Abstract: Disclosed are methods and systems for bi-directional communication between one or more vehicles and a cloud based computing system. For instance, a method may include processing, by a first digital twin of the cloud based computing system, a first request received from and/or sent to a gateway unit associated with a first vehicle, the request comprising data related to one or more vehicle operations; validating, by an avionics data processing service (ADPS) in communication with the gateway unit, the first request against an operational parameter corresponding to the one or more vehicle operations; upon validating the first request, matching, by the ADPS, the operational parameter with a flight operation; and upon matching the operational parameter with the flight operation, inserting, by the ADPS, a modified flight operation into the flight management system of the vehicle.

Abstract: The present disclosure provides compositions comprising one or more compounds of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4.

Abstract: The present disclosure provides compositions comprising one or more compounds of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIk): wherein: R2?H or Me; R3?H or Me; R4=Alkyl; R5?O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIk), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIk), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIk) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (XIII): wherein: R8=NH2, NH(Me), N(Me)2, The present disclosure further provides methods of making compounds of general formula (XIII), compositions comprising a therapeutically effective amount of a compound of general formula (XIII), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (XIII) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIi): wherein: R2?H or Me; R3?H or Me; R4=Alkyl; R5?O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIi), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIi), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIi) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIg): wherein: R2=H or Me; R3=H or Me; R4=Alkyl; R5=O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIg), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIg), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIg) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (XIII): wherein: R8=NH2, NH(Me), N(Me)2, The present disclosure further provides methods of making compounds of general formula (XIII), compositions comprising a therapeutically effective amount of a compound of general formula (XIII), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (XIII) to the subject.

Abstract: The present disclosure provides compositions comprising one or more compounds of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIk): wherein: R2?H or Me; R3?H or Me; R4=Alkyl; R5?O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIk), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIk), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIk) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIg): wherein: R2=H or Me; R3=H or Me; R4=Alkyl; R5=O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIg), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIg), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIg) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIi): wherein: R2=H or Me; R3=H or Me; R4=Alkyl; R5=O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIi), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIi), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIi) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VIIIk): wherein: R2=H or Me; R3=H or Me; R4=Alkyl; R5=O-Alkyl; and Alkyl=aliphatic C1-C4 alkyl. The present disclosure further provides methods of making compounds of general formula (VIIIm), compositions comprising a therapeutically effective amount of a compound of general formula (VIIIm), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) compositions comprising an effective amount of a compound of general formula (VIIIm) to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VI): wherein: R1 is H, Cl, F, —CF3, —OCF3, —OMe, or methyl; R8 is selected from the group consisting of: —NH2, —N(H)Alk, —N(Alk)2, R7 is H or alkyl; m is 3 to 6; p is 1 to 4; q is 1 to 4; p+g is 3 to 6; and each Alk is independently an aliphatic carbon group consisting of 1 to 6 carbon atoms, and methods of making and using same.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4. The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (VI): wherein: R1 is H, Cl, F, —CF3, —OCF3, —OMe, or methyl; R8 is selected from the group consisting of: —NH2, —N(H)Alk, —N(Alk)2, R7 is H or alkyl; m is 3 to 6; p is 1 to 4; q is 1 to 4; p+q is 3 to 6; and each Alk is independently an aliphatic carbon group consisting of 1 to 6 carbon atoms, and methods of making and using same.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4. The present disclosure further provides compositions comprising a therapeutically effective amount of a compound of general formula (I), and methods of treating or preventing pain in a subject by administering (e.g., topically applying) such compositions to the subject.

Abstract: Disclosed are methods and systems for bi-directional communication between one or more vehicles and a cloud based computing system. For instance, a method may include processing, by a first digital twin of the cloud based computing system, a first request received from and/or sent to a gateway unit associated with a first vehicle, the request comprising data related to one or more vehicle operations; validating, by an avionics data processing service (ADPS) in communication with the gateway unit, the first request against an operational parameter corresponding to the one or more vehicle operations; upon validating the first request, matching, by the ADPS, the operational parameter with a flight operation; and upon matching the operational parameter with the flight operation, inserting, by the ADPS, a modified flight operation into the flight management system of the vehicle.

Abstract: The present disclosure provides compounds useful as anesthetics, such as topical anesthetics, of general formula (I): wherein: R1 is H, —OMe, Me, or one or more electron withdrawing groups; R2 and R3 are each independently H or alkyl or, taken together, form a 4- to 8-membered heterocyclic ring with the adjacent nitrogen atom; R4 is H or alkyl; R5 is H or one or more electron donating groups; and n is 1 to 4.

Abstract: A frame apparatus for holding a flexible lance positioning mechanism adjacent to and spaced from a heat exchanger tube sheet includes an upper guide rail, a lower guide rail, a positioner rail supported from one of the upper and lower guide rails and guided by the other of the upper and lower guide rails, and a rail clamp assembly fastened to a portion of a tube sheet. This rail clamp assembly has a flat plate member fastened to the tube sheet, a base plate spaced from the flat plate by one or more threaded shafts, and one or more clamp fingers rotatably fastened to the base plate. Each clamp fingers is operable to rotate toward the base plate when the base plate is drawn against the flat plate or beam member by rotating the threaded shaft, thus drawing the rail securely to the flat plate of the clamp assembly.