Abstract: Small cell lung cancer (SCLC) exhibits distinct molecular subtypes characterized by activation of transcription factors (TFs) such as ASCL1, NEUROD1, POU2F3, and REST, but clinical translation has been limited by tissue scarcity. Here, a cell-free DNA (cfDNA) targeted sequencing assay is disclosed that analyzes DNA fragmentation patterns to infer nucleosome profiles at TF binding sites and gene transcription start sites (TSSs) and also detects exonic mutations in certain genes. Application to plasma cfDNA from SCLC patient-derived xenograft models faithfully captured signatures of TF activity and gene expression and revealed a subset of highly informative nucleosome profiling loci including TSSs of key genes including ATOH1, POU2AF2, and targets of SCLC subtype defining TFs. Prediction models of ASCL1, NEUROD1, and REST activity achieved AUCs (0.82-1.00) in SCLC patient samples while a predictor of SCLC vs NSCLC histology achieved an AUC of 0.99.

Abstract: The invention relates to a novel process for preparing ?-carboxamide pyrrolidine derivatives, in particular (2S, 5R)-5-(4-((2-fluorobenzyl)oxy)phenyl)pyrrolidine-2-carboxamide, and to novel intermediates for use in said process along with processes for preparing said intermediates.

Abstract: The invention relates to a novel process for preparing ?-carboxamide pyrrolidine derivatives, in particular (2S, 5R)-5-(4-((2-fluorobenzyl)oxy)phenyl)pyrrolidine-2-carboxamide, and to novel intermediates for use in said process along with processes for preparing said intermediates.

Abstract: Compounds of formula (I) and pharmaceutically acceptable salts thereof: wherein; each of R1 to R4 is independently selected from hydrogen and C1-4 alkyl and each of rings A and B independently is optionally further substituted by up to three substituents, each of which is independently selected from the group consisting of halogen, hydroxy, C1-4alkoxy, C1-4alkyl, C1-5alkanoyl, CF3, CF3O and cyano; with the proviso that ring A must contain at least one CF3 group, are useful in the treatment of diseases and conditions mediated by modulation of use-dependent voltage-gated sodium channels.

Abstract: The present invention relates to novel hydroxyethylamine compounds having Asp2 (?-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease.

Abstract: The present invention relates to novel hydroxyethylene compounds having Asp2 (?-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease.

Abstract: An instant replay system for a bowling scoring system is disclosed in which a video clip of a bowler's approach and deliver of a bowling ball and a video clip of the bowling ball subsequently entering a pin-fall area are filmed, compressed, and stored in a memory device, such as a hard drive. The instant replay system includes a controller for receiving user requests from a user input terminal of the bowling scoring system and for responding to such user requests by selecting a stored video clip and controlling playback of the selected video clip on a display monitor of the bowling scoring system. In this manner, a user may request that the replay video clip be played in at any selected rate, that the controller freeze the display on a specific video frame, and that the controller fast-forward or rewind the video clip. Further, the user may request the replay of any previously stored video clip by specifying the bowler, game, frame and ball of which the video clip is taken.