Author: "Roberts, Lewis" / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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49 results on '"Roberts, Lewis"'

1. Parametric analysis of transient stability in power systems using classical models

Author: Roberts, Lewis George Wilson
Subjects: 621.319
Abstract: This thesis aims to strengthen the bridge between mathematical and practical research into the transient stability of power systems. Literature that exploits the mathematical parallels between models for transient dynamics in power systems and the phenomenon of synchronisation in complex networks is explored. However, it is contended that research at the intersection of complex systems and power system stability can limit its applications to practical issues in power engineering. This thesis focuses on the measurement of transient stability in power systems in terms of a traditional stability metric for short-circuit faults on a power network, the critical clearing time (CCT). The CCT provides an upper bound on the duration of a short circuit on a power network before it is removed - cleared - by the action of protection mechanisms to isolate the faulted circuit such that the system will regain synchrony once the fault is cleared. Approaches that use energetic methods for assessing the transient stability of a power system are extended by developing metrics that can measure stability trends for different scenarios in a power system via the numerical continuation of equilibrium configurations under the variation of system parameters. An analytical CCT (ACCT) approximation is derived from this energetic framework in order to capture trends in stability with respect to a system parameter. The performance of the ACCT is compared to more accurate computations of CCT that use slower numerical simulation techniques. Attention is given to how well the ACCT approximation can capture stability trends under variation of key network design parameters such as load admittance and generator inertia. It is found for a two-machine infinite bus (TMIB) system that load parameter values that can improve stability can be identified using the ACCT. Also, the general dependence of a fault's CCT on the inertia of a generator in a TMIB power system is identifiable using the ACCT. For power systems with stationary generator inertia values, a method to provide a contingency analysis of fault locations is proposed. The method ranks the locations of short-circuit faults by their CCT; the more severe a fault the shorter its CCT. It is found in a TMIB system that the ACCT can identify the general location of severe faults under different inertia scenarios. It is shown that in larger power systems, energetic methods can be used to accurately identify the locations of faults with short CCTs. These results, together with relevant literature are used to suggest possible strategies to monitor transient stability within modern power systems.
Published: 2016

2. 'The "Perfyt Scyens" of the Map; a Study of the Meaning and Interpretation of Local Maps in Early Tudor England 1509-1547'

Author: Roberts, Lewis John Kaye
Subjects: 942.05, Cartography Sixteenth-Century, Henry VIII, Maps Sixteenth century
Abstract: This thesis begins by examining an unexplored contextual background for sixteenth century local maps. It argues that the architectural drawing techniques developed by master masons in the late twelfth century continued to be taught to the King’s masons well into the sixteenth, and that these drawing techniques lie behind the innovations in sixteenth century topographical mapping. Having provided a history of the craft skills that were adapted to make sixteenth century local maps this thesis moves on to consider why masons adapted craft skills traditionally used in full scale drawings on stone and plaster surfaces to make small, paper maps in the sixteenth century. It examines the way in which sixteenth century local maps were used and argues that the changing demands of patrons put pressure on master masons to alter the way in which local maps portrayed their subjects. The surviving archival evidence suggests that Henry VIII was the principle patron of local maps and my research examines the influence of the king over the shifting form of the map. It uses the letters and drawings sent between Henry VIII and his craftsmen to examine the decisive changes that Henry VIII made to the nature of the relationship between patron and builder, and the consequent effects of these changes over the forms of the image used to communicate between them. My argument suggests that Henry employs and promotes the craftsmen whose drawings allow him the greatest level of design control over the works he finances and that through this system maps and plans rapidly advance to include the technical drawing techniques which had, during the Middle Ages, been used exclusively among masons as on-site, working drawings. This thesis focuses attention on the technical aspects of map making, examining the material skills used to construct Henrician local maps and arguing that sixteenth centry local maps need to be related back to the craft skills of an older tradition of masonic drawing. It also suggests that map historians needs to look more closely at the correspondence sent between the king and his craftsmen and it argues this archival evidence provides a new contextual background with which to understand the changing forms of the Henrican local map.
Published: 2014

3. Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

Author: Spencer, Kristen, Spencer, Kristen, Pappas, Leontios, Baiev, Islam, Maurer, Jordan, Bocobo, Andrea Grace, Zhang, Karen, Jain, Apurva, De Armas, Anaemy Danner, Reyes, Stephanie, Le, Tri Minh, Rahma, Osama E, Stanton, Jennifer, DeLeon, Thomas T, Roth, Marc, Peters, Mary Linton B, Zhu, Andrew X, Lennerz, Jochen K, Iafrate, A John, Boyhen, Kylie, VanCott, Christine, Roberts, Lewis R, Lindsey, Stacie, Horick, Nora, Goff, Laura Williams, Mody, Kabir, Borad, Mitesh J, Shroff, Rachna T, Kelley, Robin Kate, Javle, Milind M, Goyal, Lipika, Spencer, Kristen, Spencer, Kristen, Pappas, Leontios, Baiev, Islam, Maurer, Jordan, Bocobo, Andrea Grace, Zhang, Karen, Jain, Apurva, De Armas, Anaemy Danner, Reyes, Stephanie, Le, Tri Minh, Rahma, Osama E, Stanton, Jennifer, DeLeon, Thomas T, Roth, Marc, Peters, Mary Linton B, Zhu, Andrew X, Lennerz, Jochen K, Iafrate, A John, Boyhen, Kylie, VanCott, Christine, Roberts, Lewis R, Lindsey, Stacie, Horick, Nora, Goff, Laura Williams, Mody, Kabir, Borad, Mitesh J, Shroff, Rachna T, Kelley, Robin Kate, Javle, Milind M, and Goyal, Lipika
Abstract: BackgroundTreatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.MethodsThis multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided.ResultsAmong 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P < .00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver-directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%) (all P < .001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months; P < .001).ConclusionsPatients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.
Published: 2023

4. The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

Author: Pappas, Leontios, Pappas, Leontios, Baiev, Islam, Reyes, Stephanie, Bocobo, Andrea, Jain, Apurva, Spencer, Kristen, Le, Tri, Rahma, Osama, Maurer, Jordan, Stanton, Jen, Zhang, Karen, De Armas, Anaemy, Deleon, Thomas, Roth, Marc, Peters, Mary, Zhu, Andrew, Boyhen, Kylie, VanCott, Christine, Patel, Tushar, Roberts, Lewis, Lindsey, Stacie, Horick, Nora, Lennerz, Jochen, Iafrate, A, Goff, Laura, Mody, Kabir, Borad, Mitesh, Shroff, Rachna, Javle, Milind, Goyal, Lipika, Kelley, Robin, Pappas, Leontios, Pappas, Leontios, Baiev, Islam, Reyes, Stephanie, Bocobo, Andrea, Jain, Apurva, Spencer, Kristen, Le, Tri, Rahma, Osama, Maurer, Jordan, Stanton, Jen, Zhang, Karen, De Armas, Anaemy, Deleon, Thomas, Roth, Marc, Peters, Mary, Zhu, Andrew, Boyhen, Kylie, VanCott, Christine, Patel, Tushar, Roberts, Lewis, Lindsey, Stacie, Horick, Nora, Lennerz, Jochen, Iafrate, A, Goff, Laura, Mody, Kabir, Borad, Mitesh, Shroff, Rachna, Javle, Milind, Goyal, Lipika, and Kelley, Robin
Abstract: PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.
Published: 2023

5. MicroRNA-27a-3p targets FoxO signalling to induce tumour-like phenotypes in bile duct cells

Author: Duwe, Lea, Munoz-Garrido, Patricia, Lewinska, Monika, Lafuente-Barquero, Juan, Satriano, Letizia, Høgdall, Dan, Taranta, Andrzej, Nielsen, Boye S., Ghazal, Awaisa, Matter, Matthias S., Banales, Jesus M., Aldana, Blanca I., Gao, Yu-Tang, Marquardt, Jens U., Roberts, Lewis R., Oliveira, Rui C., Koshiol, Jill, O'Rourke, Colm J., Andersen, Jesper B., Duwe, Lea, Munoz-Garrido, Patricia, Lewinska, Monika, Lafuente-Barquero, Juan, Satriano, Letizia, Høgdall, Dan, Taranta, Andrzej, Nielsen, Boye S., Ghazal, Awaisa, Matter, Matthias S., Banales, Jesus M., Aldana, Blanca I., Gao, Yu-Tang, Marquardt, Jens U., Roberts, Lewis R., Oliveira, Rui C., Koshiol, Jill, O'Rourke, Colm J., and Andersen, Jesper B.
Abstract: Background & Aims: Cholangiocarcinoma (CCA) is a heterogeneous and lethal malignancy, the molecular origins of which remain poorly understood. MicroRNAs (miRs) target diverse signalling pathways, functioning as potent epigenetic regulators of transcriptional output. We aimed to characterise miRNome dysregulation in CCA, including its impact on transcriptome homeostasis and cell behaviour. Methods: Small RNA sequencing was performed on 119 resected CCAs, 63 surrounding liver tissues, and 22 normal livers. High-throughput miR mimic screens were performed in three primary human cholangiocyte cultures. Integration of patient transcriptomes and miRseq together with miR screening data identified an oncogenic miR for characterization. MiR-mRNA interactions were investigated by a luciferase assay. MiR-CRISPR knockout cells were generated and phenotypically characterized in vitro (proliferation, migration, colony, mitochondrial function, glycolysis) and in vivo using subcutaneous xenografts. Results: In total, 13% (140/1,049) of detected miRs were differentially expressed between CCA and surrounding liver tissues, including 135 that were upregulated in tumours. CCA tissues were characterised by higher miRNome heterogeneity and miR biogenesis pathway expression. Unsupervised hierarchical clustering of tumour miRNomes identified three subgroups, including distal CCA-enriched and IDH1 mutant-enriched subgroups. High-throughput screening of miR mimics uncovered 71 miRs that consistently increased proliferation of three primary cholangiocyte models and were upregulated in CCA tissues regardless of anatomical location, among which only miR-27a-3p had consistently increased expression and activity in several cohorts. FoxO signalling was predominantly downregulated by miR-27a-3p in CCA, partially through targeting of FOXO1. MiR-27a knockout increased FOXO1 levels in vitro and in vivo, impeding tumour behaviour and growth. Conclusions: The miRNomes of CCA tissues are highly re
Published: 2023

6. Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes

Author: National Institutes of Health (US), National Cancer Institute (US), Antwi, Samuel O., Heckman, Michael, White, Launia, Yan, Irene, Sarangi, Vivekananda, Lauer, Kimberly P., Reddy, Joseph, Ahmed, Fowsiyo, Veliginti, Swathi, Mejías Febres, Ellis D., Hatia, Rikita I., Chang, Ping, Izquierdo-Sanchez, Laura, Boix, Loreto, Rojas, Ángela, Banales, Jesús M., Reig, María, Stål, Per, Romero-Gómez, Manuel, Singal, Amit G., Li, Donghui, Hassan, Manal M., Roberts, Lewis R., Patel, Tushar, National Institutes of Health (US), National Cancer Institute (US), Antwi, Samuel O., Heckman, Michael, White, Launia, Yan, Irene, Sarangi, Vivekananda, Lauer, Kimberly P., Reddy, Joseph, Ahmed, Fowsiyo, Veliginti, Swathi, Mejías Febres, Ellis D., Hatia, Rikita I., Chang, Ping, Izquierdo-Sanchez, Laura, Boix, Loreto, Rojas, Ángela, Banales, Jesús M., Reig, María, Stål, Per, Romero-Gómez, Manuel, Singal, Amit G., Li, Donghui, Hassan, Manal M., Roberts, Lewis R., and Patel, Tushar
Abstract: Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in the overall sample and among non-Hispanic whites. The results show that among non-Hispanic whites, presence of rare functional variants in ABCC2 was associated with 7-fold higher risk of metabolic HCC (OR = 6.92, 95% CI: 2.38–20.15, P = 0.0004), and this association remained significant when analyses were restricted to functional rare variants observed in ≥2 participants (cases 3.2% versus controls 0.0%, P = 1.02 × 10−5). In the overall multiethnic sample, presence of rare functional variants in ABCC2 was nominally associated with metabolic HCC (OR = 3.60, 95% CI: 1.52–8.58, P = 0.004), with similar nominal association when analyses were restricted to functional rare variants observed in ≥2 participants (cases 2.9% versus controls 0.2%, P = 0.006). A common variant in PNPLA3 (rs738409[G]) was associated with higher HCC risk in the overall sample (P = 6.36 × 10−6) and in non-Hispanic whites (P = 0.0002). Our findings indicate that rare functional variants in ABCC2 are associated with susceptibility to metabolic HCC in non-Hispanic whites. PNPLA3-rs738409 is also associated with metabolic HCC risk.
Published: 2023

7. Criteria for preclinical models of cholangiocarcinoma:scientific and medical relevance

Author: Calvisi, Diego F., Boulter, Luke, Vaquero, Javier, Saborowski, Anna, Fabris, Luca, Rodrigues, Pedro M., Coulouarn, Cédric, Castro, Rui E., Segatto, Oreste, Raggi, Chiara, van der Laan, Luc J.W., Carpino, Guido, Goeppert, Benjamin, Roessler, Stephanie, Kendall, Timothy J., Evert, Matthias, Gonzalez-Sanchez, Ester, Valle, Juan W., Vogel, Arndt, Bridgewater, John, Borad, Mitesh J., Gores, Gregory J., Roberts, Lewis, Marin, Jose J.G., Andersen, Jesper B., Alvaro, Domenico, Forner, Alejandro, Banales, Jesus M., Cardinale, Vincenzo, Macias, Rocio I.R., Vicent, Silve, Chen, Xin, Braconi, Chiara, Verstegen, Monique M.A., Fouassier, Laura, Scheiter, Alexander, Selaru, Florin M., Evert, Katja, Utpatel, Kirsten, Broutier, Laura, Cadamuro, Massimiliano, Huch, Meritxell, Goldin, Robert, Gradilone, Sergio A., Saito, Yoshimasa, Calvisi, Diego F., Boulter, Luke, Vaquero, Javier, Saborowski, Anna, Fabris, Luca, Rodrigues, Pedro M., Coulouarn, Cédric, Castro, Rui E., Segatto, Oreste, Raggi, Chiara, van der Laan, Luc J.W., Carpino, Guido, Goeppert, Benjamin, Roessler, Stephanie, Kendall, Timothy J., Evert, Matthias, Gonzalez-Sanchez, Ester, Valle, Juan W., Vogel, Arndt, Bridgewater, John, Borad, Mitesh J., Gores, Gregory J., Roberts, Lewis, Marin, Jose J.G., Andersen, Jesper B., Alvaro, Domenico, Forner, Alejandro, Banales, Jesus M., Cardinale, Vincenzo, Macias, Rocio I.R., Vicent, Silve, Chen, Xin, Braconi, Chiara, Verstegen, Monique M.A., Fouassier, Laura, Scheiter, Alexander, Selaru, Florin M., Evert, Katja, Utpatel, Kirsten, Broutier, Laura, Cadamuro, Massimiliano, Huch, Meritxell, Goldin, Robert, Gradilone, Sergio A., and Saito, Yoshimasa
Abstract: Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes. Preclinical research involves developing and managing complementary experimental models, from in vitro assays using primary cells or cell lines cultured in 2D or 3D to in vivo models with engrafted material, chemically induced CCA or genetically engineered models. All are valuable tools with well-defined advantages and limitations. The choice of a preclinical model is guided by the question(s) to be addressed; ideally, results should be recapitulated in independent approaches. In this Consensus Statement, a task force of 45 experts in CCA molecular and cellular biology and clinicians, including pathologists, from ten countries provides recommendations on the minimal criteria for preclinical models to provide a uniform approach. These recommendations are based on two rounds of questionnaires completed by 35 (first round) and 45 (second round) experts to reach a consensus with 13 statements. An agreement was defined when at least 90% of the participants voting anonymously agreed with a statement. The ultimate goal was to transfer basic laboratory research to the clinics through increased disease understanding and to develop clinical biomarkers and innovative therapies for patients with CCA.
Published: 2023

8. Elevated rates of horizontal gene transfer in the industrialized human microbiome

Author: Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences, Groussin, Mathieu, Poyet, Mathilde, Sistiaga Guiterrez, Maria Ainara, Kearney, Sean Michael, Moniz, Katya H, Noel, Mary, Hooker, Jeff, Gibbons, Sean Michael, Segurel, Laure, Froment, Alain, Mohamed, Rihlat Said, Fezeu, Alain, Juimo, Vanessa A., Lafosse, Sophie, Tabe, Francis E., Girard, Catherine, Iqaluk, Deborah, Nguyen, Le Thanh Tu, Shapiro, B. Jesse, Lehtimäki, Jenni, Ruokolainen, Lasse, Kettunen, Pinja P., Vatanen, Tommi, Sigwazi, Shani, Mabulla, Audax, Domínguez-Rodrigo, Manuel, Nartey, Yvonne A., Agyei-Nkansah, Adwoa, Duah, Amoako, Awuku, Yaw A., Valles, Kenneth A., Asibey, Shadrack O., Afihene, Mary Y., Roberts, Lewis R., Plymoth, Amelie, Onyekwere, Charles A., Summons, Roger E, Xavier, Ramnik Joseph, Alm, Eric J, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences, Groussin, Mathieu, Poyet, Mathilde, Sistiaga Guiterrez, Maria Ainara, Kearney, Sean Michael, Moniz, Katya H, Noel, Mary, Hooker, Jeff, Gibbons, Sean Michael, Segurel, Laure, Froment, Alain, Mohamed, Rihlat Said, Fezeu, Alain, Juimo, Vanessa A., Lafosse, Sophie, Tabe, Francis E., Girard, Catherine, Iqaluk, Deborah, Nguyen, Le Thanh Tu, Shapiro, B. Jesse, Lehtimäki, Jenni, Ruokolainen, Lasse, Kettunen, Pinja P., Vatanen, Tommi, Sigwazi, Shani, Mabulla, Audax, Domínguez-Rodrigo, Manuel, Nartey, Yvonne A., Agyei-Nkansah, Adwoa, Duah, Amoako, Awuku, Yaw A., Valles, Kenneth A., Asibey, Shadrack O., Afihene, Mary Y., Roberts, Lewis R., Plymoth, Amelie, Onyekwere, Charles A., Summons, Roger E, Xavier, Ramnik Joseph, and Alm, Eric J
Abstract: Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.
Published: 2022

9. Comparison of Surgical Resection and Systemic Treatment for Hepatocellular Carcinoma with Vascular Invasion: National Cancer Database Analysis.

Author: Govalan, Rajalakshmi, Govalan, Rajalakshmi, Lauzon, Marie, Luu, Michael, Ahn, Joseph C, Kosari, Kambiz, Todo, Tsuyoshi, Kim, Irene K, Noureddin, Mazen, Kuo, Alexander, Walid, Ayoub S, Sundaram, Vinay, Lu, Shelly C, Roberts, Lewis R, Singal, Amit G, Heimbach, Julie K, Agopian, Vatche G, Nissen, Nicholas, Yang, Ju Dong, Govalan, Rajalakshmi, Govalan, Rajalakshmi, Lauzon, Marie, Luu, Michael, Ahn, Joseph C, Kosari, Kambiz, Todo, Tsuyoshi, Kim, Irene K, Noureddin, Mazen, Kuo, Alexander, Walid, Ayoub S, Sundaram, Vinay, Lu, Shelly C, Roberts, Lewis R, Singal, Amit G, Heimbach, Julie K, Agopian, Vatche G, Nissen, Nicholas, and Yang, Ju Dong
Abstract: IntroductionSmall studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population.MethodsHCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection.ResultsOf 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426-0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection.ConclusionHCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.
Published: 2021

10. Elevated rates of horizontal gene transfer in the industrialized human microbiome

Author: Groussin, Mathieu, Poyet, Mathilde, Sistiaga, Ainara, Kearney, Sean M., Moniz, Katya, Noel, Mary, Hooker, Jeff, Gibbons, Sean M., Segurel, Laure, Froment, Alain, Mohamed, Rihlat Said, Fezeu, Alain, Juimo, Vanessa A., Lafosse, Sophie, Tabe, Francis E., Girard, Catherine, Iqaluk, Deborah, Nguyen, Le Thanh Tu, Shapiro, B. Jesse, Lehtimäki, Jenni, Ruokolainen, Lasse, Kettunen, Pinja P., Vatanen, Tommi, Sigwazi, Shani, Mabulla, Audax, Domínguez-Rodrigo, Manuel, Nartey, Yvonne A., Agyei-Nkansah, Adwoa, Duah, Amoako, Awuku, Yaw A., Valles, Kenneth A., Asibey, Shadrack O., Afihene, Mary Y., Roberts, Lewis R., Plymoth, Amelie, Onyekwere, Charles A., Summons, Roger E., Xavier, Ramnik J., Alm, Eric J., Groussin, Mathieu, Poyet, Mathilde, Sistiaga, Ainara, Kearney, Sean M., Moniz, Katya, Noel, Mary, Hooker, Jeff, Gibbons, Sean M., Segurel, Laure, Froment, Alain, Mohamed, Rihlat Said, Fezeu, Alain, Juimo, Vanessa A., Lafosse, Sophie, Tabe, Francis E., Girard, Catherine, Iqaluk, Deborah, Nguyen, Le Thanh Tu, Shapiro, B. Jesse, Lehtimäki, Jenni, Ruokolainen, Lasse, Kettunen, Pinja P., Vatanen, Tommi, Sigwazi, Shani, Mabulla, Audax, Domínguez-Rodrigo, Manuel, Nartey, Yvonne A., Agyei-Nkansah, Adwoa, Duah, Amoako, Awuku, Yaw A., Valles, Kenneth A., Asibey, Shadrack O., Afihene, Mary Y., Roberts, Lewis R., Plymoth, Amelie, Onyekwere, Charles A., Summons, Roger E., Xavier, Ramnik J., and Alm, Eric J.
Abstract: Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.
Published: 2021

11. Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.

Author: Roberts, Lewis R, Roberts, Lewis R, Sirlin, Claude B, Zaiem, Feras, Almasri, Jehad, Prokop, Larry J, Heimbach, Julie K, Murad, M Hassan, Mohammed, Khaled, Roberts, Lewis R, Roberts, Lewis R, Sirlin, Claude B, Zaiem, Feras, Almasri, Jehad, Prokop, Larry J, Heimbach, Julie K, Murad, M Hassan, and Mohammed, Khaled
Abstract: Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast-enhanced MRI, and gadoxetate-enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow-up with the same versus alternative imaging is best for CT-indeterminate or MRI-indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast-enhanced MRI or gadoxetate-enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate-enhanced or extracellular contrast-enhanced MRI over CT.ConclusionCT, extracellular contrast-enhanced MRI, or gadoxetate-enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparin
Published: 2018

12. Evaluation and management of liver masses

Author: Roberts, Lewis R., editor, Yang, Ju Dong, editor, Venkatesh, Sudhakar K., editor, Roberts, Lewis R., editor, Yang, Ju Dong, editor, and Venkatesh, Sudhakar K., editor
Published: 2020

13. Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Author: Medicina, Medikuntza, Bañales Asurmendi, Jesús María, García Marín, Jose Juan, Lamarca, Angela, Rodrigues, Pedro M., Khan, Shahid A., Roberts, Lewis R., Cardinale, Vincenzo, Carpino, Guido, Andersen, Jesper B., Braconi, Chiara, Calvisi, Diego, Perugorria Montiel, María Jesús, Fabris, Luca, Boulter, Luke, Macias, Rocio I. R., Gaudio, Eugenio, Alvaro, Domenico, Gradilone, Sergio A., Strazzabosco, Mario, Marzioni, Marco, Coulouarn, Cédric, Fouassier, Laura, Raggi, Chiara, Invernizzi, Pietro, Mertens, Joachim C., Moncsek, Anja, Rizvi, Sumera, Heimbach, Julie, Groot Koerkamp, Bas, Bruix, Jordi, Forner, Alejandro, Bridgewater, John, Valle, Juan W., Gores, Gregory J., Medicina, Medikuntza, Bañales Asurmendi, Jesús María, García Marín, Jose Juan, Lamarca, Angela, Rodrigues, Pedro M., Khan, Shahid A., Roberts, Lewis R., Cardinale, Vincenzo, Carpino, Guido, Andersen, Jesper B., Braconi, Chiara, Calvisi, Diego, Perugorria Montiel, María Jesús, Fabris, Luca, Boulter, Luke, Macias, Rocio I. R., Gaudio, Eugenio, Alvaro, Domenico, Gradilone, Sergio A., Strazzabosco, Mario, Marzioni, Marco, Coulouarn, Cédric, Fouassier, Laura, Raggi, Chiara, Invernizzi, Pietro, Mertens, Joachim C., Moncsek, Anja, Rizvi, Sumera, Heimbach, Julie, Groot Koerkamp, Bas, Bruix, Jordi, Forner, Alejandro, Bridgewater, John, Valle, Juan W., and Gores, Gregory J.
Abstract: [EN] Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non- invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted
Published: 2020

14. Therapeutic Rationale to Target Highly Expressed Aurora kinase A Conferring Poor Prognosis in Cholangiocarcinoma

Author: Ding, Xiwei, Huang, Tianlu, Peng, Chunyan, Ahn, Keun Soo, Andersen, Jesper B, Lewinska, Monika, Cao, Yu, Xu, Guifang, Chen, Gang, Kong, Bo, Friess, Helmut, Shen, Shanshan, Roberts, Lewis R, Wang, Lei, Zou, Xiaoping, Ding, Xiwei, Huang, Tianlu, Peng, Chunyan, Ahn, Keun Soo, Andersen, Jesper B, Lewinska, Monika, Cao, Yu, Xu, Guifang, Chen, Gang, Kong, Bo, Friess, Helmut, Shen, Shanshan, Roberts, Lewis R, Wang, Lei, and Zou, Xiaoping
Published: 2020

15. Pan-cancer analysis of whole genomes

Author: Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. 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M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, Zhang, Jiashan, Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, and Zhang, Jiashan
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).
Published: 2020

16. Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

Author: Leiting, Jennifer L., Murphy, Stephen J., Bergquist, John R., Hernandez, Matthew C., Ivanics, Tommy, Abdelrahman, Amro M., Yang, Lin, Lynch, Isaac, Smadbeck, James B., Cleary, Sean P., Nagorney, David M., Torbenson, Michael S., Graham, Rondell P., Roberts, Lewis R., Gores, Gregory J., Smoot, Rory L., Truty, Mark J., Leiting, Jennifer L., Murphy, Stephen J., Bergquist, John R., Hernandez, Matthew C., Ivanics, Tommy, Abdelrahman, Amro M., Yang, Lin, Lynch, Isaac, Smadbeck, James B., Cleary, Sean P., Nagorney, David M., Torbenson, Michael S., Graham, Rondell P., Roberts, Lewis R., Gores, Gregory J., Smoot, Rory L., and Truty, Mark J.
Published: 2020
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17. Cholangiocarcinoma 2020:the next horizon in mechanisms and management

Author: Banales, Jesus M, Marin, Jose J G, Lamarca, Angela, Rodrigues, Pedro M, Khan, Shahid A, Roberts, Lewis R, Cardinale, Vincenzo, Carpino, Guido, Andersen, Jesper B, Braconi, Chiara, Calvisi, Diego F, Perugorria, Maria J, Fabris, Luca, Boulter, Luke, Macias, Rocio I R, Gaudio, Eugenio, Alvaro, Domenico, Gradilone, Sergio A, Strazzabosco, Mario, Marzioni, Marco, Coulouarn, Cédric, Fouassier, Laura, Raggi, Chiara, Invernizzi, Pietro, Mertens, Joachim C, Moncsek, Anja, Rizvi, Sumera, Heimbach, Julie, Koerkamp, Bas Groot, Bruix, Jordi, Forner, Alejandro, Bridgewater, John, Valle, Juan W, Gores, Gregory J, Banales, Jesus M, Marin, Jose J G, Lamarca, Angela, Rodrigues, Pedro M, Khan, Shahid A, Roberts, Lewis R, Cardinale, Vincenzo, Carpino, Guido, Andersen, Jesper B, Braconi, Chiara, Calvisi, Diego F, Perugorria, Maria J, Fabris, Luca, Boulter, Luke, Macias, Rocio I R, Gaudio, Eugenio, Alvaro, Domenico, Gradilone, Sergio A, Strazzabosco, Mario, Marzioni, Marco, Coulouarn, Cédric, Fouassier, Laura, Raggi, Chiara, Invernizzi, Pietro, Mertens, Joachim C, Moncsek, Anja, Rizvi, Sumera, Heimbach, Julie, Koerkamp, Bas Groot, Bruix, Jordi, Forner, Alejandro, Bridgewater, John, Valle, Juan W, and Gores, Gregory J
Abstract: Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
Published: 2020

18. Ccne1 Overexpression Causes Chromosome Instability in Liver Cells and Liver Tumor Development in Mice

Author: dPB RMSC, LS Pathobiologie, Aziz, Khaled, Limzerwala, Jazeel F, Sturmlechner, Ines, Hurley, Erin, Zhang, Cheng, Jeganathan, Karthik B, Nelson, Grace, Bronk, Steve, Velasco, Raul Fierro, van Deursen, Erik-Jan, O'Brien, Daniel R, Kocher, Jean-Pierre A, Youssef, Sameh A, van Ree, Janine H, de Bruin, Alain, van den Bos, Hilda, Spierings, Diana C J, Foijer, Floris, van de Sluis, Bart, Roberts, Lewis R, Gores, Gregory, Li, Hu, van Deursen, Jan M, dPB RMSC, LS Pathobiologie, Aziz, Khaled, Limzerwala, Jazeel F, Sturmlechner, Ines, Hurley, Erin, Zhang, Cheng, Jeganathan, Karthik B, Nelson, Grace, Bronk, Steve, Velasco, Raul Fierro, van Deursen, Erik-Jan, O'Brien, Daniel R, Kocher, Jean-Pierre A, Youssef, Sameh A, van Ree, Janine H, de Bruin, Alain, van den Bos, Hilda, Spierings, Diana C J, Foijer, Floris, van de Sluis, Bart, Roberts, Lewis R, Gores, Gregory, Li, Hu, and van Deursen, Jan M
Published: 2019

19. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma.

Author: Yarchoan, Mark, Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, Ahmed, Mansoor M, Yarchoan, Mark, Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, and Ahmed, Mansoor M
Abstract: Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.
Published: 2019

20. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author: Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Kwong, Lawrence N, Roberts, Lewis R, Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, and Kwong, Lawrence N
Published: 2016

21. Direct Imaging in Reflected Light: Characterization of Older, Temperate Exoplanets With 30-m Telescopes

Author: Artigau, Etienne, Artigau, Etienne, Bernstein, Rebecca A, Brandt, Timothy, Chilcote, Jeffrey, Close, Laird, Crossfield, Ian, Delorme, Jacques-Robert, Dressing, Courtney, Fitzgerald, Michael P, Fortney, Jonathan, Howard, Andrew, Frazin, Richard, Jovanovic, Nemanja, Konopacky, Quinn, Lozi, Julien, Males, Jared R, Marois, Christian, Mazin, Benjamin A, Millar-Blanchaer, Max A, Morzinski, Katie M, Roberts, Lewis, Serabyn, Eugene, Vasisht, Gautam, Wallace, J Kent, Wang, Ji, Artigau, Etienne, Artigau, Etienne, Bernstein, Rebecca A, Brandt, Timothy, Chilcote, Jeffrey, Close, Laird, Crossfield, Ian, Delorme, Jacques-Robert, Dressing, Courtney, Fitzgerald, Michael P, Fortney, Jonathan, Howard, Andrew, Frazin, Richard, Jovanovic, Nemanja, Konopacky, Quinn, Lozi, Julien, Males, Jared R, Marois, Christian, Mazin, Benjamin A, Millar-Blanchaer, Max A, Morzinski, Katie M, Roberts, Lewis, Serabyn, Eugene, Vasisht, Gautam, Wallace, J Kent, and Wang, Ji
Abstract: Direct detection, also known as direct imaging, is a method for discovering and characterizing the atmospheres of planets at intermediate and wide separations. It is the only means of obtaining spectra of non-transiting exoplanets. Characterizing the atmospheres of planets in the <5 AU regime, where RV surveys have revealed an abundance of other worlds, requires a 30-m-class aperture in combination with an advanced adaptive optics system, coronagraph, and suite of spectrometers and imagers - this concept underlies planned instruments for both TMT (the Planetary Systems Imager, or PSI) and the GMT (GMagAO-X). These instruments could provide astrometry, photometry, and spectroscopy of an unprecedented sample of rocky planets, ice giants, and gas giants. For the first time habitable zone exoplanets will become accessible to direct imaging, and these instruments have the potential to detect and characterize the innermost regions of nearby M-dwarf planetary systems in reflected light. High-resolution spectroscopy will not only illuminate the physics and chemistry of exo-atmospheres, but may also probe rocky, temperate worlds for signs of life in the form of atmospheric biomarkers (combinations of water, oxygen and other molecular species). By completing the census of non-transiting worlds at a range of separations from their host stars, these instruments will provide the final pieces to the puzzle of planetary demographics. This whitepaper explores the science goals of direct imaging on 30-m telescopes and the technology development needed to achieve them.
Published: 2018

22. AASLD guidelines for the treatment of hepatocellular carcinoma.

Author: Heimbach, Julie K, Heimbach, Julie K, Kulik, Laura M, Finn, Richard S, Sirlin, Claude B, Abecassis, Michael M, Roberts, Lewis R, Zhu, Andrew X, Murad, M Hassan, Marrero, Jorge A, Heimbach, Julie K, Heimbach, Julie K, Kulik, Laura M, Finn, Richard S, Sirlin, Claude B, Abecassis, Michael M, Roberts, Lewis R, Zhu, Andrew X, Murad, M Hassan, and Marrero, Jorge A
Published: 2018

23. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases.

Author: Marrero, Jorge A, Marrero, Jorge A, Kulik, Laura M, Sirlin, Claude B, Zhu, Andrew X, Finn, Richard S, Abecassis, Michael M, Roberts, Lewis R, Heimbach, Julie K, Marrero, Jorge A, Marrero, Jorge A, Kulik, Laura M, Sirlin, Claude B, Zhu, Andrew X, Finn, Richard S, Abecassis, Michael M, Roberts, Lewis R, and Heimbach, Julie K
Published: 2018

24. Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Author: Graham, Rondell P, Graham, Rondell P, Yeh, Matthew M, Lam-Himlin, Dora, Roberts, Lewis R, Terracciano, Luigi, Cruise, Michael W, Greipp, Patricia T, Zreik, Riyam T, Jain, Dhanpat, Zaid, Nida, Salaria, Safia N, Jin, Long, Wang, Xiaoke, Rustin, Jeanette G, Kerr, Sarah E, Sukov, William R, Solomon, David A, Kakar, Sanjay, Waterhouse, Emily, Gill, Ryan M, Ferrell, Linda, Alves, Venancio Af, Nart, Deniz, Yilmaz, Funda, Roessler, Stephanie, Longerich, Thomas, Schirmacher, Peter, Torbenson, Michael S, Graham, Rondell P, Graham, Rondell P, Yeh, Matthew M, Lam-Himlin, Dora, Roberts, Lewis R, Terracciano, Luigi, Cruise, Michael W, Greipp, Patricia T, Zreik, Riyam T, Jain, Dhanpat, Zaid, Nida, Salaria, Safia N, Jin, Long, Wang, Xiaoke, Rustin, Jeanette G, Kerr, Sarah E, Sukov, William R, Solomon, David A, Kakar, Sanjay, Waterhouse, Emily, Gill, Ryan M, Ferrell, Linda, Alves, Venancio Af, Nart, Deniz, Yilmaz, Funda, Roessler, Stephanie, Longerich, Thomas, Schirmacher, Peter, and Torbenson, Michael S
Abstract: Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.
Published: 2018

25. The Planetary Systems Imager: 2-5 Micron Channel

Author: Evans, Christopher J., Simard, Luc, Takami, Hideki, Skemer, Andrew J., Stelter, Deno, Mawet, Dimitri, Fitzgerald, Michael, Mazin, Benjamin, Guyon, Olivier, Marois, Christian, Briesemeister, Zackery, Brandt, Timothy, Chilcote, Jeffrey, Delorme, Jacques-Robert, Jovanovic, Nemanja, Lu, Jessica, Millar-Blanchaer, Maxwell, Wallace, James, Vasisht, Gautam, Roberts, Lewis C., Jr., Wang, Ji, Evans, Christopher J., Simard, Luc, Takami, Hideki, Skemer, Andrew J., Stelter, Deno, Mawet, Dimitri, Fitzgerald, Michael, Mazin, Benjamin, Guyon, Olivier, Marois, Christian, Briesemeister, Zackery, Brandt, Timothy, Chilcote, Jeffrey, Delorme, Jacques-Robert, Jovanovic, Nemanja, Lu, Jessica, Millar-Blanchaer, Maxwell, Wallace, James, Vasisht, Gautam, Roberts, Lewis C., Jr., and Wang, Ji
Abstract: We summarize the red channel (2-5 micron) of the Planetary Systems Imager (PSI), a proposed second-generation instrument for the TMT. Cold exoplanets emit the majority of their light in the thermal infrared, which means these exoplanets can be detected at a more modest contrast than at other wavelengths. PSI-Red will be able to detect and characterize a wide variety of exoplanets, including radial-velocity planets on wide orbits, accreting protoplanets in nearby star-forming regions, and reflected-light planets around the nearest stars. PSI-Red will feature an imager, a low-resolution lenslet integral field spectrograph, a medium-resolution lenslet+slicer integral field spectrograph, and a fiber-fed high-resolution spectrograph.
Published: 2018

26. Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma

Author: Nepal, Chirag, O'Rourke, Colm J, Oliveira, Douglas Vnp, Taranta, Andrzej, Shema, Steven, Gautam, Prson, Calderaro, Julien, Barbour, Andrew, Raggi, Chiara, Wennerberg, Krister, Wang, Xin W, Lautem, Anja, Roberts, Lewis R, Andersen, Jesper B, Nepal, Chirag, O'Rourke, Colm J, Oliveira, Douglas Vnp, Taranta, Andrzej, Shema, Steven, Gautam, Prson, Calderaro, Julien, Barbour, Andrew, Raggi, Chiara, Wennerberg, Krister, Wang, Xin W, Lautem, Anja, Roberts, Lewis R, and Andersen, Jesper B
Abstract: Intrahepatic cholangiocarcinoma (iCCA) remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients, and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, 'undetermined'). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, co-mutation profiles and enriched pathways. High-throughput drug repositioning in seven patient-matched cell lines, chosen to reflect the genetic alterations specific for each patient group, confirmed in silico predictions of subgroup-specific vulnerabilities linked to enriched pathways. Intriguingly, patients lacking all 3 mutations ('undetermined') harbored the most extensive structural alterations while IDH mutant tumors displayed the most extensive DNA methylome dysregulation, consistent with previous findings.CONCLUSION: Stratification of iCCA patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epi-mutational) that influence pharmacologic response in drug repositioning protocols. This genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. This article is protected by copyright. All rights reserved.
Published: 2018

27. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

Author: Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N
Abstract: Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.
Published: 2017

28. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles - correction

Author: Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, Kwong, Lawrence N, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn Kyong, Bowlby, Reanne, Borad, Mitesh J, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N
Published: 2017

29. CHARACTERIZATION OF THE COMPANION mu HER

Author: Roberts, Lewis C., Mason, Brian D., Aguilar, Jonathan, Carson, Joseph, Crepp, Justin, Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Luszcz-Cook, Statia, Dekany, Richard, Hillenbrand, Lynne, Hinkley, Sasha, King, David, Lockhart, Thomas G., Nilsson, Ricky, Oppenheimer, Rebecca, Parry, Ian R., Pueyo, Laurent, Rice, Emily L., Sivaramakrishnan, Anand, Soummer, Remi, Vasisht, Gautam, Veicht, Aaron, Wang, Ji, Zhai, Chengxing, Zimmerman, Neil T., Roberts, Lewis C., Mason, Brian D., Aguilar, Jonathan, Carson, Joseph, Crepp, Justin, Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Luszcz-Cook, Statia, Dekany, Richard, Hillenbrand, Lynne, Hinkley, Sasha, King, David, Lockhart, Thomas G., Nilsson, Ricky, Oppenheimer, Rebecca, Parry, Ian R., Pueyo, Laurent, Rice, Emily L., Sivaramakrishnan, Anand, Soummer, Remi, Vasisht, Gautam, Veicht, Aaron, Wang, Ji, Zhai, Chengxing, and Zimmerman, Neil T.
Abstract: mu Her is a nearby quadruple system with a G-subgiant primary and several low-mass companions arranged in a 2+2 architecture. While the BC components have been well characterized, the Ab component has been detected astrometrically and with direct imaging but there has been some confusion over its nature, in particular, whether the companion is stellar or substellar. Using near-infrared spectroscopy, we are able to estimate the spectral type of the companion as an M4 +/- 1V star. In addition, we have measured the astrometry of the system for over a decade. We combined the astrometry with archival radial velocity measurements to compute an orbit of the system. From the combined orbit, we are able to compute the mass sum of the system. Using the estimated mass of the primary, we estimate the mass of the secondary as 0.32 MG, which agrees with the estimated spectral type. Our computed orbit is preliminary due to the incomplete orbital phase coverage, but it should be sufficient to predict ephemerides over the next decade.
Published: 2016
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30. Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis

Author: Bergquist, John R., Ivanics, Tommy, Storlie, Curtis B., Groeschl, Ryan T., Tee, May C., Habermann, Elizabeth B., Smoot, Rory L., Kendrick, Michael L., Farnell, Michael B., Roberts, Lewis R., Gores, Gregory J., Nagorney, David M., Truty, Mark J., Bergquist, John R., Ivanics, Tommy, Storlie, Curtis B., Groeschl, Ryan T., Tee, May C., Habermann, Elizabeth B., Smoot, Rory L., Kendrick, Michael L., Farnell, Michael B., Roberts, Lewis R., Gores, Gregory J., Nagorney, David M., and Truty, Mark J.
Published: 2016
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31. p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer.

Author: Duran, Angeles, Duran, Angeles, Hernandez, Eloy D, Reina-Campos, Miguel, Castilla, Elias A, Subramaniam, Shankar, Raghunandan, Sindhu, Roberts, Lewis R, Kisseleva, Tatiana, Karin, Michael, Diaz-Meco, Maria T, Moscat, Jorge, Duran, Angeles, Duran, Angeles, Hernandez, Eloy D, Reina-Campos, Miguel, Castilla, Elias A, Subramaniam, Shankar, Raghunandan, Sindhu, Roberts, Lewis R, Kisseleva, Tatiana, Karin, Michael, Diaz-Meco, Maria T, and Moscat, Jorge
Abstract: Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSCs, whose activation supports HCC.
Published: 2016

32. Integration of extracellular RNA profiling data using metadata, biomedical ontologies and Linked Data technologies.

Author: Subramanian, Sai Lakshmi, Subramanian, Sai Lakshmi, Kitchen, Robert R, Alexander, Roger, Carter, Bob S, Cheung, Kei-Hoi, Laurent, Louise C, Pico, Alexander, Roberts, Lewis R, Roth, Matthew E, Rozowsky, Joel S, Su, Andrew I, Gerstein, Mark B, Milosavljevic, Aleksandar, Subramanian, Sai Lakshmi, Subramanian, Sai Lakshmi, Kitchen, Robert R, Alexander, Roger, Carter, Bob S, Cheung, Kei-Hoi, Laurent, Louise C, Pico, Alexander, Roberts, Lewis R, Roth, Matthew E, Rozowsky, Joel S, Su, Andrew I, Gerstein, Mark B, and Milosavljevic, Aleksandar
Abstract: The large diversity and volume of extracellular RNA (exRNA) data that will form the basis of the exRNA Atlas generated by the Extracellular RNA Communication Consortium pose a substantial data integration challenge. We here present the strategy that is being implemented by the exRNA Data Management and Resource Repository, which employs metadata, biomedical ontologies and Linked Data technologies, such as Resource Description Framework to integrate a diverse set of exRNA profiles into an exRNA Atlas and enable integrative exRNA analysis. We focus on the following three specific data integration tasks: (a) selection of samples from a virtual biorepository for exRNA profiling and for inclusion in the exRNA Atlas; (b) retrieval of a data slice from the exRNA Atlas for integrative analysis and (c) interpretation of exRNA analysis results in the context of pathways and networks. As exRNA profiling gains wide adoption in the research community, we anticipate that the strategies discussed here will increasingly be required to enable data reuse and to facilitate integrative analysis of exRNA data.
Published: 2015

33. DIRECT SPECTRUM OF THE BENCHMARK T DWARF HD 19467 B

Author: Crepp, Justin R., Rice, Emily L., Veicht, Aaron, Aguilar, Jonathan, Pueyo, Laurent, Giorla, Paige, Nilsson, Ricky, Luszcz-Cook, Statia H., Oppenheimer, Rebecca, Hinkley, Sasha, Brenner, Douglas, Vasisht, Gautam, Cady, Eric, Beichman, Charles A., Hillenbrand, Lynne A., Lockhart, Thomas, Matthews, Christopher T., Roberts, Lewis C., Jr., Sivaramakrishnan, Anand, Soummer, Remi, Zhai, Chengxing, Crepp, Justin R., Rice, Emily L., Veicht, Aaron, Aguilar, Jonathan, Pueyo, Laurent, Giorla, Paige, Nilsson, Ricky, Luszcz-Cook, Statia H., Oppenheimer, Rebecca, Hinkley, Sasha, Brenner, Douglas, Vasisht, Gautam, Cady, Eric, Beichman, Charles A., Hillenbrand, Lynne A., Lockhart, Thomas, Matthews, Christopher T., Roberts, Lewis C., Jr., Sivaramakrishnan, Anand, Soummer, Remi, and Zhai, Chengxing
Abstract: HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R approximate to 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5 +/- 1 dwarf with effective temperature T-eff = 978(-43)(+20) K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits., AuthorCount:21
Published: 2015
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34. KNOW THE STAR, KNOW THE PLANET. V. CHARACTERIZATION OF THE STELLAR COMPANION TO THE EXOPLANET HOST STAR HD 177830

Author: Roberts, Lewis C., Oppenheimer, Rebecca, Crepp, Justin R., Baranec, Christoph, Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Luszcz-Cook, Statia, Dekany, Richard, Hillenbrand, Lynne, Hinkley, Sasha, King, David, Lockhart, Thomas G., Nilsson, Ricky, Parry, Ian R., Pueyo, Laurent, Sivaramakrishnan, Anand, Soummer, Rémi, Rice, Emily L., Veicht, Aaron, Vasisht, Gautam, Zhai, Chengxing, Zimmerman, Neil T., Roberts, Lewis C., Oppenheimer, Rebecca, Crepp, Justin R., Baranec, Christoph, Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Luszcz-Cook, Statia, Dekany, Richard, Hillenbrand, Lynne, Hinkley, Sasha, King, David, Lockhart, Thomas G., Nilsson, Ricky, Parry, Ian R., Pueyo, Laurent, Sivaramakrishnan, Anand, Soummer, Rémi, Rice, Emily L., Veicht, Aaron, Vasisht, Gautam, Zhai, Chengxing, and Zimmerman, Neil T.
Abstract: HD 177830 is an evolved K0IV star with two known exoplanets. In addition to the planetary companions it has a late-type stellar companion discovered with adaptive optics imagery. We observed the binary star system with the PHARO near-IR camera and the Project 1640 coronagraph. Using the Project 1640 coronagraph and integral field spectrograph we extracted a spectrum of the stellar companion. This allowed us to determine that the spectral type of the stellar companion is a M4 +/- 1 V. We used both instruments to measure the astrometry of the binary system. Combining these data with published data, we determined that the binary star has a likely period of approximately 800 years with a semimajor axis of 100-200 AU. This implies that the stellar companion has had little or no impact on the dynamics of the exoplanets. The astrometry of the system should continue to be monitored, but due to the slow nature of the system, observations can be made once every 5-10 years.
Published: 2015
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35. Platelet-derived growth factor primes cancer-associated fibroblasts for apoptosis

Author: Rizvi, Sumera, Mertens, Joachim C, Bronk, Steven F, Hirsova, Petra, Dai, Haiming, Roberts, Lewis R, Kaufmann, Scott H, Gores, Gregory J, Rizvi, Sumera, Mertens, Joachim C, Bronk, Steven F, Hirsova, Petra, Dai, Haiming, Roberts, Lewis R, Kaufmann, Scott H, and Gores, Gregory J
Abstract: Desmoplastic malignancies such as cholangiocarcinoma (CCA) are characterized by a dense stroma containing an abundance of myofibroblasts termed cancer-associated fibroblasts (CAF). The CAF phenotype represents an "activated state" in which cells are primed for cell death triggered by BH3 mimetics. Accordingly, this primed state may be therapeutically exploited. To elucidate the mechanisms underlying this poorly understood apoptotic priming, we examined the role of platelet-derived growth factor (PDGF) in CAF priming for cell death given its prominent role in CAF activation. PDGF isomers PDGF-B and PDGF-D are abundantly expressed in CCA cells derived from human specimens. Either isomer sensitizes myofibroblasts to cell death triggered by BH3 mimetics. Similar apoptotic sensitization was observed with co-culture of myofibroblasts and CCA cells. Profiling of Bcl-2 proteins expressed by PDGF-primed myofibroblasts demonstrated an increase in cellular levels of Puma. PDGF-mediated increases in cellular Puma levels induced proapoptotic changes in Bak, which resulted in its binding to Bcl-2. Short hairpin RNA-mediated down-regulation of Puma conferred resistance to PDGF-mediated apoptotic priming. Conversely, the BH3 mimetic navitoclax disrupted Bcl-2/Bak heterodimers, allowing Bak to execute the cell death program. Treatment with a Bcl-2-specific BH3 mimetic, ABT-199, reduced tumor formation and tumor burden in a murine model of cholangiocarcinoma. Collectively, these findings indicate that apoptotic priming of CAF by PDGF occurs via Puma-mediated Bak activation, which can be converted to active full-blown apoptosis by navitoclax or ABT-199 for therapeutic benefit.
Published: 2014

36. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma

Author: Mertens, Joachim C, Fingas, Christian D, Christensen, John D, Smoot, Rory L, Bronk, Steven F, Werneburg, Nathan W, Gustafson, Michael P, Dietz, Allan B, Roberts, Lewis R, Sirica, Alphonse E, Gores, Gregory J, Mertens, Joachim C, Fingas, Christian D, Christensen, John D, Smoot, Rory L, Bronk, Steven F, Werneburg, Nathan W, Gustafson, Michael P, Dietz, Allan B, Roberts, Lewis R, Sirica, Alphonse E, and Gores, Gregory J
Abstract: Cancer-associated fibroblasts (CAF) are abundant in the stroma of desmoplastic cancers where they promote tumor progression. CAFs are "activated" and as such may be uniquely susceptible to apoptosis. Using cholangiocarcinoma as a desmoplastic tumor model, we investigated the sensitivity of liver CAFs to the cytotoxic drug navitoclax, a BH3 mimetic. Navitoclax induced apoptosis in CAF and in myofibroblastic human hepatic stellate cells but lacked similar effects in quiescent fibroblasts or cholangiocarcinoma cells. Unlike cholangiocarcinoma cells, neither CAF nor quiescent fibroblasts expressed Mcl-1, a known resistance factor for navitoclax cytotoxicity. Explaining this paradox, we found that mitochondria isolated from CAFs or cells treated with navitoclax both released the apoptogenic factors Smac and cytochrome c, suggesting that they are primed for cell death. Such death priming in CAFs appeared to be due, in part, to upregulation of the proapoptotic protein Bax. Short hairpin RNA-mediated attenuation of Bax repressed navitoclax-mediated mitochondrial dysfunction, release of apoptogenic factors, and apoptotic cell death. In a syngeneic rat model of cholangiocarcinoma, navitoclax treatment triggered CAF apoptosis, diminishing expression of the desmoplastic extracellular matrix protein tenascin C, suppressing tumor outgrowth, and improving host survival. Together, our findings argue that navitoclax may be useful for destroying CAFs in the tumor microenvironment as a general strategy to attack solid tumors.
Published: 2013

37. Project 1640: the world's first ExAO coronagraphic hyperspectral imager for comparative planetary science

Author: Ellerbroek, Brent L., Marchetti, Enrico, Véran, Jean-Pierre, Oppenheimer, Ben R., Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Crepp, Justin, Hillenbrand, Lynne, Hinkley, Sasha, Ligon, E. R., Lockhart, Thomas, Parry, Ian, Pueyo, Laurent, Rice, Emily, Roberts, Lewis C., Roberts, Jennifer, Shao, Michael, Sivaramakrishnan, Anand, Soummer, Rémi, Vasisht, Gautam, Vescelus, Fred, Wallace, J. Kent, Zhai, Chengxing, Zimmerman, Neil, Ellerbroek, Brent L., Marchetti, Enrico, Véran, Jean-Pierre, Oppenheimer, Ben R., Beichman, Charles, Brenner, Douglas, Burruss, Rick, Cady, Eric, Crepp, Justin, Hillenbrand, Lynne, Hinkley, Sasha, Ligon, E. R., Lockhart, Thomas, Parry, Ian, Pueyo, Laurent, Rice, Emily, Roberts, Lewis C., Roberts, Jennifer, Shao, Michael, Sivaramakrishnan, Anand, Soummer, Rémi, Vasisht, Gautam, Vescelus, Fred, Wallace, J. Kent, Zhai, Chengxing, and Zimmerman, Neil
Abstract: Project 1640, a high-contrast spectral-imaging effort involving a coordinated set of instrumentation and software, built at AMNH, JPL, Cambridge and Caltech, has been commissioned and is fully operational. This novel suite of instrumentation includes a 3388+241-actuator adaptive optics system, an optimized apodized pupil Lyot coronagraph, an integral field spectrograph, and an interferometric calibration wave front sensor. Project 1640 is the first of its kind of instrumentation, designed to image and characterize planetary systems around nearby stars, employing a variety of techniques to break the speckle-noise barrier. It is operational roughly one year before any similar project, with the goal of reaching a contrast of 10^(-7) at 1 arcsecond separation. We describe the instrument, highlight recent results, and document on-sky performance at the start of a 3-year, 99-night survey at the Palomar 5-m Hale telescope.
Published: 2012

38. Coronagraphic Imaging of Debris Disks From a High Altitude Balloon Platform

Author: Clampin, Mark C., Fazio, Giovanni G., MacEwen, Howard A., Oschmann, Jacobus M., Jr., Unwin, Stephen, Traub, Wesley, Bryden, Geoffrey, Brugarolas, Paul, Chen, Pin, Guyon, Olivier, Hillenbrand, Lynne, Krist, John, Macintosh, Bruce, Mawet, Dimitri, Mennesson, Bertrand, Moody, Dwight, Roberts, Lewis C., Jr., Stapelfeldt, Karl, Stuchlik, David, Trauger, John, Vasisht, Gautam, Clampin, Mark C., Fazio, Giovanni G., MacEwen, Howard A., Oschmann, Jacobus M., Jr., Unwin, Stephen, Traub, Wesley, Bryden, Geoffrey, Brugarolas, Paul, Chen, Pin, Guyon, Olivier, Hillenbrand, Lynne, Krist, John, Macintosh, Bruce, Mawet, Dimitri, Mennesson, Bertrand, Moody, Dwight, Roberts, Lewis C., Jr., Stapelfeldt, Karl, Stuchlik, David, Trauger, John, and Vasisht, Gautam
Abstract: Debris disks around nearby stars are tracers of the planet formation process, and they are a key element of our understanding of the formation and evolution of extrasolar planetary systems. With multi-color images of a significant number of disks, we can probe important questions: can we learn about planetary system evolution; what materials are the disks made of; and can they reveal the presence of planets? Most disks are known to exist only through their infrared flux excesses as measured by the Spitzer Space Telescope, and through images measured by Herschel. The brightest, most extended disks have been imaged with HST, and a few, such as Fomalhaut, can be observed using ground-based telescopes. But the number of good images is still very small, and there are none of disks with densities as low as the disk associated with the asteroid belt and Edgeworth Kuiper belt in our own Solar System. Direct imaging of disks is a major observational challenge, demanding high angular resolution and extremely high dynamic range close to the parent star. The ultimate experiment requires a space-based platform, but demonstrating much of the needed technology, mitigating the technical risks of a space-based coronagraph, and performing valuable measurements of circumstellar debris disks, can be done from a high-altitude balloon platform. In this paper we present a balloon-borne telescope concept based on the Zodiac II design that could undertake compelling studies of a sample of debris disks.
Published: 2012

39. Spectral typing of late-type stellar companions to young stars from low-dispersion near-infrared integral field unit data

Author: Roberts, Lewis C., Rice, Emily L., Beichman, Charles A., Brenner, Douglas, Burruss, Rick, Crepp, Justin R., Dekany, Richard G., Hillenbrand, Lynne A., Hinkley, Sasha, Ligon, E. Robert, Lockhart, Thomas G., King, David, Metchev, Stanimir, Oppenheimer, Ben R., Parry, Ian R., Pueyo, Laurent, Roberts, Jennifer E., Shao, Michael, Sivaramakrishnan, Anand, Soummer, Rémi, Vasisht, Gautam, Vescelus, Fred E., Wallace, J. Kent, Zimmerman, Neil T., Zhai, Chengxing, Roberts, Lewis C., Rice, Emily L., Beichman, Charles A., Brenner, Douglas, Burruss, Rick, Crepp, Justin R., Dekany, Richard G., Hillenbrand, Lynne A., Hinkley, Sasha, Ligon, E. Robert, Lockhart, Thomas G., King, David, Metchev, Stanimir, Oppenheimer, Ben R., Parry, Ian R., Pueyo, Laurent, Roberts, Jennifer E., Shao, Michael, Sivaramakrishnan, Anand, Soummer, Rémi, Vasisht, Gautam, Vescelus, Fred E., Wallace, J. Kent, Zimmerman, Neil T., and Zhai, Chengxing
Abstract: We used the Project 1640 near-infrared coronagraph and integral field spectrograph to observe 19 young solar-type stars. Five of these stars are known binary stars and we detected the late-type secondaries and were able to measure their JH spectra with a resolution of R 30. The reduced, extracted, and calibrated spectra were compared to template spectra from the IRTF spectral library. With this comparison, we test the accuracy and consistency of spectral-type determination with the low-resolution near-infrared spectra from P1640. Additionally, we determine effective temperature and surface gravity of the companions by fitting synthetic spectra calculated with the PHOENIX model atmosphere code. We also present several new epochs of astrometry of each of the systems. Together, these data increase our knowledge and understanding of the stellar make up of these systems. In addition to the astronomical results, the analysis presented helps validate the Project 1640 data reduction and spectral extraction processes and the utility of low-resolution, near-infrared spectra for characterizing late-type companions in multiple systems. © 2012. The American Astronomical Society. All rights reserved.
Published: 2012

40. Zodiac II: Debris Disk Science from a Balloon

Author: Shaklan, Stuart, Bryden, Geoffrey, Traub, Wesley, Roberts, Lewis C., Jr., Bruno, Robin, Unwin, Stephen, Backovsky, Stan, Brugarolas, Paul, Chakrabarti, Supriya, Chen, Pin, Hillenbrand, Lynne, Krist, John, Lillie, Charles, Macintosh, Bruce, Mawet, Dimitri, Mennesson, Bertrand, Moody, Dwight, Rahman, Zahidul, Rey, Justin, Stapelfeldt, Karl, Stuchlik, David, Trauger, John, Vasisht, Gautam, Shaklan, Stuart, Bryden, Geoffrey, Traub, Wesley, Roberts, Lewis C., Jr., Bruno, Robin, Unwin, Stephen, Backovsky, Stan, Brugarolas, Paul, Chakrabarti, Supriya, Chen, Pin, Hillenbrand, Lynne, Krist, John, Lillie, Charles, Macintosh, Bruce, Mawet, Dimitri, Mennesson, Bertrand, Moody, Dwight, Rahman, Zahidul, Rey, Justin, Stapelfeldt, Karl, Stuchlik, David, Trauger, John, and Vasisht, Gautam
Abstract: Zodiac II is a proposed balloon-borne science investigation of debris disks around nearby stars. Debris disks are analogs of the Asteroid Belt (mainly rocky) and Kuiper Belt (mainly icy) in our Solar System. Zodiac II will measure the size, shape, brightness, and color of a statistically significant sample of disks. These measurements will enable us to probe these fundamental questions: what do debris disks tell us about the evolution of planetary systems; how are debris disks produced; how are debris disks shaped by planets; what materials are debris disks made of; how much dust do debris disks make as they grind down; and how long do debris disks live? In addition, Zodiac II will observe hot, young exoplanets as targets of opportunity. The Zodiac II instrument is a 1.1-m diameter SiC telescope and an imaging coronagraph on a gondola carried by a stratospheric balloon. Its data product is a set of images of each targeted debris disk in four broad visiblewavelength bands. Zodiac II will address its science questions by taking high-resolution, multi-wavelength images of the debris disks around tens of nearby stars. Mid-latitude flights are considered: overnight test flights within the United States followed by half-global flights in the Southern Hemisphere. These longer flights are required to fully explore the set of known debris disks accessible only to Zodiac II. On these targets, it will be 100 times more sensitive than the Hubble Space Telescope's Advanced Camera for Surveys (HST/ACS); no existing telescope can match the Zodiac II contrast and resolution performance. A second objective of Zodiac II is to use the near-space environment to raise the Technology Readiness Level (TRL) of SiC mirrors, internal coronagraphs, deformable mirrors, and wavefront sensing and control, all potentially needed for a future space-based telescope for high-contrast exoplanet imaging.
Published: 2011

41. Control System Modeling for the Thirty Meter Telescope Primary Mirror

Author: Andresen, Torben, Enmark, Anita, MacMynowski, Douglas G., Thompson, Peter M., Shelton, J. Chris, Roberts, Lewis C., Jr., Colavita, M. Mark, Sirota, Mark J., Andresen, Torben, Enmark, Anita, MacMynowski, Douglas G., Thompson, Peter M., Shelton, J. Chris, Roberts, Lewis C., Jr., Colavita, M. Mark, and Sirota, Mark J.
Abstract: The Thirty Meter Telescope primary mirror is composed of 492 segments that are controlled to high precision in the presence of wind and vibration disturbances, despite the interaction with structural dynamics. The higher bandwidth and larger number of segments compared with the Keck telescopes requires greater attention to modeling to ensure success. We focus here on the development and validation of a suite of quasi-static and dynamic modeling tools required to support the design process, including robustness verification, performance estimation, and requirements flowdown. Models are used to predict the dynamic response due to wind and vibration disturbances, estimate achievable bandwidth in the presence of control-structure-interaction (CSI) and uncertainty in the interaction matrix, and simulate and analyze control algorithms and strategies, e.g. for control of focus-mode, and sensor calibration. Representative results illustrate TMT performance scaling with parameters, but the emphasis is on the modeling framework itself.
Published: 2011

42. High fidelity optical modeling for the TMT

Author: Andersen, Torben, Enmark, Anita, Nissly, Carl, Seo, Byoung-Joon, Troy, Mitchell, Angeli, George, Cho, Myung, Ellerbroek, Brent, Piatrou, Piotr, Roberts, Lewis C., Jr., Shelton, J. Chris, Wang, Lianqi, Andersen, Torben, Enmark, Anita, Nissly, Carl, Seo, Byoung-Joon, Troy, Mitchell, Angeli, George, Cho, Myung, Ellerbroek, Brent, Piatrou, Piotr, Roberts, Lewis C., Jr., Shelton, J. Chris, and Wang, Lianqi
Abstract: The Thirty Meter Telescope (TMT) is a Ritchey-Chritien optical telescope with a 30-meter diameter primary mirror made up of 492 hexagonal segments. Such a large and complex optical system requires detailed modeling of the optical performance during the design phase. An optical modeling computational framework has been developed to support activities related to wavefront & image performance prediction. The model includes effects related to mirror shape sensing & control, mirror alignment & phasing, M1 segment control, low order wavefront correction, adaptive optics simulation for high order wavefront correction, and high contrast imaging. Here we give an overview of this optical simulation framework, the modeling tools and algorithms that are used, and a set of sample analyses. These tools have been used in many aspects of the system design process from mirror specification to instrument & sensor design to algorithm development and beyond.
Published: 2011

43. High fidelity optical modeling for the TMT

Author: Nissly, Carl, Seo, Byoung-Lee, Troy, Mitchell, Angeli, George, Cho, Myung, Ellerbroek, Brent, Piatrou, Piotr, Roberts, Lewis C, Jr, Shelton, J Chris, Wang, Lianqi, Nissly, Carl, Seo, Byoung-Lee, Troy, Mitchell, Angeli, George, Cho, Myung, Ellerbroek, Brent, Piatrou, Piotr, Roberts, Lewis C, Jr, Shelton, J Chris, and Wang, Lianqi
Abstract: The Thirty Meter Telescope (TMT) is a Ritchey-Chritien optical telescope with a 30-meter diameter primary mirror made up of 492 hexagonal segments. Such a large and complex optical system requires detailed modeling of the optical performance during the design phase. An optical modeling computational framework has been developed to support activities related to wavefront & image performance prediction. The model includes effects related to mirror shape sensing & control, mirror alignment & phasing, M1 segment control, low order wavefront correction, adaptive optics simulation for high order wavefront correction, and high contrast imaging. Here we give an overview of this optical simulation framework, the modeling tools and algorithms that are used, and a set of sample analyses. These tools have been used in many aspects of the system design process from mirror specification to instrument & sensor design to algorithm development and beyond.
Published: 2011

44. Robustness of the Thirty Meter Telescope Primary Mirror Control System

Author: Stepp, Larry M., Gilmozzi, Roberto, Hall, Helen J., MacMynowski, Douglas G., Thompson, Peter M., Shelton, Chris, Roberts, Lewis C., Stepp, Larry M., Gilmozzi, Roberto, Hall, Helen J., MacMynowski, Douglas G., Thompson, Peter M., Shelton, Chris, and Roberts, Lewis C.
Abstract: The primary mirror control system for the Thirty Meter Telescope (TMT) maintains the alignment of the 492 segments in the presence of both quasi-static (gravity and thermal) and dynamic disturbances due to unsteady wind loads. The latter results in a desired control bandwidth of 1Hz at high spatial frequencies. The achievable bandwidth is limited by robustness to (i) uncertain telescope structural dynamics (control-structure interaction) and (ii) small perturbations in the ill-conditioned influence matrix that relates segment edge sensor response to actuator commands. Both of these effects are considered herein using models of TMT. The former is explored through multivariable sensitivity analysis on a reduced-order Zernike-basis representation of the structural dynamics. The interaction matrix ("A-matrix") uncertainty has been analyzed theoretically elsewhere, and is examined here for realistic amplitude perturbations due to segment and sensor installation errors, and gravity and thermal induced segment motion. The primary influence of A-matrix uncertainty is on the control of "focusmode"; this is the least observable mode, measurable only through the edge-sensor (gap-dependent) sensitivity to the dihedral angle between segments. Accurately estimating focus-mode will require updating the A-matrix as a function of the measured gap. A-matrix uncertainty also results in a higher gain-margin requirement for focus-mode, and hence the A-matrix and CSI robustness need to be understood simultaneously. Based on the robustness analysis, the desired 1 Hz bandwidth is achievable in the presence of uncertainty for all except the lowest spatial-frequency response patterns of the primary mirror.
Published: 2010

45. Iao: The New Adaptive Optics Visible Imaging and Photometric System for AEOS

Author: AIR FORCE RESEARCH LAB KIRTLAND AFB NM DIRECTED ENERGY DIRECTORATE, Skinner, Mark A., Anast, Fred, Mooney, John, Kono, Daryn, Roberts, Lewis C., Hassall, Arthur, Hunt, Scott, AIR FORCE RESEARCH LAB KIRTLAND AFB NM DIRECTED ENERGY DIRECTORATE, Skinner, Mark A., Anast, Fred, Mooney, John, Kono, Daryn, Roberts, Lewis C., Hassall, Arthur, and Hunt, Scott
Abstract: The Iao camera is a totally new camera system that will be replacing the existing visible imager (VisIM) camera. It functions as the science camera, and is capable of collecting uncompensated, as well as adaptive-optics compensated images. Iao offers a number of improvements over the existing system, including higher speed, greater sensitivity, as well as improved flexibility in control of the imaging system. We describe the Iao camera system, the current state of progress, as well as the plans for integration of the new system into AEOS., Advanced Maui Optical and Space Surveillance Technologies Conference held 16-19 September 2008 in Maui, HI. The original document contains color images.
Published: 2008

46. Adaptive Optics Photometry and Astrometry of Binary Stars. III. A Faint Companion Search of O-Star Systems

Author: NAVAL OBSERVATORY WASHINGTON DC ASTROMETRY DEPT, Turner, Nils H., Brummelaar, Theo A., Roberts, Lewis C., Mason, Brian D., Hartkoff, William I., Gies, Douglas R., NAVAL OBSERVATORY WASHINGTON DC ASTROMETRY DEPT, Turner, Nils H., Brummelaar, Theo A., Roberts, Lewis C., Mason, Brian D., Hartkoff, William I., and Gies, Douglas R.
Abstract: We present the results of an adaptive optics survey for faint companions among Galactic O-type star systems (with V 8) using the Advanced Electro-Optical System (AEOS) 3.6 m telescope on Haleakala. We surveyed these O-star systems in the I -band, typically being able to detect a companion with a magnitude difference of deltam(sub I) < or ~ 6 in the projected separation range 0".5 < rho < 1".0, and deltam(sub I) < or ~ 9.5 in the range 1".0 < rho < 5".0. In the course of the survey, we discovered 40 new companions among 31 of the 116 objects examined and made astrometric and differential magnitude measurements of 24 additional known pairs, several of them being confirmation detections. We present new astrometric orbits for two binaries, BU 1032AB (WDS 05387- 0236; sigma Ori AB) and SEE 322 (WDS 17158-3344; HD 155889AB). We lack magnitude differences for other filter bands, so it is difficult to determine physical from line-of-sight companions, but we present empirical arguments for the limiting magnitude difference where field contamination is significant., Pub. in the Astronomical Journal, v136, p554-565, Aug 2008. Sponsored in part by NSF grant AST-0506573 and AST-0606861
Published: 2008

47. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.

Author: [KUL], Lee, Ju-Seog, Heo, Jeonghoon, Libbrecht, Louis, Chu, In-Sun, Kaposi-Novak, Pal, Calvisi, Diego F, Mikaelyan, Arsen, Roberts, Lewis R, Demetris, Anthony J, Sun, Zongtang, Nevens, Frederik, Roskams, Tania, Thorgeirsson, Snorri S, [KUL], Lee, Ju-Seog, Heo, Jeonghoon, Libbrecht, Louis, Chu, In-Sun, Kaposi-Novak, Pal, Calvisi, Diego F, Mikaelyan, Arsen, Roberts, Lewis R, Demetris, Anthony J, Sun, Zongtang, Nevens, Frederik, Roskams, Tania, and Thorgeirsson, Snorri S
Abstract: The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development.
Published: 2006

48. Maui Space Surveillance System Phased Array

Author: BOEING CO KIHEI HI, Roberts, Lewis C., BOEING CO KIHEI HI, and Roberts, Lewis C.
Abstract: Long baseline Interferometry is a technique where light from two or more telescopes is combined, creating interference fringes. Analysis of the interference fringes allows information to be exacted that has the angular resolution of a telescope with the diameter of the separation of the two telescopes. Since it is currently unfeasible to build telescopes with diameters of hundreds of meters, this is the only method to achieve resolution on the order of micro arcseconds. If interferometry could be applied to space surveillance it would offer the potential for sub-centimeter resolution of low-Earth objects. This report investigates the feasibility of constructing an instrument to observe satellites and of placing that instrument at the Maui Space Surveillance System., The original document contains color images.
Published: 2004

49. The Lyot project: toward exoplanet imaging and spectroscopy

Author: Bonaccini Calia, Domenico, Ellerbroek, Brent L., Ragazzoni, Roberto, Oppenheimer, Ben R., Digby, Andrew P., Newburgh, Laura, Brenner, Douglas, Shara, Michael, Mey, Jacob, Mandeville, Charles, Makidon, Russell B., Sivaramakrishnan, Anand, Soummer, Remi, Graham, James R., Kalas, Paul, Perrin, Marshall, Roberts, Lewis C., Jr., Kuhn, Jeffrey, Whitman, Kathryn, Lloyd, James P., Bonaccini Calia, Domenico, Ellerbroek, Brent L., Ragazzoni, Roberto, Oppenheimer, Ben R., Digby, Andrew P., Newburgh, Laura, Brenner, Douglas, Shara, Michael, Mey, Jacob, Mandeville, Charles, Makidon, Russell B., Sivaramakrishnan, Anand, Soummer, Remi, Graham, James R., Kalas, Paul, Perrin, Marshall, Roberts, Lewis C., Jr., Kuhn, Jeffrey, Whitman, Kathryn, and Lloyd, James P.
Abstract: Among the adaptive optics systems available to astronomers, the US Air Force Advanced Electro-Optical System (AEOS) is unique because it delivers very high order wave front correction. The Lyot Project includes the construction and installation of the world’s first diffraction-limited, optimized coronagraph that exploits the full astronomical potential of AEOS and represents a critical step toward the long-term goal of directly imaging and studying extrasolar planets (a.k.a. “exoplanets”). We provide an update on the Project, whose coronagraph saw first light in March 2004. The coronagraph is operating at least as well as predicted by simulations, and a survey of nearby stars has begun.
Published: 2004

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