Abstract: In some examples, a system receives sensor data from sensors on board a vehicle. Based at least on the sensor data indicating an anomaly has occurred and is affecting a travel path of the vehicle, an uncertainty threshold is compared with an uncertainty value associated with a prediction model. For instance, the uncertainty value may be indicative of a difference between a predicted value predicted by the prediction model and an actual measured value related to at least one operation parameter of the vehicle. Based at least on determining that the anomaly has occurred and that the uncertainty value is within the uncertainty threshold, sending, by the system, a communication for obtaining an updated prediction model.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the present invention relates to pharmaceutical agents which function as inhibitors of TDP-43 activity. The invention further relates to methods of treating and/or ameliorating symptoms related to conditions associated with TDP-43 activity (e.g., neurodevelopmental disorders), comprising administering to a subject (e.g., a human patient) a composition comprising one or more pharmaceutical agents which function as inhibitors of TDP-43 activity.

Abstract: This invention relates generally to neurodegenerative diseases and conditions (e.g., Alzheimer's disease) characterized with aberrant RIPK1/RIPK3 binding, RIPK3/MLKL binding, necrosome formation, and/or necroptosis activation. This invention further relates to methods and compositions for treating such neurodegenerative diseases and conditions with pharmaceutical compositions comprising agents capable of inhibiting RIPK1/RIPK3 binding and/or RIPK3/MLKL binding.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quindoline (or similar) structure which function as stabilizers of G-quadruplex (G4) formation, and their use as therapeutics for the treatment of cancer (e.g., castration-resistant prostate cancer), and other conditions mediated by G4 stabilization.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperazine (or similar) structure which function as antagonists of androgen receptor activity, and their use as therapeutics for the treatment of cancer (e.g., castration-resistant prostate cancer) and other conditions characterized with androgen receptor activity and/or androgen receptor expression.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperidinyl-benzoimidazole structure which function as antagonists of small ubiquitin like modifier (SUMO) related modification (SUMOylation) of collapsin response mediator protein 2 (CRMP2), and their use as therapeutics for the treatment of voltage gated sodium channel 1.7 (Nav1.7) related itch, anosmia, migraine event, and/or pain (e.g., neuropathic pain).

Abstract: The present invention provides hTERT modulators and methods for producing and using the same. In particular, the present invention provide a compound of the formula: whereas, n, R1, R2, R3, RH and R12 are as defined herein.

Abstract: The present invention provides compounds that can modulate the amount of Nav1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: The present invention provides hTERT modulators and methods for producing and using the same. In particular, the present invention provide a compound of the formula: where a, n, R1, R2, R3, R11 and R12 are as defined herein.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperidinyl-benzoimidazole structure which function as antagonists of small ubiquitin like modifier (SUMO) related modification (SUMOylation) of collapsin response mediator protein 2 (CRMP2), and their use as therapeutics for the treatment of voltage gated sodium channel 1.7 (Nav1.7) related itch, anosmia, migraine event, and/or pain (e.g., neuropathic pain).

Abstract: The present invention relates to a compound of the formula: where n, R1 and R2 are those defined herein. The present invention also relates to use of a compound of Formula 1 in treating a clinical condition associated with fibrotic disorder.

Abstract: The present invention provides compounds that can modulate the amount of Nav1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: The present invention provides hTERT modulators and methods for producing and using the same. In particular, the present invention provide a compound of the formula as described herein. Some aspects of the invention are based on the characterization of the effect of hTERT core promoter region mutants on the 5-12 G-quadruplex structure and its stability. It is believed that some of the compounds of the invention bind selectively to the G-quadruplex in the hTERT core promoter mutant, which results in reversal of the effect of mutant promoter activation.

Abstract: The present invention provides compounds that can modulate the amount of Nav 1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav 1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav 1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: The present invention relates to a compound of the formula: where n, R and R are those defined herein. The present invention also relates to use of a compound of Formula 1 in treating a clinical condition associated with fibrotic disorder.

Abstract: The present invention provides hTERT modulators and methods for producing and using the same. In particular, the present invention provide a compound of the formula as described herein. Some aspects of the invention are based on the characterization of the effect of hTERT core promoter region mutants on the 5-12 G-quadruplex structure and its stability. It is believed that some of the compounds of the invention bind selectively to the G-quadruplex in the hTERT core promoter mutant, which results in reversal of the effect of mutant promoter activation.

Abstract: The present invention provides compounds that can modulate the amount of Nav 1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav 1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav 1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein.