Abstract: Methods of enhancing efficiency of downstream chromatography steps for purification of proteins comprising: (a) passing a composition comprising a polypeptide of interest and various contaminants through an ion exchange membrane, wherein the polypeptide and the membrane have opposite charge, at operating conditions comprised of a buffer having a pH sufficiently distinct from the pi of the polypeptide to enhance the charge of the polypeptide and a low ionic strength effective to prevent the shielding of charges by buffer ions, which cause the membrane to bind the polypeptide and at least one contaminant, (b) overloading the ion exchange membrane such that at least one contaminant remains bound to the membrane while the polypeptide of interest is primarily in the effluent; (c) collecting the effluent from the ion exchange membrane comprising the polypeptide of interest; (d) subjecting the membrane effluent comprising the polypeptide of interest to a purification step of similar charge as the previous membrane,

Abstract: Timing-based methods, systems, and computer readable mediums for a gated linear accelerator include synchronising a local clock of the linear accelerator with a clock of a patient monitoring system, determining latencies within one or more MR-gated radiotherapy processes and implementing latency based interlocks.

Abstract: Provided herein is a method of characterising a target polynucleotide as it moves with respect to a nanopore using a motor protein. Also provided are polynucleotide adapters and kits comprising such adapters. The methods, kits and adapters find use in characterising polynucleotides, for example in sequencing.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R3, R4a, R4b, R4c, R4d, R4f, X1, X2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating or preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R2a, R3, R4, R4a, R4b, R4c, R4d, R4e, R4f, R5, R6 have the meaning as indicated in the description and claims The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating or preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: A network element includes at least two Time Division Multiplexing (TDM) modules each including a TDM client interface, TDM processing circuitry, and circuit emulation circuitry; and a packet switch fabric connected to the at least two TDM modules in a Link Aggregation Group (LAG) for a protected TDM service, and configured to output a packet interface, wherein the protected TDM service is provided as a single packetized TDM stream via the packet interface from the packet switch fabric.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R2a, R3, Ra1, Ra2, Ra3, Ra4, Ra5, Ra6, A1 and A2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating and preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R2a, R3, Ra1, Ra2, Ra4, Ra5, X1, X1a, A1 and A2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating and preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: Provided herein are certain isoindolinone compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.

Abstract: A peptide that binds to elongation initiation factor 4E (eIF4E) comprising the amino acid sequence CEX1GX2X3X4X5C (SEQ ID NO: 1), where X1 is an amino acid selected from the group consisting of threonine (T), methionine (M) or leucine (L), X2 and X3 is an amino acid selected from the group consisting of phenylalanine (F), modified phenylalanine and tyrosine (Y), X4 and X5 is any amino acid, wherein the two cysteine residues are joined by a disulphide bond. Further, pharmaceutical compositions and uses of the peptide, and pharmaceutical compositions are provided.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R2a, R3, Ra2, Ra4, Ra5, Ra6, Ra7, X1, X1a, A1 and A2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating and preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1 to R3, A1 and A2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating and preventing one or more diseases or disorders associated with integrated stress response.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

Abstract: The present invention relates to non-membrane disruptive and p53 activating stapled peptides, as well as methods of treatment of cancer involving the use of these peptides. In one embodiment, the peptide comprises or consist of the amino acid sequence of TSFXaa1EY-WXaa3LLXaa2, where Xaa1 is (R)-2-(7?-octenyl)alanine or derivative thereof, or is (R)-2-(4?-pentenyl)alanine or derivative thereof; and Xaa2 and Xaa3 are independently any type of amino acid or modified amino acid. In another embodiment, the peptide comprising or consisting of the amino acid sequence of TSFXaa1EYW Xaa3LLXaa2ENXaa5, wherein Xaa1 and Xaa3 are any type of amino acid or modified amino acid; Xaa2 is S, or P, or (S)-2-(4?-pentenyl)alanine or a derivative of (S)-2-(4?-pentenyl)alanine; and wherein Xaa5 is F or Y.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

Abstract: A network element includes at least two Time Division Multiplexing (TDM) modules each including a TDM client interface, TDM processing circuitry, and circuit emulation circuitry; and a packet switch fabric connected to the at least two TDM modules in a Link Aggregation Group (LAG) for a protected TDM service, and configured to output a packet interface, wherein the protected TDM service is provided as a single packetized TDM stream via the packet interface from the packet switch fabric.

Abstract: Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.