Abstract: Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.

Abstract: Radio frequency (RF) generators are disclosed. A RF generator may include a modulator configured to receive an arbitrary waveform and an RF carrier, and generate a pulsed radio frequency (RF). The arbitrary waveform may be generated via an analog signal generator external to the RF generator. Further, the RF generator may include an amplification stage configured to amplify the pulsed RF signal. RF generation systems and methods of generating a pulsed RF signal also disclosed.

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities.

Abstract: Systems and methods for heteroaromatic silicon fluoride compounds as radiopharmaceuticals with theranostic properties are described. The theranostic heteroaromatic silicon fluoride compounds can be conjugated with various disease binding ligands and/or chelators for imaging and therapeutic applications.

Abstract: Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.

Abstract: The disclosure provides amino acid sequence variants of Bacillus thuringiensis (Bt) toxins and methods of producing the same. Some aspects of this disclosure provide methods for generating Bt toxin variants by continuous directed evolution. Some aspects of this disclosure provide compositions and methods for pest control using the disclosed variant Bt toxins.

Abstract: One or more example relate, generally, to generating radio frequency (RF) signals. An apparatus may include a signal generator, an amplification stage, and a feedback control loop. The signal generator may generate a pulsed radio frequency (RF) signal at least partially responsive to a digital pulsed waveform defined by one or more commands. The amplification stage may amplify the pulsed RF signal. The feedback control loop may be coupled to the amplification stage to regulate a power level of respective steps of the pulsed RF signal.

Abstract: A method, system, and computer program product for implementing machine learning visual code and action generation is provided. The method includes receiving from a plurality of hardware and software sources, digital description data associated with visual presentations and an action for execution. A resulting code-based class for each portion of the digital description data is generated with respect to the visual presentation. Self learning software code is executed and a type of visual presentation is selected with respect to associated visual features and the code-based class. Additionally, a visual presentation is selected and an action is executed resulting in hardware and software of a server hardware device being operationally modified. The visual presentation is presented to a user.

Abstract: Radio frequency (RF) generators are disclosed. A RF generator may include a modulator configured to receive an arbitrary waveform and an RF carrier, and generate a pulsed radio frequency (RF). The arbitrary waveform may be generated via an analog signal generator external to the RF generator. Further, the RF generator may include an amplification stage configured to amplify the pulsed RF signal. RF generation systems and methods of generating a pulsed RF signal also disclosed.

Abstract: Some aspects of this disclosure relate to systems, apparatuses, compositions (e.g., isolated nucleic acids and vectors), and methods for improving the stability and/or solubility of proteins evolved using phage-assisted continuous evolution (PACE). In some embodiments, vectors described herein comprise nucleic acids encoding selection systems (e.g., positive and/or negative selection systems) that link expression of genes required for production of infectious phage particles to a desirable physiochemical (e.g., stability or solubility) and/or desired function of an evolved protein.

Abstract: A heat exchanger (4) has fluid flow channels (6) with at least one heat exchanging surface (10) which has an undulating surface section for which the surface profile varies along a predetermined direction such that at a first edge (E1) the surface profile follows a first transverse wave (20), at a second edge (E)2 the surface profile follows a second transverse wave (22) and at an intermediate point I between the edges the surface profile follows a third transverse wave (24). The third transverse wave (24) has a different phase, frequency or amplitude to the first and second transverse waves so that chevron-shaped ridges and valleys are formed. This improves the mixing of fluid passing through the channel and hence the heat exchange efficiency.

Abstract: Radio frequency (RF) generators are disclosed. A RF generator may include an analog signal generator configured to generate a pulsed analog signal responsive to a digital pulsed waveform defined by one or more commands. The RF generator may also include a modulator configured to generate a pulsed radio frequency (RF) signal by modulating an RF carrier using the pulsed analog signal as a modulating signal. Further, the RF generator may include an amplification stage configured to amplify the pulsed RF signal output by the modulator. RF generation systems and methods of generating a pulsed RF signal also disclosed.

Abstract: The disclosure provides amino acid sequence variants of Bacillus thuringiensis (Bt) toxins and methods of producing the same. Some aspects of this disclosure provide methods for generating Bt toxin variants by continuous directed evolution. Some aspects of this disclosure provide compositions and methods for pest control using the disclosed variant Bt toxins.

Abstract: A method, system, and computer program product for implementing machine learning visual code and action generation is provided. The method includes receiving from a plurality of hardware and software sources, digital description data associated with visual presentations and an action for execution. A resulting code-based class for each portion of the digital description data is generated with respect to the visual presentation. Self learning software code is executed and a type of visual presentation is selected with respect to associated visual features and the code-based class. Additionally, a visual presentation is selected and an action is executed resulting in hardware and software of a server hardware device being operationally modified. The visual presentation is presented to a user.

Abstract: Strategies, reagents, methods, and systems for modulating the mutation rate in cells are provided herein. The strategies, reagents, methods, and systems are broadly applicable for the modulation of mutation rates in cells where high mutation rates and/or control over a broad range of mutation rates is desired, for example, in the context of diversifying a nucleic acid sequence or a plurality of such sequences within a population of cells, for the generation of diversified nucleic acid libraries, and for directed evolution of nucleic acids and encoded products.

Abstract: A heat exchanger (4) comprises a heat exchanger core (20) comprising first fluid channels (22) and second fluid flow channels (24) for exchange of heat between the first and second fluids. First and second manifold portions (42, 44) are provided to guide the first and second fluids between the first and second fluid flow channels (22, 249 and first and second fluid interface portions (48, 49) which comprise fewer channels than the heat exchanger core (20). The first manifold portion (42) includes at least one tunnel portion (46) extending through the second manifold portion (44) at an angle to the direction of second fluid flow. Hence at least part of the first fluid is directed through the inside of the tunnel portion while the second fluid passes around the outside of the tunnel portion. This enables more compact heat exchanger design.

Abstract: Strategies, reagents, methods, and systems for modulating the mutation rate in cells are provided herein. The strategies, reagents, methods, and systems are broadly applicable for the modulation of mutation rates in cells where high mutation rates and/or control over a broad range of mutation rates is desired, for example, in the context of diversifying a nucleic acid sequence or a plurality of such sequences within a population of cells, for the generation of diversified nucleic acid libraries, and for directed evolution of nucleic acids and encoded products.

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities.

Abstract: A computer-implemented method, system and computer program product for creating a descriptor for a dashboard template. The column-to-visualization mappings are extracted from a dashboard of a created or modified dashboard (or a created or modified dashboard template). Furthermore, the concept combinations from each visualization of the dashboard are extracted. Additionally, topics from the dashboard are extracted. The concept combinations, topics and column-to-visualization mappings are aggregated into a dashboard template descriptor. The dashboard template descriptor is then stored. In this manner, the dashboard template descriptor captures how concept combinations are used in the visualizations of the dashboard as well as how high-level concepts (topics) are incorporated in the dashboard. Furthermore, the dashboard template descriptor captures how the concepts of the columns of a dataset are mapped to the visualizations of the dashboard.

Abstract: A computer-implemented method, system and computer program product for recommending a template or a dataset. A descriptor (input descriptor) of the input, corresponding to a dataset or a dashboard template, is extracted or fetched. The input descriptor may be the descriptor of the dataset which includes topics and concept combinations. Alternatively, the input descriptor may be the descriptor of the dashboard template which includes topics, concept combinations and column-to-visualization mappings. Scores are then generated for the candidate targets, corresponding to dashboard templates or datasets, based on one or more of the following: matching topics in the input descriptor with topics in the candidate target descriptors, matching concept combinations in the input descriptor with concept combinations in the candidate target descriptors, and determining compatibility of the datasets with the dashboard templates.