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2. Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies

Author

Barbara Mair, Jelena Tomic, Sanna N. Masud, Peter Tonge, Alexander Weiss, Matej Usaj, Amy Hin Yan Tong, Jamie J. Kwan, Kevin R. Brown, Emily Titus, Michael Atkins, Katherine S.K. Chan, Lise Munsie, Andrea Habsid, Hong Han, Marion Kennedy, Brenda Cohen, Gordon Keller, and Jason Moffat

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology. : Mair et al. establish a robust, inducible CRISPR screening platform for forward genetics in human pluripotent stem cells (hPSCs). Genome-wide proliferation screens identified core essential genes for hPSCs and revealed context-dependent genetic requirements on different substrates. This underlines hPSC plasticity and helps us to understand the genetic wiring of hPSCs. Keywords: human pluripotent stem cells, genome-wide CRISPR screen, functional genomics, essential genes, DRICH1

Published
2019
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5. Supplementary Figure 4 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Graphical distributions of CD3+ and CD8+ T lymphocyte densities in the TI and IM.

Published
2023
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6. Supplementary Figure 3 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

ImageJ plug-in code for image analysis.

Published
2023
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7. Supplementary Figure 5 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Bivariate analysis of TIL pattern and tumor stage, cellular differentiation, and vascular invasion.

Published
2023
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8. Data from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.

Published
2023
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9. Supplementary Figure 6 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Kaplan-Meier analysis of RFS stratified by pattern of CD3+ and CD8+ T lymphocytes.

Published
2023
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10. Supplementary Figure 2 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Example of computer-assisted evaluation of infiltrate densities.

Published
2023
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11. Supplementary Figure 7 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Bivariate analysis of CD3+ and CD8+ cell density and beta-catenin expression.

Published
2023
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12. Supplementary Figure 1 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Flowchart of image analysis process.

Published
2023
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13. Supplementary Figure 8 from Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Author

Aiwu Ruth He, Michael Atkins, Louis Weiner, John Marshall, Christopher Loffredo, Petra Prins, Anteneh Tesfaye, Tiger Zhang, Perry Feng, Jaydeep Kachhela, Reena Jha, Filip Banovac, Rohit Satoskar, Eddie Island, Lynt Johnson, Thomas Fishbein, David Kleiner, Sandeep Reddy, Zoran Gatalica, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Yunan Wu, and Andrew Gabrielson

Abstract

Bivariate analysis of tumor stage with vascular invasion and cellular differentiation.

Published
2023
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15. Supplementary Data from FCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma

Author

Paul M. Sondel, David F. McDermott, David J. Panka, James W. Mier, Alexander Carlson, Michael Atkins, Sabina Signoretti, Su-Chun Cheng, Jacquelyn A. Hank, Yiqiang Song, Eneida A. Mendonca, Dustin Hess, Lakeesha Carmichael, KyungMann Kim, Mikayla Gallenberger, Jacob Goldberg, Wei Wang, and Amy K. Erbe

Abstract

Supplementary Table 1. Frequency of FCGR genotypes and HWE test. Supplementary Table 2. PFS Clinical Outcome Assessment of FCGR2A, FCGR3A and FCGR2C SNPs. Supplementary Table 3. Clinical Outcome Parameters were Assessed for FCGR3A, FCGR2A and FCGR2C SNPs within the Group of 100 Patients with Clear Cell Histology that were Genotyped.

Published
2023
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17. Data from FCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma

Author

Paul M. Sondel, David F. McDermott, David J. Panka, James W. Mier, Alexander Carlson, Michael Atkins, Sabina Signoretti, Su-Chun Cheng, Jacquelyn A. Hank, Yiqiang Song, Eneida A. Mendonca, Dustin Hess, Lakeesha Carmichael, KyungMann Kim, Mikayla Gallenberger, Jacob Goldberg, Wei Wang, and Amy K. Erbe

Abstract

Purpose: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of patients with cancer treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines. The previously published “SELECT” trial of high-dose aldesleukin (HD-IL2) for metastatic renal cell carcinoma resulted in an objective response rate of 25%. We evaluated the patients in this SELECT trial to determine whether higher-affinity FCGR polymorphisms are associated with outcome.Experimental Design: SNPs in FCGR2A, FCGR3A, and FCGR2C were analyzed, individually and in combination, for associations between genotype and clinical outcome.Results: When higher-affinity genotypes for FCGR2A, FCGR3A, and FCGR2C were considered together, they were associated with significantly increased tumor shrinkage and prolonged survival in response to HD-IL2.Conclusions: Although associations of higher-affinity FCGR genotype with clinical outcome have been demonstrated with mAb therapy and with idiotype vaccines, to our knowledge, this is the first study to show associations of FCGR genotypes with outcome following HD-IL2 treatment. We hypothesize that endogenous antitumor antibodies may engage immune cells through their FCGRs, and HD-IL2 may enhance antibody-induced tumor destruction, or antibody-enhanced tumor antigen presentation, via augmented activation of innate or adaptive immune responses; this FCGR-mediated immune activity would be augmented through immunologically favorable FCGRs. Clin Cancer Res; 23(9); 2159–68. ©2016 AACR.

Published
2023
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19. Data from Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

Author

Ronald Bukowski, Robert Motzer, Toni K. Choueiri, Daniel Y.C. Heng, Michael Atkins, Janice Dutcher, Tim Eisen, Bernard Escudier, Sylvie Négrier, Madhu Mazumdar, Jennifer Bacik McCormack, Paul Elson, Patrick Royston, and Judith Manola

Abstract

Purpose: To develop a single validated model for survival in metastatic renal cell carcinoma (mRCC) using a comprehensive international database.Experimental Design: A comprehensive database of 3,748 patients including previously reported clinical prognostic factors was established by pooling patient-level data from clinical trials. Following quality control and standardization, descriptive statistics were generated. Univariate analyses were conducted using proportional hazards models. Multivariable analysis using a log–logistic model stratified by center and multivariable fractional polynomials was conducted to identify independent predictors of survival. Missing data were handled using multiple imputation methods. Three risk groups were formed using the 25th and 75th percentiles of the resulting prognostic index. The model was validated using an independent data set of 645 patients treated with tyrosine kinase inhibitor (TKI) therapy.Results: Median survival in the favorable, intermediate and poor risk groups was 26.9 months, 11.5 months, and 4.2 months, respectively. Factors contributing to the prognostic index included treatment, performance status, number of metastatic sites, time from diagnosis to treatment, and pretreatment hemoglobin, white blood count, lactate dehydrogenase, alkaline phosphatase, and serum calcium. The model showed good concordance when tested among patients treated with TKI therapy (C statistic = 0.741, 95% CI: 0.714–0.768).Conclusions: Nine clinical factors can be used to model survival in mRCC and form distinct prognostic groups. The model shows utility among patients treated in the TKI era. Clin Cancer Res; 17(16); 5443–50. ©2011 AACR.

Published
2023
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20. Data from Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

Author

Augusto C. Ochoa, Rosa Sierra, Jovanny Zabaleta, Michael Atkins, Claudia Hernandez, Marc S. Ernstoff, and Paulo C. Rodriguez

Abstract

Myeloid-derived suppressor cells (MDSC) producing arginase I are increased in the peripheral blood of patients with renal cell carcinoma (RCC). MDSC inhibit T-cell function by reducing the availability of l-arginine and are therefore considered an important tumor escape mechanism. We aimed to determine the origin of arginase I–producing MDSC in RCC patients and to identify the mechanisms used to deplete extracellular l-arginine. The results show that human MDSC are a subpopulation of activated polymorphonuclear (PMN) cells expressing high levels of CD66b, CD11b, and VEGFR1 and low levels of CD62L and CD16. In contrast to murine MDSC, human MDSC do not deplete l-arginine by increasing its uptake but instead release arginase I into the circulation. Activation of normal PMN induces phenotypic and functional changes similar to MDSC and also promotes the release of arginase I from intracellular granules. Interestingly, although activation of normal PMN usually ends with apoptosis, MDSC showed no increase in apoptosis compared with autologous PMN or PMN obtained from normal controls. High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I. These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response. [Cancer Res 2009;69(4):1553–60]

Published
2023
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23. Supplementary Figure Legends 1-2 from Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

Author

Augusto C. Ochoa, Rosa Sierra, Jovanny Zabaleta, Michael Atkins, Claudia Hernandez, Marc S. Ernstoff, and Paulo C. Rodriguez

Abstract

Supplementary Figure Legends 1-2 from Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

Published
2023
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25. Disability as a Determinant of Health

Author

Shannon Mace, Michael Atkins, David P Donohue, Maija Woodruff, Elizabeth Ashford, Marissa Band, and Robert L. Hayman

Subjects
Health (social science), business.industry, Health Policy, Environmental health, Pandemic, Public Health, Environmental and Occupational Health, Medicine, business, Article, A determinant
Published
2021

26. Inestimable Harms

Author

Shannon Mace, Maija Woodruff, Michael Atkins, Caleb W Hayman, Elizabeth Ashford, David P Donohue, and Daniel G Atkins

Subjects
2019-20 coronavirus outbreak, Health (social science), Coronavirus disease 2019 (COVID-19), business.industry, Health Policy, Environmental health, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Public Health, Environmental and Occupational Health, MEDLINE, Vulnerability, Medicine, business
Published
2021
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27. Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Author

Julie Stein Deutsch, Evan J. Lipson, Ludmila Danilova, Suzanne L. Topalian, Jaroslaw Jedrych, Ezra Baraban, Yasser Ged, Nirmish Singla, Toni K. Choueiri, Saurabh Gupta, Robert J. Motzer, David McDermott, Sabina Signoretti, Michael Atkins, and Janis M. Taube

Subjects
General Biochemistry, Genetics and Molecular Biology
Published
2023
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29. Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis

Author

Dongyu Zhang, Neil Shah, Michael Cook, Matthew Blackburn, Michael Serzan, Shailesh Advani, Arnold Potosky, Subha Madhavan, Anas Belouali, Michael Atkins, and Dejana Braithwaite

Subjects
immune checkpoint inhibitor, body mass index, immune-related adverse events, epidemiology, Cancer Research, Oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Article, RC254-282
Abstract

Simple Summary Currently, clinical studies exploring the impact of high body fat on toxicities after receiving immune checkpoint inhibitors (ICIs) among cancer patients are limited. Here, we analyze data from a health care system serving the mid-Atlantic geographic region to assess how body fat can affect the development of toxicities of ICIs. In our study, body mass index (BMI) was used as the measure of body fat, and the results suggested that cancer patients with a high BMI were more likely to have toxicities after receiving ICIs. Our study suggests that symptom management should be incorporated in the cancer care continuum of patients who receive ICIs, especially those with high BMI. In clinical settings, oncologists should inform cancer patients receiving ICIs with high BMI that their risk of post-treatment toxicities can be higher compared to their counterparts with lower BMI. Abstract Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (

Published
2021

30. Experiences of individuals self-directing Medicaid Home and Community-Based Services during COVID-19

Author

Joseph Caldwell, Miriam Heyman, Michael Atkins, and Sandy Ho

Subjects
Medicaid, Public Health, Environmental and Occupational Health, COVID-19, Humans, Disabled Persons, General Medicine, Community Health Services, Home Care Services, United States
Abstract

In response to COVID-19, many state Medicaid Home and Community-Based Services (HCBS) programs increased flexibilities and options for self-direction.Our study sought to investigate the experiences of individuals self-directing during COVID-19. In particular we explored the following areas: 1) How have individuals maintained access to HCBS and workers?; 2) how have individuals maintained safety against COVID-19?; and 3) how have individuals maintained their health and well-being?We partnered with community-based and national disability organizations for recruitment. We used a semi-structured interview guide to conduct remote interviews with 36 individuals from eleven states. The sample was diverse with regard to age, race/ethnicity, gender, and disability type.Three main themes emerged related to maintaining access to HCBS and direct care workers: 1) Benefits of authority to hire and fire; 2) benefits of ability to hire family members; and 3) fluctuations in needs and availability of workers. Two themes emerged related to maintaining safety against COVID-19: 1) Strategies for staying safe with workers; and 2) barriers in public health and service system response. Three themes emerged related to maintaining health and well-being: 1) Barriers to basic needs; 2) delaying needed care; and 3) use of telehealth and technology.This study was among the first to examine the experiences of individuals self-directing their HCBS during COVID-19. The flexibility of the model provided many benefits, which have implications for future policy and practice. Findings also highlight barriers in maintaining health and well-being during COVID-19, illustrating the importance of planning for future public health emergencies.

Published
2021

32. Abstract 5625: Molecular and immunologic characterization of HRAS mutations in a cohort of 6,329 patients with cutaneous melanoma

Author

Leonel F. Hernandez-Aya, Estelamari Rodriguez, Aparna Nallagangula, Jun Yin, Phillip Walker, Joanne Xiu, Justin Moser, Gino K. In, David Spetzler, Geoffery T. Gibney, Matthew Oberley, Thuy Phung, Michael Atkins, Dave S. Hoon, Wolfgang Michael Korn, Jose Lutzky, and Gilberto Lopes

Subjects
Cancer Research, Oncology
Abstract

Background: Activation in RAS pathway has been associated with cancer development. Three RAS family members, including NRAS, KRAS and HRAS are frequently mutated across various cancer types, where NRAS mutations are present in 15-20% of melanomas. NRAS-mutant melanomas (NRASm) have been extensively characterized. However, molecular and clinical implications of HRAS mutations (HRASm) in melanoma are less well understood. Methods: A total of 6329 melanoma samples were subjected to comprehensive molecular profiling at Caris Life Sciences. Analyses included next generation sequencing of DNA (592 Gene Panel, NextSeq; whole exome sequencing, NovaSEQ), RNA (NovaSeq, whole transcriptome sequencing, WTS) and IHC. MPAS scores to evaluate MAPK pathway activation, IFN scores, QuantiSeq, neoantigen load (high, intermediate, low binding affinity: HBA, IBA and LBA) and GSEA were calculated from mRNA expression data. Wilcoxon, Fisher’s exact were used to determined statistical significance (p value without and q value with multi comparison correction; FDR for GSEA). The reference cohort was the entire melanoma cohort (MC). Results: HRASm were identified in 69 (1.09%) of melanoma samples (hotspots mutations: G13, 40%; Q61, 34%; G12, 18% and others, 9%). HRASm and NRASm had different genomic landscapes: HRASm were significantly associated with a higher mutation rate of NF1 (43.2% vs 27.7%, p Conclusions: The genomic landscape of HRASm are significantly different from that of NRASm, implying their distinct roles in tumorigenesis. HRASm also demonstrated higher MAPK activation, suggesting that they could potentially benefit from agents targeting on this pathway. In addition, HRASm displayed more immunogenic features, associated with down-regulation of angiogenesis pathway, revealing a potential higher susceptibility of HRASm to immunotherapy. Citation Format: Leonel F. Hernandez-Aya, Estelamari Rodriguez, Aparna Nallagangula, Jun Yin, Phillip Walker, Joanne Xiu, Justin Moser, Gino K. In, David Spetzler, Geoffery T. Gibney, Matthew Oberley, Thuy Phung, Michael Atkins, Dave S. Hoon, Wolfgang Michael Korn, Jose Lutzky, Gilberto Lopes. Molecular and immunologic characterization of HRAS mutations in a cohort of 6,329 patients with cutaneous melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5625.

Published
2022
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33. Investigation of a Modified Wells Turbine for Wave Energy Extraction

Author

Mohammad Nasim Uddin, Frimpong Opoku, and Michael Atkinson

Subjects
hybrid airfoil, Wells turbine, wave energy, grid independence, bidirectional airflow, Technology
Abstract

The Oscillating Water Column (OWC) is the most promising self-rectifying device for power generation from ocean waves; over the past decade, its importance has been rekindled. The bidirectional airflow inside the OWC drives the Wells turbine connected to a generator to harness energy. This study evaluated the aerodynamic performance of two hybrid airfoil (NACA0015 and NACA0025) blade designs with variable chord distribution along the span of a Wells turbine. The present work examines the aerodynamic impact of the variable chord turbine and compares it with one with a constant chord. Ideally, Wells rotor blades with variable chords perform better since they have an even axial velocity distribution on their leading edge. The variable chord rotor blade configurations differ from hub to tip with taper ratios (Chord at Tip/Chord at Hub) of 1.58 and 0.63. The computation is performed in ANSYS™ CFX 2023 R2 by solving three-dimensional, steady-state, incompressible Reynolds Averaged Navier–Stokes (RANS) equations coupled with a k-ω Shear Stress Transport (SST) turbulence model in a non-inertial reference frame rotating with the turbine. The accuracy of the numerical results was achieved by performing a grid independence study. A refined mesh showed good agreement with the available experimental and numerical data in terms of efficiency, torque, and pressure drop at different flow coefficients. A variable chord Wells turbine with a taper ratio of 1.58 had a peak efficiency of 59.6%, as opposed to the one with a taper ratio of 0.63, which had a peak efficiency of 58.2%; the constant chord Wells turbine only had a peak efficiency of 58.5%. Furthermore, the variable chord rotor with the higher taper ratio had a larger operating range than others. There are significant improvements in the aerodynamic performance of the modified Wells turbine, compared to the conventional Wells turbine, which makes it suitable for wave energy harvesting. The flow field investigation around the turbine blades was conducted and analyzed.

Published
2024
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34. Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies

Author

Michael Atkins, Marion Kennedy, Kevin R. Brown, Sanna Masud, Katherine S. K. Chan, Lise Munsie, Matej Usaj, Gordon Keller, Brenda Cohen, Amy Hin Yan Tong, Barbara Mair, Alexander Weiss, Emily Titus, Andrea Habsid, Jamie J. Kwan, Jason Moffat, Hong Han, Peter Tonge, and Jelena Tomic

Subjects
0301 basic medicine, Pluripotent Stem Cells, Genes, Essential, Cas9, Context (language use), Cell Differentiation, Computational biology, Biology, Regenerative medicine, General Biochemistry, Genetics and Molecular Biology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, lcsh:Biology (General), Gene Expression Regulation, Essential gene, CRISPR, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, Stem cell, Induced pluripotent stem cell, lcsh:QH301-705.5, Functional genomics, 030217 neurology & neurosurgery
Abstract

Summary: Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology. : Mair et al. establish a robust, inducible CRISPR screening platform for forward genetics in human pluripotent stem cells (hPSCs). Genome-wide proliferation screens identified core essential genes for hPSCs and revealed context-dependent genetic requirements on different substrates. This underlines hPSC plasticity and helps us to understand the genetic wiring of hPSCs. Keywords: human pluripotent stem cells, genome-wide CRISPR screen, functional genomics, essential genes, DRICH1

Published
2018

35. Under the surface of the village: public and private negotiations of urban space in Manchester

Author

Michael Atkins

Abstract

Combining narratives of success and community with imagery and maps characterises and regulates Manchester’s Gay Village as a distinct, bordered, hedonistic and particularly tolerant place. This chapter describes the use of collaboratively produced graphic stories, created using combinations of drawings, text, photographs and found images. These 'ethno-graphics' describe lived experiences of men seeking sex in public and engaging in exchanges of intimacy, money, goods and services that challenge the master narratives of that are openly recognised and spoken about in the village.

Published
2018
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37. Unacknowledged Pain and Disenfranchised Grief: A Narrative Analysis of Physical and Emotional Pain in Complex MAiD Bereavement Stories

Author

Kristie Serota, Michael Atkinson, and Daniel Z Buchman

Subjects
Medical assistance in dying, emotional pain, bereavement, family, disenfranchised grief, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

ABSTRACTBackground Pain can influence an individual’s choice to pursue medical assistance in dying (MAiD) and may also influence how family members experience that decision. Family conflict or discordance surrounding a loved one’s MAiD decision can cause unique challenges affecting grief and bereavement, including disenfranchised grief. There is limited knowledge of how individuals with complex MAiD bereavement experiences describe the role of physical and emotional pain in their bereavement stories.Aims This article explores the role of physical and emotional pain in the stories of family members with complex MAiD bereavement and identifies opportunities to improve care for individuals and families experiencing disagreement around MAiD.Methods We conducted qualitative interviews and utilized a narrative and ethics of care approach to analyze the data.Results We conducted N = 12 narrative interviews with participants in three provinces: Ontario, British Columbia, and Alberta. Descriptions of physical pain were used to justify the morality, or immorality, of MAiD in the context of patient suffering. Emotional pain described experiences where participants’ feelings about MAiD went unacknowledged by their family or friends, institutions, and sociopolitical environments. We conceptualize this unacknowledged emotional pain as disenfranchised grief and make recommendations to improve care for individuals experiencing complex MAiD bereavement.Conclusions Experiences of physical and emotional pain leave a lasting impact on family members with complex MAiD bereavement. Health care professionals should continue to improve care for family members following MAiD, especially where there is disagreement or family conflict.

Published
2023
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38. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. Beckett, Helena J. Mauceri, Yang-Xin Fu, Ralph R. Weichselbaum, Whitney Lewis, Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Dongyun Wu, Jin Li, Xiaoling Liang, Xiangjun Zhou, Jinlin Hou, Raffit Hassan, Thierry Jahan, Scott J. Antonia, Hedy L. Kindler, Evan W. Alley, Somayeh Honarmand, Weiqun Liu, Meredith L. Leong, Chan C. Whiting, Nitya Nair, Amanda Enstrom, Edward E. Lemmens, Takahiro Tsujikawa, Sushil Kumar, Lisa M. Coussens, Aimee L. Murphy, Dirk G. Brockstedt, Sven D. Koch, Martin Sebastian, Christian Weiss, Martin Früh, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geissler, Frank Griesinger, Jens Kollmeier, Alexandros Papachristofilou, Fatma Doener, Mariola Fotin-Mleczek, Madeleine Hipp, Henoch S. Hong, Karl-Josef Kallen, Ute Klinkhardt, Claudia Stosnach, Birgit Scheel, Andreas Schroeder, Tobias Seibel, Ulrike Gnad-Vogt, Alfred Zippelius, Ha-Ram Park, Yong-Oon Ahn, Tae Min Kim, Soyeon Kim, Seulki Kim, Yu Soo Lee, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Shari Pilon-Thomas, Amy Weber, Jennifer Morse, Krithika Kodumudi, Hao Liu, John Mullinax, Amod A. Sarnaik, Luke Pike, Andrew Bang, Tracy Balboni, Allison Taylor, Alexander Spektor, Tyler Wilhite, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal Aizer, Elizabeth Buchbinder, Mark Awad, Leena Ghandi, Jonathan Schoenfeld, Elizabeth Lessey-Morillon, Lisa Ridnour, Neil H. Segal, Manish Sharma, Dung T. Le, Robert L. Ferris, Andrew D. Zelenetz, Ronald Levy, Izidore S. Lossos, Caron Jacobson, Radhakrishnan Ramchandren, John Godwin, A. Dimitrios Colevas, Roland Meier, Suba Krishnan, Xuemin Gu, Jaclyn Neely, John Timmerman, Claire I. Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Erik Wennerberg, Aranzazu Mediero, Bruce N. Cronstein, Michael P. Gustafson, AriCeli DiCostanzo, Courtney Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A. Gastineau, Bruce D. Johnson, Allan B. Dietz, Cameron MacDonald, Mark Bucsek, Guanxi Qiao, Bonnie Hylander, Elizabeth Repasky, William J. Turbitt, Yitong Xu, Andrea Mastro, Connie J. Rogers, Sita Withers, Ziming Wang, Lam T. Khuat, Cordelia Dunai, Bruce R. Blazar, Dan Longo, Robert Rebhun, Steven K. Grossenbacher, Arta Monjazeb, William J. Murphy, Scott Rowlinson, Giulia Agnello, Susan Alters, David Lowe, Nicole Scharping, Ashley V. Menk, Ryan Whetstone, Xue Zeng, Greg M. Delgoffe, Patricia M. Santos, Jian Shi, Greg Delgoffe, Misako Nagasaka, Ammar Sukari, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Natalie Collins, Robert Manguso, Hans Pope, Yashaswi Shrestha, Jesse Boehm, W. Nicholas Haining, Kyle R. Cron, Ayelet Sivan, Keston Aquino-Michaels, Marco Orecchioni, Davide Bedognetti, Wouter Hendrickx, Claudia Fuoco, Filomena Spada, Francesco Sgarrella, Gianni Cesareni, Francesco Marincola, Kostas Kostarelos, Alberto Bianco, Lucia Delogu, Jessica Roelands, Sabri Boughorbel, Julie Decock, Scott Presnell, Ena Wang, Franco M. Marincola, Peter Kuppen, Michele Ceccarelli, Darawan Rinchai, Damien Chaussabel, Lance Miller, Andrew Nguyen, J. Zachary Sanborn, Charles Vaske, Shahrooz Rabizadeh, Kayvan Niazi, Steven Benz, Shashank Patel, Nicholas Restifo, James White, Sam Angiuoli, Mark Sausen, Sian Jones, Maria Sevdali, John Simmons, Victor Velculescu, Luis Diaz, Theresa Zhang, Jennifer S. Sims, Sunjay M. Barton, Angela Kadenhe-Chiweshe, Filemon Dela Cruz, Andrew T. Turk, Christopher F. Mazzeo, Andrew L. Kung, Jeffrey N. Bruce, Darrell J. Yamashiro, Eileen P. Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. Myers, Stuart Curbishley, Sarah A. Penny, Lora Steadman, David Millar, Ellen Speers, Nicola Ruth, Gabriel Wong, Robert Thimme, David Adams, Mark Cobbold, Remy Thomas, Mariam Al-Muftah, Michael KK Wong, Michael Morse, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Tharak Rao, Janice P. Dutcher, Kai Kang, Yogen Saunthararajah, Vamsidhar Velcheti, Vikas Kumar, Firoz Anwar, Amita Verma, Zinal Chheda, Gary Kohanbash, John Sidney, Kaori Okada, Shruti Shrivastav, Diego A. Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada, Jessica J. Field, Weiping Zeng, Vincent FS Shih, Che-Leung Law, Peter D. Senter, Shyra J. Gardai, Nicole M. Okeley, Jennifer G. Abelin, Abu Z. Saeed, Stacy A. Malaker, Jeffrey Shabanowitz, Stephen T. Ward, Donald F. Hunt, Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Manuel Schmidt, Julian P. Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. Silk, Sachin Jhawar, Tomas Paneque, Jenna Newman, Pedro Beltran, Felicia Cao, Bang-Xing Hong, Tania Rodriguez-Cruz, Xiao-Tong Song, Stephen Gottschalk, Hugo Calderon, Sam Illingworth, Alice Brown, Kerry Fisher, Len Seymour, Brian Champion, Emma Eriksson, Jessica Wenthe, Ann-Charlotte Hellström, Gabriella Paul-Wetterberg, Angelica Loskog, Ioanna Milenova, Magnus Ståhle, Justyna Jarblad-Leja, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Sharad Goyal, Ann Silk, Janice Mehnert, Nashat Gabrail, Jennifer Bryan, Daniel Medina, Leah Mitchell, Kader Yagiz, Fernando Lopez, Daniel Mendoza, Anthony Munday, Harry Gruber, Douglas Jolly, Steven Fuhrmann, Sasa Radoja, Wei Tan, Aldo Pourchet, Alan Frey, Ian Mohr, Matthew Mulvey, Robert H. I. Andtbacka, Merrick Ross, Sanjiv Agarwala, Kenneth Grossmann, Matthew Taylor, John Vetto, Rogerio Neves, Adil Daud, Hung Khong, Stephanie M. Meek, Richard Ungerleider, Scott Welden, Maki Tanaka, Matthew Williams, Sigrun Hallmeyer, Bernard Fox, Zipei Feng, Christopher Paustian, Carlo Bifulco, Sadia Zafar, Otto Hemminki, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Tameem Ansari, Srividya Sundararaman, Diana Roen, Paul Lehmann, Anja C. Bloom, Lewis H. Bender, Ian B. Walters, Jay A. Berzofsky, Fanny Chapelin, Eric T. Ahrens, Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Alexander Scholz, Danhui Zhang, Gilson Baia, Yann Chong Tan, Jeremy Sokolove, Dongkyoon Kim, Kevin Williamson, Xiaomu Chen, Jillian Colrain, Gregg Espiritu Santo, Ngan Nguyen, Wayne Volkmuth, Norman Greenberg, William Robinson, Daniel Emerling, Charles G. Drake, Daniel P. Petrylak, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Tuyen Vu, Dwayne Campogan, Heather Haynes, James B. Trager, Nadeem A. Sheikh, David I. Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. Flechtner, John Facciponte, Stefano Ugel, Francesco De Sanctis, George Coukos, Sébastien Paris, Agnes Pottier, Laurent Levy, Bo Lu, Federica Cappuccini, Emily Pollock, Richard Bryant, Freddie Hamdy, Adrian Hill, Irina Redchenko, Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Esteban Celis, Ingrid Fernando, Claudia Palena, Justin M. David, Elizabeth Gabitzsch, Frank Jones, James L. Gulley, Mireia Uribe Herranz, Hiroshi Wada, Atsushi Shimizu, Toshihiro Osada, Satoshi Fukaya, Eiji Sasaki, Milad Abolhalaj, David Askmyr, Kristina Lundberg, Ann-Sofie Albrekt, Lennart Greiff, Malin Lindstedt, Dallas B. Flies, Tomoe Higuchi, Wojciech Ornatowski, Jaryse Harris, Sarah F. Adams, Todd Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis Kariolis, Dadi Jang, Rie vonEbyen, Edward Graves, Lesley Ellies, Erinn Rankin, Albert Koong, Amato Giaccia, Reham Ajina, Shangzi Wang, Jill Smith, Mariaelena Pierobon, Sandra Jablonski, Emanuel Petricoin, Louis M. Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016
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39. Book Reviews

Author

Patricia Noxolo, Kristin Hole, Michael Atkins, Rosie Cox, Roberta Hawkins, and David Storey

Subjects
Cultural Studies, Gender Studies, Arts and Humanities (miscellaneous), Demography
Published
2009
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40. Bounds on the Effective Theory of Gravity in Models of Particle Physics and Cosmology

Author

Michael Atkins and Michael Atkins

Subjects
Quantum gravity, Nuclear physics
Abstract

The effective theory of quantum gravity coupled to models of particle physics is being probed by cutting edge experiments in both high energy physics (searches for extra dimensions) and cosmology (testing models of inflation). This thesis derives new bounds that may be placed on these models both theoretically and experimentally. In models of extra dimensions, the internal consistency of the theories at high energies are investigated via perturbative unitarity bounds. Similarly it is shown that recent models of Higgs inflation suffer from a breakdown of perturbative unitarity during the inflationary period. In addition, the thesis uses the latest LHC data to derive the first ever experimental bound on the size of the Higgs boson's non-minimal coupling to gravity.

Published
2014

41. Using digital photography to record clients’ art work

Author

Michael Atkins

Subjects
Multimedia, business.industry, Art therapy, Rehabilitation, Photography, Digital photography, Legislation, Context (language use), Public relations, computer.software_genre, Mental health, Clinical Psychology, Work (electrical), Medicine, Data Protection Act 1998, business, computer
Abstract

This article considers the use of digital technology to record work made by clients. It is argued that digital photography has practical benefits over traditional photographic methods and offers new clinical opportunities. It is also suggested that these benefits need not distract us from established art therapy practice or ‘traditional’ image making. The way of working with digital photography described in this paper seeks to locate it in the context of current legislation and professional thinking using examples and illustrations drawn from the authors practice with children and adolescents with mental health problems in the National Health Service (NHS).

Published
2007
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42. A Notch-Gli2 axis sustains Hedgehog responsiveness of neural progenitors and Müller glia

Author

Erin A. Bassett, Charles Campbell, Pamela S. Lagali, Randy Ringuette, Chantal Mazerolle, Michael Atkins, Valerie A. Wallace, Alan J. Mears, and David J. Picketts

Subjects
0301 basic medicine, Male, Neurogenesis, Ependymoglial Cells, Notch signaling pathway, Kruppel-Like Transcription Factors, Biology, Zinc Finger Protein Gli2, Zinc Finger Protein GLI1, Retina, 03 medical and health sciences, Mice, Neural Stem Cells, medicine, Animals, Hedgehog Proteins, RNA, Messenger, Progenitor cell, Hedgehog, Molecular Biology, Cell Proliferation, Mice, Knockout, Receptors, Notch, Nuclear Proteins, Anatomy, Cell Biology, Neural stem cell, Cell biology, Mice, Inbred C57BL, Crosstalk (biology), 030104 developmental biology, medicine.anatomical_structure, Notch proteins, Female, Muller glia, Developmental Biology, Signal Transduction, Transcription Factors
Abstract

Neurogenesis is regulated by the dynamic and coordinated activity of several extracellular signalling pathways, but the basis for crosstalk between these pathways remains poorly understood. Here we investigated regulatory interactions between two pathways that are each required for neural progenitor cell maintenance in the postnatal retina; Hedgehog (Hh) and Notch signalling. Both pathways are activated in progenitor cells in the postnatal retina based on the co-expression of fluorescent pathway reporter transgenes at the single cell level. Disrupting Notch signalling, genetically or pharmacologically, induces a rapid downregulation of all three Gli proteins and inhibits Hh-induced proliferation. Ectopic Notch activation, while not sufficient to promote Hh signalling or proliferation, increases Gli2 protein. We show that Notch regulation of Gli2 in Muller glia renders these cells competent to proliferate in response to Hh. These data suggest that Notch signalling converges on Gli2 to prime postnatal retinal progenitor cells and Muller glia to proliferate in response to Hh.

Published
2015

43. Algorithm for the management of metastatic cutaneous melanoma

Author

Antonio C, Buzaid, Sanjiv S, Agarwala, Axel, Hauschild, and Michael, Atkins

Abstract

Over the last 4 years, various drugs have been approved for the treatment of metastatic cutaneous melanoma. Ipilimumab, an anti-CTLA-4 inhibitor that stimulates antitumor immunity, was the first agent to improve overall survival both in first line and in previously treated patients. Ipilimumab results in long term disease control in approximately 20% of the patients. Vemurafenib was the first BRAF inhibitor (BRAFi) approved and also resulted in improved overall survival compared with dacarbazine in patients with BRAF mutated metastatic melanoma. More recently, another BRAFi, dabrafenib, and a MEK inhibitor, trametinib, were approved either alone or in combination as they each showed significant antitumor activity relative to dacarbazine and the combination appeared superior to dabrafenib monotherapy. The major feature of such tumor targeted therapy is its high response rate (40-70%) and the rapidity of the responses, resulting in prompt clinical improvement. However, unlike immunotherapy, targeted therapy does not result in long-term treatment free survival. In this paper, we discuss how best to integrate the currently available treatment options including high-dose interleukin-2 (HD IL-2), systemic chemotherapy, ipilimumab and tumor targeted therapy in various clinical scenarios.

Published
2014

45. Unitarity of Models with Extra Dimensions

Author

Michael Atkins

Subjects
Extra dimensions, Theoretical physics, symbols.namesake, Large Hadron Collider, Unitarity, Hierarchy (mathematics), Computer science, Electroweak interaction, Effective field theory, symbols, Scale (descriptive set theory), Planck
Abstract

In this chapter we investigate a number of models that utilise extra dimensions in order to address the seemingly unnatural hierarchy between the electroweak and Planck scales. We specifically calculate the scale at which perturbative unitarity breaks down in order to understand the energy regime for which the effective theory used to study these models is valid. These models have been extensively researched and there are many experimental searches for signatures of these models at the LHC. The search strategies rely on comparing experimental data to predictions calculated using the effective theory and for this reason alone it is crucial to have a firm understanding of when the effective theory is valid.

Published
2014
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48. Unitarity of Gravity Coupled to Models of Particle Physics

Author

Michael Atkins

Subjects
Physics, Particle physics, Gravity (chemistry), Entropic gravity, Unitarity, Scale (ratio), Group (mathematics), Effective field theory, Quantum gravity, Action (physics)
Abstract

As discussed in the opening chapter, one of the best ways to understand the realm of validity for an effective theory is to calculate the energy scale where perturbative unitarity breaks down. In the first section of this chapter we do exactly this for the effective theory of gravity coupled to matter as given by the action ( 1.1.10). In the second section we apply the bound to various grand unified theories. In the third section we incorporate renormalisation group (RG) effects into the bounds and are then able to compare the scale at which unitarity breaks down with the scale of strong coupling. We discuss the consequences of the RG improved bounds for various models of particle physics and introduce two models which can lower the scale of quantum gravity in four dimensions. The unitarity bound derived here will also provide an important basis for later chapters.

Published
2014
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