Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Abstract: The present invention discloses mass spectrometry (MS)-based methods and tagging reagents for qualitative and quantitative analysis of post-translational modified (PTM) proteins in biological and clinical samples. The present invention utilizes thiol-containing tagging reagents which are able to bind to or derivatize biomolecules, preferably post-translational modified (PTM) polypeptides such as citrullinated and homocitrullinated polypeptides. The tagging reagents are preferably biotin-derived tags able to react with a side chain of the modified polypeptides.

Abstract: Disclosed herein are compositions, methods, cells, engineered microorganisms, and kits for increasing the production of proteins or polypeptides comprising one or more unnatural amino acids. Further provided are compositions, cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.

Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Abstract: The present invention provides improved cleavable biotin-containing isobaric tags for quantitative mass spectrometry proteomics, particularly useful in quantification of post-translational modifications (PTMs) and assessing cysteine containing proteins. The isobaric chemical tags, DiLeu-Biotin-Azide (DBA), consist of three “modules”: (1) a DiLeu reporter group for relative quantification using MS/MS; (2) a biotin moiety for selective enrichment via streptavidin beads; and (3) an azide functional group to enable biorthogonal click chemistry. The DBA tags could be used in a high-throughput quantitative pan-PTM analysis platform.

Abstract: Disclosed herein are compositions, methods, cells, engineered microorganisms, and kits for increasing the production of proteins or polypeptides comprising one or more unnatural amino acids. Further provided are compositions, cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Abstract: The present invention provides a set of novel isobaric chemical tags, also referred herein as SUGAR (Isobaric Multiplex Reagents for Carbonyl Containing Compound). These labeling tags are compact and easy to synthesize at high yield and purity in just a few steps using commercially available starting materials. The tagging reagents of the present invention comprise: a) a reporter group, having at least one atom that is optionally isotopically labeled; b) a balancing group, also having at least one atom that is optionally isotopically labeled, and c) an aldehyde, ketone, or carboxylic acid reactive group. The multiplex SUGAR tags are able to react with an aldehyde, ketone, or carboxylic acid group of the molecule to be tagged, which offers the capability for labeling and quantitation of glycans, proteins/peptides, and fatty acids.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: The present invention provides a set of novel isobaric chemical tags, also referred herein as SUGAR (Isobaric Multiplex Reagents for Carbonyl Containing Compound). These labeling tags are compact and easy to synthesize at high yield and purity in just a few steps using commercially available starting materials. The tagging reagents of the present invention comprise: a) a reporter group, having at least one atom that is optionally isotopically labeled; b) a balancing group, also having at least one atom that is optionally isotopically labeled, and c) an aldehyde, ketone, or carboxylic acid reactive group. The multiplex SUGAR tags are able to react with an aldehyde, ketone, or carboxylic acid group of the molecule to be tagged, which offers the capability for labeling and quantitation of glycans, proteins/peptides, and fatty acids.

Abstract: The systems and methods described herein can include a digital assistant application that receives sensor signals from sensors installed in a vehicle and determines an entry event into the vehicle. The digital assistant application can receive, responsive to the entry event into the vehicle, a plurality authentication input signals from a plurality of sensors associated with the vehicle. The digital assistant application can determine a plurality of authentication states based on the plurality of authentication input signals and a plurality of authentication credentials. The digital assistant application can identify an access permission level of a plurality of access permission levels based at least in part on the plurality of identifies authentication states. The digital assistant application can identify, responsive to the access permission level, a subset of a set of functionalities available via the vehicle, and provide vehicular access to the subset of functionalities.

Abstract: The present invention provides a compound having a structure of formula (I), a preparation method and use thereof, and a pharmaceutical composition containing the compound, wherein R is methyl, ethyl, propyl, vinyl or propenyl. The present invention also provides a crystalline form of the compound, a preparation method and use of the crystalline form, and a pharmaceutical composition comprising the crystalline form. The compounds having the structure of formula (I) of the present invention are present in a solid form, which not only can solve the problem of clopidogrel resistance, but also can solve the problem of severe hemorrhagic side effect and poor safety of some drugs, as well as the problem of poor stability of existing compounds. It can be developed into an ADP receptor antagonist antiplatelet agent with clear therapeutic effect, no resistance and better stability.

Abstract: The use of mass defect signatures to impart milliDalton mass differences between isotopically labeled peptides at the MS1-level allows multiplex quantification without the increased mass spectral complexity that occurs with mass difference approaches. Provided herein is a mass defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), that is compact and easy to synthesize at high purity in few steps using commercially available starting materials. The multiplex DiPyrO tags are amine-reactive and can impart a mass difference onto labeled peptides and through calculated substitution of heavy isotopes. DiPyrO offers up to 10-plex quantification on current Orbitrap or FT-ICR platforms without increasing mass spectral complexity. The synthesis of the DiPyrO tag is provided along with viability of the DiPyrO tag for labeling complex proteomics samples using yeast extract digests and its effect on labeled peptides during LC-MS2 analysis.

Abstract: The present invention discloses mass spectrometry (MS)-based methods and tagging reagents for qualitative and quantitative analysis of post-translational modified (PTM) proteins in biological and clinical samples. The present invention utilizes thiol-containing tagging reagents which are able to bind to or derivatize biomolecules, preferably post-translational modified (PTM) polypeptides such as citrullinated and homocitrullinated polypeptides. The tagging reagents are preferably biotin-derived tags able to react with a side chain of the modified polypeptides.