Abstract: A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

Abstract: A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

Abstract: The invention relates to an assistive device for positioning a medical instrument (2) inserted into a natural duct (100) or an artificial duct of a patient relative to an internal organ (P) of a patient, wherein the device comprises a support (1) that is to be inserted at least in part into the body of the patient and supports the medical instrument, means for moving the support, wherein said movement means comprise an articulated arm (9) that includes a plurality of degrees of freedom for moving a proximal end (1a) of the support, means for acquiring images of the internal organ for positioning the medical instrument relative to the internal organ, wherein the image acquisition means comprise a probe (5) supported by the support such that the medical instrument and the probe are rigidly connected, and a control unit (10) for controlling the movement means, which is connected to the image acquisition means and comprises image analyzing means (11) for generating control commands for the articulated arm in orde

Abstract: A system and method for user content presentation, including: receiving, in association with a request to establish a graph relationship between a first account and a second account, a strength of relationship from the first account to the second account, the strength of relationship selected based on input from a user of the first account; selecting, by a computer processor, a delivery attribute associated with the second account based on the strength of relationship, where the delivery attribute is positively correlated with a measure of content authored by the second account to be provided to the first account; selecting content authored by the second account for inclusion in a stream of the first account based on the delivery attribute; and providing the stream of the first account for display on a client computing device.

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumours and haematological malignancies expressing HER2, in particular breast cancer, gastric cancer, bladder cancer, ovarian cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer or osteosarcoma, and acute lymphoblastic leukaemia. In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of human solid tumours with HER2 IHC 2+ or 1+ and HER2 FISH negative tissue status. Advantageously, the present invention relates to duocarmycin-containing ADCs for use in the treatment of triple negative breast cancer (TNBC).

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: A discharge device includes a plurality of material conveying components, an adjustable shear ledge, and an adjustable shroud to convey materials from a container of a material spreader out onto an open area. The adjustable shear ledge includes at least one longitudinal mounting member such that the adjustable shear ledge may be translated towards or away from the plurality of material conveying components to maintain a predetermined gap distance. The adjustable shroud may also be pivotably connected to the adjustable shear ledge such that the adjustable shroud can be pivoted towards or away from the plurality of material conveying components. The adjustable shear ledge and the adjustable shroud may be moved accordingly to maintain a preferred gap distance and to maintain concentricity with a swing of the material conveying components in order to reduce wear on components and promote spread performance of the material spreader.

Abstract: A method of installing a flooring structure is disclosed. The method includes providing an acoustic insulating layer over a sub-floor layer. The method also includes providing an underlayment layer over the acoustic insulating layer. The provided underlayment layer includes gypsum concrete having a water-resistant additive. Also disclosed is a flooring structure. The flooring structure includes an acoustic insulating layer over a sub-floor layer. The flooring structure also includes an underlayment layer having a first side and a second side opposite the first side. The underlayment layer includes gypsum concrete having a water-resistant additive. Additionally disclosed is a gypsum concrete flooring underlayment product. The product includes a mixture of alpha calcium sulfate hemihydrate and beta calcium sulfate hemihydrate. The product also includes a silane-based powder intermixed with the mixture of alpha calcium sulfate hemihydrate and beta calcium sulfate hemihydrate.

Abstract: This invention relates to novel agents that are analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: The present invention relates to a process comprising converting a compound of formula (I) into a compound of formula (II) by reaction with an organolithium reagent, which compound can be further converted into duocarmycin analogs consisting of a DNA-alkylating and a DNA-binding part, and still further into corresponding antibody-drug conjugates.

Abstract: A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

Abstract: A discharge device includes a plurality of material conveying components, an adjustable shear ledge, and an adjustable shroud to convey materials from a container of a material spreader out onto an open area. The adjustable shear ledge includes at least one longitudinal mounting member such that the adjustable shear ledge may be translated towards or away from the plurality of material conveying components to maintain a predetermined gap distance. The adjustable shroud may also be pivotably connected to the adjustable shear ledge such that the adjustable shroud can be pivoted towards or away from the plurality of material conveying components. The adjustable shear ledge and the adjustable shroud may be moved accordingly to maintain a preferred gap distance and to maintain concentricity with a swing of the material conveying components in order to reduce wear on components and promote spread performance of the material spreader.

Abstract: A sensor including first and second electrodes can be used to determine the concentration of at least one chemical constituent in a fluid sample under test. The electrodes can be disposed in the fluid sample and a predetermined voltage can be applied to a first electrode. The voltage can cause a current to flow between the first and second electrodes through the sample, the current dependent on the concentration of the chemical constituent in the fluid sample. A sense resistor is coupled to the first electrode such that the current flowing between the electrodes flows through the sense resistor. A processor electrically isolated from the electrodes can receive data signals indicative of the voltage drop across the sense resistor and the voltage applied at the first electrode. The received signals can be used to determine the concentration of the constituent in the fluid sample.

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: The present invention relates to a monoclonal, pan-reactive antibody to duocarmycins. The monoclonal, pan-reactive antibody of the present invention may be used to detect, isolate and/or quantify a duocarmycin-containing antibody-drug conjugate in a biological or non biological sample, for example using an immunoassay.

Abstract: Certain embodiments include a sensor system for measuring chlorine concentration in water. The sensor system can have a manifold including one or more flow passages for receiving fluid flow. The sensor system can have a probe for measuring chlorine concentration in fluid communication with a flow passage of the one or more flow passages of the manifold. The probe can have a probe body oriented to direct incoming fluid from one or more flow passages of the manifold toward an end of the probe body. The probe can have a plurality of flutes defined on an outer surface of the probe body. The flutes can be shaped and oriented to direct fluid from the end proximal to the electrodes, back toward the one or more flow passages of the manifold.

Abstract: This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: A method and system for identifying a given geometrical feature of an optical component or semi-finished ophthalmic lens blank, where an optical component is made of an organic material that can emit light at an emission wavelength ?e when being lighten at an illumination wavelength ?i different from the emission wavelength ?e, a surface of the optical component is illuminated with an incident light beam including at least light at the illumination wavelength but devoid from light at the emission wavelength, light emitted at the emission wavelength by the illuminated surface is collected to build an image of the surface, and the surface image is processed to apply metrics to compare the image with reference data specific to the given geometrical feature.