640 research outputs found
Optimization under uncertainty in radiation therapy
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 175-182).In the context of patient care for life-threatening illnesses, the presence of uncertainty may compromise the quality of a treatment. In this thesis, we investigate robust approaches to managing uncertainty in radiation therapy treatments for cancer. In the first part of the thesis, we study the effect of breathing motion uncertainty on intensity-modulated radiation therapy treatments of a lung tumor. We construct a robust framework that generalizes current mathematical programming formulations that account for motion. This framework gives insight into the trade-off between sparing the healthy tissues and ensuring that the tumor receives sufficient dose. With this trade-off in mind, we show that our robust solution outperforms a nominal (no uncertainty) solution and a margin (worst-case) solution on a clinical case. Next, we perform an in-depth study into the structure of different intensity maps that were witnessed in the first part of the thesis. We consider parameterized intensity maps and investigate their ability to deliver a sufficient dose to the tumor in the presence of motion that follows a Gaussian distribution. We characterize the structure of optimal intensity maps in terms of certain conditions on the problem parameters.(cont.) Finally, in the last part of the thesis, we study intensity-modulated proton therapy under uncertainty in the location of maximum dose deposited by the beamlets of radiation. We provide a robust formulation for the optimization of proton-based treatments and show that it outperforms traditional formulations in the face of uncertainty. In our computational experiments, we see evidence that optimal robust solutions use the physical characteristics of the proton beam to create dose distributions that are far less sensitive to the underlying uncertainty.by Timothy Ching-Yee Chan.Ph.D
An Annotative Approach to Better Hyperauthoring and Associative Linking
No full textEarly hypertext visionaries proposed entire online archives of the world's literature, with everything associatively linked to everything else. Today, the most widespread hypertext system is the World-Wide Web (WWW), a publicly accessible and globally distributed medium. However, the WWW is not living up to the promise of hypertext associativity - the majority of hypertext linking on the WWW is estimated to be intended for navigational purposes only. WWW authors typically have new ideas to contribute, and assert particular relationships between these and existing ideas already published in order to demonstrate both the reliability of the conceptual foundation being built on, and the innovation and significance of the new ideas. However, these associations are rarely rendered as associative links which seamlessly link the new material into the global context. This research investigates the possibility of capturing these implicit inter-document associations through annotation, and then using these annotations to assist the hyperauthoring process. The hypothesis of this work is therefore that by capturing inter-document associations through annotation, a better hyperauthoring process will result, both in terms of the quality and coverage of the new writing, and in terms of the seamless (associative) integration with the global context, helping the WWW evolve to achieve all of its potential hypertextual richness. The Annotation LInking ENvironment (ALIEN) has been implemented to demonstrate techniques for capturing inter-document associations made by an author whilst reading, using free form annotations. Further work proposed includes the re-purposing of these captured associations to assist the authoring and linking processes through dynamic visualisation of the association structures "as-you-type", and automatic associative linking
Impact of Cardioprotective Therapies on the Edema-Based Area at Risk by CMR in Reperfused STEMI
No full text10.1016/j.jacc.2018.04.016JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY71242856-285
Stress-Induced Heat Generation and Strain Localization in Polycrystalline and Nanocrystalline Nickel
No full textCommercially available polycrystalline Ni (Ni200; grain size: 32 μm) and electrodeposited nanocrystalline Ni (grain size: 57 nm), Ni-2.6%Fe (grain size: 25 nm) and Ni-8.5%Fe (grain size: 20 nm) were analyzed for the phenomena of stress-induced heat generation and strain localization during plastic deformation at room temperature (i.e. 250C). Tensile specimens according to ASTM E8 standard dimensions were tested at strain rates of 10-2/s and 10-1/s, respectively, to record the amount of heat dissipated and the change of localized strain using a high resolution infrared (IR) detector and digital image correlation (DIC) camera, respectively. Results have shown that the maximum temperatures that were recorded in nanocrystalline Ni and Ni-Fe alloys were at least 300C lower than the onset temperatures for subgrain coalescence previously measured through differential scanning calorimetry. It can be concluded that thermally activated grain growth during tensile testing of nanocrystalline Ni and Ni-Fe alloys is not likely to occur.MAS
Stress-Induced Heat Generation and Strain Localization in Polycrystalline and Nanocrystalline Nickel
No full textCommercially available polycrystalline Ni (Ni200; grain size: 32 μm) and electrodeposited nanocrystalline Ni (grain size: 57 nm), Ni-2.6%Fe (grain size: 25 nm) and Ni-8.5%Fe (grain size: 20 nm) were analyzed for the phenomena of stress-induced heat generation and strain localization during plastic deformation at room temperature (i.e. 250C). Tensile specimens according to ASTM E8 standard dimensions were tested at strain rates of 10-2/s and 10-1/s, respectively, to record the amount of heat dissipated and the change of localized strain using a high resolution infrared (IR) detector and digital image correlation (DIC) camera, respectively. Results have shown that the maximum temperatures that were recorded in nanocrystalline Ni and Ni-Fe alloys were at least 300C lower than the onset temperatures for subgrain coalescence previously measured through differential scanning calorimetry. It can be concluded that thermally activated grain growth during tensile testing of nanocrystalline Ni and Ni-Fe alloys is not likely to occur.MAS
Development of collagen scaffold with internal channels via indirect rapid prototyping
No full text202 p.The author would like to take this opportunity to acknowledge the contribution of anumber of people for this project. The realization of the project would not have beenpossible without the advice and assistance from them.The author wishes to express her sincere gratitude and appreciation to A/P Chua CheeKai, A/P Leong Kah Fai and Dr. Margam Chandrasekaran, for their invaluable adviceand motivation throughout the project. Appreciation is also extended to As/P AlastairCampbell Ritchie from the School of Mechanical and Aerospace Engineering, NTU,and Mr Timothy Tan and Dr Peter Lee from DNA Center, NIE, for their guidance inthe project. Heartfelt thanks to Ms Hu Quijun, from SIMTech for her guidance andsupport.DOCTOR OF PHILOSOPHY (MAE
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Proceedings of the 2016 China Cancer Immunotherapy Workshop
No full textTable of contents A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzin
Pathophysiological roles and clinical importance of biomarkers in acute coronary syndrome
No full textEarly diagnosis of acute coronary syndrome (ACS) is important to guide appropriate therapy at a time when it is most likely to be of value. Accurate prognostic and risk stratification will facilitate high-risk patients to have early advanced diagnostic investigations and early appropriate interventions in a cost-effective and efficient manner, while those patients at low risk of ACS complications do not need such costly diagnostic tests and unnecessary hospital admission. Recent investigations have demonstrated that elevation of biomarkers upstream from acute-phase biomarkers, biomarkers of plaque destabilization and rupture, biomarkers of myocardial ischemia, necrosis, and dysfunction may provide an earlier assessment of patient risk and identify patients with higher risk of having an adverse event. This review provides an overview of the pathophysiology and clinical characteristics of several well-established biomarkers as well as emerging biomarkers that may have potential clinical utility in patients with ACS. Such emerging biomarkers hold promise and need to be more thoroughly evaluated before utilization in routine clinical practice
Emerg Infect Dis
No full textAn oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus evolved and emerged from zero to 52% of detectable virus within 48 hours of a patient's exposure to oseltamivir. Phylogenetic analysis and data gathered by pyrosequencing and cloning directly on clinical samples suggest that the mutant emerged de novo
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