Provided herein are methods of detecting an analyte of interest to interrogate spatial gene expression in a sample using RNA-templated ligation.

The invention relates to the use of a reverse-transcriptase inhibitor in the prevention or treatment of a degenerative disease.

The invention relates to the use of a reverse-transcriptase inhibitor in the prevention or treatment of a degenerative disease.

The present invention concerns compounds that are capable of covalently entrapping adenylating enzymes. The present invention is essentially based on the discovery that analogues of adenylating enzyme (AE) substrates, wherein a methylene group has been incorporated at the carbon atom in the α-position relative to the carboxylate group involved in the adenylation, are capable of undergoing the adenylation reaction, thereby creating an activated methylene group in situ. The resulting ‘armed’ acyladenylate can interact with the enzyme resulting in covalent entrapment. Interestingly, the acyladenylate can alternatively be transferred to the next step in the enzyme cascade, following which the activated methylene group can interact with the next (active site cysteine containing) enzyme in the enzymatic cascade. The AE substrate analogues, based on their capability of ‘entrapping’ the respective enzymes, will have utility as activity based probes in biological research and also as diagnostic and/or therapeutic agents.

The present invention concerns compounds that are capable of covalently entrapping adenylating enzymes. The present invention is essentially based on the discovery that analogues of adenylating enzyme (AE) substrates, wherein a methylene group has been incorporated at the carbon atom in the α-position relative to the carboxylate group involved in the adenylation, are capable of undergoing the adenylation reaction, thereby creating an activated methylene group in situ. The resulting ‘armed’ acyladenylate can interact with the enzyme resulting in covalent entrapment. Interestingly, the acyladenylate can alternatively be transferred to the next step in the enzyme cascade, following which the activated methylene group can interact with the next (active site cysteine containing) enzyme in the enzymatic cascade. The AE substrate analogues, based on their capability of ‘entrapping’ the respective enzymes, will have utility as activity based probes in biological research and also as diagnostic and/or therapeutic agents.

A system and method for data privacy in URL based context queries. A reference to a data object is received from a user. At least one entity that controls the data object is identified via the network. At least one permission for the data object is retrieved via the network, wherein the permission is associated with the entity that controls the data object. It is then determined, via the network, if the user is permitted to access to the data object using the permission for the data object and spatial data, temporal data social data and logical data available to the network that relates to the user and to the permission for the data object. If the user is permitted access to the data object, access is granted to the data object, and if the user is nor permitted access to the data object, access is denied to the data object.

A system and method for data privacy in URL based context queries. A reference to a data object is received from a user. At least one entity that controls the data object is identified via the network. At least one permission for the data object is retrieved via the network, wherein the permission is associated with the entity that controls the data object. It is then determined, via the network, if the user is permitted to access to the data object using the permission for the data object and spatial data, temporal data social data and logical data available to the network that relates to the user and to the permission for the data object. If the user is permitted access to the data object, access is granted to the data object, and if the user is nor permitted access to the data object, access is denied to the data object.

A method for determining a biological response of a target (41, 42) to a soluble candidate substance includes the steps: introducing a soluble candidate substance into a laminar flow of a buffer liquid (2) to form a candidate substance solute (3) having an initial concentration profile (31); dispersing the initial concentration profile (31) to form a dispersed concentration profile (32); directing the dispersed concentration profile (32) into a detection channel (12) to form a final symmetrical concentration profile (33) therein; introducing a target into the detection channel (12) to obtain a combined concentration profile including a constant target concentration profile overlying the final symmetrical concentration profile (33); holding in the detection channel (12) at least one half of the combined concentration profile; and optically scanning the combined concentration profile to detect an optical signal representative of the biological response of the target to the soluble candidate substance.

A method for determining a biological response of a target (41, 42) to a soluble candidate substance includes the steps: introducing a soluble candidate substance into a laminar flow of a buffer liquid (2) to form a candidate substance solute (3) having an initial concentration profile (31); dispersing the initial concentration profile (31) to form a dispersed concentration profile (32); directing the dispersed concentration profile (32) into a detection channel (12) to form a final symmetrical concentration profile (33) therein; introducing a target into the detection channel (12) to obtain a combined concentration profile including a constant target concentration profile overlying the final symmetrical concentration profile (33); holding in the detection channel (12) at least one half of the combined concentration profile; and optically scanning the combined concentration profile to detect an optical signal representative of the biological response of the target to the soluble candidate substance.

Cyclic-GMP-AMP (cGAMP), including 2′,3′-cGAMP, are used in pharmaceutical formulations (including vaccine adjuvants), drug screens, therapies and diagnostics.