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18. MinePlanner: A Benchmark for Long-Horizon Planning in Large Minecraft Worlds

Author

Hill, William, Liu, Ireton, Koch, Anita De Mello, Harvey, Damion, Kumar, Nishanth, Konidaris, George, and James, Steven

Subjects
Computer Science - Artificial Intelligence
Abstract

We propose a new benchmark for planning tasks based on the Minecraft game. Our benchmark contains 45 tasks overall, but also provides support for creating both propositional and numeric instances of new Minecraft tasks automatically. We benchmark numeric and propositional planning systems on these tasks, with results demonstrating that state-of-the-art planners are currently incapable of dealing with many of the challenges advanced by our new benchmark, such as scaling to instances with thousands of objects. Based on these results, we identify areas of improvement for future planners. Our framework is made available at https://github.com/IretonLiu/mine-pddl/., Comment: Accepted to the 6th ICAPS Workshop on the International Planning Competition (WIPC 2024)

Published
2023

20. The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

Author

Caswell, Deborah R, Gui, Philippe, Mayekar, Manasi K, Law, Emily K, Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D Lucas, Blakely, Collin M, Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I. Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J, Hill, William, Tomaschko, Mona, Lu, Wei-Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E, Rowan, Andrew, McCoach, Caroline E, Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James RM, Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L, Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K, Argyris, Prokopios P, Brown, William L, Yu, Elizabeth A, Rotow, Julia K, Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I, Thomas, Nicholas J, Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F, Chew, Su Kit, Reis-Filho, Jorge S, Jamal-Hanjani, Mariam, Vousden, Karen H, McGranahan, Nicholas, Van Allen, Eliezer M, Kanu, Nnennaya, Harris, Reuben S, Downward, Julian, Bivona, Trever G, and Swanton, Charles

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Biotechnology, Lung Cancer, Lung, Cancer, Women's Health, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Humans, Animals, Mice, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Mutation, Up-Regulation, ErbB Receptors, Cytidine Deaminase, Minor Histocompatibility Antigens, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

Published
2024

22. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author

Hobor, Sebastijan, Al Bakir, Maise, Hiley, Crispin T., Skrzypski, Marcin, Frankell, Alexander M., Bakker, Bjorn, Watkins, Thomas B. K., Markovets, Aleksandra, Dry, Jonathan R., Brown, Andrew P., van der Aart, Jasper, van den Bos, Hilda, Spierings, Diana, Oukrif, Dahmane, Novelli, Marco, Chakrabarti, Turja, Rabinowitz, Adam H., Ait Hassou, Laila, Litière, Saskia, Kerr, D. Lucas, Tan, Lisa, Kelly, Gavin, Moore, David A., Renshaw, Matthew J., Venkatesan, Subramanian, Hill, William, Huebner, Ariana, Martínez-Ruiz, Carlos, Black, James R. M., Wu, Wei, Angelova, Mihaela, McGranahan, Nicholas, Downward, Julian, Chmielecki, Juliann, Barrett, Carl, Litchfield, Kevin, Chew, Su Kit, Blakely, Collin M., de Bruin, Elza C., Foijer, Floris, Vousden, Karen H., Bivona, Trever G., Hynds, Robert E., Kanu, Nnennaya, Zaccaria, Simone, Grönroos, Eva, and Swanton, Charles

Published
2024
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26. Lung adenocarcinoma promotion by air pollutants

Author

Hill, William, Lim, Emilia L., Weeden, Clare E., Lee, Claudia, Augustine, Marcellus, Chen, Kezhong, Kuan, Feng-Che, Marongiu, Fabio, Evans, Jr, Edward J., Moore, David A., Rodrigues, Felipe S., Pich, Oriol, Bakker, Bjorn, Cha, Hongui, Myers, Renelle, van Maldegem, Febe, Boumelha, Jesse, Veeriah, Selvaraju, Rowan, Andrew, Naceur-Lombardelli, Cristina, Karasaki, Takahiro, Sivakumar, Monica, De, Swapnanil, Caswell, Deborah R., Nagano, Ai, Black, James R. M., Martínez-Ruiz, Carlos, Ryu, Min Hyung, Huff, Ryan D., Li, Shijia, Favé, Marie-Julie, Magness, Alastair, Suárez-Bonnet, Alejandro, Priestnall, Simon L., Lüchtenborg, Margreet, Lavelle, Katrina, Pethick, Joanna, Hardy, Steven, McRonald, Fiona E., Lin, Meng-Hung, Troccoli, Clara I., Ghosh, Moumita, Miller, York E., Merrick, Daniel T., Keith, Robert L., Al Bakir, Maise, Bailey, Chris, Hill, Mark S., Saal, Lao H., Chen, Yilun, George, Anthony M., Abbosh, Christopher, Kanu, Nnennaya, Lee, Se-Hoon, McGranahan, Nicholas, Berg, Christine D., Sasieni, Peter, Houlston, Richard, Turnbull, Clare, Lam, Stephen, Awadalla, Philip, Grönroos, Eva, Downward, Julian, Jacks, Tyler, Carlsten, Christopher, Malanchi, Ilaria, Hackshaw, Allan, Litchfield, Kevin, DeGregori, James, Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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33. Heterotypic cell-cell interactions between KrasG12D cells and normal neighbours in early pancreatic cancer

Author

Hill, William

Subjects
616.99
Abstract

At the initial stages of tumourigenesis, transformation occurs in a single cell within a healthy epithelial sheet. Competitive interactions between normal and Ras-transformed cells can drive the elimination of mutant cells from tissues to protect from carcinogenesis. Moreover, we have previously demonstrated that normal cells detect and eliminate Ras-transformed cells via differential EphA2 signalling. KrasG12D expressing cells (KrasG12D cells) initiate and drive the earliest stages of pancreatic cancer yet it is unclear if normal pancreatic cells can eliminate oncogenic cells. Here we use low level, stochastic induction of KrasG12D mutations in the pancreas to model the interaction of normal and transformed epithelial cells. We show that Ras-transformed cells adopt a contractile morphology and are eliminated from healthy tissue when present at low numbers. When surrounded by normal cells, KrasG12D cells become segregated, increase in compactness and are often extruded. We find that E-cadherin-based cell-cell contacts are downregulated and internalised in mutant cells when surrounded by normal neighbours in an EphA2-dependent manner. Our evidence also suggests that normal cells suppress progression of Ras-transformed cells to an early disease state. Together, this study suggests that non-transformed pancreatic epithelial cells can eliminate KrasG12D cells from the tissue via EphA2 signalling. These data identify a novel putative tumour-suppressive mechanism in the adult pancreas that mutant cells must first overcome to drive tumourigenesis. Understanding the earliest stages of pancreatic carcinogenesis will provide insight into how risk factors promote disease and may elucidate how pancreatic cancer spreads around the body.

Published
2018

34. Postoperative outcomes and trends in computer-navigated and robotic-assisted total hip arthroplasty.

Author

Piple, Amit S, Wang, Jennifer C, Hill, William, Chen, Matthew S, Gettleman, Brandon S, Liu, Kevin C, Heckmann, Nathanael D, and Christ, Alexander B

Subjects
SURGICAL robots, RISK assessment, TOTAL hip replacement, MORPHINE, PROSTHESIS-related infections, TREATMENT effectiveness, MULTIVARIATE analysis, DESCRIPTIVE statistics, COMPUTER-assisted surgery, SURGICAL complications, JOINT dislocations, OPIOID analgesics, STATISTICS, POSTOPERATIVE period, BLOOD transfusion, PERIPROSTHETIC fractures, DISEASE risk factors
Abstract

Introduction: As the volume of technology-assisted total hip arthroplasty (THA) increases, there is a need to characterise the outcomes of robotic-assisted (RA) and computer-navigated (CN) THA. The goal of this study was to assess outcomes and opioid consumption following CN-THA and RA-THA compared to conventionally-instrumented (CON) THA. Methods: The Premier Database was queried for all patients who underwent primary, elective THA from 2015-2020. Patients were divided into 3 groups: CN, RA, or CON-THA. Yearly usage trends were assessed. Univariate and multivariate analyses were performed to assess the 90-day risk of postoperative complications. Opioid consumption was reported in morphine milligram equivalents (MME) for postoperative days (POD) 0 and 1. Results: Overall, 474,707 elective THAs were identified (95.7% CON, 2.1% CN, 2.2% RA. After accounting for confounders, CN-THA patients were at decreased risk for periprosthetic joint infection (PJI) (aOR: 0.55, p < 0.001) and dislocation (aOR 0.45, p < 0.001), but increased risk for blood transfusion (aOR 1.97, <0.001) compared to CON-THA. RA-THA patients were at decreased risk of dislocation (aOR:0.66, p < 0.001) but increased risk for transfusion (aOR 1.20, p < 0.001), prosthesis breakage (aOR 3.88, p < 0.001), and periprosthetic fracture (aOR 1.72, p < 0.001). Opioid consumption for CN-THA patients was lower on POD1 and lower for RA-THA patients POD0 and 2 compared to CON-THA. Discussion: CN-THA was associated with reduced rates of PJI and dislocation, but increased rates of blood transfusion while RA-THA was associated with decreased rates of dislocation, but increased rates of blood transfusion, prosthesis complications, and periprosthetic fracture compared to CON-THA. Technology-assisted THA was associated with lower postoperative opioid consumption. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression

Author

Eisa, Nada H., Sudharsan, Periyasamy T., Herrero, Sergio Mas, Herberg, Samuel A., Volkman, Brian F., Aguilar-Pérez, Alexandra, Kondrikov, Dmitry, Elmansi, Ahmed M., Reitman, Charles, Shi, Xingming, Fulzele, Sadanand, McGee-Lawrence, Meghan E., Isales, Carlos M., Hamrick, Mark W., Johnson, Maribeth H., Chen, Jie, and Hill, William D.

Published
2021
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36. Deciphering the Influence of Socioeconomic Status on Brain Structure: Insights from Mendelian Randomization

Author

Xia, Charley, primary, Lu, Yuechen, additional, Zhou, Zhuzhuoyu, additional, Marchi, Mattia, additional, Kweon, Hyeokmoon, additional, Ning, Yuchen, additional, Liewald, David C.M., additional, Anderson, Emma L., additional, Koellinger, Philipp D., additional, Cox, Simon R., additional, Boks, Marco P., additional, and Hill, William David, additional

Published
2024
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38. Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells

Author

Potter Matthew L., Smith Kathryn, Vyavahare Sagar, Kumar Sandeep, Periyasamy-Thandavan Sudharsan, Hamrick Mark, Isales Carlos M., Hill William D., and Fulzele Sadanand

Subjects
bone marrow stromal cells, sdf-1, mirna, Biology (General), QH301-705.5
Abstract

Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.

Published
2021
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39. On the Spectra of Real and Complex Lam\'e Operators

Author

Haese-Hill, William A., Hallnäs, Martin A., and Veselov, Alexander P.

Subjects
Mathematics - Spectral Theory, Mathematics - Classical Analysis and ODEs
Abstract

We study Lam\'e operators of the form $$L = -\frac{d^2}{dx^2} + m(m+1)\omega^2\wp(\omega x+z_0),$$ with $m\in\mathbb{N}$ and $\omega$ a half-period of $\wp(z)$. For rectangular period lattices, we can choose $\omega$ and $z_0$ such that the potential is real, periodic and regular. It is known after Ince that the spectrum of the corresponding Lam\'e operator has a band structure with not more than $m$ gaps. In the first part of the paper, we prove that the opened gaps are precisely the first $m$ ones. In the second part, we study the Lam\'e spectrum for a generic period lattice when the potential is complex-valued. We concentrate on the $m=1$ case, when the spectrum consists of two regular analytic arcs, one of which extends to infinity, and briefly discuss the $m=2$ case, paying particular attention to the rhombic lattices.

Published
2016
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41. Contributors

Author

Anderson, Kate, primary, Barmanray, Rahul D., additional, Beauchamp, Alison, additional, Boschiero, Dario, additional, Brennan-Olsen, Sharon L., additional, Colón-Emeric, Cathleen, additional, Cordero, Natanael Perez, additional, Cvijetic, Selma, additional, Darling, Andrea L., additional, Dian, Larry, additional, Duckham, Rachel L., additional, Duque, Gustavo, additional, Farr, Joshua N., additional, Feehan, Jack, additional, Fulzele, Sadanand, additional, Ghasem-Zadeh, Ali, additional, Gilman, Jennifer C., additional, Hassan, Ebrahim Bani, additional, Hill, William D., additional, Hiruma, Eisuke, additional, Huang, Yushu, additional, Ilich, Jasminka Z., additional, Imani, Mahdi, additional, Karasik, David, additional, Kaur, Japneet, additional, Kelly, Owen J., additional, Khrystoforova, Iryna, additional, Lee, Peter, additional, Leng, Sean X., additional, Li, Yukang, additional, Liu, Ching-Ti, additional, MacDonald, Brian Alexander, additional, Malekipour, Fatemeh, additional, Mokhtarzadeh, Hossein, additional, Negm, Ahmed M., additional, O’Connor, Jordan, additional, Papaioannou, Alexandra, additional, Parmar, Naaz, additional, Schoenlein, Patricia V., additional, Seldeen, Kenneth Ladd, additional, Sharda, Neema, additional, Stefanaki, Charikleia, additional, Troen, Bruce Robert, additional, Waters, Debra L., additional, and Yates, Christopher J., additional

Published
2022
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43. Association of Plasma SDF-1 with Bone Mineral Density, Body Composition, and Hip Fractures in Older Adults: The Cardiovascular Health Study

Author

Carbone, Laura D, Bůžková, Petra, Fink, Howard A, Robbins, John A, Bethel, Monique, Hamrick, Mark W, and Hill, William D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Aging, Cardiovascular, Stem Cell Research - Nonembryonic - Non-Human, Osteoporosis, Stem Cell Research, Musculoskeletal, Aged, Aged, 80 and over, Body Composition, Bone Density, Bone and Bones, Cardiovascular Diseases, Chemokine CXCL12, Female, Hip Fractures, Humans, Male, Osteoclasts, Risk Factors, Sex Factors, DXA, Cytokines, Epidemiology, Body composition, Biochemistry and Cell Biology, Biomedical Engineering, Endocrinology & Metabolism, Clinical sciences, Biomedical engineering
Abstract

Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures. In 1536 CHS participants, SDF-1 plasma levels were significantly associated with increasing age (p

Published
2017

45. Complex exceptional orthogonal polynomials and quasi-invariance

Author

Haese-Hill, William A., Hallnäs, Martin A., and Veselov, Alexander P.

Subjects
Mathematical Physics, Nonlinear Sciences - Exactly Solvable and Integrable Systems
Abstract

Consider the Wronskians of the classical Hermite polynomials $$H_{\lambda, l}(x):=\mathrm{Wr}(H_l(x),H_{k_1}(x),\ldots, H_{k_n}(x)), \quad l \in \mathbb Z_{\geq 0},$$ where $k_i=\lambda_i+n-i, \,\, i=1,\dots, n$ and $\lambda=(\lambda_1, \dots, \lambda_n)$ is a partition. G\'omez-Ullate et al showed that for a special class of partitions the corresponding polynomials are orthogonal and dense among all polynomials with certain inner product, but in contrast to the usual case have some degrees missing (so called exceptional orthogonal polynomials). We generalise their results to all partitions by considering complex contours of integration and non-positive Hermitian products. The corresponding polynomials are orthogonal and dense in a finite-codimensional subspace of $\mathbb C[x]$ satisfying certain quasi-invariance conditions. A Laurent version of exceptional orthogonal polynomials, related to monodromy-free trigonometric Schr\"odinger operators, is also presented., Comment: 18 pages

Published
2015
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