Abstract: An insert for an EPR probehead is disclosed. The insert comprises a directional coupler and an amplifier. The directional coupler receives microwave power from a source at a first port and transfers a portion of the received microwave power to a second port for transmission to a sample space. The directional coupler is also arranged to receive a microwave signal from the sample space at the second port and to pass the majority of the received microwave signal to a third port. The amplifier has an input and an output; the input is arranged to receive the microwave signal from the third port of the directional coupler and to produce an amplified version of the received microwave signal at the output for transmission to a detector.

Abstract: The present invention generally relates to the field of dietary therapies for treating disorders associated with mitochondrial dysfunction, including epilepsy.

Abstract: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocyte biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

Abstract: The present invention is directed to a nanoparticle or microparticle for binding to the surface of a cell, wherein the nanoparticle or microparticle comprises (i) multiple different ligand types on its external surface which are capable of binding to different respective receptor types on said cell surface, and (ii) a polymer brush on its external surface. The present invention is further directed to pharmaceutical compositions comprising a plurality of nanoparticles or microparticles of the invention, medical uses of such nanoparticles or microparticles, and a vaccine comprising such nanoparticles or microparticles.

Abstract: The invention relates to cartridges for thin layer chromatography (TLC) which hermetically seal the TLC mobile phase during loading, performance of the TLC process, and analysis of the chromatogram. It further relates to associated methods of use—for example for detecting or quantifying an analyte in a sample. It further relates to processes for assembling the cartridge, to associated equipment adapted for use with them, and kits of parts.

Abstract: The present invention relates to analgesic treatments to reduce pain through use of an inhibitor of fatty-acid amide hydrolase pseudogene (FAAH-OUT).

Abstract: The invention provides improved adeno-associated virus (AAV) Factor VIII (FVIII) vectors, including AAV FVIII vectors that produce a functional Factor VIII polypeptide and AAV FVIII vectors with high expression activity.

Abstract: The present invention relates to an engineered regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a myelin basic protein (MBP) peptide or variant or fragment thereof when the peptide is presented by a major histocompatibility complex (MHC) molecule. The present invention further relates to methods for providing an engineered Treg and to methods and uses of said engineered Treg and vectors and kits of vectors encoding said Treg.

Abstract: The invention relates to protein-based T-cell receptor knockdown, and its use in T-cell therapies.

Abstract: The present invention relates to polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising a CD21-binding domain, a transmembrane domain and an intracellular domain.

Abstract: There is described a compound for use in the treatment of a mitochondrial DNA disorder, wherein the compound is a glycolysis inhibitor, an inhibitor of glutamine consumption or is L-asparaginase or pegaspargase. The glycolysis inhibitor may be a glucose analogue such as 2-deoxy-D-glucose (2DG) or 5-thioglucose (5TG). Also described is a method of treating a mitochondrial DNA disorder comprising administering a therapeutically effective amount of the compound above to a patient suffering from a mitochondrial DNA disorder. In addition, there is described a method of reducing the mtDNA heteroplasmy in the cells of a patient comprising administering a therapeutically effective amount of the compound above to the patient.

Abstract: The invention relates to a method for determining the level and type of mutation events associated with the use of a targeted genetic modification, such as in the use of designer nucleases, to modify a target site of nucleic acid in a cell or virus population. The method comprises carrying out a mutation event determination on a targeted nucleic acid in a population of modified nucleic acids that have been treated with the targeted genetic modification, and a reference control analysis on a non-targeted nucleic acid. The invention further relates to the use of the method for screening of potential targeted genetic modification agents for therapeutic use and to estimate the genomic integrity and stability of a nucleic acid such as a viral vector or genomic DNA.

Abstract: There is described a vector for treating a ciliopathy such as Bardet-Biedl syndrome, wherein the vector comprises a promoter operably linked to a ciliopathy gene, wherein the vector can provide transduction of the ciliopathy gene into multiple organs, wherein the promoter is a ubiquitous promoter which can provide expression of the ciliopathy gene in the transduced organs, and wherein the ciliopathy gene encodes a functional protein corresponding to the protein that is mutated in the ciliopathy. Also described is the use of the above vector in a method of treating a ciliopathy, the method comprising administering a therapeutically effective amount of the vector to a patient suffering from a ciliopathy.

Abstract: Systems and methods are described for rendering garments. The system includes a first machine learning model trained to generate coarse garment templates of a garment and a second machine learning model trained to render garment images. The first machine learning model generates a coarse garment template based on position data. The system produces a neural texture for the garment, the neural texture comprising a multi-dimensional feature map characterizing detail of the garment. The system provides the coarse garment template and the neural texture to the second machine learning model trained to render garment images. The second machine learning model generates a rendered garment image of the garment based on the coarse garment template of the garment and the neural texture.

Abstract: A computer-implemented method of enhancing object detection in a digital image of known underlying structure using pre-processed images with underlying structure and with any objects detected and bounding boxes inserted over the objects, the method comprising: extracting or generating images with the underlying structure but without objects detected as negative images; extracting images with the underlying structure and with an object detected as positive images; inputting pairs of negative and positive images through a feature extraction section in a neural network to extract feature vectors of the images; contrasting feature vectors of each pair of positive and negative images and thereby provide a contrast vector and gating the result to form an attention vector; processing the attention vector and the feature vector of the positive image to produce an output.

Abstract: Antisense oligonucleotides (ASOs) are provided which are capable of modulating splicing by preventing inclusion of an UNC13A cryptic exon into an UNC13A mature mRNA. Such ASOs may be used as a medicament, for example, to treat neurodegenerative disorders, particularly those associated with TDP-43 pathology.

Abstract: The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as modulators of alpha 1 antitrypsin and treating diseases associated with alpha 1 antitrypsin, particularly liver diseases.

Abstract: A computer-implemented method of active learning for computer vision in digital images, comprising: inputting labelled image training examples into an artificial neural network in a training phase; training a computer vision model using the labelled training examples; carrying out a prediction task on each image of an unlabelled training set of unlabelled, unseen images using the model; calculating an uncertainty metric for the predictions in each image of the unlabelled training set; calculating a similarity metric for the unlabelled training set representing similarities between the images in the training set; selecting images from the unlabelled training set, in dependence upon both the similarity metric and the uncertainty metric of each image, to design a training set for labelling which tends to both lower the similarity between the selected images and increase the uncertainty of the selected images.

Abstract: Provided herein is a composition comprising (i) a nucleic acid sequence encoding a CasRx/Cas13d polypeptide; and (ii) a guide RNA that binds specifically to a target sequence in C9orf72 RNA. Also provided are associated pharmaceutical compositions, guide RNAs, complexes, vectors and cells, and uses of the compositions to neurodegenerative disorders.