framing Light Rail Projects

DEFF Research Database (Denmark)

Olesen, Mette

2014-01-01

In Europe, there has been a strong political will to implement light rail. This article contributes to the knowledge concerning policies around light rail by analysing how local actors frame light rail projects and which rationalities and arguments are present in this decision-making process....... The article draws on the socio-technical approach to mobilities studies in order to reassemble the decision-making process in three European cases: Bergen, Angers, and Bern. This article provides insights into the political, discursive and material production of light rail mobilities in a European context....... It identifies the planning rationales behind the systems and the policies that have been supportive of this light rail vision. Finally, the article identifies the practical challenges and potentials that have been connected to the different local frames of light rail mobility which can be used in future...

Identification and prioritization of rail squat defects in the field using rail magnetisation technology

Science.gov (United States)

Kaewunruen, Sakdirat

2015-04-01

Inevitably, rail squats and studs are continuing to be a serious problem for railway organisations around the world in the 21st century. They are typically classified as the growth of any cracks that have grown longitudinally through the subsurface and some of the cracks propagating to the bottom of rails transversely, and have branched from initial longitudinal cracks with a depression of rail surface. The horizontal crack, which results in a depression of rail surface, induces increased maintenance level, more frequent monitoring, compromised rail testing (as the crack shields the signal echoes), and possible broken rails. This paper presents field investigations using a magnetised-rail testing device developed by MRX Technologies to identify and prioritise the rail squats. Most of the in situ squats were found on the high rail of the transition (variable-radius curved track), which is associated with rolling contact fatigue (RCF). This investigation highlights the field performance of the MRX's surface crack detection technology in comparison with the traditional ultrasonic method and detailed walking inspection. Visually, it was found in the field that the size of the RCF squats varies from very small to moderate. The predicted crack data were obtained by scanning the magnitised rails. The comparison of the actual crack depths (ultrasonic) and the predicted crack depths (MRX device) shows: • A possible correlation for small RCF/ squat cracks. • Poor interpretation of larger defects and welds. The field assessment also suggests some practical issues required for further development, including the detection of rail spalling, deep transverse crack, welding, and so on.

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

Bronze railing from Mediana

Directory of Open Access Journals (Sweden)

Vasić Miloje R.

2003-01-01

Full Text Available The hoard containing components of bronze railing was discovered in trench 7 during excavations at Mediana in 2000. Railing consists of cancelli and herms with busts of deities between them. Railing was constructed in such a way that it was possible to disassemble and reassemble it. Three cancelli one fragmented semicancellus cast together with herm and herms, one with bust of Aesculapius and other with bust of Luna. It could be concluded that railing consisted of two segments with passage between them. Male deities were represented on the left segment of the railing and female deities on the right segment. Detailed analysis revealed that Aesculapius as well as Luna bear strong mark of classical Greek and Hellenistic art, which experienced some kind of renaissance in the time of Constantine I. It is very probable that we can recognize the portrait of Faustina, Constantine’s wife in the portrait of Luna. According to the historical events the railing could have been produced before 325 AD when Constantine definitively accepted Christianity at Council of Nicaea. It is difficult to say where the railing had been produced. It had been most probably brought to Mediana during the stay of emperor Julian in Niš in 361. The sculptures found in one room of the villa with peristyle had probably been brought at the same time. The apse of triclinium of this villa had most likely been arranged as small shrine with bronze railing at its entrance. The railing was buried in 378 after battle of Adrianople and invasion of Goths in diocese Dacia.

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

NARCIS (Netherlands)

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

Activation of Notch signaling requires intracellular routing of the receptor, but the mechanisms controlling the distinct steps in the routing process is poorly understood. We identify PKCζ as a key regulator of Notch receptor intracellular routing. When PKCζ was inhibited in the developing chick

Notch filters for port-Hamiltonian systems

NARCIS (Netherlands)

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

2012-01-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

A low-voltage Op Amp with rail-to-rail constant-gm input stage and a class AB rail-to-rail output stage

NARCIS (Netherlands)

Botma, J.H.; Wassenaar, R.F.; Wiegerink, Remco J.

1993-01-01

In this paper a low-voltage two-stage Op Amp is presented. The Op Amp features rail-to-rail operation and has an @put stage with a constant transconductance (%) over the entire common-mode input range. The input stage consists of an n- and a PMOS differential pair connected in parallel. The constant

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.

RESIDUAL RESOURCE STUDY OF DEFECTIVE RAILS FOR TYPE P 50 CYCLE TEST OF ENDURANCE

Directory of Open Access Journals (Sweden)

R. M. Yosyfovych

2015-11-01

Full Text Available Purpose. The paper is devoted to the study and evaluation of residual life for defective rails P50 operated on the roads of the Kyiv subway, which are taken out of service because of defects 11.1-2 on the side of the rolling surface of the rail head. Methodology. The studies were performed with the use of experimental methods: testing of samples of defective rails in the cyclical strength of the pulse machine and testing of defective rails in the static load limit on the hydraulic vertical press. Findings. The performed experiments indicate that on the tests basis in 2 million cycles is only a small development (increase in size 0.5-0.7 mm of existing code defects 11.2 as a result of shedding the particles of crumble out metal on the side of the rails head of working prototypes. The intensity and the catastrophic development of defects, such as 11.2, or transformation of these defects in defects such as 21.2 or 30G.2 did not happen in any case. Originality. For the first time in Ukraine with the theoretical calculations substantiated the greater possibility of defects formation of contact fatigue origin in the form of spall and jag of metal on the surface of the rail, at the edge of the head. It is the result of the creation of a high degree of stress nonequilibrium compression in this area, due to the high values of principal normal stresses and appearance of large shear stresses in the body of the head at a depth of 2.5-3.5 mm, exceeding the yield strength and metal endurance. The tests of experimental prototypes of defective rails on high cycle endurance (based № = 2,1h10 cycles with periodic defectoscopic control were conducted. Practical value. In experiments, the new data of the resistance ability to spall rail defects on the surface of the head of rolling on the code 11.1-2 long-term cyclic loading equal to operational magnitude at the wheel load test of 2 million cycles was obtained. That is, the defective rails can have residual life

Rail vehicle dynamics

CERN Document Server

Knothe, Klaus

2017-01-01

This book on the dynamics of rail vehicles is developed from the manuscripts for a class with the same name at TU Berlin. It is directed mainly to master students with pre-knowledge in mathematics and mechanics and engineers that want to learn more. The important phenomena of the running behaviour of rail vehicles are derived and explained. Also recent research results and experience from the operation of rail vehicles are included. One focus is the description of the complex wheel-rail contact phenomena that are essential to understand the concept of running stability and curving. A reader should in the end be able to understand the background of simulation tools that are used by the railway industry and universities today.

Design of Low Voltage Low Power CMOS OP-AMPS with Rail-to-Rail Input/Output Swing

OpenAIRE

Gopalaiah, SV; Shivaprasad, AP; Panigrahi, Sukanta K

2004-01-01

A novel input and output biasing circuit to extend the input common mode (CM) voltage range and the output swing to rail-to-rail in a low voltage op-amp in standard CMOS technology is presented. The input biasing circuit uses a Switched Capacitor Based Attenuator (SCBA) approach to establish rail-to-rail common mode input voltage range. And the output biasing circuit uses an Output Driver (OD), with floating bias to give the rail-to-rail swing at output stage. Three different OD schemes in op...

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.

High speed rails. Fatigue behaviour

International Nuclear Information System (INIS)

Duart, J. M.; Pero-Sanz, J. A.; Verdeja, J. I.

2005-01-01

In recent years, passenger train speed and freight train load have increased to enhance efficiency of rail road transportation. These trends have increased the severity of rail service conditions, calling for rails with greater wear resistance, strength and fatigue behaviour. In the United Stated and Europe, track site weld rails are made entirely by aluminothermic process. This work describes the results of experimental study conducted on bending fatigue strength of plain rails and aluminothermic welded rails with preheating procedures (oxipropane and air-induced propane) approved by railways authorities. Compliance with the required fatigue strength shall be ascertained by 4 point pulsating bending test in accordance with European standards by aluminothermic welding in rails. The locati method, based in the empirical Miner's law about the cumulative damage on a fatigue tested material, allows, once known the Wohler curve of the welding process in use to settle the fatigue tensile limit at 50% with only one test. The values obtained at 2.10''6 cycles for plain rails (S f =353 MPa), oxipropane preheated aluminothermic weld rails (S f =225 MPa), and propane-air induced aluminothermic weld rails (S f =210 MPa) are very similar to those resulting from test method stated in the European Standard. From our point of view and due to its ease, speediness and savings, this is the most suitable test to check the quality and compare the aluminothermic processes in use. (Author) 15 refs

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...

Burkhardt plaanib rajada Rail Balticat / Liis Kängsepp

Index Scriptorium Estoniae

Kängsepp, Liis, 1981-

2007-01-01

Eesti Raudteest loobuma pidanud Edward Burkhardt hakkab arendama Rail Balticat ning otsib võimalust panna Eesti ja Soome vahele käima vagunipraam. Vt. samas: Raudtee müüjad endiselt nördinud. Küsimustele vastab Eesti Raudtee uus juht Kaido Simmermann

Simply rails 2 the ultimate beginner's guide to Ruby on rails

CERN Document Server

Lenz, Patrick

2008-01-01

Want to learn all about Ruby on Rails 2.0, the web application framework that is inspiring developers around the world? The second edition of this practical, hands on book will: show you how to install Ruby on Rails on Windows, Mac, or Linux walk you, step by step, through the development of a Web 2.0 social news application, just like digg.com show you how to test, debug, benchmark, and deploy your Rails application Unlike other Rails books, this book doesn't assume that you are an experienced web developer, or that you've used Ruby before. An entire chapter is devoted to learning Ruby in a fun way, using the interactive Ruby console, so you can follow along at home. You'll be an accomplished Ruby programmer in no time! The example application that the book builds - a user-generated news web site - is built upon with each following chapter, and concepts such as sessions, cookies and basic AJAX usage are gradually introduced. Different aspects of Rails, such as user authentication, session cookies, and automa...

Optimization of wheel-rail interface friction using top-of-rail friction modifiers: State of the art

Science.gov (United States)

Khan, M. Roshan; Dasaka, Satyanarayana Murty

2018-05-01

High Speed Railways and Dedicated Freight Corridors are the need of the day for fast and efficient transportation of the ever growing population and freight across long distances of travel. With the increase in speeds and axle loads carried by these trains, wearing out of rails and train wheel sections are a common issue, which is due to the increase in friction at the wheel-rail interfaces. For the cases where the wheel-rail interface friction is less than optimum, as in case of high speed trains with very low axle loads, wheel-slips are imminent and loss of traction occurs when the trains accelerate rapidly or brake all of a sudden. These vast variety of traction problems around the wheel-rail interface friction need to be mitigated carefully, so that the contact interface friction neither ascents too high to cause material wear and need for added locomotive power, nor be on the lower side to cause wheel-slips and loss of traction at high speeds. Top-of-rail friction modifiers are engineered surface coatings applied on top of rails, to maintain an optimum frictional contact between the train wheels and the rails. Extensive research works in the area of wheel-rail tribology have revealed that the optimum frictional coefficients at wheel-rail interfaces lie at a value of around 0.35. Application of top-of-rail (TOR) friction modifiers on rail surfaces add an extra layer of material coating on top of the rails, with a surface frictional coefficient of the desired range. This study reviews the common types of rail friction modifiers, the methods for their application, issues related with the application of friction modifiers, and a guideline on selection of the right class of coating material based on site specific requirements of the railway networks.

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.

Head first rails a learner's companion to ruby on rails

CERN Document Server

Griffiths, David

2009-01-01

Ready to transport your web applications into the Web 2.0 era? Head First Rails takes your programming -- and productivity -- to the max. You'll learn everything from the fundamentals of Rails scaffolding to building customized interactive web apps using Rails' rich set of tools and the MVC framework. By the time you're finished, you'll have learned more than just another web framework. You'll master database interactions, integration with Ajax and XML, rich content, and even dynamic graphing of your data -- all in a fraction of the time it takes to build the same apps with Java, PHP, ASP.NE

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 ...

Scheduling freight trains in rail-rail transshipment yards

OpenAIRE

Nils Boysen; Erwin Pesch

2008-01-01

Transshipment yards, where gantry cranes allow for an effcient transshipment of containers between different freight trains, are important entities in modern railway systems and facilitate the general shift from point-to-point transport to hub-and-spoke railway systems. Modern rail-rail transshipment yards accelerate container handling, so that multiple smaller trains with equal destination can be consolidated to a reduced number of trains without jeopardizing on time deliveries. An important...

Rail inspection of RCF defects

Directory of Open Access Journals (Sweden)

Z. Popović

2013-10-01

Full Text Available Rail defects due to rolling contact fatigue (RCF threaten the traffic safety around the world. That hazard is more distinct on railways without adequate maintenance strategy. Realization of interoperability of European railway network demands from every infrastructure manager to have a maintenance plan for the infrastructure subsystem. Besides that, this plan includes rail inspection and strategy against RCF defects. This paper emphasizes the importance of rail inspection and early detection of RCF because the most of RCF crack should be removed in rail grinding campaigns (preventive, cyclical and corrective activities during the whole rail service life.

Light rail project in Copenhagen

DEFF Research Database (Denmark)

Andersen, Jonas Lohmann Elkjær; Landex, Alex; Nielsen, Otto Anker

2006-01-01

The need for high class public transport service of the increasing travel across the radial urban structure of the greater Copenhagen region was examined through planning of a light rail. The exact corridor (defined as the Ring 2½ corridor) and alignment of the light rail were documented and the ......The need for high class public transport service of the increasing travel across the radial urban structure of the greater Copenhagen region was examined through planning of a light rail. The exact corridor (defined as the Ring 2½ corridor) and alignment of the light rail were documented...... light rail projects...

A survey of wheel-rail contact models for rail vehicles

Science.gov (United States)

Meymand, Sajjad Z.; Keylin, Alexander; Ahmadian, Mehdi

2016-03-01

Accurate and efficient contact models for wheel-rail interaction are essential for the study of the dynamic behaviour of a railway vehicle. Assessment of the contact forces and moments, as well as contact geometry provide a fundamental foundation for such tasks as design of braking and traction control systems, prediction of wheel and rail wear, and evaluation of ride safety and comfort. This paper discusses the evolution and the current state of the theories for solving the wheel-rail contact problem for rolling stock. The well-known theories for modelling both normal contact (Hertzian and non-Hertzian) and tangential contact (Kalker's linear theory, FASTSIM, CONTACT, Polach's theory, etc.) are reviewed. The paper discusses the simplifying assumptions for developing these models and compares their functionality. The experimental studies for evaluation of contact models are also reviewed. This paper concludes with discussing open areas in contact mechanics that require further research for developing better models to represent the wheel-rail interaction.

75 FR 55631 - U. S. Rail Corporation-Construction and Operation Exemption-Brookhaven Rail Terminal

Science.gov (United States)

2010-09-13

... the proposed construction is to enable U. S. Rail to serve the BRT as a common carrier and to deliver... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35141] U. S. Rail Corporation--Construction and Operation Exemption-- Brookhaven Rail Terminal AGENCY: Surface Transportation...

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)

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

Directory of Open Access Journals (Sweden)

Cedric S Wesley

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

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

Science.gov (United States)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Quasi-static and dynamic forced shear deformation behaviors of Ti-5Mo-5V-8Cr-3Al alloy

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhiming; Chen, Zhiyong, E-mail: czysh@netease.com; Zhan, Congkun; Kuang, Lianjun; Shao, Jianbo; Wang, Renke; Liu, Chuming

2017-04-13

The mechanical behavior and microstructure characteristics of Ti-5Mo-5V-8Cr-3Al alloy were investigated with hat-shaped samples compressed under quasi-static and dynamic loading. Compared with the quasi-static loading, a higher shear stress peak and a shear instability stage were observed during the dynamic shear response. The results showed that an adiabatic shear band consisting of ultrafine equiaxed grains was only developed in the dynamic specimen, while a wider shear region was formed in the quasi-static specimen. The microhardness measurements revealed that shear region in the quasi-static specimen and adiabatic shear band in the dynamic specimen exhibited higher hardness than that of adjacent regions due to the strain hardening and grain refining, respectively. A stable orientation, in which the crystallographic {110} planes and <111> directions were respectively parallel to the shear plane and shear direction, developed in both specimens. And the microtexture of the adiabatic shear band was more well-defined than that of the shear region in the quasi-static specimen. Rotational dynamic recrystallization mechanism was suggested to explain the formation of ultrafine equiaxed grains within the adiabatic shear band by thermodynamic and kinetic calculations.

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

Performance criteria for EM rail launchers with solid or transition armatures and laminated rails

International Nuclear Information System (INIS)

James, T.E.

1991-01-01

Velocity limitations of EM Rail Launchers with solid armatures due to the velocity skin-effect are assessed for a range of homogeneous materials (copper, aluminium, molybdenum and tungsten). Performance criteria as limited by armature melting in the region adjacent to the rail/armature contact surface and by rail surface melting are deduced analytically based on defined electro-thermal reference conditions. The performance criteria predict the reference transition velocity at which the solid contact surface changes to mainly a melted contact surface which is shown to be a fundamental property of the materials. The paper shows that the critical factors in obtaining a high transition velocity are a relatively high resistivity armature material combined with high temperature rail surface coatings. For example a transition velocity of >2.0 km/s for a molybdenum armature and a tungsten rail surface coating on a copper rail are predicted compared with <0.5 km/s for the aluminium/copper combination frequently used

Rail-induced Traffic in China

Directory of Open Access Journals (Sweden)

Nan He

2017-11-01

Full Text Available The rapid development of China’s railway has exerted an enormous influence on the intercity passenger transport structure in recent years. However, it has not satisfied the passengers’ travel demand due to induced traffic. This paper is committed to solving such issue, with the aim of satisfying the current travel demand, and of anticipating the demand of the predicted traffic growth over the next 20 to 30 years. The paper has considered the increase in rail passenger kilometres caused by the growth of rail kilometres as rail-induced traffic. Based on the concept and former research of induced traffic, the panel data of 26 provinces and 3 municipalities of China between the year 2000 and 2014 were collected, and the elasticity models (including elasticity-based model, distributed lag model, high-speed rail (HSR elasticity model and rail efficiency model have been constructed. The results show the importance of model formation incorporation of rail-induced traffic. It is better to get the correct value in divided zones with different train frequencies or incorporation rail efficiency in cities or provinces. The lag time and rail types also need to be considered. In summary, the results analysis not only confirms the existence of rail-induced traffic, but also provides substantial recommendations to train operation planning.

Notch3 signalling promotes tumour growth in colorectal cancer.

Science.gov (United States)

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

2011-08-01

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

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

Science.gov (United States)

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

2014-09-01

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

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.

Multiaxial creep of fine grained 0.5Cr-0.5Mo-0.25V and coarse grained 1Cr-0.5Mo steels

International Nuclear Information System (INIS)

Browne, R.J.; Flewitt, P.E.J.; Lonsdale, D.

1991-01-01

To explore the multiaxial creep response of materials used for electrical power generating plant, two steels, a fine grained 0.5Cr-0.5Mo-0.25V steel in a normalised and tempered condition with high creep ductility and a coarse grained 1Cr-0.5Mo steel in a quenched and tempered condition with low uniaxial creep ductility, have been selected. A range of multiaxial stress testing techniques which span the stress states that would allow identification of any technique dependent variables has been used. The deformation and failure of the normalised and tempered 0.5Cr-0.5Mo-0.25V steel for a range of multiaxial test techniques and, therefore, stress states may be described by an equivalent stress criterion. The results from the multiaxial tests carried out on the fully bainitic 1Cr-0.5Mo steel show that the multiaxial stress rupture criterion (MSRC) varies with stress state; at high triaxiality (notch), it is controlled by the maximum principal stress, whereas at low triaxiality (shear) it is dependent on both maximum principal stress and equivalent stress. Furthermore, a simple description of stress state based on maximum principal and equivalent stress does not define this uniquely, since the MSRC derived from uniaxial and torsion testing does not describe the failure of notch, tube, or double shear tests. (author)

46 CFR 169.329 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Storm rails. 169.329 Section 169.329 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction and Arrangement Rails and Guards § 169.329 Storm rails. Suitable storm rails or hand grabs must be...

46 CFR 177.920 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Storm rails. 177.920 Section 177.920 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) CONSTRUCTION AND ARRANGEMENT Rails and Guards § 177.920 Storm rails. Suitable storm rails or hand grabs must be...

46 CFR 127.320 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Storm rails. 127.320 Section 127.320 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS CONSTRUCTION AND ARRANGEMENTS Rails and Guards § 127.320 Storm rails. Suitable storm rails must be installed in each passageway and at...

Rail abandonments in the South and their effect on NWPA rail shipments

International Nuclear Information System (INIS)

1988-02-01

The railroad industry will have a very critical role in the eventual shipping of commercial spent fuel and defense high-level waste as provided under the Nuclear Waste Policy Act of 1982 and the 1987 amendments. The transport of spent fuel is expected to be accomplished by rail from 19 of the South's 27 reactor sites to the proposed Yucca Mountain repository or possible monitored retrievable storage facility. The decline in total track availability, however, could significantly impact the federal government's transportation program. Particularly the situation of continuing abandonments may limit rail opportunities at numerous reactor locations. Commercial nuclear reactor sites have the unfortunate problem of not being located on Class I railroad mainline tracks. The reactor sites are generally located in areas with limited rail traffic and thus vulnerable to rail abandonment procedures. The general deregulation of the railroad industry under the Staggers Act of 1980 also assisted in making rail abandonment, through the Interstate Commerce Commission, a rather simple and quick process. The effects of deregulation, however, have provided alternatives to abandonment. In particular, the Staggers Act has led to an enormous surge in the growth of short line and regional railroads. Such railroads have been able to effectively operate rail lines which Class I railroads found unprofitable. The short lines and regionals were also encouraged to competitively negotiate contracts directly with shippers. While these railroads may help reduce the number of abandonment applications, they may also represent higher shipping costs. The South has experienced a great number of abandonments since the 1960's. Many of the abandonments have been significant in length and have affected areas near nuclear plants expected to ship by rail

78 FR 10581 - Rail Vehicles Access Advisory Committee

Science.gov (United States)

2013-02-14

... guideway systems (e.g., rapid rail, light rail, commuter rail, and intercity rail). We are establishing a... vehicles that operate on fixed guideway systems (e.g., rapid rail, light rail, commuter rail, and intercity... for their service. We may pay travel expenses for a limited number of persons who would otherwise be...

46 CFR 108.221 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Storm rails. 108.221 Section 108.221 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Construction and Arrangement Rails § 108.221 Storm rails. Each unit must have a storm rail in the following...

Notch signaling and progenitor/ductular reaction in steatohepatitis.

Directory of Open Access Journals (Sweden)

Carola M Morell

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

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

Science.gov (United States)

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

2016-07-01

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

Role of Notch signaling in the mammalian heart

Energy Technology Data Exchange (ETDEWEB)

Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

2013-12-12

Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

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

Science.gov (United States)

Lina, Ioan A; Lauer, Amanda M

2013-04-01

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

49 CFR 214.523 - Hi-rail vehicles.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hi-rail vehicles. 214.523 Section 214.523..., DEPARTMENT OF TRANSPORTATION RAILROAD WORKPLACE SAFETY On-Track Roadway Maintenance Machines and Hi-Rail Vehicles § 214.523 Hi-rail vehicles. (a) The hi-rail gear of all hi-rail vehicles shall be inspected for...

THE BAINITIC STEELS FOR RAILS APPLICATIONS

Directory of Open Access Journals (Sweden)

Ivo Hlavatý

2009-10-01

Full Text Available Actual trends of worldwide railway transport development are characterized by increasing speed and growth of railway’s axels load. Increasing load together with transverse, longitudinal wheel displacement and braking on the rails results into heavy surface tension. One of many applications for bainitic steel is in railway transport for highly strength and wear resistant rails. Rail steel must be designed to be able to resist plastic deformation, wear, rolling contact fatigue, bending stress and thermal stress during rail welding process and rails resurfacing.

Effects of anchoring and arc structure on the control authority of a rail plasma actuator

International Nuclear Information System (INIS)

Choi, Young-Joon; Gray, Miles; Sirohi, Jayant; Raja, Laxminarayan L

2017-01-01

Experiments were conducted on a rail plasma actuator (RailPAc) with different electrode cross sections (rails or rods) to assess methods to improve the actuation authority, defined as the impulse generated for a given electrical input. The arc was characterized with electrical measurements and high-speed images, while impulse measurements quantified the actuation authority. A RailPAc power supply capable of delivering  ∼1 kA of current at  ∼100 V was connected to rod electrodes (free-floating with circular cross-section) and rail electrodes (flush-mounted in a flat plate with rectangular cross-section). High-speed images show that the rail electrodes cause the arc to anchor itself to the anode electrode and transit in discrete jumps, while rod electrodes permit the arc to transit smoothly without anchoring. The impulse measurements reveal that the anchoring reduces the actuation authority by  ∼21% compared to a smooth transit, and the effect of anchoring can be suppressed by reducing the gap between the rails to 2 mm. The study further demonstrates that if a smooth transit is achieved, the control authority can be increased with a larger gap and larger arc current. In conclusion, the actuation authority of a RailPAc can be maximized by carefully choosing a gap width that prevents anchoring. Further study is warranted to increase the RailPAc actuation authority by introducing multiple turns of wires beneath the RailPAc to augment the induced magnetic field. (paper)

Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

Science.gov (United States)

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

2017-04-04

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

Essential Role of Endothelial Notch1 in Angiogenesis

Science.gov (United States)

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

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-09-17

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Failure analysis of edge flat-slab column connections with shear reinforcement

OpenAIRE

Bompa, Dan V.; Muttoni, Aurelio

2013-01-01

Flat-slab column connections are susceptible to brittle failure, which lead to the necessity of improving ductility and ultimate strength. In case of edge connections, the behaviour at ultimate state is highly influenced by nonsymmetrical distribution of stresses originated by a moment transfer between the slab and the column. The paper presents the test results of three full-scale reinforced concrete flat-slab edge connections with stud-rail shear reinforcement subjected to concentrated load...

Determination of rail wear and short-time wear measurements of rails applying radioisotopes

International Nuclear Information System (INIS)

Grohmann, H.D.

1981-01-01

An energetic model has been developed for calculating rail wear. Short-time wear tests on rails after surface activation and following activity measurements showed a good agreement with the calculated values

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

Fast rail corrugation detection based on texture filtering

Science.gov (United States)

Xiao, Jie; Lu, Kaixia

2018-02-01

The condition detection of rails in high-speed railway is one of the important means to ensure the safety of railway transportation. In order to replace the traditional manual inspection, save manpower and material resources, and improve the detection speed and accuracy, it is of great significance to develop a machine vision system for locating and identifying defects on rails automatically. Rail defects exhibit different properties and are divided into various categories related to the type and position of flaws on the rail. Several kinds of interrelated factors cause rail defects such as type of rail, construction conditions, and speed and/or frequency of trains using the rail. Rail corrugation is a particular kind of defects that produce an undulatory deformation on the rail heads. In high speed train, the corrugation induces harmful vibrations on wheels and its components and reduces the lifetime of rails. This type of defects should be detected to avoid rail fractures. In this paper, a novel method for fast rail corrugation detection based on texture filtering was proposed.

Active current management for four-rail railguns

International Nuclear Information System (INIS)

Beno, J.H.; Weldon, W.F.

1991-01-01

In this paper a system of auxiliary conductors designed to reduce current density peaks in railgun rails for four-rail, round-bore railguns is described. The effects on rail current density and projectile force are discussed. Railgun cross-sectional designs are presented for round-bore, four-rail railguns which operate at lower peak current densities and develop greater projectile forces than conventional two-rail, round-bore railguns

Rail projects gather steam

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-01-15

The global recession hit rail companies hard, as demand for bulk commodities such as coal was affected. But green shoots of recovery are now appearing, with many rail companies announcing new haulage contracts. 3 figs.

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 ...

SELF-DIAGNOSIS METHOD FOR CHECKING THE WAYSIDE SYSTEMS FOR WHEEL-RAIL VERTICAL LOAD MEASUREMENT

Directory of Open Access Journals (Sweden)

Daniele CORTIS

2017-12-01

Full Text Available Nowadays, wayside measurement systems of wheel-rail contact forces have acquired great relevance for the monitoring of rolling stock, especially for freight trains. Thanks to these solutions, infrastructure managers can check and monitor the status of rolling stock and, when necessary, impose corrective actions for the railway companies. On the other hand, the evaluation of contact forces is part of the rolling stock authorisation process [1] and a mainstone for the study of the running stability. The data provided by these measurements could give useful information to correlate the wear of the track with the frequency of applied loads, helping in the development of a better maintenance strategy of railway networks [2]. In this paper, the monitoring of vertical forces is based on the SMCV (Vertical Loads Monitoring System method, where shear strains of the rail web are measured with a simple combination of four electrical strain gauges, placed on both sides of the rail web along each span. The research has identified self-diagnosis methods for the SMCV system to ensure the reliability and the quality of the measurements and to extend the knowledge of the system. The recorded signals have been processed and converted into easily interpretable physical quantities by means of MATLAB® algorithm.

Rail Access to Yucca Mountain: Critical Issues

International Nuclear Information System (INIS)

Halstead, R. J.; Dilger, F.; Moore, R. C.

2003-01-01

The proposed Yucca Mountain repository site currently lacks rail access. The nearest mainline railroad is almost 100 miles away. Absence of rail access could result in many thousands of truck shipments of spent nuclear fuel and high-level radioactive waste. Direct rail access to the repository could significantly reduce the number of truck shipments and total shipments. The U.S. Department of Energy (DOE) identified five potential rail access corridors, ranging in length from 98 miles to 323 miles, in the Final Environmental Impact Statement (FEIS) for Yucca Mountain. The FEIS also considers an alternative to rail spur construction, heavy-haul truck (HHT) delivery of rail casks from one of three potential intermodal transfer stations. The authors examine the feasibility and cost of the five rail corridors, and DOE's alternative proposal for HHT transport. The authors also address the potential for rail shipments through the Las Vegas metropolitan area

Rail base corrosion and cracking prevention

Science.gov (United States)

2014-07-01

Rail base corrosion combined with fatigue or damage can significantly reduce rail life. Studies were done to examine the relative contribution of damage, corrosion, and fatigue on rail life. The combined effects can be separated into constituent fact...

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

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.)

Undergraduate Certificate in Rail Transportation/Engineering.

Science.gov (United States)

2016-05-05

A shift in the U.S. transportation environment has led to a revival in rail transport, especially in : freight rail1. In the meantime, an aging rail employee demographic presents a severe threat to : sufficient level of individuals equipped to handle...

Ruby on Rails for dummies

CERN Document Server

Burd

2007-01-01

Quickly create Web sites with this poweful tool Use this free and easy programming language for e-commerce sites and blogs If you need to build Web and database applications quickly but you don''t dream in computer code, take heart! Ruby on Rails was created for you, and this book will have you up and running in no time. The Ruby scripting language and the Rails framework let you create full-featured Web applications fast. It''s even fun! Discover how toInstall and run Ruby and RailsUse the RadRails IDECreate a blog with RubyConnect your Web site to a databaseBuild a shopping cartExplore Ruby'

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

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.

Rail transportation of Fernald remediation waste

International Nuclear Information System (INIS)

Fellman, R.T.; Lojek, D.A.; Motl, G.P.; Weddendorf, W.K.

1995-01-01

Remediation of the Department of Energy (DOE) Fernald site located north of Cincinnati will generate large quantities of low-level radwaste. This volume includes approximately 1,050,000 tons of material to be removed from eight waste pits comprising Operable Unit 1 (OU-1). The remedial alternative selected includes waste material excavation, drying and transportation by rail to a burial site in the arid west for disposal. Rail transportation was selected not only because rail transportation is safer than truck transportation, but also because of the sheer magnitude of the project and the availability of bulk rail car unloading facilities at a representative disposal site. Based upon current waste quantity estimates as presented in the Feasibility Study for OUI, a fully-loaded 47-car unit train would depart the Fernald site weekly for five years. This paper illustrates the steps taken to obtain agency and public acceptance of the Record of Decision for the remedy which hinged on rail transportation. A preliminary, but detailed, rail transportation plan was prepared for the project to support a series of CERCLA public meetings conducted in late 1994. Some of the major issues addressed in the plan included the following: (1) Scope of project leading to selection of rail transportation; (2) Waste classification; (3) Rail Company overview; (4) Train configuration and rail car selection; (5) Routing; (6) Safety; (7) Prior Notification Requirements (8) Emergency Response. A series of three public meetings identified a number of issues of prime concern to Fernald stakeholders. Following resolution of these issues during the public comment period, a Record of Decision (ROD) approving implementation of the rail transportation strategy was approved pending incorporation of EPA and State of Ohio comments on December 22, 1994

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.

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

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

Directory of Open Access Journals (Sweden)

Vanessa de Oliveira-Carlos

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

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

Directory of Open Access Journals (Sweden)

Pawel K Mazur

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

Superconducting augmented rail gun (SARG)

International Nuclear Information System (INIS)

Homan, C.G.; Cummings, C.E.; Fowler, C.M.

1986-01-01

Superconducting augmentation consists of a superconducting coil operating in the persistent mode closely coupled magnetically with a normally conducting rail gun. A theoretical investigation of the effect of this system on a rail gun has shown that two benefits occur. Projectile velocities and launch efficiencies increase significantly depending on the magnetic coupling between the rail and augmentation circuits. Previous work evaluated an idealized system by neglecting energy dissipation effects. In this paper, the authors extend the analysis to include the neglected terms and show improved actual launch efficiencies for the SARG configuration. In this paper, the authors discuss details of projectile design in depth and present preliminary results of rail gun performance

High levels of Notch signaling down-regulate Numb and Numblike

NARCIS (Netherlands)

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

2006-01-01

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

Magnetoresistance effect in permalloy nanowires with various types of notches

Directory of Open Access Journals (Sweden)

Y. Gao

2018-05-01

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

Inhibitory role of Notch1 in calcific aortic valve disease.

Directory of Open Access Journals (Sweden)

Asha Acharya

Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

The pathological significance of Notch1 in oral squamous cell carcinoma.

Science.gov (United States)

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

2013-10-01

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

46 CFR 190.25-10 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Storm rails. 190.25-10 Section 190.25-10 Shipping COAST... ARRANGEMENT Rails and Guards § 190.25-10 Storm rails. (a) On vessels in ocean and coastwise service, suitable storm rails shall be installed in all passageways and at the deckhouse sides where persons on board...

46 CFR 72.40-10 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Storm rails. 72.40-10 Section 72.40-10 Shipping COAST... and Guards § 72.40-10 Storm rails. (a) Suitable storm rails shall be installed in all passageways and at the deckhouse sides where passengers or crew might have normal access. Storm rails shall be...

46 CFR 92.25-10 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Storm rails. 92.25-10 Section 92.25-10 Shipping COAST... ARRANGEMENT Rails and Guards § 92.25-10 Storm rails. (a) On vessels in ocean and coastwise service, suitable storm rails shall be installed in all passageways and at the deckhouse sides where persons on board...

High-strength chromium--molybdenum rails

International Nuclear Information System (INIS)

Smith, Y.E.; Sawhill, J.M. Jr.; Cias, W.W.; Eldis, G.T.

1976-01-01

A laboratory study was conducted with the aim of developing an as-rolled rail of over 100 ksi (689 N/mm 2 ) yield strength. A series of compositions providing both pearlitic and bainitic microstructures was evaluated. A fine pearlitic structure was developed in a 0.73 percent C -- 0.83 percent Mn -- 0.16 percent Si -- 0.75 percent Cr -- 0.21 percent Mo steel by simulating the mill cooling rate of 132-lb/yd (65.5-kg/m) rail. Two 100-ton commercial heats were made of this approximate composition and processed into 132-lb/yd (65.5-kg/m) rail. Samples tested in the laboratory ranged from 109 to 125 ksi (750 to 860 N/mm 2 ) in yield strength. The chromium-molybdenum rails also exhibited excellent fracture toughness and fatigue properties. Sections of the rail were joined by both flash-butt welding and thermite welding. The hardness peaks produced in the flash-butt welds could be reduced by applying either a postweld current or an induction heating cycle. The high-strength chromium-molybdenum rails have been in service for over eight months in curved sections of an ore railway that carries over 55 million gross long tons per year. 7 tables, 18 figs

Analysis of rail welding methods for mine rail access with the use of modern technologies

Science.gov (United States)

Usoltsev, A. A.; Shevchenko, R. A.; Kozyrev, N. A.; Kriukov, R. E.; Shishkin, P. E.

2017-09-01

Welded joint zones are weak sections of the railway track for all traffic cases (in the case of high-speed traffic and heavy traffic). In the paper advantages and disadvantages of the basic ways of rails welding, which are widely used today, are considered: electrocontact and aluminothermic. Carefully selected mode of differentially thermally strengthened rails string will allow the process of correction after heat treatment to be minimized and internal residual compressive stresses to be kept. Particular attention should be paid to the method of rails welding, in which after rails welding during their cooling it is offered to perform quasi-isothermal exposure in the temperature range of fine structure formation by passing pulses of alternating electric current through the welded joint maintaining this temperature until the end of the transformation. The use of quasi-isothermal exposure at a temperature of 600 - 650 °C makes it possible to obtain a finely dispersed structure of the welded seam of rails without additional heat treatment.

Rail inspection using noncontact laser ultrasonics

International Nuclear Information System (INIS)

Kim, Nak Hyeon; Sohn, Hoon; Han, Soon Woo

2012-01-01

In this study, a noncontact laser ultrasonic system is proposed for rail defect detection. An Nd Yag pulse laser is used for generation of ultrasonic waves, and the corresponding ultrasonic responses are measured by a laser Doppler vibrometer. For the detection of rail surface damages, the shape of the excitation laser beam is transformed into a line. On the other hand, a point source laser beam is used for the inspection of defects inside a rail head. Then, the interactions of propagating ultrasonic waves with defects are examined using actual rail specimens. Amplitude attenuation was mainly observed for a surface crack, and reflections were most noticeable from an internal damage. Finally, opportunities and challenges associated with real time rail inspection from a high speed train are discussed

Model for predicting the frequency of broken rails

Directory of Open Access Journals (Sweden)

S. Vesković

2012-04-01

Full Text Available Broken rails can cause train delays, trains cancelations and, unfortunately, they are common causes of accidents. This affects planning of a resources, budget and organization of railway track maintenance. Planning of railway track maintenance cannot be done without an estimation of number of rails that will be replaced due to the broken rail incidents. There are many factors that influence broken rails and the most common are: rail age, annual gross tonnage, degree of curve and temperature in the time of breakage. The fuzzy logic model uses acquired data as input variables to predict the frequency of broken rails for the certain rail types on some Sections.

Rail Baltica uus tee viiks rongid nelja tunniga Varssavisse / Tiina Rekand

Index Scriptorium Estoniae

Rekand, Tiina, 1985-

2011-01-01

Rail Baltica tasuvusuuringus on välja töötatud neli optimaalsemat marsruuti. Aecom Ltd Balti regiooni direktor Arnis Kakulis peab parimaks kiireimat ja lühimat teed, mis kulgeks Tallinnast Varssavisse Pärnu, Riia ja Kaunase kaudu

46 CFR 116.920 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Storm rails. 116.920 Section 116.920 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... and Guards § 116.920 Storm rails. Suitable storm rails or hand grabs must be installed where necessary...

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

Dependency of Shear Strength on Test Rate in SiC/BSAS Ceramic Matrix Composite at Elevated Temperature

Science.gov (United States)

Choi, Sung R.; Bansal, Narottam P.; Gyekenyesi, John P.

2003-01-01

Both interlaminar and in-plane shear strengths of a unidirectional Hi-Nicalon(TM) fiber-reinforced barium strontium aluminosilicate (SiC/BSAS) composite were determined at 1100 C in air as a function of test rate using double notch shear test specimens. The composite exhibited a significant effect of test rate on shear strength, regardless of orientation which was either in interlaminar or in in-plane direction, resulting in an appreciable shear-strength degradation of about 50 percent as test rate decreased from 3.3 10(exp -1) mm/s to 3.3 10(exp -5) mm/s. The rate dependency of composite's shear strength was very similar to that of ultimate tensile strength at 1100 C observed in a similar composite (2-D SiC/BSAS) in which tensile strength decreased by about 60 percent when test rate varied from the highest (5 MPa/s) to the lowest (0.005 MPa/s). A phenomenological, power-law slow crack growth formulation was proposed and formulated to account for the rate dependency of shear strength of the composite.

46 CFR 177.900 - Deck rails.

Science.gov (United States)

2010-10-01

...) high. (4) While engaged in big game angling, the minimum rail height may be reduced to not less than... section as applicable must be installed when big game angling is not being conducted. (e) Where the... that a higher rail would interfere with the fishing operation and the lower rail would not...

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

Evidence of non-canonical NOTCH signaling

DEFF Research Database (Denmark)

Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads

2016-01-01

Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si...

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

Directory of Open Access Journals (Sweden)

Daniel Mauricio Meza Lasso

2016-01-01

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

Notch and the awesome power of genetics.

Science.gov (United States)

Greenwald, Iva

2012-07-01

Notch is a receptor that mediates cell-cell interactions in animal development, and aberrations in Notch signal transduction can cause cancer and other human diseases. Here, I describe the major advances in the Notch field from the identification of the first mutant in Drosophila almost a century ago through the elucidation of the unusual mechanism of signal transduction a little over a decade ago. As an essay for the GENETICS Perspectives series, it is my personal and critical commentary as well as an historical account of discovery.

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

International Nuclear Information System (INIS)

Al-Abduljabbar, Abdulhamid

2003-01-01

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

Numerical Simulation of Adiabatic Shear Bands in Ti-6Al-4V Alloy Due to Fragment Impact

National Research Council Canada - National Science Library

Fermen-Coker, Muege

2004-01-01

... and lethality technologies for the Army's Future Combat Systems. Onset and propagation of adiabatic shear bands are investigated both experimentally and computationally by studying the ballistic impact of 20-mm steel fragments against Ti-6Al-4V plates...

Modifiers of notch transcriptional activity identified by genome-wide RNAi

Directory of Open Access Journals (Sweden)

Firnhaber Christopher B

2010-10-01

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

On short cracks that depart from elastoplastic notch tips

Directory of Open Access Journals (Sweden)

Verônica Miquelin Machado

2017-07-01

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

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

Science.gov (United States)

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

2018-02-20

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

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)

Assessment of Rail Seat Abrasion Patterns and Environment

Science.gov (United States)

2012-05-01

Rail seat abrasion (RSA) of concrete ties is manifested by the loss of material under the rail seat area and, in extreme cases, results in loss of rail clip holding power, reverse rail cant, and gauge widening. RSA was measured in several curves on t...

Applying the polluter-pays principle to rail: Environmental differentiation of rail access charges

Energy Technology Data Exchange (ETDEWEB)

Pons-Rigat, A.; Turro Calvet, M.; Ubalde Claver, Ll.

2016-07-01

Environmental charges to rail service operators are still at an early stage of implementation in Europe. Current schemes are dissimilar and most of them have a very limited scope or do not provide effective incentives to abate environmental impacts. This is due to several practical difficulties in implementing internalisation pricing schemes in the railway sector. The first difficulty arises from the lack of internalisation in other transport modes and the small competitive margin of railways. Increasing the overall level of rail charges could affect their survival. A second difficulty is due to the uncertainties in the valuation of external costs and in the establishment of the optimal level of charges. On top of that, the imperfect competition in the rail market and its operational and financial rigidities imply that pricing decisions could be unfair and produce undesired demand effects. These difficulties should not prevent, however, advancing towards the application to rail of adequate charging methods for its environmental costs. This paper addresses the problem of setting environmentally differentiated rail charges through an analytical approach. A generalised formulation is developed that sets the level of charges as a function of the degree of internalisation in other modes. Then, the optimal trade-off in the level of differentiation is assessed to extract general guidelines. Based on this, both the derived overall costs and benefits and the impacts on each agent are quantified. (Author)

Significance of a notch in the otoacoustic emission stimulus spectrum.

Science.gov (United States)

Grenner, J

2012-09-01

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

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

Science.gov (United States)

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

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

Rail gun powered by an integral explosive generator

International Nuclear Information System (INIS)

Peterson, D.R.; Fowler, C.M.

1979-01-01

We propose the use of a rail gun powered by an explosive magnetic flux compression generator built into the rail gun itself in which the rails of the gun are driven together behind the projectile by explosives. The magnetic field established between the rails by an initial current supplied by an external source at the breech of the gun is trapped and compressed by the collapsing rails to accelerate the projectile down the bore of the gun

Dombrovskis: toetus Rail Balticule sõltub Siim Kallasest / Valdis Dombrovskis ; intervjueerinud Andres Reimer

Index Scriptorium Estoniae

Dombrovskis, Valdis, 1971-

2011-01-01

Intervjuu Läti peaministriga Swedbankiga seotud sularahapaanikast, LNG terminali asukohast, Läti ettepanekust peatada Baltimaade eletrkisüsteemide Euroopaga sünkroniseerimise projekt, Poola väljumisest kavandatavast Visaginase tuumajaama projektist, Rail Balticust

The importance of Notch signaling in peripheral T-cell lymphomas

DEFF Research Database (Denmark)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

78 FR 57450 - State Rail Plan Guidance

Science.gov (United States)

2013-09-18

... of impact assessment required for the rail infrastructure, facilities, and service improvements contained in State rail plans. Other issues raised by commenters included the importance of involving... to emphasize the importance of preparing State rail plans within the policy and procedural contexts...

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.

Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

Institute of Scientific and Technical Information of China (English)

Zhao Li; Ma Yongjie; Gu Feng; Fu Li

2014-01-01

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

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Mauro Di Ianni

2018-04-01

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

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

Science.gov (United States)

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

2018-01-01

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

Momentum equation for arc-driven rail guns

International Nuclear Information System (INIS)

Batteh, J.H.

1984-01-01

In several models of arc-driven rail guns, the rails are assumed to be infinitely high to simplify the calculation of the electromagnetic fields which appear in the momentum equation for the arc. This assumption leads to overestimates of the arc pressures and accelerations by approximately a factor of 2 for typical rail-gun geometries. In this paper, we develop a simple method for modifying the momentum equation to account for the effect of finite-height rails on the performance of the rail gun and the properties of the arc. The modification is based on an integration of the Lorentz force across the arc cross section at each axial location in the arc. Application of this technique suggests that, for typical rail-gun geometries and moderately long arcs, the momentum equation appropriate for infinite-height rails can be retained provided that the magnetic pressure term in the equation is scaled by a factor which depends on the effective inductance of the gun. The analysis also indicates that the magnetic pressure gradient actually changes sign near the arc/projectile boundary because of the magnetic fields associated with the arc current

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.

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

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Matthew R. Broadus

2016-05-01

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

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

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

2015-10-01

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

Interpretation of Core Length in Shear Coaxial Rocket Injectors from X-ray Radiography Measurements

Science.gov (United States)

2014-06-01

interrogating the near field of a number of dense sprays including diesel injectors , aerated liquid jets, solid-cone sprays, impinging-jet sprays and gas...Measurements of Mass Distributions in the Near- Nozzle Region of Sprays form Standard Multi-hole Common-rail Diesel Injection Systems,” 11th Triennial...Shear Coaxial Rocket Injectors from X-ray Radiography Measurements 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

In vivo analysis of the Notch receptor S1 cleavage.

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Robert J Lake

2009-08-01

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

The functional role of Notch signaling in human gliomas

DEFF Research Database (Denmark)

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

2010-01-01

have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

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

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Maria De Salvo

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

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

Science.gov (United States)

Dominguez, Maria

2014-04-01

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

PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

Science.gov (United States)

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

2015-06-06

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

Electron emission at the rail surface

International Nuclear Information System (INIS)

Thornhill, L.; Battech, J.

1991-01-01

In this paper the authors examine the processes by which current is transferred from the cathode rail to the plasma armature in an arc-driven railgun. Three electron emission mechanisms are considered, namely thermionic emission, field-enhanced thermionic emission (or Schottky emission), and photoemission. The author's calculations show that the dominant electron emission mechanism depends, to a great extent, on the work function of the rail surface, the rail surface temperature, the electric field at the rail surface, and the effective radiation temperature of the plasma. For conditions that are considered to be typical of a railgun armature, Schottky emission is the dominant electron emission mechanism, providing current densities on the order of 10 9 A/m 2

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.

78 FR 36017 - MCM Rail Services LLC, d/b/a Baltimore Industrial Railroad-Operation Exemption-Hilco SP Rail, LLC

Science.gov (United States)

2013-06-14

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35725] MCM Rail Services LLC, d/b/a Baltimore Industrial Railroad-- Operation Exemption--Hilco SP Rail, LLC MCM Rail Services LLC, d/b/a Baltimore Industrial Railroad (MCM), a noncarrier, has filed a verified notice of exemption...

Rail-guided robotic end-effector position error due to rail compliance and ship motion

NARCIS (Netherlands)

Borgerink, Dian; Stegenga, J.; Brouwer, Dannis Michel; Woertche, H.J.; Stramigioli, Stefano

2014-01-01

A rail-guided robotic system is currently being designed for the inspection of ballast water tanks in ships. This robotic system will manipulate sensors toward the interior walls of the tank. In this paper, the influence of rail compliance on the end-effector position error due to ship movement is

A three-dimensional analysis of the sigmoid notch

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Evan D. Collins

2011-12-01

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

Far infrared promotes wound healing through activation of Notch1 signaling.

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

2017-11-01

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

Mandibular Ramus Notching As a Tool for Sexual Dimorphism

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Bibhuti Bhusana Panda

2016-02-01

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

Keeping rail on track: preliminary findings on safety culture in Australian rail.

Science.gov (United States)

Blewett, Verna; Rainbird, Sophia; Dorrian, Jill; Paterson, Jessica; Cattani, Marcus

2012-01-01

'Safety culture' is identified in the literature as a critical element of healthy and safe workplaces. How can rail organizations ensure that consistently effective work health and safety cultures are maintained across the diversity of their operations? This paper reports on research that is currently underway in the Australian rail industry aimed at producing a Model of Best Practice in Safety Culture for the industry. Located in rail organizations dedicated to the mining industry as well as urban rail and national freight operations, the research examines the constructs of organizational culture that impact on the development and maintenance of healthy and safe workplaces. The research uses a multi-method approach incorporating quantitative (survey) and qualitative (focus groups, interviews and document analysis) methods along with a participative process to identify interventions to improve the organization and develop plans for their implementation. The research uses as its analytical framework the 10 Platinum Rules, from the findings of earlier research in the New South Wales (Australia) mining industry, Digging Deeper. Data collection is underway at the time of writing and preliminary findings are presented at this stage. The research method may be adapted for use as a form of organizational review of safety and health in organizational culture.

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.

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

Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.

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Hong-Mei Zhang

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

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

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Floriane Auderset

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

Research on Miniature Calibre Rail-Guns for the Mechanical Arm

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Ronggang Cao

2017-01-01

Full Text Available Rail-gun should not only be used to military applications, but also can be developed as applications in the civilian aspects of the market. With the development of the electromagnetic launch technology, based on the similarity theory, using the existing rail-gun model to guide the construction of more economical miniature calibre rail-guns, and apply it in some machinery and equipment, this idea will open up a wider rail-gun application space. This article will focus on the feasibility of application of miniature calibre rail-guns in the mechanical arm. This paper designs the schematic diagram, then theoretical analyzes force conditions of the armature in the mechanical arm, calculates the possible range of the current amplitude and so on. The existing rail-gun model can be used to guides design the circuit diagram of the miniature calibre rail-gun. Based on the similarity theory and many simulation experiments, designed the experimental parameters of a miniature rail-gun and analyzed the current, Lorentz force, velocity, and location of the existing rail-gun and miniature rail-gun. The results show that the rail-gun launching technology applied to robot arms is feasibility. The application of miniature calibre rail-guns in the mechanical arm will benefit to the further development of rail-guns.

Analysis and tests of TF magnet insulation samples for the JET upgrade to 4 tesla

CERN Document Server

Miele, P; Bettinali, L; Kaye, A; Last, J; Papastergiou, S; Riccardo, V; Visca, E

2000-01-01

The JET Toroidal Field (TF) coils were originally designed for operation at 3.4 tesla. In order to upgrade the field to 4 tesla and thus improve the performance of the JET machine, new mechanical tests and analysis were carried out on the insulation of TF coil samples. They are aimed at investigating the mechanical properties and the status of the insulation in order to set allowable stresses and force limits. In particular since the shear stress in the insulation is strongly affected by the shear modulus of elasticity G, it is important to measure this parameter. A method for the measurement of G in glass-resin fibres, the V-notched beam method (Iosipescu method) , was applied. The particular shape of the rectangular Iosipescu V- notched sample and the particular modality of force application produce pure shear stress for a reliable measurement of the G value and of the shear strength of the insulation. The effect of temperature on these mechanical properties was also investigated. Results show higher averag...

Complete Absence of Suprascapular Notch: A Case Report

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Rohini Mohan Pawar

2015-10-01

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

Femoral intercondylar notch shape and dimensions in ACL-injured patients

NARCIS (Netherlands)

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

2010-01-01

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

Flex Cargo Rail. Developing new service, collection and distribution concepts for the transport of freight by rail.; Flex Cargo Rail. Wege zu neuen Bedien-, Sammel- und Verteilkonzepten im Schienengueterverkehr

Energy Technology Data Exchange (ETDEWEB)

Kochsiek, Joachim [Fraunhofer-Institut fuer Materialfluss und Logistik (IML), Dortmund (Germany). Gruppe Multimodale Logistik

2010-07-01

FlexCargoRail is a concept for self propelled electric freight wagons. This will enhance rail operations on first and last mile. The concept can be integrated in the existing rail system, so migration is possible without any lost investments. Standard components from industry and rail are used to realise the FCR wagon. Motors, transmissions, control and batteries are available and approved. One of the effects is to enhance service for loading terminals. This can become independent from factory siding operation. From the economic point of view, FCR is realisable. This is shown by target costing. Efficiency of FCR is dependent from high frequent use of FCR rail cars and the use of the possibility to shunt also conventional freight wagons with FCR wagons. Migration should be carried out in logistical networks with frequent operations between plants and sidings with a closed wagon pool. (orig.)

A Rails / Django Comparison

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2008-06-01

Full Text Available Ruby on Rails (“Rails” is the dominant web programming framework for Ruby and, even outside the Ruby community, is considered the epitome of the latest generation of high-productivity, open source web development tools. Django is one of many competing web development frameworks for Python. It is notable, first, for being highly regarded amongst Python programmers, and second, for being one of the few of the new generation of framework that does not ape Ruby on Rails. Both Rails and Django claim greatly enhanced productivity, compared with more traditional web development frameworks. In this paper, we compare the two frameworks from the point of view of a developer attempting to choose one of the two frameworks for a new project.

Excitation of Surface Electromagnetic Waves on Railroad Rail

Science.gov (United States)

1978-03-31

UMTA's Office of Rail Technology research programs aim to improve urban rail transportation systems safety. This rail-transit research study attempts to develop an onboard, separate and independent obstacle-detection system--Surface Electromagnetic W...

DISEÑO DE UN AMPLIFICADOR RIEL A RIEL CON TECNOLOGÍA CMOS 0,18 µm DESENHO DE UM AMPLIFICADOR DO TRILHO-A-TRILHO COM TECNOLOGIA CMOS 0,18 µm DESIGN OF A RAIL-TO-RAIL AMPLIFIER WITH 0.18 µm TECHNOLOGY

Directory of Open Access Journals (Sweden)

Diego F. Hernández

2012-06-01

Full Text Available En este artículo se realiza el análisis, diseño y simulación de un amplificador rail to rail R-R (riel a riel a la entrada y a la salida utilizando una fuente sencilla de 3,3 V. La tecnología usada fue CMOS TSMC de 0,18 µm, de bajo costo relativo para uso académico. El proceso de implementación se hizo con herramientas industrial Synopsys. En el artículo se detalla la etapa de entrada R-R complementaria, se describen el circuito sumador y la etapa de salida R-R clase AB. Finalmente, se muestran el layout definitivo y los resultados de la evaluación del diseño.Em este artigo realiza-se a análise, desenho e simulação de um amplificador rail to rail R-R (trilho a trilho à entrada e à saída utilizando uma fonte singela de 3,3 V. A tecnologia usada foi CMOS TSMC de 0,18 µm, de relativo baixo custo para uso acadêmico. O processo de implementação realizou-se com ferramentas industrial Synopsys. No artigo detalha-se a etapa de entrada R-R complementar, descreve-se o circuito somador e a etapa de saída R-R classe AB. Finalmente, mostra-se o layout definitivo e os resultados da avaliação do desenho.This paper shows the full analysis, design and simulation of a 3.3 V CMOS input/output rail to rail or R-R operational amplifier using the design kit for the Synopsys tools. The technology used was CMOS TSMC 0.18µm whose cost is low for academic purposes. This paper details the complementary input stage R-R, the summing circuit and the R-R output stage class AB. At last the final layout and the results of simulation are shown.

Siim Kallas: Rail Baltica edeneb, aga veel pole mõtet kiirrongi oodata / Urmas Jaagant

Index Scriptorium Estoniae

Jaagant, Urmas

2010-01-01

Euroopa Komisjoni voliniku Siim Kallase sõnul pole mingit põhjust, miks Eestis ei võiks sõita 200 km/h liikuvad kiirrongid, vajaliku raudtee ehitamine võib olla isegi odavam kui uus maantee. Kuid oluline on küsimus, kuidas tekitada erasektoris piisavalt suur kindlustunne, et Rail Baltica projekt ära tasub

Future Parking Demand at Rail Stations in Klang Valley

Directory of Open Access Journals (Sweden)

Ho Phooi Wai

2017-01-01

Full Text Available Klang Valley, Malaysia is currently undergoing a massive development of rail transportation system expansion where the current integrated rail transit system will see new extensions of two MRT lines and an LRT line by year 2020. By year 2017, the first MRT line will be ready to run with 31 new rail stations connected to the current passenger rail network. The existing Park and Ride facilities in Klang Valley are commonly known as being unable to sufficiently cater for the current parking space demand. Therefore, with the expansion of many additional rail stations which are rapidly under construction, there are doubts that the future parking space at rail stations will be able to accommodate the sudden rise of rail passengers. Although the authorities are increasing parking bays at various locations, will the future parking demand at rail stations be sufficient? This paper studies the factors influencing parking demand in terms of population, car ownership, new car registrations and passenger rail ridership and estimating the future parking demand using Linear Regression method. Result shows that the forecasted parking demand at rail stations after the implementation of the first new MRT system in 2017 is 2.7 times more than in 2014.

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.

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.

Laserově svařovaný tlakový zásobník systému Common Rail

OpenAIRE

Vyskočil, Lukáš

2014-01-01

Tato práce se zabývá změnou ve výrobním procesu tlakového zásobníku za účelem zvýšení kvality výsledného produktu za současného snížení kvalitativních a technických výpadků. Mimo to je v práci zahrnuta rešerše systému Common Rail se zaměřením na výrobu a konstrukci tlakových zásobníků a analýza technického stavu svařovacího zařízení. The thesis “Laser welded Common Rail” deals with changes in the manufacturing process of Rail for the purpose of increasing the quality of the final product w...

Vibroacoustical analysis of rail vehicle

Directory of Open Access Journals (Sweden)

Králíček J.

2007-11-01

Full Text Available The article deals with the vibroacoustical analysis of rail vehicle and is the extension of the previously presented work “Modelování podvozku kolejového vozidla s poddajným rámem”. The vibroacoustical analysis uses the outcomes of the dynamical analysis of rail vehicle bogie i.e. surface velocities of the bogie frame to compute the acoustic power radiated by the bogie frame and forces acting in the bogie-body interface. The radiated power and the force spectra are then used as the excitation to the rail body model in the environment Auto-SEA to compute the interior acoustic quantities.

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.

Thrombus Formation at High Shear Rates.

Science.gov (United States)

Casa, Lauren D C; Ku, David N

2017-06-21

The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

Complex eigenvalue analysis of railway wheel/rail squeal

African Journals Online (AJOL)

DR OKE

Squeal noise from wheel/rail and brake disc/pad frictional contact is typical in railways. ... squeal noise by multibody simulation of a rail car running on rigid rails. ... system, traditional complex eigenvalue analysis by finite element was used.

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.

High Speed Rail (HSR) in the United States

Science.gov (United States)

2009-12-08

announced that it will expand the capacity on its aging high speed line between Tokyo and Osaka, the most heavily traveled intercity rail segment in the...United States, in most of these countries intercity rail travel (including both conventional and high speed rail) represents less than 10% of all...that is sometimes mentioned by its advocates. Intercity passenger rail transport is relatively safe, at least compared with highway travel . And HSR in

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

International Nuclear Information System (INIS)

Fett, T.

1993-12-01

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

Notched K-wire for low thermal damage bone drilling.

Science.gov (United States)

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

2017-07-01

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

Sectional Rail System as Base for a Plate Covering

DEFF Research Database (Denmark)

2015-01-01

The present invention concerns a sectional rail system which is constructed with the known outer rails with U-shaped cross-section and intermediate rails with C-shaped cross-section, and which is peculiar in that each of the retention means of the outer rail includes at least one stop pin which i...

75 FR 17462 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2010-04-06

... decision may be purchased by contacting the office of Public Assistance, Governmental Affairs, and...-2)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the second quarter 2010 Rail Cost...

Role of Notch Signaling in Human Breast Cancer Pathogenesis

Science.gov (United States)

2006-11-01

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

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

Directory of Open Access Journals (Sweden)

Siar CH

2011-11-01

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

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.

The rail abandonment process: A southern perspective

International Nuclear Information System (INIS)

1988-12-01

One factor in evaluating the desirability of rail transport for high-level radioactive wastes or spent fuels is the frequency, or lack thereof, with which railroad and railroad lines have been, and are, abandoned. If DOE makes a decision to use the rail option and a line is subsequently abandoned, the choice results in increased cost, time delays and possibly safety problems: Information is therefore needed prior to the decision-making process to evaluate the desirability of the rail shipping option. One result of the abandonments mentioned herein, as well as other later abandonments, is the creation of a US rail system undergoing an evolutionary process in the 1980s as far-reaching as the changes that occurred when the industry was in its infancy a century and-a-half ago. The purpose of this paper is to examine the factors leading to some of these changes by tracing the historical development of the rail abandonment process, with particular emphasis on the rise of regional railroads, their problems in the modern era and current trends in rail abandonments as well as their effects on the southeastern United States

49 CFR 37.79 - Purchase or lease of new rail vehicles by public entities operating rapid or light rail systems.

Science.gov (United States)

2010-10-01

... entities operating rapid or light rail systems. 37.79 Section 37.79 Transportation Office of the Secretary... operating rapid or light rail systems. Each public entity operating a rapid or light rail system making a... system shall ensure that the vehicle is readily accessible to and usable by individuals with disabilities...

Can urban rail transit curb automobile energy consumption?

International Nuclear Information System (INIS)

Lin, Boqiang; Du, Zhili

2017-01-01

With the rapid development of China's economy and the speed of urbanization, China's automobile sector has experienced rapid development. The rapid development of the automobile sector has increased energy consumption. According to the results of this paper, automobile energy consumption accounted for about 10.73% of total energy consumption in China in 2015, about 3.6 times the proportion a decade ago. With the deterioration of urban traffic conditions, relying on expanding the amount of vehicles and city road network cannot solve the problem. Urban rail transit is energy-saving and less-polluting, uses less space, has large capacity, and secure. Urban rail transit, according to the principle of sustainable development, is a green transportation system and should be especially adopted for large and medium-sized cities. The paper uses the binary choice model (Probit and Logit) to analyze the main factors influencing the development of rail transit in Chinese cities, and whether automobile energy consumption is the reason for the construction of urban rail transit. Secondly, we analyze the influence of urban rail transit on automobile energy consumption using DID model. The results indicate that the construction of urban rail traffic can restrain automobile energy consumption significantly, with continuous impact in the second year. - Highlights: • Investigate the main factors influencing the building of rail transit for Chinese cities. • Analyze the influence of urban rail transit on automobile energy consumption by DID model. • The results indicate that the construction of urban rail traffic can restrain automobile energy consumption significantly.

Two-Dimensional Impact Reconstruction Method for Rail Defect Inspection

Directory of Open Access Journals (Sweden)

Jie Zhao

2014-01-01

Full Text Available The safety of train operating is seriously menaced by the rail defects, so it is of great significance to inspect rail defects dynamically while the train is operating. This paper presents a two-dimensional impact reconstruction method to realize the on-line inspection of rail defects. The proposed method utilizes preprocessing technology to convert time domain vertical vibration signals acquired by wireless sensor network to space signals. The modern time-frequency analysis method is improved to reconstruct the obtained multisensor information. Then, the image fusion processing technology based on spectrum threshold processing and node color labeling is proposed to reduce the noise, and blank the periodic impact signal caused by rail joints and locomotive running gear. This method can convert the aperiodic impact signals caused by rail defects to partial periodic impact signals, and locate the rail defects. An application indicates that the two-dimensional impact reconstruction method could display the impact caused by rail defects obviously, and is an effective on-line rail defects inspection method.

Environmental impact assessment of rail infrastructure.

Science.gov (United States)

2016-01-29

This project resulted in three products: a comprehensive "Sustainable Rail Checklist," a rail planning GIS database, and a web GIS tool that integrates sustainability metrics and facilitates a rapid assessment before a formal NEPA process is implemen...

Three-dimensional rail-current distribution near the armature of simple, square-bore, two-rail railguns

International Nuclear Information System (INIS)

Beno, J.H.

1991-01-01

In this paper vector potential is solved as a three dimensional, boundary value problem for a conductor geometry consisting of square-bore railgun rails and a stationary armature. Conductors are infinitely conducting and perfect contact is assumed between rails and the armature. From the vector potential solution, surface current distribution is inferred

Adiabatic shear banding and scaling laws in chip formation with application to cutting of Ti-6Al-4V

Science.gov (United States)

Molinari, A.; Soldani, X.; Miguélez, M. H.

2013-11-01

The phenomenon of adiabatic shear banding is analyzed theoretically in the context of metal cutting. The mechanisms of material weakening that are accounted for are (i) thermal softening and (ii) material failure related to a critical value of the accumulated plastic strain. Orthogonal cutting is viewed as a unique configuration where adiabatic shear bands can be experimentally produced under well controlled loading conditions by individually tuning the cutting speed, the feed (uncut chip thickness) and the tool geometry. The role of cutting conditions on adiabatic shear banding and chip serration is investigated by combining finite element calculations and analytical modeling. This leads to the characterization and classification of different regimes of shear banding and the determination of scaling laws which involve dimensionless parameters representative of thermal and inertia effects. The analysis gives new insights into the physical aspects of plastic flow instability in chip formation. The originality with respect to classical works on adiabatic shear banding stems from the various facets of cutting conditions that influence shear banding and from the specific role exercised by convective flow on the evolution of shear bands. Shear bands are generated at the tool tip and propagate towards the chip free surface. They grow within the chip formation region while being convected away by chip flow. It is shown that important changes in the mechanism of shear banding take place when the characteristic time of shear band propagation becomes equal to a characteristic convection time. Application to Ti-6Al-4V titanium are considered and theoretical predictions are compared to available experimental data in a wide range of cutting speeds and feeds. The fundamental knowledge developed in this work is thought to be useful not only for the understanding of metal cutting processes but also, by analogy, to similar problems where convective flow is also interfering with

77 FR 69769 - Solid Waste Rail Transfer Facilities

Science.gov (United States)

2012-11-21

...] Solid Waste Rail Transfer Facilities AGENCY: Surface Transportation Board, DOT. ACTION: Final rules. SUMMARY: These final rules govern land-use-exemption permits for solid waste rail transfer facilities. The... Transportation Board over solid waste rail transfer facilities. The Act also added three new statutory provisions...

76 FR 80448 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2011-12-23

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. EP 290 (Sub-No. 5) (2012-1)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the first quarter 2012 rail cost adjustment factor (RCAF...

76 FR 59483 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2011-09-26

... the decision may be purchased by contacting the Office of Public Assistance, Governmental Affairs, and...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the fourth quarter 2011 Rail Cost Adjustment...

The Rail Alignment Environmental Impact Statement: An Update

International Nuclear Information System (INIS)

Sweeney, R.

2005-01-01

On July 23,2002, the President of the United States signed into law a joint resolution of the United States Congress designating the Yucca Mountain site in Nye County, Nevada, for development as a geologic repository for the disposal of spent nuclear fuel and high-level radioactive waste. If the US. Nuclear Regulatory Commission authorizes construction of the repository and receipt and possession of spent nuclear fuel and high-level radioactive at Yucca Mountain, the U.S. Department of Energy (DOE) would be responsible for transporting these materials to the Yucca Mountain repository as part of its obligation under the Nuclear Waste Policy Act. Part of the site recommendation decision included the analysis of a nation-wide shipping campaign to the proposed repository site. The ''Final Environmental Impact Statement for a Geologic Repository for the Disposal of Spent Nuclear Fuel and High-Level Radioactive Waste at Yucca Mountain, Nye County, Nevada'' (February 2002) (Repository EIS) evaluated the potential impacts of the transportation of 70,000 Metric Tons of Heavy Metal spent nuclear fuel and high-level radioactive waste from 77 locations around the nation to the potential repository in Nevada over a 24 year shipping campaign. In the Repository EIS, DOE identified mostly rail as its preferred mode of transportation, both nationally and in the State of Nevada. In December 2003, based on public comments and the environmental analyses in the Repository EIS, DOE identified a preference for the Caliente rail corridor in Nevada. On April 8, 2004, DOE issued a Record of Decision (ROD) on the Mode of Transportation and Nevada Rail Corridor for the Disposal of Spent Nuclear Fuel and High-Level Radioactive Waste at Yucca Mountain, Nye County, Nevada. In this ROD, the DOE announced that it had decided to select the mostly rail scenario analyzed in the Repository EIS as the transportation mode both on a national basis and in the State of Nevada. Under the mostly rail

49 CFR 37.81 - Purchase or lease of used rail vehicles by public entities operating rapid or light rail systems.

Science.gov (United States)

2010-10-01

... entities operating rapid or light rail systems. 37.81 Section 37.81 Transportation Office of the Secretary... operating rapid or light rail systems. (a) Except as provided elsewhere in this section, each public entity operating a rapid or light rail system which, after August 25, 1990, purchases or leases a used rapid or...

Aeg on otsustada : Rail Baltica : rahvusvaheline raudtee toob Eestile kasu / Vilja Savisaar-Toomast

Index Scriptorium Estoniae

Savisaar-Toomast, Vilja, 1962-

2011-01-01

Vilja Savisaar-Toomast on kindel, et Rail Baltica projekt tuleb esitada Euroopa Liidu finantsperioodiks 2014-2020 ning eelistab marsruuti Tallinn-Pärnu-Riia-Kaunas. Tõenäoliselt on võimalik saada projektile Euroopa Liidult ka maksimumtoetus ehk määraga 60-70%

Capistrano and the Rails Application Lifecycle

CERN Document Server

Mornini, Tom

2006-01-01

Learn how to make your Rails deployments pain-free with Capistrano! This Short Cut shows you how to use Capistrano to automate the deployment of your Rails applications. It teaches you the basics, but also goes far beyond. It shows you realistic deployment scenarios, including some with complex server farms. It includes a quick reference to Capistrano. As your Rails applications grow, it becomes increasingly important to automate deployment and to keep your development environment well organized. Capistrano is the right tool for the job, and this PDF shows you how to use it effectively.

Electromagnetic acceleration studies with augmented rails

International Nuclear Information System (INIS)

Maruo, T.; Fujioka, K.; Nagaoka, K.; Okamoto, A.; Ikuta, K.; Nemoto, K.

1991-01-01

A comparative study of electromagnetic acceleration in the rail-type accelerators with two kinds of rail geometry was carried out experimentally. The accelerators were energized by 200kJ capacitor bank and the weight of loaded projectiles was about 1.3 grams with 10mm x 10mm square bore. The attained velocity was 4.3km/s in the augmented accelerator, while it was 3.8km/s in the classical device. In this paper these differences in attained velocity are briefly discussed. A theoretical understanding of the rail erosion is also described

75 FR 35877 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2010-06-23

... available on our Web site, http://www.stb.dot.gov . Copies of the decision may be purchased by contacting...-3)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the third quarter 2010 rail cost...

76 FR 37191 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2011-06-24

... our Web site, http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the third quarter 2011 Rail Cost Adjustment...

75 FR 80895 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2010-12-23

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the first quarter 2011 Rail Cost Adjustment...

77 FR 37958 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2012-06-25

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the third quarter 2012 rail cost adjustment...

78 FR 37660 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2013-06-21

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board approves the third quarter 2013 Rail Cost Adjustment Factor...

78 FR 17764 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2013-03-22

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the second quarter 2013 Rail Cost Adjustment...

76 FR 16037 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2011-03-22

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the second quarter 2011 Rail Cost Adjustment...

75 FR 58019 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2010-09-23

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the fourth quarter 2010 Rail Cost Adjustment...

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.

Hard-driven rail-gun tests

International Nuclear Information System (INIS)

Peterson, D.R.; Adams, D.F.; Cummings, C.E.; Fowler, C.M.; Kerrisk, J.F.; Marsh, S.P.; Parker, J.V.

1983-01-01

A number of prototype rail-gun designs have been tested, powered by explosive magnetic flux compression generators. Peak currents as high as 1.3 MA were delivered. Rail guns with 50-mm-thick Kevlar fiberwound structural shells were able to survive these high currents with minimum mechanical damage and were refired after enlarging the bores 0.2 to 0.4 mm to remove arc damage. In some tests, mechanical damage occurred that was apparently caused by the rebound of the gun after firing. Although the Kevlar shells had more than adequate strength, they appeared to lack sufficient stiffness, allowing excessive deflections. The use of a steel structural shell with a Kevlar sleeve was an improvement. Intrusion into the seams of the rail guns and condensation of material from the plasma armature were observed. Improved sealing of seams is indicated. In some cases, we suspect maldistribution of current within the gun; that is, not all the current delivered to the breech of the gun seemed to reach the plasma armature. Experiments are being designed to quantify the effects discussed. Rail guns of advanced design are being fabricated. An 18-g titanium projectile was accelerated to 2.4 km/s in a 16-mm-round-bore, 0.6-m-long gun, 4-6 g polycarbonate projectiles were accelerated to 3.5 km/s in 13-mm-square-bore, 1.2-m-long rail guns. All tests were conducted at atmospheric pressure

Factors affecting commuter rail energy efficiency.

Science.gov (United States)

2016-02-17

The objective of this study is to develop a planninglevel model of commuter rail energy efficiency. The : environmental benefits of commuter rail are often cited as one of the key benefits and motivators for its rapid development as a public trans...

78 FR 71724 - Rail Depreciation Studies

Science.gov (United States)

2013-11-29

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board Rail Depreciation Studies AGENCY: Surface Transportation Board, DOT. ACTION: Notice of OMB Approval of Information Collection. SUMMARY... collection, Rail Depreciation Studies. See 78 FR 18676 (Mar. 27, 2013). This collection, codified at 49 CFR...

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

Science.gov (United States)

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

2018-05-16

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

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Eriksson Robert

2018-01-01

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

77 FR 58910 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2012-09-24

..., http://www.stb.dot.gov . Copies of the decision may be purchased by contacting the Office of Public...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the fourth quarter 2012 rail cost adjustment factor (RCAF...

Analysis of minimum rail size in heavy axle load environment

Science.gov (United States)

2013-04-15

The effects of increasing axle loads on rail integrity are examined in this paper. In the present context, rail integrity refers to the prevention and control of rail failures. Rail failures usually occur because cracks or defects develop and grow fr...

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.

Detection method based on Kalman filter for high speed rail defect AE signal on wheel-rail rolling rig

Science.gov (United States)

Hao, Qiushi; Shen, Yi; Wang, Yan; Zhang, Xin

2018-01-01

Nondestructive test (NDT) of rails has been carried out intermittently in traditional approaches, which highly restricts the detection efficiency under rapid development of high speed railway nowadays. It is necessary to put forward a dynamic rail defect detection method for rail health monitoring. Acoustic emission (AE) as a practical real-time detection technology takes advantage of dynamic AE signal emitted from plastic deformation of material. Detection capacities of AE on rail defects have been verified due to its sensitivity and dynamic merits. Whereas the application under normal train service circumstance has been impeded by synchronous background noises, which are directly linked to the wheel speed. In this paper, surveys on a wheel-rail rolling rig are performed to investigate defect AE signals with varying speed. A dynamic denoising method based on Kalman filter is proposed and its detection effectiveness and flexibility are demonstrated by theory and computational results. Moreover, after comparative analysis of modelling precision at different speeds, it is predicted that the method is also applicable for high speed condition beyond experiments.

The Homogeneity Research of Urban Rail Transit Network Performance

Directory of Open Access Journals (Sweden)

Wang Fu-jian

2016-01-01

Full Text Available Urban Rail Transit is an important part of the public transit, it is necessary to carry out the corresponding network function analysis. Previous studies mainly about network performance analysis of a single city rail transit, lacking of horizontal comparison between the multi-city, it is difficult to find inner unity of different Urban Rail Transit network functions. Taking into account the Urban Rail Transit network is a typical complex networks, so this paper proposes the application of complex network theory to research the homogeneity of Urban Rail Transit network performance. This paper selects rail networks of Beijing, Shanghai, Guangzhou as calculation case, gave them a complex network mapping through the L, P Space method and had a static topological analysis using complex network theory, Network characteristics in three cities were calculated and analyzed form node degree distribution and node connection preference. Finally, this paper studied the network efficiency changes of Urban Rail Transit system under different attack mode. The results showed that, although rail transport network size, model construction and construction planning of the three cities are different, but their network performance in many aspects showed high homogeneity.

75 FR 17203 - National Rail Plan

Science.gov (United States)

2010-04-05

... Rail Plan AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION... input into the development of the long-range National Rail Plan (NRP) through an open docket. In addition, the notice presents the overall plan design, Federal Railroad Administration's (FRA) goals in...

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

Ceramic Rail-Race Ball Bearings

Science.gov (United States)

Balzer, Mark A.; Mungas, Greg S.; Peters, Gregory H.

2010-01-01

Non-lubricated ball bearings featuring rail races have been proposed for use in mechanisms that are required to function in the presence of mineral dust particles in very low-pressure, dry environments with extended life. Like a conventional ball bearing, the proposed bearing would include an inner and an outer ring separated by balls in rolling contact with the races. However, unlike a conventional ball bearing, the balls would not roll in semi-circular or gothic arch race grooves in the rings: instead, the races would be shaped to form two or more rails (see figure). During operation, the motion of the balls would push dust particles into the spaces between the rails where the particles could not generate rolling resistance for the balls

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.

Rails - Spears and Didion Ranches [ds310

Data.gov (United States)

California Natural Resource Agency — These data are the detections of Virginia rail (Rallus limicola), Sora (Porzana carolina), and California black rail (Laterallus jamaicensis) from 13 survey points...

Outcome of rail fixator system in reconstructing bone gap

Directory of Open Access Journals (Sweden)

Amit Lakhani

2014-01-01

Conclusion: All patients well tolerated rail fixator with good functional results and gap reconstruction. Easy application of rail fixator and comfortable distraction procedure suggest rail fixator a good alternative for gap reconstruction of limbs.

Chicago-St. Louis high speed rail plan

International Nuclear Information System (INIS)

Stead, M.E.

1994-01-01

The Illinois Department of Transportation (IDOT), in cooperation with Amtrak, undertook the Chicago-St. Louis High Speed Rail Financial and Implementation Plan study in order to develop a realistic and achievable blueprint for implementation of high speed rail in the Chicago-St. Louis corridor. This report presents a summary of the Price Waterhouse Project Team's analysis and the Financial and Implementation Plan for implementing high speed rail service in the Chicago-St. Louis corridor

Chicago-St. Louis high speed rail plan

Energy Technology Data Exchange (ETDEWEB)

Stead, M.E.

1994-12-31

The Illinois Department of Transportation (IDOT), in cooperation with Amtrak, undertook the Chicago-St. Louis High Speed Rail Financial and Implementation Plan study in order to develop a realistic and achievable blueprint for implementation of high speed rail in the Chicago-St. Louis corridor. This report presents a summary of the Price Waterhouse Project Team`s analysis and the Financial and Implementation Plan for implementing high speed rail service in the Chicago-St. Louis corridor.

Grinding induced martensite on the surface of rails

DEFF Research Database (Denmark)

Rasmussen, C.J.; Zhang, Xiaodan; Danielsen, Hilmar Kjartansson

2014-01-01

determined. Two different rail types R260 and R350HT that both had been ground by a grinding train were investigated. The rail sections, studied using optical and scanning electron microscopy, showed that the surface of both types of rails is covered with WELs. The hardness of the WEL is increased compared...

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.

Kinematic analysis on rail development into vacuum vessel for ITER blanket maintenance

International Nuclear Information System (INIS)

Kakudate, Satoshi; Shibanuma, Kiyoshi

2006-01-01

The vehicle manipulator system for blanket maintenance is used as a main driving mechanism for rail development, and three driving mechanisms d1, d2 (or d2') and d3 are used as cycle sequence of the repeated operations for rail development. This repeated operation can develop the articulated rail into the vacuum vessel. The rail development scenario, kinematic analysis model for rail development without any driving mechanisms in the rail joints, equations defined the angular between two rail links, identification of rail link at repeated operation, numerical analysis results on rail deployment under the forced position control of l i+1 , new rail development scenario using two driving mechanisms d1 and d2''under one cycle sequence of the repeated operations, and rail development test are reported. (S.Y.)

A low-offset low-voltage CMOS Op Amp with rail-to-rail input and output ranges

NARCIS (Netherlands)

Holzmann, Peter J.; Wiegerink, Remco J.; Gierkink, Sander L.J.; Wassenaar, R.F.; Stroet, Peter; Stroet, P.M.

1996-01-01

A low voltage CMOS op amp is presented. The circuit uses complementary input pairs to achieve a rail-to-rail common mode input voltage range. Special attention has been given to the reduction of the op amp's systematic offset voltage. Gain boost amplifiers are connected in a special way to provide

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.

Potential scenarios of concern for high speed rail operations

Science.gov (United States)

2011-03-16

Currently, multiple operating authorities are proposing the : introduction of high-speed rail service in the United States. : While high-speed rail service shares a number of basic : principles with conventional-speed rail service, the operational : ...

The latest technical solutions in rail vehicles drives

Directory of Open Access Journals (Sweden)

Andrzejewski Maciej

2017-01-01

Full Text Available The article discusses the latest trends and solutions used in the offers of rail vehicles manufacturers. The study is mainly concerned with the technical solutions used in hybrid rail vehicles, whose development has become one of the priorities for the development of rail vehicles in the European Union in recent years. Stricter emissions standards for harmful compounds in the European Union have forced manufacturers to use increasingly sophisticated technology, including hybrid drives and alternative fuels. The products and solutions offered by the major manufacturers on the market, along with their capabilities and future applications are described. The predicted trends in the development of propulsion technology for rail and road-rail vehicles are also indicated in view of the current legislative aspirations among the EU Member States.

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.

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

Science.gov (United States)

Gates, Nicholas R.

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

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.

Linear friction welding for constructing and repairing rail for high speed and intercity passenger service rail : final report.

Science.gov (United States)

2016-08-01

This project developed a solid-state welding process based on linear friction welding (LFW) technology. While resistance flash welding or : thermite techniques are tried and true methods for joining rails and performing partial rail replacement repai...

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

Acces to railway stations and its potential in increasing rail use

NARCIS (Netherlands)

Brons, M.R.E.; Givoni, M.; Rietveld, P.

2008-01-01

The propensity to travel by rail, and not, for example by car, can be considered to be a factor of the rail service offered, the access to it and the characteristics of the population served. Efforts to increase rail use usually focus on the rail service itself while the accessibility of the rail

Assessment of rail long-pitch corrugation

Science.gov (United States)

Valehrach, Jan; Guziur, Petr; Riha, Tomas; Plasek, Otto

2017-09-01

The paper focuses on defects of the running surface of the rail, namely the rail corrugation defect and specifically long-pitch corrugation in curves of small radii. These defects cause a shorter life of the rails, greater maintenance costs and increase the noise and vibration pollution. Therefore, it is very important to understand the formation and development of the imperfection of the rails. In the paper, various sections of railway tracks in the Czech Republic are listed, each of them completed with comparison of defect development, the particular track superstructure, rolling stock, axle load, traffic load etc. Based on performed measurements, defect development has been proved as different on sections with similar (or even same) parameters. The paper assumes that a train velocity is the significant circumstance for defect development rates. Assessment of track section with under sleeper pads, which are expected to be the one of the possible ways to suppress the corrugation defect development, is included in evaluation.

Rail Vehicle Vibrations Control Using Parameters Adaptive PID Controller

Directory of Open Access Journals (Sweden)

Muzaffer Metin

2014-01-01

Full Text Available In this study, vertical rail vehicle vibrations are controlled by the use of conventional PID and parameters which are adaptive to PID controllers. A parameters adaptive PID controller is designed to improve the passenger comfort by intuitional usage of this method that renews the parameters online and sensitively under variable track inputs. Sinusoidal vertical rail misalignment and measured real rail irregularity are considered as two different disruptive effects of the system. Active vibration control is applied to the system through the secondary suspension. The active suspension application of rail vehicle is examined by using 5-DOF quarter-rail vehicle model by using Manchester benchmark dynamic parameters. The new parameters of adaptive controller are optimized by means of genetic algorithm toolbox of MATLAB. Simulations are performed at maximum urban transportation speed (90 km/h of the rail vehicle with ±5% load changes of rail vehicle body to test the robustness of controllers. As a result, superior performance of parameters of adaptive controller is determined in time and frequency domain.

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

How to Park Freight Trains on Rail-Rail Transshipment Yards: The Train Location Problem

OpenAIRE

Michael Kellner; Nils Boysen; Malte Fliedner

2010-01-01

In modern rail-rail transshipment yards huge gantry cranes spanning all railway tracks allow for an efficent transshipment of containers between different freight trains. This way, multiple trains loaded with cargo for varying destinations can be consolidated to a reduced number of homogeneous trains, which is an essential requirement of hub-and-spoke railway systems. An important problem during the daily operations of such a transshipment yard is the train location problem, which assigns eac...

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

Directory of Open Access Journals (Sweden)

Gabriel Olmos

2013-05-01

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

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

African Journals Online (AJOL)

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

Fatigue crack growth from blunt notches

International Nuclear Information System (INIS)

Rhodes, D.

1982-01-01

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

The physics of wheel-rail stability

Science.gov (United States)

Tan, B. T. G.

2018-05-01

This article discusses, at a simple level, the dynamics of the wheel-rail interface, which is fundamental to the stability of rail vehicles. The physics underlying this topic deserves to be better known by physicists and physics students, as it underpins such an important part of our technological infrastructure.

The Physics of Wheel-Rail Stability

Science.gov (United States)

Tan, B. T. G.

2018-01-01

This article discusses, at a simple level, the dynamics of the wheel-rail interface, which is fundamental to the stability of rail vehicles. The physics underlying this topic deserves to be better known by physicists and physics students, as it underpins such an important part of our technological infrastructure

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-10-14

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

49 CFR 174.59 - Marking and placarding of rail cars.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Marking and placarding of rail cars. 174.59... RAIL General Handling and Loading Requirements § 174.59 Marking and placarding of rail cars. No person may transport a rail car carrying hazardous materials unless it is marked and placarded as required by...

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

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.

Finite element analysis of rail-wheel interaction

International Nuclear Information System (INIS)

Rahman, F.; Kharlamov, Y.A.; Islam, S.; Khan, A.A.

2006-01-01

Damage mechanisms such as surface cracks, plastic deformation and wear can significantly reduce the service life of railway track and rolling stock. They also have a negative impact on the rolling noise as well as: on the riding comfort. A proper understanding of these mechanisms requires a detailed knowledge of physical interaction between wheel and rail. Furthermore, demands for higher train speeds and increased axle loads implies that the consequences of larger contact. forces between wheel and rail must be thoroughly investigated. Two methods have traditionally been used to investigate the rail-wheel contact, that is the Hertz analytical method and simplified numerical method based on the boundary element (BE) method. These methods rely on a half-space assumption and a linear material model. This paper presents that to overcome these limitations, a tool for FE-based quasistatic wheel-rail contact simulations has been developed. The tool is a library of ANSYS macro routines for configuring, meshing and loading of a parametric wheel-rail model. The meshing is based on measured wheel and rail profiles. The wheel and rail materials in the contact region are treated as elastic-plastic with kinematic hardening. By controlling the values of the configuration parameters, representations of various driving cases can be generated. The quasi-static loads are obtained from train motion. Interaction phenomena such as rolling, spinning and sidling can be included. The modeling tool and a methodology are described in the presented paper. Significant differences in the calculated state between the FE solution and the traditional approaches can be observed. These differences are most significant in situations with flange contact. (author)

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

Directory of Open Access Journals (Sweden)

Reza H Oskouei

2016-02-01

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

Compact microstrip bandpass filter with tunable notch

DEFF Research Database (Denmark)

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

2014-01-01

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

ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.

Science.gov (United States)

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

2012-03-13

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

Passive notch circuit for pulsed-off compression fields

International Nuclear Information System (INIS)

Nunnally, W.C.

1976-06-01

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

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

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.

The influence of friction coefficient and wheel/rail profiles on energy dissipation in the wheel/rail contact

NARCIS (Netherlands)

Idarraga Alarcon, G.A.; Burgelman, N.D.M.; Meza Meza, J.; Toro, A.; Li, Z.

2015-01-01

This work investigates the energy dissipation in a wheel/rail system through friction work modeling. In order to identify the effect of the friction coefficient on the energy dissipation in the wheel/rail contact, several simulations were performed using a 3D multibody model of a railway vehicle

A Big Data Analysis Approach for Rail Failure Risk Assessment.

Science.gov (United States)

Jamshidi, Ali; Faghih-Roohi, Shahrzad; Hajizadeh, Siamak; Núñez, Alfredo; Babuska, Robert; Dollevoet, Rolf; Li, Zili; De Schutter, Bart

2017-08-01

Railway infrastructure monitoring is a vital task to ensure rail transportation safety. A rail failure could result in not only a considerable impact on train delays and maintenance costs, but also on safety of passengers. In this article, the aim is to assess the risk of a rail failure by analyzing a type of rail surface defect called squats that are detected automatically among the huge number of records from video cameras. We propose an image processing approach for automatic detection of squats, especially severe types that are prone to rail breaks. We measure the visual length of the squats and use them to model the failure risk. For the assessment of the rail failure risk, we estimate the probability of rail failure based on the growth of squats. Moreover, we perform severity and crack growth analyses to consider the impact of rail traffic loads on defects in three different growth scenarios. The failure risk estimations are provided for several samples of squats with different crack growth lengths on a busy rail track of the Dutch railway network. The results illustrate the practicality and efficiency of the proposed approach. © 2017 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Structural response of a rail acceleration

International Nuclear Information System (INIS)

Wang, S.Y.

1984-01-01

The transient response of a 0.4 by 0.6 cm rectangular bore rail accelerator was analyzed by a three dimensional finite element code. The copper rail deflected to a peak value of 0.08 mm in compression and then oscillated at an amplitude of 0.02 mm. Simultaneously the insulating side wall of glass fabric base, epoxy resin laminate (G-10) was compressed to a peak value of 0.13 mm and rebounded to a steady state in extension. Projectile pinch or blowby due to the rail extension or compression, respectively, can be identified by examining the time history of the rail displacement. The effect of blowby was most significant at the side wall characterized by mm size displacement in compression. Dynamic stress calculations indicate that the G-10 supporting material behind the rail is subjected to over 21 MPa at which the G-10 could fail if the laminate was not carefully oriented. Results for a polycarbonate resin (Lexan) side wall show much larger displacements and stresses than for G-10. The tradeoff between the transparency of Lexan and the mechanical strength of G-10 for sidewall material is obvious. Displacement calculations from the modal method are smaller than the results from the direct integration method by almost an order of magnitude, because the high frequency effect is neglected. 12 references

Guidance for consignors, rail operators and others involved in the packaging, labelling and carriage of radioactive material by rail. Pt. 5

International Nuclear Information System (INIS)

1996-01-01

This document, part of a series of guides for those concerned with the road or rail transportation of dangerous goods, provides detailed recommendations for consignors, rail operators and others involved in the packaging, labelling and carriage of radioactive materials by rail. It covers the relevant legislation and regulations on the carriage of such dangerous goods to assist those involved with compliance. (UK)

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...

Plasma treatment of crane rails

Directory of Open Access Journals (Sweden)

Владислав Олександрович Мазур

2016-07-01

Full Text Available Crane operation results in wear and tear of rails and crane wheels. Renovation and efficiency of these details is therefore relevant. Modern technologies of wheels and rails restoration use surfacing or high-frequency currents treatment. Surface treatment with highly concentrated streams of energy- with a laser beam, plasma jet- is a promising direction.. It is proposed to increase the efficiency of crane rails by means of surface plasma treatment. The modes of treatment have been chosen.. Modelling of plasma jet thermal impact on a solid body of complex shape has been made. Plasma hardening regimes that meet the requirements of production have been defined. Structural transformation of the material in the crane rails on plasma treatment has been investigated. It has been concluded that for carbon and low alloy crane steels the plasma exposure zone is characterized by a high degree of hardened structure dispersion and higher hardness as compared to the hardness after high-frequency quenching. As this takes place phase transformations are both shift (in the upper zone of plasma influence and fluctuation (in the lower zone of the plasma. With high-speed plasma heating granular or lamellar pearlite mainly transforms into austenite. The level of service characteristics of hardened steel, which is achieved in this case is determined by the kinetics and completeness of pearlite → austenite transformation. For carbon and low alloy rail steels plasma hardening can replace bulk hardening, hardening by high-frequency currents, or surfacing. The modes for plasma treatment which make it possible to obtain a surface layer with a certain service characteristics have been defined

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.

Revisiting the reasons for contact fatigue defects in rails

Directory of Open Access Journals (Sweden)

Darenskiy Alexander

2017-01-01

Full Text Available As it is known rail is one of the most significant elements of the whole railway construction. Operation under alternating loads from wheels of the rolling stock and different ambient temperatures lead to appearance and development of rail defects and damages. A great variety of operational factors (freight traffic density, axial loads, traffic speeds, track layout and profile as well as special features of manufacturing and thermal treatment of rails create certain difficulties while identifying reasons for defects and damages. The article deals with an attempt to estimate influence of track layout and lateral forces on appearance of defects and damages in rails on the base of long-term observations of rail operation in Kharkiv Metro. On the basis of the vehicle/track mathematical model which considers structural features of both rolling stock and permanent way in underground systems, the level of lateral forces in curves was calculated. The coefficients of correlation between the track curvature, the level of forces and the amount of defected rails removed were later obtained, that made it possible to determine the dominant factor which may lead to appearance and development of contact fatigue defects in rails laid in curves.

Operations Research Approaches to Asset Management in Freight Rail

DEFF Research Database (Denmark)

Gorman, Michael F.; Harrod, Steven

2011-01-01

This article describes operations research methodologies as they apply to asset management in freight rail. We describe state-of-the-art methods for locomotive, crew, railcar, line and yard planning and management. We conclude with emerging areas of research in rail.......This article describes operations research methodologies as they apply to asset management in freight rail. We describe state-of-the-art methods for locomotive, crew, railcar, line and yard planning and management. We conclude with emerging areas of research in rail....

Investigation of the stresses in rails : Secondary effects associated with the bending of a centrically loaded rail

NARCIS (Netherlands)

Kolvoort, A.J.; Woestenburg, T.

1982-01-01

The flexural behaviour of a rail under purely vertical load acting in the plane of symmetry is investigated in this paper. For this purpose a rail ofNP 46 standard section was subjected to experimental research with the aid of electrical resistance strain gauges in the Laboratory for Highway and

Distribution and Habitat Associations of California Black Rail (Laterallus jamaicensis cortuniculus in the Sacramento–San Joaquin Delta

Directory of Open Access Journals (Sweden)

Danika C. Tsao

2015-12-01

Full Text Available doi: http://dx.doi.org/10.15447/sfews.2015v13iss4art4Past studies documenting the distribution and status of state “Threatened" California black rail (Laterallus jamaicensis coturniculus; hereafter black rail have largely omitted the Sacramento—San Joaquin Delta (hereafter Delta. During March to May of 2009–2011, we conducted call–playback surveys to assess the status of the species within a wide range of wetland habitats of the central Delta region. We detected black rails at 21 of 107 discrete wetland sites, primarily on in-channel islands with dense cover. To better understand the habitat and land cover characteristics, we developed a model of habitat suitability from these occurrence data and a fine-scale vegetation and land use dataset using MaxEnt. We also evaluated differences in the size of wetlands at sites where black rails were detected versus where they were not. Through surveys and quantitative modeling, we found black rail presence differed from other regions within California and Arizona, in that it was positively associated with tall (1 to 5 m emergent vegetation interspersed with riparian shrubs. Specific plants correlated with black rail presence included emergent wetland (Bolboschoenus acutus, B. californicus, B. acutus, Typha angustifolia, T. latifolia, Phragmites australis and riparian (Salix exigua, S. lasiolepis, Rosa californica, Rubus discolor, Cornus sericea species. Median patch size was significantly larger and perimeter-to-area ratios were significantly lower at wetland sites where black rails were found. These results provide a preliminary characterization of black rail habitat in the Delta region and highlight the need for better understanding of this listed species’ population size and habitat use in the region, in light of anticipated climate change effects and proposed large-scale restoration in the Delta.

Mode II brittle fracture: recent developments

Directory of Open Access Journals (Sweden)

A. Campagnolo

2017-10-01

Full Text Available Fracture behaviour of V-notched specimens is assessed using two energy based criteria namely the averaged strain energy density (SED and Finite Fracture Mechanics (FFM. Two different formulations of FFM criterion are considered for fracture analysis. A new formulation for calculation of the control radius Rc under pure Mode II loading is presented and used for prediction of fracture behaviour. The critical Notch Stress Intensity Factor (NSIF at failure under Mode II loading condition can be expressed as a function of notch opening angle. Different formulations of NSIFs are derived using the three criteria and the results are compared in the case of sharp V-notched brittle components under in-plane shear loading, in order to investigate the ability of each method for the fracture assessment. For this purpose, a bulk of experimental data taken from the literature is employed for the comparison among the mentioned criteria

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...

Improving fatigue performance of rail thermite welds

Science.gov (United States)

Jezzini-Aouad, M.; Flahaut, P.; Hariri, S.; Winiar, L.

2010-06-01

Rail transport development offers economic and ecological interests. Nevertheless, it requires heavy investments in rolling material and infrastructure. To be competitive, this transportation means must rely on safe and reliable infrastructure, which requires optimization of all implemented techniques and structure. Rail thermite (or aluminothermic) welding is widely used within the railway industry for in-track welding during re-rail and defect replacement. The process provides numerous advantages against other welding technology commonly used. Obviously, future demands on train traffic are heavier axle loads, higher train speeds and increased traffic density. Thus, a new enhanced weld should be developed to prevent accidents due to fracture of welds and to lower maintenance costs. In order to improve such assembly process, a detailed metallurgical study coupled to a thermomechanical modelling of the phenomena involved in the thermite welding process is carried out. Obtained data enables us to develop a new improved thermite weld (type A). This joint is made by modifying the routinely specified procedure (type B) used in a railway rail by a standard gap alumino-thermic weld. Joints of type A and B are tested and compared. Based on experimental temperature measurements, a finite element analysis is used to calculate the thermal residual stresses induced. In the vicinity of the weld, the residual stress patterns depend on the thermal conditions during welding as it also shown by litterature [1, 2]. In parallel, X-Ray diffraction has been used to map the residual stress field that is generated in welded rail of types A and B. Their effect on fatigue crack growth in rail welds is studied. An experimental study based on fatigue tests of rails welded by conventional and improved processes adjudicates on the new advances and results will be shown.

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.

Segmented rail linear induction motor

Science.gov (United States)

Cowan, Jr., Maynard; Marder, Barry M.

1996-01-01

A segmented rail linear induction motor has a segmented rail consisting of a plurality of nonferrous electrically conductive segments aligned along a guideway. The motor further includes a carriage including at least one pair of opposed coils fastened to the carriage for moving the carriage. A power source applies an electric current to the coils to induce currents in the conductive surfaces to repel the coils from adjacent edges of the conductive surfaces.

Light Rails to Sustainable Mobility?

DEFF Research Database (Denmark)

Olesen, Mette

that there is not one overall rationale for implementing light rail, many arguments are evident in various contexts. Furthermore, findings in this paper show that planners, policy makers and other stakeholders shape stories for or against the implementation of light rail through the use of narratives that are linked...... infrastructure projects and urban interventions through the political process and secure the outcome of these projects are recognisable in proportion to the visionary concept....

The literature of the California black rail

Science.gov (United States)

Wilbur, Sanford R.

1974-01-01

Few birds have remained so little known as the California black rail (Laterallus jamaicensis coturniculus). Although first collected in 1859 or before and reported in 1874 (Ridgway 1874), its life history, distribution, and status have remained so obscure that even a sight record of the bird is deemed worthy of a report in some ornithological publications. Because degradation and loss of freshwater and saltwater marshlands in California may be detrimentally affecting the black rail, both the U.S. Bureau of Sport Fisheries and Wildlife (1973) and the California Department of Fish and Game (1972) have classified it as rare and worthy of further study. The 84 papers and notes both summarized in this report and included in its bibliography include essentially all that is currently known about the California black rail. Only 11 of these papers consider the life history of this rail in any detail. The rest are distribution notes and some of the more important papers on the closely related eastern black rail (L. j. jamaicensis). The latter are included for comparative purposes, or because they may lend clues to currently unknown facets of the life history of the western race.

Three-dimensional rail cooling analysis for a repetitively fired railgun

International Nuclear Information System (INIS)

Liu, H.P.

1991-01-01

This paper reports on a three-dimensional (3-D) rail cooling analysis for fabrication and demonstration of a stand-alone repetitive fire compulsator driven 9 MJ gun system which has been performed to assure the entire rail can be maintained below its thermal limit for multiple shots. The 3-D rail thermal model can predict the temperature, pressure, and convective heat transfer coefficient variations of the coolant along the 10 m long copper rail. The 9-MJ projectiles will be fired every 20 s for 3 min. Water cooling was used in the model for its high cooling capacity. Single liquid phase heat transfer was assumed in the cooling analysis. For multiple shots, the temperature difference between the rail and the water was enhanced due to accumulated heat in the rail. As a result, the heat removal by water increased from shot-to-shot. The rail temperature initially increased and finally stabilized after a number of shots

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.

Rail inspection system based on iGPS

Science.gov (United States)

Fu, Xiaoyan; Wang, Mulan; Wen, Xiuping

2018-05-01

Track parameters include gauge, super elevation, cross level and so on, which could be calculated through the three-dimensional coordinates of the track. The rail inspection system based on iGPS (indoor/infrared GPS) was composed of base station, receiver, rail inspection frame, wireless communication unit, display and control unit and data processing unit. With the continuous movement of the inspection frame, the system could accurately inspect the coordinates of rail; realize the intelligent detection and precision measurement. According to principle of angle intersection measurement, the inspection model was structured, and detection process was given.

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

NARCIS (Netherlands)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

Ren Weiju; Nicholas, Theodore

2003-01-01

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

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

49 CFR 213.113 - Defective rails.

Science.gov (United States)

2010-10-01

... smooth, bright, or dark, round or oval surface substantially at a right angle to the length of the rail... in the head of the rail as a smooth, bright, or dark surface progressing until substantially at a... head, and extending into or through it. A crack or rust streak may show under the head close to the web...

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

DEFF Research Database (Denmark)

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

2012-01-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

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

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

Science.gov (United States)

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

2017-07-12

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

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

Science.gov (United States)

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

2018-02-12

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

Attractive Mobile Corridors - The Power of Light Rail Infrastructures

DEFF Research Database (Denmark)

Olesen, Mette; Lassen, Claus

2013-01-01

Light rail is a popular tool in urban development strategies in many European cities. One argument for choosing a rail-based solution is that it signals stability to investors and will attract development and investments in the corridor. The choice of corridor in the various light rail cities...... and redistributes urban space. Furthermore light rail is not only a physical infrastructure but also an infrastructure of power that is carefully planned and designed creating both mental and physical patterns of mobilities and immobilities. Hence it is important to underline that mobility systems, such as light...

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.

Barriers to and enablers for European rail freight transport for integrated door-to-door logistics service. Part 2: Enablers for multimodal rail freight transport

Directory of Open Access Journals (Sweden)

Dewan Md Zahurul ISLAM

2014-12-01

Full Text Available The objective of this paper is to examine and identify barriers to and enablers for the European rail freight transport services as a transport chain partner along the supply chains in the changing market scenario. The changing market scenario includes, among others, requiring 'door-to-door' rather than 'terminal to terminal' and integrated service, competitive ability to attract non-rail cargo type, changes in the customer requirements (e.g. reliable service and changes in the operational requirements and practices. Using a literature review method, the paper is presented in two parts. The part 1 focuses on the identification of barriers to the European rail freight service by reviewing freight logistics services for global supply chains followed by the current performance of European rail freight transport followed by a discussion on the rail freight market liberalisation in Europe. Then rail freight transport in the Unites States (U.S. is discussed. The research notes that although the background, scope and necessity for reform measures in Europe differ from those of the U.S., some lessons can be learned and the main lesson is that an appropriate reform measure can enhance rail sector competitive ability in Europe. The part 2 of the paper is dedicated to recommend some concrete steps and actions as enablers to remove the barriers identified in the part 1 to develop multimodal rail freight transport. The enablers for multimodal rail freight transport include: •\tEuropean rail freight transport market needs full liberalisation so that incumbent and new entrants can compete freely. •\tThe rail operators need to acquire service (e.g. customer tailored services, door to door service quality offered by road freight operators. •\tThey need to conduct a combination of ‘terminal-to-terminal’ and door-to-door operations, as and when needed; •\tThey must build partnership with freight forwarder or 3PLs to include all types of customers

Method for Predicting Thermal Buckling in Rails

Science.gov (United States)

2018-01-01

A method is proposed herein for predicting the onset of thermal buckling in rails in such a way as to provide a means of avoiding this type of potentially devastating failure. The method consists of the development of a thermomechanical model of rail...

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

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

OpenAIRE

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

2016-01-01

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

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

African Journals Online (AJOL)

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

Notch sensitivity of ductile metallic foams : A computational study

NARCIS (Netherlands)

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

2011-01-01

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

Failure of a porous solid from a deep notch

DEFF Research Database (Denmark)

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

1997-01-01

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

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

Directory of Open Access Journals (Sweden)

Yidong Wang

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

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

Science.gov (United States)

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

2015-07-01

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

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

Directory of Open Access Journals (Sweden)

Jerry S Chen

2014-06-01

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

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

Directory of Open Access Journals (Sweden)

Siar CH

2010-10-01

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

Rail for inspection/maintenance device in TOKAMAK type container of a thermonuclear reactor

International Nuclear Information System (INIS)

Takahashi, Kenji.

1996-01-01

A circular rail divided into four arcuate parts for an inspection/maintenance device which runs in a TOKAMAK type container is disposed. Each of the divided rails is supported at the center of the outer surface rotatably by extendable rail supporting shafts. Each of the divided rail is constituted such that it can be contained between limiters disposed at the outer side of the TOKAMAK container when each of the rail support shafts is contracted. With such a constitution, each of the rail support shafts and arcuate rail is contracted and rotated from the outside of the TOKAMAK type container by an actuator. In order to form a circular rail, each of the rail support shafts is extended toward the center of the TOKAMAK type container, and then each of the arcuate rails is rotated into a horizontal state. Then, the joint portions of each of the arcuate rails are connected by using remote controllable locking rods. (I.S.)

49 CFR 38.175 - High-speed rail cars, monorails and systems.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false High-speed rail cars, monorails and systems. 38....175 High-speed rail cars, monorails and systems. (a) All cars for high-speed rail systems, including... monorail systems operating primarily on dedicated rail (i.e., not used by freight trains) or guideway, in...

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.

Modeling Shear Induced Von Willebrand Factor Binding to Collagen

Science.gov (United States)

Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

2017-11-01

Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

Field homogeneity improvement of maglev NdFeB magnetic rails from joints.

Science.gov (United States)

Li, Y J; Dai, Q; Deng, C Y; Sun, R X; Zheng, J; Chen, Z; Sun, Y; Wang, H; Yuan, Z D; Fang, C; Deng, Z G

2016-01-01

An ideal magnetic rail should provide a homogeneous magnetic field along the longitudinal direction to guarantee the reliable friction-free operation of high temperature superconducting (HTS) maglev vehicles. But in reality, magnetic field inhomogeneity may occur due to lots of reasons; the joint gap is the most direct one. Joint gaps inevitably exist between adjacent segments and influence the longitudinal magnetic field homogeneity above the rail since any magnetic rails are consisting of many permanent magnet segments. To improve the running performance of maglev systems, two new rail joints are proposed based on the normal rail joint, which are named as mitered rail joint and overlapped rail joint. It is found that the overlapped rail joint has a better effect to provide a competitive homogeneous magnetic field. And the further structure optimization has been done to ensure maglev vehicle operation as stable as possible when passing through those joint gaps. The results show that the overlapped rail joint with optimal parameters can significantly reduce the magnetic field inhomogeneity comparing with the other two rail joints. In addition, an appropriate gap was suggested when balancing the thermal expansion of magnets and homogenous magnetic field, which is considered valuable references for the future design of the magnetic rails.

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

Science.gov (United States)

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

2017-12-01

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

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

Science.gov (United States)

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

2011-02-01

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

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.

Do Urban Rail Transit Facilities Affect Housing Prices? Evidence from China

Directory of Open Access Journals (Sweden)

Xu Zhang

2016-04-01

Full Text Available Urban rail transit facilities play a critical role in citizen’s social activities (e.g., residence, work and education. Using panel data on housing prices and urban rail transit facilities for 35 Chinese cities for 2002 to 2013, this study constructs a panel data model to evaluate the effect of rail transit facilities on housing prices quantitatively. A correlation test reveals significant correlations between housing prices and rail transit facilities. Empirical results demonstrate that rail transit facilities can markedly elevate real estate prices. Quantitatively, a 1% increase in rail transit mileage improves housing prices by 0.0233%. The results highlight the importance of other factors (e.g., per capita GDP, land price, investment in real estate and population density in determining housing prices. We also assess the effects of expectations of new rail transit lines on housing prices, and the results show that expectation effects are insignificant. These findings encourage Chinese policy makers to take rail transit facilities into account in achieving sustainable development of real estate markets.

Buckling analysis of continuous welded rail track

NARCIS (Netherlands)

Van, M.A.

1996-01-01

Continuous welded rail track, compared to jointed track not only reduces maintenance costs, but also increases life time of track components and the comfort of passengers. Since expansion of the rails is hardly possible in CWR-track, a temperature increase will result in high compressive stresses

75 FR 16552 - High-Speed Intercity Passenger Rail (HSIPR) Program

Science.gov (United States)

2010-04-01

...; Enhancing intercity travel options; Ensuring a state of good repair of key intercity passenger rail assets... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration High-Speed Intercity Passenger Rail... selections for the High-Speed Intercity Passenger Rail (HSIPR) Program. This notice builds on the program...

A novel permanent magnetic rail for HTS levitation propulsion system

International Nuclear Information System (INIS)

Guo, F.; Tang, Y.; Ren, L.; Li, J.

2009-01-01

The Halbach Array has a characteristic advantage that the spatial fundamental field is canceled on one side of the array while the field intensity on the other side is enhanced. So this array could be used in the design of high temperature superconducting permanent magnetic levitation rail to improve the surface magnetic field and levitation force. This paper compared the surface magnetic field of the Halbach Array rail and two conventional levitation rails at first. Then proposed the potential advantages of Halbach Array applied in permanent magnetic rail system. But the Halbach Array rail is mechanical instability. An novel improved Halbach Array rail is proposed in this paper. The new structure combined the advantages of traditional structure and Halbach Array structure, solved the problem of mechanical instability, and carried on the advantage of Halbach Array on the magnetic field distribution at the same time.

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.

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

Field monitoring of rail squats using 3D ultrasonic mapping technique

International Nuclear Information System (INIS)

Kaewunruen, S.; Ishida, M.

2014-01-01

Rail squats and studs are typically classified as the propagation of any cracks .that have grown longitudinally through the subsurface. Some of the cracks could propagate to the bottom of rails transversely, which have branched from the initial longitudinal cracks with a depression of rail surface. The rail defects are commonly referred to as 'squats' when they were initiated from a damage layer caused by rolling contact fatigue, and as 'studs' when they were associated with a white etching layer caused by the transformation from pearlitic steel due to friction heat generated by wheel sliding or excessive traction. Such above-mentioned rail defects have been often observed in railway tracks catered for either light passenger or heavy freight traffics and for low, medium or high speed trains all over the world for over 60 years except some places such as sharp curves where large wear takes place under severe friction between the wheel flange and rail gauge face. It becomes a much-more significant issue when the crack grows and sometimes flakes off the rail (by itself or by insufficient rail grinding), resulting in a rail surface irregularity. Such rail surface defects induce wheel/rail impact and large amplitude vibration of track structure and poor ride quality. In Australia, Europe, and Japan, rail squats/studs have occasionally turned into broken rails. The root cause and preventive solution to this defect are still under investigation from the fracture mechanics and material sciences point of view. Some patterns of squat/stud development related to both curve and tangent track geometries have been observed and squat growth has been monitored for individual squats using ultrasonic mapping techniques. This paper highlights the field monitoring of squat/stud distribution and its growth. Squat/stud growth has been detected and scanned using the ultrasonic measurement device on a grid applied to the rail surface. The depths of crack paths at each grid node form a

Field monitoring of rail squats using 3D ultrasonic mapping technique

Energy Technology Data Exchange (ETDEWEB)

Kaewunruen, S., E-mail: sakdirat.kaewunruen@transport.nsw.gov.au [NSW, Transport, Sydney (Australia); Ishida, M., E-mail: ishida-mk@n-koei.jp [Nippon Koei Co. Ltd., Railway Div., Railway Engineering Dept., Chiyoda-ku, Tokyo (Japan)

2014-11-15

Rail squats and studs are typically classified as the propagation of any cracks .that have grown longitudinally through the subsurface. Some of the cracks could propagate to the bottom of rails transversely, which have branched from the initial longitudinal cracks with a depression of rail surface. The rail defects are commonly referred to as 'squats' when they were initiated from a damage layer caused by rolling contact fatigue, and as 'studs' when they were associated with a white etching layer caused by the transformation from pearlitic steel due to friction heat generated by wheel sliding or excessive traction. Such above-mentioned rail defects have been often observed in railway tracks catered for either light passenger or heavy freight traffics and for low, medium or high speed trains all over the world for over 60 years except some places such as sharp curves where large wear takes place under severe friction between the wheel flange and rail gauge face. It becomes a much-more significant issue when the crack grows and sometimes flakes off the rail (by itself or by insufficient rail grinding), resulting in a rail surface irregularity. Such rail surface defects induce wheel/rail impact and large amplitude vibration of track structure and poor ride quality. In Australia, Europe, and Japan, rail squats/studs have occasionally turned into broken rails. The root cause and preventive solution to this defect are still under investigation from the fracture mechanics and material sciences point of view. Some patterns of squat/stud development related to both curve and tangent track geometries have been observed and squat growth has been monitored for individual squats using ultrasonic mapping techniques. This paper highlights the field monitoring of squat/stud distribution and its growth. Squat/stud growth has been detected and scanned using the ultrasonic measurement device on a grid applied to the rail surface. The depths of crack paths at each

Mock-up tests of rail-mounted vehicle type in-vessel transporter/manipulator

International Nuclear Information System (INIS)

Oka, K.; Kakaudate, S.; Fukatsu, S.

1995-01-01

A rail-mounted vehicle system has been developed for remote maintenance of in-vessel components for fusion experimental reactor. In this system, a rail deploying/storing system is installed at outside of the reactor core and used to deploy a rail transporter and vehicle/manipulator for the in-vessel maintenance. A prototype of the rail deploying/storing system has been fabricated for mockup tests. This paper describes structural design of the prototypical rail deploying/storing system and results of the performance tests such as payload capacity, position control and rail deployment/storage performance

Ten years of common-rail injection systems for passenger cars; Gemeine Drucksache. Zehn Jahre Common-Rail-Einspritzsystem fuer Pkw

Energy Technology Data Exchange (ETDEWEB)

Hohenthal, M.Y. von

2007-07-15

The future of the diesel engine started in 1997 with the Bosch common rail injection system which provided higher power, higher rotary momentum, lower consumption, lower noise and lower pollutant emissions. Since then, high-pressure common-rail injection systems have become state of the art. (orig.)

Barriers to and enablers for European rail freight transport for integrated door-to-door logistics service. Part 1: Barriers to multimodal rail freight transport

Directory of Open Access Journals (Sweden)

Dewan Md Zahurul ISLAM

2014-09-01

Full Text Available The objective of this paper is to examine and identify barriers to and enablers for the European rail freight transport services as a transport chain partner along the supply chains in the changing market scenario. The changing market scenario includes, among others, requiring 'door-to-door' rather than 'terminal to terminal' and integrated service, competitive ability to attract non-rail cargo type, changes in the customer requirements (e.g. reliable service and changes in the operational requirements and practices. Using a literature review method, the paper is presented in two parts. The part 1 focuses on the identification of barriers to the European rail freight service by reviewing freight logistics services for global supply chains followed by the current performance of European rail freight transport followed by a discussion on the rail freight market liberalisation in Europe. Then rail freight transport in the Unites States (U.S. is discussed. The research notes that although the background, scope and necessity for reform measures in Europe differ from those of the U.S., some lessons can be learned and the main lesson is that an appropriate reform measure can enhance rail sector competitive ability in Europe. Examining and identifying the barriers in the part 1 (with the pan-Pacific examples of rail freight transports, the part 2 of the paper focuses on recommending clear actions and steps as enablers for the rail freight industry in general and operators in particular. The research in part 1 of the paper finds that: •\tIn many European countries, the rail freight market is not fully liberalised. In such market segment, infrastructure managers do act independently for incumbents and new entrant operators that hamper the progress of building a competitive market; •\tThe rail operators have not yet achieved the service quality (e.g. customer tailored service needed for the modern supply chains; •\tThey operate �

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

Simulations of roughness initiation and growth on railway rails

Science.gov (United States)

Sheng, X.; Thompson, D. J.; Jones, C. J. C.; Xie, G.; Iwnicki, S. D.; Allen, P.; Hsu, S. S.

2006-06-01

A model for the prediction of the initiation and growth of roughness on the rail is presented. The vertical interaction between a train and the track is calculated as a time history for single or multiple wheels moving on periodically supported rails, using a wavenumber-based approach. This vertical dynamic wheel/rail force arises from the varying stiffness due to discrete supports (i.e. parametric excitation) and the roughness excitation on the railhead. The tangential contact problem between the wheel and rail is modelled using an unsteady two-dimensional approach and also using the three-dimensional contact model, FASTSIM. This enables the slip and stick regions in the contact patch to be identified from the input geometry and creepage between the wheel and rail. The long-term wear growth is then predicted by applying repeated passages of the vehicle wheelsets, as part of an iterative solution.

Prototype Rail Crossing Violation Warning Application Project Report.

Science.gov (United States)

2017-09-05

This report is the Project Report for the Rail Crossing Violation Warning (RCVW) safety application developed for the project on Rail Crossing Violation Warning Application and Infrastructure Connection, providing a means for equipped connected vehic...

77 FR 17121 - Quarterly Rail Cost Adjustment Factor

Science.gov (United States)

2012-03-23

... decision may be purchased by contacting the Office of Public Assistance, Governmental Affairs, and...)] Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, Department of Transportation. ACTION: Approval of rail cost adjustment factor. [[Page 17122

Multiphysics modeling of a rail gun launcher

Directory of Open Access Journals (Sweden)

Y W Kwon

2016-03-01

Full Text Available A finite element based multiphysics modeling was conducted for a rail gunlauncher to predict the exit velocity of the launch object, and temperaturedistribution. For this modeling, electromagnetic field analysis, heat transferanalysis, thermal stress analysis, and dynamic analysis were conducted fora system consisting of two parallel rails and a moving armature. In particular,an emphasis was given to model the contact interface between rails andthe armature. A contact theory was used to estimate the electric as well asthermal conductivities at the interface. Using the developed model, aparametric study was conducted to understand effects of variousparameters on the exit velocity as well as the temperature distribution in therail gun launcher.

Electric rail gun application to space propulsion

International Nuclear Information System (INIS)

Barber, J.P.

1979-01-01

The paper examines the possibility of using the DC electric gun principles as a space vehicle propulsion system, capable of producing intermediate thrust levels. The application of an electromagnetic launch technique, called the DC electric rail gun, to the space propulsion concept of O'Neill, is examined. It is determined that the DC electric rail gun offers very high projectile accelerations and a very significant potential for reducing the size and mass of a reaction motor for space application. A detailed description of rail gun principles is given and some simple expressions for the accelerating force, gun impedance, power supply requirements, and system performance are discussed

30 CFR 57.9102 - Movement of independently operating rail equipment.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Movement of independently operating rail... NONMETAL MINES Loading, Hauling, and Dumping Traffic Safety § 57.9102 Movement of independently operating rail equipment. Movement of two or more pieces of rail equipment operating independently on the same...

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

Science.gov (United States)

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

2014-03-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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.

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.

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

Science.gov (United States)

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

2018-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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

2018-04-24

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

A systems approach to reduce urban rail energy consumption

International Nuclear Information System (INIS)

González-Gil, A.; Palacin, R.; Batty, P.; Powell, J.P.

2014-01-01

Highlights: • An insightful overview of energy usage in urban rail systems is given. • The principal measures to reduce urban rail energy consumption are appraised. • A methodology is proposed to help implement energy saving schemes in urban rail. • Regenerative braking is shown to offer the greatest energy saving potential. - Abstract: There is increasing interest in the potential of urban rail to reduce the impact of metropolitan transportation due to its high capacity, reliability and absence of local emissions. However, in a context characterised by increasing capacity demands and rising energy costs, and where other transport modes are considerably improving their environmental performance, urban rail must minimise its energy use without affecting its service quality. Urban rail energy consumption is defined by a wide range of interdependent factors; therefore, a system wide perspective is required, rather than focusing on energy savings at subsystem level. This paper contributes to the current literature by proposing an holistic approach to reduce the overall energy consumption of urban rail. Firstly, a general description of this transport mode is given, which includes an assessment of its typical energy breakdown. Secondly, a comprehensive appraisal of the main practices, strategies and technologies currently available to minimise its energy use is provided. These comprise: regenerative braking, energy-efficient driving, traction losses reduction, comfort functions optimisation, energy metering, smart power management and renewable energy micro-generation. Finally, a clear, logical methodology is described to optimally define and implement energy saving schemes in urban rail systems. This includes general guidelines for a qualitative assessment and comparison of measures alongside a discussion on the principal interdependences between them. As a hypothetical example of application, the paper concludes that the energy consumption in existing urban

Singular point analysis during rail deployment into vacuum vessel for ITER blanket maintenance

International Nuclear Information System (INIS)

Kakudate, Satoshi; Shibanuma, Kiyoshi

2007-05-01

Remote maintenance of the ITER blanket composed of about 400 modules in the vessel is required by a maintenance robot due to high gamma radiation of ∼500Gy/h in the vessel. A concept of rail-mounted vehicle manipulator system has been developed to apply to the maintenance of the ITER blanket. The most critical issue of the vehicle manipulator system is the feasibility of the deployment of the articulated rail composed of eight rail links into the donut-shaped vessel without any driving mechanism in the rail. To solve this issue, a new driving mechanism and procedure for the rail deployment has been proposed, taking account of a repeated operation of the multi-rail links deployed in the same kinematical manner. The new driving mechanism, which is deferent from those of a usual 'articulated arm' equipped with actuator in the every joint for movement, is composed of three mechanisms. To assess the feasibility of the kinematics of the articulated rail for rail deployment, a kinematical model composed of three rail links related to a cycle of the repeated operation for rail deployment was considered. The determinant det J' of the Jacobian matrix J' was solved so as to estimate the existence of a singular point of the transformation during rail deployment. As a result, it is found that there is a singular point due to det J'=0. To avoid the singular point of the rail links, a new location of the second driving mechanism and the related rail deployment procedure are proposed. As a result of the rail deployment test based on the new proposal using a full-scale vehicle manipulator system, the respective rail links have been successfully deployed within 6 h less than the target of 8 h in the same manner of the repeated operation under a synchronized cooperation among the three driving mechanisms. It is therefore concluded that the feasibility of the rail deployment of the articulated rail composed of simple structures without any driving mechanism has been demonstrated

30 CFR 56.9102 - Movement of independently operating rail equipment.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Movement of independently operating rail... MINES Loading, Hauling, and Dumping Traffic Safety § 56.9102 Movement of independently operating rail equipment. Movement of two or more pieces of rail equipment operating independently on the same track shall...

Genetic screens to identify new Notch pathway mutants in Drosophila.

Science.gov (United States)

Giagtzoglou, Nikolaos

2014-01-01

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

Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1.

Directory of Open Access Journals (Sweden)

Zhao-Jun Liu

Full Text Available Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM. They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox embryonic fibroblasts (MEFs. Notch1-deficient (Notch1(-/- MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1 in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441, which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1. Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4 in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.

An automated system for rail transit infrastructure inspection.

Science.gov (United States)

2015-03-01

This project applied commercial remote sensing and spatial information (CRS&SI) : technologies such as Ground Penetrating Radar (GPR), laser, GIS, and GPS to passenger rail : inspections. An integrated rail inspection system that can be mounted on hi...

Fracture toughness of epoxy/multi-walled carbon nanotube nano-composites under bending and shear loading conditions

International Nuclear Information System (INIS)

Ayatollahi, M.R.; Shadlou, S.; Shokrieh, M.M.

2011-01-01

Research highlights: → Mode I and mode II fracture tests were conducted on epoxy/MWCNT nano-composites. → Addition of MWCNT to epoxy increased both K Ic and K IIc of nano-composites. → The improvement in K IIc was more pronounced than in K Ic . → Mode I and mode II fracture surfaces were studied by scanning electron microscopy. -- Abstract: The effects of multi-walled carbon nanotubes (MWCNTs) on the mechanical properties of epoxy/MWCNT nano-composites were studied with emphasis on fracture toughness under bending and shear loading conditions. Several finite element (FE) analyses were performed to determine appropriate shear loading boundary conditions for a single-edge notch bend specimen (SENB) and an equation was derived for calculating the shear loading fracture toughness from the fracture load. It was seen that the increase in fracture toughness of nano-composite depends on the type of loading. That is to say, the presence of MWCNTs had a greater effect on fracture toughness of nano-composites under shear loading compared with normal loading. To study the fracture mechanisms, several scanning electron microscopy (SEM) pictures were taken from the fracture surfaces. A correlation was found between the characteristics of fracture surface and the mechanical behaviors observed in the fracture tests.

EVALUATION OF STRAIN-STRESS STATE OF THE RAILS IN THE PRODUCTION

Directory of Open Access Journals (Sweden)

V. V. Muravev

2017-01-01

Full Text Available High values of residual stresses is one of the most common reason of breaking lots of metal constructions, including rails. These stresses can reach values of flow limit, especially in the area of faults. Estimation of residual stresses values allows to get information about technical condition of the rail and also allow to avoid abnormal situations So, the aim of the research is creating the model of stress-strain state of the rail, which was hardened in its top and bottom, and to compare modeling results with experimental measurements of stresses and discrepancy of the housing.For creating the model and making evaluations by finite element method we used a program COMSOL. Forces on the top and bottom of the rail cause tension stresses, forces on the web of the rail cause tensile stresses. We compared calculated values of stresses with discrepancy of the housing. The discrepancy of the housing is informative characteristic for estimating the residual stresses according to standards. For experimental measurements we used an acoustic structuroscope SEMA. This structuroscope uses the acoustoelastic phenomenon for measurements. We made measurements of the five rails.According to the calculation results of the model, critical discrepancy of the housing in 2 mm corresponded to the following values of maximum stresses: –54 MPa in the top of the rail, 86 MPa in the web and –62 MPa in the bottom of the rail. Experimental measurements are the following: from –48 MPa to – 64 MPa in the top of the rail, 54 MPa to 93 MPa in the web of the rail, and –59 MPA to –74 MPa in the bottom of the rail. Absolute error was ±5 MPa.Thus we created the model, which allowed to analyze strain-stress state and compare real values of stresses with discrepancy of the housing. Results of the modeling showed coincidence with structure of distribution of residual stresses in five probes of rails. 

The Influence of Wheel/Rail Contact Conditions on the Microstructure and Hardness of Railway Wheels

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Paul Molyneux-Berry

2014-01-01

Full Text Available The susceptibility of railway wheels to wear and rolling contact fatigue damage is influenced by the properties of the wheel material. These are influenced by the steel composition, wheel manufacturing process, and thermal and mechanical loading during operation. The in-service properties therefore vary with depth below the surface and with position across the wheel tread. This paper discusses the stress history at the wheel/rail contact (derived from dynamic simulations and observed variations in hardness and microstructure. It is shown that the hardness of an “in-service” wheel rim varies significantly, with three distinct effects. The underlying hardness trend with depth can be related to microstructural changes during manufacturing (proeutectoid ferrite fraction and pearlite lamellae spacing. The near-surface layer exhibits plastic flow and microstructural shear, especially in regions which experience high tangential forces when curving, with consequentially higher hardness values. Between 1 mm and 7 mm depth, the wheel/rail contacts cause stresses exceeding the material yield stress, leading to work hardening, without a macroscopic change in microstructure. These changes in material properties through the depth of the wheel rim would tend to increase the likelihood of crack initiation on wheels toward the end of their life. This correlates with observations from several train fleets.

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.

Rail renaissance based on strategic market segmentation principles

African Journals Online (AJOL)

rail renaissance, market segmentation, South Africa, state of logistics, ... The modal imbalance is the result of a historical rail investment backlog, with ..... vector that can be thought of as a chromosome in genetic terms, while the values used.

Optimal Placement Method of RFID Readers in Industrial Rail Transport for Uneven Rail Traflc Volume Management

Science.gov (United States)

Rakhmangulov, Aleksandr; Muravev, Dmitri; Mishkurov, Pavel

2016-11-01

The issue of operative data reception on location and movement of railcars is significant the constantly growing requirements of the provision of timely and safe transportation. The technical solution for efficiency improvement of data collection on rail rolling stock is the implementation of an identification system. Nowadays, there are several such systems, distinguished in working principle. In the authors' opinion, the most promising for rail transportation is the RFID technology, proposing the equipping of the railway tracks by the stationary points of data reading (RFID readers) from the onboard sensors on the railcars. However, regardless of a specific type and manufacturer of these systems, their implementation is affiliated with the significant financing costs for large, industrial, rail transport systems, owning the extensive network of special railway tracks with a large number of stations and loading areas. To reduce the investment costs for creation, the identification system of rolling stock on the special railway tracks of industrial enterprises has developed the method based on the idea of priority installation of the RFID readers on railway hauls, where rail traffic volumes are uneven in structure and power, parameters of which is difficult or impossible to predict on the basis of existing data in an information system. To select the optimal locations of RFID readers, the mathematical model of the staged installation of such readers has developed depending on the non-uniformity value of rail traffic volumes, passing through the specific railway hauls. As a result of that approach, installation of the numerous RFID readers at all station tracks and loading areas of industrial railway stations might be not necessary,which reduces the total cost of the rolling stock identification and the implementation of the method for optimal management of transportation process.

A big data analysis approach for rail failure risk assessment

NARCIS (Netherlands)

Jamshidi, A.; Faghih Roohi, S.; Hajizadeh, S.; Nunez Vicencio, Alfredo; Babuska, R.; Dollevoet, R.P.B.J.; Li, Z.; De Schutter, B.H.K.

2017-01-01

Railway infrastructure monitoring is a vital task to ensure rail transportation safety. A rail failure could result in not only a considerable impact on train delays and maintenance costs, but also on safety of passengers. In this article, the aim is to assess the risk of a rail failure by

Structural parameter optimization design for Halbach permanent maglev rail

International Nuclear Information System (INIS)

Guo, F.; Tang, Y.; Ren, L.; Li, J.

2010-01-01

Maglev rail is an important part of the magnetic levitation launch system. Reducing the manufacturing cost of magnetic levitation rail is the key problem for the development of magnetic levitation launch system. The Halbach permanent array has an advantage that the fundamental spatial field is cancelled on one side of the array while the field on the other side is enhanced. So this array used in the design of high temperature superconducting permanent maglev rail could improve the surface magnetic field and the levitation force. In order to make the best use of Nd-Fe-B (NdFeB) material and reduce the cost of maglev rail, the effect of the rail's structural parameters on levitation force and the utilization rate of NdFeB material are analyzed. The optimal ranges of these structural parameters are obtained. The mutual impact of these parameters is also discussed. The optimization method of these structure parameters is proposed at the end of this paper.

Structural parameter optimization design for Halbach permanent maglev rail

Energy Technology Data Exchange (ETDEWEB)

Guo, F., E-mail: guofang19830119@163.co [R and D Center of Applied Superconductivity, Huazhong University of Science and Technology, Wuhan 430074 (China); Tang, Y.; Ren, L.; Li, J. [R and D Center of Applied Superconductivity, Huazhong University of Science and Technology, Wuhan 430074 (China)

2010-11-01

Maglev rail is an important part of the magnetic levitation launch system. Reducing the manufacturing cost of magnetic levitation rail is the key problem for the development of magnetic levitation launch system. The Halbach permanent array has an advantage that the fundamental spatial field is cancelled on one side of the array while the field on the other side is enhanced. So this array used in the design of high temperature superconducting permanent maglev rail could improve the surface magnetic field and the levitation force. In order to make the best use of Nd-Fe-B (NdFeB) material and reduce the cost of maglev rail, the effect of the rail's structural parameters on levitation force and the utilization rate of NdFeB material are analyzed. The optimal ranges of these structural parameters are obtained. The mutual impact of these parameters is also discussed. The optimization method of these structure parameters is proposed at the end of this paper.

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

Science.gov (United States)

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

2016-01-01

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

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

Control of rolling contact fatigue on premium rails in revenue service.

Science.gov (United States)

2014-11-01

Effective rail maintenance strategies are : essential for controlling rolling contact fatigue : (RCF) and reducing wear of rails under heavy : axle load (HAL) operations. In an effort to : optimize rail maintenance strategies in revenue : service, Tr...

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)

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

NASTRAN buckling study of a linear induction motor reaction rail

Science.gov (United States)

Williams, J. G.

1973-01-01

NASTRAN was used to study problems associated with the installation of a linear induction motor reaction rail test track. Specific problems studied include determination of the critical axial compressive buckling stress and establishment of the lateral stiffness of the reaction rail under combined loads. NASTRAN results were compared with experimentally obtained values and satisfactory agreement was obtained. The reaction rail was found to buckle at an axial compressive stress of 11,400 pounds per square inch. The results of this investigation were used to select procedures for installation of the reaction rail.

Rail Base Corrosion and Cracking Prevention: Phase 2

Science.gov (United States)

2018-04-09

EWI was engaged by the Federal Railroad Administration to research rail treatments to prevent rail base corrosion in corrosive environments. A coating system was selected in Phase 1 and recommended for field trials. In Phase 2, four railroads sponsor...

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

Science.gov (United States)

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

2018-01-01

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

Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

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.

Plans for crash-tested wood bridge railings for concrete decks

Science.gov (United States)

Michael A. Ritter; Ronald K. Faller; Barry T. Rosson; Paula D. Hilbrich Lee; Sheila Rimal. Duwadi

1998-01-01

As part of a continuing cooperative research between the Midwest Roadside Safety Facility (MwRSF); the USDA Forest Service, Forest Products Laboratory (FPL); and the Federal Highway Administration (FHWA), several crashworthy wood bridge railings and approach railing transitions have been adapted for use on concrete bridge decks. These railings meet testing and...

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

International Nuclear Information System (INIS)

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

2012-01-01

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

RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice.

Science.gov (United States)

Schouwey, K; Aydin, I T; Radtke, F; Beermann, F

2011-01-20

The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jκ-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jκ, as it is rescued in mice lacking RBP-Jκ in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jκ. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.