Abstract: The disclosure provides for optimized therapeutic MECP2 polynucleotide constructs utilized for replacing or compensating for the loss of MeCP2 function in patients with Rett Syndrome. Suitably, the disclosure provides gene therapy cassettes to enable better regulatory control of the MeCP2 protein, including tunable systems that allow MECP2 gene therapy to be expressed at a desired moderate level and demonstrate expression of the vector-derived transgene within a window that alleviates the disease-causing genetic deficiency without producing undesired side effects including overexpression toxicity.

Abstract: The present invention relates to a wellbore reactor comprising a reaction chamber surrounded by a jacket, said reaction chamber comprises at least one carbon dioxide-inlet (CO2-inlet), and/or at least one hydrocarbon-inlet, and at least one hydrogen-outlet (H2-outlet).

Abstract: A connector assembly that includes an electrical connector having a connector conductor, a connector housing, a PCB substrate bonded to a base, positioning pads extending away from the PCB substrate, and metallic bumps extending away from the PCB substrate. The connector housing has a housing conductor that is electrically connected to the connector conductor. The PCB substrate is brittle, and the housing conductor contacts an electrical signal path on the PCB substrate at an oblique angle. The positioning pads keep the mounting face of the connector housing away from the PCB substrate at a standoff distance. The metallic bumps are malleable and configured to provide an electrical connection between the PCB substrate and the mounting face of the connector housing.

Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention relates to a compound of the Formula: and pharmaceutically salts thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: Ingestible devices can directly deliver therapeutic agents to desired tissue(s) of the GI tract of a subject, such as the submucosa, the mucosa, and/or the mucus layer of the GI tract, and methods of using the same. The ingestible devices can deliver therapeutic agents in a safe, effective, and reliable manner. The disclosure also provides pharmaceutical compositions for use in methods of treating a disease or condition in a subject in need thereof.

Abstract: An ingestible device, includes a storage reservoir configured to store a dispensable substance and a pressurized chamber configured so that, when a restraining force is removed from the pressurized clamber, the dispensable substance exits the ingestible device via openings in the ingestible device.

Abstract: MECP2 EXPRESSION CASSETTES. The present invention provides nucleic acid molecules comprising a MeCP2 expression cassette, the expression cassette comprising, in operable linkage from 5? to 3?: a 5? transcriptional control region comprising a promoter capable of driving transcription in neural cells; an open reading frame encoding a MeCP2 protein; translation control signals; a 3? untranslated region (3?UTR) comprising one or more of: (i) a binding site for mir-22; (ii) a binding site for mir-19; (iii) a binding site for miR-132; (iv) a binding site for miR124; and (v) an AU-rich element; and transcriptional termination signals; wherein the MeCP2 expression cassette is not more than about 5 kb in length. The invention further provides viral vectors, especially vectors derived from adeno-associated virus (AAV), for use in therapeutic delivery of such expression cassettes.

Abstract: The present invention provides nucleic acid molecules comprising a MeCP2 expression cassette, the expression cassette comprising, in operable linkage from 5? to 3?: a 5? transcriptional control region comprising a promoter capable of driving transcription in neural cells; an open reading frame encoding a MeCP2 protein; translation control signals; a 3? untranslated region (3?UTR) comprising one or more of: (i) a binding site for mir-22; (ii) a binding site for mir-19; (iii) a binding site for miR-132; (iv) a binding site for miR124; and (v) an AU-rich element; and transcriptional termination signals; wherein the MeCP2 expression cassette is not more than about 5 kb in length. The invention further provides viral vectors, especially vectors derived from adeno-associated virus (AAV), for use in therapeutic delivery of such expression cassettes.

Abstract: Ingestible devices can directly deliver therapeutic agents to desired tissue(s) of the GI tract of a subject, such as the submucosa, the mucosa, and/or the mucus layer of the GI tract, and methods of using the same. The ingestible devices can deliver therapeutic agents in a safe, effective, and reliable manner. The disclosure also provides pharmaceutical compositions for use in methods of treating a disease or condition in a subject in need thereof.

Abstract: Processing circuitry (16) and an instruction decoder (9) supports a load chunk instruction and a store chunk instruction which can be useful for implementing memory copy functions and other library functions for manipulating or comparing blocks of memory. Number of bytes to load or store in response to these instructions is determined based on an implementation specific condition. As well as loading or storing bytes of data, the load chunk instruction and (10) store chunk instruction also designated a load/store length value as data corresponding to an architecturally visible register, which provides an indication of a number of bytes loaded or stored.

Abstract: A dry powder inhaler includes an inhalation channel connected to a mouthpiece, a container for storing a powdered medicament, a de-agglomerator with a vortex chamber located at an end of the inhalation channel, a metering device including a shuttle having a dosing recess. The shuttle is movable between a filling position, in which the dosing recess is in alignment with an opening of the container, and an inhalation position, in which the dosing recess is in alignment with the vortex chamber. The opening of the container is elongated along a major axis and the dosing recess is elongated along a main axis and, when the shuttle is in the filling position, an edge of the opening of the container encloses the dosing recess.

Abstract: An in-wheel electrical generator for a vehicle is disclosed. The in-wheel generator comprises: a stator configured to be coupled to a non-rotating spindle of a vehicle; and a rotor configured to be indirectly coupled to a rotating hub of a vehicle. The in-wheel electrical generator is configured to be arranged outwardly of the rotating hub. A vehicle comprising such an in-wheel generator is also disclosed, along with an ancillary unit system for a trailer which uses such an in-wheel generator to power the ancillary unit.

Abstract: An ischemic stroke mimic is detected, or otherwise predicted, based on medical images acquired from a subject. Medical image data, which include medical images acquired from a head of the subject, are accessed with a computer system. A machine learning model (e.g., one or more deep convolutional neural networks) is trained on training data to estimate a probability of an acute intracranial abnormality being depicted in a medical image. Intracranial abnormality prediction data are generated by inputting the medical image data to the machine learning model. The intracranial abnormality prediction data include an intracranial abnormality probability score for each of the medical images in the medical image data. An ischemic stroke mimic classification for the medical image data is generated based on the intracranial abnormality prediction data, and may be displayed to a user with the computer system.

Abstract: A system to limit the expression of a vector-derived transgene within a window that alleviates the disease-causing genetic deficiency without producing overexpression toxicity is described. This provides for ‘dosage-insensitivity’, whereby cells or tissues receiving more vector-derived transgene are disproportionately suppressed through an in-built single gene circuit that can regulate adaptively.