WorldWideScience

Sample records for notched machine parts

  1. Machine Parts as Metaphor.

    Science.gov (United States)

    Porter, Gerald

    The connection between Language for Specific Purposes (LSP) and literature is discussed with examples of technical vocabulary drawn from a variety of writers, with particular attention to a sketch by the British dramatist Harold Pinter, "Trouble in the Works," which makes extensive use of the terminology of machine parts. It is noted…

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

    International Nuclear Information System (INIS)

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

    1993-09-01

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

  3. Machine Shop Fundamentals: Part I.

    Science.gov (United States)

    Kelly, Michael G.; And Others

    These instructional materials were developed and designed for secondary and adult limited English proficient students enrolled in machine tool technology courses. Part 1 includes 24 lessons covering introduction, safety and shop rules, basic machine tools, basic machine operations, measurement, basic blueprint reading, layout, and bench tools.…

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  6. Machine for dismantling metal parts

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, O.I.; Loginovskiy, V.I.; Yagudin, S.Z.

    1982-01-01

    The purpose of the invention is to reduce the outlays of time for dismantling metal parts under conditions of eliminating open gas and oil gushers in operational drilling. This goal is achieved because the machine for dismantling the metal parts is equipped with a set of clamping elements arranged on the chassis, where each of them has a drive.

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

    Science.gov (United States)

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

    2017-07-01

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

  8. Function Concepts for Machine Parts

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik

    1999-01-01

    The majority of resources, like time and costs, consumed in industrial product development can be related to detailed design, i.e. the materialisation of machine parts (German Maschinenteile). Existing design theories based on a systems approach, e.g. Haberfellner [5] all have function, i.......e. transformation from input to output or ability to deliver purposeful effects as the core concept. The units in a product which posses functions are the organs (German: Funktionsträgern). Because individual parts do not posses functions, one could argue that the design theories based on a systems approach...... to be identification of a purposeful behaviour concept, i.e. function for a machine part. The contribution is based on the theory of technical systems, Hubka and the domain theory, Andreasen....

  9. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Science.gov (United States)

    Soori, Afshin; Haghani, Elham

    2015-01-01

    Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd…

  10. Electromechanical model of machine for vibroabrasive treatment of machine parts

    OpenAIRE

    Gorbatiyk, Ruslan; Palamarchuk, Igor; Chubyk, Roman

    2015-01-01

    A lot of operations on trimming clean and finishing – stripping up treatment, first of all, removing of burrs, rounding and processing of borders, until recently time was carried out by hand, and hardly exposed to automation and became a serious obstacle in subsequent growth of the labor productivity. Machines with free kinematics connection between a tool and the treating parts is provided by the printing-down of all of the surface of the machine parts, that allows us to effectively treat bo...

  11. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Directory of Open Access Journals (Sweden)

    Afshin Soori

    2015-10-01

    Full Text Available Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd edition. Top Notch 2A & 2B have 10 Units. The number of listening comprehension parts is in the range of 2 to 4 parts in each unit through the book. So the number of listening comprehension parts is not equally distributed. The participants of this study are 10 EFL teachers of two English language Institutes in Jahrom. Strong and weak aspects of Listening Comprehension parts have indicated in this research. The weaknesses involve the pictures and visuals are not clear enough to enhance students' motivation and interest, the audio is not completely suitable for students' English level, and Discussion parts are not stimulating students' talking. Furthermore this study revealed the crucial function of teachers in listening achievement of students. Keywords: textbook evaluation, listening comprehension, ELT

  12. Intelligent Machine Parts with Surface Embedded Sensors

    OpenAIRE

    Østbø, Niels Peter

    2009-01-01

    A surface embedded temperature sensor has successfully been fabricated on a customized industrial bolt. The aluminum substrate of the bolt was electrically isolated by plasma electrolytic oxidation followed by the fabrication of a type T thermocouple and finally covered by a wear resistant DLC coating. This bolt is part of our work to develop smart machine parts that are capable of reporting their current physical status under real working conditions enabling both new tools for condition base...

  13. NEW STEPS IN SKETCHING MACHINE PARTS

    Directory of Open Access Journals (Sweden)

    Tocariu Liliana

    2009-07-01

    Full Text Available This paper presents new and main steps in sketching machine part, by using the Solid Edge program. The traditional method applied in the technical drawing is appreciably altered in the case of the computer-assisted and modern design. These modifications involve others: e.g., use of classic drawing rule in tool sketching. The author deals with them from three points of view, namely: technical drawing, technical education and advantages.

  14. 30 CFR 56.14107 - Moving machine parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Moving machine parts. 56.14107 Section 56.14107... Safety Devices and Maintenance Requirements § 56.14107 Moving machine parts. (a) Moving machine parts... takeup pulleys, flywheels, couplings, shafts, fan blades, and similar moving parts that can cause injury...

  15. Monitoring coordinate measuring machines by calibrated parts

    International Nuclear Information System (INIS)

    Weckenmann, A; Lorz, J

    2005-01-01

    Coordinate measuring machines (CMM) are essential for quality assurance and production control in modern manufacturing. Due to the necessity of assuring traceability during the use of CMM, interim checks with calibrated objects carried out periodically. For this purpose usually special artefacts like standardized ball plates, hole plates, ball bars or step gages are measured. Measuring calibrated series parts would be more advantageous. Applying the substitution method of ISO 15530-3: 2000 such parts can be used. It is less cost intensive and less time consuming than measuring expensive special standardized objects in special programmed measurement routines. Moreover, the measurement results can directly compare with the calibration values; thus, direct information on systematic measurement deviations and uncertainty of the measured features are available. The paper describes a procedure for monitoring horizontal-arm CMMs with calibrated sheet metal series parts

  16. Rotating electric machine with fluid supported parts

    Science.gov (United States)

    Smith, Jr., Joseph L.; Kirtley, Jr., James L.

    1981-01-01

    A rotating electric machine in which the armature winding thereof and other parts are supported by a liquid to withstand the mechanical stresses applied during transient overloads and the like. In particular, a narrow gap is provided between the armature winding and the stator which supports it and this gap is filled with an externally pressurized viscous liquid. The liquid is externally pressurized sufficiently to balance the static loads on the armature winding. Transient mechanical loads which deform the armature winding alter the gap dimensions and thereby additionally pressurize the viscous liquid to oppose the armature winding deformation and more nearly uniformly to distribute the resulting mechanical stresses.

  17. 30 CFR 57.14107 - Moving machine parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Moving machine parts. 57.14107 Section 57.14107... Equipment Safety Devices and Maintenance Requirements § 57.14107 Moving machine parts. (a) Moving machine parts shall be guarded to protect persons from contacting gears, sprockets, chains, drive, head, tail...

  18. LASER CUTTING MACHINES FOR 3-D THIN SHEET PARTS

    Directory of Open Access Journals (Sweden)

    Miroslav RADOVANOVIC

    2012-11-01

    Full Text Available Laser cutting machines are used for precise contour cutting thin sheet. In industrial application nowadays various types and construction of laser cutting machines can be met. For contour cutting 3-D thin sheet parts laser cutting machines with rotation movements and laser robots are used. Laser generates the light beam, that presents a tool in working process. Application of laser cutting machines made possible good quality of products, flexibility of production and enlargement of economy

  19. Trinary Associative Memory Would Recognize Machine Parts

    Science.gov (United States)

    Liu, Hua-Kuang; Awwal, Abdul Ahad S.; Karim, Mohammad A.

    1991-01-01

    Trinary associative memory combines merits and overcomes major deficiencies of unipolar and bipolar logics by combining them in three-valued logic that reverts to unipolar or bipolar binary selectively, as needed to perform specific tasks. Advantage of associative memory: one obtains access to all parts of it simultaneously on basis of content, rather than address, of data. Consequently, used to exploit fully parallelism and speed of optical computing.

  20. Application of charged particle activation for testing machine part wear

    International Nuclear Information System (INIS)

    Kosimova, M.; Tendera, P.

    1985-01-01

    The results of application of the charge particle activation method to investigate machine part wear are presented. Study of radionuclide activity and yield has been carried out at the U-120M isochronous cyclotron by means of the method of iron foil piles from 20 to 100 μm in thick. Protons and deuterons have been used. Wear measurement is based on determination of wear particle activity in a butyric medium. An example of the results of a bench test of activated piston rings and cylinder liner of the engine for trucks is given. The method of surface activation is shown to be acceptable for studying machine part wear under the regular service conditions, especially on the stage of the primary investigations and development, when sampling structural materials and estimating different lubricating oil applicability

  1. Machinability of magnesium and aluminium alloys. Part I: cutting resistance

    International Nuclear Information System (INIS)

    Balout, B.; Songmene, V.; Masounave, J.

    2002-01-01

    Aluminium (2.7 g/cm 3 ) and magnesium (1.7 g/cm 3 ) are two competing light metals with similar mechanical properties and excellent possibilities for recycling. The forming of magnesium is often seen as an impediment to its use. New forming techniques using magnesium shavings are being developed, particularly in Japan. The machining of magnesium alloys by removal of metal raises safety concerns (risk of fire), which limits many potential applications of magnesium. The purpose of this work is to clarify and compare the machining properties of these two types of metal and better understand the mechanisms that may explain the differences in behaviour. Such a comparison could eventually provide an estimate of the cost of producing shavings for the manufacture of aluminium and magnesium parts through forging and extrusion, which would limit environmental pollution. Based on an analysis of cutting resistance during machining, it was demonstrated that magnesium alloys are easier to machine than similar aluminium alloys. Magnesium shavings are shorter than those of 6061-T6, but are especially more regular than those of A356, and their size is independent of cutting speed. It was also demonstrated that the fragility of materials can be characterized based on the results of cutting resistance produced during drilling

  2. Some aspects of precise laser machining - Part 1: Theory

    Science.gov (United States)

    Wyszynski, Dominik; Grabowski, Marcin; Lipiec, Piotr

    2018-05-01

    The paper describes the role of laser beam polarization and deflection on quality of laser beam machined parts made of difficult to cut materials (used for cutting tools). Application of efficient and precise cutting tool (laser beam) has significant impact on preparation and finishing operations of cutting tools for aviation part manufacturing. Understanding the phenomena occurring in the polarized light laser cutting gave possibility to design, build and test opto-mechanical instrumentation to control and maintain process parameters and conditions. The research was carried within INNOLOT program funded by Polish National Centre for Research and Development.

  3. Part 1: Notch-sparing γ-secretase inhibitors: The identification of novel naphthyl and benzofuranyl amide analogs.

    Science.gov (United States)

    Lu, Dai; Wei, Han-Xun; Zhang, Jing; Gu, Yongli; Osenkowski, Pamela; Ye, Wenjuan; Selkoe, Dennis J; Wolfe, Michael S; Augelli-Szafran, Corinne E

    2016-05-01

    γ-Secretase is one of two proteases directly involved in the production of the amyloid β-peptide (Aβ), which is pathogenic in Alzheimer's disease. Inhibition of γ-secretase to suppress the production of Aβ should not block processing of one of its alternative substrates, Notch1 receptors, as interference with Notch1 signaling leads to severe toxic effects. In the course of our studies to identify γ-secretase inhibitors with selectivity for APP over Notch, 1 [3-(benzyl(isopropyl)amino)-1-(naphthalen-2-yl)propan-1-one] was found to inhibit γ-secretase-mediated Aβ production without interfering with γ-secretase-mediated Notch processing in purified enzyme assays. As 1 is chemically unstable, efforts to increase the stability of this compound led to the identification of 2 [naphthalene-2-carboxylic acid benzyl-isopropyl-amide] which showed similar biological activity to compound 1. Synthesis and evaluation of a series of amide analogs resulted in benzofuranyl amide analogs that showed promising Notch-sparing γ-secretase inhibitory effects. This class of compounds may serve as a novel lead series for further study in the development of γ-secretase inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Machine parts recognition using a trinary associative memory

    Science.gov (United States)

    Awwal, Abdul Ahad S.; Karim, Mohammad A.; Liu, Hua-Kuang

    1989-01-01

    The convergence mechanism of vectors in Hopfield's neural network in relation to recognition of partially known patterns is studied in terms of both inner products and Hamming distance. It has been shown that Hamming distance should not always be used in determining the convergence of vectors. Instead, inner product weighting coefficients play a more dominant role in certain data representations for determining the convergence mechanism. A trinary neuron representation for associative memory is found to be more effective for associative recall. Applications of the trinary associative memory to reconstruct machine part images that are partially missing are demonstrated by means of computer simulation as examples of the usefulness of this approach.

  6. 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.

  7. Dimensional control and check of field machining parts for reactor internals installation

    International Nuclear Information System (INIS)

    Zhang Caifang

    2010-01-01

    Some key issues of dimensional control for reactor internals installation are analyzed, and important technical requirements of crucial quality control elements on the measurement, machining, and checking of reactor internals filed machining parts are discussed. Moreover, provisions on quality control and risk prevention of reactor internals filed machining parts are presented in this paper. (author)

  8. Diagnostics of machine parts by means of reverse engineering procedures

    Directory of Open Access Journals (Sweden)

    Jacek Rysinski

    2015-05-01

    Full Text Available In this article, an application of a three-dimensional scanner for building a special diagnostic stand is described. An experimental method of detection of material defects is discussed. The considered defects are connected with cooperation of particular surfaces of machine parts. In the discussed experiments, particularly the dimensions of pitting holes can be evaluated. Availability of laboratory facilities required that the investigations were performed using geared wheels. The three-dimensional model which represents a degenerated surface, obtained based upon the diagnostic measurements, was compared with the pattern of an undamaged surface. The latter was generated by means of our pre-processor. The pre-processor enables generation of files which are compatible with the majority of the computer-aided design system formats. Therefore, the analyses were performed by means of commercial system inventor and computer-aided three-dimensional interactive application.

  9. A method of numerically controlled machine part programming

    Science.gov (United States)

    1970-01-01

    Computer program is designed for automatically programmed tools. Preprocessor computes desired tool path and postprocessor computes actual commands causing machine tool to follow specific path. It is used on a Cincinnati ATC-430 numerically controlled machine tool.

  10. On the issue of particularities of design and simulation of welded constructions of machine's basic parts

    OpenAIRE

    Mihaylov, V.; Porhynov, S.

    2010-01-01

    In current conditions of machine industry competitive strength of firms effectively to make the process equipment has an essential value. It predetermines the necessity of wide application of welded constructions of machine tools basic parts. The solution of this task involves development o technique permitting to calculate and optimize the basic parts of machine tools depending on conditions in each case. In the present paper the results of research of deflected mode of machine tool basic pa...

  11. National machine guarding program: Part 1. Machine safeguarding practices in small metal fabrication businesses

    OpenAIRE

    Parker, David L.; Yamin, Samuel C.; Brosseau, Lisa M.; Xi, Min; Gordon, Robert; Most, Ivan G.; Stanley, Rodney

    2015-01-01

    Background Metal fabrication workers experience high rates of traumatic occupational injuries. Machine operators in particular face high risks, often stemming from the absence or improper use of machine safeguarding or the failure to implement lockout procedures. Methods The National Machine Guarding Program (NMGP) was a translational research initiative implemented in conjunction with two workers' compensation insures. Insurance safety consultants trained in machine guarding used standardize...

  12. National Machine Guarding Program: Part 1. Machine safeguarding practices in small metal fabrication businesses.

    Science.gov (United States)

    Parker, David L; Yamin, Samuel C; Brosseau, Lisa M; Xi, Min; Gordon, Robert; Most, Ivan G; Stanley, Rodney

    2015-11-01

    Metal fabrication workers experience high rates of traumatic occupational injuries. Machine operators in particular face high risks, often stemming from the absence or improper use of machine safeguarding or the failure to implement lockout procedures. The National Machine Guarding Program (NMGP) was a translational research initiative implemented in conjunction with two workers' compensation insures. Insurance safety consultants trained in machine guarding used standardized checklists to conduct a baseline inspection of machine-related hazards in 221 business. Safeguards at the point of operation were missing or inadequate on 33% of machines. Safeguards for other mechanical hazards were missing on 28% of machines. Older machines were both widely used and less likely than newer machines to be properly guarded. Lockout/tagout procedures were posted at only 9% of machine workstations. The NMGP demonstrates a need for improvement in many aspects of machine safety and lockout in small metal fabrication businesses. © 2015 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals, Inc.

  13. Research on the proficient machine system. Theoretical part; Jukutatsu machine system no chosa kenkyu. Rironhen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    The basic theory of the proficient machine system to be developed was studied. Important proficient techniques in manufacturing industries are becoming extinct because of insufficient succession to next generation. The proficient machine system was proposed to cope with such situation. This machine system includes the mechanism for progress and evolution of techniques and sensibilities to be adaptable to environmental changes by learning and recognizing various motions such as work and process. Consequently, the basic research fields are composed of thought, learning, perception and action. This machine requires not only deigned fixed functions but also introduction of the same proficient concept as human being to be adaptable to changes in situation, purpose, time and machine`s complexity. This report explains in detail the basic concept, system principle, approaching procedure and practical elemental technologies of the proficient machine system, and also describes the future prospect. 133 refs., 110 figs., 7 tabs.

  14. National machine guarding program: Part 1. Machine safeguarding practices in small metal fabrication businesses

    Science.gov (United States)

    Yamin, Samuel C.; Brosseau, Lisa M.; Xi, Min; Gordon, Robert; Most, Ivan G.; Stanley, Rodney

    2015-01-01

    Background Metal fabrication workers experience high rates of traumatic occupational injuries. Machine operators in particular face high risks, often stemming from the absence or improper use of machine safeguarding or the failure to implement lockout procedures. Methods The National Machine Guarding Program (NMGP) was a translational research initiative implemented in conjunction with two workers' compensation insures. Insurance safety consultants trained in machine guarding used standardized checklists to conduct a baseline inspection of machine‐related hazards in 221 business. Results Safeguards at the point of operation were missing or inadequate on 33% of machines. Safeguards for other mechanical hazards were missing on 28% of machines. Older machines were both widely used and less likely than newer machines to be properly guarded. Lockout/tagout procedures were posted at only 9% of machine workstations. Conclusions The NMGP demonstrates a need for improvement in many aspects of machine safety and lockout in small metal fabrication businesses. Am. J. Ind. Med. 58:1174–1183, 2015. © 2015 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals, Inc. PMID:26332060

  15. Features of measurement and processing of vibration signals registered on the moving parts of electrical machines

    OpenAIRE

    Gyzhko, Yuri

    2011-01-01

    Measurement and processing of vibration signals registered on the moving parts of the electrical machines using the diagnostic information-measuring system that uses Bluetooth wireless standard for the transmission of the measured data from moving parts of electrical machine is discussed.

  16. Production Machine Shop Employment Competencies. Part Three: The Engine Lathe.

    Science.gov (United States)

    Bishart, Gus; Werner, Claire

    Competencies for production machine shop are provided for the third of four topic areas: the engine lathe. Each competency appears in a one-page format. It is presented as a goal statement followed by one or more "indicator" statements, which are performance objectives describing an ability that, upon attainment, will establish…

  17. 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)

  18. The IBM PC as an Online Search Machine--Part 2: Physiology for Searchers.

    Science.gov (United States)

    Kolner, Stuart J.

    1985-01-01

    Enumerates "hardware problems" associated with use of the IBM personal computer as an online search machine: purchase of machinery, unpacking of parts, and assembly into a properly functioning computer. Components that allow transformations of computer into a search machine (combination boards, printer, modem) and diagnostics software…

  19. Surface Coating of Plastic Parts for Business Machines (Industrial Surface Coating): New Source Performance Standards (NSPS)

    Science.gov (United States)

    Learn more about the new source performance standards (NSPS) for surface coating of plastic parts for business machines by reading the rule summary and history and finding the code of federal regulations as well as related rules.

  20. 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.

  1. Magnetoresistance effect in permalloy nanowires with various types of notches

    Science.gov (United States)

    Gao, Y.; You, B.; Wang, J.; Yuan, Y.; Wei, L. J.; Tu, H. Q.; Zhang, W.; Du, J.

    2018-05-01

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

  2. A Support Vector Machine Approach to Dutch Part-of-Speech Tagging

    NARCIS (Netherlands)

    Poel, Mannes; Stegeman, L.; op den Akker, Hendrikus J.A.; Berthold, M.R.; Shawe-Taylor, J.; Lavrac, N.

    Part-of-Speech tagging, the assignment of Parts-of-Speech to the words in a given context of use, is a basic technique in many systems that handle natural languages. This paper describes a method for supervised training of a Part-of-Speech tagger using a committee of Support Vector Machines on a

  3. Hidden Identification on Parts: Magnetic Machine-Readable Matrix Symbols

    Science.gov (United States)

    Schramm, Harry F.; Jones, Clyde S.; Roxby, Donald L.; Teed, James D.; Shih, William C. L.; Fitzpatrick, Gerald L.; Knisely, Craig

    2005-01-01

    All NASA parts have identification, usually expressed in terms of part number, serial number, and the like. In most cases, this identification is permanently marked directly on the part for tracking throughout its life cycle. NASA has developed a method for reading the matrix symbol through up to 15 mils (25 m) of paint (5 or 6 layers). This method of part identification involves coating selected patches on the objects with magnetic materials in matrix symbol patterns and reading the patterns by use of magneto-optical imaging equipment.

  4. Transducer-actuator systems and methods for performing on-machine measurements and automatic part alignment

    Science.gov (United States)

    Barkman, William E.; Dow, Thomas A.; Garrard, Kenneth P.; Marston, Zachary

    2016-07-12

    Systems and methods for performing on-machine measurements and automatic part alignment, including: a measurement component operable for determining the position of a part on a machine; and an actuation component operable for adjusting the position of the part by contacting the part with a predetermined force responsive to the determined position of the part. The measurement component consists of a transducer. The actuation component consists of a linear actuator. Optionally, the measurement component and the actuation component consist of a single linear actuator operable for contacting the part with a first lighter force for determining the position of the part and with a second harder force for adjusting the position of the part. The actuation component is utilized in a substantially horizontal configuration and the effects of gravitational drop of the part are accounted for in the force applied and the timing of the contact.

  5. Life time evaluation of spectrum loaded machine parts

    Energy Technology Data Exchange (ETDEWEB)

    Rabb, R. [Waertsilae NSD Corporation, Vaasa (Finland)

    1998-12-31

    In a medium speed diesel engine there are some important components, such as the cylinder head, the piston and the cylinder liner, which are subjected to a specific load spectrum consisting of mainly two distinct parts. One is the low cycle part which is due to the temperature field that builds up after that the engine has been started. This low cycle part causes a big stress amplitude but consists of only a couple of thousand cycles during the engine life time. The other part of the load spectrum is the high cycle part due to the firing pressure. The high cycle part has a smaller amplitude but consists of billions of cycles during the engine life time. The cylinder head and the cylinder liner are made of cast iron. In this investigation the true extension into the high cycle domain of the S-N curve for grey cast iron grade 300/ISO 185 was established through fatigue tests with a load spectrum resembling the existing one. This testing resulted in much new and improved knowledge about the fatigue properties of grey cast iron and it was even possible to generalize the outcome of the spectrum fatigue tests into a simple design curve. (orig.) 11 refs.

  6. Programming and machining of complex parts based on CATIA solid modeling

    Science.gov (United States)

    Zhu, Xiurong

    2017-09-01

    The complex parts of the use of CATIA solid modeling programming and simulation processing design, elaborated in the field of CNC machining, programming and the importance of processing technology. In parts of the design process, first make a deep analysis on the principle, and then the size of the design, the size of each chain, connected to each other. After the use of backstepping and a variety of methods to calculate the final size of the parts. In the selection of parts materials, careful study, repeated testing, the final choice of 6061 aluminum alloy. According to the actual situation of the processing site, it is necessary to make a comprehensive consideration of various factors in the machining process. The simulation process should be based on the actual processing, not only pay attention to shape. It can be used as reference for machining.

  7. Method for assembling dynamoelectric machine end shield parts

    International Nuclear Information System (INIS)

    Thomson, J.M.

    1984-01-01

    Methods, apparatus, and systems are provided for automatically assembling end shield assemblies of subassemblies for electric motors. In a preferred form, a system and methods are provided that utilize a non-palletized, non-synchronous concept to convey end shields through a number of assembly stations. At process stations situated along a conveyor, operations are performed on components. One method includes controlling traffic of sub-assemblies by toggle type escapements. A stop or latch of unique design stops end shield components in midstream, and ''lifts'' of unique design disengage parts from the conveyor and also support such parts during various operations. Photo-optic devices and proximity and reed switch mechanisms are utilized for control purposes. The work stations involved in one system include a unique assembly and pressing station involving oil well covers; a unique feed wick seating system; a unique lubricant adding operation; and unique ''building block'' mechanisms and methods

  8. Abbreviated machining schedule for fabricating beryllium parts free of surface damage

    International Nuclear Information System (INIS)

    Beitscher, S.; Capes, J.F.; Leslie, W.W.; Luckow, J.R.; Riegel, R.L.

    1979-01-01

    This study was performed to develop a more economical method of machining damage-free beryllium components at Rocky Flats. The present method involves a 9-pass schedule of lathe turning followed by a chemical etch. Prototype beryllium hemispherical shell parts and cylindrical tensile specimens machined to simulate the parts were utilized in this study. The main investigative methods used to evaluate the amount of machining damage were metallography and tensile tests. It was found that damage-free parts could be produced by carefully controlled machining if the number of machining passes was reduced to 4 or even 3, if followed by the standard etching treatment. These findings were made on Select S-65 grade beryllium, and probably apply to other common grades of powder source beryllium but not necessarily to ingot-source beryllium. It is recommended that the 4-pass schedule becomes the standard method to produce damage-free beryllium derived from powder. Significant savings in time, labor, and equipment can be realized by this change in method without decreasing the quality of the product

  9. Effect of power quality on windings temperature of marine induction motors. Part I: Machine model

    Energy Technology Data Exchange (ETDEWEB)

    Gnacinski, P. [Gdynia Maritime Univ., Dept. of Ship Electrical Power Engineering, Morska Str. 83, 81-225 Gdynia (Poland)

    2009-10-15

    Marine induction machines are exposed to various power quality disturbances appearing simultaneously in ship power systems: frequency and voltage rms value deviation, voltage unbalance and voltage waveform distortions. As a result, marine induction motors can be seriously overheated due to lowered supply voltage quality. Improvement of the protection of marine induction machines requires an appropriate method of power quality assessment and modification of the power quality regulations of ship classification societies. This paper presents an analytical model of an induction cage machine supplied with voltage of lowered quality, used in part II of the work (effect of power quality on windings temperature of marine induction motors. Part II. Results of investigations and recommendations for related regulations) for power quality assessment in ship power systems, and for justification of the new power quality regulations proposal. The presented model is suitable for implementation in an on-line measurement system. (author)

  10. Revitalization of the damaged machine parts by hard facing as a way of saving funds

    Directory of Open Access Journals (Sweden)

    Vukić Lazić

    2016-09-01

    Full Text Available The objective of the research, presented in this paper, was to demonstrate the superiority of the hard facing as the revitalization technology of various damaged machine parts. The analysis of the two different revitalization methods of the damaged machine parts is presented – the replacement of the damaged part by the new – spare part and reparation by hard facing. The comparison is done on the example of hard facing and replacing of damaged loader's teeth. The paper presents a method for calculating costs of the two revitalization technologies based on their profitability and their comparison. That method could be applied for similar calculations for any machine part, with smallest or no adjustments. The paper presents a verification of advantage of applying the hard facing as the machine parts reparatory technology with respect to the other revitalization technology. The savings realized by application of hard facing reparation of the loader's teeth reach 73.5 % for one set of teeth and 82.40per annum of the costs for purchasing the new spare parts. The analysis was conducted under an assumption that organization of the maintenance function is at the exceptionally high level so that the purchasing of the new part/repairing of the damaged one is always done in time. This idealized approach was adopted since in that way one obtains the least economic effects of the reparatory technology application with respect to replacing the part with the spare one. In any other case the economic effects would be significantly higher, namely even more positive in favor of the hard facing revitalization technology.

  11. Process acceptance and adjustment techniques for Swiss automatic screw machine parts. Final report

    International Nuclear Information System (INIS)

    Robb, J.M.

    1976-01-01

    Product tolerance requirements for small, cylindrical, piece parts produced on swiss automatic screw machines have progressed to the reliability limits of inspection equipment. The miniature size, configuration, and tolerance requirements (plus or minus 0.0001 in.) (0.00254 mm) of these parts preclude the use of screening techniques to accept product or adjust processes during setup and production runs; therefore, existing means of product acceptance and process adjustment must be refined or new techniques must be developed. The purpose of this endeavor has been to determine benefits gained through the implementation of a process acceptance technique (PAT) to swiss automatic screw machine processes. PAT is a statistical approach developed for the purpose of accepting product and centering processes for parts produced by selected, controlled processes. Through this endeavor a determination has been made of the conditions under which PAT can benefit a controlled process and some specific types of screw machine processes upon which PAT could be applied. However, it was also determined that PAT, if used indiscriminately, may become a record keeping burden when applied to more than one dimension at a given machining operation

  12. A low-cost machine vision system for the recognition and sorting of small parts

    Science.gov (United States)

    Barea, Gustavo; Surgenor, Brian W.; Chauhan, Vedang; Joshi, Keyur D.

    2018-04-01

    An automated machine vision-based system for the recognition and sorting of small parts was designed, assembled and tested. The system was developed to address a need to expose engineering students to the issues of machine vision and assembly automation technology, with readily available and relatively low-cost hardware and software. This paper outlines the design of the system and presents experimental performance results. Three different styles of plastic gears, together with three different styles of defective gears, were used to test the system. A pattern matching tool was used for part classification. Nine experiments were conducted to demonstrate the effects of changing various hardware and software parameters, including: conveyor speed, gear feed rate, classification, and identification score thresholds. It was found that the system could achieve a maximum system accuracy of 95% at a feed rate of 60 parts/min, for a given set of parameter settings. Future work will be looking at the effect of lighting.

  13. Application of FIB technique to introduction of a notch into a carbon fiber for direct measurement of fracture toughness

    International Nuclear Information System (INIS)

    Ogihara, S; Imafuku, Y; Yamamoto, R; Kogo, Y

    2009-01-01

    For the direct measurement of the fracture toughness of the carbon fiber, a new technique was proposed and examined its applicability. At first, machining condition of the notch was examined. The notch was introduced using focused ion beam (FIB). The ion beam can be electronically scanned to introduce a sharp notch on the carbon fiber. Notches with various notch width and length were introduced by changing beam and scanning conditions. Tensile tests on notched carbon fibers were carried out following the test method for carbon fiber monofilaments. Fractured specimens were successfully corrected without secondary damage using protection films. SEM observations revealed that a crack propagated from a notch-tip, and notch size was able to be determined successfully. Effect of notch root radius was also examined to investigate the validity of the fracture toughness obtained by this method.

  14. 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.

  15. Understanding dental CAD/CAM for restorations - dental milling machines from a mechanical engineering viewpoint. Part A: chairside milling machines.

    Science.gov (United States)

    Lebon, Nicolas; Tapie, Laurent; Duret, Francois; Attal, Jean-Pierre

    2016-01-01

    The dental milling machine is an important device in the dental CAD/CAM chain. Nowadays, dental numerical controlled (NC) milling machines are available for dental surgeries (chairside solution). This article provides a mechanical engineering approach to NC milling machines to help dentists understand the involvement of technology in digital dentistry practice. First, some technical concepts and definitions associated with NC milling machines are described from a mechanical engineering viewpoint. The technical and economic criteria of four chairside dental NC milling machines that are available on the market are then described. The technical criteria are focused on the capacities of the embedded technologies of these milling machines to mill both prosthetic materials and types of shape restorations. The economic criteria are focused on investment costs and interoperability with third-party software. The clinical relevance of the technology is assessed in terms of the accuracy and integrity of the restoration.

  16. MOUNTABILITY PARTS OF MACHINE WITH ROTATING SURFACE, FITTED WITH POSITIVE CLEARANCE

    Directory of Open Access Journals (Sweden)

    Zbigniew BUDNIAK

    2014-06-01

    Full Text Available In this paper demonstrates the conditions of automatic assembly the parts of machines with rotating surfaces, fitted with positive clearance. Determination of the general condition of asseblability allowed for designation of the acceptable relative displacement and torsion axle, combined parts on the mounting position. The designation of depending allowed for assess the technological capacity of the installation equipment. On the basis of this mathematical model was developed a computer program that allows to determine the effect of geometric, strength and dynamic parameters of the assembly process. The examples of results of numerical calculations are shown in the graphs

  17. 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 ...

  18. Evaluation influence of machining parameters on shape form errors in turning of machine parts clamped in the chuck with adaptive jaws

    Directory of Open Access Journals (Sweden)

    I.V. Lutsiv

    2017-12-01

    Full Text Available The paper deals with the derivation problem of the dependence of machine part geometric form deviation in cross section area on clamping diameter as well as cutting speed, feed and cutting depth in semi finish machining. The analysis of single factor circular deviation dependences on machining conditions values is performed. Using the special software application package the laboratory conditions experiment results are analyzed. The dispersion analysis including options for main linear and quadratic effects evaluation is given and the simplification model of experiment results is obtained. It presents the evaluation empiric dependence of cutting conditions and clamping diameter influence on shape error forming (dynamic error. It is found that to obtain the necessary form accuracy in machining with lathe chuck equipped with the adaptive clamping jaws it is desirable to control the most statistically significant factors that actually are the cutting depth and feed.

  19. THE FOURIER SERIES USED IN ANALYSE OF THE CAM MECHANISMS FOR THE SHOEMAKING MACHINES (PART I

    Directory of Open Access Journals (Sweden)

    IOVAN-DRAGOMIR Alina

    2016-05-01

    Full Text Available A computer assisted procedure for the cinematic analysis of the mechanism of a cam is essential in making a certain type of research operations. They mainly refer to the optimization of operations running on specific machinery, or to the re-design of the mechanism, in order to make the mechanism digital. This analysis seems even more important, when we consider the fact that most of the machines used in shoe industry nowadays use a cam mechanism. The paper is devided in two parts. In first part, it is elaborated a method of finding of a function G(x, belonging to a Fourier series, which approximates the numerical values {xi, yi}, with the biggest accuracy. Finding the function that approximates the most accurately the data set, for the position parameters of the follower S(ω, ( will lead to a complete kinematic and dynamic analysis of the cam mechanism. These values repeat with T = 2π period. In second part, the method is tasted using MatCAD work sessions which allow a numerical and graphical analysis of the mathematical relations involved, in order to test the reability of the method. The set of experimental data are resulted after measuring a cam mechanism of a machine used in shoemaking.

  20. Balancing fast-rotating parts of hand-held machine drive

    Science.gov (United States)

    Korotkov, V. S.; Sicora, E. A.; Nadeina, L. V.; Yongzheng, Wang

    2018-03-01

    The article considers the issues related to the balancing of fast rotating parts of the hand-held machine drive including a wave transmission with intermediate rolling elements, which is constructed on the basis of the single-phase collector motor with a useful power of 1 kW and a nominal rotation frequency of 15000 rpm. The forms of balancers and their location are chosen. The method of balancing is described. The scheme for determining of residual unbalance in two correction planes is presented. Measurement results are given in tables.

  1. A New Apparatus for Measuring the Temperature at Machine Parts Rotating at High Speeds

    Science.gov (United States)

    Gnam, E.

    1945-01-01

    After a brief survey of the available methods for measuring the temperatures of machine parts at high speed, in particular turbine blades and rotors, an apparatus is described which is constructed on the principle of induction. Transmission of the measuring current by sliding contacts therefore is avoided. Up-to-date experiments show that it is possible to give the apparatus a high degree of sensitivity and accuracy. In comparison with sliding contact types, the present apparatus shows the important advantage that it operates for any length of time without wear, and that the contact difficulties, particularly occurring at high sliding speeds,are avoided.

  2. 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.

  3. Efficient Parallel Sorting for Migrating Birds Optimization When Solving Machine-Part Cell Formation Problems

    Directory of Open Access Journals (Sweden)

    Ricardo Soto

    2016-01-01

    Full Text Available The Machine-Part Cell Formation Problem (MPCFP is a NP-Hard optimization problem that consists in grouping machines and parts in a set of cells, so that each cell can operate independently and the intercell movements are minimized. This problem has largely been tackled in the literature by using different techniques ranging from classic methods such as linear programming to more modern nature-inspired metaheuristics. In this paper, we present an efficient parallel version of the Migrating Birds Optimization metaheuristic for solving the MPCFP. Migrating Birds Optimization is a population metaheuristic based on the V-Flight formation of the migrating birds, which is proven to be an effective formation in energy saving. This approach is enhanced by the smart incorporation of parallel procedures that notably improve performance of the several sorting processes performed by the metaheuristic. We perform computational experiments on 1080 benchmarks resulting from the combination of 90 well-known MPCFP instances with 12 sorting configurations with and without threads. We illustrate promising results where the proposal is able to reach the global optimum in all instances, while the solving time with respect to a nonparallel approach is notably reduced.

  4. Research status in ultra-precision machining of silicon carbide parts by oxidation-assisted polishing

    Directory of Open Access Journals (Sweden)

    Xinmin SHEN

    2016-10-01

    Full Text Available Oxidation-assisted polishing is an important machining method for obtaining SiC parts with high precision. Through plasma oxidation, thermal oxidation, and anodic oxidation, soft oxide can be obtained on the RS-SiC substrate. With the assistance of abrasive polishing to remove the oxide rapidly, the material removal rate can be increased and the surface quality can be improved. The research results indicate that the surface roughness root-mean-square (RMS and roughness-average (Ra can reach 0.626 nm and 0.480 nm by plasma oxidation-assisted polishing; in thermal oxidation-assisted polishing, the RMS and Ra can be 0.920 nm and 0.726 nm; in anodic oxidation, the calculated oxidation rate is 5.3 nm/s based on Deal-Grove model, and the RMS and Ra are 4.428 nm and 3.453 nm respectively in anodic oxidation-assisted polishing. The oxidation-assisted polishing can be propitious to improve the process level in machining RS-SiC, which would promote the application of SiC parts in optics and ceramics fields.

  5. Finite Element Analysis of Warpage in Laminated Aluminium Alloy Plates for Machining of Primary Aeronautic Parts

    International Nuclear Information System (INIS)

    Reis, A. C.; Moreira Filho, L. A.; Menezes, M. A.

    2007-01-01

    The aim of this paper consists in presenting a method of simulating the warpage in 7xxx series aluminium alloy plates. To perform this simulation finite element software MSC.Patran and MSC.Marc were used. Another result of this analysis will be the influence on material residual stresses induced on the raw material during the rolling process upon the warpage of primary aeronautic parts, fabricated through machining (milling) at Embraer. The method used to determinate the aluminium plate residual stress was Layer Removal Test. The numerical algorithm Modified Flavenot Method was used to convert layer removal and beam deflection in stress level. With such information about the level and profile of residual stresses become possible, during the step that anticipate the manufacturing to incorporate these values in the finite-element approach for modelling warpage parts. Based on that warpage parameter surely the products are manufactured with low relative vulnerability propitiating competitiveness and price

  6. 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

  7. Mechanical and Acoustic Characteristics of the Weld and the Base Metal Machine Part of Career Transport

    Science.gov (United States)

    Smirnov, Alexander N.; Knjaz'kov, Victor L.; Levashova, Elena E.; Ababkov, Nikolay V.; Pimonov, Maksim V.

    2018-01-01

    Currently, many industries use foreign-made machinery. There is no opportunity to purchase quality original spare parts for which machinery. Therefore, enterprises operating this equipment are looking for producers of analogues of various parts and assemblies. Quite often, the metal of such analog components turns out to be substandard, which leads to their breakdown at a much earlier date and the enterprises incur material losses. Due to the fact that the complex of performance characteristics and the resource of products are laid at the stage of their production, it is extremely important to control the quality of the raw materials. The structure, mechanical, acoustic and magnetic characteristics of metal samples of such destroyed details of quarry transport as hydraulic cylinders and detail “axis” of an excavator are investigated. A significant spread of data on the chemical composition of metal, hardness and characteristics of non-destructive testing is established, which gives grounds to recommend to manufacturers and suppliers of parts is more responsible to approach the incoming quality control. The results of the investigation of metal samples by destructive and non-destructive methods of control are compared, which showed that the spectral-acoustic method of nondestructive testing can be used to control the quality of the responsible machine parts under conditions of import substitution.

  8. 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)

  9. Integration of Error Compensation of Coordinate Measuring Machines into Feature Measurement: Part I—Model Development

    Science.gov (United States)

    Calvo, Roque; D’Amato, Roberto; Gómez, Emilio; Domingo, Rosario

    2016-01-01

    The development of an error compensation model for coordinate measuring machines (CMMs) and its integration into feature measurement is presented. CMMs are widespread and dependable instruments in industry and laboratories for dimensional measurement. From the tip probe sensor to the machine display, there is a complex transformation of probed point coordinates through the geometrical feature model that makes the assessment of accuracy and uncertainty measurement results difficult. Therefore, error compensation is not standardized, conversely to other simpler instruments. Detailed coordinate error compensation models are generally based on CMM as a rigid-body and it requires a detailed mapping of the CMM’s behavior. In this paper a new model type of error compensation is proposed. It evaluates the error from the vectorial composition of length error by axis and its integration into the geometrical measurement model. The non-explained variability by the model is incorporated into the uncertainty budget. Model parameters are analyzed and linked to the geometrical errors and uncertainty of CMM response. Next, the outstanding measurement models of flatness, angle, and roundness are developed. The proposed models are useful for measurement improvement with easy integration into CMM signal processing, in particular in industrial environments where built-in solutions are sought. A battery of implementation tests are presented in Part II, where the experimental endorsement of the model is included. PMID:27690052

  10. Integration of Error Compensation of Coordinate Measuring Machines into Feature Measurement: Part I—Model Development

    Directory of Open Access Journals (Sweden)

    Roque Calvo

    2016-09-01

    Full Text Available The development of an error compensation model for coordinate measuring machines (CMMs and its integration into feature measurement is presented. CMMs are widespread and dependable instruments in industry and laboratories for dimensional measurement. From the tip probe sensor to the machine display, there is a complex transformation of probed point coordinates through the geometrical feature model that makes the assessment of accuracy and uncertainty measurement results difficult. Therefore, error compensation is not standardized, conversely to other simpler instruments. Detailed coordinate error compensation models are generally based on CMM as a rigid-body and it requires a detailed mapping of the CMM’s behavior. In this paper a new model type of error compensation is proposed. It evaluates the error from the vectorial composition of length error by axis and its integration into the geometrical measurement model. The non-explained variability by the model is incorporated into the uncertainty budget. Model parameters are analyzed and linked to the geometrical errors and uncertainty of CMM response. Next, the outstanding measurement models of flatness, angle, and roundness are developed. The proposed models are useful for measurement improvement with easy integration into CMM signal processing, in particular in industrial environments where built-in solutions are sought. A battery of implementation tests are presented in Part II, where the experimental endorsement of the model is included.

  11. Machine Learning and Infrared Thermography for Fiber Orientation Assessment on Randomly-Oriented Strands Parts

    Science.gov (United States)

    Maldague, Xavier

    2018-01-01

    The use of fiber reinforced materials such as randomly-oriented strands has grown in recent years, especially for manufacturing of aerospace composite structures. This growth is mainly due to their advantageous properties: they are lighter and more resistant to corrosion when compared to metals and are more easily shaped than continuous fiber composites. The resistance and stiffness of these materials are directly related to their fiber orientation. Thus, efficient approaches to assess their fiber orientation are in demand. In this paper, a non-destructive evaluation method is applied to assess the fiber orientation on laminates reinforced with randomly-oriented strands. More specifically, a method called pulsed thermal ellipsometry combined with an artificial neural network, a machine learning technique, is used in order to estimate the fiber orientation on the surface of inspected parts. Results showed that the method can be potentially used to inspect large areas with good accuracy and speed. PMID:29351240

  12. Machine Learning and Infrared Thermography for Fiber Orientation Assessment on Randomly-Oriented Strands Parts.

    Science.gov (United States)

    Fernandes, Henrique; Zhang, Hai; Figueiredo, Alisson; Malheiros, Fernando; Ignacio, Luis Henrique; Sfarra, Stefano; Ibarra-Castanedo, Clemente; Guimaraes, Gilmar; Maldague, Xavier

    2018-01-19

    The use of fiber reinforced materials such as randomly-oriented strands has grown in recent years, especially for manufacturing of aerospace composite structures. This growth is mainly due to their advantageous properties: they are lighter and more resistant to corrosion when compared to metals and are more easily shaped than continuous fiber composites. The resistance and stiffness of these materials are directly related to their fiber orientation. Thus, efficient approaches to assess their fiber orientation are in demand. In this paper, a non-destructive evaluation method is applied to assess the fiber orientation on laminates reinforced with randomly-oriented strands. More specifically, a method called pulsed thermal ellipsometry combined with an artificial neural network, a machine learning technique, is used in order to estimate the fiber orientation on the surface of inspected parts. Results showed that the method can be potentially used to inspect large areas with good accuracy and speed.

  13. Attacking Machine Learning models as part of a cyber kill chain

    OpenAIRE

    Nguyen, Tam N.

    2017-01-01

    Machine learning is gaining popularity in the network security domain as many more network-enabled devices get connected, as malicious activities become stealthier, and as new technologies like Software Defined Networking emerge. Compromising machine learning model is a desirable goal. In fact, spammers have been quite successful getting through machine learning enabled spam filters for years. While previous works have been done on adversarial machine learning, none has been considered within...

  14. 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.

  15. Machining NiTi micro-parts by micro-milling

    International Nuclear Information System (INIS)

    Weinert, K.; Petzoldt, V.

    2008-01-01

    The machinability of NiTi by milling has been examined using solid carbide end milling cutters. First results were obtained from machining simple slots applying TiAlN-coated tools with a diameter of 0.4 mm. The machining process was evaluated in terms of tool wear, cutting forces and machining quality. The tool wear and work piece quality was analysed with a scanning electron microscope and a white-light confocal microscope. Despite the poor machinability of NiTi good results concerning tool wear and shape accuracy of the milled slots were achieved. Essential for a good machining result is the application of minimum quantity lubrication. This clearly reduces NiTi adherences compared to dry machining. Work piece quality is improved and tool life is extended. Based on these results different structures could be produced by micro-milling

  16. Mandibular Ramus Notching As a Tool for Sexual Dimorphism

    Directory of Open Access Journals (Sweden)

    Bibhuti Bhusana Panda

    2016-02-01

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

  17. 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)

  18. 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.

  19. Candida and Fusarium species known as opportunistic human pathogens from customer-accessible parts of residential washing machines.

    Science.gov (United States)

    Babič, Monika Novak; Zalar, Polona; Ženko, Bernard; Schroers, Hans-Josef; Džeroski, Sašo; Gunde-Cimerman, Nina

    2015-03-01

    Energy constraints have altered consumer practice regarding the use of household washing machines. Washing machines were developed that use lower washing temperatures, smaller amounts of water and biodegradable detergents. These conditions may favour the enrichment of opportunistic human pathogenic fungi. We focused on the isolation of fungi from two user-accessible parts of washing machines that often contain microbial biofilms: drawers for detergents and rubber door seals. Out of 70 residential washing machines sampled in Slovenia, 79% were positive for fungi. In total, 72 strains belonging to 12 genera and 26 species were isolated. Among these, members of the Fusarium oxysporum and Fusarium solani species complexes, Candida parapsilosis and Exophiala phaeomuriformis represented 44% of fungi detected. These species are known as opportunistic human pathogens and can cause skin, nail or eye infections also in healthy humans. A machine learning analysis revealed that presence of detergents and softeners followed by washing temperature, represent most critical factors for fungal colonization. Three washing machines with persisting malodour that resulted in bad smelling laundry were analysed for the presence of fungi and bacteria. In these cases, fungi were isolated in low numbers (7.5 %), while bacteria Micrococcus luteus, Pseudomonas aeruginosa, and Sphingomonas species prevailed. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  20. Intensification of the Students' Self-Development Process When Performing Design and Settlement Works on the "Machine Parts" Course

    Science.gov (United States)

    Timerbaev, Rais Mingalievich; Muhutdinov, Rafis Habreevich; Danilov, Valeriy Fedorovich

    2015-01-01

    The article addresses issues related to the methodology of intensifying self-development process when performing design and settlement works on the "Machine Parts" course for the students studying in such areas of training as "Technology" and "Vocational Education" with the use of computer technologies. At the same…

  1. Bibliography of papers, reports, and presentations related to point-sample dimensional measurement methods for machined part evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, J.M. [Sandia National Labs., Livermore, CA (United States). Integrated Manufacturing Systems

    1996-04-01

    The Dimensional Inspection Techniques Specification (DITS) Project is an ongoing effort to produce tools and guidelines for optimum sampling and data analysis of machined parts, when measured using point-sample methods of dimensional metrology. This report is a compilation of results of a literature survey, conducted in support of the DITS. Over 160 citations are included, with author abstracts where available.

  2. Complete Absence of Suprascapular Notch: A Case Report

    Directory of Open Access Journals (Sweden)

    Rohini Mohan Pawar

    2015-10-01

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

  3. Machine Shop Suggested Job and Task Sheets. Part II. 21 Advanced Jobs.

    Science.gov (United States)

    Texas A and M Univ., College Station. Vocational Instructional Services.

    This volume consists of advanced job and task sheets adaptable for use in the regular vocational industrial education programs for the training of machinists and machine shop operators. Twenty-one advanced machine shop job sheets are included. Some or all of this material is provided for each job: an introductory sheet with aim, checking…

  4. Machine Shop Suggested Job and Task Sheets. Part I. 25 Elementary Jobs.

    Science.gov (United States)

    Texas A and M Univ., College Station. Vocational Instructional Services.

    This volume consists of elementary job and task sheets adaptable for use in the regular vocational industrial education programs for the training of machinists and machine shop operators. Twenty-five simple machine shop job sheets are included. Some or all of this material is provided for each job sheet: an introductory sheet with aim, checking…

  5. Effect of strain rate and notch geometry on tensile properties and fracture mechanism of creep strength enhanced ferritic P91 steel

    Science.gov (United States)

    Pandey, Chandan; Mahapatra, M. M.; Kumar, Pradeep; Saini, N.

    2018-01-01

    Creep strength enhanced ferritic (CSEF) P91 steel were subjected to room temperature tensile test for quasi-static (less than 10-1/s) strain rate by using the Instron Vertical Tensile Testing Machine. Effect of different type of notch geometry, notch depth and angle on mechanical properties were also considered for different strain rate. In quasi-static rates, the P91 steel showed a positive strain rate sensitivity. On the basis of tensile data, fracture toughness of P91 steel was also calculated numerically. For 1 mm notch depth (constant strain rate), notch strength and fracture toughness were found to be increased with increase in notch angle from 45° to 60° while the maximum value attained in U-type notch. Notch angle and notch depth has found a minute effect on P91 steel strength and fracture toughness. The fracture surface morphology was studied by field emission scanning electron microscopy (FESEM).

  6. Machinability evaluation of titanium alloys (Part 2)--Analyses of cutting force and spindle motor current.

    Science.gov (United States)

    Kikuchi, Masafumi; Okuno, Osamu

    2004-12-01

    To establish a method of determining the machinability of dental materials for CAD/CAM systems, the machinability of titanium, two titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb), and free-cutting brass was evaluated through cutting force and spindle motor current. The metals were slotted using a milling machine and square end mills at four cutting conditions. Both the static and dynamic components of the cutting force represented well the machinability of the metals tested: the machinability of Ti-6Al-4V and Ti-6Al-7Nb was worse than that of titanium, while that of free-cutting brass was better. On the other hand, the results indicated that the spindle motor current was not sensitive enough to detect the material difference among the titanium and its alloys.

  7. Concepts of increasing productivity and reducing the processing cost of machine parts

    Directory of Open Access Journals (Sweden)

    О. С. Кленов

    2017-06-01

    tools. Practical recommendations for improving the machining of machine parts have been made

  8. 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

  9. Electricity of machine tool

    International Nuclear Information System (INIS)

    Gijeon media editorial department

    1977-10-01

    This book is divided into three parts. The first part deals with electricity machine, which can taints from generator to motor, motor a power source of machine tool, electricity machine for machine tool such as switch in main circuit, automatic machine, a knife switch and pushing button, snap switch, protection device, timer, solenoid, and rectifier. The second part handles wiring diagram. This concludes basic electricity circuit of machine tool, electricity wiring diagram in your machine like milling machine, planer and grinding machine. The third part introduces fault diagnosis of machine, which gives the practical solution according to fault diagnosis and the diagnostic method with voltage and resistance measurement by tester.

  10. MACHINE LEARNING IMPLEMENTATION FOR THE CLASSIFICATION OF ATTACKS ON WEB SYSTEMS. PART 2

    Directory of Open Access Journals (Sweden)

    K. Smirnova

    2017-11-01

    Full Text Available The possibility of applying machine learning for the classification of malicious requests to aWeb application is considered. This approach excludes the use of deterministic analysis systems (for example, expert systems,and is based on the application of a cascade of neural networks or perceptrons on an approximate model to the real humanbrain. The main idea of the work is to enable to describe complex attack vectors consisting of feature sets, abstract terms forcompiling a training sample, controlling the quality of recognition and classifying each of the layers (networks participatingin the work, with the ability to adjust not the entire network, but only a small part of it, in the training of which a mistake orinaccuracy crept in. The design of the developed network can be described as a cascaded, scalable neural network.When using neural networks to detect attacks on web systems, the issue of vectorization and normalization of features isacute. The most commonly used methods for solving these problems are not designed for the case of deliberate distortion ofthe signs of an attack.The proposed approach makes it possible to obtain a neural network that has been studied in more detail by small features,and also to eliminate the normalization issues in order to avoid deliberately bypassing the intrusion detection system. Byisolating one more group of neurons in the network and teaching it to samples containing various variants of circumvention ofthe attack classification, the developed intrusion detection system remains able to classify any types of attacks as well as theiraggregates, putting forward more stringent measures to counteract attacks. This allows you to follow the life cycle of theattack in more detail: from the starting trial attack to deliberate sophisticated attempts to bypass the system and introducemore decisive measures to actively counteract the attack, eliminating the chances of a false alarm system.

  11. MACHINE LEARNING IMPLEMENTATION FOR THE CLASSIFICATION OF ATTACKS ON WEB SYSTEMS. PART 1

    Directory of Open Access Journals (Sweden)

    K. Smirnova

    2017-08-01

    Full Text Available The possibility of applying machine learning is considered for the classification of malicious requests to a Web application. This approach excludes the use of deterministic analysis systems (for example, expert systems, and based on the application of a cascade of neural networks or perceptrons on an approximate model to the real human brain. The main idea of the work is to enable to describe complex attack vectors consisting of feature sets, abstract terms for compiling a training sample, controlling the quality of recognition and classifying each of the layers (networks participating in the work, with the ability to adjust not the entire network, But only a small part of it, in the training of which a mistake or inaccuracy crept in.  The design of the developed network can be described as a cascaded, scalable neural network.  The developed system of intrusion detection uses a three-layer neural network. Layers can be built independently of each other by cascades. In the first layer, for each class of attack recognition, there is a corresponding network and correctness is checked on this network. To learn this layer, we have chosen classes of things that can be classified uniquely as yes or no, that is, they are linearly separable. Thus, a layer is obtained not just of neurons, but of their microsets, which can best determine whether is there some data class in the query or not. The following layers are not trained to recognize the attacks themselves, they are trained that a set of attacks creates certain threats. This allows you to more accurately recognize the attacker's attempts to bypass the defense system, as well as classify the target of the attack, and not just its fact. Simple layering allows you to minimize the percentage of false positives.

  12. Modernity of parts in casting machines and coefficients of total productive maintenance

    Directory of Open Access Journals (Sweden)

    S. Borkowski

    2010-10-01

    Full Text Available The goal of this study is to investigate the impact of equipment efficiency in casting machines on the quality of die castings made of Al-Si alloys in consideration of their modernity. Analysis focused on two cold-chamber die-casting machines. The assessment of modernity ofthe equipment was made based on ABC analysis of technology and Parker’s scale. Then, the coefficients of total productive maintenance(TPM were employed for assessment of the efficiency of both machines. Using correlation coefficients r allowed authors to demonstrate the relationships between individual TPM coefficients and the number of non-conforming products. The finding of the study is pointing to the differences between the factors which determine the quality of castings resulting from the level of modernity of machines.

  13. Dynamic Characteristics of a New Machine for Fatigue Testing of Railway Axles – Part 2

    Directory of Open Access Journals (Sweden)

    Karel FRYDRÝŠEK

    2012-06-01

    Full Text Available There were done some proposal calculations for a new testing machine. This new testing machine is determined for a dynamic fatigue testing of railway axles. The railway axles are subjected to bending and rotation (centrifugal effects. For the right proposition of a new machine is very important to know the basic dynamic characteristics of whole system. These dynamic characteristics are solved via FEM (MSC.Marc/Mentat software in combination with SBRA (Simulation-Based Reliability Assessment Method (probabilistic Monte Carlo approach, Anthill and Python software. The proposed dimensions and springs of a new machine for fatigue testing of railway axles were used for manufacturing. Application of the SBRA method connected with FEM in these areas is a new and innovative trend in mechanics. This paper is continuation of former work (i.e. easier deterministic approach already presented in this journal in 2007.

  14. Self-Calibrated In-Process Photogrammetry for Large Raw Part Measurement and Alignment before Machining.

    Science.gov (United States)

    Mendikute, Alberto; Yagüe-Fabra, José A; Zatarain, Mikel; Bertelsen, Álvaro; Leizea, Ibai

    2017-09-09

    Photogrammetry methods are being used more and more as a 3D technique for large scale metrology applications in industry. Optical targets are placed on an object and images are taken around it, where measuring traceability is provided by precise off-process pre-calibrated digital cameras and scale bars. According to the 2D target image coordinates, target 3D coordinates and camera views are jointly computed. One of the applications of photogrammetry is the measurement of raw part surfaces prior to its machining. For this application, post-process bundle adjustment has usually been adopted for computing the 3D scene. With that approach, a high computation time is observed, leading in practice to time consuming and user dependent iterative review and re-processing procedures until an adequate set of images is taken, limiting its potential for fast, easy-to-use, and precise measurements. In this paper, a new efficient procedure is presented for solving the bundle adjustment problem in portable photogrammetry. In-process bundle computing capability is demonstrated on a consumer grade desktop PC, enabling quasi real time 2D image and 3D scene computing. Additionally, a method for the self-calibration of camera and lens distortion has been integrated into the in-process approach due to its potential for highest precision when using low cost non-specialized digital cameras. Measurement traceability is set only by scale bars available in the measuring scene, avoiding the uncertainty contribution of off-process camera calibration procedures or the use of special purpose calibration artifacts. The developed self-calibrated in-process photogrammetry has been evaluated both in a pilot case scenario and in industrial scenarios for raw part measurement, showing a total in-process computing time typically below 1 s per image up to a maximum of 2 s during the last stages of the computed industrial scenes, along with a relative precision of 1/10,000 (e.g. 0.1 mm error in 1 m) with

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

    International Nuclear Information System (INIS)

    Armbruster, M.

    1977-01-01

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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Mechanics of Cutting and Boring. Part 7. Dynamics and Energetics of Axial Rotation Machines,

    Science.gov (United States)

    1981-12-01

    systematic analytical scheme that can be used to facilitate future work on the mechanics of cutting and boring machines. In the industrial sector, rock...Proceedings. Chapter 66, p. 1149-1158. Mellor, M. and I. Hawkes (1972) How to rate a hard-rock borer. World Construction, Sept, p. 21-23. (Also in Ingenieria

  2. 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.

  3. Rotating electrical machines part 2 : methods for determining losses and efficiency of rotating electrical machinery form tests (excl. machines for traction vehicles)

    CERN Document Server

    International Electrotechnical Commission. Geneva

    1972-01-01

    Applies to d.c. machines and to a.c. synchronous and induction machines. The principles can be applied to other types of machines such as rotary converters, a.c. commutator motors and single-phase induction motors for which other methods of determining losses are used.

  4. STUDY ON THE USAGE OF SPECIAL MATERIALS FOR HIGH-STRENGTH PARTS USED IN THE MACHINES MANUFACTURING INDUSTRY

    Directory of Open Access Journals (Sweden)

    BIBU Marius

    2016-09-01

    Full Text Available Whereas formerly metallic materials were used extensively and for various purposes in the machines manufacturing industry, nowadays new materials are sought that can replace the "conventional" machines manufacturing materials with new ones. This is especially challenging in areas where parts need to be able to withstand very tough conditions, such as high temperatures or large forces applied to them. The current paper intends to analyze some of the most widely used materials for high-strength applications. A special focus in this regard is on the one hand in fiber-reinforced composite materials with the polymer matrix and on the other hand on basalt. The most important properties, processing technologies and applications of these materials are analyzed and discussed and conclusions are drawn regarding their compatibility with the intended purpose.

  5. National machine guarding program: Part 2. Safety management in small metal fabrication enterprises

    OpenAIRE

    Parker, David L.; Yamin, Samuel C.; Brosseau, Lisa M.; Xi, Min; Gordon, Robert; Most, Ivan G.; Stanley, Rodney

    2015-01-01

    Background Small manufacturing businesses often lack important safety programs. Many reasons have been set forth on why this has remained a persistent problem. Methods The National Machine Guarding Program (NMGP) was a nationwide intervention conducted in partnership with two workers' compensation insurers. Insurance safety consultants collected baseline data in 221 business using a 33?question safety management audit. Audits were completed during an interview with the business owner or manag...

  6. Machine Shop Grinding Machines.

    Science.gov (United States)

    Dunn, James

    This curriculum manual is one in a series of machine shop curriculum manuals intended for use in full-time secondary and postsecondary classes, as well as part-time adult classes. The curriculum can also be adapted to open-entry, open-exit programs. Its purpose is to equip students with basic knowledge and skills that will enable them to enter the…

  7. 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

  8. 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.

  9. Ultra-Wideband Notched Characteristic Fed by Coplanar Waveguide

    Directory of Open Access Journals (Sweden)

    Rastanto Hadinegoro

    2015-02-01

    Full Text Available In this paper, a novel Ultra-Wide Band (UWB notch patch antenna with co-planar waveguide (CPW fed is presented. This antenna only used one layer and the patch antenna is constructed on the first layer and back to back with CPW fed and bottom part is ground plane. The width notch is used to achieve the UWB characteristic. The results shown that the impedance bandwidth is 1130 MHz (1.662–2.792 GHz or about 50.7% for VSWR <2.

  10. 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

  11. 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

  12. 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...

  13. An illustration of new methods in machine condition monitoring, Part I: stochastic resonance

    International Nuclear Information System (INIS)

    Worden, K.; Antoniadou, I.; Marchesiello, S.; Mba, C.; Garibaldi, L.

    2017-01-01

    There have been many recent developments in the application of data-based methods to machine condition monitoring. A powerful methodology based on machine learning has emerged, where diagnostics are based on a two-step procedure: extraction of damage-sensitive features, followed by unsupervised learning (novelty detection) or supervised learning (classification). The objective of the current pair of papers is simply to illustrate one state-of-the-art procedure for each step, using synthetic data representative of reality in terms of size and complexity. The first paper in the pair will deal with feature extraction. Although some papers have appeared in the recent past considering stochastic resonance as a means of amplifying damage information in signals, they have largely relied on ad hoc specifications of the resonator used. In contrast, the current paper will adopt a principled optimisation-based approach to the resonator design. The paper will also show that a discrete dynamical system can provide all the benefits of a continuous system, but also provide a considerable speed-up in terms of simulation time in order to facilitate the optimisation approach. (paper)

  14. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. 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

  16. Machine Vision System for Color Sorting Wood Edge-Glued Panel Parts

    Science.gov (United States)

    Qiang Lu; S. Srikanteswara; W. King; T. Drayer; Richard Conners; D. Earl Kline; Philip A. Araman

    1997-01-01

    This paper describes an automatic color sorting system for hardwood edge-glued panel parts. The color sorting system simultaneously examines both faces of a panel part and then determines which face has the "better" color given specified color uniformity and priority defined by management. The real-time color sorting system software and hardware are briefly...

  17. National machine guarding program: Part 2. Safety management in small metal fabrication enterprises

    Science.gov (United States)

    Yamin, Samuel C.; Brosseau, Lisa M.; Xi, Min; Gordon, Robert; Most, Ivan G.; Stanley, Rodney

    2015-01-01

    Background Small manufacturing businesses often lack important safety programs. Many reasons have been set forth on why this has remained a persistent problem. Methods The National Machine Guarding Program (NMGP) was a nationwide intervention conducted in partnership with two workers' compensation insurers. Insurance safety consultants collected baseline data in 221 business using a 33‐question safety management audit. Audits were completed during an interview with the business owner or manager. Results Most measures of safety management improved with an increasing number of employees. This trend was particularly strong for lockout/tagout. However, size was only significant for businesses without a safety committee. Establishments with a safety committee scored higher (55% vs. 36%) on the safety management audit compared with those lacking a committee (P management programs were frequently absent. A safety committee appears to be a more important factor than business size in accounting for differences in outcome measures. Am. J. Ind. Med. 58:1184–1193, 2015. © 2015 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:26345591

  18. National Machine Guarding Program: Part 2. Safety management in small metal fabrication enterprises.

    Science.gov (United States)

    Parker, David L; Yamin, Samuel C; Brosseau, Lisa M; Xi, Min; Gordon, Robert; Most, Ivan G; Stanley, Rodney

    2015-11-01

    Small manufacturing businesses often lack important safety programs. Many reasons have been set forth on why this has remained a persistent problem. The National Machine Guarding Program (NMGP) was a nationwide intervention conducted in partnership with two workers' compensation insurers. Insurance safety consultants collected baseline data in 221 business using a 33-question safety management audit. Audits were completed during an interview with the business owner or manager. Most measures of safety management improved with an increasing number of employees. This trend was particularly strong for lockout/tagout. However, size was only significant for businesses without a safety committee. Establishments with a safety committee scored higher (55% vs. 36%) on the safety management audit compared with those lacking a committee (P < 0.0001). Critical safety management programs were frequently absent. A safety committee appears to be a more important factor than business size in accounting for differences in outcome measures. © 2015 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc.

  19. The IBM PC as an Online Search Machine. Part 5: Searching through Crosstalk.

    Science.gov (United States)

    Kolner, Stuart J.

    1985-01-01

    This last of a five-part series on using the IBM personal computer for online searching highlights a brief review, search process, making the connection, switching between screens and modes, online transaction, capture buffer controls, coping with options, function keys, script files, processing downloaded information, note to TELEX users, and…

  20. Sequence-dependent clustering of parts and machines : a Fuzzy ART neural network approach

    NARCIS (Netherlands)

    Suresh, N.; Slomp, J.; Kaparthi, S.

    1999-01-01

    This study addresses the problem of identifying families of parts having a similar sequence of operations. This is a prerequisite for the implementation of cellular manufacturing, group technology, just-in-time manufacturing systems, and for streamlining material flows in general. A pattern

  1. corrosion and wear resistant ternary Cr-C-N coatings deposited by the ARC PVD process for machining tools and machining parts

    International Nuclear Information System (INIS)

    Knotek, O.; Lugscheider, E.; Zimmermann, H.; Bobzin, K.

    1997-01-01

    With the deposition of PVD hard coatings on the tools applied in machining operations it is possible to achieve significant improvements in the performance and quality of the machining processes. Depending on the machined material and the operating principle, e.g. turning, milling or drilling, not only different machining parameters but also different coating materials are necessary. In interrupted cut machining of tempered steel, for example, the life time of Ti-C-N coated inserts is several times greater than the Ti-C-N coated ones. This is a result of the favourable thermophysical and tribological properties of Ti-N-C. The potential for tool protection by CrN coatings is a result of the high ductility and low internal stress of this coating materials. CrN films can be deposited with greater film thickness, still maintaining very good adhesion. This paper presents the development of new arc PVD coatings in the system Cr-C-N. Owing to the carbon content in the coating an increased hardness and a better wear behavior in comparison to CrN was expected. The effects of various carbon carrier gases on the coating properties were examined. The coating properties were investigated by mechanical tests. X-ray diffraction, SEM analysis and corrosion tests. Some of the coatings were tested in machining tests. The results of these tests are presented in this paper. (author)

  2. Your Sewing Machine.

    Science.gov (United States)

    Peacock, Marion E.

    The programed instruction manual is designed to aid the student in learning the parts, uses, and operation of the sewing machine. Drawings of sewing machine parts are presented, and space is provided for the student's written responses. Following an introductory section identifying sewing machine parts, the manual deals with each part and its…

  3. A method for simultaneous determination of wear-resistance of structurally identical machine parts with mutual friction

    International Nuclear Information System (INIS)

    Valigura, V.; Volyn'ski, A.

    1979-01-01

    There are mechanisms in the technique, boundary state of separate parts of which is determined by the process of wear of three elements of the mechanism, made of the same material (for example antifriction bearings). The main concept of wear determination in the case of such a mechanism is to conduct measurements by means of simultaneous application of three different methods, for example: the method of roentgen-fluorescence; the tracer technique with application of activation by means of irradiation by different elementary particles, practically by means of neutrons and protons; the method of artifical bases application. In the paper the method is presented having been developed in the Institute of Working Machines of the Poznan Polytechnic. This method of simultaneous investigation in the wear process of bearing rings, inner and outer, and rolling elements of roller bearings. All these elements of bearings are made of LX-15 steel. The method developed, permits to determine the wear sufficient for practical purposes sensitivity [ru

  4. Effect of Built-Up Edge Formation during Stable State of Wear in AISI 304 Stainless Steel on Machining Performance and Surface Integrity of the Machined Part.

    Science.gov (United States)

    Ahmed, Yassmin Seid; Fox-Rabinovich, German; Paiva, Jose Mario; Wagg, Terry; Veldhuis, Stephen Clarence

    2017-10-25

    During machining of stainless steels at low cutting -speeds, workpiece material tends to adhere to the cutting tool at the tool-chip interface, forming built-up edge (BUE). BUE has a great importance in machining processes; it can significantly modify the phenomenon in the cutting zone, directly affecting the workpiece surface integrity, cutting tool forces, and chip formation. The American Iron and Steel Institute (AISI) 304 stainless steel has a high tendency to form an unstable BUE, leading to deterioration of the surface quality. Therefore, it is necessary to understand the nature of the surface integrity induced during machining operations. Although many reports have been published on the effect of tool wear during machining of AISI 304 stainless steel on surface integrity, studies on the influence of the BUE phenomenon in the stable state of wear have not been investigated so far. The main goal of the present work is to investigate the close link between the BUE formation, surface integrity and cutting forces in the stable sate of wear for uncoated cutting tool during the cutting tests of AISI 304 stainless steel. The cutting parameters were chosen to induce BUE formation during machining. X-ray diffraction (XRD) method was used for measuring superficial residual stresses of the machined surface through the stable state of wear in the cutting and feed directions. In addition, surface roughness of the machined surface was investigated using the Alicona microscope and Scanning Electron Microscopy (SEM) was used to reveal the surface distortions created during the cutting process, combined with chip undersurface analyses. The investigated BUE formation during the stable state of wear showed that the BUE can cause a significant improvement in the surface integrity and cutting forces. Moreover, it can be used to compensate for tool wear through changing the tool geometry, leading to the protection of the cutting tool from wear.

  5. THE PROJECT OF THE EXPERT SYSTEM TO SUPPORTING OF SELECTION OF PARTS AND ASSEMBLIES OF MACHINES

    Directory of Open Access Journals (Sweden)

    Sebastian RZYDZIK

    2014-06-01

    Full Text Available This paper the design of the expert system that supports mechanical engineer in the process of selecting the parts and assemblies was presented. In the description of the proposed expert system, was made reference to the general form of such systems, that consist of such components as: user interface, inference engine, knowledge base and database. It also, scenario that describes the steps of the use of the proposed expert system was presented. Finally, an example of the use the expert system during the selection of the components of the drive system was shown.

  6. Understanding dental CAD/CAM for restorations--dental milling machines from a mechanical engineering viewpoint. Part B: labside milling machines.

    Science.gov (United States)

    Lebon, Nicolas; Tapie, Laurent; Duret, Francois; Attal, Jean-Pierre

    2016-01-01

    Nowadays, dental numerical controlled (NC) milling machines are available for dental laboratories (labside solution) and dental production centers. This article provides a mechanical engineering approach to NC milling machines to help dental technicians understand the involvement of technology in digital dentistry practice. The technical and economic criteria are described for four labside and two production center dental NC milling machines available on the market. The technical criteria are focused on the capacities of the embedded technologies of milling machines to mill prosthetic materials and various restoration shapes. The economic criteria are focused on investment cost and interoperability with third-party software. The clinical relevance of the technology is discussed through the accuracy and integrity of the restoration. It can be asserted that dental production center milling machines offer a wider range of materials and types of restoration shapes than labside solutions, while labside solutions offer a wider range than chairside solutions. The accuracy and integrity of restorations may be improved as a function of the embedded technologies provided. However, the more complex the technical solutions available, the more skilled the user must be. Investment cost and interoperability with third-party software increase according to the quality of the embedded technologies implemented. Each private dental practice may decide which fabrication option to use depending on the scope of the practice.

  7. Towards Compatible and Interderivable Semantic Specifications for the Scheme Programming Language, Part I: Denotational Semantics, Natural Semantics, and Abstract Machines

    DEFF Research Database (Denmark)

    Danvy, Olivier

    2009-01-01

    We derive two big-step abstract machines, a natural semantics, and the valuation function of a denotational semantics based on the small-step abstract machine for Core Scheme presented by Clinger at PLDI'98. Starting from a functional implementation of this small-step abstract machine, (1) we fus...

  8. 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

  9. 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 ...

  10. Tracer techniques for the investigation of wear mechanisms in coated or surface-treated machine parts

    International Nuclear Information System (INIS)

    Goedecke, T.; Grosch, J.

    1990-01-01

    Tracer techniques allow wear measurement down to rates of only some μg/h, and these measurements can be done continuously within an inspection test run, not requiring dismantling of the parts to be examined. The measurements revealed the materials pair of a chilled cast iron camshaft and a hard metal coated rocker arm to be superior in terms of wear behaviour over the materials pair of a malleable cast iron camshaft with induction hardening and a rocker arm with hard chromium plating. The total wear of a chilled cast iron camshaft was measured to be approx. 90% less than that of the malleable cast iron camshaft, under equal loading conditions. With the rocker arms, this ratio is approx. 1:3. Another disadvantage of the latter pair is the overall wear ratio of 19:1. The best wear resistance was measured with a TiN-coated rocker arm combined with a chilled cast iron camshaft. (orig./MM) [de

  11. 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

  12. Effects of Range of Stress and of Special Notches on Fatigue Properties of Aluminum Alloys Suitable for Airplane Propellers

    Science.gov (United States)

    Dolan, Thomas J

    1942-01-01

    Laboratory tests were made to obtain information on the load-resisting properties of X76S-T aluminum alloy when subjected to static, impact, and repeated loads. Results are presented from static-load test of unnotched specimens in tension and in torsion and of notched specimens in tension. Charpy impact values obtained from bend tests on notched specimens and tension impact values for both notched and unnotched specimens tested at several different temperatures are included. The endurance limits obtained from repeated bending fatigue tests made on three different types of testing machine are given for unnotched polished specimens, and the endurance limits of notched specimens subjected to six different ranges of bending stress are also reported. The results indicated that: (a) polished rectangular specimens had an endurance limit about 30 percent less than that obtained for round specimens; (b) a comparison of endurance limits obtained from tests on three different types of machine indicated that there was no apparent effect of speed of testing on the endurance limit for the range of speeds used (1,750 to 13,000 rpm). (c) the fatigue strength (endurance limit) of the X76S-T alloy was greatly decreased by the presence of a notch in the specimens; (d) no complete fractures of the entire specimens occurred in notched fatigue specimens when subjected to stress cycles for which the mean stress at the notch during the cycle was a compressive stress; for this test condition a microscopic cracking occurred near the root of the notch and was used as a criterion of failure of the specimen. (e) as the mean stress at the notch was decreased from a tensile (+) stress to a compressive (-) stress, it was found that the alternating stress that could be superimposed on the mean stress in the cycle without causing failure of the specimens was increased.

  13. Towards Compatible and Interderivable Semantic Specifications for the Scheme Programming Language, Part I: Denotational Semantics, Natural Semantics, and Abstract Machines

    DEFF Research Database (Denmark)

    Danvy, Olivier

    2008-01-01

    We derive two big-step abstract machines, a natural semantics, and the valuation function of a denotational semantics based on the small-step abstract machine for Core Scheme presented by Clinger at PLDI'98. Starting from a functional implementation of this small-step abstract machine, (1) we fuse...... its transition function with its driver loop, obtaining the functional implementation of a big-step abstract machine; (2) we adjust this big-step abstract machine so that it is in defunctionalized form, obtaining the functional implementation of a second big-step abstract machine; (3) we...... refunctionalize this adjusted abstract machine, obtaining the functional implementation of a natural semantics in continuation style; and (4) we closure-unconvert this natural semantics, obtaining a compositional continuation-passing evaluation function which we identify as the functional implementation...

  14. 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.

  15. Identification of internal defects of hardfacing coatings in regeneration of machine parts

    Directory of Open Access Journals (Sweden)

    Józwik Jerzy

    2017-01-01

    Full Text Available The quality control of hardfacing is one of the areas where non-destructive testing is applied. To detect defects and inconsistencies in the industrial practice one uses the same methods as in the testing of welded joints. Computed Tomography is a type of X-ray spectroscopy. It is used as a diagnostic method that allows to obtain layered images of examined hardfacing. The paper presents the use of Computed Tomography for the evaluation of defects of hardfacing parts and errors. Padding welds were produced using GMA consumable electrode welding with CO2 active gas. The padding material used were cored wires FILTUB DUR 16, and ones produced from a Fe-Mn-C-Si-Cr-Mo-Ti-W alloy. The layers were padded on to different surfaces: C45, 165CrV12, 42CrMo4, S235JR steel. Typical defects occurring in the pads and the influence of the type of wire on the concentration of defects were characterized. The resulting pads were characterized by occurring inconsistencies taking the form of pores, intrusions and fractures.

  16. Identification of internal defects of hardfacing coatings in regeneration of machine parts

    Science.gov (United States)

    Józwik, Jerzy; Dziedzic, Krzysztof; Pashechko, Mykhalo; Łukasiewicz, Andrzej

    2017-10-01

    The quality control of hardfacing is one of the areas where non-destructive testing is applied. To detect defects and inconsistencies in the industrial practice one uses the same methods as in the testing of welded joints. Computed Tomography is a type of X-ray spectroscopy. It is used as a diagnostic method that allows to obtain layered images of examined hardfacing. The paper presents the use of Computed Tomography for the evaluation of defects of hardfacing parts and errors. Padding welds were produced using GMA consumable electrode welding with CO2 active gas. The padding material used were cored wires FILTUB DUR 16, and ones produced from a Fe-Mn-C-Si-Cr-Mo-Ti-W alloy. The layers were padded on to different surfaces: C45, 165CrV12, 42CrMo4, S235JR steel. Typical defects occurring in the pads and the influence of the type of wire on the concentration of defects were characterized. The resulting pads were characterized by occurring inconsistencies taking the form of pores, intrusions and fractures.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Pseudointercondylar notch sign: manifestation of osteochondritis dissecans of the trochlea

    International Nuclear Information System (INIS)

    Pruthi, Sumit; Parnell, Shawn E.; Thapa, Mahesh M.

    2009-01-01

    Osteochondritis dissecans (OCD) is an idiopathic condition affecting the articular epiphysis. Initially described in the knee, this entity affects several other parts of the body such as the talar dome, tarsal navicular, and femoral capital epiphysis. OCD of the elbow primarily involves the capitellum. OCD involving the trochlea has rarely been reported. We describe an unusual and interesting case of OCD affecting the trochlea, mimicking a pseudointercondylar notch. (orig.)

  19. Notch Signaling Is Associated With ALDH Activity And An Aggressive Metastatic Phenotype In Murine Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong eMu

    2013-06-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone, and pulmonary metastatic disease accounts for nearly all mortality. However, little is known about the biochemical signaling alterations that drive the progression of metastatic disease. Two murine OS cell populations, K7M2 and K12, are clonally related but differ significantly in their metastatic phenotypes and therefore represent excellent tools for studying metastatic OS molecular biology. K7M2 cells are highly metastatic, whereas K12 cells display limited metastatic potential. Here we report that the expression of Notch genes (Notch1, 2, 4 are up-regulated, including downstream targets Hes1 and Stat3, in the highly metastatic K7M2 cells compared to the less metastatic K12 cells, indicating that the Notch signaling pathway is more active in K7M2 cells. We have previously described that K7M2 cells exhibit higher levels of aldehyde dehydrogenase (ALDH activity. Here we report that K7M2 cell ALDH activity is reduced with Notch inhibition, suggesting that ALDH activity may be regulated in part by the Notch pathway. Notch signaling is also associated with increased resistance to oxidative stress, migration, invasion, and VEGF expression in vitro. However, Notch inhibition did not significantly alter K7M2 cell proliferation. In conclusion, we provide evidence that Notch signaling is associated with ALDH activity and increased metastatic behavior in OS cells. Both Notch and ALDH are putative molecular targets for the treatment and prevention of OS metastasis.

  20. Towards Compatible and Interderivable Semantic Specifications for the Scheme Programming Language, Part II: Reduction Semantics and Abstract Machines

    DEFF Research Database (Denmark)

    Biernacka, Malgorzata; Danvy, Olivier

    2008-01-01

    We present a context-sensitive reduction semantics for a lambda-calculus with explicit substitutions and store and we show that the functional implementation of this small-step semantics mechanically corresponds to that of an abstract machine. This abstract machine is very close to the abstract m...... machine for Core Scheme presented by Clinger at PLDI'98. This lambda-calculus with explicit substitutions and store therefore aptly accounts for Core Scheme....

  1. 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.

  2. 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...

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

    Science.gov (United States)

    Hill, Charles S.; Oliveras, Ovidio M.

    2011-01-01

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

  4. Observations of the severity of notch-root radius in initiation of subcritical crack growth

    International Nuclear Information System (INIS)

    Reuter, W.G.; Eiholzer, C.R.; Tupper, M.A.

    1981-01-01

    Slow bend tests were conducted on Charpy specimens containing precracks or machined notches of 0.10 or 0.25 mm radius. The test specimens were fabricated from three heats of annealed Type 304 stainless steel. The purpose of these tests was to examine the effects of notch root radius, in very ductile materials, on initiation of subcritical crack growth. In addition, it was intended to establish the critical values of J, COD, etc. for the single-edge notch specimen for comparison with results obtained from specimens containing surface flaws. This paper will briefly describe only those results of the calculation for J. The tests were monitored by acoustic emission to identify the load corresponding to initiation of subcritical crack growth, by a crack-opening displacement gage (COD), by cross-head displacement, and by stop-action photography

  5. The neural network as a part of decision support system for quality management for production objects in machining process

    Directory of Open Access Journals (Sweden)

    Cherepanska I.Yu.

    2017-04-01

    Full Text Available The research discusses the use of artificial neural networks (ANN as components of a decision support system (DSS to automate quality control manufacturing facilities machining business at the production, which should be focused on the analysis of large amounts of heterogeneous information. The necessity to use ANN as a part of DSS is justified by the fact that quality control during production is multistage and time-consuming process that is formalized difficult, and moreover requires considerable information and material costs for the efficiency of manufacturing operations performed. Taking into account the existing experience of successful use of ANN to solve difficult formal problems associated with handling large volumes of diverse and rapidly changing information, the authors synthesized ANN for automated determination of the causes deterioration of the quality of production objects (PO in the performance of manufacturing operations application. Particular attention is paid to the definition of the dimension of the hidden layer ANN synthesized due to the fact that today still there is no analytical expression to determine the dimension of the hidden layer ANN and size of the latter is determined only by the experimental results of ANN several different structures by comparison the results, in particular the value of mean square error.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Lijun Zhang

    2014-01-01

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

  8. Analysis of machining and machine tools

    CERN Document Server

    Liang, Steven Y

    2016-01-01

    This book delivers the fundamental science and mechanics of machining and machine tools by presenting systematic and quantitative knowledge in the form of process mechanics and physics. It gives readers a solid command of machining science and engineering, and familiarizes them with the geometry and functionality requirements of creating parts and components in today’s markets. The authors address traditional machining topics, such as: single and multiple point cutting processes grinding components accuracy and metrology shear stress in cutting cutting temperature and analysis chatter They also address non-traditional machining, such as: electrical discharge machining electrochemical machining laser and electron beam machining A chapter on biomedical machining is also included. This book is appropriate for advanced undergraduate and graduate mechani cal engineering students, manufacturing engineers, and researchers. Each chapter contains examples, exercises and their solutions, and homework problems that re...

  9. Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

  10. Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

  11. Size effect studies on notched tensile specimens at room temperature and 400 {sup o}C

    Energy Technology Data Exchange (ETDEWEB)

    Krompholz, K.; Kamber, J.; Groth, E.; Kalkhof, D

    2000-07-01

    One of the objectives of the REVISA project (REactor Vessel Integrity in Severe Accidents) is to assess the size effect related to deformation and failure models as well as material data under quasistatic and dynamic conditions in homogeneous and non-homogeneous states of strain. For these investigations the reactor pressure vessel material 20 MnMoNi 55 was selected. It was subjected to a size effect study on notched scaled tensile specimens of three sizes. Two strain rates (2*10{sup -5}/s and 10{sup -3}/s) and two temperatures (room temperature and 400 {sup o}C) were selected. The investigations are aimed at a support for a gradient plasticity approach to size effects. Test on the small specimens (diameters 2.4 and 7.2 mm) were performed at an electromechanical test machine, while the large specimens (diameter 24 mm) had to be tested at a servohydraulical closed loop test machine with a force capacity of 1000 kN. All characteristic values were found to be size dependent. A selected semicircular notch retains its shape. The notch opening becomes a chord of a segment of a circle, the notch shape at fracture is a segment of a circle. (author)

  12. 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.

  13. Maintenance Of The EPS 3000 Electron Beam Machine As Part Of Quality Assurance Program For Irradiation Service At ALURTRON, Nuclear Malaysia

    International Nuclear Information System (INIS)

    Siti Aiasah Hashim; Shari Jahar; Ayub Muhammad; Azmi Ali; Abdul Basit Shafiei; Sarada Idris

    2012-01-01

    The EPS 3000 electron beam machine is the first of its kind in the country and was installed in Nuclear Malaysia in 1991. It was manufactured by Nissin High Voltage having variable energies from 0.5 to 3.0 MeV and maximum power of 90 kW. The machine is currently used for commercial irradiation that serves local industries. The Alurtron facility where the EPS is housed is an ISO 9000 certified plant. Maintenance program for the EPS is an essential part of Alurtron's Quality Assurance program. This is to ensure that the machine is in good condition and can serve the customer as the demand requires. Preventive maintenance is carried out at scheduled period based on recommendation of the machine's manufacturer. Corrective maintenance and repairs are carried out in-house by Alurtron's technical staff. Assistance may be sought from the manufacturer if necessary. Over the years, Alurtron had built its own capabilities in term of operation and maintenance of Cockcroft Walton type electron beam machine. (author)

  14. Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo.

    Directory of Open Access Journals (Sweden)

    Kristina Preuße

    2015-06-01

    Full Text Available Notch signalling is a fundamental pathway that shapes the developing embryo and sustains adult tissues by direct communication between ligand and receptor molecules on adjacent cells. Among the ligands are two Delta paralogues, DLL1 and DLL4, that are conserved in mammals and share a similar structure and sequence. They activate the Notch receptor partly in overlapping expression domains where they fulfil redundant functions in some processes (e.g. maintenance of the crypt cell progenitor pool. In other processes, however, they appear to act differently (e.g. maintenance of foetal arterial identity raising the questions of how similar DLL1 and DLL4 really are and which mechanism causes the apparent context-dependent divergence. By analysing mice that conditionally overexpress DLL1 or DLL4 from the same genomic locus (Hprt and mice that express DLL4 instead of DLL1 from the endogenous Dll1 locus (Dll1Dll4ki, we found functional differences that are tissue-specific: while DLL1 and DLL4 act redundantly during the maintenance of retinal progenitors, their function varies in the presomitic mesoderm (PSM where somites form in a Notch-dependent process. In the anterior PSM, every cell expresses both Notch receptors and ligands, and DLL1 is the only activator of Notch while DLL4 is not endogenously expressed. Transgenic DLL4 cannot replace DLL1 during somitogenesis and in heterozygous Dll1Dll4ki/+ mice, the Dll1Dll4ki allele causes a dominant segmentation phenotype. Testing several aspects of the complex Notch signalling system in vitro, we found that both ligands have a similar trans-activation potential but that only DLL4 is an efficient cis-inhibitor of Notch signalling, causing a reduced net activation of Notch. These differential cis-inhibitory properties are likely to contribute to the functional divergence of DLL1 and DLL4.

  15. Notch and VEGF Interactions in Breast Cancer

    National Research Council Canada - National Science Library

    Shawber, Carrie J

    2006-01-01

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

  16. Notch signaling in embryology and cancer

    National Research Council Canada - National Science Library

    Reichrath, J; Reichrath, Sandra

    2012-01-01

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

  17. Machine testning

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with a laboratory exercise of 3 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercise includes a series of tests carried out by the student on a conventional and a numerically controled lathe, respectively. This document...

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

    Science.gov (United States)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  20. Optimization processing of the elementary surfaces of the composite body parts on machines such as «machining center»

    Directory of Open Access Journals (Sweden)

    Євген Іванович Іванов

    2015-11-01

    Full Text Available This article describes the processing optimization and minimizing the number of tool changes. Two versions for setting the processing scheme, according to the rules for processing scheme setting for the «processing center» machines were offered. In the first version, according to the classical technology processing of each hole is carried out over all the passes, providing for the required accuracy of sizes and shapes. In the second version the number of tool changes is minimized. This method consists of dividing all the holes into groups according to their diameters. All the holes of the same diameter are processed over one pass; then the tools are changed and the holes of some other diameter are processed and so on. Let us consider the optimization problem. The traveling salesman problem - is one of the most famous problems in the theory of combinatorics. The problem is as follows: a travelling salesman (hawker must find the most advantageous route coming out of a town and visiting all other towns from 2,3,…to...n just once in an unknown order and come back to the first town. The distances between all the towns are known. It is necessary to determine in what order the Salesman must visit the towns so that the route should be the shortest. There exists just one absolutely precise algorithm - sorting options. This option is the longest, so the most inefficient. There are also simpler methods to solve the traveling salesman problem: the branch and bound algorithm and ant colony method and method of genetic algorithms

  1. 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

  2. The learning machine in quantitative chemical analysis : Part I. Anodic Stripping Voltammetry of Cadmium, Lead and Thallium

    NARCIS (Netherlands)

    Bos, M.; Jasink, G.

    1978-01-01

    The linear learning machine method was applied to the determination of cadmium, lead and thallium down to 10-8 M by anodic stripping voltammetry at a hanging mercury drop electrode. With a total of three trained multicategory classifiers, concentrations of Cd, Pb and Tl could be predicted with an

  3. Towards Compatible and Interderivable Semantic Specifications for the Scheme Programming Language, Part II: Reduction Semantics and Abstract Machines

    DEFF Research Database (Denmark)

    Biernacka, Malgorzata; Danvy, Olivier

    2009-01-01

    We present a context-sensitive reduction semantics for a lambmda-calculus with explicit substitutions and we show that the functional implementation of this small-step semantics mechanically corresponds to that of the abstract machine for Core Scheme presented by Clinger at PLDI'98, including fir...

  4. Machine Protection

    International Nuclear Information System (INIS)

    Zerlauth, Markus; Schmidt, Rüdiger; Wenninger, Jörg

    2012-01-01

    The present architecture of the machine protection system is being recalled and the performance of the associated systems during the 2011 run will be briefly summarized. An analysis of the causes of beam dumps as well as an assessment of the dependability of the machine protection systems (MPS) itself is being presented. Emphasis will be given to events that risked exposing parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems will be evaluated along with their impact on the 2012 run. The role of rMPP during the various operational phases (commissioning, intensity ramp up, MDs...) will be discussed along with a proposal for the intensity ramp up for the start of beam operation in 2012

  5. Machine Protection

    CERN Document Server

    Zerlauth, Markus; Wenninger, Jörg

    2012-01-01

    The present architecture of the machine protection system is being recalled and the performance of the associated systems during the 2011 run will be briefly summarized. An analysis of the causes of beam dumps as well as an assessment of the dependability of the machine protection systems (MPS) itself is being presented. Emphasis will be given to events that risked exposing parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems will be evaluated along with their impact on the 2012 run. The role of rMPP during the various operational phases (commissioning, intensity ramp up, MDs...) will be discussed along with a proposal for the intensity ramp up for the start of beam operation in 2012.

  6. Machine Protection

    Energy Technology Data Exchange (ETDEWEB)

    Zerlauth, Markus; Schmidt, Rüdiger; Wenninger, Jörg [European Organization for Nuclear Research, Geneva (Switzerland)

    2012-07-01

    The present architecture of the machine protection system is being recalled and the performance of the associated systems during the 2011 run will be briefly summarized. An analysis of the causes of beam dumps as well as an assessment of the dependability of the machine protection systems (MPS) itself is being presented. Emphasis will be given to events that risked exposing parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems will be evaluated along with their impact on the 2012 run. The role of rMPP during the various operational phases (commissioning, intensity ramp up, MDs...) will be discussed along with a proposal for the intensity ramp up for the start of beam operation in 2012.

  7. Feasibility Study for Using a Linear Transverse Flux Machine as part of the Structure of Point Absorber Wave Energy Converter

    Directory of Open Access Journals (Sweden)

    Ilana Pereira da Costa Cunha

    2017-10-01

    Full Text Available This is a feasibility study for the generation of wave energy by means of a transverse flux machine connected to a device for converting wave energy known as Point Absorber. The article contains literature review on the topic and analysis of data obtained by means of a prototype built in the laboratory. Based on the results, the study concludes that this use is feasible.

  8. An Investigation into the Comparative Costs of Additive Manufacture vs. Machine from Solid for Aero Engine Parts

    Science.gov (United States)

    2006-05-01

    welding power sources are not totally efficient at converting power drawn from the wall into heat energy used for the welding process . TIG sources are...Powder bed + Laser • Wire + Laser • Wire + Electron Beam • Wire + TIG Each system has its own unique attributes in terms of process variables...relative economics of producing a near net shape by Additive Manufacturing (AM) processes compared with traditional machine from solid processes (MFS

  9. 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)

  10. 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....

  11. Mechanism of Notch Pathway Activation and Its Role in the Regulation of Olfactory Plasticity in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Simon Kidd

    Full Text Available The neural plasticity of sensory systems is being increasingly recognized as playing a role in learning and memory. We have previously shown that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila melanogaster olfactory receptor neurons (ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. In this paper we address how long-term exposure to odor activates Notch and how Notch in conjunction with chronic odor mediates olfactory plasticity. We show that upon chronic odor exposure a non-canonical Notch pathway mediates an increase in the volume of glomeruli by a mechanism that is autonomous to ORNs. In addition to activating a pathway that is autonomous to ORNs, chronic odor exposure also activates the Notch ligand Delta in second order projection neurons (PNs, but this does not appear to require acetylcholine receptor activation in PNs. Delta on PNs then feeds back to activate canonical Notch signaling in ORNs, which restricts the extent of the odor induced increase in glomerular volume. Surprisingly, even though the pathway that mediates the increase in glomerular volume is autonomous to ORNs, nonproductive transsynaptic Delta/Notch interactions that do not activate the canonical pathway can block the increase in volume. In conjunction with chronic odor, the canonical Notch pathway also enhances cholinergic activation of PNs. We present evidence suggesting that this is due to increased acetylcholine release from ORNs. In regulating physiological plasticity, Notch functions solely by the canonical pathway, suggesting that there is no direct connection between morphological and physiological plasticity.

  12. 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.

  13. Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

    Directory of Open Access Journals (Sweden)

    Angelo Sparaneo

    2016-01-01

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

  14. 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

  15. 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

  16. The Buttonhole Machine. Module 13.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bottonhole machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: performing special operations on the buttonhole machine (parts and purpose) and performing special operations on the buttonhole machine (gauged buttonholes). For each topic these components are…

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

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2009-08-01

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

  18. 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.

  19. 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.

  20. 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.

  1. MANAGEMENT PROCEDURE OF SUPPLIES OF UNITS, MATERIALS AND CONSTITUENT PARTS FOR REPAIR AND MAINTENANCE SUPPORT OF TRANSPORT AND PRODUCTION MACHINES

    Directory of Open Access Journals (Sweden)

    Victor Yurievich Stroganov

    2017-05-01

    Full Text Available This article considers a question of creation of schemes and sequence of passing of the main stages of process of execution of repair and maintenance works order taking into account formation of stocks of necessary spare parts, materials and constituent parts. Models of an input stream are offered for inventory control system, which are rather adequately described by autoregressive models of order two.

  2. 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.

  3. Non-conventional electrical machines

    CERN Document Server

    Rezzoug, Abderrezak

    2013-01-01

    The developments of electrical machines are due to the convergence of material progress, improved calculation tools, and new feeding sources. Among the many recent machines, the authors have chosen, in this first book, to relate the progress in slow speed machines, high speed machines, and superconducting machines. The first part of the book is dedicated to materials and an overview of magnetism, mechanic, and heat transfer.

  4. 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

  5. Self-Improving CNC Milling Machine

    OpenAIRE

    Spilling, Torjus

    2014-01-01

    This thesis is a study of the ability of a CNC milling machine to create parts for itself, and an evaluation of whether or not the machine is able to improve itself by creating new machine parts. This will be explored by using off-the-shelf parts to build an initial machine, using 3D printing/rapid prototyping to create any special parts needed for the initial build. After an initial working machine is completed, the design of the machine parts will be adjusted so that the machine can start p...

  6. Task 3: new man-machine interfaces in nuclear power plants. Part 1 executive summary and summary of reports

    International Nuclear Information System (INIS)

    1993-11-01

    The present document summarises the reports provided by the member countries reflecting the actual status of consideration of Human Factors principles for the nuclear power plants. The adoption of Human Factor principles, in conjunction with the availability of advanced digital technology, has already led to the addition of computerised operator aids to almost all the operating plants in the member countries and to the study and the design of fully digitized control rooms for the future plants in some of them. As regards the licensing issue, many uncertainties still exist on the methodology and tools to be used and no internationally accepted standards have been established by now, especially for the software to be used in safety systems of nuclear power plants. The licensing of Man-Machine Interfaces (MMIs) is, in conclusion, at the very beginning of the process as in the past not enough attention has been given to human factor and software licensing aspects. In some countries the preparation of new ad hoc guidelines, or the updating of the existing one for digital equipment, are under way. Several examples of licensing of MMIs in countries where control room systems are safety classified, are described in the report highlighting the different approaches adopted. Important aspects of the design and implementation process of MMIs are the evaluation / validation phase, the provision of advanced alarm system supporting the operator in his supervisory tasks (and avoiding at the same time the problems related to information overload); the use of Artificial Intelligence under the form of Expert Systems is another opportunity that can be applied to several areas of plant supervision and control such as real time diagnostics, decision support, emergency response in order to enhance operator understanding of the plant status in whatever situation and therefore to help him in the operational decision-making process. The proper balance between automation and human actions is

  7. Design of UWB Filter with WLAN Notch

    Directory of Open Access Journals (Sweden)

    Harish Kumar

    2012-01-01

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

  8. Machine Tool Software

    Science.gov (United States)

    1988-01-01

    A NASA-developed software package has played a part in technical education of students who major in Mechanical Engineering Technology at William Rainey Harper College. Professor Hack has been using (APT) Automatically Programmed Tool Software since 1969 in his CAD/CAM Computer Aided Design and Manufacturing curriculum. Professor Hack teaches the use of APT programming languages for control of metal cutting machines. Machine tool instructions are geometry definitions written in APT Language to constitute a "part program." The part program is processed by the machine tool. CAD/CAM students go from writing a program to cutting steel in the course of a semester.

  9. A nucleonic weighing machine

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The design and operation of a nucleonic weighing machine fabricated for continuous weighing of material over conveyor belt are described. The machine uses a 40 mCi cesium-137 line source and a 10 litre capacity ionization chamber. It is easy to maintain as there are no moving parts. It can also be easily removed and reinstalled. (M.G.B.)

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

    Directory of Open Access Journals (Sweden)

    Hong-Mei Zhang

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

  11. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Liu, Jianwen, E-mail: liujian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Ni, Lei, E-mail: nilei625@yahoo.com [Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai 200025 (China)

    2014-07-18

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

  12. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

    International Nuclear Information System (INIS)

    Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei

    2014-01-01

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-10

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

  14. Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct.

    Directory of Open Access Journals (Sweden)

    Ming Ma

    2007-01-01

    Full Text Available Pronephros, a developmental model for adult mammalian kidneys (metanephros and a functional kidney in early teleosts, consists of glomerulus, tubule, and duct. These structural and functional elements are responsible for different kidney functions, e.g., blood filtration, waste extraction, salt recovery, and water balance. During pronephros organogenesis, cell differentiation is a key step in generating different cell types in specific locations to accomplish designated functions. However, it is poorly understood what molecules regulate the differentiation of different cell types in different parts of the kidney. Two types of epithelial cells, multi-cilia cells and principal cells, are found in the epithelia of the zebrafish distal pronephric duct. While the former is characterized by at least 15 apically localized cilia and expresses centrin2 and rfx2, the latter is characterized by a single primary cilium and sodium pumps. Multi-cilia cells and principal cells differentiate from 17.5 hours post-fertilization onwards in a mosaic pattern. Jagged2a-Notch1a/Notch3-Her9 is responsible for specification and patterning of these two cell types through a lateral inhibition mechanism. Furthermore, multi-cilia cell hyperplasia was observed in mind bomb mutants and Mind bomb was shown to interact with Jagged2a and facilitate its internalization. Taken together, our findings add a new paradigm of Notch signaling in kidney development, namely, that Jagged2a-Notch signaling modulates cell fate choice in a nephric segment, the distal pronephric duct.

  15. 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

  16. 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

  17. Report of the Error and Emittance Task Force on the superconducting super collider: Part 1, Resistive machines

    International Nuclear Information System (INIS)

    1993-10-01

    A review of the design and specifications of the resistive accelerators in the SSC complex was conducted during the past year. This review was initiated in response to a request from the SSC Project Manager. The Error and Emittance Task Force was created October 30, 1992, and charged with reviewing issues associated with the specification of errors and tolerances throughout the injector chain and in the Collider, and to optimize the global error budget. Effects which directly impact the emittance budget were of prime importance. The Task Force responded to three charges: Examination of the resistive accelerators and their injection and extraction systems; examination of the connecting beamlines and the overall approach taken in their design; and global filling, timing, and synchronization issues. The High Energy Booster and the Collider were deemed to be sufficiently different from the resistive accelerators that it was decided to treat them as a separate group. They will be the subject of a second part to this report

  18. 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 ...

  19. 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...

  20. Precision machining commercialization

    International Nuclear Information System (INIS)

    1978-01-01

    To accelerate precision machining development so as to realize more of the potential savings within the next few years of known Department of Defense (DOD) part procurement, the Air Force Materials Laboratory (AFML) is sponsoring the Precision Machining Commercialization Project (PMC). PMC is part of the Tri-Service Precision Machine Tool Program of the DOD Manufacturing Technology Five-Year Plan. The technical resources supporting PMC are provided under sponsorship of the Department of Energy (DOE). The goal of PMC is to minimize precision machining development time and cost risk for interested vendors. PMC will do this by making available the high precision machining technology as developed in two DOE contractor facilities, the Lawrence Livermore Laboratory of the University of California and the Union Carbide Corporation, Nuclear Division, Y-12 Plant, at Oak Ridge, Tennessee

  1. 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.

  2. 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.

  3. Precracking of round notched bars. Progress Report

    International Nuclear Information System (INIS)

    Scibetta, M.

    1996-02-01

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

  4. 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.

  5. Notch signaling, the segmentation clock, and the patterning of vertebrate somites

    Directory of Open Access Journals (Sweden)

    Lewis Julian

    2009-05-01

    Full Text Available Abstract The Notch signaling pathway has multifarious functions in the organization of the developing vertebrate embryo. One of its most fundamental roles is in the emergence of the regular pattern of somites that will give rise to the musculoskeletal structures of the trunk. The parts it plays in the early operation of the segmentation clock and the later definition and differentiation of the somites are beginning to be understood.

  6. 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)

  7. 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 ...

  8. 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...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Yafei Ma

    2017-05-01

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

  11. Nuclear reactor machine refuelling system

    International Nuclear Information System (INIS)

    Cashen, W.S.; Erwin, D.

    1977-01-01

    Part of an on-line fuelling machine for a CANDU pressure-tube reactor is described. The present invention provides a refuelling machine wherein the fuelling components, including the fuel carrier and the closure adapter, are positively positioned and retained within the machine magazine or positively secured to the machine charge tube head, and cannot be accidentally disengaged as in former practice. The positive positioning devices include an arcuate keeper plate. Simplified hooked fingers are used. (NDH)

  12. Inductive Displacement Sensors with a Notch Filter for an Active Magnetic Bearing System

    Directory of Open Access Journals (Sweden)

    Seng-Chi Chen

    2014-07-01

    Full Text Available Active magnetic bearing (AMB systems support rotating shafts without any physical contact, using electromagnetic forces. Each radial AMB uses two pairs of electromagnets at opposite sides of the rotor. This allows the rotor to float in the air gap, and the machine to operate without frictional losses. In active magnetic suspension, displacement sensors are necessary to detect the radial and axial movement of the suspended object. In a high-speed rotating machine equipped with an AMB, the rotor bending modes may be limited to the operating range. The natural frequencies of the rotor can cause instability. Thus, notch filters are a useful circuit for stabilizing the system. In addition, commercial displacement sensors are sometimes not suitable for AMB design, and cannot filter the noise caused by the natural frequencies of rotor. Hence, implementing displacement sensors based on the AMB structure is necessary to eliminate noises caused by natural frequency disturbances. The displacement sensor must be highly sensitive in the desired working range, and also exhibit a low interference noise, high stability, and low cost. In this study, we used the differential inductive sensor head and lock-in amplifier for synchronous demodulation. In addition, an active low-pass filter and a notch filter were used to eliminate disturbances, which caused by natural frequencies. As a consequence, the inductive displacement sensor achieved satisfactory linearity, high sensitivity, and disturbance elimination. This sensor can be easily produced for AMB applications. A prototype of these displacement sensors was built and tested.

  13. Inductive displacement sensors with a notch filter for an active magnetic bearing system.

    Science.gov (United States)

    Chen, Seng-Chi; Le, Dinh-Kha; Nguyen, Van-Sum

    2014-07-15

    Active magnetic bearing (AMB) systems support rotating shafts without any physical contact, using electromagnetic forces. Each radial AMB uses two pairs of electromagnets at opposite sides of the rotor. This allows the rotor to float in the air gap, and the machine to operate without frictional losses. In active magnetic suspension, displacement sensors are necessary to detect the radial and axial movement of the suspended object. In a high-speed rotating machine equipped with an AMB, the rotor bending modes may be limited to the operating range. The natural frequencies of the rotor can cause instability. Thus, notch filters are a useful circuit for stabilizing the system. In addition, commercial displacement sensors are sometimes not suitable for AMB design, and cannot filter the noise caused by the natural frequencies of rotor. Hence, implementing displacement sensors based on the AMB structure is necessary to eliminate noises caused by natural frequency disturbances. The displacement sensor must be highly sensitive in the desired working range, and also exhibit a low interference noise, high stability, and low cost. In this study, we used the differential inductive sensor head and lock-in amplifier for synchronous demodulation. In addition, an active low-pass filter and a notch filter were used to eliminate disturbances, which caused by natural frequencies. As a consequence, the inductive displacement sensor achieved satisfactory linearity, high sensitivity, and disturbance elimination. This sensor can be easily produced for AMB applications. A prototype of these displacement sensors was built and tested.

  14. Notch is required in adult Drosophila sensory neurons for morphological and functional plasticity of the olfactory circuit.

    Directory of Open Access Journals (Sweden)

    Simon Kidd

    2015-05-01

    Full Text Available Olfactory receptor neurons (ORNs convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs. We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse.

  15. Scalable Notch Antenna System for Multiport Applications

    Directory of Open Access Journals (Sweden)

    Abdurrahim Toktas

    2016-01-01

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

  16. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  17. 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

  18. 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

  19. LHC Report: machine development

    CERN Multimedia

    Rogelio Tomás García for the LHC team

    2015-01-01

    Machine development weeks are carefully planned in the LHC operation schedule to optimise and further study the performance of the machine. The first machine development session of Run 2 ended on Saturday, 25 July. Despite various hiccoughs, it allowed the operators to make great strides towards improving the long-term performance of the LHC.   The main goals of this first machine development (MD) week were to determine the minimum beam-spot size at the interaction points given existing optics and collimation constraints; to test new beam instrumentation; to evaluate the effectiveness of performing part of the beam-squeezing process during the energy ramp; and to explore the limits on the number of protons per bunch arising from the electromagnetic interactions with the accelerator environment and the other beam. Unfortunately, a series of events reduced the machine availability for studies to about 50%. The most critical issue was the recurrent trip of a sextupolar corrector circuit –...

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

    Science.gov (United States)

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

    2018-01-17

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

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

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

    Science.gov (United States)

    Kuhn, Paul; Hardrath, Herbert F

    1952-01-01

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

  4. Modeling and design of a two-axis elliptical notch flexure hinge

    Science.gov (United States)

    Wu, Jianwei; Zhang, Yin; Lu, Yunfeng; Wen, Zhongpu; Bin, Deer; Tan, Jiubin

    2018-04-01

    As an important part of the joule balance system, the two-axis elliptical notch flexure hinge (TENFH) which typically consists of two single-axis elliptical notch flexure hinges was studied. First, a 6 degrees of freedom (6-DOF) compliance model was established based on the coordinate transformation method. In addition, the maximum stress of the TENFH was derived. The compliance and maximum stress model was verified using finite element analysis simulation. To decouple the attitude of the suspended coil system and reduce the offset between the centroid of the suspended coil mechanism and the mass comparator in the joule balance system, a new mechanical structure of TENFH was designed based on the compliance model and stress model proposed in this paper. The maximum rotation range is up to 10°, and the axial load is more than 5 kg, which meets the requirements of the system. The compliance model was also verified by deformation experimentation with the designed TENFH.

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

    Science.gov (United States)

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

    2011-01-01

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

  6. Machine Protection

    International Nuclear Information System (INIS)

    Schmidt, R

    2014-01-01

    The protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent. It is related to the increasing beam power of high-power proton accelerators such as ISIS, SNS, ESS and the PSI cyclotron, to the emission of synchrotron light by electron–positron accelerators and FELs, and to the increase of energy stored in the beam (in particular for hadron colliders such as LHC). Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping the beam at low energy) and an interlock system providing the glue between these systems. The most recent accelerator, the LHC, will operate with about 3 × 10 14 protons per beam, corresponding to an energy stored in each beam of 360 MJ. This energy can cause massive damage to accelerator equipment in case of uncontrolled beam loss, and a single accident damaging vital parts of the accelerator could interrupt operation for years. This article provides an overview of the requirements for protection of accelerator equipment and introduces the various protection systems. Examples are mainly from LHC, SNS and ESS

  7. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceabilit...... and uncertainty during coordinate measurements, 3) Digitalisation and Reverse Engineering. This document contains a short description of each step in the exercise and schemes with room for taking notes of the results.......This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceability...

  8. Tattoo machines, needles and utilities.

    Science.gov (United States)

    Rosenkilde, Frank

    2015-01-01

    Starting out as a professional tattooist back in 1977 in Copenhagen, Denmark, Frank Rosenkilde has personally experienced the remarkable development of tattoo machines, needles and utilities: all the way from home-made equipment to industrial products of substantially improved quality. Machines can be constructed like the traditional dual-coil and single-coil machines or can be e-coil, rotary and hybrid machines, with the more convenient and precise rotary machines being the recent trend. This development has resulted in disposable needles and utilities. Newer machines are more easily kept clean and protected with foil to prevent crosscontaminations and infections. The machines and the tattooists' knowledge and awareness about prevention of infection have developed hand-in-hand. For decades, Frank Rosenkilde has been collecting tattoo machines. Part of his collection is presented here, supplemented by his personal notes. © 2015 S. Karger AG, Basel.

  9. Fundamentals of machine design

    CERN Document Server

    Karaszewski, Waldemar

    2011-01-01

    A forum of researchers, educators and engineers involved in various aspects of Machine Design provided the inspiration for this collection of peer-reviewed papers. The resultant dissemination of the latest research results, and the exchange of views concerning the future research directions to be taken in this field will make the work of immense value to all those having an interest in the topics covered. The book reflects the cooperative efforts made in seeking out the best strategies for effecting improvements in the quality and the reliability of machines and machine parts and for extending

  10. 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.

  11. 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.

  12. High levels of Notch signaling down-regulate Numb and Numblike

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank

    2010-01-01

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

  14. Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

    Science.gov (United States)

    Gao, Wei; Sweeney, Catherine; Connolly, Mary; Kennedy, Aisling; Ng, Chin Teck; McCormick, Jennifer; Veale, Douglas J; Fearon, Ursula

    2012-07-01

    To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. Our

  15. An HTS machine laboratory prototype

    DEFF Research Database (Denmark)

    Mijatovic, Nenad; Jensen, Bogi Bech; Træholt, Chresten

    2012-01-01

    This paper describes Superwind HTS machine laboratory setup which is a small scale HTS machine designed and build as a part of the efforts to identify and tackle some of the challenges the HTS machine design may face. One of the challenges of HTS machines is a Torque Transfer Element (TTE) which...... conduction compared to a shaft. The HTS machine was successfully cooled to 77K and tests have been performed. The IV curves of the HTS field winding employing 6 HTS coils indicate that two of the coils had been damaged. The maximal value of the torque during experiments of 78Nm was recorded. Loaded with 33...

  16. 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.)

  17. Simple machines

    CERN Document Server

    Graybill, George

    2007-01-01

    Just how simple are simple machines? With our ready-to-use resource, they are simple to teach and easy to learn! Chocked full of information and activities, we begin with a look at force, motion and work, and examples of simple machines in daily life are given. With this background, we move on to different kinds of simple machines including: Levers, Inclined Planes, Wedges, Screws, Pulleys, and Wheels and Axles. An exploration of some compound machines follows, such as the can opener. Our resource is a real time-saver as all the reading passages, student activities are provided. Presented in s

  18. Late Holocene tectonic implications deduced from tidal notches in Leukas and Meganisi islands (Ionian Sea)

    International Nuclear Information System (INIS)

    Evelpidou, N.; Karkani, A.; Pirazzoli, P.

    2017-01-01

    In this paper the tectonic behavior of Leukas and Meganisi islands (Ionian Sea) is examined through underwater research carried out in both islands. A possible Late Holocene correlation between coseismic subsidences is attempted and evidenced by submerged tidal notches in both islands. These subsidence events probably occurred after the uplift that affected the northernmost part of Leukas around 4 to 5ka BP. In conclusion, although the whole area was affected by a similar tectonic strain, certain coseismic events were only recorded in one of the two islands and in some cases they affected only part of the study area.

  19. Late Holocene tectonic implications deduced from tidal notches in Leukas and Meganisi islands (Ionian Sea)

    Energy Technology Data Exchange (ETDEWEB)

    Evelpidou, N.; Karkani, A.; Pirazzoli, P.

    2017-11-01

    In this paper the tectonic behavior of Leukas and Meganisi islands (Ionian Sea) is examined through underwater research carried out in both islands. A possible Late Holocene correlation between coseismic subsidences is attempted and evidenced by submerged tidal notches in both islands. These subsidence events probably occurred after the uplift that affected the northernmost part of Leukas around 4 to 5ka BP. In conclusion, although the whole area was affected by a similar tectonic strain, certain coseismic events were only recorded in one of the two islands and in some cases they affected only part of the study area.

  20. 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

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

    International Nuclear Information System (INIS)

    Norris, D.M. Jr.

    1977-01-01

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

  2. 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.

  3. 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.

  4. Face machines

    Energy Technology Data Exchange (ETDEWEB)

    Hindle, D.

    1999-06-01

    The article surveys latest equipment available from the world`s manufacturers of a range of machines for tunnelling. These are grouped under headings: excavators; impact hammers; road headers; and shields and tunnel boring machines. Products of thirty manufacturers are referred to. Addresses and fax numbers of companies are supplied. 5 tabs., 13 photos.

  5. Electric machine

    Science.gov (United States)

    El-Refaie, Ayman Mohamed Fawzi [Niskayuna, NY; Reddy, Patel Bhageerath [Madison, WI

    2012-07-17

    An interior permanent magnet electric machine is disclosed. The interior permanent magnet electric machine comprises a rotor comprising a plurality of radially placed magnets each having a proximal end and a distal end, wherein each magnet comprises a plurality of magnetic segments and at least one magnetic segment towards the distal end comprises a high resistivity magnetic material.

  6. Machine Learning.

    Science.gov (United States)

    Kirrane, Diane E.

    1990-01-01

    As scientists seek to develop machines that can "learn," that is, solve problems by imitating the human brain, a gold mine of information on the processes of human learning is being discovered, expert systems are being improved, and human-machine interactions are being enhanced. (SK)

  7. Nonplanar machines

    International Nuclear Information System (INIS)

    Ritson, D.

    1989-05-01

    This talk examines methods available to minimize, but never entirely eliminate, degradation of machine performance caused by terrain following. Breaking of planar machine symmetry for engineering convenience and/or monetary savings must be balanced against small performance degradation, and can only be decided on a case-by-case basis. 5 refs

  8. A three-dimensional analysis of the sigmoid notch

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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

  11. Understanding and Writing G & M Code for CNC Machines

    Science.gov (United States)

    Loveland, Thomas

    2012-01-01

    In modern CAD and CAM manufacturing companies, engineers design parts for machines and consumable goods. Many of these parts are cut on CNC machines. Whether using a CNC lathe, milling machine, or router, the ideas and designs of engineers must be translated into a machine-readable form called G & M Code that can be used to cut parts to precise…

  12. Mechanical design of machine components

    CERN Document Server

    Ugural, Ansel C

    2015-01-01

    Mechanical Design of Machine Components, Second Edition strikes a balance between theory and application, and prepares students for more advanced study or professional practice. It outlines the basic concepts in the design and analysis of machine elements using traditional methods, based on the principles of mechanics of materials. The text combines the theory needed to gain insight into mechanics with numerical methods in design. It presents real-world engineering applications, and reveals the link between basic mechanics and the specific design of machine components and machines. Divided into three parts, this revised text presents basic background topics, deals with failure prevention in a variety of machine elements and covers applications in design of machine components as well as entire machines. Optional sections treating special and advanced topics are also included.Key Features of the Second Edition:Incorporates material that has been completely updated with new chapters, problems, practical examples...

  13. Soft computing in machine learning

    CERN Document Server

    Park, Jooyoung; Inoue, Atsushi

    2014-01-01

    As users or consumers are now demanding smarter devices, intelligent systems are revolutionizing by utilizing machine learning. Machine learning as part of intelligent systems is already one of the most critical components in everyday tools ranging from search engines and credit card fraud detection to stock market analysis. You can train machines to perform some things, so that they can automatically detect, diagnose, and solve a variety of problems. The intelligent systems have made rapid progress in developing the state of the art in machine learning based on smart and deep perception. Using machine learning, the intelligent systems make widely applications in automated speech recognition, natural language processing, medical diagnosis, bioinformatics, and robot locomotion. This book aims at introducing how to treat a substantial amount of data, to teach machines and to improve decision making models. And this book specializes in the developments of advanced intelligent systems through machine learning. It...

  14. Fifth Fundamental Catalogue (FK5). Part 1: Basic fundamental stars (Fricke, Schwan, and Lederle 1988): Documentation for the machine-readable version

    Science.gov (United States)

    Warren, Wayne H., Jr.

    1990-01-01

    The machine-readable version of the catalog, as it is currently being distributed from the Astronomical Data Center, is described. The Basic FK5 provides improved mean positions and proper motions for the 1535 classical fundamental stars that had been included in the FK3 and FK4 catalogs. The machine version of the catalog contains the positions and proper motions of the Basic FK5 stars for the epochs and equinoxes J2000.0 and B1950.0, the mean epochs of individual observed right ascensions and declinations used to determine the final positions, and the mean errors of the final positions and proper motions for the reported epochs. The cross identifications to other designations used for the FK5 stars that are given in the published catalog were not included in the original machine versions, but the Durchmusterung numbers have been added at the Astronomical Data Center.

  15. Face detection and facial feature localization using notch based templates

    International Nuclear Information System (INIS)

    Qayyum, U.

    2007-01-01

    We present a real time detection off aces from the video with facial feature localization as well as the algorithm capable of differentiating between the face/non-face patterns. The need of face detection and facial feature localization arises in various application of computer vision, so a lot of research is dedicated to come up with a real time solution. The algorithm should remain simple to perform real time whereas it should not compromise on the challenges encountered during the detection and localization phase, keeping simplicity and all challenges i.e. algorithm invariant to scale, translation, and (+-45) rotation transformations. The proposed system contains two parts. Visual guidance and face/non-face classification. The visual guidance phase uses the fusion of motion and color cues to classify skin color. Morphological operation with union-structure component labeling algorithm extracts contiguous regions. Scale normalization is applied by nearest neighbor interpolation method to avoid the effect of different scales. Using the aspect ratio of width and height size. Region of Interest (ROI) is obtained and then passed to face/non-face classifier. Notch (Gaussian) based templates/ filters are used to find circular darker regions in ROI. The classified face region is handed over to facial feature localization phase, which uses YCbCr eyes/lips mask for face feature localization. The empirical results show an accuracy of 90% for five different videos with 1000 face/non-face patterns and processing rate of proposed algorithm is 15 frames/sec. (author)

  16. Trastuzumab Resistance: Role for Notch Signaling

    Directory of Open Access Journals (Sweden)

    Kinnari Mehta

    2009-01-01

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

  17. 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

  18. The Machine within the Machine

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    Although Virtual Machines are widespread across CERN, you probably won't have heard of them unless you work for an experiment. Virtual machines - known as VMs - allow you to create a separate machine within your own, allowing you to run Linux on your Mac, or Windows on your Linux - whatever combination you need.   Using a CERN Virtual Machine, a Linux analysis software runs on a Macbook. When it comes to LHC data, one of the primary issues collaborations face is the diversity of computing environments among collaborators spread across the world. What if an institute cannot run the analysis software because they use different operating systems? "That's where the CernVM project comes in," says Gerardo Ganis, PH-SFT staff member and leader of the CernVM project. "We were able to respond to experimentalists' concerns by providing a virtual machine package that could be used to run experiment software. This way, no matter what hardware they have ...

  19. Machine translation

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, M

    1982-04-01

    Each language has its own structure. In translating one language into another one, language attributes and grammatical interpretation must be defined in an unambiguous form. In order to parse a sentence, it is necessary to recognize its structure. A so-called context-free grammar can help in this respect for machine translation and machine-aided translation. Problems to be solved in studying machine translation are taken up in the paper, which discusses subjects for semantics and for syntactic analysis and translation software. 14 references.

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

    Science.gov (United States)

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

    2015-10-01

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

  1. Simulation of Fatigue Crack Initiation at Corrosion Pits With EDM Notches

    Science.gov (United States)

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

    2003-01-01

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

  2. Fracture toughness evaluation using circumferential notched tensile specimens by the tensile test and ANSYS software

    Energy Technology Data Exchange (ETDEWEB)

    Meydanlik, N. [Mechanical Engineering Department, Trakya University, Edirne (Turkey)

    2013-07-01

    Fracture toughness (K{sub Ic} ) is the most important parameter that defines mechanical behaviour of the materials using machine design. Since, fracture tests are both difficult and time consuming, the researchers have been investigating for the easier evaluation of K{sub Ic} for many years. In this work; K{sub Ic} values have been obtained by using ANSYS software based on the experimental values evaluated in the previous studies. It was shown that there is no significant difference between the experimental ones and the ones obtained by ANSYS. This procedure can provide an important advantage on obtaining of the K{sub IC} values. Key words: Fracture toughness (K{sub Ic} ), circumferential notched tensile specimens, ANSYS.

  3. 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.

  4. Machine Learning

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    Machine learning, which builds on ideas in computer science, statistics, and optimization, focuses on developing algorithms to identify patterns and regularities in data, and using these learned patterns to make predictions on new observations. Boosted by its industrial and commercial applications, the field of machine learning is quickly evolving and expanding. Recent advances have seen great success in the realms of computer vision, natural language processing, and broadly in data science. Many of these techniques have already been applied in particle physics, for instance for particle identification, detector monitoring, and the optimization of computer resources. Modern machine learning approaches, such as deep learning, are only just beginning to be applied to the analysis of High Energy Physics data to approach more and more complex problems. These classes will review the framework behind machine learning and discuss recent developments in the field.

  5. Machine Translation

    Indian Academy of Sciences (India)

    Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.

  6. No evidence for induction of key components of the Notch signaling pathway (Notch-1, Jagged-1) by treatment with UV-B, 1,25(OH)(2)D(3), and/or epigenetic drugs (TSA, 5-Aza) in human keratinocytes in vitro.

    Science.gov (United States)

    Reichrath, Sandra; Reichrath, Jörg

    2012-01-01

    Notch signaling is of high importance for growth and survival of various cell types. We now analyzed the protein expression of two key components of the Notch signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and in malignant (SCL-1) human keratinocytes, using western analysis. We found that Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines, with no marked change following UV-B treatment. Moreover, treatment of both cell lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D(3), the biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5-Aza) did not result in a marked modulation of the protein expression of Notch-1 or Jagged-1. Under the experimental conditions of this study, treatment with 1,25(OH)(2)D(3) protected human keratinocytes in part against the antiproliferative effects of UV-B-radiation. In conclusion, our findings do not point at a differential expression of these two key components of Notch signaling in non-malignant as compared to malignant human keratinocytes, indicating that alterations in their expression are not of importance for the photocarcinogenesis of human squamous cell carcinomas. Moreover, our findings do not support the hypothesis that modulation of Notch signaling may be involved in the photoprotective effect of 1,25-dihydroxyvitamin D(3), that we and others reported previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5-Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated human keratinocytes in vitro.

  7. The Blindstitch Machine. Module 11.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the purpose and use of the blindstitch machine, one in a series on clothing construction for industrial sewing machine operators designed for student self-study, contains three sections. Each section includes the following parts: an introduction, directions, an objective, learning activities, student information, student self-check,…

  8. Man and Machines: Three Criticisms.

    Science.gov (United States)

    Schneider, Edward F.

    As machines have become a more common part of daily life through the passage of time, the idea that the line separating man and machine is slowly fading has become more popular as well. This paper examines three critics of change through their most famous works. One of the most popular views of Mary Shelley's "Frankenstein" is that it is a…

  9. ADAM: ADaptive Autonomous Machine

    NARCIS (Netherlands)

    van Oosten, Daan C.; Nijenhuis, Lucas F.J.; Bakkers, André; Vervoort, Wiek

    1996-01-01

    This paper describes a part of the development of an adaptive autonomous machine that is able to move in an unknown world extract knowledge out of the perceived data, has the possibility to reason, and finally has the capability to exchange experiences and knowledge with other agents. The agent is

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Investigation of an experimental ejector refrigeration machine operating with refrigerant R245fa at design and off-design working conditions. Part 1. Theoretical analysis

    KAUST Repository

    Shestopalov, K.O.

    2015-07-01

    © 2015 Elsevier Ltd and IIR.All rights reserved. The ejector refrigeration machine (ERM) offers several advantages over other heat-driven refrigeration machine, including simplicity in design and operation, high reliability and low installation cost, which enable its wide application in the production of cooling. In this paper the theoretical analysis of ejector design and ejector refrigeration cycle performance is presented. It is shown that ERM performance characteristics depend strongly on the operating conditions, the efficiency of the ejector used, and the thermodynamic properties of the refrigerant used. A 1-D model for the prediction of the entrainment ratio ω, and an optimal design for ejectors with cylindrical and conical-cylindrical mixing chambers are presented in this paper. In order to increase ERM performance values, it is necessary first of all to improve the performance of the ejector.

  16. 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.

  17. 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.

  18. Machine learning an artificial intelligence approach

    CERN Document Server

    Banerjee, R; Bradshaw, Gary; Carbonell, Jaime Guillermo; Mitchell, Tom Michael; Michalski, Ryszard Spencer

    1983-01-01

    Machine Learning: An Artificial Intelligence Approach contains tutorial overviews and research papers representative of trends in the area of machine learning as viewed from an artificial intelligence perspective. The book is organized into six parts. Part I provides an overview of machine learning and explains why machines should learn. Part II covers important issues affecting the design of learning programs-particularly programs that learn from examples. It also describes inductive learning systems. Part III deals with learning by analogy, by experimentation, and from experience. Parts IV a

  19. Acoustic emission during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches

    International Nuclear Information System (INIS)

    Mukhopadhyay, C.K.; Jayakumar, T.; Baldev Raj

    1996-01-01

    Acoustic emission generated during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches has been studied. The extent of acoustic activity generated depends on notch tip severity, notch tip blunting and tearing of the notches. The equation N=AK m applied to the acoustic emission data of the notched specimens has shown good correlation. Acoustic emission technique can be used to estimate the size of an unknown notch. (author)

  20. Electrical machines diagnosis

    CERN Document Server

    Trigeassou, Jean-Claude

    2013-01-01

    Monitoring and diagnosis of electrical machine faults is a scientific and economic issue which is motivated by objectives for reliability and serviceability in electrical drives.This book provides a survey of the techniques used to detect the faults occurring in electrical drives: electrical, thermal and mechanical faults of the electrical machine, faults of the static converter and faults of the energy storage unit.Diagnosis of faults occurring in electrical drives is an essential part of a global monitoring system used to improve reliability and serviceability. This diagnosis is perf

  1. Digital notch filter based active damping for LCL filters

    DEFF Research Database (Denmark)

    Yao, Wenli; Yang, Yongheng; Zhang, Xiaobin

    2015-01-01

    . In contrast, the active damping does not require any dissipation elements, and thus has become of increasing interest. As a result, a vast of active damping solutions have been reported, among which multi-loop control systems and additional sensors are necessary, leading to increased cost and complexity....... In this paper, a notch filter based active damping without the requirement of additional sensors is proposed, where the inverter current is employed as the feedback variable. Firstly, a design method of the notch filter for active damping is presented. The entire system stability has then been investigated...... in the z-domain. Simulations and experiments are carried out to verify the proposed active damping method. Both results have confirmed that the notch filter based active damping can ensure the entire system stability in the case of resonances with a good system performance....

  2. 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

  3. 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.

  4. 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.

  5. 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.

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

    National Research Council Canada - National Science Library

    Kwon, Y

    1999-01-01

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

  7. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    DEFF Research Database (Denmark)

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large...

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

    Indian Academy of Sciences (India)

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

  9. Machine safety: proper safeguarding techniques.

    Science.gov (United States)

    Martin, K J

    1992-06-01

    1. OSHA mandates certain safeguarding of machinery to prevent accidents and protect machine operators. OSHA specifies moving parts that must be guarded and sets criteria for the guards. 2. A 1989 OSHA standard for lockout/tagout requires locking the energy source during maintenance, periodically inspecting for power transmission, and training maintenance workers. 3. In an amputation emergency, first aid for cardiopulmonary resuscitation, shock, and bleeding are the first considerations. The amputated part should be wrapped in moist gauze, placed in a sealed plastic bag, and placed in a container of 50% water and 50% ice for transport. 4. The role of the occupational health nurse in machine safety is to conduct worksite analyses to identify proper safeguarding and to communicate deficiencies to appropriate personnel; to train workers in safe work practices and observe compliance in the use of machine guards; to provide care to workers injured by machines; and to reinforce safe work practices among machine operators.

  10. Notch3 is dispensable for thymocyte β-selection and Notch1-induced T cell leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Sara Suliman

    Full Text Available Notch1 (N1 signaling induced by intrathymic Delta-like (DL ligands is required for T cell lineage commitment as well as self-renewal during "β-selection" of TCRβ⁺CD4⁻CD8⁻ double negative 3 (DN3 T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1 renders N1 activation ligand-independent and drives leukemic transformation during β-selection. DN3 progenitors also express Notch3 (N3 mRNA, and over-expression of ligand-independent mutant N3 (ICN3 influences β-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting β-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate β-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1⁺/⁻ DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4.

  11. Machine Learning

    Energy Technology Data Exchange (ETDEWEB)

    Chikkagoudar, Satish; Chatterjee, Samrat; Thomas, Dennis G.; Carroll, Thomas E.; Muller, George

    2017-04-21

    The absence of a robust and unified theory of cyber dynamics presents challenges and opportunities for using machine learning based data-driven approaches to further the understanding of the behavior of such complex systems. Analysts can also use machine learning approaches to gain operational insights. In order to be operationally beneficial, cybersecurity machine learning based models need to have the ability to: (1) represent a real-world system, (2) infer system properties, and (3) learn and adapt based on expert knowledge and observations. Probabilistic models and Probabilistic graphical models provide these necessary properties and are further explored in this chapter. Bayesian Networks and Hidden Markov Models are introduced as an example of a widely used data driven classification/modeling strategy.

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

    Directory of Open Access Journals (Sweden)

    Galina Dvoriantchikova

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

  13. Teletherapy machine

    International Nuclear Information System (INIS)

    Panyam, Vinatha S.; Rakshit, Sougata; Kulkarni, M.S.; Pradeepkumar, K.S.

    2017-01-01

    Radiation Standards Section (RSS), RSSD, BARC is the national metrology institute for ionizing radiation. RSS develops and maintains radiation standards for X-ray, beta, gamma and neutron radiations. In radiation dosimetry, traceability, accuracy and consistency of radiation measurements is very important especially in radiotherapy where the success of patient treatment is dependent on the accuracy of the dose delivered to the tumour. Cobalt teletherapy machines have been used in the treatment of cancer since the early 1950s and India had its first cobalt teletherapy machine installed at the Cancer Institute, Chennai in 1956

  14. 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

  15. Peripheral Osteoma of the Mandibular Notch: Report of a Case

    International Nuclear Information System (INIS)

    Iwai, Toshinori; Izumi, Toshiharu; Baba, Junichi; Maegawa, Jiro; Mitsudo, Kenji; Tohnai, Iwai

    2013-01-01

    Osteoma is a benign, slow-growing osteogenic tumor that sometimes arises from the craniomaxillofacial region, such as the sinus, temporal or jaw bones. Osteoma consists of compact or cancellous bone that may be peripheral, central or extraskeletal type. Peripheral osteoma arises from the periosteum and is commonly a unilateral, pedunculated mushroom-like mass. Peripheral osteoma of the mandible is relatively uncommon, and peripheral osteoma of the mandibular notch is extremely rare, although many cases arise from the mandibular body, angle, condyle, or coronoid process. We report here an unusual peripheral osteoma of the mandibular notch in a 78-year-old nonsyndromic female

  16. 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...

  17. 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.)

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Maria De Salvo

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

  20. 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.

  1. 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

  2. Machine-readable files developed for the High Plains Regional Aquifer-System analysis in parts of Colorado, Kansas, Nebraska, New Mexico, Oklahoma, South Dakota, Texas, and Wyoming

    Science.gov (United States)

    Ferrigno, C.F.

    1986-01-01

    Machine-readable files were developed for the High Plains Regional Aquifer-System Analysis project are stored on two magnetic tapes available from the U.S. Geological Survey. The first tape contains computer programs that were used to prepare, store, retrieve, organize, and preserve the areal interpretive data collected by the project staff. The second tape contains 134 data files that can be divided into five general classes: (1) Aquifer geometry data, (2) aquifer and water characteristics , (3) water levels, (4) climatological data, and (5) land use and water use data. (Author 's abstract)

  3. Apparel Manufacturing (Course Outline), Industrial Single Needle Machines and Machine Practice: 9377.02.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    This course includes a study of the industrial single needle machine, its principal parts, general care, threading, and basic skills in machine practice. Instructional materials include films, illustration, information sheets, and other materials. (CK)

  4. Improving Machining Accuracy of CNC Machines with Innovative Design Methods

    Science.gov (United States)

    Yemelyanov, N. V.; Yemelyanova, I. V.; Zubenko, V. L.

    2018-03-01

    The article considers achieving the machining accuracy of CNC machines by applying innovative methods in modelling and design of machining systems, drives and machine processes. The topological method of analysis involves visualizing the system as matrices of block graphs with a varying degree of detail between the upper and lower hierarchy levels. This approach combines the advantages of graph theory and the efficiency of decomposition methods, it also has visual clarity, which is inherent in both topological models and structural matrices, as well as the resiliency of linear algebra as part of the matrix-based research. The focus of the study is on the design of automated machine workstations, systems, machines and units, which can be broken into interrelated parts and presented as algebraic, topological and set-theoretical models. Every model can be transformed into a model of another type, and, as a result, can be interpreted as a system of linear and non-linear equations which solutions determine the system parameters. This paper analyses the dynamic parameters of the 1716PF4 machine at the stages of design and exploitation. Having researched the impact of the system dynamics on the component quality, the authors have developed a range of practical recommendations which have enabled one to reduce considerably the amplitude of relative motion, exclude some resonance zones within the spindle speed range of 0...6000 min-1 and improve machining accuracy.

  5. The Bearingless Electrical Machine

    Science.gov (United States)

    Bichsel, J.

    1992-01-01

    Electromagnetic bearings allow the suspension of solids. For rotary applications, the most important physical effect is the force of a magnetic circuit to a high permeable armature, called the MAXWELL force. Contrary to the commonly used MAXWELL bearings, the bearingless electrical machine will take advantage of the reaction force of a conductor carrying a current in a magnetic field. This kind of force, called Lorentz force, generates the torque in direct current, asynchronous and synchronous machines. The magnetic field, which already exists in electrical machines and helps to build up the torque, can also be used for the suspension of the rotor. Besides the normal winding of the stator, a special winding was added, which generates forces for levitation. So a radial bearing, which is integrated directly in the active part of the machine, and the motor use the laminated core simultaneously. The winding was constructed for the levitating forces in a special way so that commercially available standard ac inverters for drives can be used. Besides wholly magnetic suspended machines, there is a wide range of applications for normal drives with ball bearings. Resonances of the rotor, especially critical speeds, can be damped actively.

  6. Support vector machine in machine condition monitoring and fault diagnosis

    Science.gov (United States)

    Widodo, Achmad; Yang, Bo-Suk

    2007-08-01

    Recently, the issue of machine condition monitoring and fault diagnosis as a part of maintenance system became global due to the potential advantages to be gained from reduced maintenance costs, improved productivity and increased machine availability. This paper presents a survey of machine condition monitoring and fault diagnosis using support vector machine (SVM). It attempts to summarize and review the recent research and developments of SVM in machine condition monitoring and diagnosis. Numerous methods have been developed based on intelligent systems such as artificial neural network, fuzzy expert system, condition-based reasoning, random forest, etc. However, the use of SVM for machine condition monitoring and fault diagnosis is still rare. SVM has excellent performance in generalization so it can produce high accuracy in classification for machine condition monitoring and diagnosis. Until 2006, the use of SVM in machine condition monitoring and fault diagnosis is tending to develop towards expertise orientation and problem-oriented domain. Finally, the ability to continually change and obtain a novel idea for machine condition monitoring and fault diagnosis using SVM will be future works.

  7. 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...

  8. 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

  9. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    NARCIS (Netherlands)

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal.

  10. 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 ...

  11. 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

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Robert Wunderlich

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

  15. Effects of sulfur addition on pitting corrosion and machinability behavior of super duplex stainless steel containing rare earth metals: Part 2

    International Nuclear Information System (INIS)

    Jeon, Soon-Hyeok; Kim, Soon-Tae; Lee, In-Sung; Park, Yong-Soo

    2010-01-01

    Research highlights: → The mechanisms on the effects of rare earth metals (REM) and sulfur (S) additions on the initiation and propagation of pitting corrosion and machinabillity of a super duplex stainless steel (SDSS) were elucidated → It was found that, in consideration of the ratio of lifetime (the resistance to pitting corrosion) to cost (machining and raw material), a costly austenitic stainless steel with high Ni , medium Mo and low N can be replaced by the high S and REM added SDSS with 7 wt.% Ni-4 wt% Mo-0.3 wt.% N → The resistance to pitting corrosion of the tested super duplex stainless steel was affected by the type of inclusions, the preferential interface areas between inclusions and the substrate, and the PREN difference between the γ-phase and the α-phase for the initiation and propagation of the pitting corrosion. - Abstract: To elucidate the effects of sulfur addition on pitting corrosion and machinability behavior of alloys containing rare earth metals, a potentiostatic polarization test, a critical pitting temperature test, a SEM-EDS analysis of inclusions, and a tool life test were conducted. As sulfur content increased, the resistance to pitting corrosion decreased due to the formation of numerous manganese sulfides deteriorating the corrosion resistance and an increase in the preferential interface areas for the initiation of the pitting corrosion. With an increase in sulfur content, the tool life increased due to the lubricating films of manganese sulfides adhering to tool surface.

  16. Machine rates for selected forest harvesting machines

    Science.gov (United States)

    R.W. Brinker; J. Kinard; Robert Rummer; B. Lanford

    2002-01-01

    Very little new literature has been published on the subject of machine rates and machine cost analysis since 1989 when the Alabama Agricultural Experiment Station Circular 296, Machine Rates for Selected Forest Harvesting Machines, was originally published. Many machines discussed in the original publication have undergone substantial changes in various aspects, not...

  17. Dual Mechanism of Action of Resveratrol in Notch Signaling ...

    African Journals Online (AJOL)

    activation of Notch signaling in osteosarcoma cells. ... HeyL in U2OS cells. Treatment of U2OS cells with 20 µM concentration of resveratrol for 48 h induced a ... Cell lines and culture .... concentration of resveratrol required for induced.

  18. Notch Signaling in Prostate Cancer Cells Promotes Osteoblastic Metastasis

    Science.gov (United States)

    2017-06-01

    information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this...function and number while inducing osteoblast proliferation. Our results suggest that Notch signaling from cancer cells promotes osteoblastic...Participants and other collaborating organizations: I initiated collaboration with Dr. Evan Keller at University of Michigan to interrogate PCa bone

  19. Dual Mechanism of Action of Resveratrol in Notch Signaling ...

    African Journals Online (AJOL)

    Results: The results revealed that resveratrol treatment exhibited dual mechanisms of action on the activation of Notch signaling in osteosarcoma cells. The osteosarcoma cell lines, MG-63 and U2OS, when exposed to 20 μM concentration of resveratrol for 48 h showed significant toxicity compared to untreated cells.

  20. On-line identification, flutter testing and adaptive notching of ...

    Indian Academy of Sciences (India)

    multiple modes simultaneously from sine sweep and other multifrequency data, ... envelope expansion and to adjust the notch filter frequencies and suppress aero- .... estimated frequency and damping values were compared with those ..... The current configuration results in a phase delay of (p И 0X19 s, while the Kalman.

  1. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    DEFF Research Database (Denmark)

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  2. 105 GHz Notch Filter Design for Collective Thomson Scattering

    DEFF Research Database (Denmark)

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank

    2011-01-01

    A millimeter-wave notch filter with 105-GHz center frequency, >20-GHz passband coverage, and 1-GHz rejection bandwidth has been constructed. The design is based on a fundamental rectangular waveguide with cylindrical cavities coupled by narrow iris gaps, i.e., small elongated holes of negligible...

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

    Science.gov (United States)

    Aidi, Bilel; Case, Scott W.

    2015-12-01

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

  4. The non-canonical NOTCH1 ligand Delta-like 1 homolog (DLK1) self interacts in mammals

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte Harken; Garcia Ramirez, Jose Javier

    2017-01-01

    the proposed DLK1-IGFBP1 interaction was not supported by MTH. Very little has previously been described on the DLK1 self-interaction. Herein, we showed by immunoprecipitation as well as Sulfo-SBED label transfer that the DLK1-DLK1 interaction likely is part of Dlk1's function in preadipocytes. Furthermore our......Delta-like 1 homolog (DLK1) is an imprinted gene, which is widely expressed during mammalian development and plays a pivotal role in differentiation of various tissue types. Most recently, we have shown that DLK1 interacts with NOTCH1, yet several Notch independent mechanisms have previously been...... suggested as well, but only poorly confirmed in a mammalian context. In the present study, we employed the mammalian two-hybrid (MTH) system, a genetic in vivo protein-protein interaction system, to show robust DLK1-DLK1, DLK1-FnI (Fibronectin) and DLK1-CFR (cysteine-rich FGF receptor) interactions, whereas...

  5. 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....

  6. Electric machines

    CERN Document Server

    Gross, Charles A

    2006-01-01

    BASIC ELECTROMAGNETIC CONCEPTSBasic Magnetic ConceptsMagnetically Linear Systems: Magnetic CircuitsVoltage, Current, and Magnetic Field InteractionsMagnetic Properties of MaterialsNonlinear Magnetic Circuit AnalysisPermanent MagnetsSuperconducting MagnetsThe Fundamental Translational EM MachineThe Fundamental Rotational EM MachineMultiwinding EM SystemsLeakage FluxThe Concept of Ratings in EM SystemsSummaryProblemsTRANSFORMERSThe Ideal n-Winding TransformerTransformer Ratings and Per-Unit ScalingThe Nonideal Three-Winding TransformerThe Nonideal Two-Winding TransformerTransformer Efficiency and Voltage RegulationPractical ConsiderationsThe AutotransformerOperation of Transformers in Three-Phase EnvironmentsSequence Circuit Models for Three-Phase Transformer AnalysisHarmonics in TransformersSummaryProblemsBASIC MECHANICAL CONSIDERATIONSSome General PerspectivesEfficiencyLoad Torque-Speed CharacteristicsMass Polar Moment of InertiaGearingOperating ModesTranslational SystemsA Comprehensive Example: The ElevatorP...

  7. Charging machine

    International Nuclear Information System (INIS)

    Medlin, J.B.

    1976-01-01

    A charging machine for loading fuel slugs into the process tubes of a nuclear reactor includes a tubular housing connected to the process tube, a charging trough connected to the other end of the tubular housing, a device for loading the charging trough with a group of fuel slugs, means for equalizing the coolant pressure in the charging trough with the pressure in the process tubes, means for pushing the group of fuel slugs into the process tube and a latch and a seal engaging the last object in the group of fuel slugs to prevent the fuel slugs from being ejected from the process tube when the pusher is removed and to prevent pressure liquid from entering the charging machine. 3 claims, 11 drawing figures

  8. Genesis machines

    CERN Document Server

    Amos, Martyn

    2014-01-01

    Silicon chips are out. Today's scientists are using real, wet, squishy, living biology to build the next generation of computers. Cells, gels and DNA strands are the 'wetware' of the twenty-first century. Much smaller and more intelligent, these organic computers open up revolutionary possibilities. Tracing the history of computing and revealing a brave new world to come, Genesis Machines describes how this new technology will change the way we think not just about computers - but about life itself.

  9. An art history of machines?

    Directory of Open Access Journals (Sweden)

    Daniel Bridgman

    2016-12-01

    Full Text Available A toast offered in honor of Donald Preziosi on the cusp of his seventy-fifth birthday, this essay considers a range of machine metaphors, their art historical settings, and their implications. Addressing the mythography of Daedalus and his wonder machines in relation to art history’s machinic enterprises, an ancient art-archaeology seminar Preziosi directed at UCLA (in 1988 and the book, Rethinking Art History: Meditations on a Coy Science (1989 form the focus of my thinking about Preziosi’s work. At issue across the essay is the work of recursion, when machines make machines and in so doing create a recessive subjectivity for the maker. The essay ends with the speculation that art history’s disciplinary machinery may owe its generative strength to a perpetual need for replacement parts.

  10. Nontraditional machining processes research advances

    CERN Document Server

    2013-01-01

    Nontraditional machining employs processes that remove material by various methods involving thermal, electrical, chemical and mechanical energy or even combinations of these. Nontraditional Machining Processes covers recent research and development in techniques and processes which focus on achieving high accuracies and good surface finishes, parts machined without burrs or residual stresses especially with materials that cannot be machined by conventional methods. With applications to the automotive, aircraft and mould and die industries, Nontraditional Machining Processes explores different aspects and processes through dedicated chapters. The seven chapters explore recent research into a range of topics including laser assisted manufacturing, abrasive water jet milling and hybrid processes. Students and researchers will find the practical examples and new processes useful for both reference and for developing further processes. Industry professionals and materials engineers will also find Nontraditional M...

  11. Machine learning and medical imaging

    CERN Document Server

    Shen, Dinggang; Sabuncu, Mert

    2016-01-01

    Machine Learning and Medical Imaging presents state-of- the-art machine learning methods in medical image analysis. It first summarizes cutting-edge machine learning algorithms in medical imaging, including not only classical probabilistic modeling and learning methods, but also recent breakthroughs in deep learning, sparse representation/coding, and big data hashing. In the second part leading research groups around the world present a wide spectrum of machine learning methods with application to different medical imaging modalities, clinical domains, and organs. The biomedical imaging modalities include ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), histology, and microscopy images. The targeted organs span the lung, liver, brain, and prostate, while there is also a treatment of examining genetic associations. Machine Learning and Medical Imaging is an ideal reference for medical imaging researchers, industry scientists and engineers, advanced undergraduate and graduate students, a...

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  1. VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis

    Directory of Open Access Journals (Sweden)

    Pirjo Spuul

    2016-10-01

    Full Text Available During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.

  2. A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the AAA+ ATPase p97/VCP.

    Science.gov (United States)

    Chimenti, Michael S; Bulfer, Stacie L; Neitz, R Jeffrey; Renslo, Adam R; Jacobson, Matthew P; James, Thomas L; Arkin, Michelle R; Kelly, Mark J S

    2015-07-01

    The ubiquitous AAA+ ATPase p97 functions as a dynamic molecular machine driving several cellular processes. It is essential in regulating protein homeostasis, and it represents a potential drug target for cancer, particularly when there is a greater reliance on the endoplasmic reticulum-associated protein degradation pathway and ubiquitin-proteasome pathway to degrade an overabundance of secreted proteins. Here, we report a case study for using fragment-based ligand design approaches against this large and dynamic hexamer, which has multiple potential binding sites for small molecules. A screen of a fragment library was conducted by surface plasmon resonance (SPR) and followed up by nuclear magnetic resonance (NMR), two complementary biophysical techniques. Virtual screening was also carried out to examine possible binding sites for the experimental hits and evaluate the potential utility of fragment docking for this target. Out of this effort, 13 fragments were discovered that showed reversible binding with affinities between 140 µM and 1 mM, binding stoichiometries of 1:1 or 2:1, and good ligand efficiencies. Structural data for fragment-protein interactions were obtained with residue-specific [U-(2)H] (13)CH3-methyl-labeling NMR strategies, and these data were compared to poses from docking. The combination of virtual screening, SPR, and NMR enabled us to find and validate a number of interesting fragment hits and allowed us to gain an understanding of the structural nature of fragment binding. © 2015 Society for Laboratory Automation and Screening.

  3. 78 FR 28577 - Notification of Proposed Production Activity: Whirlpool Corporation Subzone 8I; (Washing Machines...

    Science.gov (United States)

    2013-05-15

    ... machine parts to the list of approved finished products and would also add imported components to the...; refrigeration parts; dishwashing machine parts; drying machine parts; water inlet valves; AC/DC fan motors; AC... Activity: Whirlpool Corporation Subzone 8I; (Washing Machines): Clyde and Green Springs, Ohio Whirlpool...

  4. Machining refractory alloys: an overview

    International Nuclear Information System (INIS)

    Christopher, J.D.

    1984-01-01

    Nontraditional machining is a generic term for those material removal processes that differ drastically from the historic operations such as turning, milling, drilling, tapping, and grinding. The use of primary energy modes other than mechanical, such as thermal, electrical, and chemical, sets these operations apart and reinforces their nontraditional label. Several of these newer processes have been very successful in machining close tolerance parts from refractory materials. This paper provides a general overview of both traditional and nontraditional aspects of machining refractory materials. 11 figures, 7 tables

  5. The Single Needle Lockstitch Machine. Module 1.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on parts of the machine, one in a series on the single needle lockstitch sewing machine for student self-study, contains eight sections. Each section contains the following parts: an introduction, directions, an objective, learning activities, student information, student self-check, check-out activities, and an instructor's final…

  6. Representational Machines

    DEFF Research Database (Denmark)

    Photography not only represents space. Space is produced photographically. Since its inception in the 19th century, photography has brought to light a vast array of represented subjects. Always situated in some spatial order, photographic representations have been operatively underpinned by social...... to the enterprises of the medium. This is the subject of Representational Machines: How photography enlists the workings of institutional technologies in search of establishing new iconic and social spaces. Together, the contributions to this edited volume span historical epochs, social environments, technological...... possibilities, and genre distinctions. Presenting several distinct ways of producing space photographically, this book opens a new and important field of inquiry for photography research....

  7. Shear machines

    International Nuclear Information System (INIS)

    Astill, M.; Sunderland, A.; Waine, M.G.

    1980-01-01

    A shear machine for irradiated nuclear fuel elements has a replaceable shear assembly comprising a fuel element support block, a shear blade support and a clamp assembly which hold the fuel element to be sheared in contact with the support block. A first clamp member contacts the fuel element remote from the shear blade and a second clamp member contacts the fuel element adjacent the shear blade and is advanced towards the support block during shearing to compensate for any compression of the fuel element caused by the shear blade (U.K.)

  8. Environmentally Friendly Machining

    CERN Document Server

    Dixit, U S; Davim, J Paulo

    2012-01-01

    Environment-Friendly Machining provides an in-depth overview of environmentally-friendly machining processes, covering numerous different types of machining in order to identify which practice is the most environmentally sustainable. The book discusses three systems at length: machining with minimal cutting fluid, air-cooled machining and dry machining. Also covered is a way to conserve energy during machining processes, along with useful data and detailed descriptions for developing and utilizing the most efficient modern machining tools. Researchers and engineers looking for sustainable machining solutions will find Environment-Friendly Machining to be a useful volume.

  9. Machine Protection

    CERN Document Server

    Schmidt, R

    2014-01-01

    The protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent. It is related to the increasing beam power of high-power proton accelerators such as ISIS, SNS, ESS and the PSI cyclotron, to the emission of synchrotron light by electron–positron accelerators and FELs, and to the increase of energy stored in the beam (in particular for hadron colliders such as LHC). Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping the beam at low energy) and an ...

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. The Evolution of the Maine Lobster V-Notch Practice: Cooperation in a Prisoner's Dilemma Game

    Directory of Open Access Journals (Sweden)

    James Acheson

    2011-03-01

    Full Text Available The Maine lobster industry is experiencing record high catches because, in all probability, of an effective management program. One of the most important conservation measures is the V-notch program that allows fishermen to conserve proven breeding females by notching the tails of egg-bearing lobsters. Such marked lobsters may never be taken. Although thousands of lobster fishermen participate, it is a voluntary practice. The genesis of this practice is not easily explained, because V-notching poses a prisoner's dilemma problem that gives fishermen an incentive to avoid the practice. The most common explanations for ways to overcome prisoner's dilemma problems will not work in the case of the V-notch. An unusual combination of factors explains the V-notch program: (1 a strong belief among those in the industry that the V-notch is effective in conserving the lobster stock; (2 a low discount rate because the long-term gains from V-notching are higher than the one-time gain from defection; (3 a gain in reputation for those who V-notch. At the start of the 20th century, fishermen did not V-notch; by the end of the century, V-notching was common. We explain the change in strategies using a three-parameter evolutionary model that emphasizes the importance of culture change.

  15. 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.

  16. 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.

  17. 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...

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

    Science.gov (United States)

    Tatner, Ian

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

  19. Myositis ossificans within the intercondylar notch treated arthroscopically

    International Nuclear Information System (INIS)

    Leung, Allen H.; Desai, Panna; Rybak, Leon D.; Rose, Donald J.

    2010-01-01

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  20. Myositis ossificans within the intercondylar notch treated arthroscopically

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Allen H.; Desai, Panna [Hospital for Joint Diseases/New York University, Department of Pathology, New York, NY (United States); Rybak, Leon D. [Hospital for Joint Diseases/New York University, Department of Radiology, New York, NY (United States); Rose, Donald J. [Hospital for Joint Diseases/New York University, Department of Orthopedic Surgery, New York, NY (United States)

    2010-09-15

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  1. Notch sensitivity of cast AZ31 magnesium alloy

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

  2. Hierarchical object class representation using holes and notches

    Energy Technology Data Exchange (ETDEWEB)

    Osbourn, G.C.

    1989-01-01

    A general representation approach is described which employs a hierarchy of holes and notches. A matching procedure is also described which allows non-ideal image hierarchies to be matched to class representations. The representation and matching methods are demonstrated on a set of handgun photographs. Examples of handguns which are different in detail are shown to exhibit the same class characteristics, while other similarly shaped objects are correctly distinguished from the handgun class. 6 refs., 8 figs.

  3. Case Study of Crack Initiation from Bi-material Notches

    Czech Academy of Sciences Publication Activity Database

    Klusák, Jan; Knésl, Zdeněk

    2011-01-01

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

  4. Frequency Agile Microwave Photonic Notch Filter in a Photonic Chip

    Science.gov (United States)

    2016-10-21

    Interference mitigation is crucial in modern radiofrequency (RF) communications systems with dynamically changing operating frequencies, such as cognitive...frequency measurement (IFM) system was also explored. 4. Results and discussions: a. High extinction tunable notch filter in a chalcogenide chip [Optica...Figure 2(b, lower). The measured interferer suppression in this case was 47 dB, limited by the noise floor of the measurements . This paper is in the

  5. Magnetic domain wall motion in notch patterned permalloy nanowire devices

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ting-Chieh; Kuo, Cheng-Yi; Mishra, Amit K.; Das, Bipul; Wu, Jong-Ching, E-mail: phjcwu@cc.ncue.edu.tw

    2015-11-01

    We report a study of magnetization reversal process of notch-patterned permalloy (Py) nanowires (NWs) by using an in-situ magnetic force microscopy (MFM). Three neighboring straight NWs and an individual straight NW with discs connected to the wires ends are fabricated by standard electron beam lithography through a lift-off technique. MFM images are taken in the presence of an in-plane magnetic field applied along the wires length. As a result, the nucleation, pinning and depinning of domain walls (DWs) along the NW are observed. The artificial constraints (notch) in such symmetrical geometry of NWs indeed serve as pinning sites to pin the DWs. The nature of magnetization reversal, pinning field and depinning field for the DWs that are observed in these permalloy NWs, indicate the key roles of notch depth, the terminal connection structure of NW end and the inter-wire interaction among the NWs. The in-situ MFM measurements are examined with the micromagnetic simulations. Consequently, good agreements are obtained for the DW structures and the effect of DWs pining/depinning, however a dissimilarity in experimental and simulation observations for the direction of propagation of DWs in NWs needs further investigation.

  6. 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

  7. Machine Learning for Medical Imaging.

    Science.gov (United States)

    Erickson, Bradley J; Korfiatis, Panagiotis; Akkus, Zeynettin; Kline, Timothy L

    2017-01-01

    Machine learning is a technique for recognizing patterns that can be applied to medical images. Although it is a powerful tool that can help in rendering medical diagnoses, it can be misapplied. Machine learning typically begins with the machine learning algorithm system computing the image features that are believed to be of importance in making the prediction or diagnosis of interest. The machine learning algorithm system then identifies the best combination of these image features for classifying the image or computing some metric for the given image region. There are several methods that can be used, each with different strengths and weaknesses. There are open-source versions of most of these machine learning methods that make them easy to try and apply to images. Several metrics for measuring the performance of an algorithm exist; however, one must be aware of the possible associated pitfalls that can result in misleading metrics. More recently, deep learning has started to be used; this method has the benefit that it does not require image feature identification and calculation as a first step; rather, features are identified as part of the learning process. Machine learning has been used in medical imaging and will have a greater influence in the future. Those working in medical imaging must be aware of how machine learning works. © RSNA, 2017.

  8. 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.

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

    International Nuclear Information System (INIS)

    Richard, H.A.; Theis, W.

    1982-01-01

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

  10. 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

  11. 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)

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

    Directory of Open Access Journals (Sweden)

    Silvia Fre

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

  13. Machine terms dictionary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1979-04-15

    This book gives descriptions of machine terms which includes machine design, drawing, the method of machine, machine tools, machine materials, automobile, measuring and controlling, electricity, basic of electron, information technology, quality assurance, Auto CAD and FA terms and important formula of mechanical engineering.

  14. Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi

    Directory of Open Access Journals (Sweden)

    Sebastian Boltaña

    2016-05-01

    Full Text Available The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  17. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  18. 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.

  19. 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.

  20. 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.

  1. Analysis Of Electrical – Thermal Coupling Of Induction Machine ...

    African Journals Online (AJOL)

    The interaction of the Electrical and mechanical parts of Electrical machines gives rise to the heating of the machine's constituent parts. This consequently leads to an increase in temperature which if not properly monitored may lead to the breakdown of the machine. This paper therefore presents the Electrical and thermal ...

  2. The spares provisioning problem with parts inventory

    OpenAIRE

    Abboud, Nadim E.

    1990-01-01

    In this research, we consider the spares provisioning problem, where a finite population of homogeneous machines are being deployed to meet a constant demand. While a machine is operating, it could become inoperable due to the failure of a critical built-in part in the machine. Before repairs on the machine can be initiated, however, a replacement part must be obtained. If a replacement part is available from stock, the machine is immediately transferred to the repair subsystem...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

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

  6. 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...

  7. 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.

  8. 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.

  9. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-29

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

  11. Machine Learning in Medicine.

    Science.gov (United States)

    Deo, Rahul C

    2015-11-17

    Spurred by advances in processing power, memory, storage, and an unprecedented wealth of data, computers are being asked to tackle increasingly complex learning tasks, often with astonishing success. Computers have now mastered a popular variant of poker, learned the laws of physics from experimental data, and become experts in video games - tasks that would have been deemed impossible not too long ago. In parallel, the number of companies centered on applying complex data analysis to varying industries has exploded, and it is thus unsurprising that some analytic companies are turning attention to problems in health care. The purpose of this review is to explore what problems in medicine might benefit from such learning approaches and use examples from the literature to introduce basic concepts in machine learning. It is important to note that seemingly large enough medical data sets and adequate learning algorithms have been available for many decades, and yet, although there are thousands of papers applying machine learning algorithms to medical data, very few have contributed meaningfully to clinical care. This lack of impact stands in stark contrast to the enormous relevance of machine learning to many other industries. Thus, part of my effort will be to identify what obstacles there may be to changing the practice of medicine through statistical learning approaches, and discuss how these might be overcome. © 2015 American Heart Association, Inc.

  12. Machine Learning in Medicine

    Science.gov (United States)

    Deo, Rahul C.

    2015-01-01

    Spurred by advances in processing power, memory, storage, and an unprecedented wealth of data, computers are being asked to tackle increasingly complex learning tasks, often with astonishing success. Computers have now mastered a popular variant of poker, learned the laws of physics from experimental data, and become experts in video games – tasks which would have been deemed impossible not too long ago. In parallel, the number of companies centered on applying complex data analysis to varying industries has exploded, and it is thus unsurprising that some analytic companies are turning attention to problems in healthcare. The purpose of this review is to explore what problems in medicine might benefit from such learning approaches and use examples from the literature to introduce basic concepts in machine learning. It is important to note that seemingly large enough medical data sets and adequate learning algorithms have been available for many decades – and yet, although there are thousands of papers applying machine learning algorithms to medical data, very few have contributed meaningfully to clinical care. This lack of impact stands in stark contrast to the enormous relevance of machine learning to many other industries. Thus part of my effort will be to identify what obstacles there may be to changing the practice of medicine through statistical learning approaches, and discuss how these might be overcome. PMID:26572668

  13. Air core notch-coil magnet with variable geometry for fast-field-cycling NMR.

    Science.gov (United States)

    Kruber, S; Farrher, G D; Anoardo, E

    2015-10-01

    In this manuscript we present details on the optimization, construction and performance of a wide-bore (71 mm) α-helical-cut notch-coil magnet with variable geometry for fast-field-cycling NMR. In addition to the usual requirements for this kind of magnets (high field-to-power ratio, good magnetic field homogeneity, low inductance and resistance values) a tunable homogeneity and a more uniform heat dissipation along the magnet body are considered. The presented magnet consists of only one machined metallic cylinder combined with two external movable pieces. The optimal configuration is calculated through an evaluation of the magnetic flux density within the entire volume of interest. The magnet has a field-to-current constant of 0.728 mT/A, allowing to switch from zero to 0.125 T in less than 3 ms without energy storage assistance. For a cylindrical sample volume of 35 cm(3) the effective magnet homogeneity is lower than 130 ppm. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Addiction Machines

    Directory of Open Access Journals (Sweden)

    James Godley

    2011-10-01

    Full Text Available Entry into the crypt William Burroughs shared with his mother opened and shut around a failed re-enactment of William Tell’s shot through the prop placed upon a loved one’s head. The accidental killing of his wife Joan completed the installation of the addictation machine that spun melancholia as manic dissemination. An early encryptment to which was added the audio portion of abuse deposited an undeliverable message in WB. Wil- liam could never tell, although his corpus bears the in- scription of this impossibility as another form of pos- sibility. James Godley is currently a doctoral candidate in Eng- lish at SUNY Buffalo, where he studies psychoanalysis, Continental philosophy, and nineteenth-century litera- ture and poetry (British and American. His work on the concept of mourning and “the dead” in Freudian and Lacanian approaches to psychoanalytic thought and in Gothic literature has also spawned an essay on zombie porn. Since entering the Academy of Fine Arts Karlsruhe in 2007, Valentin Hennig has studied in the classes of Sil- via Bächli, Claudio Moser, and Corinne Wasmuht. In 2010 he spent a semester at the Dresden Academy of Fine Arts. His work has been shown in group exhibi- tions in Freiburg and Karlsruhe.

  15. Machine musicianship

    Science.gov (United States)

    Rowe, Robert

    2002-05-01

    The training of musicians begins by teaching basic musical concepts, a collection of knowledge commonly known as musicianship. Computer programs designed to implement musical skills (e.g., to make sense of what they hear, perform music expressively, or compose convincing pieces) can similarly benefit from access to a fundamental level of musicianship. Recent research in music cognition, artificial intelligence, and music theory has produced a repertoire of techniques that can make the behavior of computer programs more musical. Many of these were presented in a recently published book/CD-ROM entitled Machine Musicianship. For use in interactive music systems, we are interested in those which are fast enough to run in real time and that need only make reference to the material as it appears in sequence. This talk will review several applications that are able to identify the tonal center of musical material during performance. Beyond this specific task, the design of real-time algorithmic listening through the concurrent operation of several connected analyzers is examined. The presentation includes discussion of a library of C++ objects that can be combined to perform interactive listening and a demonstration of their capability.

  16. Experimental investigation of the degree of weakening in structural notch area of 7075-T6 aluminum alloy sheet welded with the RFSSW method

    Directory of Open Access Journals (Sweden)

    Kubit Andrzej

    2017-01-01

    Full Text Available The paper presents the methodology of the research determining the degree of weakening of the welded sheet obtained by the refill friction stir spot welding (RFSSW method. The considered weakness is the effect of a structural notch resulting from penetration by the tool. RFSSW technology is a relatively new method of joining metals, which can successfully provide an alternative to resistance welding or riveting - traditionally used methods of joining thin-walled structures in the aerospace and automotive industries. The study presented in the paper focuses on the overlapping of sheet metal with 7075-T6 aluminum alloy combined in the configuration: 1.6 mm top sheet and 0.8 mm bottom sheet. Joints were assembled following the following process parameters: Welding time 1.5 s, the tool plunge depth in the range of 1.5 ÷ 1.9 mm, and the spindle speed of 2600 rpm. The analysis of the microstructure of joints revealed that along the edge of the tool path a structural notch is formed, the size and shape of which depend on the parameters applied. The paper describes the study consisting in punching the welded area along the formed notch in the upper sheet. The punching process was performed on a universal testing machine and the punching force was measured during the test. Based on the force value, the degree of sheet weakening in the notched area was determined. The smallest weakening was observed in joints made with the smallest tool depth, i.e. 1.5 mm, whereas the biggest weakening was obtained for tool depth of 1.9 mm. The load applied to the joints was equal to 5290N and 7585N respectively.

  17. Rotary Ultrasonic Machining of Poly-Crystalline Cubic Boron Nitride

    Directory of Open Access Journals (Sweden)

    Kuruc Marcel

    2014-12-01

    Full Text Available Poly-crystalline cubic boron nitride (PCBN is one of the hardest material. Generally, so hard materials could not be machined by conventional machining methods. Therefore, for this purpose, advanced machining methods have been designed. Rotary ultrasonic machining (RUM is included among them. RUM is based on abrasive removing mechanism of ultrasonic vibrating diamond particles, which are bonded on active part of rotating tool. It is suitable especially for machining hard and brittle materials (such as glass and ceramics. This contribution investigates this advanced machining method during machining of PCBN.

  18. INVESTIGATION OF MAGNESIUM ALLOYS MACHINABILITY

    Directory of Open Access Journals (Sweden)

    Berat Barıs BULDUM

    2013-01-01

    Full Text Available Magnesium is the lightest structural metal. Magnesium alloys have a hexagonal lattice structure, which affects the fundamental properties of these alloys. Plastic deformation of the hexagonal lattice is more complicated than in cubic latticed metals like aluminum, copper and steel. Magnesium alloy developments have traditionally been driven by industry requirements for lightweight materials to operate under increasingly demanding conditions. Magnesium alloys have always been attractive to designers due to their low density, only two thirds that of aluminium and its alloys [1]. The element and its alloys take a big part of modern industry needs. Especially nowadays magnesium alloys are used in automotive and mechanical (trains and wagons manufacture, because of its lightness and other features. Magnesium and magnesium alloys are the easiest of all metals to machine, allowing machining operations at extremely high speed. All standard machining operations such as turning, drilling, milling, are commonly performed on magnesium parts.

  19. 40 CFR 63.463 - Batch vapor and in-line cleaning machine standards.

    Science.gov (United States)

    2010-07-01

    .... (3) Each cleaning machine shall have an automated parts handling system capable of moving parts or... of parts through removal of cleaned parts. (4) Each vapor cleaning machine shall be equipped with a...) and appendix A to this part. (2) Each owner or operator of a batch vapor cleaning machine with a...

  20. 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.

  1. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  2. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

  5. Effect of machining fluid on the process performance of wire electrical discharge machining of nanocomposite ceramic

    Directory of Open Access Journals (Sweden)

    Zhang Chengmao

    2015-01-01

    Full Text Available Wire electric discharge machining (WEDM promise to be effective and economical techniques for the production of tools and parts from conducting ceramic blanks. However, the manufacturing of nanocomposite ceramics blanks with these processes is a long and costly process. This paper presents a new process of machining nanocomposite ceramics using WEDM. WEDM uses water based emulsion, polyvinyl alcohol and distilled water as the machining fluid. Machining fluid is a primary factor that affects the material removal rate and surface quality of WEDM. The effects of emulsion concentration, polyvinyl alcohol concentration and distilled water of the machining fluid on the process performance have been investigated.

  6. 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

  7. Effect of the Cutting Tool Geometry on the Tool Wear Resistance When Machining Inconel 625

    Directory of Open Access Journals (Sweden)

    Tomáš Zlámal

    2017-12-01

    Full Text Available The paper deals with the design of a suitable cutting geometry of a tool for the machining of the Inconel 625 nickel alloy. This alloy is among the hard-to-machine refractory alloys that cause very rapid wear on cutting tools. Therefore, SNMG and RCMT indexable cutting insert were used to machine the alloy. The selected insert geometry should prevent notch wear and extend tool life. The alloy was machined under predetermined cutting conditions. The angle of the main edge and thus the size and nature of the wear changed with the depth of the material layer being cut. The criterion for determining a more suitable cutting geometry was the tool’s durability and the roughness of the machined surface.

  8. Effect of the Cutting Tool Geometry on the Tool Wear Resistance when Machining Inconel 625

    Directory of Open Access Journals (Sweden)

    Tomáš Zlámal

    2018-03-01

    Full Text Available The paper deals with the design of a suitable cutting geometry of a tool for the machining of the Inconel 625 nickel alloy. This alloy is among the hard-to-machine refractory alloys that cause very rapid wear on cutting tools. Therefore, SNMG and RCMT indexable cutting insert were used to machine the alloy. The selected insert geometry should prevent notch wear and extend tool life. The alloy was machined under predetermined cutting conditions. The angle of the main edge and thus the size and nature of the wear changed with the depth of the material layer being cut. The criterion for determining a more suitable cutting geometry was the tool’s durability and the roughness of the machined surface.

  9. The Serger (Overlock) Machine. Module 10.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the purpose and use of the serger machine, one in a series on clothing construction for industrial sewing machine operators designed for student self-study, contains nine sections. Each section includes the following parts: an introduction, directions, an objective, learning activities, student information, student self-check,…

  10. Budker INP in the LHC Machine (2)

    CERN Multimedia

    2001-01-01

    The main BINP contributions to the LHC machine are magnets for transfer lines (26 MCHF) and bus- bar sets (23 MCHF). Budker INP is also responsible for construction of some other LHC magnets and vacuum parts. In total, the contribution to the LHC machine will reach about 90 MCHF.

  11. Device for electron beam machining

    International Nuclear Information System (INIS)

    Panzer, S.; Ardenne, T. von; Liebergeld, H.

    1984-01-01

    The invention concerns a device for electron beam machining, in particular welding. It is aimed at continuous operation of the electron irradiation device. This is achieved by combining the electron gun with a beam guiding chamber, to which vacuum chambers are connected. The working parts to be welded can be arranged in the latter

  12. Man-machine design integration

    Energy Technology Data Exchange (ETDEWEB)

    Carrera, J.P. [Westinghouse Electric Corp., Monroeville, PA (United States). Nuclear Technology Div.; Haentjens, J. [Westinghouse Electric Corp., Brussels (Belgium). Nuclear Technology Div.

    1995-12-31

    The presentation overviews the bases for Man-Machine Interface (MMI) designs that are part of three other presentations during the same conference: Advanced Alarm Management System, Functional Displays and System for Emergency Procedure Execution Monitoring. The MMD group history, team and goals are summarized to give some context to the core of the MMD philosophy and integration. (10 refs., 5 figs.).

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  14. Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch

    DEFF Research Database (Denmark)

    López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca

    2015-01-01

    Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. T...

  15. 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.

  16. Notch root strain measurement of WE43-T6 magnesium alloy using electronic speckle pattern interferometry

    International Nuclear Information System (INIS)

    Liew, H.L.; Ahmad, A.; Ramesh, S.; Purbolaksono, J.

    2013-01-01

    Highlights: • The use of ESPI for measuring total strains at the notch root of specimens. • Fine meshing in micron scale at the notch root regions. • The maximum elastic strain is shifted to be further away from the notch root tip. - Abstract: The notch root elasto-plastic strains of circumferentially grooved round specimen of cast magnesium WE43-T6 were experimentally measured using the electronic speckle pattern interferometry (ESPI) and numerically evaluated using the finite element analysis (FEA). The specimens have notch radii of 1.6 mm and 0.8 mm and an opening angle of 60°. The technique of ESPI showed its accuracy in measuring three-dimensional surface deformations on large negatively curved manifolds. The measured nominal stress for rupture is well beyond the ultimate strength, suggesting the existence of significant biaxial stress at the notch root region. The ESPI-based strains on the notch tips were shown to be in agreement with those evaluated by the FEA. The FEA also showed that the maximum elastic strain is shifted away from the notch root surface as the plastic strain is predominant

  17. Stress concentration factors for an internally pressurized circular vessel containing a radial U-notch

    International Nuclear Information System (INIS)

    Carvalho, E.A. de

    2005-01-01

    This paper evaluates the stress concentration factors for an internally pressurized cylinder containing a radial U-notch along its length. This work studies the cases where the external to internal radius ratio (Ψ) is equal to 1.26, 1.52, 2.00, and 3.00 and the notch radius to internal radius ratio (Φ) is fixed and equal to 0.026. The U-notch depth varies from 0.1 to 0.6 of the wall thickness. Results are also presented for a fixed size semi-circular notch. Hoop stresses at the external wall are presented, showing regions where the stress matches the nominal one and the favourable places to install strain sensors. The finite element method is used to determine the stress concentration factors (K t ) for the above described situations and for a special case where a varying semi-circular notch is present with Ψ=3.00. This notch depth varies from 0.013 to 0.3 of the wall thickness. It is pointed out that even relatively small notches introduce large stress concentrations and disrupt the hoop stress distribution all over the cross section. Results are also compared to an example found in the literature for semi-circular notches and K t curves for both cases present the same shape

  18. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept

    NARCIS (Netherlands)

    Rutten, J.W.; Dauwerse, H.G.; Peters, D.J.; Goldfarb, A.; Venselaar, H.; Haffner, C.; Ommen, G.J. van; Aartsma-Rus, A.M.; Oberstein, S.A.

    2016-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL, is a hereditary cerebral small vessel disease caused by characteristic cysteine altering missense mutations in theNOTCH3gene.NOTCH3mutations in CADASIL result in an uneven number of cysteine

  19. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

    NARCIS (Netherlands)

    Amsen, Derk; Antov, Andrey; Jankovic, Dragana; Sher, Alan; Radtke, Freddy; Souabni, Abdallah; Busslinger, Meinrad; McCright, Brent; Gridley, Thomas; Flavell, Richard A.

    2007-01-01

    CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Science.gov (United States)

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Machine technology: a survey

    International Nuclear Information System (INIS)

    Barbier, M.M.

    1981-01-01

    An attempt was made to find existing machines that have been upgraded and that could be used for large-scale decontamination operations outdoors. Such machines are in the building industry, the mining industry, and the road construction industry. The road construction industry has yielded the machines in this presentation. A review is given of operations that can be done with the machines available

  6. Machine Shop Lathes.

    Science.gov (United States)

    Dunn, James

    This guide, the second in a series of five machine shop curriculum manuals, was designed for use in machine shop courses in Oklahoma. The purpose of the manual is to equip students with basic knowledge and skills that will enable them to enter the machine trade at the machine-operator level. The curriculum is designed so that it can be used in…

  7. Superconducting rotating machines

    International Nuclear Information System (INIS)

    Smith, J.L. Jr.; Kirtley, J.L. Jr.; Thullen, P.

    1975-01-01

    The opportunities and limitations of the applications of superconductors in rotating electric machines are given. The relevant properties of superconductors and the fundamental requirements for rotating electric machines are discussed. The current state-of-the-art of superconducting machines is reviewed. Key problems, future developments and the long range potential of superconducting machines are assessed

  8. Machine Protection System response in 2011

    CERN Document Server

    Zerlauth, M; Wenninger, J

    2012-01-01

    The performance of the machine protection system during the 2011 run is summarized in this paper. Following an analysis of the beam dump causes in comparison to the previous 2010 run, special emphasis will be given to analyse events which risked to exposed parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems as well as in the change management will be evaluated along with their impact on the 2012 run. The role of the restricted Machine Protection Panel ( rMPP ) during the various operational phases such as commissioning, the intensity ramp up and Machine Developments is being discussed.

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

    Directory of Open Access Journals (Sweden)

    Floriane Auderset

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

  10. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  11. Mutual inactivation of Notch receptors and ligands facilitates developmental patterning.

    Directory of Open Access Journals (Sweden)

    David Sprinzak

    2011-06-01

    Full Text Available Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation. This model with mutual inactivation also exhibits robustness to correlated gene expression perturbations. For lateral inhibition, we find that mutual inactivation speeds up patterning dynamics, relieves the need for cooperative regulatory interactions, and expands the range of parameter values that permit pattern formation, compared to canonical models. Furthermore, mutual inactivation enables a simple lateral inhibition circuit architecture which requires only a single downstream regulatory step. Both model systems show how mutual inactivation can facilitate robust fine-grained patterning processes that would be difficult to implement without it, by encoding a difference-promoting feedback within the signaling system itself. Together, these results provide a framework for analysis of more complex Notch-dependent developmental systems.

  12. Neuropsychological findings in a patient with Kernohan's notch.

    Science.gov (United States)

    Clement, V L; Sherer, M

    1996-05-01

    This case report describes the use of neuropsychological testing to Iocalize and diagnose lesions The testing was instrumental in disentangling contradictory symptoms to reveal a Kernohan's notch (later confirmed by MRI), thus ruling out incorrect diagnoses We describe the case of a 36-year-old right-handed man who developed a left epidural hematoma after suffering head trauma from a blunt instrument Sequelae 2 months post-injury included left hemiparesis (ipsilateral to the lesion), dysphonic speech, severe naming/word-finding deficits, and severe memory impairment This patient's symptom pattern presented somewhat of a mystery as his cognitive deficits appeared consistent with left hemisphere damage, while his left motor symptoms suggested right hemisphere damage Medical records were inconsistent Deficits on neuropsychological testing at 3 months post-injury included impairment in verbal and visual memory, confrontation naming, and left-sided motor function Attention, visual-spatial skills, nonverbal problem solving, and right motor speed and coordination were intact A herniation syndrome, Kernohan's notch, was considered to be the most likely explanation This phenomenon occurs when a mass occupying lesion causes significant midline shift of the midbrain, pressing the contralateral cerebral peduncle against the tentorium This pressure produces an ischemic infact in the region of the corticospinal (motor) pathways Subsequent MRI confirmed a lesion in the right cerebral crus The pattern of neuropsychological finding in this patient is discussed.

  13. Design of Two Novel Dual Band-Notched UWB Antennas

    Directory of Open Access Journals (Sweden)

    Bing Li

    2012-01-01

    Full Text Available Two novel dual band-notched ultra-wideband (UWB printed monopole antennas with simple structure and small size are presented. The size of both antennas is 25×25×0.8 mm3. The bandwidth of one of the proposed antenna can be from 2.7 GHz to 36.8 GHz, except the bandwidth of 3.2–3.9 GHz for WiMAX applications and 5.14–5.94 GHz for WLAN applications. The bandwidth of the other is ranging for 2.7 to 41.1 GHz, except the bandwidth of 3.2–3.9 GHz for WiMAX applications and 4.8–5.9 GHz for WLAN applications. Bandwidths of the antennas are about 512% and 455% wider than those of conventional band-notched UWB antennas, respectively. In addition, the time-domain characteristics of the two antennas are investigated to show the difference between both antennas.

  14. Machine drawing

    CERN Document Server

    Narayana, KL; Reddy, K Venkata

    2006-01-01

    About the Book: Written by three distinguished authors with ample academic and teaching experience, this textbook, meant for diploma and degree students of Mechanical Engineering as well as those preparing for AMIE examination, incorporates the latest standards. The new edition includes the features of assembly drawings, part drawings and computer-aided drawings to cater to the needs of students pursuing various courses. The text of the new edition has been thoroughly revised to include new concepts and practices in the subject. It should prove an ideal textbook. Contents: Introduction

  15. 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.

  16. 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.

  17. Modularity Design Approach for Preventive Machine Maintenance

    Science.gov (United States)

    Ernawati, D.; Pudji, E.; Ngatilah, Y.; Handoyo, R.

    2018-01-01

    In a company, machine maintenance system will be very influential in production process activity. The company should have a scheduled engine maintenance system that does not require high costs when repairing and replacing machine parts. Modularity Design method is able to provide solutions to the engine maintenance scheduling system and can prevent fatal damage to the engine components. It can minimize the cost of repair and replacement of these machine components.The paper provides a solution to machine maintenance problems. The paper is also completed with case study of milling machines. That case studies can give us a real description about impact implementation of modularity design to prevent fatal damage to components and minimize the cost of repair and replacement of components of the machine.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  19. Controls and Machine Protection Systems

    CERN Document Server

    Carrone, E.

    2016-01-01

    Machine protection, as part of accelerator control systems, can be managed with a 'functional safety' approach, which takes into account product life cycle, processes, quality, industrial standards and cybersafety. This paper will discuss strategies to manage such complexity and the related risks, with particular attention to fail-safe design and safety integrity levels, software and hardware standards, testing, and verification philosophy. It will also discuss an implementation of a machine protection system at the SLAC National Accelerator Laboratory's Linac Coherent Light Source (LCLS).

  20. 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

  1. Machine intelligence. Part 2. Biological foundations

    Energy Technology Data Exchange (ETDEWEB)

    Scanlon, R.; Johnson, M.

    1990-08-01

    This report describes the material aspects of how perceptions, existing as codons within the neocortex, are formed through synaptogenesis, synaptic potentiation, depotentiation, and shedding. A simulation of this process on an array of transputers is also discussed.

  2. Determining minimum lubrication film for machine parts

    Science.gov (United States)

    Hamrock, B. J.; Dowson, D.

    1978-01-01

    Formula predicts minimum film thickness required for fully-flooded ball bearings, gears, and cams. Formula is result of study to determine complete theoretical solution of isothermal elasto-hydrodynamic lubrication of fully-flooded elliptical contacts.

  3. Paleo-watertable definition using cave ferromanganese stromatolites and associated cave-wall notches (Sierra de Arnero, Spain)

    Science.gov (United States)

    Rossi, Carlos; Villalaín, Juan J.; Lozano, Rafael P.; Hellstrom, John

    2016-05-01

    The steeply-dipping-dolostone-hosted caves of the Sierra de Arnero (N Spain) contain low-gradient relict canyons with up to ten mapped levels of ferromanganese stromatolites and associated wall notches over a vertical range of 85 m, the highest occurring 460 m above base level. Despite a plausible speleogenetic contribution by pyrite oxidation, and the irregular cave-wall mesomorphologies suggestive of hypogenic speleogenesis, the Arnero relict caves are dominantly epigenic, as indicated by the conduit pattern and the abundant allogenic sediments. Allogenic input declined over time due to a piracy-related decrease in the drainage area of allogenic streams, explaining the large size of the relict Arnero caves relative to the limited present-day outcrop area of the karstified carbonates. Allogenic-sediment input also explains the observed change from watertable canyons to phreatic conduits in the paleo-downstream direction. Stromatolites and notches arguably formed in cave-stream passages at the watertable. The best-defined paleo-watertables show an overall slope of 1.7°, consistent with the present-day relief of the watertable, with higher-slope segments caused by barriers related to sulfide mineralization. The formation of watertable stromatolites favored wall notching by the combined effect of enhanced acidity by Mn-Fe oxidation and shielding of cave floors against erosion. Abrasive bedload further contributed to notch formation by promoting lateral mechanical erosion and protecting passage floors. The irregular wallrock erosional forms of Arnero caves are related partly to paragenesis and partly to the porous nature of the host dolostones, which favored irregular dissolution near passage walls, generating friable halos. Subsequent mechanical erosion contributed to generate spongework patterns. The dolostone porosity also contributes to explain the paradox that virtually all Arnero caves are developed in dolostone despite being less soluble than adjacent

  4. Mineral mining machines

    Energy Technology Data Exchange (ETDEWEB)

    Mc Gaw, B H

    1984-01-01

    A machine for mining minerals is patented. It is a cutter loader with a drum actuating element of the worm type equipped with a multitude of cutting teeth reinforced with tungsten carbide. A feature of the patented machine is that all of the cutting teeth and holders on the drum have the identical design. This is achieved through selecting a slant angle for the cutting teeth which is the mean between the slant angle of the conventional radial teeth and the slant angle of the advance teeth. This, in turn, is provided thanks to the corresponding slant of the holders relative to the drum and (or) the slant of the cutting part of the teeth relative to their stems. Thus, the advance teeth projecting beyond the surface of the drum on the face side and providing upper and lateral clearances have the same angle of attack as the radial teeth, that is, from 20 to 35 degrees. A series of modifications of the cutting teeth is patented. One of the designs allows the cutting tooth to occupy a varying position relative to the drum, from the conventional vertical to an inverted, axially projecting position. In the last case the tooth in the extraction process provides the upper and lateral clearances for the drum on the face side. Among the different modifications of the cutting teeth, a design is proposed which provides for the presence of a stem which is shaped like a truncated cone. This particular stem is designed for use jointly with a wedge which unfastens the teeth and is placed in a holder. The latter is completed in a transverse slot thanks to which the rear end of the stem is compressed, which simplifies replacement of a tooth. Channels are provided in the patented machine for feeding water to the worm spiral, the holders and the cutting teeth themselves in order to deal with dust.

  5. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Science.gov (United States)

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Virtual machining considering dimensional, geometrical and tool deflection errors in three-axis CNC milling machines

    OpenAIRE

    Soori, Mohsen; Arezoo, Behrooz; Habibi, Mohsen

    2014-01-01

    Virtual manufacturing systems can provide useful means for products to be manufactured without the need of physical testing on the shop floor. As a result, the time and cost of part production can be decreased. There are different error sources in machine tools such as tool deflection, geometrical deviations of moving axis and thermal distortions of machine tool structures. Some of these errors can be decreased by controlling the machining process and environmental parameters. However other e...

  7. Virtual machining considering dimensional, geometrical and tool deflection errors in three-axis CNC milling machines

    OpenAIRE

    Soori, Mohsen; Arezoo, Behrooz; Habibi, Mohsen

    2016-01-01

    Virtual manufacturing systems can provide useful means for products to be manufactured without the need of physical testing on the shop floor. As a result, the time and cost of part production can be decreased. There are different error sources in machine tools such as tool deflection, geometrical deviations of moving axis and thermal distortions of machine tool structures. Some of these errors can be decreased by controlling the machining process and environmental parameters. However other e...

  8. Reliability assessment of the fueling machine of the CANDU reactor

    International Nuclear Information System (INIS)

    Al-Kusayer, T.A.

    1985-01-01

    Fueling of CANDU-reactors is carried out by two fueling machines, each serving one end of the reactor. The fueling machine becomes a part of the primary heat transport system during the refueling operations, and hence, some refueling machine malfunctions could result in a small scale-loss-of-coolant accident. Fueling machine failures and the failure sequences are discussed. The unavailability of the fueling machine is estimated by using fault tree analysis. The probability of mechanical failure of the fueling machine interface is estimated as 1.08 x 10 -5 . (orig.) [de

  9. Giro form reading machine

    Science.gov (United States)

    Minh Ha, Thien; Niggeler, Dieter; Bunke, Horst; Clarinval, Jose

    1995-08-01

    Although giro forms are used by many people in daily life for money remittance in Switzerland, the processing of these forms at banks and post offices is only partly automated. We describe an ongoing project for building an automatic system that is able to recognize various items printed or written on a giro form. The system comprises three main components, namely, an automatic form feeder, a camera system, and a computer. These components are connected in such a way that the system is able to process a bunch of forms without any human interactions. We present two real applications of our system in the field of payment services, which require the reading of both machine printed and handwritten information that may appear on a giro form. One particular feature of giro forms is their flexible layout, i.e., information items are located differently from one form to another, thus requiring an additional analysis step to localize them before recognition. A commercial optical character recognition software package is used for recognition of machine-printed information, whereas handwritten information is read by our own algorithms, the details of which are presented. The system is implemented by using a client/server architecture providing a high degree of flexibility to change. Preliminary results are reported supporting our claim that the system is usable in practice.

  10. Properties of Free-Machining Aluminum Alloys at Elevated Temperatures

    Science.gov (United States)

    Faltus, Jiří; Karlík, Miroslav; Haušild, Petr

    In areas close to the cutting tool the workpieces being dry machined could be heated up to 350°C and they may be impact loaded. Therefore it is of interest to study mechanical properties of corresponding materials at elevated temperatures. Free-machining alloys of Al-Cu and Al-Mg-Si systems containing Pb, Bi and Sn additions (AA2011, AA2111B, AA6262, and AA6023) were subjected to Charpy U notch impact test at the temperatures ranging from 20 to 350°C. The tested alloys show a sharp drop in notch impact strength KU at different temperatures. This drop of KU is caused by liquid metal embrittlement due to the melting of low-melting point dispersed phases which is documented by differential scanning calorimetry. Fracture surfaces of the specimens were observed using a scanning electron microscope. At room temperature, the fractures of all studied alloys exhibited similar ductile dimple fracture micromorphology, at elevated temperatures, numerous secondary intergranular cracks were observed.

  11. Machine tool structures

    CERN Document Server

    Koenigsberger, F

    1970-01-01

    Machine Tool Structures, Volume 1 deals with fundamental theories and calculation methods for machine tool structures. Experimental investigations into stiffness are discussed, along with the application of the results to the design of machine tool structures. Topics covered range from static and dynamic stiffness to chatter in metal cutting, stability in machine tools, and deformations of machine tool structures. This volume is divided into three sections and opens with a discussion on stiffness specifications and the effect of stiffness on the behavior of the machine under forced vibration c

  12. 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.

  13. 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.

  14. 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.

  15. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.

    Science.gov (United States)

    Al Jaam, Bilal; Heu, Katy; Pennarubia, Florian; Segelle, Alexandre; Magnol, Laetitia; Germot, Agnès; Legardinier, Sébastien; Blanquet, Véronique; Maftah, Abderrahman

    2016-09-01

    Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/cax) mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1(cax/cax) SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7(+)/MYOD(-) progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice. © 2016 The Authors.

  16. 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.

  17. Notch1 regulates hippocampal plasticity through interaction with the Reelin pathway, glutamatergic transmission and CREB signaling

    Directory of Open Access Journals (Sweden)

    Emanuele eBrai

    2015-11-01

    Full Text Available Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment of memory in mice. We observe that Notch1 is a postsynaptic receptor with functional interactions with the Reelin receptor, ApoER2, and the ionotropic receptor, NMDAR. Targeted loss of Notch1 in the hippocampal CA fields affects Reelin signaling by influencing Dab1 expression and impairs the synaptic potentiation achieved through Reelin stimulation. Further analysis indicates that loss of Notch1 affects the expression and composition of the NMDAR but not AMPAR. Glutamatergic signaling is further compromised through downregulation of CamKII and its secondary and tertiary messengers resulting in reduced CREB signaling. Our results identify Notch1 as an important regulator of mechanisms involved in synaptic plasticity and memory formation. These findings emphasize the possible involvement of this signaling receptor in dementia.

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

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Matthew R. Broadus

    2016-05-01

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

  1. 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.

  2. Influence of Different Rotor Teeth Shapes on the Performance of Flux Switching Permanent Magnet Machines Used for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    2014-12-01

    Full Text Available This paper investigated a 12-slot/11-pole flux switching permanent magnet (FSPM machine used for electric vehicles (EVs. Five novel rotor teeth shapes are proposed and researched to reduce the cogging torque and torque ripple of the FSPM machine. These rotor teeth shapes are notched teeth, stepped teeth, eccentric teeth, combination of notched and stepped teeth, and combination of notched and eccentric teeth. They are applied on the rotor and optimized, respectively. The influences of different rotor teeth shapes on cogging torque, torque ripple and electromagnetic torque are analyzed by the 2-D finite-element method (FEM. Then, the performance of FSPMs with different rotor teeth shapes are compared and evaluated comprehensively from the points of view of cogging torque, torque ripple, electromagnetic torque, flux linkage, back electromotive force (EMF, and so on. The results show that the presented rotor teeth shapes, especially the combination of stepped and notched teeth, can greatly reduce the cogging torque and torque ripple with only slight changes in the average electromagnetic torque.

  3. Fatigue damage mechanics of notched graphite-epoxy laminates

    Science.gov (United States)

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

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

  4. Self-collimation-based photonic crystal notch filters

    International Nuclear Information System (INIS)

    Lee, Sun-Goo; Kim, Seong-Han; Kee, Chul-Sik; Kim, Kap-Joong

    2017-01-01

    We introduce a design concept of an optical notch filter (NF) utilizing two perfectly reflecting mirrors and a beam splitter. Based on the new design concept, a photonic crystal (PC)-NF based on the self-collimation phenomenon in a two-dimensional PC is proposed and studied through finite-difference time-domain simulations and experimental measurements in a microwave region. The transmission properties of the self-collimation-based PC-NF were demonstrated to be controlled by adjusting the values of parameters such as the radius of rods in the line-defect beam splitter, distance between the two perfectly reflecting mirrors, and radius of rods on the outermost surface of the perfectly reflecting mirrors. Our results indicate that the proposed design concept could provide a new approach to manipulate light propagation, and the PC-NF could increase the applicability of the self-collimation phenomenon in a PC. (paper)

  5. Simplified elastoplastic methods of analysing fatigue in notches

    International Nuclear Information System (INIS)

    Autrusson, B.

    1993-01-01

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

  6. 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.

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

    Science.gov (United States)

    Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

    2012-09-21

    The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

  8. 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.

  9. The effect of shot peening on notched low cycle fatigue

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  12. Tunnel boring machine applications

    International Nuclear Information System (INIS)

    Bhattacharyya, K.K.; McDonald, R.; Saunders, R.S.

    1992-01-01

    This paper reports that characterization of Yucca Mountain for a potential repository requires construction of an underground Exploratory Studies Facility (ESF). Mechanical excavating methods have been proposed for construction of the ESF as they offer a number of advantages over drilling and blasting at the Yucca Mountain site, including; less ground disturbance and therefore a potential for less adverse effects on the integrity of the site, creation of a more stable excavation cross section requiring less ground support, and an inherently safer and cleaner working environment. The tunnel boring machine (TBM) provides a proven technology for excavating the welded and unwelded Yucca Mountain tuffs. The access ramps and main underground tunnels form the largest part of the ESF underground construction work, and have been designed for excavation by TBM

  13. Chondromalacia of trochlear notch after healing of olecranon stress fracture: a case report.

    Science.gov (United States)

    Lu, Cheng-Chang; Chen, Shen-Kai; Wang, Chih-Wei; Chou, Pei-Hsi

    2006-05-01

    Chondromalacia of the trochlear notch and stress fracture of olecranon are uncommon injuries in the throwing athletes. We report an 18-year-old high school pitcher who had persistent postero-lateral elbow pain after a healed olecranon stress fracture of the right elbow. Diagnostic arthroscopy revealed chondromalacia of the trochlear notch. After treatment with arthroscopic drilling and abrasion chondroplasty, he returned to competitive pitching 1 year later postsurgery. This rare association between chondromalacia and stress fracture of the olecranon has not been reported previously in the literatures. Chondromalacia of the trochlear notch should be included as a differential diagnosis in evaluating athletes with persistent elbow pain after healed olecranon stress fractures.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

  16. Notch and hydrogen effects on sensitized 21-6-9 stainless steel

    International Nuclear Information System (INIS)

    Caskey, C.R. Jr.

    1979-01-01

    Type 21-6-9 stainless steel alloy is slightly notch sensitive in the solution annealed condition, a behavior that is aggravated by sensitization anneal at 920 0 K. The lower toughness of the sensitized alloy is a measure of microstructural embrittlement associated with carbide precipitation in grain boundaries. The tendency toward grain boundary fracture in the sensitized alloy is accentuated by stress concentration at the notch. Also, there is an increase in notch sensitivity when the alloy is tested in a high pressure (69 MPa) hydrogen environment, due to susceptibility of the grain boundaries to hydrogen embrittlement

  17. UWB Filtering Power Divider with Two Narrow Notch-bands and Wide Stop-band

    Science.gov (United States)

    Wei, Feng; Wang, Xin-Yi; Zou, Xin Tong; Shi, Xiao Wei

    2017-12-01

    A compact filtering ultra-wideband (UWB) microstrip power divider (PD) with two sharply rejected notch-bands and wide stopband is analyzed and designed in this paper. The proposed UWB PD is based on a conventional Wilkinson power divider, while two stub loaded resonators (SLRs) are coupled into two symmetrical output ports to achieve a bandpass filtering response. The simplified composite right/left-handed (SCRLH) resonators are employed to generate the dual notched bands. Defected ground structure (DGS) is introduced to improve the passband performance. Good insertion/return losses, isolation and notch-band rejection are achieved as demonstrated in both simulation and experiment.

  18. Effects of Notch Introduction on 3-Point Bending Cutting Characteristics of Frozen Fish

    OpenAIRE

    Hagura, Yoshio; Suzuki, Kanichi

    2002-01-01

    We have proposed a freeze cutting method in which a three point bending load is applied on a frozen fish body to cut in round slices. Lowering the three-point bending load can facilitate the freeze cutting processing. Based on the idea that a notch in the fish body may lower the cutting load, the effect of introducing a notch was examined with respect to cutting stress and smoothness of cut surface in model fish meat and in saury. It was found that the introduced notch effectively lowered the...

  19. 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...

  20. Thermally induced high frequency random amplitude fatigue damage at sharp notches

    International Nuclear Information System (INIS)

    Lewis, M.W.J.

    1992-01-01

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

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

    Science.gov (United States)

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

    2018-06-19

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

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

    Science.gov (United States)

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

    2010-02-01

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

  3. INFLUENCE OF STRUCTURE COMPONENTS ON MACHINE TOOL ACCURACY

    Directory of Open Access Journals (Sweden)

    ConstantinSANDU

    2017-11-01

    Full Text Available For machine tools, the accuracy of the parts of the machine tool structure (after roughing should be subject to relief and natural or artificial aging. The performance of the current accuracy of machine tools as linearity or flatness was higher than 5 μm/m. Under this value there are great difficulties. The performance of the structure of the machine tools in the manufacture of structural parts of machine tools, with a flatness accuracy that the linearity of about 2 μm/m, are significant deviations form of their half-finished. This article deals with the influence of errors of form of semifinished and machined parts on them, on their shape and especially what happens to structure machine tools when the components of the structure were assembling this.

  4. MITS machine operations

    International Nuclear Information System (INIS)

    Flinchem, J.

    1980-01-01

    This document contains procedures which apply to operations performed on individual P-1c machines in the Machine Interface Test System (MITS) at AiResearch Manufacturing Company's Torrance, California Facility

  5. Brain versus Machine Control.

    Directory of Open Access Journals (Sweden)

    Jose M Carmena

    2004-12-01

    Full Text Available Dr. Octopus, the villain of the movie "Spiderman 2", is a fusion of man and machine. Neuroscientist Jose Carmena examines the facts behind this fictional account of a brain- machine interface

  6. Applied machining technology

    CERN Document Server

    Tschätsch, Heinz

    2010-01-01

    Machining and cutting technologies are still crucial for many manufacturing processes. This reference presents all important machining processes in a comprehensive and coherent way. It includes many examples of concrete calculations, problems and solutions.

  7. Machining with abrasives

    CERN Document Server

    Jackson, Mark J

    2011-01-01

    Abrasive machining is key to obtaining the desired geometry and surface quality in manufacturing. This book discusses the fundamentals and advances in the abrasive machining processes. It provides a complete overview of developing areas in the field.

  8. Machine medical ethics

    CERN Document Server

    Pontier, Matthijs

    2015-01-01

    The essays in this book, written by researchers from both humanities and sciences, describe various theoretical and experimental approaches to adding medical ethics to a machine in medical settings. Medical machines are in close proximity with human beings, and getting closer: with patients who are in vulnerable states of health, who have disabilities of various kinds, with the very young or very old, and with medical professionals. In such contexts, machines are undertaking important medical tasks that require emotional sensitivity, knowledge of medical codes, human dignity, and privacy. As machine technology advances, ethical concerns become more urgent: should medical machines be programmed to follow a code of medical ethics? What theory or theories should constrain medical machine conduct? What design features are required? Should machines share responsibility with humans for the ethical consequences of medical actions? How ought clinical relationships involving machines to be modeled? Is a capacity for e...

  9. Learning Activity Packets for Milling Machines. Unit I--Introduction to Milling Machines.

    Science.gov (United States)

    Oklahoma State Board of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This learning activity packet (LAP) outlines the study activities and performance tasks covered in a related curriculum guide on milling machines. The course of study in this LAP is intended to help students learn to identify parts and attachments of vertical and horizontal milling machines, identify work-holding devices, state safety rules, and…

  10. The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele.

    Science.gov (United States)

    Zanotti, Stefano; Canalis, Ernesto

    2016-05-01

    Activation of Notch1 in osteocytes of Rosa(Notch) mice, where a loxP-flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling. To determine whether Sost downregulation mediates the effects of Notch activation in osteocytes, Rosa(Notch) mice were crossed with transgenics expressing Cre recombinase or SOST under the control of the dentin matrix protein (Dmp)1 promoter. Dmp1-SOST transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous Dmp1-Cre transgenics heterozygous for the Rosa(Notch) allele (Dmp1-Cre;Rosa(Notch)) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in Dmp1-Cre;Rosa(Notch) mice hemizygous for the Dmp1-SOST transgene. The effect was associated with downregulated Notch signaling and suppressed Dmp1 and Rosa26 expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from Dmp1-Cre;Rosa(Notch) mice or from Rosa(Notch) control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed Dmp1, but not Cre or Rosa26, expression. These findings suggest that prevention of the Dmp1-Cre;Rosa(Notch) skeletal phenotype by Dmp1-SOST is not secondary to SOST expression but to interactions among the Dmp1-SOST and Dmp1-Cre transgenes and the Rosa26 locus. In conclusion, the Dmp1-SOST transgene suppresses the expression of the Dmp1-Cre transgene and of Rosa26. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Taslima T. Lina

    2016-07-01

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

  12. Machine protection systems

    CERN Document Server

    Macpherson, A L

    2010-01-01

    A summary of the Machine Protection System of the LHC is given, with particular attention given to the outstanding issues to be addressed, rather than the successes of the machine protection system from the 2009 run. In particular, the issues of Safe Machine Parameter system, collimation and beam cleaning, the beam dump system and abort gap cleaning, injection and dump protection, and the overall machine protection program for the upcoming run are summarised.

  13. Machine and plasma diagnostic instrumentation systems for the Tandem Mirror Experiment Upgrade

    International Nuclear Information System (INIS)

    Coutts, G.W.; Coffield, F.E.; Lang, D.D.; Hornady, R.S.

    1981-01-01

    To evaluate performance of a second generation Tandem Mirror Machine, an extensive instrumentation system is being designed and installed as part of the major device fabrication. The systems listed will be operational during the start-up phase of the TMX Upgrade machine and provide bench marks for future performance data. In addition to plasma diagnostic instrumentation, machine parameter monitoring systems will be installed prior to machine operation. Simultaneous recording of machine parameters will permit evaluation of plasma parameters sensitive to machine conditions

  14. Dictionary of machine terms

    International Nuclear Information System (INIS)

    1990-06-01

    This book has introduction of dictionary of machine terms, and a compilation committee and introductory remarks. It gives descriptions of the machine terms in alphabetical order from a to Z and also includes abbreviation of machine terms and symbol table, way to read mathematical symbols and abbreviation and terms of drawings.

  15. Mankind, machines and people

    Energy Technology Data Exchange (ETDEWEB)

    Hugli, A

    1984-01-01

    The following questions are addressed: is there a difference between machines and men, between human communication and communication with machines. Will we ever reach the point when the dream of artificial intelligence becomes a reality. Will thinking machines be able to replace the human spirit in all its aspects. Social consequences and philosophical aspects are addressed. 8 references.

  16. A Universal Reactive Machine

    DEFF Research Database (Denmark)

    Andersen, Henrik Reif; Mørk, Simon; Sørensen, Morten U.

    1997-01-01

    Turing showed the existence of a model universal for the set of Turing machines in the sense that given an encoding of any Turing machine asinput the universal Turing machine simulates it. We introduce the concept of universality for reactive systems and construct a CCS processuniversal...

  17. HTS machine laboratory prototype

    DEFF Research Database (Denmark)

    machine. The machine comprises six stationary HTS field windings wound from both YBCO and BiSCOO tape operated at liquid nitrogen temperature and enclosed in a cryostat, and a three phase armature winding spinning at up to 300 rpm. This design has full functionality of HTS synchronous machines. The design...

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

    Science.gov (United States)

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

    2017-07-11

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

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

    Directory of Open Access Journals (Sweden)

    Alessandro Di Tullio

    2017-07-01

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

  20. O-Fucose Monosaccharide of Drosophila Notch Has a Temperature-sensitive Function and Cooperates with O-Glucose Glycan in Notch Transport and Notch Signaling Activation*

    Science.gov (United States)

    Ishio, Akira; Sasamura, Takeshi; Ayukawa, Tomonori; Kuroda, Junpei; Ishikawa, Hiroyuki O.; Aoyama, Naoki; Matsumoto, Kenjiroo; Gushiken, Takuma; Okajima, Tetsuya; Yamakawa, Tomoko; Matsuno, Kenji

    2015-01-01

    Notch (N) is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell fate decisions. N has many epidermal growth factor-like repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1), and the O-fut1 gene is essential for N signaling. However, the role of the monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O-fucosyltransferase activity-independent functions, including as an N-specific chaperon. Such an enzymatic activity-independent function could account for the essential role of O-fut1 in N signaling. To evaluate the role of the monosaccharide O-fucose modification in N signaling, here we generated a knock-in mutant of O-fut1 (O-fut1R245A knock-in), which expresses a mutant protein that lacks O-fucosyltransferase activity but maintains the N-specific chaperon activity. Using O-fut1R245A knock-in and other gene mutations that abolish the O-fucosylation of N, we found that the monosaccharide O-fucose modification of N has a temperature-sensitive function that is essential for N signaling. The O-fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi, function redundantly in the activation of N signaling. We also showed that the redundant function of these two modifications is responsible for the presence of N at the cell surface. Our findings elucidate how different forms of glycosylation on a protein can influence the protein's functions. PMID:25378397