Encoding higher-order structure in visual working memory: A probabilistic model

When encoding a scene into memory, people store both theoverall gist of the scene and detailed information about a few specific objects. Moreover, they use the gist to guide their choice of which specific objects to remember. However, formal models of change detection, like those used to estimate visual working memory capacity, generally assume people represent no higher-order structure about the display and choose which items to encode at random. We present a probabilistic model of change detection that attempts to bridge this gap by formalizing the encoding of both specific items and higher-order information about simple working memory displays. We show that this model successfully predicts change detection performance for individual displays of patterned dots. More generally, we show that it is necessary for the model to encode higher-order structure in order to accurately predict human performance in the change detection task. This work thus confirms and formalizes the role of higher-order structure in visual working memory

Real-World Objects Are Not Represented as Bound Units: Independent Forgetting of Different Object Details from Visual Memory

Are real-world objects represented as bound units? Although a great deal of research has examined binding between the feature dimensions of simple shapes, little work has examined whether the featural properties of real-world objects are stored in a single unitary object representation. In a first experiment, we found that information about an object's color is forgotten more rapidly than the information about an object's state (e.g., open, closed), suggesting that observers do not forget objects as entirely bound units. In a second and third experiment, we examined whether state and exemplar information are forgotten separately or together. If these properties are forgotten separately, the probability of getting one feature correct should be independent of whether the other feature was correct. We found that after a short delay, observers frequently remember both state and exemplar information about the same objects, but after a longer delay, memory for the two properties becomes independent. This indicates that information about object state and exemplar are forgotten separately over time. We thus conclude that real-world objects are not represented in a single unitary representation in visual memory.Psycholog

Modeling Visual Working Memory with the MemToolbox

The MemToolbox is a collection of MATLAB functions for modeling visual working memory. In support of its goal to provide a full suite of data analysis tools, the toolbox includes implementations of popular models of visual working memory, real and simulated data sets, Bayesian and maximum likelihood estimation procedures for fitting models to data, visualizations of data and fit, validation routines, model comparison metrics, and experiment scripts. The MemToolbox is released under the permissive BSD license and is available at http://memtoolbox.org.Psycholog

Visual Long-Term Memory Has the Same Limit on Fidelity as Visual Working Memory

Visual long-term memory can store thousands of objects with surprising visual detail, but just how detailed are these representations, and how can one quantify this fidelity? Using the property of color as a case study, we estimated the precision of visual information in long-term memory, and compared this with the precision of the same information in working memory. Observers were shown real-world objects in random colors and were asked to recall the colors after a delay. We quantified two parameters of performance: the variability of internal representations of color (fidelity) and the probability of forgetting an object’s color altogether. Surprisingly, the fidelity of color information in long-term memory was comparable to the asymptotic precision of working memory. These results suggest that long-term memory and working memory may be constrained by a common limit, such as a bound on the fidelity required to retrieve a memory representation.Psycholog

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

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

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

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

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

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