Abstract: A high pressure die casting (HPDC) system for casting ultra-large single-piece castings for vehicles. The HPDC system includes a clear feeding path from at least one ingate to a predetermined thicker section of a mold cavity, a last to solidify ingate having an equivalent or larger feeding modulus than the highest feeding modulus of the other ingates, and thermal management elements. The clear feeding path, last to solidify ingate, and thermal management elements ensure sufficient supplemental molten metal flow to the thicker portion of the mold cavity to accommodate for shrinkage of the thicker portion of an ultra large casting during the casting and solidification process.

Abstract: Disclosed herein are modified human interleukin-2 (hIL-2) proteins, human antibody molecules, or antigen-binding fragments thereof, that immunospecifically bind to human programmed cell death protein-1 (hPD-1), and immunoconjugates comprising the same.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: The disclosure provides programmable methylation “writers” and demethylation “erasers” for editing the methylation state of RNA targets, e.g., an RNA transcriptome. In particular, the disclosure provides RNA methylation editor polynucleotide contracts and vectors comprising (i) an RNA programmable RNA binding domain (RNApRNAbd); and (ii) an effector domain, wherein the effector domain is capable of adding or removing a methyl group in an RNA. The disclosed RNA methylation editor constructs are capable of achieving limited off-target modifications in RNA molecules. Further, the disclosure provides methods for making and using the programmable methylation editors to modifying the methylation state of RNA. The disclosure further provides complexes comprising a methylation writer protein and a guide RNA molecule and complexes comprising a demethylation eraser protein and a guide RNA molecule.

Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. The disclosure provides fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cas9 or variants thereof, and nucleic acid editing proteins such as cytidine deaminase domains (e.g., novel cytidine deaminases generated by ancestral sequence reconstruction), and adenosine deaminases that deaminate adenine in DNA. Aspects of the disclosure relate to fusion proteins (e.g., base editors) that have improved expression and/or localize efficiently to the nucleus. In some embodiments, base editors are codon optimized for expression in mammalian cells. In some embodiments, base editors include multiple nuclear localization sequences (e.g., bipartite NLSs), e.g., at least two NLSs.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: There is disclosed a method of forming a reflective device which generates an optically variable image which varies according to the angle of observation. The method comprises the steps of providing a primary pattern which encodes a latent image, the primary pattern having a plurality of image elements, and providing a corresponding secondary pattern which will decode the primary pattern to allow the latent image to be observed when the primary and secondary patterns are in at least one registration, wherein the secondary pattern is provided by a micro mirror array (MMA) having a plurality of each of at least two different types of micro mirror elements, wherein the primary pattern is provided such that predetermined image elements of the primary pattern render reflection effects from predetermined micro mirror elements of the MMA optically ineffective at least at one observation angle when the reflective device is illuminated with a light source to thereby enable the latent image to be observed.

Abstract: There is disclosed a method of forming a diffractive authentication device which generates an optically variable image which varies according to the angle of observation. The method comprises the steps of, providing a primary pattern which encodes a latent image, the primary pattern having a plurality of image elements, and providing a corresponding secondary pattern which will decode the primary pattern to allow the latent image to be observed when the primary and secondary patterns are in at least one registration, wherein the secondary pattern is provided by a diffraction grating microstructure having a plurality of each of at least two different types of diffraction elements.

Abstract: A modulation drive current control loop for a digitally modulated laser diode uses the small signal, square-law portion of an RF signal diode detection circuit to adjust the magnitude of laser modulation drive current, and compensate for variations in temperature and aging of the laser diode. Operating the RF signal detector diode as a non-switched device, in its square-law region, provides several advantages over large signal, switched, linear region devices. When a detector diode is operated in the large signal, switched, linear region, its output depends upon the reduced slope beyond the `knee` region of the curve, so that the diode functions essentially as a switch. In such a large signal detection mode, the diode conducts during only a portion of the input cycle, with its output voltage following peaks of the input signal waveform in accordance with a linear relationship between input voltage and output voltage.