Abstract: Provided is a compound of formula I, or pharmaceutically acceptable salt or solvate thereof, as defined herein for use in the treatment or prevention of a Dirofilaria infection in a mammal, The compounds are also for use in the treatment or prevention of diseases or conditions caused by a Dirofilaria infection in a mammal. Also described are corresponding methods of treating or preventing a Dirofilaria infection in a mammal.

Abstract: A bucket is adapted to be spaced relatively close to adjacent buckets and has sides with a contoured upper edge to facilitate carrying material above the water level capacity of the bucket.

Abstract: A bucket is adapted to be spaced relatively close to adjacent buckets and has sides with a contoured upper edge to facilitate carrying material above the water level capacity of the bucket.

Abstract: A process for the synthesis of linear ?,?-diolefins from an allylic substrate comprises the steps of a) forming the bis-Grignard reagent XMgCH2(CH2)nCH2MgX from an ?,?-acyclic dihalide with X being a halogen; b) preparing a solution comprising an allylic substrate and a copper catalyst; c) catalyzing a coupling reaction by adding to the solution of step (b) the bis-Grignard reagent of step (a); and d) isolating and purifying the ?,?-olefin coupling reaction product.

Abstract: A process for the synthesis of linear ?,?-diolefins from an allylic substrate comprises the steps of a) forming the bis-Grignard reagent XMgCH2(CH2)nCH2MgX from an ?,?-acyclic dihalide with X being a halogen; b) preparing a solution comprising an allylic substrate and a copper catalyst; c) catalyzing a coupling reaction by adding to the solution of step (b) the bis-Grignard reagent of step (a); and d) isolating and purifying the ?,?-olefin coupling reaction product.

Abstract: The invention relates to methods for identifying the sequence of one or more variant nucleotides in a nucleic acid molecule. The method involves cleaving a double-stranded nucleic acid molecule containing a mismatch with a mismatch-specific endonuclease which cleaves on the 3? side of the mismatch, and preserving the integrity of the variant nucleotide by ligating a double-stranded linker with a 3?-overhang to said variant nucleotide. Because the variant nucleotide is immediately adjacent to the linker, PCR and/or sequence-by-synthesis analysis can be readily carried out.

Abstract: The invention relates to methods for identifying the sequence of one or more variant nucleotides in nucleic acid molecules. The method involves cleaving a double-stranded nucleic acid molecule containing a mismatch with a mismatch-specific endonuclease which cleaves on the 3? side of the mismatch, and preserving the integrity of the variant nucleotide by ligating a Double-Stranded Linker with a degenerate 3?-overhang to said variant nucleotide. Because the variant nucleotide is immediately adjacent to the linker, PCR and/or sequence-by-synthesis analysis can be readily carried out.

Abstract: The invention relates to methods for identifying the sequence of one or more variant nucleotides in nucleic acid molecules. The method involves cleaving a double-stranded nucleic acid molecule containing a mismatch with a mismatch-specific endonuclease which cleaves on the 3? side of the mismatch, and preserving the integrity of the variant nucleotide by ligating a Double-Stranded Linker with a degenerate 3?-overhang to said variant nucleotide. Because the variant nucleotide is immediately adjacent to the linker, PCR and/or sequence-by-synthesis analysis can be readily carried out.

Abstract: The invention relates to methods for identifying the sequence of one or more variant nucleotides in a nucleic acid molecule. The method involves cleaving a double-stranded nucleic acid molecule containing a mismatch with a mismatch-specific endonuclease which cleaves on the 3? side of the mismatch, and preserving the integrity of the variant nucleotide by ligating a double-stranded linker with a 3?-overhang to said variant nucleotide. Because the variant nucleotide is immediately adjacent to the linker, PCR and/or sequence-by-synthesis analysis can be readily carried out.

Abstract: A process for making high specific viscosity copolymers of maleic anhydride and an alkyl vinyl either having as specific viscosity of at least 7, preferably 10-50, are made by copolymerizing maleic anhydride and an alkly vinyl ether monomers in the presence of added acetylene.

Abstract: In an extensive Matched Ion Polynucleotide Chromatography (MIPC) system and method, and the computer programs or software associated therewith, the system provides automated options for sample selection, mobile phase gradient selection and control, column and mobile phase temperature control, and fragment collection for a wide variety of MIPC separation processes. MIPC separation processes can be applied to effect size-based separation of DNA fragments, mutation detection, DNA fragment purification, PCR process monitoring and other novel processes. This invention is directed to the system and software which automates many of these procedures, facilitating use of the system to achieve complex separation methods. In one embodiment of the invention, a user specifies a size range of double stranded DNA fragment(s) in a mixture, the software calculates a solvent gradient to elute the fragment(s), and the system performs the chromatographic separation using the calculated gradient.

Abstract: In one aspect, the invention provides a method for separating a mixture of polynucleotides, such as DNA or RNA, including (a) applying the mixture to a polymeric separation medium having non-polar surfaces, wherein the surfaces are characterized by being substantially free from multivalent cations, such as metal ions, which are free to interfere with polynucleotide separation, and (b) eluting the mixture with a mobile phase containing organic solvent and counter ion agent. In the separation of single-stranded polynucleotides, improved separation is obtained at a temperature effective to fully denature secondary structure within the polynucleotides.

Abstract: Methods, compositions, and kits for separating heteroduplex and homoduplex DNA molecules in a test mixture by temperature-compression denaturing high performance liquid chromatography (tcDHPLC). The method includes use of nitrogen-containing additives in the mobile phase that allow detection of diverse heteroduplex molecules to be performed at the same pre-selected temperature. An example of a preferred additive is betaine. Standard mixtures of DNA fragments, such as mutation standards containing known heteroduplex and homoduplex molecules, can be used to select the concentration of additive and temperature. Compositions and kits including the mobile phase, mutation standards, PCR primers, separation media, and DNA polymerase are also provided.

Abstract: The present invention describes a method for separating or partially separating heteroduplex and homoduplex DNA molecules in a mixture. In the method, the mixture is applied to an anion-exchange chromatography medium. The heteroduplex and homoduplex molecules are eluted with a mobile phase containing an eluting salt, including an anion and a cation, a buffer, and preferably including an organic solvent. The eluting is carried out under conditions effective to at least partially denature the heteroduplexes (e.g., thermal or chemical denaturing) resulting in the separation of the heteroduplexes from the homoduplexes. The method has many applications including, but not limited to, detecting mutations and comparative DNA sequencing.

Abstract: Covalently bound non-polar tags are used to increase the retention times of double stranded polynucleotides on Matched Ion Polynucleotide Chromatography (MIPC) columns. In doing so, separations of DNA mixture components is improved. Additionally, when the non-polar tags are fluorophores, detection limits are also greatly reduced. Strategically tagged primers are used in conduction with PCR to produce DNA fragments having specifically tagged strands. This improves mutation detection by MIPC in several ways. Separations are improved, detection sensitivity is enhanced, and non-stoichiometric addition of wild type DNA prior to hybridization is now possible since only tagged fragments will be observed with a fluorescence detector. Non-polar tags are also used as a novel alternative to G-C clamping during MIPC under partially denaturing conditions. Reversible DNA binding dyes, such as DNA intercalator dyes and DNA groove binding dyes, are used to reduce the detection limit of polynucleotides separated by MIPC.

Abstract: The present invention is directed to improved methods for detection of mutations in DNA using Denaturing Matched Ion Polynucleotide Chromatography (DMIPC). The invention includes the following aspects: analysis of PCR amplification products to identify factors that affect PCR replication fidelity; design of PCR primers; selection of an optimal temperature for performing DMIPC; selection of the mobile phase composition for gradient elution; methods for column preparation and maintenance; and methods for preparing polynucleotide samples prior to chromatographic analysis.

Abstract: Methods, compositions, and kits for separating heteroduplex and homoduplex DNA molecules in a test mixture by temperature-compression denaturing high performance liquid chromatography (tcDHPLC). The method includes use of nitrogen-containing additives in the mobile phase that allow detection of diverse heteroduplex molecules to be performed at the same pre-selected temperature. An example of a preferred additive is betaine. Standard mixtures of DNA fragments, such as mutation standards containing known heteroduplex and homoduplex molecules, can be used to select the concentration of additive and temperature. Compositions and kits including the mobile phase, mutation standards, PCR primers, separation media, and DNA polymerase are also provided.

Abstract: A batch process for obtaining polynucleotide fragments, such as dsDNA, having a selected size from a mixture of polynucleotide fragments including the steps of a) applying a solution of the mixture of polynucleotide fragments and a counterion agent to a binding medium having a hydrophobic surface; b) contacting the binding medium with a first stripping solvent and counterion agent, the first stripping solvent having a concentration of organic component sufficient to release from the binding medium all polynucleotide fragments having a size smaller than the selected size, and removing the first stripping solvent from the binding medium; and c) contacting the binding medium with a second stripping solvent having a concentration of organic component sufficient to release from the binding medium the polynucleotide fragments having the selected size, and removing the second stripping solvent from the binding medium. The binding medium can be organic polymer or inorganic particle beads.

Abstract: In one aspect, a method for DNA mutation detection including the steps of PCR amplification using preferably Pho DNA polymerase, hybridization, and analysis by denaturing high performance liquid chromatography (DHPLC), the method preferably utilizing a PCR buffer and other solutions that are compatible with DHPLC analysis. In other aspects, compositions and kits including a proofreading DNA polymerase, preferably Pho DNA polymerase, and a DHPLC compatible PCR buffer are provided.