Abstract: An apparatus for controlling a discharge pressure of a fluid includes: a pump configured to suck the fluid through an inlet or to discharge the sucked fluid through an outlet; a distributor connected to the pump and to an injection nozzle provided by a sensor and configured to distribute the fluid discharged from the pump to the sensor; and a controller. The controller is configured to control the pump to operate selectively in accordance with detection of contamination of the sensor and to control operation of the distributor to be forcibly delayed during operation of the pump such that the fluid distributed to the sensor, when detected as being contaminated, is controlled to reach a selected required discharge pressure of different required discharge pressures selected in accordance with water amount information and a degree of contamination of the sensor.

Abstract: Gapmers or pharmaceutically acceptable salt of the gapmers and methods of making the gapmers are provided. The gapmers include a gap region that contains deoxyribonucleosides linked to each other by phosphorothioate bonds, a 5? wing region positioned at the 5? end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds, and a 3? wing region positioned at the 3? end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds. Antisense oligonucleotides are also provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription.

Abstract: The invention provides methods utilizing Prins reaction in the preparation of compounds that may be useful as intermediates in the synthesis of halichondrin macrolides and analogs thereof. The invention also provides compounds that may be useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Abstract: The invention provides methods utilizing Prins reaction in the preparation of compounds that may be useful as intermediates in the synthesis of halichondrin macrolides and analogs thereof. The invention also provides compounds that may be useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Abstract: We provide compounds given by Formula I, which is shown in FIG. 3, or pharmaceutically acceptable salts thereof, as well as formulations thereof and methods of use of those compounds and formulations for treatment of cancer.

Abstract: Antisense oligonucleotides are provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription. Inhibition of Tau mRNA transcription may result in decrease of amounts of Tau protein in a subject, allowing treatment of diseases and disorders related to expression of Tau, including Alzheimer's disease and primary tauopathies.

Abstract: Provided herein are compounds useful for the treatment of cancer.

Abstract: We provide compounds given by Formula I, which is shown in FIG. 3, or pharmaceutically acceptable salts thereof, as well as formulations thereof and methods of use of those compounds and formulations for treatment of cancer.

Abstract: The invention provides methods for the synthesis of a halichondrin macrolides or analogs thereof through a cyclization reaction strategy. The strategy of the present invention involves subjecting an intermediate to Prins reaction conditions to afford a macrolide. The invention also provides compounds useful as intermediates in the synthesis of a halichondrin macrolides or analogs thereof and methods for preparing the same.

Abstract: Provided herein are methods for the treatment of bladder cancer.

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Abstract: We provide diastereomerically pure or substantially diastereomerically pure activated phosphoramidochloridate morpholino nucleosides, methods of their preparation, and methods of their use in stereospecific coupling for stereospecific synthesis of diastereomerically pure phosphorodiamidate morpholino oligomers (PMOs).

Abstract: The present invention relates to methods and intermediates for synthesizing 2?-deoxy-2?,2?-difluorotetrahydrouridine compounds.

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Abstract: The invention provides methods for the synthesis of a halichondrin macrolides or analogs thereof through a cyclization reaction strategy. The strategy of the present invention involves subjecting an intermediate to Prins reaction conditions to afford a macrolide. The invention also provides compounds useful as intermediates in the synthesis of a halichondrin macrolides or analogs thereof and methods for preparing the same.

Abstract: We provide compounds given by Formula I, which is shown in FIG. 3, or pharmaceutically acceptable salts thereof, as well as formulations thereof and methods of use of those compounds and formulations for treatment of cancer.

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.