MProtoNet: A Case-Based Interpretable Model for Brain Tumor Classification with 3D Multi-parametric Magnetic Resonance Imaging

Recent applications of deep convolutional neural networks in medical imaging raise concerns about their interpretability. While most explainable deep learning applications use post hoc methods (such as GradCAM) to generate feature attribution maps, there is a new type of case-based reasoning models, namely ProtoPNet and its variants, which identify prototypes during training and compare input image patches with those prototypes. We propose the first medical prototype network (MProtoNet) to extend ProtoPNet to brain tumor classification with 3D multi-parametric magnetic resonance imaging (mpMRI) data. To address different requirements between 2D natural images and 3D mpMRIs especially in terms of localizing attention regions, a new attention module with soft masking and online-CAM loss is introduced. Soft masking helps sharpen attention maps, while online-CAM loss directly utilizes image-level labels when training the attention module. MProtoNet achieves statistically significant improvements in interpretability metrics of both correctness and localization coherence (with a best activation precision of $0.713\pm0.058$) without human-annotated labels during training, when compared with GradCAM and several ProtoPNet variants. The source code is available at https://github.com/aywi/mprotonet.Comment: 15 pages, 5 figures, 1 table; accepted for oral presentation at MIDL 2023 (https://openreview.net/forum?id=6Wbj3QCo4U4); camera-ready versio

Augmenting Auto-context with Global Geometric Features for Spinal Cord Segmentation

Abstract. Anatomical shape variations are typically difficult to model and parametric or hand-crafted models can lead to ill-fitting segmentations. This difficulty can be addressed with a framework like autocontext, that learns to jointly detect and regularize a segmentation. However, mis-segmentation can still occur when a desired structure, such as the spinal cord, has few locally distinct features. High-level knowledge at a global scale (e.g. an MRI contains a single connected spinal cord) is needed to regularize these candidate segmentations. To encode highlevel knowledge, we propose to augment the auto-context framework with global geometric features extracted from the detected candidate shapes. Our classifier then learns these high-level rules and rejects falsely detected shapes. To validate our method we segment the spinal cords from 20 MRI volumes composed of patients with and without multiple sclerosis and demonstrate improvements in accuracy, speed, and manual effort required when compared to state-of-the-art methods.

Characterization and comparative sequence analysis of the DNA mismatch repair MSH2 and MSH7 genes from tomato

DNA mismatch repair proteins play an essential role in maintaining genomic integrity during replication and genetic recombination. We successfully isolated a full length MSH2 and partial MSH7 cDNAs from tomato, based on sequence similarity between MutS and plant MSH homologues. Semi-quantitative RT-PCR reveals higher levels of mRNA expression of both genes in young leaves and floral buds. Genetic mapping placed MSH2 and MSH7 on chromosomes 6 and 7, respectively, and indicates that these genes exist as single copies in the tomato genome. Analysis of protein sequences and phylogeny of the plant MSH gene family show that these proteins are evolutionarily conserved, and follow the classical model of asymmetric protein evolution. Genetic manipulation of the expression of these MSH genes in tomato will provide a potentially useful tool for modifying genetic recombination and hybrid fertility between wide crosses

Scanner Invariant Multiple Sclerosis Lesion Segmentation from MRI

This paper presents a simple and effective generalization method for magnetic resonance imaging (MRI) segmentation when data is collected from multiple MRI scanning sites and as a consequence is affected by (site-)domain shifts. We propose to integrate a traditional encoder-decoder network with a regularization network. This added network includes an auxiliary loss term which is responsible for the reduction of the domain shift problem and for the resulting improved generalization. The proposed method was evaluated on multiple sclerosis lesion segmentation from MRI data. We tested the proposed model on an in-house clinical dataset including 117 patients from 56 different scanning sites. In the experiments, our method showed better generalization performance than other baseline networks

Wide-band multipath A to D converter for Cognitive Radio applications

This article presents a digital-enhanced radio frequency receiver for fast wide-band spectrum sensing. It is based on charge sampling and hybrid filter bank techniques. The charge sampling method is employed to design analog bandpass filters. Using a hybrid filter bank for wide-band analog-to-digital conversion improves the speed and resolution of the conversion. We propose to use these techniques in combination of frequencydivision multiplexing with time-division multiplexing to design an integrated, completely software reconfigurable and reliable backend of radio frequency receiver for cognitive radio applications

Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types

Binding interactions of Peptide Aptamers

Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface of protein receptors (e.g., GCPR), which take part in cell-to-cell communications either directly or via the intermediary of hormones or signalling molecules. To confer on aptamers the same sort of conformational rigidity that characterises an antibody binding site, aptamers are often constructed in the form of cyclic peptides, on the assumption that this will encourage stronger binding interactions than would occur if the aptamers were simply linear chains. However, no formal studies have been conducted to confirm the hypothesis that linear peptides will engage in stronger binding interactions with cyclic peptides than with other linear peptides. In this study, the interaction of a model cyclic decamer with a series of linear peptide constructs was compared with that of a linear peptide with the same sequence, showing that the cyclic configuration does confer benefits by increasing the strength of binding

The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate

The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels–Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG–GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.: Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/40684/2007, Science 2007 Programe, PTDC/SAU-BMA/114059/2009).Ontario Ministry of Research and Innovation (Ontario Neurotrauma FoundationCanadian Institute of Health Research (MSS)Stem Cell Network (MJC

A Superglass Phase of Interacting Bosons

We introduce a Bose-Hubbard Hamiltonian with random disordered interactions as a model to study the interplay of superfluidity and glassiness in a system of three-dimensional hard-core bosons at half-filling. Solving the model using large-scale quantum Monte Carlo simulations, we show that these disordered interactions promote a stable superglass phase, where superflow and glassy density localization coexist in equilibrium without exhibiting phase separation. The robustness of the superglass phase is underlined by its existence in a replica mean-field calculation on the infinite-dimensional Hamiltonian.Comment: 4 pages 3 figures: to appear in Phys. Rev. Lett