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1. Design and production of the high voltage electrode grids and electron extraction region for the LZ dual-phase xenon time projection chamber

Author

Linehan, R., Mannino, R. L., Fan, A., Ignarra, C. M., Luitz, S., Skarpaas, K., Shutt, T. A., Akerib, D. S., Alsum, S. K., Anderson, T. J., Araújo, H. M., Arthurs, M., Auyeung, H., Bailey, A. J., Biesiadzinski, T. P., Breidenbach, M., Cherwinka, J. J., Conley, R. A., Genovesi, J., Gilchriese, M. G. D., Glaenzer, A., Gonda, T. G., Hanzel, K., Hoff, M. D., Ji, W., Kaboth, A. C., Kravitz, S., Kurita, N. R., Lambert, A. R., Lesko, K. T., Lorenzon, W., Majewski, P. A., Miller, E. H., Monzani, M. E., Palladino, K. J., Ratcliff, B. N., Saba, J. S., Santone, D., Shutt, G. W., Stifter, K., Szydagis, M., Tomás, A., Va'vra, J., Waldron, W. L., Webb, R. C., White, R. G., Whitis, T. J., Wilson, K., and Wisniewski, W. J.

Subjects
Physics - Instrumentation and Detectors, Astrophysics - Instrumentation and Methods for Astrophysics, High Energy Physics - Experiment
Abstract

The dual-phase xenon time projection chamber (TPC) is a powerful tool for direct-detection experiments searching for WIMP dark matter, other dark matter models, and neutrinoless double-beta decay. Successful operation of such a TPC is critically dependent on the ability to hold high electric fields in the bulk liquid, across the liquid surface, and in the gas. Careful design and construction of the electrodes used to establish these fields is therefore required. We present the design and production of the LUX-ZEPLIN (LZ) experiment's high-voltage electrodes, a set of four woven mesh wire grids. Grid design drivers are discussed, with emphasis placed on design of the electron extraction region. We follow this with a description of the grid production process and a discussion of steps taken to validate the LZ grids prior to integration into the TPC., Comment: 23 pages, 20 figures, to be submitted to Nuclear Instruments and Methods in Physics Research Section A. Corresponding authors: rlinehan@stanford.edu and mannino2@wisc.edu

Published
2021
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2. The LUX-ZEPLIN (LZ) radioactivity and cleanliness control programs

Author

Akerib, D. S., Akerlof, C. W., Akimov, D. Yu., Alquahtani, A., Alsum, S. K., Anderson, T. J., Angelides, N., Araújo, H. M., Arbuckle, A., Armstrong, J. E., Arthurs, M., Auyeung, H., Aviles, S., Bai, X., Bailey, A. J., Balajthy, J., Balashov, S., Bang, J., Barry, M. J., Bauer, D., Bauer, P., Baxter, A., Belle, J., Beltrame, P., Bensinger, J., Benson, T., Bernard, E. P., Bernstein, A., Bhatti, A., Biekert, A., Biesiadzinski, T. P., Birch, H. J., Birrittella, B., Boast, K. E., Bolozdynya, A. I., Boulton, E. M., Boxer, B., Bramante, R., Branson, S., Brás, P., Breidenbach, M., Brew, C. A. J., Buckley, J. H., Bugaev, V. V., Bunker, R., Burdin, S., Busenitz, J. K., Cabrita, R., Campbell, J. S., Carels, C., Carlsmith, D. L., Carlson, B., Carmona-Benitez, M. C., Cascella, M., Chan, C., Cherwinka, J. J., Chiller, A. A., Chiller, C., Chott, N. I., Cole, A., Coleman, J., Colling, D., Conley, R. A., Cottle, A., Coughlen, R., Cox, G., Craddock, W. W., Curran, D., Currie, A., Cutter, J. E., da Cunhaw, J. P., Dahl, C. E., Dardin, S., Dasu, S., Davis, J., Davison, T. J. R., de Viveiros, L., Decheine, N., Dobi, A., Dobson, J. E. Y., Druszkiewicz, E., Dushkin, A., Edberg, T. K., Edwards, W. R., Edwards, B. N., Edwards, J., Elnimr, M. M., Emmet, W. T., Eriksen, S. R., Faham, C. H., Fan, A., Fayer, S., Fiorucci, S., Flaecher, H., Florang, I. M. Fogarty, Ford, P., Francis, V. B., Fraser, E. D., Froborg, F., Fruth, T., Gaitskell, R. J., Gantos, N. J., Garcia, D., Gehman, V. M., Gelfand, R., Genovesi, J., Gerhard, R. M., Ghag, C., Gibson, E., Gilchriese, M. G. D., Gokhale, S., Gomber, B., Gonda, T. G., Greenall, A., Greenwood, S., Gregerson, G., van der Grinten, M. G. D., Gwilliam, C. B., Hall, C. R., Hamilton, D., Hans, S., Hanzel, K., Harrington, T., Harrison, A., Harrison, J., Hasselkus, C., Haselschwardt, S. J., Hemer, D., Hertel, S. A., Heise, J., Hillbrand, S., Hitchcock, O., Hjemfelt, C., Hoff, M. D., Holbrook, B., Holtom, E., Hor, J. Y-K., Horn, M., Huang, D. Q., Hurteau, T. W., Ignarra, C. M., Irving, M. N., Jacobsen, R. G., Jahangir, O., Jeffery, S. N., Ji, W., Johnson, M., Johnson, J., Johnson, P., Jones, W. G., Kaboth, A. C., Kamaha, A., Kamdin, K., Kasey, V., Kazkaz, K., Keefner, J., Khaitan, D., Khaleeq, M., Khazov, A., Khromov, A. V., Khurana, I., Kim, Y. D., Kim, W. T., Kocher, C. D., Kodroff, D., Konovalov, A. M., Korley, L., Korolkova, E. V., Koyuncu, M., Kras, J., Kraus, H., Kravitz, S. W., Krebs, H. J., Kreczko, L., Krikler, B., Kudryavtsev, V. A., Kumpan, A. V., Kyre, S., Lambert, A. R., Landerud, B., Larsen, N. A., Laundrie, A., Leason, E. A., Lee, H. S., Lee, J., Lee, C., Lenardo, B. G., Leonard, D. S., Leonard, R., Lesko, K. T., Levy, C., Li, J., Liu, Y., Liao, J., Liao, F. -T., Lin, J., Lindote, A., Linehan, R., Lippincott, W. H., Liu, R., Liu, X., Loniewski, C., Lopes, M. I., Lopez-Asamar, E., Paredes, B. López, Lorenzon, W., Lucero, D., Luitz, S., Lyle, J. M., Lynch, C., Majewski, P. A., Makkinje, J., Malling, D. C., Manalaysay, A., Manenti, L., Mannino, R. L., Marangou, N., Markley, D. J., MarrLaundrie, P., Martin, T. J., Marzioni, M. F., Maupin, C., McConnell, C. T., McKinsey, D. N., McLaughlin, J., Mei, D. -M., Meng, Y., Miller, E. H., Minaker, Z. J., Mizrachi, E., Mock, J., Molash, D., Monte, A., Monzani, M. E., Morad, J. A., Morrison, E., Mount, B. J., Murphy, A. St. J., Naim, D., Naylor, A., Nedlik, C., Nehrkorn, C., Nelson, H. N., Nesbit, J., Neves, F., Nikkel, J. A., Nikoleyczik, J. A., Nilima, A., O'Dell, J., Oh, H., O'Neill, F. G., O'Sullivan, K., Olcina, I., Olevitch, M. A., Oliver-Mallory, K. C., Oxborough, L., Pagac, A., Pagenkopf, D., Pal, S., Palladino, K. J., Palmaccio, V. M., Palmer, J., Pangilinan, M., Parveen, N., Patton, S. J., Pease, E. K., Penning, B. P., Pereira, G., Pereira, C., Peterson, I. B., Piepke, A., Pierson, S., Powell, S., Preece, R. M., Pushkin, K., Qie, Y., Racine, M., Ratcliff, B. N., Reichenbacher, J., Reichhart, L., Rhyne, C. A., Richards, A., Riffard, Q., Rischbieter, G. R. C., Rodrigues, J. P., Rose, H. J., Rosero, R., Rossiter, P., Rucinski, R., Rutherford, G., Saba, J. S., Sabarots, L., Santone, D., Sarychev, M., Sazzad, A. B. M. R., Schnee, R. W., Schubnell, M., Scovell, P. R., Severson, M., Seymour, D., Shaw, S., Shutt, G. W., Shutt, T. A., Silk, J. J., Silva, C., Skarpaas, K., Skulski, W., Smith, A. R., Smith, R. J., Smith, R. E., So, J., Solmaz, M., Solovov, V. N., Sorensen, P., Sosnovtsev, V. V., Stancu, I., Stark, M. R., Stephenson, S., Stern, N., Stevens, A., Stiegler, T. M., Stifter, K., Studley, R., Sumner, T. J., Sundarnath, K., Sutcliffe, P., Swanson, N., Szydagis, M., Tan, M., Taylor, W. C., Taylor, R., Taylor, D. J., Temples, D., Tennyson, B. P., Terman, P. A., Thomas, K. J., Thomson, J. A., Tiedt, D. R., Timalsina, M., To, W. H., Tomás, A., Tope, T. E., Tripathi, M., Tronstad, D. R., Tull, C. E., Turner, W., Tvrznikova, L., Utes, M., Utku, U., Uvarov, S., Va'vra, J., Vacheret, A., Vaitkus, A., Verbus, J. R., Vietanen, T., Voirin, E., Vuosalo, C. O., Walcott, S., Waldron, W. L., Walker, K., Wang, J. J., Wang, R., Wang, L., Wang, W., Wang, Y., Watson, J. R., Migneault, J., Weatherly, S., Webb, R. C., Wei, W. -Z., While, M., White, R. G., White, J. T., White, D. T., Whitis, T. J., Wisniewski, W. J., Wilson, K., Witherell, M. S., Wolfs, F. L. H., Wolfs, J. D., Woodward, D., Worm, S. D., Xiang, X., Xiao, Q., Xu, J., Yeh, M., Yin, J., Young, I., Zhang, C., and Zarzhitsky, P.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above $1.4 \times 10^{-48}$ cm$^{2}$ for a WIMP mass of 40 GeV/c$^{2}$ and a 1000 d exposure. LZ achieves this sensitivity through a combination of a large 5.6 t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented., Comment: 45 pages (79 inc. tables), 7 figures, 9 tables

Published
2020
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3. The LUX-ZEPLIN (LZ) Experiment

Author

The LZ Collaboration, Akerib, D. S., Akerlof, C. W., Akimov, D. Yu., Alquahtani, A., Alsum, S. K., Anderson, T. J., Angelides, N., Araújo, H. M., Arbuckle, A., Armstrong, J. E., Arthurs, M., Auyeung, H., Bai, X., Bailey, A. J., Balajthy, J., Balashov, S., Bang, J., Barry, M. J., Barthel, J., Bauer, D., Bauer, P., Baxter, A., Belle, J., Beltrame, P., Bensinger, J., Benson, T., Bernard, E. P., Bernstein, A., Bhatti, A., Biekert, A., Biesiadzinski, T. P., Birrittella, B., Boast, K. E., Bolozdynya, A. I., Boulton, E. M., Boxer, B., Bramante, R., Branson, S., Brás, P., Breidenbach, M., Buckley, J. H., Bugaev, V. V., Bunker, R., Burdin, S., Busenitz, J. K., Campbell, J. S., Carels, C., Carlsmith, D. L., Carlson, B., Carmona-Benitez, M. C., Cascella, M., Chan, C., Cherwinka, J. J., Chiller, A. A., Chiller, C., Chott, N. I., Cole, A., Coleman, J., Colling, D., Conley, R. A., Cottle, A., Coughlen, R., Craddock, W. W., Curran, D., Currie, A., Cutter, J. E., da Cunha, J. P., Dahl, C. E., Dardin, S., Dasu, S., Davis, J., Davison, T. J. R., de Viveiros, L., Decheine, N., Dobi, A., Dobson, J. E. Y., Druszkiewicz, E., Dushkin, A., Edberg, T. K., Edwards, W. R., Edwards, B. N., Edwards, J., Elnimr, M. M., Emmet, W. T., Eriksen, S. R., Faham, C. H., Fan, A., Fayer, S., Fiorucci, S., Flaecher, H., Florang, I. M. Fogarty, Ford, P., Francis, V. B., Froborg, F., Fruth, T., Gaitskell, R. J., Gantos, N. J., Garcia, D., Geffre, A., Gehman, V. M., Gelfand, R., Genovesi, J., Gerhard, R. M., Ghag, C., Gibson, E., Gilchriese, M. G. D., Gokhale, S., Gomber, B., Gonda, T. G., Greenall, A., Greenwood, S., Gregerson, G., van der Grinten, M. G. D., Gwilliam, C. B., Hall, C. R., Hamilton, D., Hans, S., Hanzel, K., Harrington, T., Harrison, A., Hasselkus, C., Haselschwardt, S. J., Hemer, D., Hertel, S. A., Heise, J., Hillbrand, S., Hitchcock, O., Hjemfelt, C., Hoff, M. D., Holbrook, B., Holtom, E., Hor, J. Y-K., Horn, M., Huang, D. Q., Hurteau, T. W., Ignarra, C. M., Irving, M. N., Jacobsen, R. G., Jahangir, O., Jeffery, S. N., Ji, W., Johnson, M., Johnson, J., Johnson, P., Jones, W. G., Kaboth, A. C., Kamaha, A., Kamdin, K., Kasey, V., Kazkaz, K., Keefner, J., Khaitan, D., Khaleeq, M., Khazov, A., Khromov, A. V., Khurana, I., Kim, Y. D., Kim, W. T., Kocher, C. D., Konovalov, A. M., Korley, L., Korolkova, E. V., Koyuncu, M., Kras, J., Kraus, H., Kravitz, S. W., Krebs, H. J., Kreczko, L., Krikler, B., Kudryavtsev, V. A., Kumpan, A. V., Kyre, S., Lambert, A. R., Landerud, B., Larsen, N. A., Laundrie, A., Leason, E. A., Lee, H. S., Lee, J., Lee, C., Lenardo, B. G., Leonard, D. S., Leonard, R., Lesko, K. T., Levy, C., Li, J., Liu, Y., Liao, J., Liao, F. -T., Lin, J., Lindote, A., Linehan, R., Lippincott, W. H., Liu, R., Liu, X., Loniewski, C., Lopes, M. I., Paredes, B. López, Lorenzon, W., Lucero, D., Luitz, S., Lyle, J. M., Lynch, C., Majewski, P. A., Makkinje, J., Malling, D. C., Manalaysay, A., Manenti, L., Mannino, R. L., Marangou, N., Markley, D. J., MarrLaundrie, P., Martin, T. J., Marzioni, M. F., Maupin, C., McConnell, C. T., McKinsey, D. N., McLaughlin, J., Mei, D. -M., Meng, Y., Miller, E. H., Minaker, Z. J., Mizrachi, E., Mock, J., Molash, D., Monte, A., Monzani, M. E., Morad, J. A., Morrison, E., Mount, B. J., Murphy, A. St. J., Naim, D., Naylor, A., Nedlik, C., Nehrkorn, C., Nelson, H. N., Nesbit, J., Neves, F., Nikkel, J. A., Nikoleyczik, J. A., Nilima, A., O'Dell, J., Oh, H., O'Neill, F. G., O'Sullivan, K., Olcina, I., Olevitch, M. A., Oliver-Mallory, K. C., Oxborough, L., Pagac, A., Pagenkopf, D., Pal, S., Palladino, K. J., Palmaccio, V. M., Palmer, J., Pangilinan, M., Patton, S. J., Pease, E. K., Penning, B. P., Pereira, G., Pereira, C., Peterson, I. B., Piepke, A., Pierson, S., Powell, S., Preece, R. M., Pushkin, K., Qie, Y., Racine, M., Ratcliff, B. N., Reichenbacher, J., Reichhart, L., Rhyne, C. A., Richards, A., Riffard, Q., Rischbieter, G. R. C., Rodrigues, J. P., Rose, H. J., Rosero, R., Rossiter, P., Rucinski, R., Rutherford, G., Rynders, D., Saba, J. S., Sabarots, L., Santone, D., Sarychev, M., Sazzad, A. B. M. R., Schnee, R. W., Schubnell, M., Scovell, P. R., Severson, M., Seymour, D., Shaw, S., Shutt, G. W., Shutt, T. A., Silk, J. J., Silva, C., Skarpaas, K., Skulski, W., Smith, A. R., Smith, R. J., Smith, R. E., So, J., Solmaz, M., Solovov, V. N., Sorensen, P., Sosnovtsev, V. V., Stancu, I., Stark, M. R., Stephenson, S., Stern, N., Stevens, A., Stiegler, T. M., Stifter, K., Studley, R., Sumner, T. J., Sundarnath, K., Sutcliffe, P., Swanson, N., Szydagis, M., Tan, M., Taylor, W. C., Taylor, R., Taylor, D. J., Temples, D., Tennyson, B. P., Terman, P. A., Thomas, K. J., Thomson, J. A., Tiedt, D. R., Timalsina, M., To, W. H., Tomás, A., Tope, T. E., Tripathi, M., Tronstad, D. R., Tull, C. E., Turner, W., Tvrznikova, L., Utes, M., Utku, U., Uvarov, S., Va'vra, J., Vacheret, A., Vaitkus, A., Verbus, J. R., Vietanen, T., Voirin, E., Vuosalo, C. O., Walcott, S., Waldron, W. L., Walker, K., Wang, J. J., Wang, R., Wang, L., Wang, Y., Watson, J. R., Migneault, J., Weatherly, S., Webb, R. C., Wei, W. -Z., While, M., White, R. G., White, J. T., White, D. T., Whitis, T. J., Wisniewski, W. J., Wilson, K., Witherell, M. S., Wolfs, F. L. H., Wolfs, J. D., Woodward, D., Worm, S. D., Xiang, X., Xiao, Q., Xu, J., Yeh, M., Yin, J., Young, I., and Zhang, C.

Subjects
Physics - Instrumentation and Detectors, Astrophysics - Instrumentation and Methods for Astrophysics, High Energy Physics - Experiment
Abstract

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements.

Published
2019
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4. Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry

Author

Smith, MS, Cash, B, Konda, V, Trindade, AJ, Gordon, S, DeMeester, S, Joshi, V, Diehl, D, Ganguly, E, Mashimo, H, Singh, S, Jobe, B, McKinley, M, Wallace, M, Komatsu, Y, Thakkar, S, Schnoll-Sussman, F, Sharaiha, R, Kahaleh, M, Tarnasky, P, Wolfsen, H, Hawes, R, Lipham, J, Khara, H, Pleskow, D, Navaneethan, U, Kedia, P, Hasan, M, Sethi, A, Samarasena, J, Siddiqui, UD, Gress, F, Rodriguez, R, Lee, C, Gonda, T, Waxman, I, Hyder, S, Poneros, J, Sharzehi, K, Di Palma, JA, Sejpal, DV, Oh, D, Hagen, J, Rothstein, R, Sawhney, M, Berzin, T, Malik, Z, and Chang, K

Subjects
Digestive Diseases, Biomedical Imaging, Clinical Research, Cancer, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adult, Aged, Aged, 80 and over, Barrett Esophagus, Biopsy, Clinical Decision-Making, Computer Systems, Female, Humans, Male, Middle Aged, Practice Patterns, Physicians', Prospective Studies, Registries, Tomography, Optical Coherence, United States, Barrett's esophagus, dysplasia, endomicroscopy, imaging
Abstract

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Published
2019

5. Achieving stationary high performance plasmas at Wendelstein 7-X

Author

Langenberg, A., Warmer, F., Fuchert, G., Ford, O., Bozhenkov, S., Andreeva, T., Lazerson, S., Pablant, N. A., Gonda, T., Beurskens, M. N.A., Brunner, K. J., Buttenschön, B., Dinklage, A., Hartmann, D., Knauer, J., Marchuk, O., Pasch, E., Reimold, F., Stange, T., Wegner, Th, Grulke, O., Wolf, R. C., Langenberg, A., Warmer, F., Fuchert, G., Ford, O., Bozhenkov, S., Andreeva, T., Lazerson, S., Pablant, N. A., Gonda, T., Beurskens, M. N.A., Brunner, K. J., Buttenschön, B., Dinklage, A., Hartmann, D., Knauer, J., Marchuk, O., Pasch, E., Reimold, F., Stange, T., Wegner, Th, Grulke, O., and Wolf, R. C.

Abstract

This work reports on recent results on the search for high performance plasma scenarios at the magnetically confined stellarator fusion device Wendelstein 7-X. In four new designed scenarios, the development from transient toward stationary plasmas of improved performance has been realized. In particular, a high performance duration of up to 5 s, an energy confinement time of 0.3 s, a diamagnetic energy of 1.1 MJ, a central ion temperature of 2.2 keV, and a fusion triple product of 3.4 × 10 19 m − 3 · keV · s have been achieved, and previously observed limitations of the machine have been overcome, regarding both the performance and its duration. The two main experimental techniques for stationary high performance are neutral beam injection core fueling on the one hand and the use of a magnetic field configuration with internal islands on the other hand. Two of the developed scenarios are expected to be extendable straightforward toward a duration of several tens of seconds, making use of the long pulse operation capabilities of W7-X.

Published
2024

6. Erratum to: The LUX-ZEPLIN (LZ) radioactivity and cleanliness control programs

Author

Akerib, D. S., Akerlof, C. W., Akimov, D. Yu., Alquahtani, A., Alsum, S. K., Anderson, T. J., Angelides, N., Araújo, H. M., Arbuckle, A., Armstrong, J. E., Arthurs, M., Auyeung, H., Aviles, S., Bai, X., Bailey, A. J., Balajthy, J., Balashov, S., Bang, J., Barry, M. J., Bauer, D., Bauer, P., Baxter, A., Belle, J., Beltrame, P., Bensinger, J., Benson, T., Bernard, E. P., Bernstein, A., Bhatti, A., Biekert, A., Biesiadzinski, T. P., Birch, H. J., Birrittella, B., Boast, K. E., Bolozdynya, A. I., Boulton, E. M., Boxer, B., Bramante, R., Branson, S., Brás, P., Breidenbach, M., Brew, C. A. J., Buckley, J. H., Bugaev, V. V., Bunker, R., Burdin, S., Busenitz, J. K., Cabrita, R., Campbell, J. S., Carels, C., Carlsmith, D. L., Carlson, B., Carmona-Benitez, M. C., Cascella, M., Chan, C., Cherwinka, J. J., Chiller, A. A., Chiller, C., Chott, N. I., Cole, A., Coleman, J., Colling, D., Conley, R. A., Cottle, A., Coughlen, R., Cox, G., Craddock, W. W., Curran, D., Currie, A., Cutter, J. E., da Cunha, J. P., Dahl, C. E., Dardin, S., Dasu, S., Davis, J., Davison, T. J. R., de Viveiros, L., Decheine, N., Dobi, A., Dobson, J. E. Y., Druszkiewicz, E., Dushkin, A., Edberg, T. K., Edwards, W. R., Edwards, B. N., Edwards, J., Elnimr, M. M., Emmet, W. T., Eriksen, S. R., Faham, C. H., Fan, A., Fayer, S., Fiorucci, S., Flaecher, H., Florang, I. M. Fogarty, Ford, P., Francis, V. B., Fraser, E. D., Froborg, F., Fruth, T., Gaitskell, R. J., Gantos, N. J., Garcia, D., Gehman, V. M., Gelfand, R., Genovesi, J., Gerhard, R. M., Ghag, C., Gibson, E., Gilchriese, M. G. D., Gokhale, S., Gomber, B., Gonda, T. G., Greenall, A., Greenwood, S., Gregerson, G., van der Grinten, M. G. D., Gwilliam, C. B., Hall, C. R., Hamilton, D., Hans, S., Hanzel, K., Harrington, T., Harrison, A., Harrison, J., Hasselkus, C., Haselschwardt, S. J., Hemer, D., Hertel, S. A., Heise, J., Hillbrand, S., Hitchcock, O., Hjemfelt, C., Hoff, M. D., Holbrook, B., Holtom, E., Hor, J. Y-K., Horn, M., Huang, D. Q., Hurteau, T. W., Ignarra, C. M., Irving, M. N., Jacobsen, R. G., Jahangir, O., Jeffery, S. N., Ji, W., Johnson, M., Johnson, J., Johnson, P., Jones, W. G., Kaboth, A. C., Kamaha, A., Kamdin, K., Kasey, V., Kazkaz, K., Keefner, J., Khaitan, D., Khaleeq, M., Khazov, A., Khromov, A. V., Khurana, I., Kim, Y. D., Kim, W. T., Kocher, C. D., Kodroff, D., Konovalov, A. M., Korley, L., Korolkova, E. V., Koyuncu, M., Kras, J., Kraus, H., Kravitz, S. W., Krebs, H. J., Kreczko, L., Krikler, B., Kudryavtsev, V. A., Kumpan, A. V., Kyre, S., Lambert, A. R., Landerud, B., Larsen, N. A., Laundrie, A., Leason, E. A., Lee, H. S., Lee, J., Lee, C., Lenardo, B. G., Leonard, D. S., Leonard, R., Lesko, K. T., Levy, C., Li, J., Liu, Y., Liao, J., Liao, F.-T., Lin, J., Lindote, A., Linehan, R., Lippincott, W. H., Liu, R., Liu, X., Loniewski, C., Lopes, M. I., Lopez-Asamar, E., Paredes, B. López, Lorenzon, W., Lucero, D., Luitz, S., Lyle, J. M., Lynch, C., Majewski, P. A., Makkinje, J., Malling, D. C., Manalaysay, A., Manenti, L., Mannino, R. L., Marangou, N., Markley, D. J., MarrLaundrie, P., Martin, T. J., Marzioni, M. F., Maupin, C., McConnell, C. T., McKinsey, D. N., McLaughlin, J., Mei, D.-M., Meng, Y., Miller, E. H., Minaker, Z. J., Mizrachi, E., Mock, J., Molash, D., Monte, A., Monzani, M. E., Morad, J. A., Morrison, E., Mount, B. J., Murphy, A. St. J., Naim, D., Naylor, A., Nedlik, C., Nehrkorn, C., Nelson, H. N., Nesbit, J., Neves, F., Nikkel, J. A., Nikoleyczik, J. A., Nilima, A., O’Dell, J., Oh, H., O’Neill, F. G., O’Sullivan, K., Olcina, I., Olevitch, M. A., Oliver-Mallory, K. C., Oxborough, L., Pagac, A., Pagenkopf, D., Pal, S., Palladino, K. J., Palmaccio, V. M., Palmer, J., Pangilinan, M., Parveen, N., Patton, S. J., Pease, E. K., Penning, B. P., Pereira, G., Pereira, C., Peterson, I. B., Piepke, A., Pierson, S., Powell, S., Preece, R. M., Pushkin, K., Qie, Y., Racine, M., Ratcliff, B. N., Reichenbacher, J., Reichhart, L., Rhyne, C. A., Richards, A., Riffard, Q., Rischbieter, G. R. C., Rodrigues, J. P., Rose, H. J., Rosero, R., Rossiter, P., Rucinski, R., Rutherford, G., Saba, J. S., Sabarots, L., Santone, D., Sarychev, M., Sazzad, A. B. M. R., Schnee, R. W., Schubnell, M., Scovell, P. R., Severson, M., Seymour, D., Shaw, S., Shutt, G. W., Shutt, T. A., Silk, J. J., Silva, C., Skarpaas, K., Skulski, W., Smith, A. R., Smith, R. J., Smith, R. E., So, J., Solmaz, M., Solovov, V. N., Sorensen, P., Sosnovtsev, V. V., Stancu, I., Stark, M. R., Stephenson, S., Stern, N., Stevens, A., Stiegler, T. M., Stifter, K., Studley, R., Sumner, T. J., Sundarnath, K., Sutcliffe, P., Swanson, N., Szydagis, M., Tan, M., Taylor, W. C., Taylor, R., Taylor, D. J., Temples, D., Tennyson, B. P., Terman, P. A., Thomas, K. J., Thomson, J. A., Tiedt, D. R., Timalsina, M., To, W. H., Tomás, A., Tope, T. E., Tripathi, M., Tronstad, D. R., Tull, C. E., Turner, W., Tvrznikova, L., Utes, M., Utku, U., Uvarov, S., Va’vra, J., Vacheret, A., Vaitkus, A., Verbus, J. R., Vietanen, T., Voirin, E., Vuosalo, C. O., Walcott, S., Waldron, W. L., Walker, K., Wang, J. J., Wang, R., Wang, L., Wang, W., Wang, Y., Watson, J. R., Migneault, J., Weatherly, S., Webb, R. C., Wei, W.-Z., While, M., White, R. G., White, J. T., White, D. T., Whitis, T. J., Wisniewski, W. J., Wilson, K., Witherell, M. S., Wolfs, F. L. H., Wolfs, J. D., Woodward, D., Worm, S. D., Xiang, X., Xiao, Q., Xu, J., Yeh, M., Yin, J., Young, I., Zhang, C., and Zarzhitsky, P.

Published
2022
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7. Advanced endoscopy meets molecular diagnosis of cholangiocarcinoma

Author

Cadamuro, M, Al-Taee, A, Gonda, T, Gonda, TA, Cadamuro, M, Al-Taee, A, Gonda, T, and Gonda, TA

Abstract

Cholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. We present our diagnostic and theranostic approach to the initial evaluation of cholangiocarcinomas, focusing on extrahepatic cholangiocarcinoma. This involves a multipronged strategy incorporating advanced imaging, endoscopic methods, multiple approaches to tissue sampling, and molecular markers. We also provide an algorithm for the sequential use of these tools. (c) 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Published
2023

15. The LUX-ZEPLIN (LZ) radioactivity and cleanliness control programs

Author

Akerib, D. S., primary, Akerlof, C. W., additional, Akimov, D. Yu., additional, Alquahtani, A., additional, Alsum, S. K., additional, Anderson, T. J., additional, Angelides, N., additional, Araújo, H. M., additional, Arbuckle, A., additional, Armstrong, J. E., additional, Arthurs, M., additional, Auyeung, H., additional, Aviles, S., additional, Bai, X., additional, Bailey, A. J., additional, Balajthy, J., additional, Balashov, S., additional, Bang, J., additional, Barry, M. J., additional, Bauer, D., additional, Bauer, P., additional, Baxter, A., additional, Belle, J., additional, Beltrame, P., additional, Bensinger, J., additional, Benson, T., additional, Bernard, E. P., additional, Bernstein, A., additional, Bhatti, A., additional, Biekert, A., additional, Biesiadzinski, T. P., additional, Birch, H. J., additional, Birrittella, B., additional, Boast, K. E., additional, Bolozdynya, A. I., additional, Boulton, E. M., additional, Boxer, B., additional, Bramante, R., additional, Branson, S., additional, Brás, P., additional, Breidenbach, M., additional, Brew, C. A. J., additional, Buckley, J. H., additional, Bugaev, V. V., additional, Bunker, R., additional, Burdin, S., additional, Busenitz, J. K., additional, Cabrita, R., additional, Campbell, J. S., additional, Carels, C., additional, Carlsmith, D. L., additional, Carlson, B., additional, Carmona-Benitez, M. C., additional, Cascella, M., additional, Chan, C., additional, Cherwinka, J. J., additional, Chiller, A. A., additional, Chiller, C., additional, Chott, N. I., additional, Cole, A., additional, Coleman, J., additional, Colling, D., additional, Conley, R. A., additional, Cottle, A., additional, Coughlen, R., additional, Cox, G., additional, Craddock, W. W., additional, Curran, D., additional, Currie, A., additional, Cutter, J. E., additional, da Cunha, J. P., additional, Dahl, C. E., additional, Dardin, S., additional, Dasu, S., additional, Davis, J., additional, Davison, T. J. R., additional, de Viveiros, L., additional, Decheine, N., additional, Dobi, A., additional, Dobson, J. E. Y., additional, Druszkiewicz, E., additional, Dushkin, A., additional, Edberg, T. K., additional, Edwards, W. R., additional, Edwards, B. N., additional, Edwards, J., additional, Elnimr, M. M., additional, Emmet, W. T., additional, Eriksen, S. R., additional, Faham, C. H., additional, Fan, A., additional, Fayer, S., additional, Fiorucci, S., additional, Flaecher, H., additional, Florang, I. M. Fogarty, additional, Ford, P., additional, Francis, V. B., additional, Fraser, E. D., additional, Froborg, F., additional, Fruth, T., additional, Gaitskell, R. J., additional, Gantos, N. J., additional, Garcia, D., additional, Gehman, V. M., additional, Gelfand, R., additional, Genovesi, J., additional, Gerhard, R. M., additional, Ghag, C., additional, Gibson, E., additional, Gilchriese, M. G. D., additional, Gokhale, S., additional, Gomber, B., additional, Gonda, T. G., additional, Greenall, A., additional, Greenwood, S., additional, Gregerson, G., additional, van der Grinten, M. G. D., additional, Gwilliam, C. B., additional, Hall, C. R., additional, Hamilton, D., additional, Hans, S., additional, Hanzel, K., additional, Harrington, T., additional, Harrison, A., additional, Harrison, J., additional, Hasselkus, C., additional, Haselschwardt, S. J., additional, Hemer, D., additional, Hertel, S. A., additional, Heise, J., additional, Hillbrand, S., additional, Hitchcock, O., additional, Hjemfelt, C., additional, Hoff, M. D., additional, Holbrook, B., additional, Holtom, E., additional, Hor, J. Y-K., additional, Horn, M., additional, Huang, D. Q., additional, Hurteau, T. W., additional, Ignarra, C. M., additional, Irving, M. N., additional, Jacobsen, R. G., additional, Jahangir, O., additional, Jeffery, S. N., additional, Ji, W., additional, Johnson, M., additional, Johnson, J., additional, Johnson, P., additional, Jones, W. G., additional, Kaboth, A. C., additional, Kamaha, A., additional, Kamdin, K., additional, Kasey, V., additional, Kazkaz, K., additional, Keefner, J., additional, Khaitan, D., additional, Khaleeq, M., additional, Khazov, A., additional, Khromov, A. V., additional, Khurana, I., additional, Kim, Y. D., additional, Kim, W. T., additional, Kocher, C. D., additional, Kodroff, D., additional, Konovalov, A. M., additional, Korley, L., additional, Korolkova, E. V., additional, Koyuncu, M., additional, Kras, J., additional, Kraus, H., additional, Kravitz, S. W., additional, Krebs, H. J., additional, Kreczko, L., additional, Krikler, B., additional, Kudryavtsev, V. A., additional, Kumpan, A. V., additional, Kyre, S., additional, Lambert, A. R., additional, Landerud, B., additional, Larsen, N. A., additional, Laundrie, A., additional, Leason, E. A., additional, Lee, H. S., additional, Lee, J., additional, Lee, C., additional, Lenardo, B. G., additional, Leonard, D. S., additional, Leonard, R., additional, Lesko, K. T., additional, Levy, C., additional, Li, J., additional, Liu, Y., additional, Liao, J., additional, Liao, F.-T., additional, Lin, J., additional, Lindote, A., additional, Linehan, R., additional, Lippincott, W. H., additional, Liu, R., additional, Liu, X., additional, Loniewski, C., additional, Lopes, M. I., additional, Lopez-Asamar, E., additional, Paredes, B. López, additional, Lorenzon, W., additional, Lucero, D., additional, Luitz, S., additional, Lyle, J. M., additional, Lynch, C., additional, Majewski, P. A., additional, Makkinje, J., additional, Malling, D. C., additional, Manalaysay, A., additional, Manenti, L., additional, Mannino, R. L., additional, Marangou, N., additional, Markley, D. J., additional, MarrLaundrie, P., additional, Martin, T. J., additional, Marzioni, M. F., additional, Maupin, C., additional, McConnell, C. T., additional, McKinsey, D. N., additional, McLaughlin, J., additional, Mei, D.-M., additional, Meng, Y., additional, Miller, E. H., additional, Minaker, Z. J., additional, Mizrachi, E., additional, Mock, J., additional, Molash, D., additional, Monte, A., additional, Monzani, M. E., additional, Morad, J. A., additional, Morrison, E., additional, Mount, B. J., additional, Murphy, A. St. J., additional, Naim, D., additional, Naylor, A., additional, Nedlik, C., additional, Nehrkorn, C., additional, Nelson, H. N., additional, Nesbit, J., additional, Neves, F., additional, Nikkel, J. A., additional, Nikoleyczik, J. A., additional, Nilima, A., additional, O’Dell, J., additional, Oh, H., additional, O’Neill, F. G., additional, O’Sullivan, K., additional, Olcina, I., additional, Olevitch, M. A., additional, Oliver-Mallory, K. C., additional, Oxborough, L., additional, Pagac, A., additional, Pagenkopf, D., additional, Pal, S., additional, Palladino, K. J., additional, Palmaccio, V. M., additional, Palmer, J., additional, Pangilinan, M., additional, Parveen, N., additional, Patton, S. J., additional, Pease, E. K., additional, Penning, B. P., additional, Pereira, G., additional, Pereira, C., additional, Peterson, I. B., additional, Piepke, A., additional, Pierson, S., additional, Powell, S., additional, Preece, R. M., additional, Pushkin, K., additional, Qie, Y., additional, Racine, M., additional, Ratcliff, B. N., additional, Reichenbacher, J., additional, Reichhart, L., additional, Rhyne, C. A., additional, Richards, A., additional, Riffard, Q., additional, Rischbieter, G. R. C., additional, Rodrigues, J. P., additional, Rose, H. J., additional, Rosero, R., additional, Rossiter, P., additional, Rucinski, R., additional, Rutherford, G., additional, Saba, J. S., additional, Sabarots, L., additional, Santone, D., additional, Sarychev, M., additional, Sazzad, A. B. M. R., additional, Schnee, R. W., additional, Schubnell, M., additional, Scovell, P. R., additional, Severson, M., additional, Seymour, D., additional, Shaw, S., additional, Shutt, G. W., additional, Shutt, T. A., additional, Silk, J. J., additional, Silva, C., additional, Skarpaas, K., additional, Skulski, W., additional, Smith, A. R., additional, Smith, R. J., additional, Smith, R. E., additional, So, J., additional, Solmaz, M., additional, Solovov, V. N., additional, Sorensen, P., additional, Sosnovtsev, V. V., additional, Stancu, I., additional, Stark, M. R., additional, Stephenson, S., additional, Stern, N., additional, Stevens, A., additional, Stiegler, T. M., additional, Stifter, K., additional, Studley, R., additional, Sumner, T. J., additional, Sundarnath, K., additional, Sutcliffe, P., additional, Swanson, N., additional, Szydagis, M., additional, Tan, M., additional, Taylor, W. C., additional, Taylor, R., additional, Taylor, D. J., additional, Temples, D., additional, Tennyson, B. P., additional, Terman, P. A., additional, Thomas, K. J., additional, Thomson, J. A., additional, Tiedt, D. R., additional, Timalsina, M., additional, To, W. H., additional, Tomás, A., additional, Tope, T. E., additional, Tripathi, M., additional, Tronstad, D. R., additional, Tull, C. E., additional, Turner, W., additional, Tvrznikova, L., additional, Utes, M., additional, Utku, U., additional, Uvarov, S., additional, Va’vra, J., additional, Vacheret, A., additional, Vaitkus, A., additional, Verbus, J. R., additional, Vietanen, T., additional, Voirin, E., additional, Vuosalo, C. O., additional, Walcott, S., additional, Waldron, W. L., additional, Walker, K., additional, Wang, J. J., additional, Wang, R., additional, Wang, L., additional, Wang, W., additional, Wang, Y., additional, Watson, J. R., additional, Migneault, J., additional, Weatherly, S., additional, Webb, R. C., additional, Wei, W.-Z., additional, While, M., additional, White, R. G., additional, White, J. T., additional, White, D. T., additional, Whitis, T. J., additional, Wisniewski, W. J., additional, Wilson, K., additional, Witherell, M. S., additional, Wolfs, F. L. H., additional, Wolfs, J. D., additional, Woodward, D., additional, Worm, S. D., additional, Xiang, X., additional, Xiao, Q., additional, Xu, J., additional, Yeh, M., additional, Yin, J., additional, Young, I., additional, Zhang, C., additional, and Zarzhitsky, P., additional

Published
2020
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19. Vállalkozói percepciók az Európa Gasztrorégió Cím elnyerésével kapcsolatban

Author

Horeczki Réka and Gonda Tibor

Subjects
vendéglátás, gasztroturizmus, turizmusfejlesztés, History (General) and history of Europe, Economic history and conditions, HC10-1085, Economic growth, development, planning, HD72-88, Sociology (General), HM401-1281, International relations, JZ2-6530
Abstract

A világban a jelenlegi sokkok, traumák – külső tényezők eredői – megkövetelik nemcsak az állampolgárok, hanem régiók, országok közös cselekvési terveinek kialakítását is. A Covid-19 okozta járvány az élet szinte minden területén változást kívánt. Eltérő módon és mértékben, de jellemzően negatívan érintette a különböző ágazatokat, térségeket és társadalmi csoportokat. A turizmus és a vendéglátás szenvedte el talán a legnagyobb károkat. 2020. március második felétől Magyarországon bezártak a kereskedelmi szálláshelyek, korlátozták a nemzetközi utazásokat és a vendéglátóhelyek nyitva tartását, a lakosság óvatossága miatt pedig további jelentős bevétel- és forgalomcsökkenést prognosztizáltak. A turisztikai irányú beruházások, fejlesztések mégis jelentősnek tekinthetők ebben az időszakban. Úgy véljük, a fejlesztési tendenciákat a különböző címekre beadott pályázatok is módosíthatják. Az elsődleges kutatási kérdés, hogy képes-e felismerni és azonosítani egy adott régió érintett (vendéglátáshoz kötődő) szektora az Európa Gasztronómiai Régiója cím értékeit és adott térségre gyakorolható hatásait. A vizsgálat további tárgya a támogatottság mértéke az érintett szektorban. A fókusz Baranya megye és Pécs városa. Egy kérdőíves felmérés segítségével igazoljuk, hogy a megyében nagyszabású, pozitív jövőképet közvetítő összefogásra van szükség. A jelenlegi adatok alapján Baranya megye turizmusának minőségi fejlesztésére és mennyiségi mutatóinak jelentős emelésére van szükség. A megye és a megyeszékhely turisztikai erőforrásai alapján az országban és Európában is nagyobb láthatóságot, látogatottságot és magasabb turisztikai bevételt érdemelne. A megyében több évtizedes tapasztalat támasztja alá, hogy a minőségi borkultúra, párosulva a gasztronómiával, borturizmussal, kultúrával és a helyi értékesítéssel jelentős és átfogó település- és területfejlesztési erővé és eszközzé váltható. A tanulmány kiemelt célja, hogy bemutassuk, miként járulhat hozzá a gasztronómiai örökség egy adott térség fejlődéséhez.

Published
2023
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20. MYB elongation is regulated by the nucleic acid binding of NFekB p50 to the intronic stem-loop region

Author

Pereira, L., Hugo, H., Malaterre, J., Huiling, X., Sonza, S., Cures, A., Purcell, D., Ramsland, Paul, Gerondakis, S., Gonda, T., Ramsay, R., Pereira, L., Hugo, H., Malaterre, J., Huiling, X., Sonza, S., Cures, A., Purcell, D., Ramsland, Paul, Gerondakis, S., Gonda, T., and Ramsay, R.

Abstract

MYB transcriptional elongation is regulated by an attenuator sequence within intron 1 that has been proposed to encode a RNA stem loop (SLR) followed by a polyU tract. We report that NFekBp50 can bind the SLR polyU RNA and promote MYB transcriptional elongation together with NFekBp65. We identified a conserved lysine-rich motif within the Rel homology domain (RHD) of NFekBp50, mutation of which abrogated the interaction of NFekBp50 with the SLR polyU and impaired NFekBp50 mediated MYB elongation. We observed that the TAR RNA-binding region of Tat is homologous to the NFekBp50 RHD lysine-rich motif, a finding consistent with HIV Tat acting as an effector of MYB transcriptional elongation in an SLR dependent manner. Furthermore, we identify the DNA binding activity of NFekBp50 as a key component required for the SLR polyU mediated regulation of MYB. Collectively these results suggest that the MYB SLR polyU provides a platform for proteins to regulate MYB and reveals novel nucleic acid binding properties of NFekBp50 required for MYB regulation.

Published
2015

21. The Role of Local Products in Tourism

Author

Gonda Tibor, Angler Kinga, and Csóka László

Subjects
local food products, local economy, environment awareness, rural development, Agriculture, Social Sciences
Abstract

There is a resurgence of regional and local products in Hungary today. Thanks to the development of local businesses, communities and towns are also able to derive a number of economic, environmental, social and cultural advantage. The products in focus are emerging in tourism more often, frequently acting as foundations of tourist attractions built upon them, providing the receiving end with a unique and authentic force of attraction that follow the present trends. The aim of our study was to explore tourists’ needs for local products and the role of local food in regional tourism services. The region of our empirical research was the area of Baranya and Tolna counties in Southern Hungary where we analyzed local producers’ and their consumers’ attitudes towards local products.

Published
2021
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22. Myb-Binding Protein 1A (MYBBP1A) Is Essential for Early Embryonic Development, Controls Cell Cycle and Mitosis, and Acts as a Tumor Suppressor

Author

Mori, S, Bernardi, R, Laurent, A, Resnati, M, Crippa, A, Gabrieli, A, Keough, R, Gonda, T, Blasi, F, MORI, SILVIA, Blasi, F., Mori, S, Bernardi, R, Laurent, A, Resnati, M, Crippa, A, Gabrieli, A, Keough, R, Gonda, T, Blasi, F, MORI, SILVIA, and Blasi, F.

Abstract

MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation via acetylation. However little further information is available as to its function. Here we report that MYBBP1A is developmentally essential in the mouse prior to blastocyst formation. In cell culture, down-regulation of MYBBP1A decreases the growth rate of wild type mouse embryonic stem cells, mouse embryo fibroblasts (MEFs) and of human HeLa cells, where it also promotes apoptosis. HeLa cells either arrest at G2/M or undergo delayed and anomalous mitosis. At mitosis, MYBBP1A is localized to a parachromosomal region and gene-expression profiling shows that its down-regulation affects genes controlling chromosomal segregation and cell cycle. However, MYBBP1A down-regulation increases the growth rate of the immortalized NIH3T3 cells. Such Mybbp1a down-regulated NIH3T3 cells are more susceptible to Ras-induced transformation and cause more potent Ras-driven tumors. We conclude that MYBBP1A is an essential gene with novel roles at the pre-mitotic level and potential tumor suppressor activity. © 2012 Mori et al

Published
2012

25. Hyperplastic innervation of vasoactive intestinal peptide in human gallbladder with cholelithiasis

Author

Gonda, T., Akiyoshi, H., and Ichihara, K.

Subjects
VIP, Cholelithiasis, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], hormones, hormone substitutes, and hormone antagonists
Abstract

The vasoactive intestinal peptide (VIP) immunoreactive nerve fibres in the gallbladder from 14 human patients with cholelithiasis was examined by immunohistochemical method. In the chronic cholecystitis, hyperplastic VIP immunoreactive nerves were observed around the hypertrophied muscle bundles, Rokitansky Aschoff Sinus and in the mucosal layer. However, in the acute cholecystitis and gangrenous cholecystitis, reduction or disappearance of VIP nerve fibres was observed. These reductions or disappearances of VIP immunoreactive nerves may secondly result from severe tissue damage. These results suggest that hyperplastic VIP nerves cause gallbladder relaxation, stasis and mucosal fluid unbalance, which may closely correlate to gallstone formation.

Published
1995

42. The role of disulfide-linked dimerization in interleukin-3 receptor signaling and biological activity.

Author

Le, F, Stomski, F, Woodcock, J M, Lopez, A F, and Gonda, T J

Abstract

Cysteine residues 86 and 91 of the beta subunit of the human interleukin (hIL)-3 receptor (hbetac) participate in disulfide-linked receptor subunit heterodimerization. This linkage is essential for receptor tyrosine phosphorylation, since the Cys-86 --> Ala (Mc4) and Cys-91 --> Ala (Mc5) mutations abolished both events. Here, we used these mutants to examine whether disulfide-linked receptor dimerization affects the biological and biochemical activities of the IL-3 receptor. Murine T cells expressing hIL-3Ralpha and Mc4 or Mc5 did not proliferate in hIL-3, whereas cells expressing wild-type hbetac exhibited rapid proliferation. However, a small subpopulation of cells expressing each mutant could be selected for growth in IL-3, and these proliferated similarly to cells expressing wild-type hbetac, despite failing to undergo IL-3-stimulated hbetac tyrosine phosphorylation. The Mc4 and Mc5 mutations substantially reduced, but did not abrogate, IL-3-mediated anti-apoptotic activity in the unselected populations. Moreover, the mutations abolished IL-3-induced JAK2, STAT, and AKT activation in the unselected cells, whereas activation of these molecules in IL-3-selected cells was normal. In contrast, Mc4 and Mc5 showed a limited effect on activation of Erk1 and -2 in unselected cells. These data suggest that whereas disulfide-mediated cross-linking and hbetac tyrosine phosphorylation are normally important for receptor activation, alternative mechanisms can bypass these requirements.

Published
2000

44. A cell type-specific constitutive point mutant of the common beta-subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors requires the GM-CSF receptor alpha-subunit for activation.

Author

Jenkins, B J, Le, F, and Gonda, T J

Abstract

The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMRalpha) and a common signal-transducing beta-subunit (hbetac) that is shared with the interleukin-3 and -5 receptors. We have previously identified a constitutively active extracellular point mutant of hbetac, I374N, that can confer factor independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B. J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287). This restricted activity suggested the involvement of cell type-specific signaling molecules in the activation of this mutant. We report here that one such molecule is the mouse GMRalpha (mGMRalpha) subunit, since introduction of mGMRalpha, but not hGMRalpha, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred factor independence. Experiments utilizing mouse/human chimeric GMRalpha subunits indicated that the species specificity lies in the extracellular domain of GMRalpha. Importantly, the requirement for mGMRalpha correlated with the ability of I374N (but not wild-type hbetac) to constitutively associate with mGMRalpha. Expression of I374N in human factor-dependent UT7 cells also led to factor-independent proliferation, with concomitant up-regulation of hGMRalpha surface expression. Taken together, these findings suggest a critical role for association with GMRalpha in the constitutive activity of I374N.

Published
1999

45. A lethal myeloproliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte‐macrophage colony stimulating factor.

Author

Johnson, G. R., Gonda, T. J., Metcalf, D., Hariharan, I. K., and Cory, S.

Abstract

Murine bone marrow cells infected with a novel recombinant retrovirus, MPZen(GM‐CSF), were engrafted into lethally irradiated recipients. The transplanted animals developed extremely high circulating levels of GM‐CSF (up to 3 x 10(5) units/ml), and greatly elevated peripheral nucleated cell counts (up to 110 x 10(6) per ml). Their haemopoietic tissues contained GM‐CSF proviral DNA and produced substantial levels of GM‐CSF. The mice died within 4 weeks of transplantation with extensive neutrophil and macrophage infiltration of the spleen, lung, liver and peritoneal cavity and significant infiltration of both heart and skeletal muscle by neutrophils, macrophages and eosinophils. The thymus and lymph nodes were deficient in lymphoid cells. No disease occurred when infected cells from haemopoietic tissues of the primary transplanted animals were injected into normal or sub‐lethally irradiated mice. Dysregulated GM‐CSF expression by haemopoietic cells thus produces a fatal albeit non‐neoplastic myeloproliferative syndrome.

Published
1989
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46. Activation of c‐myb by carboxy‐terminal truncation: relationship to transformation of murine haemopoietic cells in vitro.

Author

Gonda, T. J., Buckmaster, C., and Ramsay, R. G.

Abstract

Murine retroviruses which encode c‐myb proteins that have either complete or truncated carboxy (C) termini were used to infect haemopoietic cells from murine fetal liver. Using an agar colony assay, we could show that infection with the virus encoding the truncated protein resulted in the persistence of colony‐forming cells well beyond the short period for which such cells are present in uninfected cultures. The resultant colonies failed to give rise to cell lines; however, clonal cell lines occasionally emerged from the original infected liquid cultures. The virus which encoded a myb protein with a complete C‐terminus was virtually inactive in the colony assay; surprisingly, however, this virus could enhance proliferation in liquid cultures and has led to the generation of at least one cell line. In addition to demonstrating ‘activation’ of c‐myb by C‐terminal truncation, our results imply that an unaltered c‐myb protein can also contribute to cellular transformation and that a second event is required to establish myb‐transformed cells as a permanent cell line.

Published
1989
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47. Murine myeloid cell lines derived by in vitro infection with recombinant c‐myb retroviruses express myb from rearranged vector proviruses.

Author

Gonda, T. J., Ramsay, R. G., and Johnson, G. R.

Abstract

To date, cellular transformation in vitro by the myb oncogene has been described for avian haemopoietic cells only. In order to exploit the well‐characterized murine haemopoietic system to study transformation by myb, we have infected fetal liver cells with retroviral vectors carrying cDNAs that encode either complete or carboxy‐terminally truncated c‐myb proteins. We describe four cell lines which, despite our ability to efficiently infect haemopoietic target cells, were generated at low frequency. This was due, as least in part, to the requirement for a rearrangement within the vector that allowed expression of myb sequences. Three of the lines express a truncated myb protein while the fourth apparently expresses a normal c‐myb protein, and thus constitutes an exception to the general association of truncation with transformation by myb. All four cell lines resemble immature cells of the myelomonocytic lineage and are dependent on colony‐stimulating factors (CSFs) for their growth in vitro. One representative line could be converted to CSF‐independence by infection with either Abelson murine leukaemia virus or a recombinant granulocyte‐macrophage‐CSF‐encoding retrovirus; unlike the parental line, the resultant sublines were highly tumorigenic when injected into syngeneic mice.

Published
1989
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48. A new diabetic strain of rat (WBN/Kob)

Author

Tsuchitani, M., Saegusa, T., Narama, I., Nishikawa, T., and Gonda, T.

Abstract

A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decrease in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity-onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals.

Published
1985
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49. Interacting residues in the extracellular region of the common beta subunit of the human granulocyte-macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 receptors involved in constitutive activation.

Author

Jenkins, B J, Bagley, C J, Woodcock, J, Lopez, A F, and Gonda, T J

Abstract

A previous study using random mutagenesis identified an activating mutation in the common beta subunit (hbetac) of the human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5 receptors in which an isoleucine residue (Ile374) in the extracellular region of hbetac is replaced by asparagine (Jenkins, B. J., D'Andrea, R., and Gonda, T. J. (1995) EMBO J 14, 4276-4287). To investigate the mechanism by which this mutation (I374N) acts, we employed site-directed mutagenesis to explore predictions based on a structural model of hbetac. We focused on possible interactions between Ile374 and other hydrophobic residues in its vicinity and found that replacement of two such residues, Leu356 and Trp358, with asparagine resulted in constitutive activation of hbetac. Hydrophilic substitutions at both of these positions and at position 374 resulted in the greatest degree of activation, as measured by the growth rate of factor-independent cells, while hydrophobic substitutions had lesser or no effects. Moreover, these "weak" substitutions appeared to synergize, since factor-independent cells expressing the double mutants I374F/W358F and I374F/L356A showed substantially higher growth rates than the single mutants. Taken together, these results suggest that Ile374 normally interacts with Leu356 and Trp358, and that disruption of these interactions results in a conformational change in hbetac that leads to constitutive activity. A model relating this notion to the predicted structure and to ligand- and alpha subunit-dependent activation of hbetac is proposed.

Published
1996

50. Generation of altered transcripts by retroviral insertion within the c-myb gene in two murine monocytic leukemias

Author

Gonda, T J, Cory, S, Sobieszczuk, P, Holtzman, D, and Adams, J M

Abstract

Two murine monocytic leukemia cell lines, WEHI-265 and WEHI-274, were found to carry a rearranged c-myb gene. The rearrangements are due to insertion of a deleted Moloney murine leukemia virus (Mo-MLV) provirus in the 5' region of the c-myb gene and thus are similar to rearrangements in the ABPL tumors (G. L. C. Shen-Ong, M. Potter, J. F. Mushinski, S. Lavu, and E. P. Reddy, Science 226:1077-1080, 1984). In each cell line, the retroviral insertion has induced high levels of two aberrant RNA species, which, as in the ABPL tumors (G. L. C. Shen-Ong, H. C. Morse, M. Potter, and J. F. Mushinski, Mol. Cell. Biol. 6:380-392, 1986), contain both viral (Mo-MLV) and cellular (myb) sequences. Both species lack the sequences encoding the amino terminus of the c-myb protein and thus could encode a protein which, like the v-myb gene products (and the predicted ABPL myb proteins), is truncated at the amino terminus. We have found that the larger (5.3 kilobase [kb]) and more abundant of the tumor-specific myb RNAs was predominantly nuclear, while the smaller species (3.9 kb) was cytoplasmic. Furthermore, our data imply that the 3.9-kb RNA was derived from the 5.3-kb RNA by an additional splice which utilized a cryptic splice acceptor site within the viral gag sequences. On the basis of subcellular distribution and predicted translational potential, we conclude that the 3.9-kb RNA is probably the mRNA which encodes a truncated myb protein. We also show that, due to different insertion points in W265 and W274, the W274 myb RNAs contained sequences from a c-myb exon upstream of the exons represented in the W265 (and ABPL) RNAs. The significance of our findings with regard to transformation by myb in these tumors is discussed.

Published
1987
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