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1. Genomic and epigenomic basis of breast invasive lobular carcinomas lacking CDH1 genetic alterations

Author

Dopeso, Higinio, Gazzo, Andrea M., Derakhshan, Fatemeh, Brown, David N., Selenica, Pier, Jalali, Sahar, Da Cruz Paula, Arnaud, Marra, Antonio, da Silva, Edaise M., Basili, Thais, Gusain, Laxmi, Colon-Cartagena, Lorraine, Bhaloo, Shirin Issa, Green, Hunter, Vanderbilt, Chad, Oesterreich, Steffi, Grabenstetter, Anne, Kuba, M. Gabriela, Ross, Dara, Giri, Dilip, Wen, Hannah Y., Zhang, Hong, Brogi, Edi, Weigelt, Britta, Pareja, Fresia, and Reis-Filho, Jorge S.

Published
2024
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4. Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry

Author

Robbins, Charles J., Fernandez, Aileen I., Han, Gang, Wong, Serena, Harigopal, Malini, Podoll, Mirna, Singh, Kamaljeet, Ly, Amy, Kuba, M. Gabriela, Wen, Hannah, Sanders, Mary Ann, Brock, Jane, Wei, Shi, Fadare, Oluwole, Hanley, Krisztina, Jorns, Julie, Snir, Olivia L., Yoon, Esther, Rabe, Kim, Soong, T. Rinda, Reisenbichler, Emily S., and Rimm, David L.

Published
2023
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9. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer

Author

Reisenbichler, Emily S., Han, Gang, Bellizzi, Andrew, Bossuyt, Veerle, Brock, Jane, Cole, Kimberly, Fadare, Oluwole, Hameed, Omar, Hanley, Krisztina, Harrison, Beth T., Kuba, M. Gabriela, Ly, Amy, Miller, Dylan, Podoll, Mirna, Roden, Anja C., Singh, Kamaljeet, Sanders, Mary Ann, Wei, Shi, Wen, Hannah, Pelekanou, Vasiliki, Yaghoobi, Vesal, Ahmed, Fahad, Pusztai, Lajos, and Rimm, David L.

Published
2020
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10. Interobserver Variation of PD-L1 SP142 Immunohistochemistry Interpretation in Breast Carcinoma: A Study of 79 Cases Using Whole Slide Imaging

Author

Hoda, Raza S., Brogi, Edi, D'Alfonso, Timothy M., Grabenstetter, Anne, Giri, Dilip, Hanna, Matthew G., Kuba, M. Gabriela, Murray, Melissa P., Vallejo, Christina E., Zhang, Hong, Reis-Filho, Jorge S., and Wen, Hannah Y.

Subjects
Diagnostic immunohistochemistry -- Methods, Membrane proteins -- Health aspects, Pathologists -- Psychological aspects, Biochemical assays -- Usage, Health
Abstract

* Context.--The Ventana programmed death ligand-1 (PD-L1) SP142 immunohistochemical assay (IHC) is approved by the US Food and Drug Administration as the companion diagnostic assay to identify patients with locally advanced or metastatic triple-negative breast cancer for immunotherapy with atezolizumab, a monoclonal antibody targeting PD-L1. Objective.--To determine interobserver variability in PD-L1 SP142 IHC interpretation in invasive breast carcinoma. Design.--The pathology database was interrogated for all patients diagnosed with primary invasive, locally recurrent, or metastatic breast carcinoma on which PD-L1 SP142 IHC was performed from November 2018 to June 2019 at our institution. A subset of cases was selected using a computerized random-number generator. PD-L1 IHC was evaluated in stromal tumor-infiltrating immune cells using the IMpassion130 trial criteria, with positive cases defined as immunoreactivity in immune cells in 1% or more of the tumor area. IHC was interpreted on whole slide images by staff pathologists with breast pathology expertise. Interobserver variability was calculated using unweighted k. Results.--A total of 79 cases were assessed by 8 pathologists. Interobserver agreement was substantial (k = 0.727). There was complete agreement among all 8 pathologists in 62% (49 of 79) of cases, 7 pathologists or more in 84% (66 of 79) of cases, and 6 pathologists or more in 92% (73 of 79) of cases. In 4% (3 of 79) of cases, all of which were small biopsies, pathologists' interpretations were evenly split between scores of positive and negative. Conclusions.--The findings show substantial agreement in PD-L1 SP142 IHC assessment of breast carcinoma cases among 8 pathologists at a single institution. Further study is warranted to define the basis for discrepant results. (Arch Pathol Lab Med. 2021;145:1132-1137; doi: 10.5858/arpa.2020-0441-OA, Triple-negative breast carcinomas (TNBCs) lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) and are associated with aggressive clinical behavior. Median overall survival for [...]

Published
2021
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11. Supplemental Figure 5 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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12. Supplemental Figure 1 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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13. Supplemental Figure 4 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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14. Supplemental Figure 2 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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15. Supplemental Figure 3 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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16. Supplementary legend from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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17. Supplemental Table 1 from A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., primary, Mayer, Erica L., primary, Abramson, Vandana G., primary, Bardia, Aditya, primary, Sanders, Melinda E., primary, Kuba, M. Gabriela, primary, Estrada, Monica V., primary, Beeler, J. Scott, primary, Shaver, Timothy M., primary, Johnson, Kimberly C., primary, Sanchez, Violeta, primary, Rosenbluth, Jennifer M., primary, Dillon, Patrick M., primary, Forero-Torres, Andres, primary, Chang, Jenny C., primary, Meszoely, Ingrid M., primary, Grau, Ana M., primary, Lehmann, Brian D., primary, Shyr, Yu, primary, Sheng, Quanhu, primary, Chen, Sheau-Chiann, primary, Arteaga, Carlos L., primary, and Pietenpol, Jennifer A., primary

Published
2023
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21. Zrakové evokované potenciály lze vyšetřit novým mobilním přístrojem kdekoliv.

Author

Kuba, M., Kremláček, J., Vít, F., Kubová, Z., Szanyi, J., Chutná, M., Ramešová, L., and Langrová, J.

Subjects
*VISUAL evoked potentials, *ANALOG-to-digital converters, *EVOKED potentials (Electrophysiology), *ELECTROPHYSIOLOGY, *NEUROPHYSIOLOGY
Abstract

Aim: Visual evoked potentials (VEP) represent an objective non-invasive and inexpensive dia­gnostic method, particularly in neuro-ophthalmology. A lot of possible dia­gnostic applications are limited because they are only examined with the use of robust equipment which is hardly transportable and immobile and handicapped patients cannot visit the specialized labs. The aim of our research work was the development of a portable inexpensive VEP device that could be used almost anywhere. Methods: All parts of the last prototype of the device (built-in visual stimulator, recording electrodes, 4-channel EEG amplifier, analog-digital converter, and control unit) with a total weight of 390 g are placed in a headset (plastic "shield" with an adjustable strap). The software for VEP recording and evaluation is used on a standard notebook (PC). The parameters of the device fulfill recommendations of the international societies for clinical electrophysiology of vision and clinical neurophysiology also enabling new applications of so far not routinely used variants of evoked potentials. Testing of the device was done so far in 91 control subjects and 135 neuroophthalmological patients. Results: Pilot studies proved comparable parameters of VEP and dia­gnostic sensitivity as in standard devices (equal results in 93% of cases). It was verified that the device is usable in various environments, at the patient's bedside, and also for basic self-examination. Conclusion: The portable device for VEP significantly increases the availability of their examination and thus enables much broader dia­gnostic applications of this method. [ABSTRACT FROM AUTHOR]

Published
2023

22. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue

Author

Fernandez, Aileen I., primary, Liu, Matthew, additional, Bellizzi, Andrew, additional, Brock, Jane, additional, Fadare, Oluwole, additional, Hanley, Krisztina, additional, Harigopal, Malini, additional, Jorns, Julie M., additional, Kuba, M. Gabriela, additional, Ly, Amy, additional, Podoll, Mirna, additional, Rabe, Kimmie, additional, Sanders, Mary Ann, additional, Singh, Kamaljeet, additional, Snir, Olivia L., additional, Soong, T. Rinda, additional, Wei, Shi, additional, Wen, Hannah, additional, Wong, Serena, additional, Yoon, Esther, additional, Pusztai, Lajos, additional, Reisenbichler, Emily, additional, and Rimm, David L., additional

Published
2022
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27. Influence of Solvent Temperature and Type on Naphthalene Solubility for Tar Removal in a Dual Fluidized Bed Biomass Gasification Process

Author

Tonpakdee, P., Hongrapipat, J., Siriwongrungson, V., Rauch, R., Pang, S., Thaveesri, J., Messner, M., Kuba, M., and Hofbauer, H.

Subjects
oil scrubber, Chemical engineering, tar removal, dual fluidized bed biomass gasification, ddc:660, naphthalene, food and beverages, solvent scrubbing, complex mixtures
Abstract

Tar condensation is a cause of blockage in downstream application of the gasification process. An oil scrubber is considered as an effective method for tar removal. In this research, the naphthalene solubility in different local Thai oils and water was investigated in a laboratory-scale test-rig. The solubility value was conducted at 30, 50, 70, and 80°C. Biodiesels investigated were rapeseed methyl ester (RME) and two different palm methyl esters (PME 1 and PME 2). Furthermore, vegetable oils including sunflower oil, rice bran oil, crude palm oil, and refined palm oil were examined. The results showed that higher temperature enhanced naphthalene solubility in all types of investigated oils. Biodiesel has the highest value of naphthalene solubility. All scrubbing oils have similar naphthalene solubility trends at the temperature range of 50-80°C in the order of RME > PME 1 > PME 2 > diesel > sunflower oil > refined palm oil > rice bran oil > crude palm oil. Based on these experimental investigations, PME 1 has a naphthalene solubility value similar to RME. Therefore, PME 1 has been selected to be tested as scrubbing solvent in the 1 MWel prototype dual fluidized gasifier located in Nong Bua district, Nakhon Sawan province, Thailand.

Published
2021
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28. Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

Author

Mifsud, EJ, Kuba, M, Barr, IG, Mifsud, EJ, Kuba, M, and Barr, IG

Abstract

The innate immune system is the host's first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

Published
2021

29. GA4GH: International policies and standards for data sharing across genomic research and healthcare

Author

Rehm, HL, Page, AJH, Smith, L, Adams, JB, Alterovitz, G, Babb, LJ, Barkley, MP, Baudis, M, Beauvais, MJS, Beck, T, Beckmann, JS, Beltran, S, Bernick, D, Bernier, A, Bonfield, JK, Boughtwood, TF, Bourque, G, Bowers, SR, Brookes, AJ, Brudno, M, Brush, MH, Bujold, D, Burdett, T, Buske, OJ, Cabili, MN, Cameron, DL, Carroll, RJ, Casas-Silva, E, Chakravarty, D, Chaudhari, BP, Chen, SH, Cherry, JM, Chung, J, Cline, M, Clissold, HL, Cook-Deegan, RM, Courtot, M, Cunningham, F, Cupak, M, Davies, RM, Denisko, D, Doerr, MJ, Dolman, LI, Dove, ES, Dursi, LJ, Dyke, SOM, Eddy, JA, Eilbeck, K, Ellrott, KP, Fairley, S, Fakhro, KA, Firth, HV, Fitzsimons, MS, Fiume, M, Flicek, P, Fore, IM, Freeberg, MA, Freimuth, RR, Fromont, LA, Fuerth, J, Gaff, CL, Gan, W, Ghanaim, EM, Glazer, D, Green, RC, Griffith, M, Griffith, OL, Grossman, RL, Groza, T, Auvil, JMG, Guigo, R, Gupta, D, Haendel, MA, Hamosh, A, Hansen, DP, Hart, RK, Hartley, DM, Haussler, D, Hendricks-Sturrup, RM, Ho, CWL, Hobb, AE, Hoffman, MM, Hofmann, OM, Holub, P, Hsu, JS, Hubaux, J-P, Hunt, SE, Husami, A, Jacobsen, JO, Jamuar, SS, Janes, EL, Jeanson, F, Jene, A, Johns, AL, Joly, Y, Jones, SJM, Kanitz, A, Kato, K, Keane, TM, Kekesi-Lafrance, K, Kelleher, J, Kerry, G, Khor, S-S, Knoppers, BM, Konopko, MA, Kosaki, K, Kuba, M, Lawson, J, Leinonen, R, Li, S, Lin, MF, Linden, M, Liu, X, Liyanage, IU, Lopez, J, Lucassen, AM, Lukowski, M, Mann, AL, Marshall, J, Mattioni, M, Metke-Jimenez, A, Middleton, A, Milne, RJ, Molnar-Gabor, F, Mulder, N, Munoz-Torres, MC, Nag, R, Nakagawa, H, Nasir, J, Navarro, A, Nelson, TH, Niewielska, A, Nisselle, A, Niu, J, Nyronen, TH, O'Connor, BD, Oesterle, S, Ogishima, S, Wang, VO, Paglione, LAD, Palumbo, E, Parkinson, HE, Philippakis, AA, Pizarro, AD, Prlic, A, Rambla, J, Rendon, A, Rider, RA, Robinson, PN, Rodarmer, KW, Rodriguez, LL, Rubin, AF, Rueda, M, Rushton, GA, Ryan, RS, Saunders, GI, Schuilenburg, H, Schwede, T, Scollen, S, Senf, A, Sheffield, NC, Skantharajah, N, Smith, AV, Sofia, HJ, Spalding, D, Spurdle, AB, Stark, Z, Stein, LD, Suematsu, M, Tan, P, Tedds, JA, Thomson, AA, Thorogood, A, Tickle, TL, Tokunaga, K, Tomroos, J, Torrents, D, Upchurch, S, Valencia, A, Guimera, RV, Vamathevan, J, Varma, S, Vears, DF, Viner, C, Voisin, C, Wagner, AH, Wallace, SE, Walsh, BP, Williams, MS, Winkler, EC, Wold, BJ, Wood, GM, Woolley, JP, Yamasaki, C, Yates, AD, Yung, CK, Zass, LJ, Zaytseva, K, Zhang, J, Goodhand, P, North, K, Birney, E, Rehm, HL, Page, AJH, Smith, L, Adams, JB, Alterovitz, G, Babb, LJ, Barkley, MP, Baudis, M, Beauvais, MJS, Beck, T, Beckmann, JS, Beltran, S, Bernick, D, Bernier, A, Bonfield, JK, Boughtwood, TF, Bourque, G, Bowers, SR, Brookes, AJ, Brudno, M, Brush, MH, Bujold, D, Burdett, T, Buske, OJ, Cabili, MN, Cameron, DL, Carroll, RJ, Casas-Silva, E, Chakravarty, D, Chaudhari, BP, Chen, SH, Cherry, JM, Chung, J, Cline, M, Clissold, HL, Cook-Deegan, RM, Courtot, M, Cunningham, F, Cupak, M, Davies, RM, Denisko, D, Doerr, MJ, Dolman, LI, Dove, ES, Dursi, LJ, Dyke, SOM, Eddy, JA, Eilbeck, K, Ellrott, KP, Fairley, S, Fakhro, KA, Firth, HV, Fitzsimons, MS, Fiume, M, Flicek, P, Fore, IM, Freeberg, MA, Freimuth, RR, Fromont, LA, Fuerth, J, Gaff, CL, Gan, W, Ghanaim, EM, Glazer, D, Green, RC, Griffith, M, Griffith, OL, Grossman, RL, Groza, T, Auvil, JMG, Guigo, R, Gupta, D, Haendel, MA, Hamosh, A, Hansen, DP, Hart, RK, Hartley, DM, Haussler, D, Hendricks-Sturrup, RM, Ho, CWL, Hobb, AE, Hoffman, MM, Hofmann, OM, Holub, P, Hsu, JS, Hubaux, J-P, Hunt, SE, Husami, A, Jacobsen, JO, Jamuar, SS, Janes, EL, Jeanson, F, Jene, A, Johns, AL, Joly, Y, Jones, SJM, Kanitz, A, Kato, K, Keane, TM, Kekesi-Lafrance, K, Kelleher, J, Kerry, G, Khor, S-S, Knoppers, BM, Konopko, MA, Kosaki, K, Kuba, M, Lawson, J, Leinonen, R, Li, S, Lin, MF, Linden, M, Liu, X, Liyanage, IU, Lopez, J, Lucassen, AM, Lukowski, M, Mann, AL, Marshall, J, Mattioni, M, Metke-Jimenez, A, Middleton, A, Milne, RJ, Molnar-Gabor, F, Mulder, N, Munoz-Torres, MC, Nag, R, Nakagawa, H, Nasir, J, Navarro, A, Nelson, TH, Niewielska, A, Nisselle, A, Niu, J, Nyronen, TH, O'Connor, BD, Oesterle, S, Ogishima, S, Wang, VO, Paglione, LAD, Palumbo, E, Parkinson, HE, Philippakis, AA, Pizarro, AD, Prlic, A, Rambla, J, Rendon, A, Rider, RA, Robinson, PN, Rodarmer, KW, Rodriguez, LL, Rubin, AF, Rueda, M, Rushton, GA, Ryan, RS, Saunders, GI, Schuilenburg, H, Schwede, T, Scollen, S, Senf, A, Sheffield, NC, Skantharajah, N, Smith, AV, Sofia, HJ, Spalding, D, Spurdle, AB, Stark, Z, Stein, LD, Suematsu, M, Tan, P, Tedds, JA, Thomson, AA, Thorogood, A, Tickle, TL, Tokunaga, K, Tomroos, J, Torrents, D, Upchurch, S, Valencia, A, Guimera, RV, Vamathevan, J, Varma, S, Vears, DF, Viner, C, Voisin, C, Wagner, AH, Wallace, SE, Walsh, BP, Williams, MS, Winkler, EC, Wold, BJ, Wood, GM, Woolley, JP, Yamasaki, C, Yates, AD, Yung, CK, Zass, LJ, Zaytseva, K, Zhang, J, Goodhand, P, North, K, and Birney, E

Abstract

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

Published
2021

30. Characterisation of putative lactate synthetic pathways of Coxiella burnetii

Author

Voth, DE, Hofmann, J, Bitew, MA, Kuba, M, De Souza, DP, Newton, HJ, Sansom, FM, Voth, DE, Hofmann, J, Bitew, MA, Kuba, M, De Souza, DP, Newton, HJ, and Sansom, FM

Abstract

The zoonotic pathogen Coxiella burnetii, the causative agent of the human disease Q fever, is an ever-present danger to global public health. Investigating novel metabolic pathways necessary for C. burnetii to replicate within its unusual intracellular niche may identify new therapeutic targets. Recent studies employing stable isotope labelling established the ability of C. burnetii to synthesize lactate, despite the absence of an annotated synthetic pathway on its genome. A noncanonical lactate synthesis pathway could provide a novel anti-Coxiella target if it is essential for C. burnetii pathogenesis. In this study, two C. burnetii proteins, CBU1241 and CBU0823, were chosen for analysis based on their similarities to known lactate synthesizing enzymes. Recombinant GST-CBU1241, a putative malate dehydrogenase (MDH), did not produce measurable lactate in in vitro lactate dehydrogenase (LDH) activity assays and was confirmed to function as an MDH. Recombinant 6xHis-CBU0823, a putative NAD+-dependent malic enzyme, was shown to have both malic enzyme activity and MDH activity, however, did not produce measurable lactate in either LDH or malolactic enzyme activity assays in vitro. To examine potential lactate production by CBU0823 more directly, [13C]glucose labelling experiments compared label enrichment within metabolic pathways of a cbu0823 transposon mutant and the parent strain. No difference in lactate production was observed, but the loss of CBU0823 significantly reduced 13C-incorporation into glycolytic and TCA cycle intermediates. This disruption to central carbon metabolism did not have any apparent impact on intracellular replication within THP-1 cells. This research provides new information about the mechanism of lactate biosynthesis within C. burnetii, demonstrating that CBU1241 is not multifunctional, at least in vitro, and that CBU0823 also does not synthesize lactate. Although critical for normal central carbon metabolism of C. burnetii, loss of CBU0823

Published
2021

35. Abstract PD5-01: Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays in triple negative breast cancer

Author

Reisenbichler, Emily Suzanne, primary, Han, Gang, additional, Pelekanou, Vasiliki, additional, Yaghoobi, Vesal, additional, Ahmed, Fahad S, additional, Bellizzi, Andrew, additional, Bossuyt, Veerle, additional, Brock, Jane, additional, Cole, Kimberly, additional, Fadare, Oluwole, additional, Hameed, Omar, additional, Hanley, Krisztina, additional, Harrison, Beth T, additional, Kuba, M G, additional, Ly, Amy, additional, Miller, Dylan, additional, Podoll, Mirna, additional, Roden, Anja C, additional, Sanders, Mary A, additional, Singh, Kamaljeet, additional, Wei, Shi, additional, Wen, Hannah, additional, Pusztai, Lajos, additional, and Rimm, David L, additional

Published
2020
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36. Promising Directions of Investment Diplomacy of Azerbaijan

Author

Kuba Mehdiyeva

Subjects
encouragement, investment, negotiations, agreement, investment diplomacy, Education
Abstract

The purpose of the study is to identify promising areas of investment diplomacy in encouraging foreign investment in the economy of Azerbaijan. As a result of the study, the tasks of identifying areas of agreements with countries of the world to encourage foreign investment and identify areas belonging to attracting foreign investment have been solved. The author considers investments made in Azerbaijan; studies investments directed abroad. A limitation in the study was the lack of open information before 2000 on benefits and other measures in agreements between Azerbaijan and other countries, the lack of information on investment investments abroad by sectors of the economy, and the discrepancy in figures between the CBA and UNCTAD. The study used the methods of grouping, analysis and comparison. The legal framework, information from reports of international organizations, forums were used. The scientific novelty of the study is that the author considered new trends in the field of investment attractiveness and made proposals on the directions of Azerbaijan’s investment diplomacy. The author found that agreements, conventions and protocols have a different structure and significant differences in the content of bilateral investment treaties allow the country to retain certain leverage. In the sectoral context, the largest flows of investments were directed to the development of industry, construction and transport. Since 2006, there has been an increase in investment in the transport sector, and since 2014 in construction. Despite the growth of foreign investment in these sectors, statistics still recorded an increase in the inflow of foreign investment in the sector of crude oil and natural gas production. Also, 30% of Azerbaijan’s direct investment abroad is in the oil sector. In order to implement promising areas of Azerbaijan’s investment diplomacy in the near future, it was proposed to introduce active investment diplomacy.

Published
2023
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39. Abstract of the 68th Meeting (Spring Meeting) 6–9 March 1990, Heidelberg

Author

Sakmann, B., Schrader, J., Brenner, B., Murer, H., Boeckh, J., Handwerker, H. O., HonerjÄger, P., Dugas, M., Wang, G., DeLuca, A., Brinkmeier, H., Fakler, B., Pröbstle, T., Rüdel, R., Pohl, J. -A., Meves, H., Kroll, B., Bremer, S., Tümmler, B., Frömter, E., Schwegler, J. S., Steigner, W., Silbernagl, S., Pusch, Michael, Niemann, P., Schmidtmayer, J., Ulbricht, W., Hansen, G., Lönnendonker, U., Neumcke, B., Eickhorn, R., Hornung, D., Antoni, H., Penner, R., Neher, E., Takeshima, H., Nishimura, S., Numa, S., Melzer, W., Feldmeyer, D., Pohl, B., Zöllner, P., Müller, T. H., Swandulla, D., Misgeld, U, Ganitkevich, V. Ya., Isenberg, G., Cavalié, A., Allen, T. J. A., Trautwein, W., Pelzer, Siegried, Shuba, Yaroslav M., Asai, Tatsuya, Trautwein, Wolfgang, Brown, Arthur M., Birnbauner, Lutz, McDonald, Terence F., Pelzer, Dieter, Eckert, R., Hescheler, J., Rosenthal, W., Offermann, S., Krautwurst, D., Schultz, G., Kettenmahn, Helmut, Trotter, J., Verkhratsky, Alexe J N., Savtchenko, Alexej N., Verkhratsky, Alexej N., Schiefer, A., Klöckner, U., Partridge, L. D., SchÄfer, S., Jonas, P., Koh, D. S., Kampe, K., Hermsteiner, M., Vogel, W., Bauer, C. K., Schwarz, J. R., Fink, R. H. A., Wettwer, E., Weik, R., Schlatter, E., Bleich, M., Granitzer, M., Leal, T., Nagel, W., Crabbé, J., Lang, F., Kahn, E., Friedrich, F., Paulmichl, M., Hammerer, M., Maly, K., Grunicke, H., Böhm, T., Nilius, B., Gögelein, H., Dahlem, D., Weiss, H., Waldegger, S., Woell, E., Paulmichl, R., Ruppersberg, J. P., Schröter, K. H., Stocker, M., Pongs, O., Wittka, R., Boheim, G., Lichtinghagen, R, Augustine, C. K., Stühmer, W., Hoppe, Dorothe, Hoppe, D., Zittlau, K. E., Walther, C., Hatt, H., Franke, C., Quasthoff, S., Wischmeyer, E., Jockusch, H., Friedrich, M., Benndorf, K., Bollmann, G., Hirche, Hj., Hollunder-Reese, F., Mohrmann, M., Greger, R., Weber-Schürholz, S., Schürholz, T., Akabas, M., Landry, D., Al-Awqati, Q., Guse, A. H., Gercken, G., Meyerhof, W., Westphale, H. -J., Kerstins, U., Oberleithner, H., Tilmann, M., Kunzelmann, K., Klitsch, T., Siemen, D., Draguhn, A., Verdoorn, T. A., Pritchett, D. B., Seeburg, P. H., Malherbe, P., Möhler, H., Sakmann, B., Hatt H., Dudel, J., Stern, P., Zufall, F., Rosenheimer, J., Smith, D. O., Dörner, R., Ballanyi, K., Schlue, W. -R., Kalthof, B., Pott, L., Busch, C., Konno, T., Stenql, M., Reinhardt, Ch., Kaiser, H., Baumann, R., Wilimzig, M., Eichenlaub, R., Neumann, E., Lessmann, V., Gottmann, K., Dietzel, I. D., Keller, B. U., Yaari, Y., Konnerth, A., Backus, K. H., Giller, T., Knoflach, F., Pflimlin, P., Trübe, G., von Blankenfeld, G., Ymer, S., Sontheimer, H., Ewert, M., Seeburg, P. H., Kettenmann, H., Schneggenburger, R., Paschke, D., Hülser, D. F., Ubl, J., Kolb, H. A., Ströttchen, J., Boheim, S., Wehner, F., Guth, D., Kinne, R. K. H., Hülser, D. F., Polder, H. R., Bödeker, D., Hoppe, Susanne, Höller, H., Hampe, W., Ruf, H., Schulz, I., Dehlinger-Kremer, M., Ozawa, T., Vasilets, L., Schmalzing, G., MÄdefessel, K., Biel, H., Schwarz, W., Burckhardt, B. C., Stallmach, N., MairbÄurl, H., Hoffman, J. F., Schömig, E., Heuner, A., Göbel, B. O., Siffert, W., Butke, A., Hoffmann, G., zu Brickwedde, M. -K. Meyer, Vetter, H., Düsing, R., Rosskopf, D., Osswald, U., Steffgen, J., Koepsell, H., Martens, H., Rübbelke, M., GÄbel, G., Arens, J., Stabel, J., Fischer, Y., Thomas, J., Rose, H., Kammermeier, H., Munsch, Thomas, Deitmer, Joachim W., Engelmann, B., Duhm, J., Deitmer, Joachim W., Gunzel, D., Galler, S., Fischer, H., Clauss, W., Van Driessche, W., Köckerling, A, Schulzke, JD, Sorgenfrei, D, Fromm, M, Simon, B., Ganapathy, V., Leibach, F. H., Burckhardt, G., Krattenmacher, R., Voigt, Rosita, Dietrich, S., Leyssens, A., Zhang, S. L., Weltens, R., Steels, P., Hoffmann, B., Heinz, M., Habura, B., Dörge, A., Rechkemmer, G., von Engelhardt, W., StrauB, O., Wiederholt, M., Margineanu, D. -G., Van Driessche, W., Kreusel, K. M., Fromm, M., Lempart, U., Sorgenfrei, D., Hegel, U., Augustin, A. J., . Goldstein, R., Purucker, E., Lutz, J., Illek, B., Thiele, K -P., Schwealer, JS., Dittmer J., Bauer C., Eckardt, K. -U., Dittmer, J., Neumann, R., Bauer, C., Kurtz, A., Fromm, H., Schulzke, J. D., Clausen, P., Krohn, A., Lüderitz, S., Hierholzer, K., Kersting, U., Woinowski, L., Gro\mann, R., Bin, X. U., Ellendorff, F., Nitschke, R., Fröbe, U., Scholz, H., della Bruna, R., Ehmke, H., Persson, P. B., Seyfarth, M., Kirchheim, H. R., Dietrich, M. S., Parekh, N., Steinhausen, M., Bührle, C. P., Nobiling, R., Ullrich, K. J., Rumrich, G., Klöss, S., Papavassiliou, F., Hoyer, J., Schmitt, C., Jungwirth, A., Ritter, M., Westphale, H. 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G., Pusch, H., Zylka, Ch., Brāndle, M., Jacob, R., Stein, T., Isselhard, W., Sturz, J., Minor, T., Wingenfeld, P., Siegmund, B., Klietz, T., Schwartz, P., Piper, H. M., Linder, Christa, SchÄfer, Stefan, Heusch, Gerd, Becker, B. F., Reinholz, N., Raschke, P., Leipert, B., Gerlach, E., Dierberger, B., Gülch, R. W., Leverkus, M., Mitsuiye, T., Pohl, U., Wang, S. Y., Meyer, R., Haas, H. G., Christmann, H. Ph, Dörner, Th, Hock, D., Hertel, R., Gagelmann, M., Forssmann, W. G., Leijendekker, W. J., Kissling, G., Michel, H., Goetz, A., Freya, M., Fleckenstein-Grün, G., Schipke, Jochen D., Harasawa, Yasuhiko, Sugiura, Seiryo, Alexander, Joe, Burkhoff, Daniel, Kling, L., Müller-Beckmann, B., Schroth, M., Sponer, G., Böhm, E., Strein, K., Dorszewski, A., Arnold, G., Pike, G. K., Bryant, D. J., Roberts, M. L., Fink, R. H., Ross, Ch., Skyschally, A., Schulz, R., Linder, C., Heusch, G., Schipke, J. D., Burkhoff, D., Alexander, J., Gollnick, F., Peter, Kh., Franken-Weyers, R., Borst, M. 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J., Blankenbach, K., Asmussen, G., Kunze, I., Pieper, K. -S., Steinmetz, J., Schmidt, H., Krippeit-Drews, P., Hübschen, U., Nacimiento, A. C., Günzel, D., Rathmayer, W., Gaunitz, U., Költgen, D., Zachar, E., Soltau, B., De Martino, L., Hasselbach, W., Kössler, F., Lange, P., Küchler, G., Zeugner, C., Van Eyk, J., Hodges, R. S., Lorkovic, H., Clemens, N., Scheid, P., Noack, Th., Deitmer, P., Golenhofen, K., Lammel, E., Welling, Andrea, Felbel, Jochen, Hofmann, Franz, Katoch, S., Watanabe, T., Mandrek, K., Milenov, K., Hammer, K., Rössler, W., Sann, H., Pierau, Fr -K., Nguyen-Duong, H., Schneider, P., Stahl, F., Lepple-Wienhues, A., Korbmacher, C., Haller, H., Gebauer, M., Willner, U., Bialojan, C., Lengsfeld, M., Kyrtatas, V., Dartsch, Peter C., Boels, P. J., Fischer, W., Lenz, T., Thei\, U., Kreye, V. A. 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L., Schönrock, B., Altrup, U., Reith, H., Speckmann, E. -J., Alzheimer, C., Bruagencate, G. ten, Fruhstorfer, B., Mignot, E., Nishino, S., Dement, W. C., Guilleminault, C., Simon-Oppermann, Christa, Günther, Olaf, Stehle, J., Reuss, S., Seidel, A., Riemann, R., Vollrath, L., Reimer, Susanne, HölIt, Volker, Sonnhof, U., Krupp, J., Claus, H, Hinckel, P., Dick, H. B. H., Hiemke, C., Jussofie, A., Dorn, T., Uhlig, S., Witte, O. W., Bother B., Eiselt M., Witte H., Zwiener ö, Rother M, Eiseit H., Taghavy, A., KrÄtzer, A., Clusmann, H., Heinemann, U., Block, F., Sonatg, K. -H., Falkeristein, M., Hohnsbein, J., Hoormann, J., Frieling, A., Tarkka, I. M., Kullmann, W., Bromm, B., Hirsch, M. Chr, Wissing, H., Braun, H. A., Igelmund, P., Klu\mann, F. W., Ehrenstein, W. H., Yakimoff, N., Mateeff, S., Zeise, M. L., Arriagada, J., Teschemacher, A., ZieglgÄnsberger, W., Pöppelmann, T., Köhling, R., Boerrigter, P., Reith, H., Anders, K., Ohndorf, W., Dermietzel, R., Richter, D. W., Tölle, T. 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W., Mueller-Klieser, W., Vaupel, P., Okunieff, P., Mayer, W. -K., Stohrer, M., Krüger, W., Müller-Klieser, W., Strupp, M., Weial, P., Bostock, H., Piwernetz, K., Renner, R., Grafe, P., Lankers, J., Zangemeister, W., Kunze, K., Tries, S., Heinle, H., Beckerath, N. V., Maier-Rudolph, W., Mehrke, G., Günther, K., Goedel-Meinen, L., Daut, J., Piper, H. M., Kopp, A., Noll, T., Goellner, A., Gerlach, S., Teutsch, H. F., Schienger, K., Schwab, R., Höckel, M., Fotev, Z., Nienhaus, M., Kaczmarczyk, Gabriele, Richter, Dinah, Korte, Gabriele, Förther, J., Reinhardt, H. W., Schreiber, R., Rupp, J., Murphy, G., Fingerle, J., Kloiber, O., Miyazawa, T., Höhn-Berlage, M., Hossmann, K. -A., Schad, H., Heimisch, W., Blasini, R., Haas, F., Mendier, M., Spuler, A., Lehmann-Hom, F., Wolfram, U., Fenske, M., Sachser, N., Weis, Ch., Marktl, W., Kopta, B., Klammer, N., Rudas, B., Pohl, H., Nienartowicz, A., Moll, W., Klempt, M., Blum, S., Bühler, H., Lichtenstein, I., Novak, A., Siebe, H., Hierholzer, K., and Peper, K.

Published
1990
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41. Coxiella burnetii utilizes both glutamate and glucose during infection with glucose uptake mediated by multiple transporters

Author

Kuba, M, Neha, N, De Souza, DP, Dayalan, S, Newson, JPM, Tull, D, McConville, MJ, Sansom, FM, Newton, HJ, Kuba, M, Neha, N, De Souza, DP, Dayalan, S, Newson, JPM, Tull, D, McConville, MJ, Sansom, FM, and Newton, HJ

Abstract

Coxiella burnetii is a Gram-negative bacterium which causes Q fever, a complex and life-threatening infection with both acute and chronic presentations. C. burnetii invades a variety of host cell types and replicates within a unique vacuole derived from the host cell lysosome. In order to understand how C. burnetii survives within this intracellular niche, we have investigated the carbon metabolism of both intracellular and axenically cultivated bacteria. Both bacterial populations were shown to assimilate exogenous [13C]glucose or [13C]glutamate, with concomitant labeling of intermediates in glycolysis and gluconeogenesis, and in the TCA cycle. Significantly, the two populations displayed metabolic pathway profiles reflective of the nutrient availabilities within their propagated environments. Disruption of the C. burnetii glucose transporter, CBU0265, by transposon mutagenesis led to a significant decrease in [13C]glucose utilization but did not abolish glucose usage, suggesting that C. burnetii express additional hexose transporters which may be able to compensate for the loss of CBU0265. This was supported by intracellular infection of human cells and in vivo studies in the insect model showing loss of CBU0265 had no impact on intracellular replication or virulence. Using this mutagenesis and [13C]glucose labeling approach, we identified a second glucose transporter, CBU0347, the disruption of which also showed significant decreases in 13C-label incorporation but did not impact intracellular replication or virulence. Together, these analyses indicate that C. burnetii may use multiple carbon sources in vivo and exhibits greater metabolic flexibility than expected.

Published
2019

44. A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67

Author

Jovanović, Bojana, primary, Mayer, Ingrid A., additional, Mayer, Erica L., additional, Abramson, Vandana G., additional, Bardia, Aditya, additional, Sanders, Melinda E., additional, Kuba, M. Gabriela, additional, Estrada, Monica V., additional, Beeler, J. Scott, additional, Shaver, Timothy M., additional, Johnson, Kimberly C., additional, Sanchez, Violeta, additional, Rosenbluth, Jennifer M., additional, Dillon, Patrick M., additional, Forero-Torres, Andres, additional, Chang, Jenny C., additional, Meszoely, Ingrid M., additional, Grau, Ana M., additional, Lehmann, Brian D., additional, Shyr, Yu, additional, Sheng, Quanhu, additional, Chen, Sheau-Chiann, additional, Arteaga, Carlos L., additional, and Pietenpol, Jennifer A., additional

Published
2017
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45. Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

Author

Kinoshita, A, Fukuda, M, Soda, H, Nagashima, S, Takatani, H, Kuba, M, Nakamura, Y, Tsurutani, J, Kohno, S, and Oka, M

Subjects
Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Phases of clinical research, Neutropenia, chemotherapy, Irinotecan, Gastroenterology, Carboplatin, chemistry.chemical_compound, Internal medicine, Clinical Studies, Antineoplastic Combined Chemotherapy Protocols, small-cell lung cancer, medicine, Humans, Carcinoma, Small Cell, Lung cancer, Aged, Chemotherapy, Performance status, business.industry, clinical trial, Middle Aged, medicine.disease, Survival Analysis, Surgery, Treatment Outcome, Oncology, chemistry, Disease Progression, Camptothecin, Female, business, Progressive disease, medicine.drug
Abstract

To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0-2), ageor=75 years, and adequate organ function. The patients' characteristics were: male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51-75 years); limited disease (LD)/extensive disease (ED)=27/34. The patients received irinotecan (50 mg m-2) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72-91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17-41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.

Published
2006
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47. Visual evoked potentials and event related potentials in congenitally deaf subjects

Author

Chlubnová, J., Jan Kremlacek, Kubová, Z., and Kuba, M.

Subjects
Physiology, General Medicine
Abstract

The purpose was to test parameters of visual evoked potentials (VEPs) and of event-related potentials (ERPs) in deaf subjects to verify visual and cognitive CNS functions in a handicapped group of the population. Three types of visual stimuli (with dominating parvocellular or magnocellular system activation or with cognitive tasks) were used in the study. Six deaf persons (4 women, 2 men, mean age 17 years) and 6 persons with normal hearing (sex- and age-matched) were included in this pilot study. In all types of stimulation, latencies and amplitudes of main VEPs and ERPs components were evaluated. No significant latency differences were found. However, significantly reduced amplitudes were found in the occipital area for responses to motion and cognitive stimuli which might be interpreted as a part of functional reorganization of the extrastriate and cognitive cortical areas of deaf subjects.

Published
2005
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48. Investigations on the Catalytic Activity of Bed Material Coating Regarding the Water-Gas-Shift Reaction and Steam Reforming of Model Compounds for Lighter and Heavier Hydrocarbons

Author

Kuba, M., Havlik, F., Kirnbauer, F., and Hofbauer, H.

Subjects
Biomass
Abstract

An innovative process to produce synthesis gas from a solid feedstock is dual fluidbed (DFB) steam gasification of biomass. The principle of this technology is the separation of the fluidized bed into a gasification and a combustion zone. Bed material, nowadays olivine, is circulating, between them, which has two functions. Firstly, it acts as heat carrier from the combustion to the gasification zone. Secondly, it has the role of a catalyst regarding the reduction of hydrocarbons. In this work, the catalytic activity of different fresh and also used bed materials, such as olivine and silica sand was tested regarding their ability to enhance the water-gas-shift reaction and also reduce hydrocarbons. Calcite is known as active material in this respect and, therefore, used as reference substance. Experiments showed a correlation between the enhancement of the water-gas-shift reaction and the reduction of lighter and heavier hydrocarbons by steam reforming. Results show that as long as a bed material particle has built up a calcium-rich layer, satisfying conversion of carbon monoxide and the hydrocarbons can be achieved. As model substances for hydrocarbons ethane and toluene were used. These results are the basis for further research of catalytic characteristics of potential bed materials for the dual fluidized bed steam gasification of biomass., Proceedings of the 23rd European Biomass Conference and Exhibition, 1-4 June 2015, Vienna, Austria, pp. 562-567

Published
2015
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49. Optimization of a 50 Mw Bubbling Fluidized Bed Biomass Combustion Furnace by Means of Computational Particle Fluid Dynamics

Author

Kraft, S., Kuba, M., Kirnbauer, F., Bosch, K., and Hofbauer, H.

Subjects
Biomass
Abstract

An efficient utilization of biomass fuels in CHP plants is often limited by the melting behavior of the biomass ash which causes unplanned shutdowns of the plants. If temperatures exceed the ash melting temperature deposits can affect the operation negatively: The deposits are observed mainly in the freeboard of the combustion chamber where the highest temperatures are measured. These layers will grow and also could break off the wall and fall into the bed region. In this work a bubbling fluidized bed combustion chamber with 50 MW biomass input is numerically investigated by means of computational particle fluid dynamics to detect zones where ash melting can occur. For this purpose the CPFD code Barracuda Version 16 is used. Areas where the deposits are formed were detected by simulation runs and compared with fouling observed on the furnace walls in the freeboard of the combustion chamber. In a second step the model is used to find an optimized operational point with a reduced number of areas with critical temperature. Based on the findings in this work the model is suitable for further investigations and optimizations of the reactor., Proceedings of the 23rd European Biomass Conference and Exhibition, 1-4 June 2015, Vienna, Austria, pp. 485-492

Published
2015
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50. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies

Author

Sutton, C. R., Cook, R. S., Kuba, M. G., Perou, C. M., Balko, J. M., Sanchez, V., Cheng, H., Hanker, A. B., Young, C. D., Zhao, J. J., Arteaga, C. L., and Pfefferle, A. D.

Subjects
skin and connective tissue diseases, neoplasms
Abstract

Human epidermal growth factor receptor 2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer. Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been shown to correlate with a diminished response to HER2-directed therapies. We generated a mouse model of HER2-overexpressing (HER2+), PIK3CAH1047R-mutant breast cancer. Mice expressing both human HER2 and mutant PIK3CA in the mammary epithelium developed tumors with shorter latencies compared with mice expressing either oncogene alone. HER2 and mutant PIK3CA also cooperated to promote lung metastases. By microarray analysis, HER2-driven tumors clustered with luminal breast cancers, whereas mutant PIK3CA tumors were associated with claudin-low breast cancers. PIK3CA and HER2+/PIK3CA tumors expressed elevated transcripts encoding markers of epithelial-to-mesenchymal transition and stem cells. Cells from HER2+/PIK3CA tumors more efficiently formed mammospheres and lung metastases. Finally, HER2+/PIK3CA tumors were resistant to trastuzumab alone and in combination with lapatinib or pertuzumab. Both drug resistance and enhanced mammosphere formation were reversed by treatment with a PI3K inhibitor. In sum, PIK3CAH1047R accelerates HER2-mediated breast epithelial transformation and metastatic progression, alters the intrinsic phenotype of HER2-overexpressing cancers, and generates resistance to approved combinations of anti-HER2 therapies.

Published
2013
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