3,301 results on '"Chan, Timothy"'
Search Results
52. Genomic Landscape of Superficial Malignant Peripheral Nerve Sheath Tumor
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McAfee, John L., Alban, Tyler J., Makarov, Vladimir, Rupani, Amit, Parthasarathy, Prerana B., Tu, Zheng, Ronen, Shira, Billings, Steven D., Diaz, C. Marcela, Chan, Timothy A., and Ko, Jennifer S.
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- 2025
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53. Ultrafast disinfection of SARS-CoV-2 viruses
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Xu, Yang, Chin, Alex Wing Hong, Zhong, Haosong, Lee, Connie Kong Wai, Chen, Yi, Chan, Timothy Yee Him, Fan, Zhiyong, Duan, Molong, Poon, Leo Lit Man, and Li, Mitch Guijun
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Physics - Medical Physics ,Physics - Biological Physics - Abstract
The wide use of surgical masks has been proven effective for mitigating the spread of respiration diseases, such as COVID-19, alongside social distance control, vaccines, and other efforts. With the newly reported variants, such as Delta and Omicron, a higher spread rate had been found compared to the initial strains. People might get infected even by inhaling fewer loading of viruses. More frequent sterilization of surgical masks is needed to protect the wearers. However, it is challenging to sterilize the commodity surgical masks with a fast and effective method. Herein, we reported the sterilization of the SARS-CoV-2 viruses within an ultra-short time, while retaining the mask performance. Silver thin film is coated on commercial polyimide film by physical vapor deposition and patterned by laser scribing to form a Joule heating electrode. Another layer of the gold thin film was coated onto the opposite side of the device to promote the uniformity of the Joule heating through nano-heat transfer regulation. As a result, the surgical mask can be heated to inactivation temperature within a short time and with high uniformity. By Joule-heating the surgical mask with the temperature at 90 {\deg}C for 3 minutes, the inactivation of the SARS-CoV-2 showed an efficacy of 99.89%. Normal commodity surgical masks can be sterilized faster, more frequently, and efficiently against SARS-CoV-2 viruses and the new invariants.
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- 2022
54. Equity, diversity, and inclusion in sports analytics
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Fernandes, Craig, Vescovi, Jason D., Norman, Richard, Bradish, Cheri L., Taback, Nathan, and Chan, Timothy C. Y.
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Statistics - Applications - Abstract
This paper presents a landmark study of equity, diversity and inclusion (EDI) in the field of sports analytics. We developed a survey that examined personal and job-related demographics, as well as individual perceptions and experiences about EDI in the workplace. We sent the survey to individuals in the five major North American professional leagues, representatives from the Olympic and Paralympic Committees in Canada and the U.S., the NCAA Division I programs, companies in sports tech/analytics, and university research groups. Our findings indicate the presence of a clear dominant group in sports analytics identifying as: young (72.0%), White (69.5%), heterosexual (89.7%) and male (82.0%). Within professional sports, males in management positions earned roughly 30,000 USD (27%) more on average compared to females. A smaller but equally alarming pay gap of 17,000 USD (14%) was found between White and non-White management personnel. Of concern, females were nearly five times as likely to experience discrimination and twice as likely to have considered leaving their job due to isolation or feeling unwelcome. While they had similar levels of agreement regarding fair processes for rewards and compensation, females "strongly agreed" less often than males regarding equitable support, equitable workload, having a voice, and being taken seriously. Over one third (36.3%) of females indicated that they "strongly agreed" that they must work harder than others to be valued equally, compared to 9.8% of males. We conclude the paper with concrete recommendations that could be considered to create a more equitable, diverse and inclusive environment for individuals working within the sports analytics sector.
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- 2022
55. Hardness for Triangle Problems under Even More Believable Hypotheses: Reductions from Real APSP, Real 3SUM, and OV
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Chan, Timothy M., Williams, Virginia Vassilevska, and Xu, Yinzhan
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Computer Science - Computational Complexity ,Computer Science - Data Structures and Algorithms - Abstract
The $3$SUM hypothesis, the APSP hypothesis and SETH are the three main hypotheses in fine-grained complexity. So far, within the area, the first two hypotheses have mainly been about integer inputs in the Word RAM model of computation. The "Real APSP" and "Real $3$SUM" hypotheses, which assert that the APSP and $3$SUM hypotheses hold for real-valued inputs in a reasonable version of the Real RAM model, are even more believable than their integer counterparts. Under the very believable hypothesis that at least one of the Integer $3$SUM hypothesis, Integer APSP hypothesis or SETH is true, Abboud, Vassilevska W. and Yu [STOC 2015] showed that a problem called Triangle Collection requires $n^{3-o(1)}$ time on an $n$-node graph. Our main result is a nontrivial lower bound for a slight generalization of Triangle Collection, called All-Color-Pairs Triangle Collection, under the even more believable hypothesis that at least one of the Real $3$SUM, the Real APSP, and the OV hypotheses is true. Combined with slight modifications of prior reductions, we obtain polynomial conditional lower bounds for problems such as the (static) ST-Max Flow problem and dynamic Max Flow, now under the new weaker hypothesis. Our main result is built on the following two lines of reductions. * Real APSP and Real $3$SUM hardness for the All-Edges Sparse Triangle problem. Prior reductions only worked from the integer variants of these problems. * Real APSP and OV hardness for a variant of the Boolean Matrix Multiplication problem. Along the way we show that Triangle Collection is equivalent to a simpler restricted version of the problem, simplifying prior work. Our techniques also have other interesting implications, such as a super-linear lower bound of Integer All-Numbers $3$SUM based on the Real $3$SUM hypothesis, and a tight lower bound for a string matching problem based on the OV hypothesis., Comment: To appear at STOC'22. Abstract shortened to fit arXiv requirements
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- 2022
56. Dynamic Control of Service Systems with Returns: Application to Design of Post-Discharge Hospital Readmission Prevention Programs
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Chan, Timothy C. Y., Huang, Simon Y., and Sarhangian, Vahid
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Electrical Engineering and Systems Science - Systems and Control ,Mathematics - Optimization and Control - Abstract
We study a control problem for queueing systems where customers may return for additional episodes of service after their initial service completion. At each service completion epoch, the decision maker can choose to reduce the probability of return for the departing customer but at a cost that is convex increasing in the amount of reduction in the return probability. Other costs are incurred as customers wait in the queue and every time they return for service. Our primary motivation comes from post-discharge Quality Improvement (QI) interventions (e.g., follow up phone-calls, appointments) frequently used in a variety of healthcare settings to reduce unplanned hospital readmissions. Our objective is to understand how the cost of interventions should be balanced with the reductions in congestion and service costs. To this end, we consider a fluid approximation of the queueing system and characterize the structure of optimal long-run average and bias-optimal transient control policies for the fluid model. Our structural results motivate the design of intuitive surge protocols whereby different intensities of interventions (corresponding to different levels of reduction in the return probability) are provided based on the congestion in the system. Through extensive simulation experiments, we study the performance of the fluid policy for the stochastic system and identify parameter regimes where it leads to significant cost savings compared to a fixed long-run average optimal policy that ignores holding costs and a simple policy that uses the highest level of intervention whenever the queue is non-empty. In particular, we find that in a parameter regime relevant to our motivating application, dynamically adjusting the intensity of interventions could result in up to 25.4% reduction in long-run average cost and 33.7% in finite-horizon costs compared to the simple aggressive policy.
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- 2022
57. OpenKBP-Opt: An international and reproducible evaluation of 76 knowledge-based planning pipelines
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Babier, Aaron, Mahmood, Rafid, Zhang, Binghao, Alves, Victor G. L., Barragán-Montero, Ana Maria, Beaudry, Joel, Cardenas, Carlos E., Chang, Yankui, Chen, Zijie, Chun, Jaehee, Diaz, Kelly, Eraso, Harold David, Faustmann, Erik, Gaj, Sibaji, Gay, Skylar, Gronberg, Mary, Guo, Bingqi, He, Junjun, Heilemann, Gerd, Hira, Sanchit, Huang, Yuliang, Ji, Fuxin, Jiang, Dashan, Giraldo, Jean Carlo Jimenez, Lee, Hoyeon, Lian, Jun, Liu, Shuolin, Liu, Keng-Chi, Marrugo, José, Miki, Kentaro, Nakamura, Kunio, Netherton, Tucker, Nguyen, Dan, Nourzadeh, Hamidreza, Osman, Alexander F. I., Peng, Zhao, Muñoz, José Darío Quinto, Ramsl, Christian, Rhee, Dong Joo, Rodriguez, Juan David, Shan, Hongming, Siebers, Jeffrey V., Soomro, Mumtaz H., Sun, Kay, Hoyos, Andrés Usuga, Valderrama, Carlos, Verbeek, Rob, Wang, Enpei, Willems, Siri, Wu, Qi, Xu, Xuanang, Yang, Sen, Yuan, Lulin, Zhu, Simeng, Zimmermann, Lukas, Moore, Kevin L., Purdie, Thomas G., McNiven, Andrea L., and Chan, Timothy C. Y.
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Physics - Medical Physics ,Computer Science - Artificial Intelligence ,Computer Science - Computer Vision and Pattern Recognition - Abstract
We establish an open framework for developing plan optimization models for knowledge-based planning (KBP) in radiotherapy. Our framework includes reference plans for 100 patients with head-and-neck cancer and high-quality dose predictions from 19 KBP models that were developed by different research groups during the OpenKBP Grand Challenge. The dose predictions were input to four optimization models to form 76 unique KBP pipelines that generated 7600 plans. The predictions and plans were compared to the reference plans via: dose score, which is the average mean absolute voxel-by-voxel difference in dose a model achieved; the deviation in dose-volume histogram (DVH) criterion; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models. The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50 to 0.62, which indicates that the quality of the predictions is generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P<0.05; one-sided Wilcoxon test) on 18 of 23 DVH criteria. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for a conventional planning model. This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. In the interest of reproducibility, our data and code is freely available at https://github.com/ababier/open-kbp-opt., Comment: 19 pages, 7 tables, 6 figures
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- 2022
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58. Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial
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Vos, Joris L., Burman, Bharat, Jain, Swati, Fitzgerald, Conall W. R., Sherman, Eric J., Dunn, Lara A., Fetten, James V., Michel, Loren S., Kriplani, Anuja, Ng, Kenneth K., Eng, Juliana, Tchekmedyian, Vatche, Haque, Sofia, Katabi, Nora, Kuo, Fengshen, Han, Catherine Y., Nadeem, Zaineb, Yang, Wei, Makarov, Vladimir, Srivastava, Raghvendra M., Ostrovnaya, Irina, Prasad, Manu, Zuur, Charlotte L., Riaz, Nadeem, Pfister, David G., Klebanoff, Christopher A., Chan, Timothy A., Ho, Alan L., and Morris, Luc G. T.
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- 2023
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59. Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial.
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Dianti, Jose, Fard, Samira, Wong, Jenna, Chan, Timothy, Del Sorbo, Lorenzo, Fan, Eddy, Amato, Marcelo, Granton, John, Burry, Lisa, Reid, W, Zhang, Binghao, Ratano, Damian, Keshavjee, Shaf, Slutsky, Arthur, Brochard, Laurent, Ferguson, Niall, and Goligher, Ewan
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Diaphragm-protective ventilation ,Hypoxemic respiratory failure ,Lung-protective ventilation ,Mechanical ventilation ,Diaphragm ,Humans ,Lung ,Positive-Pressure Respiration ,Respiration ,Artificial ,Respiratory Insufficiency - Abstract
BACKGROUND: Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF. METHODS: In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. RESULTS: Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. CONCLUSION: Respiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. TRIAL REGISTRATION: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).
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- 2022
60. On the Number of Incidences When Avoiding an Induced Biclique in Geometric Settings
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Chan, Timothy M. and Har-Peled, Sariel
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Computer Science - Computational Geometry - Abstract
Given a set of points $P$ and a set of regions $\mathcal{O}$, an incidence is a pair $(p,o ) \in P \times \mathcal{O}$ such that $p \in o$. We obtain a number of new results on a classical question in combinatorial geometry: What is the number of incidences (under certain restrictive conditions)? We prove a bound of $O\bigl( k n(\log n/\log\log n)^{d-1} \bigr)$ on the number of incidences between $n$ points and $n$ axis-parallel boxes in $\mathbb{R}^d$, if no $k$ boxes contain $k$ common points, that is, if the incidence graph between the points and the boxes does not contain $K_{k,k}$ as a subgraph. This new bound improves over previous work, by Basit, Chernikov, Starchenko, Tao, and Tran (2021), by more than a factor of $\log^d n$ for $d >2$. Furthermore, it matches a lower bound implied by the work of Chazelle (1990), for $k=2$, thus settling the question for points and boxes. We also study several other variants of the problem. For halfspaces, using shallow cuttings, we get a linear bound in two and three dimensions. We also present linear (or near linear) bounds for shapes with low union complexity, such as pseudodisks and fat triangles.
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- 2021
61. Robust Direct Aperture Optimization for Radiation Therapy Treatment Planning
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Ripsman, Danielle A., Purdie, Thomas G., Chan, Timothy C. Y., and Mahmoudzadeh, Houra
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Mathematics - Optimization and Control - Abstract
Intensity-modulated radiation therapy (IMRT) allows for the design of customized, highly-conformal treatments for cancer patients. Creating IMRT treatment plans, however, is a mathematically complex process, which is often tackled in multiple, simpler stages. This sequential approach typically separates radiation dose requirements from mechanical deliverability considerations, which may result in suboptimal treatment quality. For patient health to be considered paramount, holistic models must address these plan elements concurrently, eliminating quality loss between stages. This combined direct aperture optimization (DAO) approach is rarely paired with uncertainty mitigation techniques, such as robust optimization, due to the inherent complexity of both parts. This paper outlines a robust DAO (RDAO) model and discusses novel methodologies for efficiently integrating salient constraints. Because the highly-complex RDAO model is difficult to solve, an original candidate plan generation (CPG) heuristic is proposed. The CPG produces rapid, high-quality, feasible plans, which are immediately clinically viable, and can also be used to generate a feasible incumbent solution for warm starting the RDAO model. Computational results obtained using clinical patient datasets with motion uncertainty show the benefit of incorporating the CPG, both in terms of first incumbent solution and final output plan quality., Comment: 27 pages, 14 figures
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- 2021
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62. Hopcroft's Problem, Log-Star Shaving, 2D Fractional Cascading, and Decision Trees
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Chan, Timothy M. and Zheng, Da Wei
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Computer Science - Computational Geometry - Abstract
We revisit Hopcroft's problem and related fundamental problems about geometric range searching. Given $n$ points and $n$ lines in the plane, we show how to count the number of point-line incidence pairs or the number of point-above-line pairs in $O(n^{4/3})$ time, which matches the conjectured lower bound and improves the best previous time bound of $n^{4/3}2^{O(\log^*n)}$ obtained almost 30 years ago by Matou\v{s}ek. We describe two interesting and different ways to achieve the result: the first is randomized and uses a new 2D version of fractional cascading for arrangements of lines; the second is deterministic and uses decision trees in a manner inspired by the sorting technique of Fredman (1976). The second approach extends to any constant dimension. Many consequences follow from these new ideas: for example, we obtain an $O(n^{4/3})$-time algorithm for line segment intersection counting in the plane, $O(n^{4/3})$-time randomized algorithms for bichromatic closest pair and Euclidean minimum spanning tree in three or four dimensions, and a randomized data structure for halfplane range counting in the plane with $O(n^{4/3})$ preprocessing time and space and $O(n^{1/3})$ query time., Comment: Appeared in SODA 2022
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- 2021
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63. Dynamic Geometric Set Cover, Revisited
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Chan, Timothy M., He, Qizheng, Suri, Subhash, and Xue, Jie
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Computer Science - Computational Geometry - Abstract
Geometric set cover is a classical problem in computational geometry, which has been extensively studied in the past. In the dynamic version of the problem, points and ranges may be inserted and deleted, and our goal is to efficiently maintain a set cover solution (satisfying certain quality requirement). In this paper, we give a plethora of new dynamic geometric set cover data structures in 1D and 2D, which significantly improve and extend the previous results: 1. The first data structure for $(1+\varepsilon)$-approximate dynamic interval set cover with polylogarithmic amortized update time. Specifically, we achieve an update time of $O(\log^3 n/\varepsilon)$, improving the $O(n^\delta/\varepsilon)$ bound of Agarwal et al. [SoCG'20], where $\delta>0$ denotes an arbitrarily small constant. 2. A data structure for $O(1)$-approximate dynamic unit-square set cover with $2^{O(\sqrt{\log n})}$ amortized update time, substantially improving the $O(n^{1/2+\delta})$ update time of Agarwal et al. [SoCG'20]. 3. A data structure for $O(1)$-approximate dynamic square set cover with $O(n^{1/2+\delta})$ randomized amortized update time, improving the $O(n^{2/3+\delta})$ update time of Chan and He [SoCG'21]. 4. A data structure for $O(1)$-approximate dynamic 2D halfplane set cover with $O(n^{17/23+\delta})$ randomized amortized update time. The previous solution for halfplane set cover by Chan and He [SoCG'21] is slower and can only report the size of the approximate solution. 5. The first sublinear results for the \textit{weighted} version of dynamic geometric set cover. Specifically, we give a data structure for $(3+o(1))$-approximate dynamic weighted interval set cover with $2^{O(\sqrt{\log n \log\log n})}$ amortized update time and a data structure for $O(1)$-approximate dynamic weighted unit-square set cover with $O(n^\delta)$ amortized update time., Comment: to appear in SODA 2022
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- 2021
64. Simpler Reductions from Exact Triangle
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Chan, Timothy M., primary and Xu, Yinzhan, additional
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- 2024
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65. An Optimal Algorithm for Higher-Order Voronoi Diagrams in the Plane: The Usefulness of Nondeterminism
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Chan, Timothy M., primary, Cheng, Pingan, additional, and Zheng, Da Wei, additional
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- 2024
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66. More on Change-Making and Related Problems
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Chan, Timothy M. and He, Qizheng
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Computer Science - Data Structures and Algorithms - Abstract
Given a set of $n$ integer-valued coin types and a target value $t$, the well-known change-making problem asks for the minimum number of coins that sum to $t$, assuming an unlimited number of coins in each type. In the more general all-targets version of the problem, we want the minimum number of coins summing to $j$, for every $j=0,\ldots,t$. For example, the textbook dynamic programming algorithms can solve the all-targets problem in $O(nt)$ time. Recently, Chan and He (SOSA'20) described a number of $O(t\,\textrm{polylog}\,t)$-time algorithms for the original (single-target) version of the change-making problem, but not the all-targets version. We obtain a number of new results on change-making and related problems, including: 1. A new algorithm for the all-targets change-making problem with running time $\tilde{O}(t^{4/3})$, improving a previous $\tilde{O}(t^{3/2})$-time algorithm. 2. A very simple $\tilde{O}(u^2+t)$-time algorithm for the all-targets change-making problem, where $u$ denotes the maximum coin value. The analysis of the algorithm uses a theorem of Erd\H{o}s and Graham (1972) on the Frobenius problem. This algorithm can be extended to solve the all-capacities version of the unbounded knapsack problem (for integer item weights bounded by $u$). 3. For the original (single-target) coin changing problem, we describe a simple modification of one of Chan and He's algorithms that runs in $\tilde{O}(u)$ time (instead of $\tilde{O}(t)$). 4. For the original (single-capacity) unbounded knapsack problem, we describe a simple algorithm that runs in $\tilde{O}(nu)$ time, improving previous near-$u^2$-time algorithms. 5. We also observe how one of our ideas implies a new result on the minimum word break problem, an optimization version of a string problem studied by Bringmann et al. (FOCS'17), generalizing change-making (which corresponds to the unary special case)., Comment: This is the full version of our ESA 2020 paper
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- 2021
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67. A Markov process approach to untangling intention versus execution in tennis
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Chan, Timothy C. Y., Fearing, Douglas S., Fernandes, Craig, and Kovalchik, Stephanie
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Mathematics - Optimization and Control ,Statistics - Applications - Abstract
Value functions are used in sports applications to determine the optimal action players should employ. However, most literature implicitly assumes that the player can perform the prescribed action with known and fixed probability of success. The effect of varying this probability or, equivalently, "execution error" in implementing an action (e.g., hitting a tennis ball to a specific location on the court) on the design of optimal strategies, has received limited attention. In this paper, we develop a novel modeling framework based on Markov reward processes and Markov decision processes to investigate how execution error impacts a player's value function and strategy in tennis. We power our models with hundreds of millions of simulated tennis shots with 3D ball and 2D player tracking data. We find that optimal shot selection strategies in tennis become more conservative as execution error grows, and that having perfect execution with the empirical shot selection strategy is roughly equivalent to choosing one or two optimal shots with average execution error. We find that execution error on backhand shots is more costly than on forehand shots, and that optimal shot selection on a serve return is more valuable than on any other shot, over all values of execution error.
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- 2021
68. Inverse Optimization: Theory and Applications
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Chan, Timothy C. Y., Mahmood, Rafid, and Zhu, Ian Yihang
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Mathematics - Optimization and Control - Abstract
Inverse optimization describes a process that is the "reverse" of traditional mathematical optimization. Unlike traditional optimization, which seeks to compute optimal decisions given an objective and constraints, inverse optimization takes decisions as input and determines an objective and/or constraints that render these decisions approximately or exactly optimal. In recent years, there has been an explosion of interest in the mathematics and applications of inverse optimization. This paper provides a comprehensive review of both the methodological and application-oriented literature in inverse optimization.
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- 2021
69. Inverse Optimization on Hierarchical Networks: An Application to Breast Cancer Clinical Pathways
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Chan, Timothy C. Y., Forster, Katharina, Habbous, Steven, Holloway, Claire, Ieraci, Luciano, Shalaby, Yusuf, and Yousefi, Nasrin
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Mathematics - Optimization and Control - Abstract
Clinical pathways are standardized processes that outline the steps required for managing a specific disease. However, patient pathways often deviate from clinical pathways. Measuring the concordance of patient pathways to clinical pathways is important for health system monitoring and informing quality improvement initiatives. In this paper, we develop an inverse optimization-based approach to measuring pathway concordance in breast cancer, a complex disease. We capture this complexity in a hierarchical network that models the patient's journey through the health system. A novel inverse shortest path model is formulated and solved on this hierarchical network to estimate arc costs, which are used to form a concordance metric to measure the distance between patient pathways and shortest paths (i.e., clinical pathways). Using real breast cancer patient data from Ontario, Canada, we demonstrate that our concordance metric has a statistically significant association with survival for all breast cancer patient subgroups. We also use it to quantify the extent of patient pathway discordances across all subgroups, finding that patients undertaking additional clinical activities constitute the primary driver of discordance in the population., Comment: 24 pages + Appendices
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- 2021
70. Introducing and Integrating Machine Learning in an Operations Research Curriculum: An Application-Driven Course
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Boutilier, Justin J. and Chan, Timothy C. Y.
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Artificial intelligence (AI) and operations research (OR) have long been intertwined because of their synergistic relationship. Given the increasing popularity of AI and machine learning in particular, we face growing demand for educational offerings in this area from our students. This paper describes two courses that introduce machine learning concepts to undergraduate, predominantly industrial engineering and operations research students. Instead of taking a methods-first approach, these courses use real-world applications to motivate, introduce, and explore these machine learning techniques and highlight meaningful overlap with operations research. Significant hands-on coding experience is used to build student proficiency with the techniques. Student feedback indicates that these courses have greatly increased student interest in machine learning and appreciation of the real-world impact that analytics can have and helped students develop practical skills that they can apply. We believe that similar application-driven courses that connect machine learning and operations research would be valuable additions to undergraduate OR curricula broadly.
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- 2023
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71. Faster Algorithms for Largest Empty Rectangles and Boxes
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Chan, Timothy M.
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- 2023
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72. Assessing feasibility of proposed extracorporeal cardiopulmonary resuscitation programmes for out-of-hospital cardiac arrest in Scotland via geospatial modelling
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Leung, K.H. Benjamin, Hartley, Louise, Moncur, Lyle, Gillon, Stuart, Short, Steven, Chan, Timothy C.Y., and Clegg, Gareth R.
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- 2024
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73. Faster Algorithms for Largest Empty Rectangles and Boxes
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Chan, Timothy M.
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Computer Science - Computational Geometry - Abstract
We revisit a classical problem in computational geometry: finding the largest-volume axis-aligned empty box (inside a given bounding box) amidst $n$ given points in $d$ dimensions. Previously, the best algorithms known have running time $O(n\log^2n)$ for $d=2$ (by Aggarwal and Suri [SoCG'87]) and near $n^d$ for $d\ge 3$. We describe faster algorithms with running time (i) $O(n2^{O(\log^*n)}\log n)$ for $d=2$, (ii) $O(n^{2.5+o(1)})$ time for $d=3$, and (iii) $\widetilde{O}(n^{(5d+2)/6})$ time for any constant $d\ge 4$. To obtain the higher-dimensional result, we adapt and extend previous techniques for Klee's measure problem to optimize certain objective functions over the complement of a union of orthants., Comment: full version of a SoCG 2021 paper
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- 2021
74. More Dynamic Data Structures for Geometric Set Cover with Sublinear Update Time
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Chan, Timothy M. and He, Qizheng
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Computer Science - Computational Geometry - Abstract
We study geometric set cover problems in dynamic settings, allowing insertions and deletions of points and objects. We present the first dynamic data structure that can maintain an $O(1)$-approximation in sublinear update time for set cover for axis-aligned squares in 2D. More precisely, we obtain randomized update time $O(n^{2/3+\delta})$ for an arbitrarily small constant $\delta>0$. Previously, a dynamic geometric set cover data structure with sublinear update time was known only for unit squares by Agarwal, Chang, Suri, Xiao, and Xue [SoCG 2020]. If only an approximate size of the solution is needed, then we can also obtain sublinear amortized update time for disks in 2D and halfspaces in 3D. As a byproduct, our techniques for dynamic set cover also yield an optimal randomized $O(n\log n)$-time algorithm for static set cover for 2D disks and 3D halfspaces, improving our earlier $O(n\log n(\log\log n)^{O(1)})$ result [SoCG 2020].
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- 2021
75. Algorithms, Reductions and Equivalences for Small Weight Variants of All-Pairs Shortest Paths
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Chan, Timothy M., Williams, Virginia Vassilevska, and Xu, Yinzhan
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Computer Science - Data Structures and Algorithms ,Computer Science - Computational Complexity - Abstract
APSP with small integer weights in undirected graphs [Seidel'95, Galil and Margalit'97] has an $\tilde{O}(n^\omega)$ time algorithm, where $\omega<2.373$ is the matrix multiplication exponent. APSP in directed graphs with small weights however, has a much slower running time that would be $\Omega(n^{2.5})$ even if $\omega=2$ [Zwick'02]. To understand this $n^{2.5}$ bottleneck, we build a web of reductions around directed unweighted APSP. We show that it is fine-grained equivalent to computing a rectangular Min-Plus product for matrices with integer entries; the dimensions and entry size of the matrices depend on the value of $\omega$. As a consequence, we establish an equivalence between APSP in directed unweighted graphs, APSP in directed graphs with small $(\tilde{O}(1))$ integer weights, All-Pairs Longest Paths in DAGs with small weights, approximate APSP with additive error $c$ in directed graphs with small weights, for $c\le \tilde{O}(1)$ and several other graph problems. We also provide fine-grained reductions from directed unweighted APSP to All-Pairs Shortest Lightest Paths (APSLP) in undirected graphs with $\{0,1\}$ weights and $\#_{\text{mod}\ c}$APSP in directed unweighted graphs (computing counts mod $c$). We complement our hardness results with new algorithms. We improve the known algorithms for APSLP in directed graphs with small integer weights and for approximate APSP with sublinear additive error in directed unweighted graphs. Our algorithm for approximate APSP with sublinear additive error is optimal, when viewed as a reduction to Min-Plus product. We also give new algorithms for variants of #APSP in unweighted graphs, as well as a near-optimal $\tilde{O}(n^3)$-time algorithm for the original #APSP problem in unweighted graphs. Our techniques also lead to a simpler alternative for the original APSP problem in undirected graphs with small integer weights., Comment: abstract shortened to fit arXiv requirements
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- 2021
76. Inducibility and universality for trees
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Chan, Timothy F. N., Kral, Daniel, Mohar, Bojan, and Wood, David R.
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Mathematics - Combinatorics ,05C05, 05C35 - Abstract
We answer three questions posed by Bubeck and Linial on the limit densities of subtrees in trees. We prove there exist positive $\varepsilon_1$ and $\varepsilon_2$ such that every tree that is neither a path nor a star has inducibility at most $1-\varepsilon_1$, where the inducibility of a tree $T$ is defined as the maximum limit density of $T$, and that there are infinitely many trees with inducibility at least $\varepsilon_2$. Finally, we construct a universal sequence of trees; that is, a sequence in which the limit density of any tree is positive., Comment: 31 pages, 8 figures
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- 2021
77. Outcomes in patients with and without disability admitted to hospital with COVID-19: a retrospective cohort study.
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Brown, Hilary, Saha, Sudipta, Chan, Timothy, Cheung, Angela, Fralick, Michael, Ghassemi, Marzyeh, Herridge, Margaret, Kwan, Janice, Rawal, Shail, Rosella, Laura, Tang, Terence, Weinerman, Adina, Lunsky, Yona, Razak, Fahad, and Verma, Amol
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Aged ,Aged ,80 and over ,Brain Injuries ,Traumatic ,COVID-19 ,Cohort Studies ,Developmental Disabilities ,Disabled Persons ,Female ,Hearing Loss ,Hospital Mortality ,Hospitalization ,Hospitals ,Humans ,Intensive Care Units ,Length of Stay ,Male ,Middle Aged ,Ontario ,Patient Readmission ,Retrospective Studies ,SARS-CoV-2 ,Vision Disorders - Abstract
BACKGROUND: Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability. METHODS: We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity. RESULTS: Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19-1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14-2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability. INTERPRETATION: Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.
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- 2022
78. Inducibility and universality for trees
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Chan, Timothy F. N., Král', Daniel, Mohar, Bojan, and Wood, David R.
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Trees ,inducibility ,graph density - Abstract
We answer three questions posed by Bubeck and Linial on the limit densities of subtrees in trees. We prove there exist positive \(\varepsilon_1\) and \(\varepsilon_2\) such that every tree that is neither a path nor a star has inducibility at most \(1-\varepsilon_1\), where the inducibility of a tree \(T\) is defined as the maximum limit density of \(T\), and that there are infinitely many trees with inducibility at least \(\varepsilon_2\). Finally, we construct a universal sequence of trees; that is, a sequence in which the limit density of any tree is positive.Mathematics Subject Classifications: 05C05, 05C35Keywords: Trees, inducibility, graph density
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- 2022
79. Settling behaviour of thin curved particles in quiescent fluid and turbulence
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Chan, Timothy T. K., Esteban, Luis Blay, Huisman, Sander G., Shrimpton, John S., and Ganapathisubramani, Bharathram
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Physics - Fluid Dynamics - Abstract
The motion of thin curved falling particles is ubiquitous in both nature and industry but is not yet widely examined. Here, we describe an experimental study on the dynamics of thin cylindrical shells resembling broken bottle fragments settling through quiescent fluid and homogeneous anisotropic turbulence. The particles have Archimedes numbers based on the mean descent velocity $0.75 \times 10^4 \lesssim Ar \lesssim 2.75 \times 10^4$. Turbulence reaching a Reynolds number of $Re_\lambda \approx 100$ is generated in a water tank using random jet arrays mounted in a co-planar configuration. After the flow becomes statistically stationary, a particle is released and its three-dimensional motion is recorded using two orthogonally positioned high-speed cameras. We propose a simple pendulum model that accurately captures the velocity fluctuations of the particles in still fluid and find that differences in the falling style might be explained by a closer alignment between the particle's pitch angle and its velocity vector. By comparing the trajectories under background turbulence with the quiescent fluid cases, we measure a decrease in the mean descent velocity in turbulence for the conditions tested. We also study the secondary motion of the particles and identify descent events that are unique to turbulence such as 'long gliding' and 'rapid rotation' events. Lastly, we show an increase in the radial dispersion of the particles under background turbulence and correlate the timescale of descent events with the local settling velocity., Comment: 26 pages, 18 figures, 5 movies
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- 2020
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80. OpenKBP: The open-access knowledge-based planning grand challenge
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Babier, Aaron, Zhang, Binghao, Mahmood, Rafid, Moore, Kevin L., Purdie, Thomas G., McNiven, Andrea L., and Chan, Timothy C. Y.
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Physics - Medical Physics ,Computer Science - Computer Vision and Pattern Recognition - Abstract
The purpose of this work is to advance fair and consistent comparisons of dose prediction methods for knowledge-based planning (KBP) in radiation therapy research. We hosted OpenKBP, a 2020 AAPM Grand Challenge, and challenged participants to develop the best method for predicting the dose of contoured CT images. The models were evaluated according to two separate scores: (1) dose score, which evaluates the full 3D dose distributions, and (2) dose-volume histogram (DVH) score, which evaluates a set DVH metrics. Participants were given the data of 340 patients who were treated for head-and-neck cancer with radiation therapy. The data was partitioned into training (n=200), validation (n=40), and testing (n=100) datasets. All participants performed training and validation with the corresponding datasets during the validation phase of the Challenge, and we ranked the models in the testing phase based on out-of-sample performance. The Challenge attracted 195 participants from 28 countries, and 73 of those participants formed 44 teams in the validation phase, which received a total of 1750 submissions. The testing phase garnered submissions from 28 teams. On average, over the course of the validation phase, participants improved the dose and DVH scores of their models by a factor of 2.7 and 5.7, respectively. In the testing phase one model achieved significantly better dose and DVH score than the runner-up models. Lastly, many of the top performing teams reported using generalizable techniques (e.g., ensembles) to achieve higher performance than their competition. This is the first competition for knowledge-based planning research, and it helped launch the first platform for comparing KBP prediction methods fairly and consistently. The OpenKBP datasets are available publicly to help benchmark future KBP research, which has also democratized KBP research by making it accessible to everyone., Comment: 26 pages, 6 figures, 5 tables
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- 2020
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81. Inverse Mixed Integer Optimization: Polyhedral Insights and Trust Region Methods
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Bodur, Merve, Chan, Timothy C. Y., and Zhu, Ian Yihang
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Mathematics - Optimization and Control - Abstract
Inverse optimization, determining parameters of an optimization problem that render a given solution optimal, has received increasing attention in recent years. While significant inverse optimization literature exists for convex optimization problems, there have been few advances for discrete problems, despite the ubiquity of applications that fundamentally rely on discrete decision-making. In this paper, we present a new set of theoretical insights and algorithms for the general class of inverse mixed integer linear optimization problems. Specifically, a general characterization of optimality conditions is established and leveraged to design new cutting plane solution algorithms. Through an extensive set of computational experiments, we show that our methods provide substantial improvements over existing methods in solving the largest and most difficult instances to date.
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- 2020
82. Machine Learning as a Catalyst for Value-Based Health Care
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Crowson, Matthew G. and Chan, Timothy C. Y.
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Computer Science - Computers and Society - Abstract
In this manuscript, we present an argument that machine learning, a subfield of artificial intelligence, can drive improvement in value-based health care through reducing error in clinical decision making. Much of what has been previously published on machine learning in medicine represent single-use or proof-of-concept cases, as well as broad reviews of the advantages and limitations of machine learning. It is timely to look at the broader strategy for artificial intelligence implementation in medicine and emphasize how machine learning can positively influence value-based care.
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- 2020
83. Faster Approximation Algorithms for Geometric Set Cover
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Chan, Timothy M. and He, Qizheng
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Computer Science - Computational Geometry ,Computer Science - Data Structures and Algorithms - Abstract
We improve the running times of $O(1)$-approximation algorithms for the set cover problem in geometric settings, specifically, covering points by disks in the plane, or covering points by halfspaces in three dimensions. In the unweighted case, Agarwal and Pan [SoCG 2014] gave a randomized $O(n\log^4 n)$-time, $O(1)$-approximation algorithm, by using variants of the multiplicative weight update (MWU) method combined with geometric data structures. We simplify the data structure requirement in one of their methods and obtain a deterministic $O(n\log^3 n\log\log n)$-time algorithm. With further new ideas, we obtain a still faster randomized $O(n\log n(\log\log n)^{O(1)})$-time algorithm. For the weighted problem, we also give a randomized $O(n\log^4n\log\log n)$-time, $O(1)$-approximation algorithm, by simple modifications to the MWU method and the quasi-uniform sampling technique.
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- 2020
84. Further Results on Colored Range Searching
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Chan, Timothy M., He, Qizheng, and Nekrich, Yakov
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Computer Science - Data Structures and Algorithms ,Computer Science - Computational Geometry - Abstract
We present a number of new results about range searching for colored (or "categorical") data: 1. For a set of $n$ colored points in three dimensions, we describe randomized data structures with $O(n\mathop{\rm polylog}n)$ space that can report the distinct colors in any query orthogonal range (axis-aligned box) in $O(k\mathop{\rm polyloglog} n)$ expected time, where $k$ is the number of distinct colors in the range, assuming that coordinates are in $\{1,\ldots,n\}$. Previous data structures require $O(\frac{\log n}{\log\log n} + k)$ query time. Our result also implies improvements in higher constant dimensions. 2. Our data structures can be adapted to halfspace ranges in three dimensions (or circular ranges in two dimensions), achieving $O(k\log n)$ expected query time. Previous data structures require $O(k\log^2n)$ query time. 3. For a set of $n$ colored points in two dimensions, we describe a data structure with $O(n\mathop{\rm polylog}n)$ space that can answer colored "type-2" range counting queries: report the number of occurrences of every distinct color in a query orthogonal range. The query time is $O(\frac{\log n}{\log\log n} + k\log\log n)$, where $k$ is the number of distinct colors in the range. Naively performing $k$ uncolored range counting queries would require $O(k\frac{\log n}{\log\log n})$ time. Our data structures are designed using a variety of techniques, including colored variants of randomized incremental construction (which may be of independent interest), colored variants of shallow cuttings, and bit-packing tricks., Comment: full version of a SoCG'20 paper
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- 2020
85. Neutrophil to lymphocyte ratio (NTLR) predicts local control and overall survival after stereotactic body radiotherapy (SBRT) in metastatic sarcoma
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Somasundaram, Eashwar, Anderson, Peter M., Smile, Timothy D., Halima, Ahmed, Broughman, James B., Reddy, Chandana A., Parsai, Shireen, Scott, Jacob G., Chan, Timothy, Campbell, Shauna, Angelov, Lilyana, Zahler, Stacey, Trucco, Matteo, Thomas, Stefanie M., Johnson, Shavaughn, Qi, Peng, Magnelli, Anthony, and Murphy, Erin S.
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- 2023
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86. FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling
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Liebig, Sven, Neumann, Martin, Silva, Patricia, Ortiz-Tanchez, Jutta, Schulze, Veronika, Isaakidis, Konstandina, Schlee, Cornelia, Schroeder, Michael P., Beder, Thomas, Morris, Luc G. T., Chan, Timothy A., Bastian, Lorenz, Burmeister, Thomas, Schwartz, Stefan, Gökbuget, Nicola, Mochmann, Liliana H., and Baldus, Claudia D.
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- 2023
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87. Chinese Rituals
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Chan, Celia Hoi Yan, Chan, Timothy Hang Yee, Chan, Cecilia Lai Wan, Tognetti, Mara, Section editor, and Maggino, Filomena, editor
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- 2023
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88. VISTA promotes the metabolism and differentiation of myeloid-derived suppressor cells by STAT3 and polyamine-dependent mechanisms
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Zhang, Keman, Zakeri, Amin, Alban, Tyler, Dong, Juan, Ta, Hieu M., Zalavadia, Ajay H., Branicky, Andrelie, Zhao, Haoxin, Juric, Ivan, Husic, Hana, Parthasarathy, Prerana B., Rupani, Amit, Drazba, Judy A., Chakraborty, Abhishek A., Ching-Cheng Huang, Stanley, Chan, Timothy, Avril, Stefanie, and Wang, Li Lily
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- 2024
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89. Peripheral inflammatory biomarkers define biotypes of bipolar depression
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Lee, Yena, Mansur, Rodrigo B, Brietzke, Elisa, Kapogiannis, Dimitrios, Delgado-Peraza, Francheska, Boutilier, Justin J, Chan, Timothy CY, Carmona, Nicole E, Rosenblat, Joshua D, Lee, JungGoo, Maletic, Vladimir, Vinberg, Maj, Suppes, Trisha, Goldstein, Benjamin I, Ravindran, Arun V, Taylor, Valerie H, Chawla, Sahil, Nogueras-Ortiz, Carlos, Cosgrove, Victoria E, Kramer, Nicole E, Ho, Roger, Raison, Charles A, and McIntyre, Roger S
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Brain Disorders ,Clinical Research ,Neurosciences ,Depression ,Mental Health ,Biomarkers ,Bipolar Disorder ,Humans ,Infliximab ,Insulin Receptor Substrate Proteins ,MAP Kinase Signaling System ,NF-kappa B ,Tumor Necrosis Factor-alpha ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.
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- 2021
90. Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial
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Riaz, Nadeem, Sherman, Eric, Pei, Xin, Schöder, Heiko, Grkovski, Milan, Paudyal, Ramesh, Katabi, Nora, Selenica, Pier, Yamaguchi, Takafumi N, Ma, Daniel, Lee, Simon K, Shah, Rachna, Kumar, Rahul, Kuo, Fengshen, Ratnakumar, Abhirami, Aleynick, Nathan, Brown, David, Zhang, Zhigang, Hatzoglou, Vaios, Liu, Lydia Y, Salcedo, Adriana, Tsai, Chiaojung J, McBride, Sean, Morris, Luc GT, Boyle, Jay, Singh, Bhuvanesh, Higginson, Daniel S, Damerla, Rama R, da Cruz Paula, Arnaud, Price, Katharine, Moore, Eric J, Garcia, Joaquin J, Foote, Robert, Ho, Alan, Wong, Richard J, Chan, Timothy A, Powell, Simon N, Boutros, Paul C, Humm, John L, Shukla-Dave, Amita, Pfister, David, Reis-Filho, Jorge S, and Lee, Nancy
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Radiation Oncology ,Biomedical Imaging ,Clinical Research ,Rare Diseases ,Genetics ,Precision Medicine ,4.2 Evaluation of markers and technologies ,Chemoradiotherapy ,Humans ,Oropharyngeal Neoplasms ,Positron-Emission Tomography ,Prospective Studies ,Radiotherapy Dosage ,Tumor Hypoxia ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundPatients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy.MethodsIn 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided.ResultsFifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03).ConclusionsDeescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.
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- 2021
91. Public defibrillator accessibility and mobility trends during the COVID-19 pandemic in Canada.
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Leung, K, Alam, Rejuana, Brooks, Steven, and Chan, Timothy
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Accessibility ,COVID-19 ,Public access defibrillator ,COVID-19 ,Canada ,Defibrillators ,Humans ,Out-of-Hospital Cardiac Arrest ,Pandemics ,SARS-CoV-2 - Abstract
INTRODUCTION: The COVID-19 pandemic has led to closures of non-essential businesses and buildings. The impact of such closures on automated external defibrillator (AED) accessibility compared to changes in foot traffic levels is unknown. METHODS: We identified all publicly available online AED registries in Canada last updated May 1, 2019 or later. We mapped AED locations to location types and classified each location type as completely inaccessible, partially inaccessible, or unaffected based on government-issued closure orders as of May 1, 2020. Using location and mobility data from Googles COVID-19 Community Mobility Reports, we identified the change in foot traffic levels between February 15-May 1, 2020 (excluding April 10-12) compared to the baseline of January 3-February 1, 2020, and determined the discrepancy between foot traffic levels and AED accessibility. RESULTS: We identified four provincial and two municipal AED registries containing a total of 5848 AEDs. Of those, we estimated that 69.9% were completely inaccessible, 18.8% were partially inaccessible, and 11.3% were unaffected. Parks, retail and recreation locations, and workplaces experienced the greatest reduction in AED accessibility. The greatest discrepancies between foot traffic levels and AED accessibility occurred in parks, retail and recreation locations, and transit stations. CONCLUSION: A majority of AEDs became inaccessible during the COVID-19 pandemic due to government-mandated closures. In a substantial number of locations across Canada, the reduction in AED accessibility was far greater than the reduction in foot traffic.
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- 2021
92. Improving EMS response times for out-of-hospital cardiac arrest in urban areas using drone-like vertical take-off and landing air ambulances: An international, simulation-based cohort study
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Heidet, Matthieu, Benjamin Leung, K.H., Bougouin, Wulfran, Alam, Rejuana, Frattini, Benoit, Liang, Danny, Jost, Daniel, Canon, Valentine, Deakin, John, Hubert, Hervé, Christenson, Jim, Vivien, Benoît, Chan, Timothy, Cariou, Alain, Dumas, Florence, Jouven, Xavier, Marijon, Eloi, Bennington, Steven, Travers, Stéphane, Souihi, Sami, Mermet, Eric, Freyssenge, Julie, Arrouy, Laurence, Lecarpentier, Eric, Derkenne, Clément, and Grunau, Brian
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- 2023
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93. Radiopharmaceuticals as combinatorial partners for immune checkpoint inhibitors
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Pouget, Jean-Pierre, Chan, Timothy A., Galluzzi, Lorenzo, and Constanzo, Julie
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- 2023
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94. Substructure sensities in extremal combinatorics
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Chan, Timothy F. N.
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QA Mathematics - Abstract
One of the primary goals of extremal combinatorics is to understand how an object's properties are influenced by the presence or multiplicity of a given substructure. Most classical theorems in the area, such as Mantel's Theorem, are phrased in terms of substructure counts such as the number of edges or the number of triangles in a graph. Gradually, however, it has become more popular to express results in terms of the density of substructures, where the substructure counts are normalised by some natural quantity. This approach has several benefits; results are often more succinctly stated using densities, and it becomes easier to focus on the asymptotic behaviour of objects. In this thesis, we study three topics concerning density. We begin Chapter 1 by contextualising the study of combinatorial density and justifying its importance within extremal combinatorics. We also introduce the relevant combinatorial objects, results, and questions that are central to the later chapters. Particular attention is paid to developing the theory of graph limits and flag algebras, two modern fields that rely heavily on the notion of density. In Chapter 2, we investigate the interplay between the densities of cycles of length 3 and 4 in large tournaments. In particular, we prove two cases of a conjecture of Linial and Morgenstern (2016) that the minimum density of 4-cycles in a graph with a fixed density of 3-cycles is attained by a particular random construction. In Chapter 3, we explore quasirandom permutations. A permutation is said to be quasirandom if the density of every subpermutation matches the expected density in a random permutation. Our main result is that quasirandomness can be characterised by a property which, on the surface, appears significantly weaker. Lastly, in Chapter 4, we resolve a problem posed by Bubeck and Linial (2016) on the inducibility of trees. The inducibility of a tree X is defined as the maximum possible density of X in a large tree. We show that there exist non-path, non-star trees with positive inducibility, but that all such trees have inducibility bounded away from 1. We also show that there exists a sequence of trees in which every possible subtree appears asymptotically with positive density.
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- 2021
95. A physiology-based mathematical model for the selection of appropriate ventilator controls for lung and diaphragm protection.
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Zhang, Binghao, Ratano, Damian, Brochard, Laurent, Georgopoulos, Dimitrios, Duffin, James, Long, Michael, Schepens, Tom, Telias, Irene, Slutsky, Arthur, Goligher, Ewan, and Chan, Timothy
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Decision support ,Mathematical modelling ,Mechanical ventilation ,Respiration ,Diaphragm ,Humans ,Lung ,Models ,Theoretical ,Respiration ,Artificial ,Ventilators ,Mechanical - Abstract
Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed. The Lung and Diaphragm Protective Ventilation (LDPV) model centers around respiratory drive and incorporates respiratory system mechanics, ventilator mechanics, and blood acid-base balance. The model uses patient-specific parameters as inputs and outputs predictions of a patients transpulmonary and esophageal driving pressures (outputs most clinically relevant to lung and diaphragm safety), as well as their blood pH, under various ventilator and sedation conditions. Model simulations and global optimization techniques were used to evaluate and characterize the model. The LDPV model is demonstrated to describe a CO2 respiratory response that is comparable to what is found in literature. Sensitivity analysis of the model indicate that the ventilator and sedation settings incorporated in the model have a significant impact on the target output parameters. Finally, the model is seen to be able to provide robust predictions of esophageal pressure, transpulmonary pressure and blood pH for patient parameters with realistic variability. The LDPV model is a robust physiological model which produces outputs which directly target and reflect the risk of ventilator-induced lung and diaphragm injury. Ventilation and sedation parameters are seen to modulate the model outputs in accordance with what is currently known in literature.
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- 2021
96. Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area.
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Verma, Amol, Hora, Tejasvi, Jung, Hae, Fralick, Michael, Malecki, Sarah, Lapointe-Shaw, Lauren, Weinerman, Adina, Tang, Terence, Kwan, Janice, Liu, Jessica, Rawal, Shail, Chan, Timothy, Cheung, Angela, Rosella, Laura, Ghassemi, Marzyeh, Herridge, Margaret, Mamdani, Muhammad, and Razak, Fahad
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Age Factors ,Aged ,Aged ,80 and over ,COVID-19 ,Critical Care ,Female ,Hospitalization ,Humans ,Influenza ,Human ,Male ,Middle Aged ,Ontario ,Outcome Assessment ,Health Care ,Retrospective Studies ,Risk Factors ,Socioeconomic Factors ,Survival Rate - Abstract
BACKGROUND: Patient characteristics, clinical care, resource use and outcomes associated with admission to hospital for coronavirus disease 2019 (COVID-19) in Canada are not well described. METHODS: We described all adults with COVID-19 or influenza discharged from inpatient medical services and medical-surgical intensive care units (ICUs) between Nov. 1, 2019, and June 30, 2020, at 7 hospitals in Toronto and Mississauga, Ontario. We compared patient outcomes using multivariable regression models, controlling for patient sociodemographic factors and comorbidity level. We validated the accuracy of 7 externally developed risk scores to predict mortality among patients with COVID-19. RESULTS: There were 1027 hospital admissions with COVID-19 (median age 65 yr, 59.1% male) and 783 with influenza (median age 68 yr, 50.8% male). Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared with influenza, patients with COVID-19 had significantly greater in-hospital mortality (unadjusted 19.9% v. 6.1%, adjusted relative risk [RR] 3.46, 95% confidence interval [CI] 2.56-4.68), ICU use (unadjusted 26.4% v. 18.0%, adjusted RR 1.50, 95% CI 1.25-1.80) and hospital length of stay (unadjusted median 8.7 d v. 4.8 d, adjusted rate ratio 1.45, 95% CI 1.25-1.69). Thirty-day readmission was not significantly different (unadjusted 9.3% v. 9.6%, adjusted RR 0.98, 95% CI 0.70-1.39). Three points-based risk scores for predicting in-hospital mortality showed good discrimination (area under the receiver operating characteristic curve [AUC] ranging from 0.72 to 0.81) and calibration. INTERPRETATION: During the first wave of the pandemic, admission to hospital for COVID-19 was associated with significantly greater mortality, ICU use and hospital length of stay than influenza. Simple risk scores can predict in-hospital mortality in patients with COVID-19 with good accuracy.
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- 2021
97. Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors
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Zapata, Luis, Caravagna, Giulio, Williams, Marc J., Lakatos, Eszter, AbdulJabbar, Khalid, Werner, Benjamin, Chowell, Diego, James, Chela, Gourmet, Lucie, Milite, Salvatore, Acar, Ahmet, Riaz, Nadeem, Chan, Timothy A., Graham, Trevor A., and Sottoriva, Andrea
- Published
- 2023
- Full Text
- View/download PDF
98. H3K9 methylation drives resistance to androgen receptor–antagonist therapy in prostate cancer
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Baratchian, Mehdi, Tiwari, Ritika, Khalighi, Sirvan, Chakravarthy, Ankur, Yuan, Wei, Berk, Michael, Li, Jianneng, Guerinot, Amy, de Bono, Johann, Makarov, Vladimir, Chan, Timothy A., Silverman, Robert H., Stark, George R., Varadan, Vinay, De Carvalho, Daniel D., Chakraborty, Abhishek A., and Sharifi, Nima
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- 2022
99. Approximating Text-to-Pattern Hamming Distances
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Chan, Timothy M., Golan, Shay, Kociumaka, Tomasz, Kopelowitz, Tsvi, and Porat, Ely
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Computer Science - Data Structures and Algorithms - Abstract
We revisit a fundamental problem in string matching: given a pattern of length m and a text of length n, both over an alphabet of size $\sigma$, compute the Hamming distance between the pattern and the text at every location. Several $(1+\epsilon)$-approximation algorithms have been proposed in the literature, with running time of the form $O(\epsilon^{-O(1)}n\log n\log m)$, all using fast Fourier transform (FFT). We describe a simple $(1+\epsilon)$-approximation algorithm that is faster and does not need FFT. Combining our approach with additional ideas leads to numerous new results: - We obtain the first linear-time approximation algorithm; the running time is $O(\epsilon^{-2}n)$. - We obtain a faster exact algorithm computing all Hamming distances up to a given threshold k; its running time improves previous results by logarithmic factors and is linear if $k\le\sqrt m$. - We obtain approximation algorithms with better $\epsilon$-dependence using rectangular matrix multiplication. The time-bound is $\~O(n)$ when the pattern is sufficiently long: $m\ge \epsilon^{-28}$. Previous algorithms require $\~O(\epsilon^{-1}n)$ time. - When k is not too small, we obtain a truly sublinear-time algorithm to find all locations with Hamming distance approximately (up to a constant factor) less than k, in $O((n/k^{\Omega(1)}+occ)n^{o(1)})$ time, where occ is the output size. The algorithm leads to a property tester, returning true if an exact match exists and false if the Hamming distance is more than $\delta m$ at every location, running in $\~O(\delta^{-1/3}n^{2/3}+\delta^{-1}n/m)$ time. - We obtain a streaming algorithm to report all locations with Hamming distance approximately less than k, using $\~O(\epsilon^{-2}\sqrt k)$ space. Previously, streaming algorithms were known for the exact problem with \~O(k) space or for the approximate problem with $\~O(\epsilon^{-O(1)}\sqrt m)$ space.
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- 2020
100. Improved Upper and Lower Bounds for LR Drawings of Binary Trees
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Chan, Timothy M. and Huang, Zhengcheng
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Computer Science - Computational Geometry - Abstract
In SODA'99, Chan introduced a simple type of planar straight-line upward order-preserving drawings of binary trees, known as LR drawings: such a drawing is obtained by picking a root-to-leaf path, drawing the path as a straight line, and recursively drawing the subtrees along the paths. Chan proved that any binary tree with $n$ nodes admits an LR drawing with $O(n^{0.48})$ width. In SODA'17, Frati, Patrignani, and Roselli proved that there exist families of $n$-node binary trees for which any LR drawing has $\Omega(n^{0.418})$ width. In this note, we improve Chan's upper bound to $O(n^{0.437})$ and Frati et al.'s lower bound to $\Omega(n^{0.429})$., Comment: Appears in the Proceedings of the 28th International Symposium on Graph Drawing and Network Visualization (GD 2020)
- Published
- 2019
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