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1. First-in-human phase 1 study of the arginase inhibitor INCB001158 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumours

Author

Michael Smith, Aung Naing, Todd Bauer, Kyriakos P Papadopoulos, Osama Rahma, Elena Garralda, Glenn J Hanna, Michael J Pishvaian, Xuejun Chen, Sven Gogov, Omar Saavedra, Howard Kallender, LuLu Cheng, and Emil Kuriakose

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objective The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.Methods and analysis In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti−PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).Results A total of 107 patients received INCB001158 50–150 mg two times per day as monotherapy, and 153 patients, including 6 with moderate renal impairment, received INCB001158 50–100 mg two times per day combined with pembrolizumab. INCB001158 exposure was similar between groups (median, 56 days (monotherapy); 84 days (combination)). 49 patients (45.8%) on monotherapy and 76 (51.7%) on combination therapy experienced grade ≥3 treatment-emergent adverse events (AEs). The most common INCB001158-related AEs were fatigue (n=10/107 (9.3%)) and nausea (n=10/107 (9.3%)) with monotherapy and diarrhoea (n=24/147 (16.3%)) and fatigue (n=22/147 (15.0%)) with combination therapy. The highest response rate was seen in the anti–PD-1/PD-L1–naive combination therapy group with head/neck squamous cell carcinoma (overall response rate, 19.2%; 4/26 partial responses, 1/26 complete response). Consistent with arginase inhibition activity, plasma arginine dose-dependently increased. Arginase 1 expression in the tumour microenvironment did not correlate with response.Conclusions INCB001158 was generally well tolerated. Response rates did not exceed background for given tumour types despite demonstrable pharmacodynamic activity. Overall, the limited antitumour activity of arginase inhibition observed suggests that the role of arginine depletion in cancer is multifaceted.Trial registration number NCT02903914.

Published
2024
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2. Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma

Author

Craig L Slingluff, Gina R Petroni, Todd Bauer, Nipun Merchant, Osama Rahma, Rawad Elias, Scott Rodig, Matthew H G Katz, Andressa Dias Costa, Brian M Wolpin, Stephanie K Dougan, Chee-Chee Stucky, Kathleen Pfaff, Gauri R Varadhachary, Victoire Cardot-Ruffino, Matthew J Reilley, Patrick Lenehan, Tanios S Bekaii-Saab, and Jonathan Andrew Nowak

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival (OS). We hypothesized that adding programmed cell death protein 1 (PD-1) blockade to chemoradiotherapy would be well tolerated and increase TILs among patients with localized PDAC.Methods Patients were randomized 2:1 to Arm A (receiving pembrolizumab plus chemoradiotherapy (capecitabine and external beam radiation)) or Arm B (receiving chemoradiotherapy alone) before anticipated pancreatectomy. Primary endpoints were (1) incidence and severity of adverse events during neoadjuvant therapy and (2) density of TILs in resected tumor specimens. TIL density was assessed using multiplexed immunofluorescence histologic examination.Results Thirty-seven patients were randomized to Arms A (n=24) and B (n=13). Grade ≥3 adverse events related to neoadjuvant treatment were experienced by 9 (38%) and 4 (31%) patients in Arms A and B, respectively, with one patient experiencing dose-limiting toxicity in Arm A. Seventeen (71%) and 7 (54%) patients in Arms A and B, respectively, underwent pancreatectomy. Median CD8+ T-cell densities in Arms A and B were 67.4 (IQR: 39.2–141.8) and 37.9 (IQR: 22.9–173.4) cells/mm2, respectively. Arms showed no noticeable differences in density of CD8+Ki67+, CD4+, or CD4+FOXP3+ regulatory T cells; M1-like and M2-like macrophages; or granulocytes. Median OS durations were 27.8 (95% CI: 17.1 to NR) and 24.3 (95% CI: 12.6 to NR) months for Arms A and B, respectively.Conclusions Adding pembrolizumab to neoadjuvant chemoradiotherapy was safe. However, no convincing effect on CD8+ TILs was observed.

Published
2023
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3. Interrogating the CD27:CD70 axis in αCD40-dependent control of pancreatic adenocarcinoma

Author

Awndre Gamache, Claire Conarroe, Sara Adair, Todd Bauer, Frederic Padilla, and Timothy N. J. Bullock

Subjects
CD40, CD27, CD70, TIL activation, PDAC, KPC, Biology (General), QH301-705.5
Abstract

Immune checkpoint blockade immunotherapy has radically changed patient outcomes in multiple cancer types. Pancreatic cancer is one of the notable exceptions, being protected from immunotherapy by a variety of mechanisms, including the presence of a dense stroma and immunosuppressive myeloid cells. Previous studies have demonstrated that CD40 stimulation can remodel the tumor microenvironment in a manner that promotes effector immune cell responses and can cooperate with immune checkpoint inhibition for durable tumor control mediated by T cells. Here we confirm the capability of this combination therapy to dramatically, and durably, control pancreatic cancer growth in an orthotopic model and that the immune memory to this cancer is primarily a function of CD4+ T cells. We extend this understanding by demonstrating that recruitment of recently primed T cells from the draining lymph nodes is not necessary for the observed control, suggesting that the pre-existing intra-tumoral cells respond to the combination therapy. Further, we find that the efficacy of CD40 stimulation is not dependent upon CD70, which is commonly induced on dendritic cells in response to CD40 agonism. Finally, we find that directly targeting the receptor for CD70, CD27, in combination with the TLR3 agonist polyIC, provides some protection despite failing to increase the frequency of interferon gamma-secreting T cells.

Published
2023
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4. 960 Randomized multicenter study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer

Author

Tanios Bekaii-Saab, Todd Bauer, Gina Petroni, Osama Rahma, Rawad Elias, Craig Slingluff, Mathew Katz, Brian Wolpin, Chee-Chee Stucky, Andressa Dias-Costa, Jonathan Nowak, Lenehan Patrick, and Stephanie Dougan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
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5. 546 Results from Phase Ib study of tebentafusp (tebe) in combination with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM)

Author

Mark Middleton, Omid Hamid, Todd Bauer, Jessica Hassel, Friedegund Meier, Paolo Ascierto, John Kirkwood, Alexander Shoushtari, Marlana Orloff, April Salama, Paul Lorigan, Jeff Evans, Chris Holland, Shaad Abdullah, Cornelia Mauch, Ramakrishna Edukulla, and Renee Mundy

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
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6. Supplementary Table from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Author

Jason J. Luke, Jedd D. Wolchok, Taha Merghoub, Cynthia A. Sirard, Diane Piper, Lianna Sifferlen, Phillip Wong, Aliya Holland, Jingjing Qi, Walter Newman, Olivier Rixe, David Bajor, Todd Bauer, Takami Sato, Girish S. Naik, Hong Wang, Roberta Zappasodi, and Diwakar Davar

Abstract

Supplementary Table from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Published
2023

7. Data from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Author

Jason J. Luke, Jedd D. Wolchok, Taha Merghoub, Cynthia A. Sirard, Diane Piper, Lianna Sifferlen, Phillip Wong, Aliya Holland, Jingjing Qi, Walter Newman, Olivier Rixe, David Bajor, Todd Bauer, Takami Sato, Girish S. Naik, Hong Wang, Roberta Zappasodi, and Diwakar Davar

Abstract

Purpose:TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor−related protein (GITR). This open-label, phase I study (TRX518-003) evaluated the safety and efficacy of repeated dose TRX518 monotherapy and in combination with gemcitabine, pembrolizumab, or nivolumab in advanced solid tumors.Patients and Methods:TRX518 monotherapy was dose escalated (Part A) and expanded (Part B) up to 4 mg/kg loading, 1 mg/kg every 3 weeks. Parts C–E included dose-escalation (2 and 4 mg/kg loading followed by 1 mg/kg) and dose-expansion (4 mg/kg loading) phases with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Primary endpoints included incidence of dose-limiting toxicities (DLT), serious adverse events (SAE), and pharmacokinetics. Secondary endpoints were efficacy and pharmacodynamics.Results:A total of 109 patients received TRX518: 43 (Parts A+B), 30 (Part C), 26 (Part D), and 10 (Part E), respectively. A total of 67% of patients in Parts D+E had received prior anti–PD(L)1 or anti–CTLA-4. No DLTs, treatment-related SAEs, and/or grade 4 or 5 AEs were observed with TRX518 monotherapy. In Parts C–E, no DLTs were observed, although TRX518-related SAEs were reported in 3.3% (Part C) and 10.0% (Part E), respectively. Objective response rate was 3.2%, 3.8%, 4%, and 12.5% in Parts A+B, C, D, and E, respectively. TRX518 affected peripheral and intratumoral regulatory T cells (Treg) with different kinetics depending on the combination regimen. Responses with TRX518 monotherapy+anti–PD1 combination were associated with intratumoral Treg reductions and CD8 increases and activation after treatment.Conclusions:TRX518 showed an acceptable safety profile with pharmacodynamic activity. Repeated dose TRX518 monotherapy and in combination resulted in limited clinical responses associated with immune activation.See related commentary by Hernandez-Guerrero and Moreno, p. 3905

Published
2023

8. Supplementary Data from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Author

Jason J. Luke, Jedd D. Wolchok, Taha Merghoub, Cynthia A. Sirard, Diane Piper, Lianna Sifferlen, Phillip Wong, Aliya Holland, Jingjing Qi, Walter Newman, Olivier Rixe, David Bajor, Todd Bauer, Takami Sato, Girish S. Naik, Hong Wang, Roberta Zappasodi, and Diwakar Davar

Abstract

Supplementary Data from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Published
2023

9. Supplementary Figure from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Author

Jason J. Luke, Jedd D. Wolchok, Taha Merghoub, Cynthia A. Sirard, Diane Piper, Lianna Sifferlen, Phillip Wong, Aliya Holland, Jingjing Qi, Walter Newman, Olivier Rixe, David Bajor, Todd Bauer, Takami Sato, Girish S. Naik, Hong Wang, Roberta Zappasodi, and Diwakar Davar

Abstract

Supplementary Figure from Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors

Published
2023

11. Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab or Nivolumab in Patients with Advanced Solid Tumors

Author

Diwakar Davar, Roberta Zappasodi, Hong Wang, Girish S. Naik, Takami Sato, Todd Bauer, David Bajor, Olivier Rixe, Walter Newman, Jingjing Qi, Aliya Holland, Phillip Wong, Lianna Sifferlen, Diane Piper, Cynthia A. Sirard, Taha Merghoub, Jedd D. Wolchok, and Jason J. Luke

Subjects
Cancer Research, Antibodies, Monoclonal, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Deoxycytidine, T-Lymphocytes, Regulatory, Gemcitabine, Article, Nivolumab, Oncology, Cell Line, Tumor, Glucocorticoid-Induced TNFR-Related Protein, Neoplasms, Humans
Abstract

Purpose: TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor−related protein (GITR). This open-label, phase I study (TRX518-003) evaluated the safety and efficacy of repeated dose TRX518 monotherapy and in combination with gemcitabine, pembrolizumab, or nivolumab in advanced solid tumors. Patients and Methods: TRX518 monotherapy was dose escalated (Part A) and expanded (Part B) up to 4 mg/kg loading, 1 mg/kg every 3 weeks. Parts C–E included dose-escalation (2 and 4 mg/kg loading followed by 1 mg/kg) and dose-expansion (4 mg/kg loading) phases with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Primary endpoints included incidence of dose-limiting toxicities (DLT), serious adverse events (SAE), and pharmacokinetics. Secondary endpoints were efficacy and pharmacodynamics. Results: A total of 109 patients received TRX518: 43 (Parts A+B), 30 (Part C), 26 (Part D), and 10 (Part E), respectively. A total of 67% of patients in Parts D+E had received prior anti–PD(L)1 or anti–CTLA-4. No DLTs, treatment-related SAEs, and/or grade 4 or 5 AEs were observed with TRX518 monotherapy. In Parts C–E, no DLTs were observed, although TRX518-related SAEs were reported in 3.3% (Part C) and 10.0% (Part E), respectively. Objective response rate was 3.2%, 3.8%, 4%, and 12.5% in Parts A+B, C, D, and E, respectively. TRX518 affected peripheral and intratumoral regulatory T cells (Treg) with different kinetics depending on the combination regimen. Responses with TRX518 monotherapy+anti–PD1 combination were associated with intratumoral Treg reductions and CD8 increases and activation after treatment. Conclusions: TRX518 showed an acceptable safety profile with pharmacodynamic activity. Repeated dose TRX518 monotherapy and in combination resulted in limited clinical responses associated with immune activation. See related commentary by Hernandez-Guerrero and Moreno, p. 3905

Published
2022

12. First-in-human phase 1/1b study to evaluate sitravatinib in patients with advanced solid tumors

Author

Todd Bauer, Byong Chul Cho, Rebecca Heist, Lyudmila Bazhenova, Theresa Werner, Sanjay Goel, Dong-Wan Kim, Douglas Adkins, Richard D. Carvajal, Ajjai Alva, Keith Eaton, Judy Wang, Yong Liu, Xiaohong Yan, Jamie Christensen, Saskia Neuteboom, Richard Chao, and Shubham Pant

Subjects
Lung Neoplasms, Pyridines, Objective response rate, Rare Diseases, Clinical Research, Carcinoma, Non-Small-Cell Lung, Neoplasms, Tumor Microenvironment, Humans, Pharmacology (medical), Pharmacokinetics, Anilides, Oncology & Carcinogenesis, Non-Small-Cell Lung, Lung, 6.2 Cellular and gene therapies, Cancer, Pharmacology, Carcinoma, Lung Cancer, Sitravatinib, Evaluation of treatments and therapeutic interventions, Pharmacology and Pharmaceutical Sciences, Oncology, Adverse events, 6.1 Pharmaceuticals, Advanced solid tumors
Abstract

Sitravatinib (MGCD516), a spectrum-selective receptor tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MERTK) and split kinase family receptors, has demonstrated preclinical anti-tumor activity and modulation of tumor microenvironment. This first-in-human phase 1/1b study included sitravatinib dose exploration and anti-tumor activity evaluation in selected patients with advanced solid tumors. Primary objectives included assessment of safety, pharmacokinetics and clinical activity of sitravatinib. Secondary objectives included identifying doses for further investigation and exploring molecular markers for patient selection. In phase 1, 32 patients received 10–200 mg, while phase 1b dose expansion comprised 161 patients (150 mg n = 99, 120 mg n = 62). Maximum tolerated dose was determined as 150 mg daily. Dose-limiting toxicity was reported in 4/28 evaluable phase 1 patients (three at 200 mg, one at 80 mg). In phase 1b, 120 mg was defined as the recommended dose due to tolerability. Treatment-related adverse events (TRAEs) were experienced by 174/193 patients (90.2%); grade ≥ 3 TRAEs in 103 patients (53.4%). Most common TRAEs were diarrhea, fatigue, hypertension and nausea; TRAEs led to treatment discontinuation in 26 patients (13.5%) and death in one patient. Sitravatinib was steadily absorbed and declined from plasma with a terminal elimination half-life of 42.1–51.5 h following oral administration. Overall objective response rate was 11.8% in phase 1b, 13.2% in patients with non-small cell lung cancer (NSCLC) and 4.2% in patients with NSCLC with prior checkpoint inhibitor experience. Sitravatinib demonstrated manageable safety and modest clinical activity in solid tumors. NCT02219711 (first posted August 14, 2014).

Published
2022

13. Phase Ib SEASTAR Study: Combining Rucaparib and Sacituzumab Govitecan in Patients With Cancer With or Without Mutations in Homologous Recombination Repair Genes

Author

Timothy A. Yap, Erika Hamilton, Todd Bauer, Ecaterina E. Dumbrava, Rinath Jeselsohn, Aaron Enke, Sabrina Hurley, Kevin K. Lin, Jenn Habeck, Heidi Giordano, and Geoffrey I. Shapiro

Subjects
Cancer Research, Starfish, Immunoconjugates, Indoles, Oncology, Neoplasms, Mutation, Animals, Humans, Recombinational DNA Repair, Camptothecin, Antibodies, Monoclonal, Humanized
Published
2022

14. Abstract CT223: Updated efficacy and safety from the phase 3 CROWN study of first-line lorlatinib vs crizotinib in advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)

Author

Benjamin Solomon, Todd Bauer, Tony Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Mikhail Dvorkin, Jacek Jassem, Froylán López-López, Ross Soo, Anna Polli, Elisa Dall'O, Laura Iadeluca, Francesca Toffalorio, and Enriqueta Felip

Subjects
Cancer Research, Oncology
Abstract

Background: Lorlatinib improved progression-free survival (PFS) and demonstrated intracranial (IC) activity in patients (pts) with untreated advanced ALK+ NSCLC in the interim analysis of the randomized, Phase 3, CROWN study of lorlatinib vs crizotinib. We report updated 36-month follow-up data. Methods: 296 pts with previously untreated advanced ALK+ NSCLC were randomized 1:1 to oral lorlatinib (100 mg QD; n=149) or crizotinib (250 mg BID; n=147), stratified by presence of CNS metastases (mets) and ethnicity. Primary endpoint: PFS by blinded independent central review (BICR). Secondary endpoints included overall survival, PFS by investigator, and objective response (OR), IC-OR, IC time to progression (IC-TTP), duration of response (DR), IC-DR (all by BICR), and safety. Results: At data cutoff (Sep 20, 2021), median duration of follow-up for PFS was 36.7 months for lorlatinib and 29.3 months for crizotinib. Median PFS by BICR was NR (95% CI, NR-NR) for lorlatinib and 9.3 months (95% CI, 7.6-11.1) for crizotinib (HR, 0.27; 95% CI, 0.18-0.39). PFS by investigator results were similar (Table). For pts with brain mets at baseline (n=37 lorlatinib/n=39 crizotinib), the HR for IC-TTP for lorlatinib vs crizotinib was 0.10 (95% CI, 0.04-0.27), and for pts without brain mets (n=112/n=108) was 0.02 (95% CI, 0.002-0.14). OR, IC-OR, DR, and IC-DR were all improved with lorlatinib vs crizotinib (Table). All-cause grade 3-4 adverse events (AEs) and AEs leading to treatment discontinuation were reported in 76% and 7% of pts with lorlatinib and 57% and 10% of pts with crizotinib, respectively. No new safety signals emerged. Conclusions: These updated long-term data from CROWN confirm the efficacy of lorlatinib over crizotinib in pts with treatment-naïve ALK+ NSCLC, with no new safety signals detected, and support the use of lorlatinib in pts with untreated ALK+ NSCLC with and without brain mets. Summary of other efficacy resultsa Clinical trial information: NCT03052608 Funding: Pfizer Inc. ITT population Lorlatinib(n=149) Crizotinib(n=147) % alive without progression at:12 mo (95% CI) 78 (70–84) 38 (29–47) 24 68 (60–75) 22 (14–30) 36 64 (55–71) 19 (12–27) Median PFS by investigator, mo (95% CI) NR (NR–NR) 9.1 (7.4–10.9) HR (95% CI) 0.19 (0.13–0.27) Confirmed OR, n (%) [95% CI] 115 (77) [70–84] 86 (59) [50–67] Median DR,b mo (95% CI) NR (NR–NR) 9.6 (9.0–12.9) Patients with measurable or nonmeasurable brain metastases at baseline (n=37) (n=39) Median PFS, mo (95% CI) NR (18.2–NR) 7.2 (3.7–9.2) HR (95% CI) 0.21 (0.10–0.44) Confirmed IC-OR, n (%) [95% CI] 24 (65) [48–80] 7 (18) [8–34] Complete response, n (%) 22 (60) 5 (13) Median IC-DR,b mo (95% CI) NR (NR–NR) 9.4 (6.0–11.1) Patients without brain metastases at baseline (n=112) (n=108) Median PFS, mo (95% CI) NR (NR–NR) 11.0 (9.0–14.6) HR (95% CI) 0.29 (0.19–0.44) aBy blinded independent central review unless stated otherwise. bIn patients with a confirmed complete or partial response. CI, confidence interval; DR, duration of response; HR, hazard ratio; ITT, intention- to-treat; NR, not reached; IC, intracranial; OR, objective response; PFS, progression-free survival. Citation Format: Benjamin Solomon, Todd Bauer, Tony Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Mikhail Dvorkin, Jacek Jassem, Froylán López-López, Ross Soo, Anna Polli, Elisa Dall'O, Laura Iadeluca, Francesca Toffalorio, Enriqueta Felip. Updated efficacy and safety from the phase 3 CROWN study of first-line lorlatinib vs crizotinib in advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT223.

Published
2022

15. Abstract 478: Extracellular vesicle based multi-omics prediction model for the early detection of pancreatic cancer

Author

Anton Iliuk, Charles P. Hinzman, Partha P. Banerjee, Michael Girgis, Shivani Bansal, Yaoxiang Li, John B. Tyburski, Todd Bauer, Meth Jayatilake, Amrita K. Cheema, and Keith Unger

Subjects
Cancer Research, Oncology, Pancreatic cancer, medicine, Early detection, Multi omics, Extracellular vesicle, Biology, medicine.disease, Cell biology
Abstract

Introduction: Pancreas cancer (PC) is projected to become the third leading cause of cancer deaths in the US, however there is no screening test in routine clinical use. A minimally invasive test for early detection of PC is a critical unmet clinical need. Extracellular vesicles (EVs) shed into the circulation include a diverse array of surface and cargo biomolecules that can be leveraged as biomarkers for the early detection of PC. We hypothesize that systemic molecular characterization of plasma EVs, secreted by latent yet progressing precursor lesions (PL) of the pancreas, may lead to the development of high accuracy classification algorithms for stratification of patients for the early detection of PC. Herein, we developed a liquid biopsy-based PACE assay (Pancreatic Cancer Exosomics) comprised of a multi-omics (proteomics, metabolomics, and lipidomics) biomarker panel. Methods: To develop a functional EV-based multi-omics biomarker panel, we performed metabolomics, lipidomics and proteomics analysis of EVs from high quality pre-surgery, fasting plasma samples obtained from patients with early stage pancreatic cancer (IA, IB and IIA) (N= 60), normal control subjects without cancer (N = 50), patients diagnosed with pancreatitis (benign) (N= 39), and early stage colorectal cancer (N=30) as related disease cohorts. For selection of candidate biomarkers, we randomly divided 3/5th of the sample set as discovery and the remainder 2/5th as the test cohort. To consider the effect of potential correlation for predictors, we applied the elastic net penalty to generalized linear model (ELNET). A 100-fold cross-validation approach was used to determine tuning parameters and calibrate the prediction model in the discovery set. Results: These analyses allowed us to develop a 12 analyte multi-omics panel that could discriminate early stage PC from normal controls (NC) with 98.2% accuracy (Specificity (SP) = 85.2% and Sensitivity (SN) = 71.5%) and 95.4% accuracy (SP = 92.8% and SN = 59.3%) for discovery and validation sets, respectively. A unique aspect of the study design was the inclusion of control cohorts to eliminate non-specific markers. Furthermore, extensive clinical outcome data allowed us to develop multi-analyte predictors of overall survival and progression free survival with high accuracy. Validation of these findings using orthogonal methods is ongoing. Conclusions: In summary, these preliminary data provide strong support for the development of a liquid biopsy-based EV biomarker panel for the early detection of PC. We believe the positive predictive value (PPV) of this panel can be further improved in conjunction with serum CA 19-9 that is in routine clinical use. Citation Format: Yaoxiang Li, Keith Unger, Charles Hinzman, Meth Jayatilake, Anton Iliuk, Shivani Bansal, Michael Girgis, Partha Banerjee, John B. Tyburski, Todd Bauer, Amrita K. Cheema. Extracellular vesicle based multi-omics prediction model for the early detection of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 478.

Published
2021

16. Al0.68Sc0.32N Lamb wave resonators with electromechanical coupling coefficients near 10.28%

Author

Roy H. OlssonIII, Sean Yen, Zichen Tang, Todd Bauer, Giovanni Esteves, Travis Ryan Young, and Michael David Henry

Subjects
Scandium nitride, Resonator, Lamb waves, Materials science, Quality (physics), Physics and Astronomy (miscellaneous), chemistry, Aluminium, Motional resistance, Electromechanical coupling, chemistry.chemical_element, Atomic physics, Piezoelectricity
Abstract

Aluminum scandium nitride (Al1−xScxN/AlScN) (x = 0.32) Lamb wave resonators (LWR) have been fabricated and tested to demonstrate electromechanical coupling coefficients (kt2) in excess of 10%. The resonators exhibited an average kt2 and unloaded quality factor (Qu) of 10.28% and 711, respectively, when calculated from the measured data. Applying the Butterworth Van-Dyke (BVD) model to the measured data enabled the extraction of the resonator's lumped element parameters to calculate the motional quality factor (Qm), which neglects the contributions of the electrical traces. For the best measured resonator response, results from the BVD model showed a Qm of 1184 and a resulting figure-of-merit (FOM = K2 · Qm) of 100. Comparing the response of similar AlScN and AlN resonators shows that the AlScN LWR has a significantly lower motional resistance (Rm), suggesting that AlScN has a strong potential for use in piezoelectric microelectromechanical oscillators.

Published
2021

17. Genetic Markers for Western Corn Rootworm Resistance to Bt Toxin

Author

Thomas L. Clark, Andrew P. Michel, Christopher Todd Bauer, Patrick Hill, Meghan Tuscan, Lex E. Flagel, Barry S. Goldman, Raman Bansal, Graham P. Head, Shilpa Swarup, Ronald Flannagan, Mao Chen, Humphrey Wanjugi, and Matthew Carroll

Subjects
Cry3Bb1, Genetic Markers, Population, Bacillus thuringiensis, Genes, Insect, western corn rootworm, Biology, Investigations, Polymorphism, Single Nucleotide, Insecticide Resistance, Genetics, Animals, education, Molecular Biology, Genetics (clinical), education.field_of_study, Genetically modified maize, Resistance (ecology), business.industry, biology.organism_classification, Biotechnology, Coleoptera, Endotoxins, Western corn rootworm, Agronomy, Genetic marker, Diabrotica virgifera virgifera, PEST analysis, genetic marker, insect resistance, business
Abstract

Western corn rootworm (WCR) is a major maize (Zea mays L.) pest leading to annual economic losses of more than 1 billion dollars in the United States. Transgenic maize expressing insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt) are widely used for the management of WCR. However, cultivation of Bt-expressing maize places intense selection pressure on pest populations to evolve resistance. Instances of resistance to Bt toxins have been reported in WCR. Developing genetic markers for resistance will help in characterizing the extent of existing issues, predicting where future field failures may occur, improving insect resistance management strategies, and in designing and sustainably implementing forthcoming WCR control products. Here, we discover and validate genetic markers in WCR that are associated with resistance to the Cry3Bb1 Bt toxin. A field-derived WCR population known to be resistant to the Cry3Bb1 Bt toxin was used to generate a genetic map and to identify a genomic region associated with Cry3Bb1 resistance. Our results indicate that resistance is inherited in a nearly recessive manner and associated with a single autosomal linkage group. Markers tightly linked with resistance were validated using WCR populations collected from Cry3Bb1 maize fields showing significant WCR damage from across the US Corn Belt. Two markers were found to be correlated with both diet (R2 = 0.14) and plant (R2 = 0.23) bioassays for resistance. These results will assist in assessing resistance risk for different WCR populations, and can be used to improve insect resistance management strategies.

Published
2015

18. Physical Unclonable Functions: A Primer

Author

Jason Hamlet and Todd Bauer

Subjects
Authentication, Computer Networks and Communications, Computer science, business.industry, Physical unclonable function, Computer security, computer.software_genre, ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS, Embedded system, Supply chain security, Electrical and Electronic Engineering, business, Law, computer, Randomness
Abstract

Physical unclonable functions (PUFs) make use of the measurable intrinsic randomness of physical systems to establish signatures for those systems. PUFs provide a means to generate unique keys that don't need to be stored in nonvolatile memory, and they offer exciting opportunities for new authentication and supply chain security technologies.

Published
2014

19. Frequency Trimming of Aluminum Nitride Microresonators Using Rapid Thermal Annealing

Author

Travis Ryan Young, Michael David Henry, Roy H. Olsson, Janet Nguyen, and Todd Bauer

Subjects
Materials science, Fabrication, business.industry, Annealing (metallurgy), Mechanical Engineering, Temperature cycling, Nitride, Temperature measurement, Resonator, Electronic engineering, Optoelectronics, Wafer, Electrical and Electronic Engineering, Thin film, business
Abstract

To transition aluminum nitride (AlN) microresonator filters into a manufacturable technology, accurate control of the resonator frequency across a wafer is required. This paper describes a postfabrication rapid thermal anneal approach to trim resonator frequency over 27 000 ppm with an accuracy of 500 ppm. Measurements made on 22.4 MHz resonators indicate that the effect of annealing on the resonators saturates in 5 min and upshift the resonator frequency super linearly with temperature. We replicate the frequency trimming effect on hermetically sealed wafer level packaged devices to reduce the across-wafer frequency distribution from 22 000 to 4000 ppm. We confirm that this postannealing technique is permanent by temperature cycling the resonators from 50 $^{\circ}{\rm C}$ to 125 $^{\circ}{\rm C}$ . This technique provides a method to trim AlN microresonator frequency overcoming effects such as thin film variations, which are inherent to microsystems fabrication. $\hfill{[2013\hbox{--}0091]}$

Published
2014

20. A high electromechanical coupling coefficient SH0 Lamb wave lithium niobate micromechanical resonator and a method for fabrication

Author

Blythe Clark, Sara Jensen Homeijer, Roy H. Olsson, Khalid Hattar, Todd Bauer, Michael S. Baker, Janet Nguyen, Matt Eichenfield, Darren W. Branch, Michael Wiwi, and Thomas A. Friedmann

Subjects
Electromechanical coupling coefficient, business.industry, Wafer bonding, Lithium niobate, Metals and Alloys, Condensed Matter Physics, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Resonator, chemistry.chemical_compound, Lamb waves, Optics, chemistry, Optoelectronics, Figure of merit, Wafer, Electrical and Electronic Engineering, business, Instrumentation, Coupling coefficient of resonators
Abstract

We present a high coupling coefficient, k eff 2 , micromechanical resonator based on the propagation of SH0 Lamb waves in thin, suspended plates of single crystal X-cut lithium niobate (LiNbO 3 ). The thin plates are fabricated using ion implantation of He to create a damaged layer of LiNbO 3 below the wafer surface. This damaged layer is selectively wet etched in a hydrofluoric (HF) acid based chemistry to form thin, suspended plates of LiNbO 3 without the wafer bonding, layer fracturing and chemical mechanical polishing in previously reported LiNbO 3 microfabrication approaches. The highest coupling coefficient is found for resonators with acoustic propagation rotated 170° from the y -axis, where a fundamental mode SH0 Lamb wave resonator with a plate width of 20 μm and a corresponding resonant frequency of 101 MHz achieves a k eff 2 of 12.4%, a quality factor of 1300 and a resonator figure of merit ( M ) of 185. The k eff 2 and M are among the highest reported for micromechanical resonators.

Published
2014

21. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

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

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

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

Published
2016

22. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, Julie Lorent, Kristina Witt, Laia Masvidal Sanz, Shuo Liang, Shannon Murray, Ola Larsson, Rolf Kiessling, Yumeng Mao, John-William Sidhom, Catherine A. Bessell, Jonathan Havel, Jonathan Schneck, Timothy A. Chan, Eliot Sachsenmeier, David Woods, Anders Berglund, Rupal Ramakrishnan, Andressa Sodre, Jeffrey Weber, Roberta Zappasodi, Yanyun Li, Jingjing Qi, Philip Wong, Cynthia Sirard, Michael Postow, Walter Newman, Henry Koon, Vamsidhar Velcheti, Margaret K. Callahan, Jedd D. Wolchok, Taha Merghoub, Lawrence G. Lum, Minsig Choi, Archana Thakur, Abhinav Deol, Gregory Dyson, Anthony Shields, Cara Haymaker, Marc Uemura, Ravi Murthy, Marihella James, Daqing Wang, Julie Brevard, Catherine Monaghan, Suzanne Swann, James Geib, Mark Cornfeld, Srinivas Chunduru, Sudhir Agrawal, Cassian Yee, Jennifer Wargo, Sapna P. Patel, Rodabe Amaria, Hussein Tawbi, Isabella Glitza, Scott Woodman, Wen-Jen Hwu, Michael A. Davies, Patrick Hwu, Willem W. Overwijk, Chantale Bernatchez, Adi Diab, Erminia Massarelli, Neil H. Segal, Vincent Ribrag, Ignacio Melero, Tara C. Gangadhar, Walter Urba, Dirk Schadendorf, Robert L. Ferris, Roch Houot, Franck Morschhauser, Theodore Logan, Jason J. Luke, William Sharfman, Fabrice Barlesi, Patrick A. Ott, Laura Mansi, Shivaani Kummar, Gilles Salles, Cecilia Carpio, Roland Meier, Suba Krishnan, Dan McDonald, Matthew Maurer, Xuemin Gu, Jaclyn Neely, Satyendra Suryawanshi, Ronald Levy, Nikhil Khushalani, Jennifer Wu, Jinyu Zhang, Fahmin Basher, Mark Rubinstein, Mark Bucsek, Guanxi Qiao, Cameron MacDonald, Bonnie Hylander, Elizabeth Repasky, Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Kyle Toth, Megan Meek, Elizabeth Garrett-Mayer, Michael Nishimura, Chrystal Paulos, Craig Beeson, Xuezhong Yu, Shikhar Mehrotra, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nicole Scharping, Ashley V. Menk, Rebecca Moreci, Ryan Whetstone, Rebekah Dadey, Simon Watkins, Robert Ferris, Greg M. Delgoffe, Jonathan Peled, Sean Devlin, Anna Staffas, Melissa Lumish, Kori Porosnicu Rodriguez, Katya Ahr, Miguel Perales, Sergio Giralt, Ying Taur, Eric Pamer, Marcel R. M. van den Brink, Robert Jenq, Nicola Annels, Hardev Pandha, Guy Simpson, Hugh Mostafid, Kevin Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Au, Roberta Karpathy, Darren Shafren, Jacob Ricca, Dmitriy Zamarin, Luciana Batista, Florence Marliot, Angela Vasaturo, Sabrina Carpentier, Cécile Poggionovo, Véronique Frayssinet, Jacques Fieschi, Marc Van den Eynde, Franck Pagès, Jérôme Galon, Fabienne Hermitte, Sean G. Smith, Khue Nguyen, Sruthi Ravindranathan, Bhanu Koppolu, David Zaharoff, Gustavo Schvartsman, Roland Bassett, Jennifer L. McQuade, Lauren E. Haydu, Douglas Kline, Xiufen Chen, Dominick Fosco, Justin Kline, Abigail Overacre, Maria Chikina, Erin Brunazzi, Gulidanna Shayan, William Horne, Jay Kolls, Tullia C. Bruno, Creg Workman, Dario Vignali, Prasad S. Adusumilli, Ephraim A Ansa-Addo, Zihai Li, Andrew Gerry, Joseph P. Sanderson, Karen Howe, Roslin Docta, Qian Gao, Eleanor A. L. Bagg, Nicholas Tribble, Miguel Maroto, Gareth Betts, Natalie Bath, Luca Melchiori, Daniel E. Lowther, Indu Ramachandran, Gabor Kari, Samik Basu, Gwendolyn Binder-Scholl, Karen Chagin, Lini Pandite, Tom Holdich, Rafael Amado, Hua Zhang, John Glod, Donna Bernstein, Bent Jakobsen, Crystal Mackall, Ryan Wong, Jonathan D. Silk, Katherine Adams, Garth Hamilton, Alan D. Bennett, Sara Brett, Junping Jing, Adriano Quattrini, Manoj Saini, Guy Wiedermann, Joanna Brewer, MyLinh Duong, An Lu, Peter Chang, Aruna Mahendravada, Nicholas Shinners, Kevin Slawin, David M. Spencer, Aaron E. Foster, J. Henri Bayle, Cristina Bergamaschi, Sinnie Sin Man Ng, Bethany Nagy, Shawn Jensen, Xintao Hu, Candido Alicea, Bernard Fox, Barbara Felber, George Pavlakis, Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Luis Cortina, Daniel J. Powell, Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Garry Dolton, Barbara Szomolay, Sascha Ott, Rikke Lyngaa, Sine Reker Hadrup, Andrew Kelvin Sewell, Inge Marie Svane, Aaron Fan, Takumi Kumai, Esteban Celis, Ian Frank, Amanda Stramer, Michelle A. Blaskovich, Seth Wardell, Maria Fardis, James Bender, Michael T. Lotze, Stephanie L. Goff, Nikolaos Zacharakis, Yasmine Assadipour, Todd D. Prickett, Jared J. Gartner, Robert Somerville, Mary Black, Hui Xu, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John Wunderlich, Paul F. Robbins, Steven Rosenberg, Steven A. Feldman, Kasia Trebska-McGowan, Parisa Malekzadeh, Eden Payabyab, Richard Sherry, Aishwarya Gokuldass, Charlene Kopits, Brian Rabinovich, Daniel S. Green, Olena Kamenyeva, Kathryn C. Zoon, Christina M. Annunziata, Joanne Hammill, Christopher Helsen, Craig Aarts, Jonathan Bramson, Yui Harada, Yoshikazu Yonemitsu, Kenneth Mwawasi, Galina Denisova, Rajanish Giri, Benjamin Jin, Tracy Campbell, Lindsey M. Draper, Sanja Stevanovic, Zhiya Yu, Bianca Weissbrich, Nicholas P. Restifo, Cornelia L. Trimble, Christian S. Hinrichs, Kwong Tsang, Massimo Fantini, James W. Hodge, Rika Fujii, Ingrid Fernando, Caroline Jochems, Christopher Heery, James Gulley, Patrick Soon-Shiong, Jeffrey Schlom, Weiqing Jing, Jill Gershan, Grace Blitzer, James Weber, Laura McOlash, Bryon D. Johnson, Simin Kiany, Huang Gangxiong, Eugenie S. Kleinerman, Michael Klichinsky, Marco Ruella, Olga Shestova, Saad Kenderian, Miriam Kim, John Scholler, Carl H. June, Saar Gill, Duane Moogk, Shi Zhong, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Cheng Zhu, Navin Varadarajan, Alan Frey, Michelle Krogsgaard, Daniel Landi, Kristen Fousek, Malini Mukherjee, Ankita Shree, Sujith Joseph, Kevin Bielamowicz, Tiara Byrd, Nabil Ahmed, Meenakshi Hegde, Sylvia Lee, David Byrd, John Thompson, Shailender Bhatia, Scott Tykodi, Judy Delismon, Liz Chu, Siddiq Abdul-Alim, Arpy Ohanian, Anna Marie DeVito, Stanley Riddell, Kim Margolin, Isabelle Magalhaes, Jonas Mattsson, Michael Uhlin, Satoshi Nemoto, Patricio Pérez Villarroel, Ryosuke Nakagawa, James J. Mule, Adam W. Mailloux, Melinda Mata, Phuong Nguyen, Claudia Gerken, Christopher DeRenzo, Stephen Gottschalk, Mélissa Mathieu, Sandy Pelletier, John Stagg, Simon Turcotte, Nicholas Minutolo, Prannda Sharma, Andrew Tsourkas, Nadine Mockel-Tenbrinck, Daniela Mauer, Katharina Drechsel, Carola Barth, Katharina Freese, Ulrike Kolrep, Silke Schult, Mario Assenmacher, Andrew Kaiser, John Mullinax, MacLean Hall, Julie Le, Krithika Kodumudi, Erica Royster, Allison Richards, Ricardo Gonzalez, Amod Sarnaik, Shari Pilon-Thomas, Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Niels Junker, Charlotte Rivas, Robin Parihar, Cliona M. Rooney, Haiying Qin, Sang Nguyen, Paul Su, Chad Burk, Brynn Duncan, Bong-Hyun Kim, M. Eric Kohler, Terry Fry, Arjun A. Rao, Noam Teyssier, Jacob Pfeil, Nikolaos Sgourakis, Sofie Salama, David Haussler, Sarah A. Richman, Selene Nunez-Cruz, Zack Gershenson, Zissimos Mourelatos, David Barrett, Stephan Grupp, Michael Milone, Alba Rodriguez-Garcia, Matthew K. Robinson, Gregory P. Adams, João Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascón, Suvi Parviainen, Marjukka Antilla, Akseli Hemminki, Jyothi Sethuraman, Laurelis Santiago, Jie Qing Chen, Zhimin Dai, Huizi Sha, Shu Su, Naiqing Ding, Baorui Liu, Anna Pasetto, Sarah R. Helman, Steven A. Rosenberg, Melissa Burgess, Hui Zhang, Tien Lee, Hans Klingemann, Paul Nghiem, John M. Kirkwood, John M. Rossi, Marika Sherman, Allen Xue, Yueh-wei Shen, Lynn Navale, James N. Kochenderfer, Adrian Bot, Anandaraman Veerapathran, Doris Wiener, Edmund K. Waller, Jian-Ming Li, Christopher Petersen, Bruce R. Blazar, Jingxia Li, Cynthia R. Giver, Ziming Wang, Steven K. Grossenbacher, Ian Sturgill, Robert J. Canter, William J. Murphy, Congcong Zhang, Michael C. Burger, Lukas Jennewein, Anja Waldmann, Michel Mittelbronn, Torsten Tonn, Joachim P. Steinbach, Winfried S. Wels, Jason B. Williams, Yuanyuan Zha, Thomas F. Gajewski, LaTerrica C. Williams, Giedre Krenciute, Mamta Kalra, Chrystal Louis, Gang Xin, David Schauder, Aimin Jiang, Nikhil Joshi, Weiguo Cui, Xue Zeng, Zeguo Zhao, Mohamad Hamieh, Justin Eyquem, Gertrude Gunset, Neil Bander, Michel Sadelain, David Askmyr, Milad Abolhalaj, Kristina Lundberg, Lennart Greiff, Malin Lindstedt, Helen K. Angell, Kyoung-Mee Kim, Seung-Tae Kim, Sung Kim, Alan D. Sharpe, Julia Ogden, Anna Davenport, Darren R. Hodgson, Carl Barrett, Jeeyun Lee, Elaine Kilgour, Jodi Hanson, Richard Caspell, Alexey Karulin, Paul Lehmann, Tameem Ansari, Annemarie Schiller, Srividya Sundararaman, Diana Roen, Mark Ayers, Diane Levitan, Gladys Arreaza, Fang Liu, Robin Mogg, Yung-Jue Bang, Bert O’Neil, Razvan Cristescu, Philip Friedlander, Karl Wassman, Chrisann Kyi, William Oh, Nina Bhardwaj, Svetlana Bornschlegl, Michael P. Gustafson, Dennis A. Gastineau, Ian F. Parney, Allan B. Dietz, Daniel Carvajal-Hausdorf, Nikita Mani, Kurt Schalper, David Rimm, Serena Chang, John Kurland, Christoph Matthias Ahlers, Maria Jure-Kunkel, Lewis Cohen, Holden Maecker, Holbrook Kohrt, Shuming Chen, George Crabill, Theresa Pritchard, Tracee McMiller, Drew Pardoll, Fan Pan, Suzanne Topalian, Patrick Danaher, Sarah Warren, Lucas Dennis, Andrew M. White, Leonard D’Amico, Melissa Geller, Mary L. Disis, Joseph Beechem, Kunle Odunsi, Steven Fling, Roshanak Derakhshandeh, Tonya J. Webb, Sigrid Dubois, Kevin Conlon, Bonita Bryant, Jennifer Hsu, Nancy Beltran, Jürgen Müller, Thomas Waldmann, Rebekka Duhen, Thomas Duhen, Lucas Thompson, Ryan Montler, Andrew Weinberg, Max Kates, Brandon Early, Erik Yusko, Taylor H. Schreiber, Trinity J. Bivalacqua, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R. Kaufman, Andrew Albright, Jonathan Cheng, S. Peter Kang, Veena Shankaran, Sarina A. Piha-Paul, Jennifer Yearley, Tanguy Seiwert, Antoni Ribas, Terrill K. McClanahan, Xinwei Sher, Xiao Qiao Liu, Andrew Joe, Elizabeth Plimack, Alex Forrest-Hay, Cheryl A. Guyre, Kohei Narumiya, Marc Delcommenne, Heather A. Hirsch, Amit Deshpande, Jason Reeves, Jenny Shu, Tong Zi, Jennifer Michaelson, Debbie Law, Elizabeth Trehu, Sriram Sathyanaryanan, Brendan P. Hodkinson, Natalie A. Hutnick, Michael E. Schaffer, Michael Gormley, Tyler Hulett, Carmen Ballesteros-Merino, Christopher Dubay, Michael Afentoulis, Ashok Reddy, Larry David, Kumar Jayant, Swati Agrawal, Rajendra Agrawal, Ghayathri Jeyakumar, Seongho Kim, Heejin Kim, Cynthia Silski, Stacey Suisham, Elisabeth Heath, Ulka Vaishampayan, Natalie Vandeven, Natasja Nielsen Viller, Alison O’Connor, Hui Chen, Bolette Bossen, Eric Sievers, Robert Uger, Lisa Johnson, Hsiang-Fong Kao, Chin-Fu Hsiao, Shu-Chuan Lai, Chun-Wei Wang, Jenq-Yuh Ko, Pei-Jen Lou, Tsai-Jan Lee, Tsang-Wu Liu, Ruey-Long Hong, Staci J. Kearney, Joshua C. Black, Benjamin J. Landis, Sally Koegler, Brooke Hirsch, Roberto Gianani, Jeffrey Kim, Ming-Xiao He, Bingqing Zhang, Nan Su, Yuling Luo, Xiao-Jun Ma, Emily Park, Dae Won Kim, Domenico Copploa, Nishi Kothari, Young doo Chang, Richard Kim, Namyong Kim, Melvin Lye, Ee Wan, Hanna A. Knaus, Sofia Berglund, Hubert Hackl, Judith E. Karp, Ivana Gojo, Leo Luznik, Henoch S. Hong, Sven D. Koch, Birgit Scheel, Ulrike Gnad-Vogt, Karl-Josef Kallen, Volker Wiegand, Linus Backert, Oliver Kohlbacher, Ingmar Hoerr, Mariola Fotin-Mleczek, James M. Billingsley, Yoshinobu Koguchi, Valerie Conrad, William Miller, Iliana Gonzalez, Tomasz Poplonski, Tanisha Meeuwsen, Ana Howells-Ferreira, Rogan Rattray, Mary Campbell, Carlo Bifulco, Keith Bahjat, Brendan Curti, E-K Vetsika, G. Kallergi, Despoina Aggouraki, Z. Lyristi, P. Katsarlinos, Filippos Koinis, V. Georgoulias, Athanasios Kotsakis, Nathan T. Martin, Famke Aeffner, Logan Cerkovnik, Luke Pratte, Rebecca Kim, Joseph Krueger, Amaia Martínez-Usatorre, Camilla Jandus, Alena Donda, Laura Carretero-Iglesia, Daniel E. Speiser, Dietmar Zehn, Nathalie Rufer, Pedro Romero, Anshuman Panda, Janice Mehnert, Kim M. Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Levi Sokol, Mark Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann Silk, Nancy Chan, Melissa Frankel, Michael Kane, Jyoti Malhotra, Joseph Aisner, Howard L. Kaufman, Siraj Ali, Jeffrey Ross, Eileen White, Gyan Bhanot, Shridar Ganesan, Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Antigoni Morou, Daniel Kaufmann, Moishe Liberman, Igor Jurisica, Anne-Marie Mes-Masson, Kamel Hamzaoui, Rejean Lapointe, Ann Mongan, Yuan-Chieh Ku, Warren Tom, Yongming Sun, Alex Pankov, Tim Looney, Janice Au-Young, Fiona Hyland, Jeff Conroy, Carl Morrison, Sean Glenn, Blake Burgher, He Ji, Mark Gardner, Angela R. Omilian, Wiam Bshara, Omilian Angela, Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Lieping Chen, Timothy N. Bullock, Craig L. Slingluff, John T. Loffredo, Raja Vuyyuru, Sophie Beyer, Vanessa M. Spires, Maxine Fox, Jon M. Ehrmann, Katrina A. Taylor, Alan J. Korman, Robert F. Graziano, David Page, Katherine Sanchez, Maritza Martel, Mariana Petaccia De Macedo, Yong Qin, Alex Reuben, Christine Spencer, Michele Guindani, Adriana Racolta, Brian Kelly, Tobin Jones, Nathan Polaske, Noah Theiss, Mark Robida, Jeffrey Meridew, Iva Habensus, Liping Zhang, Lidija Pestic-Dragovich, Lei Tang, Ryan J. Sullivan, Thomas Olencki, Thomas Hutson, Joanna Roder, Shauna Blackmon, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Jeffrey Sosman, David F. McDermott, Harriet Kluger, Ruth Halaban, Mario Snzol, Senait Asmellash, Arni Steingrimsson, Chichung Wang, Kristin Roman, Amanda Clement, Sean Downing, Clifford Hoyt, Nathalie Harder, Guenter Schmidt, Ralf Schoenmeyer, Nicolas Brieu, Mehmet Yigitsoy, Gabriele Madonna, Gerardo Botti, Antonio Grimaldi, Paolo A. Ascierto, Ralf Huss, Maria Athelogou, Harald Hessel, Alexander Buchner, Christian Stief, Gerd Binnig, Thomas Kirchner, Shankar Sellappan, Sheeno Thyparambil, Sarit Schwartz, Fabiola Cecchi, Andrew Nguyen, Charles Vaske, Todd Hembrough, Jan Spacek, Michal Vocka, Eva Zavadova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Nicole Francis, Rau T. Tilman, Arndt Hartmann, Irena Netikova, Julia Stump, Amanda Tufman, Frank Berger, Michael Neuberger, Rudolf Hatz, Michael Lindner, Rachel E. Sanborn, John Handy, Rudolf M. Huber, Hauke Winter, Simone Reu, Cheng Sun, Weihua Xiao, Zhigang Tian, Kshitij Arora, Niyati Desai, Anupriya Kulkarni, Mihir Rajurkar, Miguel Rivera, Vikram Deshpande, David Ting, Katy Tsai, Adi Nosrati, Simone Goldinger, Omid Hamid, Alain Algazi, Paul Tumeh, Jimmy Hwang, Jacqueline Liu, Lawrence Chen, Reinhard Dummer, Michael Rosenblum, Adil Daud, Tsu-Shuen Tsao, Julia Ashworth-Sharpe, Donald Johnson, Srabani Bhaumik, Christopher Bieniarz, Joseph Couto, Michael Farrell, Mahsa Ghaffari, Antony Hubbard, Jerome Kosmeder, Cleo Lee, Erin Marner, Diana Uribe, Hongjun Zhang, Jian Zhang, Wenjun Zhang, Yifei Zhu, Larry Morrison, Takahiro Tsujikawa, Rohan N. Borkar, Vahid Azimi, Sushil Kumar, Guillaume Thibault, Motomi Mori, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Paul W. Flint, Lisa M. Coussens, Lisa Villabona, Giuseppe V. Masucci, Gary Geiss, Brian Birditt, Qian Mei, Alan Huang, Maribeth A. Eagan, Eduardo Ignacio, Nathan Elliott, Dwayne Dunaway, Jaemyeong Jung, Chris Merritt, Isaac Sprague, Philippa Webster, Yan Liang, Jessica Wenthe, Gunilla Enblad, Hannah Karlsson, Magnus Essand, Barbara Savoldo, Gianpietro Dotti, Martin Höglund, Malcolm K. Brenner, Hans Hagberg, Angelica Loskog, Matthew J. Bernett, Gregory L. Moore, Michael Hedvat, Christine Bonzon, Seung Chu, Rumana Rashid, Kendra N. Avery, Umesh Muchhal, John Desjarlais, Matthew Kraman, Katarzyna Kmiecik, Natalie Allen, Mustapha Faroudi, Carlo Zimarino, Mateusz Wydro, Jacqueline Doody, Sreesha P. Srinivasa, Nagaraja Govindappa, Praveen Reddy, Aparajita Dubey, Sankar Periyasamy, Madhukara Adekandi, Chaitali Dey, Mary Joy, Pieter Fokko van Loo, Henrike Veninga, Setareh Shamsili, Mark Throsby, Harry Dolstra, Lex Bakker, Ajjai Alva, Juergen Gschwendt, Yohann Loriot, Joaquim Bellmunt, Dai Feng, Christian Poehlein, Thomas Powles, Emmanuel S. Antonarakis, Charles G. Drake, Haiyan Wu, Johann De Bono, Rajat Bannerji, John Byrd, Gareth Gregory, Stephen Opat, Jake Shortt, Andrew J. Yee, Noopur Raje, Seth Thompson, Arun Balakumaran, Shaji Kumar, Brian I. Rini, Toni K. Choueiri, Mariangela Mariani, Laurence Albiges, John B. Haanen, James Larkin, Manuela Schmidinger, Domenico Magazzù, Alessandra di Pietro, Robert J. Motzer, Troels Holz Borch, Per Kongsted, Magnus Pedersen, Özcan Met, Karim Boudadi, Hao Wang, James Vasselli, Jan E. Baughman, Jon Wigginton, Rehab Abdallah, Ashley Ross, Jiwon Park, Steven Grossenbacher, Jesus I. Luna, Sita Withers, William Culp, Mingyi Chen, Arta Monjazeb, Michael S. Kent, Smita Chandran, David Danforth, James Yang, Christopher Klebanoff, Stephanie Goff, Biman Paria, Arvind Sabesan, Abhishek Srivastava, Udai Kammula, Jon Richards, Mark Faries, Robert H. I. Andtbacka, Luis A. Diaz, Dung T. Le, Takayuki Yoshino, Thierry André, Johanna Bendell, Minori Koshiji, Yayan Zhang, S Peter Kang, Bao Lam, Dirk Jäger, Todd M. Bauer, Judy S. Wang, Jean K. Lee, Gulam A. Manji, Ragini Kudchadkar, John S. Kauh, Shande Tang, Naomi Laing, Gerald Falchook, Edward B. Garon, Balazs Halmos, Hui Rina, Natasha Leighl, Sung Sook Lee, William Walsh, Konstanin Dragnev, Bilal Piperdi, Luis Paz-Ares Rodriguez, Nabeegha Shinwari, Ziewn Wei, Mary L Maas, Michael Deeds, Adam Armstrong, Tim Peterson, Sue Steinmetz, Thomas Herzog, Floor J. Backes, Larry Copeland, Maria Del Pilar Estevez Diz, Thomas W. Hare, Warner Huh, Byoung-Gie Kim, Kathleen M. Moore, Ana Oaknin, William Small, Krishnansu S. Tewari, Bradley J. Monk, Ashish M. Kamat, Kijoeng Nam, Maria De Santis, Robert Dreicer, Noah M. Hahn, Rodolfo Perini, Arlene Siefker-Radtke, Guru Sonpavde, Ronald de Wit, J. Alfred Witjes, Stephen Keefe, Dean Bajorin, Philippe Armand, John Kuruvilla, Craig Moskowitz, Mehdi Hamadani, Pier Luigi Zinzani, Sabine Chlosta, Nancy Bartlett, Rachel Sabado, Yvonne Saenger, Loging William, Michael Joseph Donovan, Erlinda Sacris, John Mandeli, Andres M. Salazar, John Powderly, Joshua Brody, John Nemunaitis, Leisha Emens, Amita Patnaik, Ian McCaffery, Richard Miller, Ginna Laport, Andrew L. Coveler, David C. Smith, Juneko E. Grilley-Olson, Sanjay Goel, Shyra J. Gardai, Che-Leung Law, Gary Means, Thomas Manley, Kristen A. Marrone, Gary Rosner, Valsamo Anagnostou, Joanne Riemer, Jessica Wakefield, Cynthia Zanhow, Stephen Baylin, Barbara Gitlitz, Julie Brahmer, Sabina Signoretti, Wenting Li, Charles Schloss, Jean-Marie Michot, Wei Ding, Beth Christian, Patricia Marinello, Margaret Shipp, Yana G. Najjar, null Lin, Lisa H. Butterfield, Ahmad A. Tarhini, Diwakar Davar, Hassane Zarour, Elizabeth Rush, Cindy Sander, Siqing Fu, Todd Bauer, Chris Molineaux, Mark K. Bennett, Keith W. Orford, Kyriakos P. Papadopoulos, Sukhmani K. Padda, Sumit A. Shah, A Dimitrios Colevas, Sujata Narayanan, George A. Fisher, Dana Supan, Heather A. Wakelee, Rhonda Aoki, Mark D. Pegram, Victor M. Villalobos, Jie Liu, Chris H. Takimoto, Mark Chao, Jens-Peter Volkmer, Ravindra Majeti, Irving L. Weissman, Branimir I. Sikic, Wendy Yu, Alison Conlin, Janet Ruzich, Stacy Lewis, Anupama Acheson, Kathleen Kemmer, Kelly Perlewitz, Nicole M. Moxon, Staci Mellinger, Heather McArthur, Trine Juhler-Nøttrup, Jayesh Desai, Ben Markman, Shahneen Sandhu, Hui Gan, Michael L. Friedlander, Ben Tran, Tarek Meniawy, Joanne Lundy, Duncan Colyer, Malaka Ameratunga, Christie Norris, Jason Yang, Kang Li, Lai Wang, Lusong Luo, Zhen Qin, Song Mu, Xuemei Tan, James Song, Michael Millward, Matthew H. G. Katz, Todd W. Bauer, Gauri R. Varadhachary, Nicolas Acquavella, Nipun Merchant, Gina Petroni, Osama E. Rahma, Mei Chen, Yang Song, Markus Puhlmann, Arun Khattri, Ryan Brisson, Christopher Harvey, Jatin Shah, Maria Victoria Mateos, Morio Matsumoto, Hilary Blacklock, Albert Oriol Rocafiguera, Hartmut Goldschmidt, Shinsuke Iida, Dina Ben Yehuda, Enrique Ocio, Paula Rodríguez-Otero, Sundar Jagannath, Sagar Lonial, Uma Kher, Jesus San-Miguel, Moacyr Ribeiro de Oliveira, Habte Yimer, Robert Rifkin, Fredrik Schjesvold, Razi Ghori, Anna Spreafico, Victor Lee, Roger K. C. Ngan, Ka Fai To, Myung Ju Ahn, Quan Sing Ng, Jin-Ching Lin, Ramona F. Swaby, Christine Gause, Sanatan Saraf, Anthony T. C. Chan, Elaine Lam, Nizar M. Tannir, Funda Meric-Bernstam, Matt Gross, Andy MacKinnon, Sam Whiting, Martin Voss, Evan Y. Yu, Mark R. Albertini, Erik A. Ranheim, Jacquelyn A. Hank, Cindy Zuleger, Thomas McFarland, Jennifer Collins, Erin Clements, Sharon Weber, Tracey Weigel, Heather Neuman, Greg Hartig, David Mahvi, MaryBeth Henry, Jacek Gan, Richard Yang, Lakeesha Carmichael, KyungMann Kim, Stephen D. Gillies, Paul M. Sondel, Vivek Subbiah, Lori Noffsinger, Kyle Hendricks, Marnix Bosch, Jay M. Lee, Mi-Heon Lee, Jonathan W. Goldman, Felicita E. Baratelli, Dorthe Schaue, Gerald Wang, Frances Rosen, Jane Yanagawa, Tonya C. Walser, Ying Q. Lin, Sharon Adams, Franco M. Marincola, Paul C. Tumeh, Fereidoun Abtin, Robert Suh, Karen Reckamp, William D. Wallace, Gang Zeng, David A. Elashoff, Sherven Sharma, Steven M. Dubinett, Anna C. Pavlick, Brian Gastman, Brent Hanks, Tibor Keler, Tom Davis, Laura A. Vitale, Elad Sharon, Chihiro Morishima, Martin Cheever, Christopher R. Heery, Joseph W. Kim, Elizabeth Lamping, Jennifer Marte, Sheri McMahon, Lisa Cordes, Farhad Fakhrejahani, Ravi Madan, Rachel Salazar, Maggie Zhang, Christoph Helwig, James L Gulley, Roger Li, John Amrhein, Zvi Cohen, Monique Champagne, Ashish Kamat, M. Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Manel Esteller, Juan Sandoval, Susannah D. Barbee, David I. Bellovin, John C. Timmer, Nebiyu Wondyfraw, Susan Johnson, Johanna Park, Amanda Chen, Mikayel Mkrtichyan, Amir S. Razai, Kyle S. Jones, Chelsie Y. Hata, Denise Gonzalez, Quinn Deveraux, Brendan P. Eckelman, Luis Borges, Rukmini Bhardwaj, Raj K. Puri, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Todd Bartkowiak, Ashvin Jaiswal, Casey Ager, Midan Ai, Pratha Budhani, Renee Chin, David Hong, Michael Curran, William D. Hastings, Maria Pinzon-Ortiz, Masato Murakami, Jason R. Dobson, David Quinn, Joel P. Wagner, Xianhui Rong, Pamela Shaw, Ernesta Dammassa, Wei Guan, Glenn Dranoff, Alexander Cao, Ross B. Fulton, Steven Leonardo, Kathryn Fraser, Takashi O. Kangas, Nadine Ottoson, Nandita Bose, Richard D. Huhn, Jeremy Graff, Jamie Lowe, Keith Gorden, Mark Uhlik, Thomas O’Neill, Jenifer Widger, Andrea Crocker, Li-Zhen He, Jeffrey Weidlick, Karuna Sundarapandiyan, Venky Ramakrishna, James Storey, Lawrence J. Thomas, Joel Goldstein, Henry C. Marsh, Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-jie Jey Cheng, Marlon J. Hinner, Rachida-Siham Bel Aiba, Corinna Schlosser, Thomas Jaquin, Andrea Allersdorfer, Sven Berger, Alexander Wiedenmann, Gabriele Matschiner, Julia Schüler, Ulrich Moebius, Christine Rothe, Olwill A. Shane, Brendan Horton, Stefani Spranger, Dayson Moreira, Tomasz Adamus, Xingli Zhao, Piotr Swiderski, Sumanta Pal, Marcin Kortylewski, Alyssa Kosmides, Kevin Necochea, Kathleen M. Mahoney, Sachet A. Shukla, Nikolaos Patsoukis, Apoorvi Chaudhri, Hung Pham, Ping Hua, Xia Bu, Baogong Zhu, Nir Hacohen, Catherine J. Wu, Edward Fritsch, Vassiliki A. Boussiotis, Gordon J. Freeman, Amy E. Moran, Fanny Polesso, Lisa Lukaesko, Emelie Rådestad, Lars Egevad, Berit Sundberg, Lars Henningsohn, Victor Levitsky, William Rafelson, John L. Reagan, Loren Fast, Pottayil Sasikumar, Naremaddepalli Sudarshan, Raghuveer Ramachandra, Nagesh Gowda, Dodheri Samiulla, Talapaneni Chandrasekhar, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit Dhudashia, Nagaraj Gowda, Murali Ramachandra, Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Joshua Stern, Mark Schoenberg, Xingxing Zang, Ryan Swanson, Michael Kornacker, Lawrence Evans, Erika Rickel, Martin Wolfson, Sandrine Valsesia-Wittmann, Tala Shekarian, François Simard, Rodrigo Nailo, Aurélie Dutour, Anne-Catherine Jallas, Christophe Caux, and Aurélien Marabelle

Subjects
Pharmacology, 0303 health sciences, Cancer Research, Side effect, business.industry, medicine.drug_class, Immunology, Phases of clinical research, Monoclonal antibody, Phase i study, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, Pharmacokinetics, 030220 oncology & carcinogenesis, Molecular Medicine, Immunology and Allergy, Medicine, In patient, Programmed death 1, business, 030304 developmental biology
Published
2016

23. Trends in Microfabrication Capabilities & Device Architectures

Author

Todd Bauer, John Mudrick, Arun Rodrigues, Tony Lentine, Adam Jones, and Murat Okandan

Subjects
Engineering, National security, business.industry, Feature (computer vision), Size reduction, Electrical engineering, Systems engineering, Miniaturization, Microelectronics, Electronics, business, Microfabrication
Abstract

The last two decades have seen an explosion in worldwide R&D, enabling fundamentally new capabilities while at the same time changing the international technology landscape. The advent of technologies for continued miniaturization and electronics feature size reduction, and for architectural innovations, will have many technical, economic, and national security implications. It is important to anticipate possible microelectronics development directions and their implications on US national interests. This report forecasts and assesses trends and directions for several potentially disruptive microfabrication capabilities and device architectures that may emerge in the next 5-10 years.

Published
2015

24. Silicon photonics platform for national security applications

Author

Daniel J. Savignon, Jonathan A. Cox, Christopher T. DeRose, Michael Wiwi, Andrew Starbuck, Patrick B Chu, William A. Zortman, Adam Jones, Anthony L. Lentine, Nicolas J. D. Martinez, Douglas C. Trotter, Paul Davids, Todd Bauer, and Andrew Pomerene

Subjects
Engineering, Silicon photonics, National security, Hardware_GENERAL, business.industry, Microsystem, Hardware_INTEGRATEDCIRCUITS, Electrical engineering, Optical networking, Electronics, Aerospace systems, business, Electronic circuit
Abstract

We review Sandia's silicon photonics platform for national security applications. Silicon photonics offers the potential for extensive size, weight, power, and cost (SWaP-c) reductions compared to existing III–V or purely electronics circuits. Unlike most silicon photonics foundries in the US and internationally, our silicon photonics is manufactured in a trusted environment at our Microsystems and Engineering Sciences Application (MESA) facility. The Sandia fabrication facility is certified as a trusted foundry and can therefore produce devices and circuits intended for military applications. We will describe a variety of silicon photonics devices and subsystems, including both monolithic and heterogeneous integration of silicon photonics with electronics, that can enable future complex functionality in aerospace systems, principally focusing on communications technology in optical interconnects and optical networking.

Published
2015

25. Minimization of undercutting in electrochemical micromachining of patterned aluminum–copper films

Author

L E Mosley, Chris Schwappach, Plamen Atanassov, Todd Bauer, Gabriel P. Lopez, Zariff A. Chaudhury, J T Cosse, and Dmitri A. Brevnov

Subjects
Engineering drawing, Materials science, Anodizing, Mechanical Engineering, chemistry.chemical_element, Microstructure, Isotropic etching, Electronic, Optical and Magnetic Materials, Surface micromachining, chemistry, Mechanics of Materials, Aluminium, Electrical and Electronic Engineering, Composite material, Porosity, Anisotropy, Current density
Abstract

Al–0.5%Cu films patterned with an anodization mask of barrier Al2O3 are micromachined by porous-type anodization followed by chemical dissolution of porous Al2O3. Electrochemical micromachining results in well-defined metallic pillars separated by micro-grooves. The trapezoidal shape of the pillars is due to the lateral pore propagation under the anodization mask. Regardless of undercutting, porous-type anodization shows a higher degree of anisotropy than mostly isotropic wet chemical etching. The vertical growth of pores is accelerated with respect to the lateral propagation of pores by increasing the voltage of porous-type anodization. Consequently, the lateral pore propagation is minimized and for ~3 µm thick Al–0.5%Cu films the etch factor increases from 2.6 to 4.3 when the voltage is increased from 20 V to 60 V. Comparing the results obtained with the micromachining of ~3 µm and ~10 µm thick films at the same voltage, the etch factor decreases as the depth of micro-grooves increases. The etch factor depends on the distribution of secondary current density at the pattern scale during porous-type anodization, which is defined by the anodization mask coverage. A higher degree of anisotropy of porous-type anodization (in comparison to wet chemical etching) allows for more accurate shape control of three-dimensional metallic microstructures.

Published
2006

27. URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas

Author

Maureen Jeri Bourner, Richard Mazzarella, Hamideh Zakeri, Christopher Todd Bauer, Richard D. Head, and Edward J. Weinstein

Subjects
DNA, Complementary, Lung Neoplasms, Protein family, UNC-112, Molecular Sequence Data, Protein Array Analysis, Breast Neoplasms, Biology, Exon, Gene cluster, Gene duplication, Biomarkers, Tumor, Humans, Coding region, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, DNA chip, Gene, Molecular Biology, Cancer, cDNA microarray, FERM domain, Reverse Transcriptase Polymerase Chain Reaction, PH domain, Carcinoma, Membrane Proteins, MIG-2, Molecular biology, Kidney Neoplasms, Neoplasm Proteins, Protein Structure, Tertiary, Transcript expression analysis, Gene expression profiling, URP2, Colonic Neoplasms, Molecular Medicine, Sequence Alignment, Cytoskeletal protein, URP1
Abstract

In a concerted effort to identify biomarkers for lung and colon carcinomas by genome-wide transcriptional profiling, we describe the identification and cloning of one such gene as well as two additional closely related genes. Due to the strong sequence homology to the C. elegans UNC-112 we call this gene URP1, for UNC-112 related protein. We have also isolated the full-length clones for another novel related gene, URP2 and the previously discovered MIG-2 gene. Collectively, these proteins, together with two from Drosophila, appear to form a novel membrane-associated FERM and PH domain-containing protein family. Transcriptional analysis shows that only URP1 is significantly differentially regulated, being over-expressed in 70% of the colon carcinomas and 60% of the lung carcinomas tested. Quantification of URP1 expression by qRT-PCR showed up-regulation of the gene by 60-fold in lung tumors and up to nearly 6-fold in colon tumors. Northern blot analysis of URP1 indicates that normal expression is restricted to neuromuscular tissues. In contrast, the expression of URP2 appears to be confined primarily to tissues of the immune system. SNP analysis of URP1 reveals that it is highly polymorphic, containing seven sites, four of which are in the coding region and one position that results in the interchangeable substitution of glutamic acid and lysine. Finally, we have shown that the genomic structure for all three genes is nearly identical with all encoded by 15 exons although URP1 gene localized to chromosome 20p13, URP2 to 11q12 and MIG-2 to 14q22. This conserved exon structure suggests that all three members probably arose by gene duplication from one ancestral gene. The presence of multiple FERM domains characteristic of cytoplasmic plasma membrane to cytoskeleton linkers and a PH domain typical of membrane-anchored proteins involved in signal transduction suggest an important role for URP1 in tumorigenesis.

Published
2003
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28. a Unique 3D Integration Approach for SOI Substrates - Mating Device Layer CVD W Filled Tsvs with Handle Layer ECD Cu Filled Tsvs

Author

Andrew E Hollowell, Christian L. Arrington, Todd Bauer, Matthew Blain, Jason Dominguez, Ronald S. Goeke, Edwin Heller, Robert Jarecki, Rebecca Loviza, Jaime McClain, Lyle Alexander Menk, Jamin Ryan Pillars, Paul Resnick, and Robert Timon

Abstract

In recent years microelectronic packaging development has focused on 3D integration in order to compensate for the decrease in traditional Moore’s Law scaling. 3D integration allows increased I/O counts, lower RC time constants, lower power consumption, and better thermal sinking. Furthermore, 3D integration decreases areal density through stacking chips and connecting their electrical signals with through substrate vias (TSVs) as opposed to wire bonding. A significant amount of development has been achieved integrating TSVs with standard silicon (Si) substrates; however, very little development has been made integrating this technology with silicon-on-insulator (SOI) substrates1. Certain MEMS applications take advantage of the use of SOI wafers with relatively thick device layer silicon, however the integration of TSVs with these unique SOI substrates (e.g., 600um handle, 1um buried oxide, and 25um thick device layer) presents distinct challenges when making electrical connections through the device layer Si, buried oxide (BOX), and the handle Si. This is particularly true for cases in which the handle Si is not thinned. In this work, we present a novel TSV integration approach in which electrochemical deposition (ECD) is used to connect copper (Cu) vias, filled in the handle of the substrate, to tungsten (W) vias filled by chemical vapor deposition (CVD) in the device layer of a SOI substrate. Deep reactive ion etching (DRIE) has become the most accepted process for creating TSVs when working with semiconductor materials. After forming the vias, chemical vapor deposition, atomic layer deposition (ALD), and/or electrochemical deposition are used to deposit an insulating material for electrical isolation, a barrier layer to prevent diffusion, and a conductive material for electrical connection. CVD is typically used for all three of these purposes if the film thicknesses and aspect ratios are small enough and geometries are not overly complex. ALD is utilized for both the insulating layer and the diffusion barrier when CVD is not capable of conformally coating intricate geometries. ECD is used to fill the vias with a conductive material when via dimensions are too large for CVD, which is common in MEMS applications. This work will utilize DRIE for etching topside vias through the device layer Si and CVD for filling these vias with W. DRIE is also used for etching the handle Si and BOX layers using a hardmask on the backside of the substrate. Two approaches are investigated and presented for utilizing ECD to form Cu TSVs and connect the backside of the wafer to the W TSVs imbedded in the device layer of the SOI substrate. In both of these approaches, ALD is used to deposit a conformal layer of Al2O3 to isolate the TSVs from the handle Si. A spacer etch is performed to remove the Al2O3 from horizontal surfaces, revealing the W TSVs previously fabricated in the device layer Si. The first approach is to fill the TSVs with Cu from the bottom up, initiating plating from a seed layer deposited only at the bottom of the backside vias. This approach allows a conventional makeup chemistry to be used with sulfuric acid (H2SO4) as the electrolyte in conjunction with a periodic reverse plating regime. The second approach is to fill the vias from the outside in, initiating plating from a conformal platinum (Pt) seed layer deposited by ALD and using methanesulfonic acid (MSA), rather than H2SO4, as the makeup chemistry electrolyte2. The higher solubility of Cu in MSA (80g/L) compared to H2SO4 (50g/L) reduces mass transport limited depletion of Cu ions in the vias, leading to conformal Cu deposition throughout the depth of the vias. The advantages, disadvantages, and challenges associated with each of these two integration approaches will be presented. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. G-K. Lau, J. Soon, H-Y Li, K. Chui, and Y. Mingbin, “Process Integration and Challenges of Through Silicon Via (TSV) on Silicon-On-Insulator (SOI) Substrate for 3D Heterogeneous Applications.” 17th Electron. Packaging Tech. Conf., (2015). S. K. Cho, M. J. Kim, and J. J. Kim, “MSA as a Supporting Electrolyte in Copper Electroplating for Filling of Damascene Trenches and Through Silicon Vias.” Electrochemical and Solid-State Letters, 14 (5) D52-D56 (2011).

Published
2016

29. ALD Platinum Substrate Preparation and Electrodeposition of Copper into Extremely Deep through-Silicon-Vias

Author

Lyle Alexander Menk, Christian L. Arrington, Todd Bauer, Matthew Blain, Jason Dominguez, Ronald S. Goeke, Edwin Heller, Andrew E Hollowell, Robert Jarecki, Rebecca Loviza, Jaime McClain, Jamin Ryan Pillars, Paul Resnick, and Robert Timon

Abstract

Copper electrodeposition into through-silicon-vias (TSV) is a rapidly developing and instrumental technique required for efficient high-density 3-D integration of complex semiconductor devices. The ubiquity of the electrodeposition of copper (Cu) in damascene interconnects has led to natural development towards Cu electrodeposition in TSVs. Many processes currently rely on either electroless plating or sputter deposition as a seed layer prior to the electrolytic deposition of Cu. However, these techniques are not capable of achieving a conformal seed layer throughout the full depth of the vias due to the geometric complexity of these devices. This work investigates via filling of electroplated Cu on substrates that have undergone atomic layer deposition (ALD) of a conformal seed metal. The intent of this work is to achieve uniform and void-free Cu electrodeposition into extremely deep vias (625μm) at aspect ratios as high as 10:1. Platinum (Pt) as a seed layer presents unique challenges due to the high affinity of carbon for collecting on the Pt surface, which renders the surface hydrophobic. In order to adequately wet the entire depth of the vias, the carbon compounds must be removed from the Pt to ensure the surface is hydrophilic. This work will present the results of both wet chemical and dry plasma processes to achieve this full-depth Pt via wetting. Further substrate preparation examines the impact of incubation in the electroplating chemistry under vacuum with an increased concentration of an accelerator additive. This step aims to further facilitate conformal plating into the vias by removing gas pockets from the vias while saturating these areas with accelerator to increase the initial plating rate in the bottom of the vias. In addition to these surface preparation techniques, development of an optimized electroplating bath chemistry and applied current regime will be presented. DC plating as well as various pulse regimes are investigated in order to tailor the filling profile of the vias. With regard to the bath chemistry, high Cu concentrations (80g/L) in methanesulfonic acid (MSA) electrolyte chemistries are compared to conventional Cu concentrations (40-60g/L) in sulfuric acid (H2SO4) electrolyte chemistries. The higher solubility of Cu in the MSA (80g/L) versus H2SO4 electrolyte (50g/L) reduces mass transport limited depletion of Cu ions through the vias 1. The particularly large concentration of Cu ions in this electroplating bath promotes a more rapid replenishment of these ions in the deep and high aspect ratio structures throughout the deposition period. In addition to the different chemistries and plating regimes studied herein, the effects of accelerator, suppressor, and leveler additives are examined through analysis of their affects on cyclic voltammetry curves as well as fill ratios throughout the vias. These fill ratios are examined after the vias are cross-sectioned and polished through the use of chemical mechanical planarization, and subsequent characterization of the vias is achieved using optical and scanning electron microscopy techniques. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. S. K. Cho, M. J. Kim, and J. J. Kim, “MSA as a Supporting Electrolyte in Copper Electroplating for Filling of Damascene Trenches and Through Silicon Vias.” Electrochemical and Solid-State Letters, 14 (5) D52-D56 (2011).

Published
2016

30. Three wafer stacking for 3D integration

Author

Subhash L. Shinde, K. Douglas Greth, Todd Bauer, Jeffrey W. Lantz, Robert Timon, Dale L. Hetherington, Christine L. Ford, and Carlos Anthony Sanchez

Subjects
Materials science, Silicon, Through-silicon via, business.industry, Stacking, chemistry.chemical_element, Hardware_PERFORMANCEANDRELIABILITY, Dielectric, Small form factor, chemistry, Hardware_INTEGRATEDCIRCUITS, Reticle, Electronic engineering, Deposition (phase transition), Optoelectronics, Wafer, business
Abstract

Vertical wafer stacking will enable a wide variety of new system architectures by enabling the integration of dissimilar technologies in one small form factor package. With this LDRD, we explored the combination of processes and integration techniques required to achieve stacking of three or more layers. The specific topics that we investigated include design and layout of a reticle set for use as a process development vehicle, through silicon via formation, bonding media, wafer thinning, dielectric deposition for via isolation on the wafer backside, and pad formation.

Published
2011

31. Silicon bulk micromachined hybrid dimensional artifact

Author

Andrew D. Oliver, Hy D. Tran, Andre Aman Claudet, Todd Bauer, and Katherine Meghan Shilling

Subjects
Engineering, Bulk micromachining, Artifact (error), Fabrication, Silicon, business.industry, chemistry.chemical_element, Surface micromachining, chemistry, Machining, Hardware_INTEGRATEDCIRCUITS, Electronic engineering, Measuring instrument, Miniaturization, Optoelectronics, business
Abstract

A mesoscale dimensional artifact based on silicon bulk micromachining fabrication has been developed and manufactured with the intention of evaluating the artifact both on a high precision coordina...

Published
2010

32. A randomized multicenter Phase Ib/II study to assess the immunological effect of chemoradiation therapy (CRT) in combination with pembrolizumab compared to CRT alone in resectable or borderline resectable pancreatic cancer

Author

Katz, Matthew, primary, Todd, Bauer W, additional, Varadhachary, Gauri, additional, Acquavella, Nicolas, additional, Petroni, Gina, additional, Bullock, Timothy, additional, Slingluff, Craig L, additional, and Rahma, Osama, additional

Published
2015
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33. Thermomechanical modeling of back-end-of-the-line 3D interconnects

Author

Todd Bauer, Jordan E. Massad, and Subhash L. Shinde

Subjects
Engineering, business.industry, Three-dimensional integrated circuit, Integrated circuit design, Integrated circuit, Finite element method, law.invention, Reliability (semiconductor), Mesh generation, law, Electronic engineering, Sensitivity (control systems), business, Massively parallel
Abstract

Three-dimensional (3D) integrated circuits (ICs) offer considerable advantages over traditional 2D IC designs by offering increased signal speeds and lower operation power, and by combining multiple technology functions in a low-volume, stacked design. The design complexity of 3D ICs introduces an increased sensitivity of operation and reliability due to the thermomechanical interactions among their multilevel components. Therefore, physical modeling has become a critical task in the design phase of 3D ICs to manage and reduce these sensitivities, and to increase yield and reliability. In this paper, we develop and employ a high-fidelity, 3D finite element modeling framework to examine the thermomechanical response of 3D IC interconnects. We demonstrate attributes of our framework on a back-end-of-the-line via chain. First, we generate geometry using process definitions, develop a parameterized mesh, and identify material parameters from characterization experiments. Then, using advanced, massively parallel computational resources, we simulate fabrication steps to approximate the stresses and deformations experienced by the microstructure as a result of processing temperatures. Ultimately, our modeling approach provides a capability to assess the thermomechanical response of 3D IC components and provides a basis for designing structures robust to fabrication and processing variations.

Published
2009

34. Front end of line integration of high density, electrically isolated, metallized through silicon vias

Author

Jordan E. Massad, Dale L. Hetherington, Todd Bauer, and Subhash L. Shinde

Subjects
Thermal oxidation, Interconnection, Fabrication, Materials science, Silicon, business.industry, chemistry.chemical_element, Dielectric, Tungsten, chemistry, Etching (microfabrication), Electronic engineering, Optoelectronics, business, Front end of line
Abstract

We have developed a complete process module for fabricating front end of line (FEOL) through silicon vias (TSVs). In this paper we describe the integration, which relies on using thermally deposited silicon as a sacrificial material to fill the TSV during FEOL processing, followed by its removal and replacement with tungsten after FEOL processing is complete. The uniqueness of this approach follows mainly from forming the TSVs early in the FEOL while still ultimately using metal as the via fill material. TSVs formed early in the FEOL can be formed at comparatively small diameter, high aspect ratio, and high spatial density. We have demonstrated FEOL-integrated TSVs that are 2 µm in diameter, over 45 µm deep, and on 20 µm pitch for a possible interconnect density of 250,000/cm2. Moreover, thermal oxidation of silicon can be used to form the dielectric isolation. Thermal oxidation is conformal and robust in the as-formed state. Finally, TSVs formed in the FEOL alleviate device design constraints common to vias-last integration.

Published
2009

36. Nanogap experiments for laser cooling: a progress report

Author

Babak Imangholi, Kevin J. Malloy, Andreas Stintz, Ryan P. Martin, Todd Bauer, S. T. P. Boyd, Josef Velten, Richard I. Epstein, Michael P. Hasselbeck, and Mansoor Sheik-Bahae

Subjects
Materials science, Silicon, business.industry, chemistry.chemical_element, Substrate (electronics), Optics, Semiconductor, chemistry, Etching (microfabrication), Laser cooling, Optoelectronics, Thin film, business, Buffered oxide etch, Layer (electronics)
Abstract

One of the challenges of laser cooling a semiconductor is the typically high index of refraction (greater than 3), which limits efficient light output of the upconverted photon. This challenge is proposed to be met with a novel concept of coupling the photon out via a thin, thermally insulating vacuum gap that allows light to pass efficiently by frustrated total internal reflection. This study has the goal of producing a test structure that allows investigation of heat transport across a 'nanogap' consisting of a thin film supported over a substrate by an array of nanometer-sized posts. The nanogap is fabricated monolithically by first creating a film of SiO 2 on a silicon substrate, lithographically defining holes in the SiO 2 , and covering this structure including the holes with silicon. Selective lateral etching will then remove the SiO 2 , leaving behind a thin gap between two Si layers spaced apart by nanometer-scale Si posts. Demonstration of this final step by successfully undercutting the a-Si upper layer due to the hydrophobic nature of silicon and the slow etch rate of buffered oxide etch in the small gap has proved to be problematic. Arriving at a feasible solution to this conundrum is the current objective of this project in order to begin investigating the thermal conductivity properties of the structure.

Published
2007

37. Germanium-Silicon Separate Absorption and Multiplication Avalanche Photodetectors Fabricated with Low Temperature High Density Plasma Chemical Vapor Deposited Germanium

Author

Kevin F. Saiz, Darwin K. Serkland, Kenton D. Childs, Malcolm S. Carroll, Robert L. Jarecki, and Todd Bauer

Subjects
Photocurrent, Materials science, Silicon, business.industry, chemistry.chemical_element, Germanium, Heterojunction, Chemical vapor deposition, Microbiology, Avalanche breakdown, Responsivity, chemistry, Optoelectronics, business, Plasma processing
Abstract

A desire to monolithically integrate near infrared (NIR) detectors with silicon complementary metal oxide semiconductor (CMOS) technology has motivated many investigations of single crystal germanium on silicon (Ge/Si) diodes [1-3]. Reduction of the epitaxy thermal budget below the typical chemical vapor deposition (CVD) in-situ clean temperature (Tin-situ clean > 780°C) is also increasingly desired to reduce integration complexity. Reduced temperature growth approaches have included p+-Ge/n-Si detectors formed with low temperature poly-Ge (e-beam evaporation) or heavily dislocated single crystal germanium (molecular beam epitaxy, T ~ 450°C), which have had dark currents of ~5 mA/cm2 and responsivities of ~15 mA/W at 1310 nm, despite the large number of defects in and at the Ge/Si interface. Responsivities in these materials are however low and believed to be limited by a small diffusion length (i.e., 5-30 nm [2, 4]) due to fast electron recombination in the defect rich germanium. In this paper, we evaluate a commercially available high density plasma chemical vapor deposition (HDP-CVD) process to grow low temperature (i.e., Tin-situ & Tepitaxy < ~450°C) germanium epitaxy for a p+-Ge/p-Si/n+-Si NIR separate absorption and multiplication avalanche photodetectors (SAM-APD). This device structure is of interest both to examine ways to enhance the responsivity with internal gain as well as to examine alternatives to InGaAs-InP structures for NIR Geiger mode (GM) detection. A silicon avalanche region is highly desirable for GM to reduce after-pulsing effects, which are related to defect density that are smaller in Si than in InP [5]. Despite the high defect densities in the Ge and at the interface, the Ge-Si APDs in this work are found to have relatively low dark count rates in Geiger mode.

Published
2007

38. Bendamustine, Bortezomib and Dexamethasone (BBD) As First-Line Treatment Of Patients (Pts) With Multiple Myeloma Who Are Not Candidates For High Dose Chemotherapy

Author

Jesus Berdeja, Michael Savona, Luis Chu, James Essell, Patrick Murphy, Todd Bauer, Eric Raefsky, Ralph V. Boccia, and Ian Flinn

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

Background Despite significant advances, multiple myeloma is an incurable plasma cell disorder with an eventual fatal outcome. In newly diagnosed MM, combinations of bortezomib, steroids and alkylating agents, such as melphalan and prednisone, have achieved response rates in excess of 70% and have been established as a standard of care in pts who are ineligible for high dose chemotherapy. Outcomes are more attenuated in pts > 75 yrs old. Bendamustine is a bi-functional alkylating agent with a purine-like benzimidazole ring effective as a single agent and in various combinations for the treatment of relapsed/refractory MM (Poenisch et al, 2007, Fenk et al, 2007). In this study, the combination of bendamustine, bortezomib and dexamethasone (BBD) was evaluated as a first-line therapy for pts with MM. Here we present the updated results of this ongoing trial. Methods Pts with newly diagnosed active MM who were not candidates for high-dose chemotherapy and met standard eligibility criteria with regards to renal, hepatic and hematologic function were enrolled. The original treatment schema consisted of: bendamustine 80 mg/m2 IV on days 1, 4; bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11; and dexamethasone 40 mg on days 1, 2, 3, 4 with cycles repeating every 28 days. Pts had the option to continue treatment up to 8 cycles or 2 cycles beyond confirmed CR. An interim analysis found this combination to be efficacious but relatively toxic. As a result, the treatment schema was amended to the following: bendamustine 80 mg/m2 IV on days 1, 2; bortezomib 1.3 mg/m2 IV on days 1, 8, 15; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16 every 28 days for a total of 8 cycles or 2 cycles beyond documented CR, whichever occurred first. Pts achieving at least SD continued on to maintenance bortezomib 1.3 mg/m2 IV/SQ every 2 weeks for 2 years. Acyclovir or equivalent viral prophylaxis was originally recommended and became required on the modified schema. Responses were assessed using the IMWG criteria. The overall response rate (ORR) was defined as ≥ PR. Adverse Events (AEs) were assessed using the CTCAE Version 4.0. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results As of 5/31/2013, 43 pts have been enrolled (18 on the original schema, 25 on the modified schema). The median age was 75 (45-89) and 39% of pts were > 75 (48% in the modified schema). Forty two percent of pts were ISS II and 32% were ISS III. Fifteen (35%) pts remain on treatment, all on the modified schema. Treatment-related Grade 3 hematologic AEs were seen in 30% of pts. Only 1 treatment-related Grade 4 hematologic AE of neutropenia was observed. Treatment-related Grade 3 non-hematologic AEs were seen in 21% of pts. The most common non-hematologic Grade 3 AE was neuropathy, seen in 12% of pts (all but 1 on the original schema). There was 1 treatment-related Grade 4 non-hematologic AE of atrial fibrillation and 1 treatment related death (congestive heart failure). Herpes Zoster was seen in 19% of the pts, all from the original treatment schema. A total of 40 pts were evaluable for response. The ORR was 83% (55% ≥VGPR, 28% PR) plus 17% SD and 0 PD. Of the 23 evaluable pts on the modified treatment schema, the ORR was 83% (52% ≥VGPR and 31% PR). For the 15 pts > 75, the ORR was 93% (60% ≥VGPR and 33% PR). At a median FU of 13.1 months, the 1-year PFS is 79% (0.53-0.92) and the 1-year OS is 83% (0.54-0.95). Conclusion The combination of bendamustine, bortezomib and dexamethasone is feasible and efficacious in this elderly pt population with a large number of pts over the age of 75 years. The modified schema is better tolerated allowing pts to proceed to maintenance treatment which may eventually translate to improved results. Enrollment is ongoing. Disclosures: Off Label Use: Off-label use of Bendamustine in the Treatment of Multiple Myeloma. Chu:Teva: Research Funding; Millennium: Research Funding. Boccia:Teva: Research Funding; Millennium: Research Funding. Flinn:Teva: Research Funding; Millennium: Research Funding.

Published
2013

40. Ge–Si separate absorption and multiplication avalanche photodiode for Geiger mode single photon detection

Author

Kenton D. Childs, Todd Bauer, Robert L. Jarecki, Malcolm S. Carroll, and Kevin F. Saiz

Subjects
Physics, Physics and Astronomy (miscellaneous), APDS, business.industry, Avalanche photodiode, law.invention, Photodiode, Responsivity, Optics, Single-photon avalanche diode, law, Optoelectronics, Geiger counter, business, Absorption (electromagnetic radiation), Dark current
Abstract

A Ge–Si separate absorption and multiplication avalanche photodiode (SAM-APD) is reported. The structure is grown using a low temperature in situ clean and epitaxy process, Tinsitu and Tepitaxy

Published
2008

41. Width of Anodization Mask Required to Preserve a Metallic Phase during Porous-Type Anodization of Aluminum-Copper Films

Author

Dmitri A. Brevnov, Chris Schwappach, Robin L. Womack, Gabriel P. Lopez, Larry E. Mosley, Todd Bauer, Zariff A. Chaudhury, and Plamen Atanassov

Subjects
Materials science, Renewable Energy, Sustainability and the Environment, Anodizing, chemistry.chemical_element, Nanotechnology, Condensed Matter Physics, Copper, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Aluminium, Phase (matter), Materials Chemistry, Electrochemistry, Miniaturization, Composite material, Porosity, Anisotropy, Layer (electronics)
Abstract

Patterned arrays with alternating regions of the metallic phase and porous aluminum oxide are fabricated by using a dense layer of barrier aluminum oxide as a mask for porous-type anodization of 99.5% Al and 0.5% Cu films. The pore curvature at the interface between the metallic phase and porous aluminum oxide is investigated as a function of anodization voltage. The degree of anisotropy, which is defined as a ratio between vertical and lateral propagation of pores, increases slightly as anodization voltage increases. The pore curvature compromises the mask transfer during anodization due to the lateral pore propagation under the anodization mask. For miniaturization of regions composed of Al-Cu, it is important to establish the width of anodization mask required to preserve the metallic phase between two regions of porous aluminum oxide. Our results show that a 2 μm wide anodization mask is necessary during porous-type anodization of 3 μm thick Al-Cu films at a chosen set of anodization conditions (40 V, 3% w/v H 2 C 2 O 4 , 5°C).

Published
2006

42. Electrochemical Micromachining

Author

Larry E. Mosley, Chris Schwappach, Zariff A. Chaudhury, Plamen Atanassov, Dmitri A. Brevnov, Gabriel P. Lopez, Thomas C. Gamble, and Todd Bauer

Subjects
Materials science, Anodizing, General Chemical Engineering, Isotropy, chemistry.chemical_element, Nanotechnology, Microstructure, Copper, Isotropic etching, chemistry, Aluminium, Electrochemistry, General Materials Science, Electrical and Electronic Engineering, Physical and Theoretical Chemistry, Composite material, Porosity, Dissolution
Abstract

Porous-type anodization of patterned ∼10 μm thick Al-Cu films results in microstructures with alternating regions of Al-Cu and porous Al 2 O 3 . The volumetric expansion of porous Al 2 O 3 is minimized by increasing the anodization solution temperature. The fidelity of the mask transfer (10 μm wide) is compromised by the lateral pore propagation under the anodization mask. The Al-Cu pillars formed after complete dissolution of porous Al 2 O 3 have a trapezoidal shape. The height of pillars is twice (8 μm) the distance corresponding to the lateral pore propagation (4 μm). In contrast to wet chemical etching, porous-type anodization of patterned Al-Cu films is not isotropic.

Published
2006

43. Fabrication of Patterned Arrays with Alternating Regions of Aluminum and Porous Aluminum Oxide

Author

Plamen Atanassov, Todd Bauer, Dmitri A. Brevnov, Marcos J. Barela, and Gabriel P. Lopez

Subjects
inorganic chemicals, Fabrication, Materials science, Silicon, business.industry, Anodizing, General Chemical Engineering, Metallurgy, technology, industry, and agriculture, chemistry.chemical_element, Equivalent oxide thickness, Substrate (electronics), Photoresist, complex mixtures, chemistry, parasitic diseases, Electrochemistry, Optoelectronics, General Materials Science, Wafer, Electrical and Electronic Engineering, Physical and Theoretical Chemistry, business, Layer (electronics)
Abstract

Fabrication of patterned anodic aluminum oxide arrays using a dense layer of barrier aluminum oxide as the anodization mask is described. This fabrication process includes patterning of the aluminum film with a photoresist and brief anodization at a high voltage. The photoresist is then removed and the aluminum film is again anodized at a low voltage to grow porous aluminum oxide. Using this procedure, we are able to fabricate anodic aluminum oxide arrays on silicon wafers consisting of alternating regions of porous aluminum oxide and aluminum metal perpendicular to the silicon substrate.

Published
2005

44. The Use of Fine Needle Aspiration Cytology for the Distinction of Pancreatic Mucinous Neoplasia.

Author

Edward Stelow, Vanessa Shami, Todd Abbott, Michelle Kahaleh, Reid Adams, Todd Bauer, Steven Debol, James Abraham, Shawn Mallery, and Maria Policarpio-Nicolas

Subjects
NEEDLE biopsy, PANCREATIC cancer, TUMORS, PRECANCEROUS conditions, CYTOLOGY
Abstract

Cytology frequently has some role in preoperatively distinguishing pancreatic mucus-producing neoplasia (intraductal papillary mucinous neoplasms [IPMNs] and mucinous cystic neoplasms [MCNs]) from other pancreatic cysts. We evaluated all cytologic specimens at our institutions from resected pancreatic cystic lesions for lesional extracellular and cellular material. Lesional extracellular material was identified in 32 of 38 of the cytologic samples from cystic pancreatic mucus-producing neoplasms (28 of 31 IPMNs and 4 of 7 MCNs). Lesional cellular material was seen in 22 of 38 cases (17 of 31 IPMNs and 5 of 7 MCNs). Lesional material was more commonly identified in higher grade and invasive lesions. Lesional extracellular material was seen in 3 of 14 samples of other pancreatic cysts, and lesional cellular material was seen in 6 of 14 cases. [ABSTRACT FROM AUTHOR]

Published
2008
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