Altair at Gemini North : full sky coverage laser AO correction at visible wavelengths

We present two recent upgrades to the Gemini North Adaptive Optics (AO) system, Altair. These two upgrades provide 100% sky coverage for low performance AO suitable for improving the natural seeing by factors of 25% to 3 from blue visible wavelengths (350 nm) through the near infrared (2.5 micron wavelengths). The first upgrade, dubbed LGS + P1 "Super Seeing" mode, allows correction of high order aberrations with an on-axis Laser Guide Star (LGS) while tip/tilt correction is performed with a more distant peripheral wavefront sensor (P1). Most currently operating LGS AO systems are limited in their sky coverage, primarily due to tip/tilt star availability. Although P1 provides sub-optimal tip/tilt correction due to its distance from the science source, its patrol radius allows operation in LGS + P1 mode anywhere in the sky from declinations of +70 degrees to -30 degrees. This mode was offered for science use at Gemini North in 2013A. We present typical performance and use from its first semester in science operation, with a factor 2 to 3 image quality improvement over seeing limited images. The second upgrade is the commissioning of the AO system to correct at visible wavelengths, which is expected to be completed in 2014. In this mode, Altair will feed the Gemini Multi-Object Spectrograph (GMOS), which is an optical imager as well as a long-slit, multi-slit and integral field unit spectrograph. We intend to replace the current Altair science dichroic with a sodium notch filter, passing only the 589nm wavelength light from the LGS to the AO system. The rest of the spectrum from 350 nm to the GMOS red cutoff at 1.1 microns is intended as science capable light. Tip/tilt correction will be performed close to the science target with the GMOS on-instrument wavefront sensor or with P1 as in the P1+LGS mode discussed above. We expect an image quality improvement of 25% in this mode over seeing limited observations. Since exposure time to reach a given signal-to-noise ratio scales roughly as the square of the image quality, these two upgrades represent a substantial efficiency improvement which is available to nearly all targets normally observed at Gemini North.7 page(s

Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel

Background: An early detection tool for EOC was constructed from analysis of biomarker expression data from serum collected during the UKCTOCS. Methods: This study included 49 EOC cases (19 Type I and 30 Type II) and 31 controls, representing 482 serial samples spanning seven years pre-diagnosis. A logit model was trained by analysis of dysregulation of expression data of four putative biomarkers, (CA125, phosphatidylcholine-sterol acyltransferase, vitamin K-dependent protein Z and C-reactive protein); by scoring the specificity associated with dysregulation from the baseline expression for each individual. Results: The model is discriminatory, passes k-fold and leave-one-out cross-validations and was further validated in a Type I EOC set. Samples were analysed as a simulated annual screening programme, the algorithm diagnosed cases with >30% PPV 1\u20132 years pre-diagnosis. For Type II cases (~80% were HGS) the algorithm classified 64% at 1 year and 28% at 2 years tDx as severe. Conclusions: The panel has the potential to diagnose EOC one-two years earlier than current diagnosis. This analysis provides a tangible worked example demonstrating the potential for development as a screening tool and scrutiny of its properties. Limits on interpretation imposed by the number of samples available are discussed

Abstract 6130: Cancer sensitivity to therapy is constrained by apoptosis regulation in cells of origin

Abstract Many chemotherapeutic agents target cellular components or processes that are present in all cancers, yet clinical responses to these agents vary greatly between cancer types and even patient age - the basis for these broad-scale differences are unclear. The vast majority of targeted and cytotoxic cancer therapies including ionizing radiation produce pro-apoptotic signaling in exposed cells, suggesting that the mitochondrial apoptosis sensitivity of cancer cells could act as a central signaling “node” to broadly impact therapy outcomes. To test this, we used BH3 profiling and complementary chemosensitivity assays to analyze hundreds of primary cancer specimens across twelve major cancer types. We find that cancers with typically favorable outcomes including certain hematologic malignancies, testicular cancer, and some pediatric cancers contain mitochondria that are highly primed for apoptosis, which renders them hypersensitive to cytotoxic as well as targeted agents and radiation therapy. Priming levels in many epithelial cancers including ovarian cancer and non-small cell lung cancer are highly heterogeneous, mirroring their variability in clinical outcomes. Finally, many tumor types that are typically chemoresistant including adult soft tissue sarcomas, hepatocellular carcinoma and pancreatic cancer are almost completely resistant to pro-apoptotic signaling. By analyzing in vitro and in vivo pancreatic, ovarian, hepatocellular and sarcoma tumorigenesis models, we find that apoptotic priming generally increases during neoplastic transformation, in part due to consistent upregulation of pro-apoptotic proteins BAX and BAK. However, the level of apoptotic priming in cancer cells is constrained by the baseline apoptosis sensitivity of normal cells prior to transformation. Remarkably, we find that apoptotic priming is dynamically regulated by cell lineage and differentiation state but can also be modulated by oncogenes. For instance, Myc activation typically increases apoptotic priming while activation of mutant Ras signaling decreases it - these changes in priming alter the chemosensitivity of cancer cells. Finally, we use inducible mouse tumor models to demonstrate that neoplastic transformation of cells from developmentally immature tissues yields pediatric tumors that are more primed for apoptosis than equivalent tumors arising in adults. This difference in priming causes pediatric tumors to be more sensitive to front-line therapies and BH3 mimetics targeting pro-survival BCL-2 family proteins in vitro and in vivo. Thus, lineage-determined regulation of apoptosis prior to and during neoplastic transformation leads to broad-scale differences in cancer cell chemosensitivity and can be exploited therapeutically by targeting BCL-2 family proteins. Citation Format: Cameron Fraser, Xingping Qin, Kenichi Shimada, Johan Spetz, Mary Heather Florido, Rumani Singh, Stacey Yu, Adam Presser, Zintis Inde, Gaurav Joshi, Jennifer Guerriero, Francisco Sanchez-Rivera, Alison Karst, Omar Lopez, Chendi Li, Peter Winter, Ying Yue, Peter Sorger, Jingwei Cheng, Izidore Lossos, Aaron Hata, Ronny Drapkin, Adam Palmer, James Decaprio, Manisha Thakuria, Charles Yoon, Ursula Matulonis, Matthew Meyerson, Elizabeth Stover, Diana Cardona, Kris Wood, Shayna Sarosiek, David Kirsch, Joseph Mancias, Andrew Cherniack, Anthony Letai, Kristopher Sarosiek. Cancer sensitivity to therapy is constrained by apoptosis regulation in cells of origin. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6130