Abstract: Provided herein are sustained release biodegradable intracanalicular inserts comprising a hydrogel and an active agent, methods of treating or preventing an ocular disease in a subject in need thereof by administering such inserts as well as methods of manufacturing such inserts.

Abstract: Provided herein are compounds (e.g., compounds of Formula (I) and Formula (II), that modulate HCN channels, intermembrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HCN-related disorders (e.g., pain) with the compounds in a subject, by administering the compounds and/or compositions described herein.

Abstract: Provided herein are sustained release biodegradable intracanalicular insert comprising a hydrogel and cyclosporine, methods of treating or preventing an ocular disease in a subject in need thereof by administering such inserts as well as methods of manufacturing such inserts.

Abstract: A system for measuring a target grating includes an illumination source, a reference transmission grating, a pupil filter, and a detector. The illumination source is disposed to generate an incident light beam that illuminates the reference transmission grating. The reference transmission grating splits the incident light beam into a plurality of diffraction orders. The plurality of diffraction orders interrogates a target grating. The reference transmission grating and the target grating are parallel. The pupil filter allows transmission of a subset of diffraction orders of light that has been diffracted and/or reflected from the target grating after being split again by passing through the reference transmission grating. The detector takes a measurement of the subset of diffraction orders of light after transmission through the pupil filter.

Abstract: The disclosure relates to an improved cylinder lock, key and their combination. More specifically, the disclosure relates to a locking pin assembly operable to provide added combination and increase security against burglary, such as by key bumping, a cylinder lock incorporating the locking pin assembly and key blade and key blade assemblies having the configuration to actuate the locking pin assembly.

Abstract: Provided herein are compounds (e.g., compounds of Formula (I) and Formula (II), that modulate HCN channels, intermembrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HCN-related disorders (e.g., pain) with the compounds in a subject, by administering the compounds and/or compositions described herein.

Abstract: The present application discloses pharmaceutical compositions for modified release of huperzine. The pharmaceutical compositions and methods described herein, allow for dosing of huperzine at higher therapeutic thresholds, while avoiding rapid serum peak plasma levels, thereby avoiding the adverse nausea and vomiting associated with the immediate release pharmaceutical compositions. Methods of treating neurological disorders and/or seizure disorders with the modified release compositions is also described.

Abstract: Provided herein are compounds (e.g., compounds of Formula (I) and Formula (II), that modulate HCN channels, intermembrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HCN-related disorders (e.g., pain) with the compounds in a subject, by administering the compounds and/or compositions described herein.

Abstract: Apparatus and methods of treating a hard lens region of an eye with a laser where one method includes identifying a boundary of the hard lens region, selecting a laser-parameter to enable a photo disruptive procedure in the hard lens region and to control a spreading of bubbles in the hard lens region, modifying a mechanical property of a posterior portion of the hard lens region in a proximity of the identified boundary by the photo disruptive procedure, and modifying a mechanical property of a portion anterior to the modified posterior portion of the hard lens region by the photo disruptive procedure. The laser bubbles can be applied to form incisions which are non-transverse to an axis of the eye and intersect the lens fibers.

Abstract: Compositions and methods for managing or treating chronic pain are provided. More particularly, methods are provided for managing or treating chronic pain by administering to a patient in need thereof an effective amount of propofol or a propofol derivative having limited anesthetic properties. Methods of modulating HCN channel gating are also provided. Pharmaceutically acceptable compositions for, e.g., modulating HCN channel gating are further provided.

Abstract: The present application discloses pharmaceutical compositions for modified release of huperzine. The pharmaceutical compositions and methods described herein, allow for dosing of huperzine at higher therapeutic thresholds, while avoiding rapid serum peak plasma levels, thereby avoiding the adverse nausea and vomiting associated with the immediate release pharmaceutical compositions. Methods of treating neurological disorders and/or seizure disorders with the modified release compositions is also described.

Abstract: An imaging-based laser system can include a laser-beam system, configured to generate and scan a beam of laser pulses with an adjustable laser-power parameter to points of a scan-pattern in an eye, and an imaging-based laser-controller, configured to image a layer in the eye, to control the scanning of the beam of laser pulses to the points of the scan-pattern, and to control a laser-power parameter of the laser pulses according to the distance of the points of the scan-pattern from the imaged layer.

Abstract: An imaging-based laser system can include a laser-beam system, configured to generate and scan a beam of laser pulses with an adjustable laser-power parameter to points of a scan-pattern in an eye, and an imaging-based laser-controller, configured to image a layer in the eye, to control the scanning of the beam of laser pulses to the points of the scan-pattern, and to control a laser-power parameter of the laser pulses according to the distance of the points of the scan-pattern from the imaged layer.

Abstract: An imaging-based laser system can include a laser-beam system, configured to generate and scan a beam of laser pulses with an adjustable laser-power parameter to points of a scan-pattern in an eye, and an imaging-based laser-controller, configured to image a layer in the eye, to control the scanning of the beam of laser pulses to the points of the scan-pattern, and to control a laser-power parameter of the laser pulses according to the distance of the points of the scan-pattern from the imaged layer.

Abstract: Apparatus and methods of treating a hard lens region of an eye with a laser where one method includes identifying a boundary of the hard lens region, selecting a laser-parameter to enable a photodisruptive procedure in the hard lens region and to control a spreading of bubbles in the hard lens region, modifying a mechanical property of a posterior portion of the hard lens region in a proximity of the identified boundary by the photodisruptive procedure, and modifying a mechanical property of a portion anterior to the modified posterior portion of the hard lens region by the photodisruptive procedure. The laser bubbles can be applied to form incisions which are non transverse to an axis of the eye and intersect the lens fibers.

Abstract: Techniques for assembly of genetic maps including de novo assembly of distance maps using multiple alignment consensus construction. Multiple map alignment can be performed on a defined bundle of fragment maps corresponding to biomolecule fragments to determine consensus events and corresponding locations. Fragment maps in the bundle can be removed when there is no overhang from the consensus events. When the subset of fragment maps in the bundle is less than a predetermined threshold, one or more additional fragment maps can be added based on fragment signatures, a consensus alignment score, and a pairwise alignment score. Techniques for multiple alignment can include generating a graph with edges and vertices representing each pairwise relation. An ordered set of sets of events best representing a multiple alignment reflecting all pairwise alignments can be generated by repeatedly randomly removing edges and combining vertices to identify a min cut of the graph.

Abstract: Apparatus and methods of treating a hard lens region of an eye with a laser where one method includes identifying a boundary of the hard lens region, selecting a laser-parameter to enable a photodisruptive procedure in the hard lens region and to control a spreading of bubbles in the hard lens region, modifying a mechanical property of a posterior portion of the hard lens region in a proximity of the identified boundary by the photodisruptive procedure, and modifying a mechanical property of a portion anterior to the modified posterior portion of the hard lens region by the photodisruptive procedure. The laser bubbles can be applied to form incisions which are non transverse to an axis of the eye and intersect the lens fibers.

Abstract: Methods for sequencing a biopolymer by forming local ternary complexes along the length of the double-stranded biopolymer target molecule using one or more probes and obtaining information about the location of the probe(s) using a detector. These methods offer particular advantage when implemented with nanopore (including micropore) detection systems.

Abstract: Techniques for assembly of genetic maps including de novo assembly of distance maps using multiple alignment consensus construction. Multiple map alignment can be performed on a defined bundle of fragment maps corresponding to biomolecule fragments to determine consensus events and corresponding locations. Fragment maps in the bundle can be removed when there is no overhang from the consensus events. When the subset of fragment maps in the bundle is less than a predetermined threshold, one or more additional fragment maps can be added based on fragment signatures, a consensus alignment score, and a pairwise alignment score. Techniques for multiple alignment can include generating a graph with edges and vertices representing each pairwise relation. An ordered set of sets of events best representing a multiple alignment reflecting all pairwise alignments can be generated by repeatedly randomly removing edges and combining vertices to identify a min cut of the graph.

Abstract: A method for determining a sequence of a biomolecule, the method including binding a plurality of uniform probes to a biomolecule fragment, creating a collection of binding signatures for the fragment with each binding signature representing a series of distances between binding sites within the fragment, and grouping the binding signatures into a plurality of signature clusters based at least in part on distances between the binding sites in each binding signature. For each binding signature in a first cluster, a potential successor binding signature is selected from signature clusters other than the first signature cluster, and one of the potential successor binding signatures is identified as a successor binding signature. The last two steps are repeated until the successor signature represents a terminal signature, resulting in a sequence of signatures representing at least a portion of the biomolecule.