Exploring the effects of robotic design on learning and neural control

The ongoing deep learning revolution has allowed computers to outclass humans in various games and perceive features imperceptible to humans during classification tasks. Current machine learning techniques have clearly distinguished themselves in specialized tasks. However, we have yet to see robots capable of performing multiple tasks at an expert level. Most work in this field is focused on the development of more sophisticated learning algorithms for a robot's controller given a largely static and presupposed robotic design. By focusing on the development of robotic bodies, rather than neural controllers, I have discovered that robots can be designed such that they overcome many of the current pitfalls encountered by neural controllers in multitask settings. Through this discovery, I also present novel metrics to explicitly measure the learning ability of a robotic design and its resistance to common problems such as catastrophic interference. Traditionally, the physical robot design requires human engineers to plan every aspect of the system, which is expensive and often relies on human intuition. In contrast, within the field of evolutionary robotics, evolutionary algorithms are used to automatically create optimized designs, however, such designs are often still limited in their ability to perform in a multitask setting. The metrics created and presented here give a novel path to automated design that allow evolved robots to synergize with their controller to improve the computational efficiency of their learning while overcoming catastrophic interference. Overall, this dissertation intimates the ability to automatically design robots that are more general purpose than current robots and that can perform various tasks while requiring less computation.Comment: arXiv admin note: text overlap with arXiv:2008.0639

Think / Make / Think (Exhibition Catalogue)

This exhibition featured the work of current professors in the University of Tennessee School of Art. Exhibiting faculty were: Joshua Bienko, Emily Bivens, Sally Brogden, Jason S. Brown, Paul Harrill, Paul Lee, Sarah Lowe, Beauvais Lyons, Frank Martin, Althea Murphy-Price, John Powers, Deborah Shmerler, Jered Sprecher, Cary Staples, Claire Stigliani, David Wilson, Karla Wozniak, Koichi Yamamoto, and Sam Yates

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

NEID Rossiter–McLaughlin Measurement of TOI-1268b: A Young Warm Saturn Aligned with Its Cool Host Star

Close-in gas giants present a surprising range of stellar obliquity, the angle between a planet's orbital axis and its host star's spin axis. It is unclear whether the obliquities reflect the planets' dynamical history (e.g., aligned for in situ formation or disk migration versus misaligned for high-eccentricity tidal migration) or whether other mechanisms (e.g., primordial misalignment or planet-star interactions) are more important in sculpting the obliquity distribution. Here we present the stellar obliquity measurement of TOI-1268 (TIC-142394656, V mag ∼10.9), a young K-type dwarf hosting an 8.2 day period, Saturn-sized planet. TOI-1268's lithium abundance and rotation period suggest the system age between the ages of the Pleiades cluster (∼120 Myr) and the Prasepe cluster (∼670 Myr). Using the newly commissioned NEID spectrograph, we constrain the stellar obliquity of TOI-1268 via the Rossiter-McLaughlin effect from both radial velocity and Doppler tomography signals. The 3σ upper bounds of the projected stellar obliquity λ from both models are below 60°. The large host star separation (a/R ∗ ∼17), combined with the system's young age, makes it unlikely that the planet has realigned its host star. The stellar obliquity measurement of TOI-1268 probes the architecture of a young gas giant beyond the reach of tidal realignment (a/R ∗ ≲10) and reveals an aligned or slightly misaligned system

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation