Classification of functional brain data for multimedia retrieval

This study introduces new signal processing methods for extracting meaningful information from brain signals (functional magnetic resonance imaging and single unit recording) and proposes a content-based retrieval system for functional brain data. First, a new method that combines maximal overlapped discrete wavelet transforms (MODWT) and dynamic time warping (DTW) is presented as a solution for dynamically detecting the hemodynamic response from fMRI data. Second, a new method for neuron spike sorting is presented that uses the maximal overlap discrete wavelet transform and rotated principal component analysis. Third, a procedure to characterize firing patterns of neuron spikes from the human brain, in both the temporal domain and the frequency domain, is presented. The combination of multitaper spectral estimation and a polynomial curve-fitting method is employed to transform the firing patterns to the frequency domain. To generate temporal shapes, eight local maxima are smoothly connected by a cubic spline interpolation. A rotated principal component analysis is used to extract common firing patterns as templates from a training set of 4100 neuron spike signals. Dynamic time warping is then used to assign each neuron firing to the closest template without shift error. These techniques are utilized in the development of a content-based retrieval system for human brain data

Elucidating the Interactive Roles of Glia in Alzheimer's Disease Using Established and Newly Developed Experimental Models

Alzheimer's disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation. While such neuroinflammatory responses may function in a neuroprotective manner by clearing neurotoxic factors, they can also be neurotoxic by contributing to neurodegeneration via elevated levels of proinflammatory mediators and oxidative stress, and altered levels of neurotransmitters, that underlie pathological symptoms including synaptic and cognitive impairment, neuronal death, reduced memory, and neocortex and hippocampus malfunctions. Glial cells, particularly activated microglia and reactive astrocytes, appear to play critical and interactive roles in such dichotomous responses. Accumulating evidences clearly point to their critical involvement in the prevention, initiation, and progression, of neurodegenerative diseases, including AD. Here, we review recent findings on the roles of astrocyte-microglial interactions in neurodegeneration in the context of AD and discuss newly developed in vitro and in vivo experimental models that will enable more detailed analysis of glial interplay. An increased understanding of the roles of glia and the development of new exploratory tools are likely to be crucial for the development of new interventions for early stage AD prevention and cures

Proxy Anchor-based Unsupervised Learning for Continuous Generalized Category Discovery

Recent advances in deep learning have significantly improved the performance of various computer vision applications. However, discovering novel categories in an incremental learning scenario remains a challenging problem due to the lack of prior knowledge about the number and nature of new categories. Existing methods for novel category discovery are limited by their reliance on labeled datasets and prior knowledge about the number of novel categories and the proportion of novel samples in the batch. To address the limitations and more accurately reflect real-world scenarios, in this paper, we propose a novel unsupervised class incremental learning approach for discovering novel categories on unlabeled sets without prior knowledge. The proposed method fine-tunes the feature extractor and proxy anchors on labeled sets, then splits samples into old and novel categories and clusters on the unlabeled dataset. Furthermore, the proxy anchors-based exemplar generates representative category vectors to mitigate catastrophic forgetting. Experimental results demonstrate that our proposed approach outperforms the state-of-the-art methods on fine-grained datasets under real-world scenarios.Comment: Accepted to ICCV 202

AI-KD: Adversarial learning and Implicit regularization for self-Knowledge Distillation

We present a novel adversarial penalized self-knowledge distillation method, named adversarial learning and implicit regularization for self-knowledge distillation (AI-KD), which regularizes the training procedure by adversarial learning and implicit distillations. Our model not only distills the deterministic and progressive knowledge which are from the pre-trained and previous epoch predictive probabilities but also transfers the knowledge of the deterministic predictive distributions using adversarial learning. The motivation is that the self-knowledge distillation methods regularize the predictive probabilities with soft targets, but the exact distributions may be hard to predict. Our method deploys a discriminator to distinguish the distributions between the pre-trained and student models while the student model is trained to fool the discriminator in the trained procedure. Thus, the student model not only can learn the pre-trained model's predictive probabilities but also align the distributions between the pre-trained and student models. We demonstrate the effectiveness of the proposed method with network architectures on multiple datasets and show the proposed method achieves better performance than state-of-the-art methods.Comment: 12 pages, 7 figure

Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin–Biotin Interactions

Cell-adhesive particles are of significant interest in biotechnology, the bioengineering of complex tissues, and biomedical research. Their applications range from platforms to increase the efficiency of anchorage-dependent cell culture to building blocks to loading cells in heterogeneous structures to clonal-population growth monitoring to cell sorting. Although useful, currently available cell-adhesive particles can accommodate only homogeneous cell culture. Here, we report the design of anisotropic hydrogel microparticles with tunable cell-adhesive regions as first step toward micropatterned cell cultures on particles. We employed stop flow lithography (SFL), the coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin–biotin chemistry to adjust the localization of conjugated collagen and poly-l-lysine on the surface of microscale particles. Using the new particles, we demonstrate the attachment and formation of tight junctions between brain endothelial cells. We also demonstrate the geometric patterning of breast cancer cells on particles with heterogeneous collagen coatings. This new approach avoids the exposure of cells to potentially toxic photoinitiators and ultraviolet light and decouples in time the microparticle synthesis and the cell culture steps to take advantage of the most recent advances in cell patterning available for traditional culture substrates.National Institutes of Health (U.S.) (GM092804)National Science Foundation (U.S.) (CMMI-1120724 and DMR-1006147)Samsung Scholarship Foundatio

Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier

Nanoparticle (NP)-assisted procedures including laser tissue soldering (LTS) offer advantages compared to conventional microsuturing, especially in the brain. In this study, effects of polymer-coated silica NPs used in LTS were investigated in human brain endothelial cells (ECs) and blood-brain barrier models. In the co-culture setting with ECs and pericytes, only the cell type directly exposed to NPs displayed a time-dependent internalization. No transfer of NPs between the two cell types was observed. Cell viability was decreased relatively to NP exposure duration and concentration. Protein expression of the nuclear factor k-light-chain-enhancer of activated B cells and various endothelial adhesion molecules indicated no initiation of inflammation or activation of ECs after NP exposure. Differentiation of CD34+ ECs into brain-like ECs co-cultured with pericytes, blood-brain barrier (BBB) characteristics were obtained. The established endothelial layer reduced the passage of integrity tracer molecules. NP exposure did not result in alterations of junctional proteins, BBB formation or its integrity. In a 3-dimensional setup with an endothelial tube formation and tight junctions, barrier formation was not disrupted by the NPs and NPs do not seem to cross the blood-brain barrier. Our findings suggest that these polymer-coated silica NPs do not damage the BBB

Microfluidic Chemotaxis Platform for Differentiating the Roles of Soluble and Bound Amyloid-β on Microglial Accumulation

Progressive microglial accumulation at amyloid-β (Aβ) plaques is a well-established signature of the pathology of Alzheimer's disease, but how and why microglia accumulate in the vicinity of Aβ plaques is unknown. To understand the distinct roles of Aβ on microglial accumulation, we quantified microglial responses to week-long lasting gradients of soluble Aβ and patterns of surface-bound Aβ in microfluidic chemotaxis platforms. We found that human microglia chemotaxis in gradients of soluble Aβ42 was most effective at two distinct concentrations of 23 pg.mL−1 and 23 ng.mL−1 Aβ42 in monomers and oligomers. We uncovered that while the chemotaxis at higher Aβ concentrations was exclusively due to Aβ gradients, chemotaxis at lower concentrations was enhanced by Aβ-induced microglial production of MCP-1. Microglial migration was inhibited by surface-bound Aβ42 in oligomers and fibrils above 45 pg.mm−2. Better understanding of microglial migration can provide insights into the pathophysiology of senile plaques in AD

Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology

Blood–brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases

Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development