Abstract: Provided herein is a method and system for imaging a biological sample. The method may include scanning a biological sample using one or more light sheets, where the biological sample is in a field of view of a microscope that includes an objective and a direction of observation of the objective defines a z-axis, where a point spread function of the microscope is elongated in the z-axial direction, and the biological sample is at a z-axial distance from the objective, thereby illuminating a plurality of z-axial slices of the biological sample, and recording a plurality of images corresponding to a plurality of z-axial slices of the sample, where the images are generated by light patterns emitted from the scanned biological sample, thereby generating an image stack that includes a plurality of images of the biological sample.

Abstract: High affinity PD-1 mimic polypeptides are provided, which (i) comprise at least one amino acid change relative to a wild-type PD-1 protein; and (ii) have an increased affinity for PD-L1 relative to the wild-type protein. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.

Abstract: Compositions and methods are provided for measuring population size for a plurality of clonal cell populations in the same individual, e.g., for measuring tumor size for a plurality of clonally independent tumors within the same individual. A subject method can include: (a) contacting an individual with a plurality of cell markers that are heritable and distinguishable from one another, to generate a plurality of distinguishable lineages of heritably marked cells; (b) after sufficient time has passed for the heritably marked cells to undergo at least one round of division, detecting and measuring quantities of at least two of the plurality of cell markers present in the contacted tissue, thereby generating a set of measured values; and (c) using the set of measured values to calculate the number of heritably marked cells that are present (e.g., for at least two of the distinguishable lineages of heritably marked cells).

Abstract: The present invention provides a method for producing a chimeric animal using a primed pluripotent stem cell, a tissue stem cell, a progenitor cell, a somatic cell, or a germ cell. The method for producing a chimeric animal according to the present invention comprises introducing a mammal-derived cell into the embryo of a mammal, the cell being primed pluripotent stem cell, tissue stem cell, progenitor cell, somatic cell, or germ cell.

Abstract: A passive cavitation mapping method is provided that includes capturing a channel signal from at least one ultrasound transducer in an array of ultrasound transducers, isolating a cavitation signal in the channel signal, time-gating the channel signal about the cavitation signal, computing a time-delay between neighboring the cavitation signals in adjacent the channel signals, computing a modified parabolic fit to the square of the arrival times, where the modified parabolic fit includes a coordinate transformation using an x location of a leading edge of wavefronts of the cavitation signal and a maximum arrival time of the cavitation signal, extracting a location of a cavitation signal source at point (x, z) in the coordinate transformation, computing a cavitation magnitude for each non-eliminated cavitation signal, creating a passive cavitation map by convolving the cavitation magnitude and the source location with an uncertainty function, and using the cavitation map for therapeutic ultrasound applications

Abstract: A radiation therapy treatment method includes providing a patient model, dosimetric constraints, delivery motion constraints, and delivery coordinate space of a radiation delivery device, where the delivery coordinate space is represented as a mesh with vertices connected by edges, where the vertices correspond to directions of a beam eye view (BEV) of the radiation delivery device. BEV region connectivity manifolds are constructed from the patient model, the dosimetric constraints, the delivery coordinate space, and existing beam trajectories, wherein each of the BEV region connectivity manifolds represents connections between contiguous 2D target regions. Beam trajectories are selected based on region connectedness information in the BEV region connectivity manifolds, the dosimetric constraints, the delivery motion constraints, and the existing beam trajectories. Radiation is delivered using the radiation delivery device in accordance with the selected beam trajectories.

Abstract: A monolithic optical device for light manipulation and control at visible wavelengths includes a device layer deposited on an sacrificial layer deposited on a reflective substrate. The device layer comprises an elastic support structure and nanoscale optical antenna elements, arranged such that the nanoscale optical antenna elements are capable of moving vertically in response to application of an electrostatic potential between the device layer and the reflective substrate. The sacrificial layer joins the elastic support structure to the reflective substrate. The reflective substrate is reflective at optical wavelengths.

Abstract: Methods are provided for stimulating ovarian preantral and antral follicles in a mammal.

Abstract: The present invention relates to fluorophenyl substituted muscarinic receptor ligands with selectivity for M3 over M2 and to the use of these compounds in the treatment of various diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD) and urinary incontinence.

Abstract: Systems and methods for synthetic medical image generation in accordance with embodiments of the invention are illustrated. One embodiment includes a synthetic medical image generation system, including a processor, and a memory containing an image synthesis application, where the image synthesis application directs the processor to obtain source image data generated by at least one medical imaging device, where the source image data describes a functional medical image taken of a patient administered with a first imaging agent, and synthesize a predicted medical image of the patient that depicts the patient as if they were administered with a second imaging agent, wherein the first imaging agent and the second imaging agent are different imaging agents.

Abstract: Methods are provided for the generation of mesodermal cell types and derivatives thereof. Also provided are methods for generating purified populations of mesodermal cell types and derivatives thereof. The instant disclosure also provides methods of screening for cellular responses of the generated mesodermal cell types and derivatives thereof. Also provide are methods for screening for organismal phenotypes induced by introduction of the generated mesodermal cell types and derivatives thereof. Treatment methods making use of the generated mesodermal cell types and derivatives thereof are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

Abstract: Among other aspects, various embodiments include encoding wavelength-based characteristics, in addition to three-dimensional positions, of a plurality of objects of a plurality of different wavelengths directly in an image of the objects.

Abstract: Various aspects of the present disclosure are directed toward methods and apparatuses for interacting a first liquid and a second liquid in one or more fluidic channels of a capillary structure. The methods and apparatuses can include providing at least one capillary barrier that positions a meniscus of the first liquid at a fluid-interface region using capillary forces within the capillary structure. Additionally, a path is provided along one of the channels for the second liquid to flow toward the fluid-interface region. Additionally, gas pressure is released, via a gas-outflow port, from the fluid-interface region while flow of the first liquid is arrested. Further, the first liquid and the second liquid contact in the fluid-interface region with the capillary barrier holding the first liquid at the fluid-interface region.

Abstract: A method is provided for detecting one or more analytes in a sample. The method relies, in part, on the ability of functionalized particles added to the sample to partially or completely inhibit the transmission of electromagnetic radiation into and out of the sample through a detection surface in a reaction vessel containing the sample. In a microarray format, the invention can be used to screen millions, billions or more biological elements, such as an organism, cell, protein, nucleic acid, lipid, saccharide, metabolite, or small molecules. Methods, apparatuses and kits are described.

Abstract: A novel method for preparing sequence-verified oligonucleotides is disclosed. In particular, the invention relates to a simple, affordable, and scalable method that combines high-throughput mating of yeast clones, a unique selectable system for combining DNA sequences in yeast, and next-generation sequencing. This method allows sequence-verified oligonucleotides to be readily isolated from complex libraries.

Abstract: Fiber-based gain elements, such as fiber lasers, fiber amplifiers, and the like, that have higher power and better frequency stability than can be achieved in the prior art are presented. Embodiments include a fiber-based gain element having a first portion in which anti-Stokes fluorescence (ASF) reduces its temperature below that of an ambient environment and a second portion whose temperature is not reduced below that of the ambient environment, which are thermally coupled so heat can flow from the second portion into the first portion, thereby reducing the average temperature of the gain element. In some embodiments, a core configured to provide optical gain is thermally coupled with a first cladding configured to exhibit ASF cooling via an intervening cladding layer that acts to confine a first pump signal to the core.

Abstract: Compounds useful as contrast agents in image-guided surgery are provided. The compounds comprise a latent cationic lysosomotropic fragment that is detectable upon cleavage by lysosomal proteases within treated tissues, particularly within tumors and other diseased tissues. Also provided are compositions comprising the compounds and methods for using the compounds, for example in dynamically monitoring protease activity in vivo during image-guided tumor resection surgery.

Abstract: The compound 2-(3-tert-Butylphenyl)-4,6-difluoro-1H-benzo[d]imidazole and its use are disclosed: The compound activates Ppargc1a and, as a consequence, is useful for treating neuroinflammation and for treating a variety of neurodegenerative diseases.

Abstract: A medical method performed by a medical device, includes: generating a ECG tracing using a first electrode placed on a surface of a patient and a second electrode at a catheter inside the patient; and outputting the ECG tracing for presentation to a user; wherein the first electrode is fixed in position with respect to the patient; and wherein an amplitude of the ECG tracing corresponds with a relative distance between the first electrode and the second electrode. A medical device includes: a first electrode configured for placement on a surface of a patient; a second electrode configured for coupling with a catheter; and a processing unit configured to generate a ECG tracing using the first electrode on the surface of the patient and the second electrode inside the patient.

Abstract: Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade.