Abstract: The present disclosure provides systems and methods for high throughput genetic manipulation. Particularly, systems and methods are provided for scalable gene insertions in mammalian cells, the systems and methods comprise a donor nucleic acid comprising a cargo sequence encoding one or more selectable markers; a first guide RNA complementary to at least a portion of the donor nucleic acid; a plurality of second guide RNAs each of which is complementary to at least a portion of one of a plurality of target nucleic acids; a first RNA-guided endonuclease configured to bind to the first guide RNA; a second RNA-guided endonuclease configured to bind to the plurality of second guide RNAs; or one or more nucleic acids encoding thereof.

Abstract: The present disclosure provides viral vectors which decrease undesired or off-target gene expression. Particularly, the present disclosure provides recombinant viral vectors comprising a transcription termination sequence adjacent to an inverted terminal repeat sequence (e.g., downstream of a first inverted terminal repeat sequence and upstream of an expression cassette), and virus or virus-like particles, compositions, and methods of using thereof.

Abstract: The present disclosure provides to systems, methods, and compositions for rescuing protein misfolding and preventing protein aggregation. Particularly the present disclosure provides methods and compositions comprising DNAJB6 or variants thereof, or polynucleotides encoding DNAJB6 or variants thereof. The present disclosure also provides methods for treating protein misfolding and/or protein aggregation diseases (e.g., multiple amyotrophic lateral sclerosis and frontotemporal dementia) by administering the systems or compositions to a subject in need thereof.

Abstract: A method of screening is provided including providing a combination of a plurality of proliferating cell types wherein each proliferating cell type has a unique associated barcode within its genome that is different from other proliferating cell types of the plurality and wherein each proliferating cell type includes an exogenous gene that when expressed produces an associated phenotype to the proliferating cell type which alters proliferation of the cell type, introducing a perturbation to one or more of the plurality of proliferating cell types, inducing expression of one or more of the exogenous genes, determining the relative number of unique associated barcodes after a period of proliferation, and comparing the relative number of unique associated barcodes to a control relative number of unique associated barcodes to indicate the effect of the perturbation on the one or more of the plurality of proliferating cell types.

Abstract: A lighting device with multiple light sources includes a housing, a first illuminating source, a second illuminating source, a lens assembly, a light reflecting and transmitting filter, a first power switch, a second power switch, and a power source. The first illuminating source and the second illuminating source are mounted within the housing and perpendicularly positioned of each other. The lens assembly is operatively coupled to the housing, wherein the lens assembly focus the first illuminating source and the second illuminating source between a spot position and a collimating potion. The light reflecting and transmitting filter is angularly mounted in between the first illuminating source and the second illuminating source, The first power switch and the second power switch are mounted onto the housing. The power source being electrically connected to the first illuminating source through the first power switch and the second illuminating source through the second power switch.

Abstract: The present disclosure provides systems, kits, and methods for nucleic acid integration utilizing engineered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated transposon (CRISPR-Tn) system. More particularly, the present disclosure provides systems comprising: an engineered CRISPR-Tn system or one or more nucleic acids encoding the engineered CRISPR-Tn system, wherein the CRISPR-Tn system comprises at least one or both of: a) at least one Cas protein (e.g., Cas6, Cas7, Cas5, and/or Cas8); and b) one or more transposon-associated proteins (e.g., TnsA, TnsB, TnsC, TnsD, and/or TniQ). The present disclosure also provides systems, kits, and methods for nucleic acid integration in a eukaryotic cell.

Abstract: A lighting device with multiple light sources includes a housing, a first illuminating source, a second illuminating source, a lens assembly, a light reflecting and transmitting filter, a first power switch, a second power switch, and a power source. The first illuminating source and the second illuminating source are mounted within the housing and perpendicularly positioned of each other. The lens assembly is operatively coupled to the housing, wherein the lens assembly focus the first illuminating source and the second illuminating source between a spot position and a collimating potion. The light reflecting and transmitting filter is angularly mounted in between the first illuminating source and the second illuminating source, The first power switch and the second power switch are mounted onto the housing. The power source being electrically connected to the first illuminating source through the first power switch and the second illuminating source through the second power switch.

Abstract: Optical sights for mounting on a firearm are provided, each of the sights having a base defining a barrel end and a rear end; a frame extending upwardly from the base at the barrel end and defining an opening; an optical element received in the opening; and an illumination device operable to display an aiming point on the optical element to generate said aiming point.

Abstract: Expressing guide nucleic acids (e.g., gRNA) from the same oligonucleotide that contains donor sequence permits the high efficiency, simultaneous transformation of a population of cells with both substrates. Using oligonucleotide chip array technology, one can construct thousands of oligonucleotides with customized gRNA and donor sequence in a cost effective manner. In combination, one can efficiently modify endogenous and exogenous genes.

Abstract: A system, method, and device for configuring an optical aiming device for ballistic drop compensation (BDC). The optical aiming device can include a housing with a reticle pane defining a reticle display field viewable by a user and indicating a zero point, the housing further including a plurality of axially spaced lenses and defining an optical path therethrough. In various embodiments the system includes a display device configured to project an image generated from a display, a processor, and a non-transitory computer readable storage medium. The computer readable data storage medium can include instructions executable by the processor to receive a first set of ballistics input data indicating a first type of ammunition, determine a BDC pattern including at least two holdover marks corresponding to at least two ranges for the first type of ammunition, and project the BDC pattern onto the reticle display field.

Abstract: Optical sights for mounting on a firearm are provided, each of the sights having a base defining a barrel end and a rear end; a frame extending upwardly from the base at the barrel end and defining an opening; an optical element received in the opening; and an illumination device operable to display an aiming point on the optical element to generate said aiming point.

Abstract: The present disclosure provides methods and compositions of modulating expression of a target nucleic acid sequence in a cell. The method comprises introducing into the cell a nucleic acid sequence encoding a Cas9 fusion protein and a guide RNA, wherein the Cas9 fusion protein and the guide RNA are expressed and co-localize at a target site and modulate the expression of the target nucleic acid sequence.

Abstract: A system, method, and device for configuring an optical aiming device for ballistic drop compensation (BDC). The optical aiming device can include a housing with a reticle pane defining a reticle display field viewable by a user and indicating a zero point, the housing further including a plurality of axially spaced lenses and defining an optical path therethrough. In various embodiments the system includes a display device configured to project an image generated from a display, a processor, and a non-transitory computer readable storage medium. The computer readable data storage medium can include instructions executable by the processor to receive a first set of ballistics input data indicating a first type of ammunition, determine a BDC pattern including at least two holdover marks corresponding to at least two ranges for the first type of ammunition, and project the BDC pattern onto the reticle display field.

Abstract: The present disclosure provides methods and compositions of modulating expression of a target nucleic acid sequence in a cell. The method comprises introducing into the cell a nucleic acid sequence encoding a Cas9 fusion protein and a guide RNA, wherein the Cas9 fusion protein and the guide RNA are expressed and co-localize at a target site and modulate the expression of the target nucleic acid sequence.

Abstract: A gunsight for aiming a firearm may comprise a display and an eyepiece optic positioned rearward of the display for allowing a user to view the display through the eyepiece optic and a motion sensing module. The eyepiece optic may comprise one or more eyepiece lenses. Circuitry of the gunsight is operatively coupled to the microbolometer and the display. The circuitry may comprise one or more processors and a non-transitory computer readable medium storing one or more instruction sets. In some embodiments, the one or more instruction sets include instructions configured to be executed by the one or more processors to receive a stream of motion signals from the motion sensing module and display an image to the user in response to the stream of motion signals.

Abstract: The present disclosure provides methods and compositions of modulating expression of a target nucleic acid in a eukaryotic cell. The methods include providing to the cell a guide RNA complementary to the target nucleic acid sequence, providing to the cell a fusion protein, wherein the fusion protein comprises a nuclease null Cas9 protein and a transcriptional effector domain, wherein the nuclease null Cas9 protein interacts with the guide RNA and binds to the target nucleic acid sequence in a site specific manner and wherein the transcriptional effector domain modulates expression of the target nucleic acid.

Abstract: A system, method, and device for configuring an optical aiming device for ballistic drop compensation (BDC). The optical aiming device can include a housing with a reticle pane defining a reticle display field viewable by a user and indicating a zero point, the housing further including a plurality of axially spaced lenses and defining an optical path therethrough. In various embodiments the system includes a display device configured to project an image generated from a display, a processor, and a non-transitory computer readable storage medium. The computer readable data storage medium can include instructions executable by the processor to receive a first set of ballistics input data indicating a first type of ammunition, determine a BDC pattern including at least two holdover marks corresponding to at least two ranges for the first type of ammunition, and project the BDC pattern onto the reticle display field.

Abstract: The present invention relates to in vitro genetic manipulation. In particular, it relates to RNA templated genome editing.