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Mesoscopic calcium imaging enables studies of cell-type specific neural activity over large areas. A growing body of literature suggests that neural activity can be different when animals are free to move compared to when they are restrained. Unfortunately, existing systems for imaging calcium dynamics over large areas in non-human primates (NHPs) are table-top devices that require restraint of the animal’s head. Here, we demonstrate an imaging device capable of imaging mesoscale calcium activity in a head-unrestrained male non-human primate. We successfully miniaturize our system by replacing lenses with an optical mask and computational algorithms. The resulting lensless microscope can fit comfortably on an NHP, allowing its head to move freely while imaging. We are able to measure orientation columns maps over a 20 mm²field-of-view in a head-unrestrained macaque. Our work establishes mesoscopic imaging using a lensless microscope as a powerful approach for studying neural activity under more naturalistic conditions.

 

Deep Learning (DL) has recently enabled unprecedented advances in one of the grand challenges in computational biology: the half-century-old problem of protein structure prediction. In this paper we discuss recent advances, limitations, and future perspectives of DL on five broad areas: protein structure prediction, protein function prediction, genome engineering, systems biology and data integration, and phylogenetic inference. We discuss each application area and cover the main bottlenecks of DL approaches, such as training data, problem scope, and the ability to leverage existing DL architectures in new contexts. To conclude, we provide a summary of the subject-specific and general challenges for DL across the biosciences.

 

We present a novel architecture for the design of single-photon detecting arrays that captures relative intensity or timing information from a scene, rather than absolute. The proposed method for capturing relative information between pixels or groups of pixels requires very little circuitry, and thus allows for a significantly higher pixel packing factor than is possible with per-pixel TDC approaches. The inherently compressive nature of the differential measurements also reduces data throughput and lends itself to physical implementations of compressed sensing, such as Haar wavelets. We demonstrate this technique for HDR imaging and LiDAR, and describe possible future applications.

 

Laser speckle contrast imaging is widely used in clinical studies to monitor blood flow distribution. Speckle contrast tomography, similar to diffuse optical tomography, extends speckle contrast imaging to provide deep tissue blood flow information. However, the current speckle contrast tomography techniques suffer from poor spatial resolution and involve both computation and memory intensive reconstruction algorithms. In this work, we present SpeckleCam, a camera-based system to reconstruct high resolution 3D blood flow distribution deep inside the skin. Our approach replaces the traditional forward model using diffuse approximations with Monte-Carlo simulations-based convolutional forward model, which enables us to develop an improved deep tissue blood flow reconstruction algorithm. We show that our proposed approach can recover complex structures up to 6 mm deep inside a tissue-like scattering medium in the reflection geometry. We also conduct human experiments to demonstrate that our approach can detect reduced flow in major blood vessels during vascular occlusion.

 

Deep Neural Networks (DNNs) trained for classification tasks are vulnerable to adversarial attacks. But not all the classes are equally vulnerable. Adversarial training does not make all classes or groups equally robust as well. For example, in classification tasks with long-tailed distributions, classes are asymmetrically affected during adversarial training, with lower robust accuracy for less frequent classes. In this regard, we propose a provable robustness method by leveraging the continuous piecewise-affine (CPA) nature of DNNs. Our method can impose linearity constraints on the decision boundary, as well as the DNN CPA partition, without requiring any adversarial training. Using such constraints, we show that the margin between the decision boundary and minority classes can be increased in a provable manner. We also present qualitative and quantitative validation of our method for class-specific robustness. Our code is available at https: //github.com/Josuelmet/CROP 

Traditional miniaturized fluorescence microscopes are critical tools for modern biology. Invariably, they struggle to simultaneously image with a high spatial resolution and a large field of view (FOV). Lensless microscopes offer a solution to this limitation. However, real-time visualization of samples is not possible with lensless imaging, as image reconstruction can take minutes to complete. This poses a challenge for usability, as real-time visualization is a crucial feature that assists users in identifying and locating the imaging target. The issue is particularly pronounced in lensless microscopes that operate at close imaging distances. Imaging at close distances requires shift-varying deconvolution to account for the variation of the point spread function (PSF) across the FOV. Here, we present a lensless microscope that achieves real-time image reconstruction by eliminating the use of an iterative reconstruction algorithm. The neural network-based reconstruction method we show here, achieves more than 10000 times increase in reconstruction speed compared to iterative reconstruction. The increased reconstruction speed allows us to visualize the results of our lensless microscope at more than 25 frames per second (fps), while achieving better than 7 µm resolution over a FOV of 10 mm². This ability to reconstruct and visualize samples in real-time empowers a more user-friendly interaction with lensless microscopes. The users are able to use these microscopes much like they currently do with conventional microscopes.

 

Diffraction-limited optical imaging through scattering media has the potential to transform many applications such as airborne and space-based imaging (through the atmosphere), bioimaging (through skin and human tissue), and fiber-based imaging (through fiber bundles). Existing wavefront shaping methods can image through scattering media and other obscurants by optically correcting wavefront aberrations using high-resolution spatial light modulators—but these methods generally require (i) guidestars, (ii) controlled illumination, (iii) point scanning, and/or (iv) statics scenes and aberrations. We propose neural wavefront shaping (NeuWS), a scanning-free wavefront shaping technique that integrates maximum likelihood estimation, measurement modulation, and neural signal representations to reconstruct diffraction-limited images through strong static and dynamic scattering media without guidestars, sparse targets, controlled illumination, nor specialized image sensors. We experimentally demonstrate guidestar-free, wide field-of-view, high-resolution, diffraction-limited imaging of extended, nonsparse, and static/dynamic scenes captured through static/dynamic aberrations.

 

Current Deep Network (DN) visualization and inter-pretability methods rely heavily on data space visualizations such as scoring which dimensions of the data are responsible for their associated prediction or generating new data features or samples that best match a given DN unit or representation. In this paper, we go one step further by developing the first provably exact method for computing the geometry of a DN's mapping - including its decision boundary - over a specified region of the data space. By lever-aging the theory of Continuous Piece- Wise Linear (CPWL) spline DNs, SplineCam exactly computes a DN's geometry without resorting to approximations such as sampling or architecture simplification. SplineCam applies to any DN architecture based on CPWL activation nonlinearities, including (leaky) ReLU, absolute value, maxout, and max-pooling and can also be applied to regression DNs such as implicit neural representations. Beyond decision boundary visualization and characterization, SplineCam enables one to compare architectures, measure generalizability, and sample from the decision boundary on or off the data manifold. Project website: bit.ly/splinecam. 

Generating new molecules with specified chemical and biological properties via generative models has emerged as a promising direction for drug discovery. However, existing methods require extensive training/fine-tuning with a large dataset, often unavailable in real-world generation tasks. In this work, we propose a new retrieval-based framework for controllable molecule generation. We use a small set of exemplar molecules, i.e., those that (partially) satisfy the design criteria, to steer the pre-trained generative model towards synthesizing molecules that satisfy the given design criteria. We design a retrieval mechanism that retrieves and fuses the exemplar molecules with the input molecule, which is trained by a new self-supervised objective that predicts the nearest neighbor of the input molecule. We also propose an iterative refinement process to dynamically update the generated molecules and retrieval database for better generalization. Our approach is agnostic to the choice of generative models and requires no task-specific fine-tuning. On various tasks ranging from simple design criteria to a challenging real-world scenario for designing lead compounds that bind to the SARS-CoV-2 main protease, we demonstrate our approach extrapolates well beyond the retrieval database, and achieves better performance and wider applicability than previous methods.