Abstract: The present invention relates to compounds of formula (I) that function as inhibitors of METTL3 (N6-adenosine-methyltransferase 70 kDa subunit) enzyme activity: W—X—Y—Z (I) wherein X, Y and Z are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, and autoimmune diseases, as well as other diseases or conditions in which METTL3 activity is implicated.

Abstract: A non-combustible aerosol provision device for generating an aerosol from an aerosol-generating material is provided. The device includes a chamber for receiving a consumable including aerosol-generating material to enable the non-combustible aerosol provision device to generate an aerosol from the aerosol-generating material. The device further includes an adjustment mechanism to allow a user to adjust a dimension of the chamber to allow the chamber to accommodate, one at a time, each of a plurality of consumables having different sizes.

Abstract: A non-combustible aerosol provision device for generating an aerosol from aerosol-generating material included in a consumable, the non-combustible aerosol provision device having: a receptacle for receiving the consumable; and an adaptor configured to adapt the non-combustible aerosol provision device by varying an effective length of the receptacle such that each of a plurality consumables of different lengths, which are individually receivable in the receptacle, when received in the receptacle for use, protrude from the non-combustible aerosol provision device by substantially equal amounts.

Abstract: A non-combustible aerosol provision device for generating an aerosol from aerosol-generating material in a consumable is disclosed. The non-combustible aerosol provision device includes a retention apparatus configured to hold in position, one at a time, each of the plurality of consumables comprising aerosol-generating material of different sizes.

Abstract: The present invention relates to preparation, sequencing and analysis of a sequencing library of adaptor-tagged fragments, wherein the fragments have different orientations relative to a sequencing adaptor.

Abstract: The present application relates to an aerosol provision device. The device has a chamber configured to receive a consumable including aerosol-generating material, a body including a portion of the chamber, a mouthpiece through which aerosol generated from the aerosol-generating material is drawn by a user of the device, and a barrier discrete from the mouthpiece and movably coupled to the body. When the device is in a closed state, the barrier inhibits ingress of the consumable into the portion of the chamber and egress of the consumable from the portion of the chamber, and, when the device is in an open state, the barrier allows ingress of the consumable into the portion of the chamber and egress of the consumable from the portion of the chamber.

Abstract: The present application describes an aerosol provision device. The device has a chamber configured to receive a consumable including an aerosol-generating material, a body, and a mouthpiece through which aerosol generated is drawn by a user when the mouthpiece is arranged in an open position. The device is configured so that movement of the consumable towards or into the chamber causes the mouthpiece to move relative to the body from a closed position to the open position.

Abstract: An aerosol provision device is disclosed comprising a chamber (110) for receiving a consumable (10) comprising aerosol-generating material, wherein, in use, part (12) of the consumable (10) protrudes from the chamber (110). The device further comprises an aerosol generator (120) for generating an inhalable medium from the consumable 10 received in the chamber (110) and a controller (130) for controlling the supply of power from a power source (140) to the aerosol generator (120). A movable component (150) is provided for at least partially covering the part (12) of the consumable (10) that protrudes from the chamber (110) in use, wherein the movable component 150 is movable between a first position, in which the part (12) of the consumable (10) is exposed, and a second position, in which the part (12) of the consumable (10) is at least partially covered.

Abstract: A consumable configured to be fully inserted into an aerosol provision device. The consumable includes an aerosol generating material for use in generating aerosol by an aerosol provision device; an insertion portion configured for insertion into an aerosol generation zone a the aerosol provision device; and a removal facilitator that extends away from or is located on a surface of the insertion portion and is configured to enhance gripping by a user of the consumable to assist in the removal of the insertion portion from the aerosol generation zone. Also provided is an aerosol provision device for use with such a consumable, and a method of removing such a consumable from an aerosol provision device.

Abstract: An aerosol provision device has an aerosol generator for generating aerosol from aerosol-generating material, a first coupling mechanism, a first part and a second part moveably restrained with respect to each other by the first coupling mechanism, and an accommodation zone, formed by the first part and the second part, for accommodating an article including, or for holding, the aerosol-generating material. The first part and the second part occupy a first volume when the device is in an unaccommodated state, and when the accommodation zone accommodates the article in an accommodated state of the aerosol provision device, the first part and the second part of the aerosol provision device together with the article occupy a second volume that is greater than the first volume.

Abstract: A vitrector that includes an adjustable illumination aperture is described. The vitrector may include a probe and a light sleeve assembly extending along and substantially surrounding the probe. The light sleeve assembly may include a plurality of optical fibers. At least a portion of the optical fibers are operable to provide illumination so as to define an illumination aperture about the vitrectomy probe. A portion of the optical fibers may be encapsulated. The light sleeve assembly may be adjustable along a length of the probe, providing adjustment of the illumination aperture to increase or decrease an area of illumination provided thereby.

Abstract: Described herein is an adapter comprising a population of first oligonucleotides, a second oligonucleotide and a third oligonucleotide, wherein the first oligonucleotides, the second oligonucleotide and the third oligonucleotide are hybridized together to produce a complex that comprises: (i) a first end comprising a transposase recognition sequence, (ii) a central single-stranded region of variable sequence and (iii) a second end comprising sequences that are non-complementary. A method, as well as a kit for practicing the method, are also provided.

Abstract: A method of enriching for a fragment of a genome, as well as corresponding compositions and kits, are provided. In certain embodiments, the method comprises: (a) contacting a sample comprising fragmented DNA with a Cas9-gRNA complex comprising mutant Cas9 protein that has inactivated nuclease activity and a Cas9-associated guide RNA that is complementary to a site in the DNA, to produce a Cas9-fragment complex that comprises a fragment of the fragmented DNA; and (b) isolating the complex. In addition, other methods and compositions for Cas9/CRISPR-mediated nucleic acid manipulation are also provided.

Abstract: The present disclosure is generally directed to detecting nucleic acids. In particular, disclosed herein are methods and compositions for determining the sequence (or identity) and location of RNA and other molecules in situ. The present invention is generally related to a method for detecting nucleic acids, the method including providing a tissue sample; providing an array comprising a plurality of oligonucleotide probes attached to a surface of the array, in which each oligonucleotide probe, of the plurality of oligonucleotide probes, includes a location barcode sequence, a primer binding sequence, and a priming sequence; releasing the plurality of oligonucleotide probes from the array surface; contacting the tissue sample with the released oligonucleotide probes; and allowing the released oligonucleotide probes to diffuse into the tissue sample.

Abstract: Systems and methods for a real time embedded trace are provided. In certain embodiments, a system for acquiring data that uses a real time embedded trace includes a first computing system. The first computing system includes a memory unit; and a processing unit executing software, wherein the software comprises at least one real time trace instruction. Further, the at least one real time trace instruction directs the processing unit to directly store data onto the memory unit; and wherein the stored data is translated for a user after it is stored onto the memory unit.

Abstract: A method for making an asymmetrically-tagged sequencing library is provided. In some embodiments, the method may comprise: obtaining a symmetrically-tagged library of cDNA or genomic DNA fragments, hybridizing a tailed first primer to the 3? sequence tag of the library and extending the same to produce primer extension products, and amplifying the primer extension products using a pair of tailed primers to produce asymmetrically-tagged library.

Abstract: In some embodiments, the amplification method may comprise producing a reaction mix comprising: a nucleic acid sample, a polymerase, nucleotides, a forward primer that hybridizes to a sequence in the bottom strand of a fragment in the sample, and a reverse primer. The reverse primer has a hairpin structure comprising a loop, a stem and a 3? overhang of at least 8 nucleotides, wherein the 3? overhang hybridizes to a sequence in the top strand of the fragment. Subjecting the reaction mix at least two rounds of denaturation, renaturation and primer extension conditions results in extension the forward and reverse primers to produce an amplification product that contains: a double stranded region comprising a nick adjacent to the 5? end of the reverse primer, and the loop of the first hairpin primer. Primer sets and kits for performing the methods are also provided.

Abstract: A method for fragmenting a genome is provided. In certain embodiments, the method comprises: (a) combining a genomic sample containing genomic DNA with a plurality of Cas9-gRNA complexes, wherein the Cas9-gRNA complexes comprise a Cas9 protein and a set of at least 10 Cas9-associated guide RNAs that are complementary to different, pre-defined, sites in a genome, to produce a reaction mixture; and (b) incubating the reaction mixture to produce at least 5 fragments of the genomic DNA. Also provided is a composition comprising at least 100 Cas9-associated guide RNAs that are each complementary to a different, pre-defined, site in a genome. Kits for performing the method are also provided. In addition, other methods, compositions and kits for manipulating nucleic acids are also provided.

Abstract: A method for sequencing a nucleic acid is provided. In certain embodiments the method comprises obtaining a duplex comprising a nucleic acid and a primer, wherein the primer has a nuclease resistant 3? end, combining the duplex with a chain terminator nucleotide and a proof-reading polymerase to produce a reaction in which the polymerase idles on the added chain terminator nucleotide, identifying the chain terminator nucleotide added to the end of the primer; and adding a nuclease-resistant nucleotide to the end of the primer after the polymerase has idled on and removed the added chain terminator nucleotide, thereby producing a duplex comprising the template and an extended primer that has a nuclease resistant 3? end.

Abstract: A method for fragmenting a genome is provided. In certain embodiments, the method comprises: (a) combining a genomic sample containing genomic DNA with a plurality of Cas9-gRNA complexes, wherein the Cas9-gRNA complexes comprise a Cas9 protein and a set of at least 10 Cas9-associated guide RNAs that are complementary to different, pre-defined, sites in a genome, to produce a reaction mixture; and (b) incubating the reaction mixture to produce at least 5 fragments of the genomic DNA. Also provided is a composition comprising at least 100 Cas9-associated guide RNAs that are each complementary to a different, pre-defined, site in a genome. Kits for performing the method are also provided. In addition, other methods, compositions and kits for manipulating nucleic acids are also provided.