Abstract: The present invention includes dead-guide RNA (dgRNA) libraries and methods of use in immunology and immunotherapy thereof. Also provided are engineered primary or chimeric antigen receptor (CAR) T cells that overexpress Prodh2, Ccnblip1, Sreklip1, or Wdr37 or a fragment thereof, and methods of use in immunology and immunotherapy thereof.

Abstract: The present invention includes compositions and methods for identification of membrane targets for enhancement of T cell activity against a disease, disorder or condition, and/or enhancing T cell anti-tumor activity in a subject in need thereof. In some embodiments, the disease is cancer. In further embodiments, the cancer is glioblastoma (GBM) or breast cancer.

Abstract: The current disclosure includes coronavirus vaccines that protect against pathogenic coronavirus species, as well as their variants. In certain embodiments, SARS-CoV-2 variant specific and multivalent coronavirus vaccines are described. The vaccines typically include a modified mRNA which encodes at least one coronavirus derived immunogen, such as a spike protein or a fragment thereof. The mRNA can be encapsulated into lipid nanoparticles or other carriers and formulated as pharmaceutical compositions which can be used to generate an immune response to coronavirus in a subject. The vaccines can be used to elicit potent B and T cell responses against SARS-CoV-2 variants and to confer protective immunity against SARS-CoV-2, as well as other pathogenic coronavirus species such as SARS-CoV and/or MERS-CoV.

Abstract: A method may include generating, by a camera having a view of an interior portion of a computer-numerically-controlled machine, an image comprising a pattern. The image can be transformed into a set of machine instructions for controlling the computer-numerically-controlled machine to effect a change in a material. The change can correspond to at least a portion of the pattern. At least one machine instruction from the set of machine instructions can be executed to control the computer-numerically-controlled machine to effect at least a portion of the change. The execution can include operating, in accordance with the at least one machine instruction, a tool coupled with the computer-numerically-controlled machine. The tool can be configured to effect the change on the material. Related systems and articles of manufacture, including computer program products, are also provided.

Abstract: Systems and methods for gas lift in the main bore and lateral legs of a multilateral well. The systems and methods can allow for gas lift below the junction of a multilateral well.

Abstract: Embodiments include one or more computing systems configured to perform functions comprising: (i) receiving a natural language description of a desired fabrication result; (ii) causing a software engine to generate machine-created rendering instructions based on the natural language description of the desired fabrication result; and (iii) executing, by a laser CNC machine, the machine-created rendering instructions to generate a rendered fabrication result.

Abstract: A method may include generating, by a camera having a view of an interior portion of a computer-numerically-controlled machine, an image comprising a pattern. The image can be transformed into a set of machine instructions for controlling the computer-numerically-controlled machine to effect a change in a material. The change can correspond to at least a portion of the pattern. At least one machine instruction from the set of machine instructions can be executed to control the computer-numerically-controlled machine to effect at least a portion of the change. The execution can include operating, in accordance with the at least one machine instruction, a tool coupled with the computer-numerically-controlled machine. The tool can be configured to effect the change on the material. Related systems and articles of manufacture, including computer program products, are also provided.

Abstract: Systems and methods for gas lift in the main bore and lateral legs of a multilateral well. The systems and methods can allow for gas lift below the junction of a multilateral well.

Abstract: Compositions and methods for cellular genome engineering that permit simple and efficient targeted knock-in of a CAR and simultaneous knockout of individual genes are described. The compositions and methods are especially applicable to massively parallel engineering, selection, and identification of CAR T cell variants exhibiting a desired phenotype. AAV vectors containing crRNA and CAR expression cassettes and homology arms for targeted genomic integration thereof are provided. Also provided are libraries containing a plurality of AAV vectors and methods of use thereof in screens for identifying desirable CAR T cell variants. Methods of treatment using CAR T cell variants exhibiting improvements in one or more phenotypes are also provided.

Abstract: The present invention includes compositions and methods for identification of membrane targets for enhancement of T cell activity against a disease, disorder or condition, and/or enhancing T cell anti-tumor activity in a subject in need thereof. In some embodiments, the disease is cancer. In further embodiments, the cancer is glioblastoma (GBM) or breast cancer.

Abstract: A method may include generating, by a camera having a view of an interior portion of a computer-numerically-controlled machine, an image comprising a pattern. The image can be transformed into a set of machine instructions for controlling the computer-numerically-controlled machine to effect a change in a material. The change can correspond to at least a portion of the pattern. At least one machine instruction from the set of machine instructions can be executed to control the computer-numerically-controlled machine to effect at least a portion of the change. The execution can include operating, in accordance with the at least one machine instruction, a tool coupled with the computer-numerically-controlled machine. The tool can be configured to effect the change on the material. Related systems and articles of manufacture, including computer program products, are also provided.

Abstract: A method for dithering can include receiving, at a computer numerically controlled machine comprising a laser, a motion plan corresponding to a first image. The output of the laser can be dithered, in accordance with the motion plan, to effect a change in a material within an interior space of the computer numerically controlled machine. The change can substantially reproduce at least a portion of the first image on the material. The dithering can include providing laser energy to the material at a native resolution based at least on a spot size of the laser. The spot size can be determined based at least on one or more parameters of the computer numerically controlled machine and/or one or more properties of the material. The laser energy can be delivered at locations separated by a distance no less than the spot size.

Abstract: A method may include generating, by a camera having a view of an interior portion of a computer-numerically-controlled machine, an image comprising a pattern. The image can be transformed into a set of machine instructions for controlling the computer-numerically-controlled machine to effect a change in a material. The change can correspond to at least a portion of the pattern. At least one machine instruction from the set of machine instructions can be executed to control the computer-numerically-controlled machine to effect at least a portion of the change. The execution can include operating, in accordance with the at least one machine instruction, a tool coupled with the computer-numerically-controlled machine. The tool can configured to effect the change on the material. Related systems and articles of manufacture, including computer program products, are also provided.

Abstract: The present invention includes dead-guide RNA (dgRNA) libraries and methods of use in immunology and immunotherapy thereof. Also provided are engineered primary or chimeric antigen receptor (CAR) T cells that overexpress Prodh2, Ccnblip1, Sreklip1, or Wdr37or a fragment thereof, and methods of use in immunology and immunothereapy thereof.

Abstract: A method for dithering can include receiving, at a computer numerically controlled machine comprising a laser, a motion plan corresponding to a first image. The output of the laser can be dithered, in accordance with the motion plan, to effect a change in a material within an interior space of the computer numerically controlled machine. The change can substantially reproduce at least a portion of the first image on the material. The dithering can include providing laser energy to the material at a native resolution based at least on a spot size of the laser. The spot size can be determined based at least on one or more parameters of the computer numerically controlled machine and/or one or more properties of the material. The laser energy can be delivered at locations separated by a distance no less than the spot size.

Abstract: A method for dithering can include receiving, at a computer numerically controlled machine comprising a laser, a motion plan corresponding to a first image. The output of the laser can be dithered, in accordance with the motion plan, to effect a change in a material within an interior space of the computer numerically controlled machine. The change can substantially reproduce at least a portion of the first image on the material. The dithering can include providing laser energy to the material at a native resolution based at least on a spot size of the laser. The spot size can be determined based at least on one or more parameters of the computer numerically controlled machine and/or one or more properties of the material. The laser energy can be delivered at locations separated by a distance no less than the spot size.

Abstract: A packoff device is disclosed for sealing an annulus within a wellbore, and for bypassing the sealed annulus. The packoff device may include a mandrel having a bore formed axially therethrough and first and second ports extending radially from the bore. A sealing element that extends radially-outwardly from the mandrel may be positioned axially between the first and second ports, and may create a seal within an annulus between the mandrel and a casing, to isolate a portion of the annulus above the sealing element from a portion below the sealing element. A sleeve within the bore may, with the mandrel, form a channel providing fluid communication between the first and second ports. The sleeve may be movable between open and closed states. The first and second ports may be unobstructed by the sleeve in the open state, one or more may be obstructed in the closed state.

Abstract: A base cell of a gate array architecture includes an increased number of transistors that can be interconnected or not interconnected so as to realize similar advantages as a having a library of transistors of different sizes. In one embodiment, each column a base cell contains two PMOS transistors and two NMOS transistors connected so as to share a single polysilicon (“poly”) gate electrode. Such an arrangement of the transistors in metal only programmable base cell architecture provides three different P and N transistor widths per poly gate and may provide nine different combinations transistor widths for P and N for design. The number of gate electrodes is minimized and their arrangement simplified such that the size of the base cell may be same size compared to traditional gate array base cell with four transistors. Moreover, only a single type of base cell need be provided, simplifying layout and design.

Abstract: A packoff device is disclosed for sealing an annulus within a wellbore, and for bypassing the sealed annulus. The packoff device may include a mandrel having a bore formed axially therethrough and first and second ports extending radially from the bore. A sealing element that extends radially-outwardly from the mandrel may be positioned axially between the first and second ports, and may create a seal within an annulus between the mandrel and a casing, to isolate a portion of the annulus above the sealing element from a portion below the sealing element. A sleeve within the bore may, with the mandrel, form a channel providing fluid communication between the first and second ports. The sleeve may be movable between open and closed states. The first and second ports may be unobstructed by the sleeve in the open state, one or more may be obstructed in the closed state.

Abstract: A packoff device is disclosed for sealing an annulus within a wellbore, and for bypassing the sealed annulus. The packoff device may include a mandrel having a bore formed axially therethrough and first and second ports extending radially from the bore. A sealing element that extends radially-outwardly from the mandrel may be positioned axially between the first and second ports, and may create a seal within an annulus between the mandrel and a casing, to isolate a portion of the annulus above the sealing element from a portion below the sealing element. A sleeve within the bore may, with the mandrel, form a channel providing fluid communication between the first and second ports. The sleeve may be movable between open and closed states. The first and second ports may be unobstructed by the sleeve in the open state, one or more may be obstructed in the closed state.