To acquire statistical regularities from the world, the brain must reliably process, and learn from, spatio-temporally structured information. Although an increasing number of computational models have attempted to explain how such sequence learning may be implemented in the neural hardware, many remain limited in functionality or lack biophysical plausibility. If we are to harvest the knowledge within these models and arrive at a deeper mechanistic understanding of sequential processing in cortical circuits, it is critical that the models and their findings are accessible, reproducible, and quantitatively comparable. Here we illustrate the importance of these aspects by providing a thorough investigation of a recently proposed sequence learning model. We re-implement the modular columnar architecture and reward-based learning rule in the open-source NEST simulator, and successfully replicate the main findings of the original study. Building on these, we perform an in-depth analysis of the model's robustness to parameter settings and underlying assumptions, highlighting its strengths and weaknesses. We demonstrate a limitation of the model consisting in the hard-wiring of the sequence order in the connectivity patterns, and suggest possible solutions. Finally, we show that the core functionality of the model is retained under more biologically-plausible constraints.
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http://dx.doi.org/10.3389/fnint.2023.935177 | DOI Listing |
EClinicalMedicine
December 2024
Department of Pathology and Genetics, Laboratory of Cancer Medical Science, Hokuto Hospital, Obihiro, Hokkaido, Japan.
Background: Pancreatic cancer is highly aggressive and has a low survival rate primarily due to late-stage diagnosis and the lack of effective early detection methods. We introduce here a novel, noninvasive urinary extracellular vesicle miRNA-based assay for the detection of pancreatic cancer from early to late stages.
Methods: From September 2019 to July 2023, Urine samples were collected from patients with pancreatic cancer (n = 153) from five distinct sites (Hokuto Hospital, Kawasaki Medical School Hospital, National Cancer Center Hospital, Kagoshima University Hospital, and Kumagaya General Hospital) and non-cancer participants (n = 309) from two separate sites (Hokuto Hospital and Omiya City Clinic).
Exp Biol Med (Maywood)
December 2024
Department of Pediatric Surgery, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a poor prognosis. Its non-specific clinical symptoms make accurate prediction of disease progression challenging. This study aimed to develop molecular-level prognostic models to personalize treatment strategies for IPF patients.
View Article and Find Full Text PDFPurpose: Reliable image quality assessment is crucial for evaluating new motion correction methods for magnetic resonance imaging. In this work, we compare the performance of commonly used reference-based and reference-free image quality metrics on a unique dataset with real motion artifacts. We further analyze the image quality metrics' robustness to typical pre-processing techniques.
View Article and Find Full Text PDFMost genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells.
View Article and Find Full Text PDFThe relentless emergence of antibiotic-resistant pathogens, particularly Gram-negative bacteria, highlights the urgent need for novel therapeutic interventions. Drug-resistant infections account for approximately 5 million deaths annually, yet the antibiotic development pipeline has largely stagnated. Venoms, representing a remarkably diverse reservoir of bioactive molecules, remain an underexploited source of potential antimicrobials.
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