No abstract

Accurate microvascular morphometric information has significant implications in several fields, including the quantification of angiogenesis in cancer research, understanding the immune response for neural prosthetics, and predicting the nature of blood flow as it relates to stroke. We report imaging of the whole mouse brain microvascular system at resolutions sufficient to perform accurate morphometry. Imaging was performed using Knife-Edge Scanning Microscopy (KESM) and is the first example of this technique that can be directly applied to clinical research. We are able to achieve ≈ 0.7μm resolution laterally with 1μm depth resolution using serial sectioning. No alignment was necessary and contrast was sufficient to allow segmentation and measurement of vessels.

Pre-trained BERT contextualized representations have achieved state-of-the-art results on multiple downstream NLP tasks by fine-tuning with task-specific data. While there has been a lot of focus on task-specific fine-tuning, there has been limited work on improving the pretrained representations. In this paper, we explore ways of improving the pre-trained contextual representations for the task of automatic short answer grading, a critical component of intelligent tutoring systems. We show that the pre-trained BERT model can be improved by augmenting data from the domainspecific resources like textbooks. We also present a new approach to use labeled short answering grading data for further enhancement of the language model. Empirical evaluation on multi-domain datasets shows that task-specific fine-tuning on the enhanced pretrained language model achieves superior performance for short answer grading.

Connectomics is the study of the full connection matrix of the brain. Recent advances in high-throughput, high-resolution 3D microscopy methods have enabled the imaging of whole small animal brains at a sub-micrometer resolution, potentially opening the road to full-blown connectomics research. One of the first such instruments to achieve whole-brain-scale imaging at sub-micrometer resolution is the Knife-Edge Scanning Microscope (KESM). KESM whole-brain data sets now include Golgi (neuronal circuits), Nissl (soma distribution), and India ink (vascular networks). KESM data can contribute greatly to connectomics research, since they fill the gap between lower resolution, large volume imaging methods (such as diffusion MRI) and higher resolution, small volume methods (e.g., serial sectioning electron microscopy). Furthermore, KESM data are by their nature multiscale, ranging from the subcellular to the whole organ scale. Due to this, visualization alone is a huge challenge, before we even start worrying about quantitative connectivity analysis. To solve this issue, we developed a web-based neuroinformatics framework for efficient visualization and analysis of the multiscale KESM data sets. In this paper, we will first provide an overview of KESM, then discuss in detail the KESM data sets and the web-based neuroinformatics framework, which is called the KESM brain atlas (KESMBA). Finally, we will discuss the relevance of the KESMBA to connectomics research, and identify challenges and future directions.

In this paper, we will review a novel microscopy modality called Knife-Edge Scanning Microscopy (KESM) that we have developed over the past twelve years (since 1999) and discuss its relevance to connectomics and neural networks research. The operational principle of KESM is to simultaneously section and image small animal brains embedded in hard polymer resin so that a near-isotropic, sub-micrometer voxel size of 0.6 µm × 0.7 µm × 1.0 µm can be achieved over ∼1 cm 3 volume of tissue which is enough to hold an entire mouse brain. At this resolution, morphological details such as dendrites, dendritic spines, and axons are visible (for sparse stains like Golgi). KESM has been successfully used to scan whole mouse brains stained in Golgi (neuronal morphology), Nissl (somata), and India ink (vasculature), providing unprecedented insights into the system-level architectural layout of microstructures within the mouse brain. In this paper, we will present whole-brain-scale data sets from KESM and discuss challenges and opportunities posed to connectomics and neural networks research by such detailed yet system-level data.