Abstract: Provided are crystalline forms of a KRAS G12C inhibitor compound and to processes for their preparation. Furthermore, provided is pharmaceutical composition comprising said crystalline forms, and at least one pharmaceutically acceptable excipient. The pharmaceutical composition can be used as a medicament, in particular for the treatment of cancer, and KRAS G12C-mutant cancer.

Abstract: It relates to a pharmaceutical combination comprising a KRAS G12C inhibitor, in particular 1-{6-[(4M)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro [3.3] heptan-2-yl} prop-2-en-1-one (Compound A) and one or more therapeutically active agents selected from a SHP2 inhibitor (e.g. TNO155) and a PD-1 inhibitor, pharmaceutical compositions comprising the same; and methods of using such combinations and compositions in the treatment or prevention of a cancer or a tumor, in particular wherein the cancer or tumor is KRAS G12C mutated.

Abstract: A fiber optic sensing (FOS) system may include a Brillouin Optical Time Domain Analyzer (BOTDA) unit, a first fiber optical cable optically connected to the BOTDA interrogator unit at a first end, and an optical feedthrough system (OFS) optically connected the first fiber optical cable at a second end of the first fiber optical cable. The FOS system may further comprise a fiber optic cable forming a loop within a wellbore that is optically connected to the first fiber optical cable at the OFS and a second fiber optical cable optically connected to the loop at the OFS and wherein the second fiber optical cable is optically connected to the BOTDA interrogator unit.

Abstract: Described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating a neurological condition (e.g., a neurodegenerative disease (e.g., Alzheimer's disease)) in a subject, based on caspase-1 inhibition. Also described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating cognitive impairment in a subject, based on caspase-1 inhibition. Corresponding uses and kits are also described. In an embodiment, the caspase-1 inhibitor is VX-765 or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating a neurological condition (e.g., a neurodegenerative disease (e.g., Alzheimer's disease)) in a subject, based on caspase-1 inhibition. Also described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating cognitive impairment in a subject, based on caspase-1 inhibition. Corresponding uses and kits are also described. In an embodiment, the caspase-1 inhibitor is VX-765 or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating a neurological condition (e.g., a neurodegenerative disease (e.g., Alzheimer's disease)) in a subject, based on caspase-1 inhibition. Also described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating cognitive impairment in a subject, based on caspase-1 inhibition. Corresponding uses and kits are also described. In an embodiment, the caspase-1 inhibitor is VX-765 or a pharmaceutically acceptable salt thereof.

Abstract: While the extracellular accumulation of amyloid-&bgr; in the brain parenchyma is a pathological hallmark of Alzheimer's disease, its role as a cause or a consequence of AD is still debated. As described herein, intracellular A&bgr;1-42 is shown to be selectively toxic to neurons. The present invention provides methods of screening for compounds for the prevention and treatment of A amyloid associated diseases such as Alzheimer's disease, Down's Syndrome, cerebral amyloid angiopathy, and inclusion body myositis.

Abstract: The present invention relates to a method of protecting neurons against bax-mediated apoptosis and assays to identify agents which modulate neuron apoptosis. The present invention further relates to apoptosis modulation in other tissues in which prion protein is expressed, such as heart and lung. The invention further comprises a method of modulating apoptosis in a cell comprising an administration of an apoptosis-modulating effective amount of an agent which interferes with prion protein (PrP)-bax interaction.

Abstract: The present invention relates to the identification of a caspase inhibitory factor (CIF) and to the establishment of a screening procedure to find caspase inhibitors in human neurons. More particularly, the invention relates to a 17-&bgr;-estradiol inducible caspase-6 inhibitory factor.