Novel benzamide derivatives of formula (I)

##STR00001##

wherein W.sup.1, W.sup.2, R.sup.1 to R.sup.10 and X have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The invention encompasses methods for increasing genetic progress in livestock, and for genetic dissemination, including the use of amniocentesis to obtain fetal amniocytes for use in genomic evaluation and cloning.

The invention encompasses methods for increasing genetic progress in livestock, and for genetic dissemination, including the use of amniocentesis to obtain fetal amniocytes for use in genomic evaluation and cloning.

A method of in vitro fertilization wherein the embryo is implanted into the uterus of a female patient at least two, and preferably three to twelve months after the eggs are retrieved from the patient in order to reduce the effect of autoimmune rejection of the embryo by the patient's autoimmune system and increase the probability and success of pregnancy and wherein prior to embryo implantation, the endometrium in the uterus is prepared for embryo implantation by introducing peripheral blood mononuclear cells (PBMCs) into the uterus. The procedure is combined with cryopreservation techniques to preserve the oocytes or the IVF-produced embryos of the patient.

A method of in vitro fertilization wherein the embryo is implanted into the uterus of a female patient at least two, and preferably three to twelve months after the eggs are retrieved from the patient in order to reduce the effect of autoimmune rejection of the embryo by the patient's autoimmune system and increase the probability and success of pregnancy and wherein prior to embryo implantation, the endometrium in the uterus is prepared for embryo implantation by introducing peripheral blood mononuclear cells (PBMCs) into the uterus. The procedure is combined with cryopreservation techniques to preserve the oocytes or the IVF-produced embryos of the patient.

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.

The present invention relates to a microfluidic device for denudation of a cumulus oocyte complex. The device includes a substrate. A first channel having a width of about 200 μm to about 1 mm is located within the substrate. The first channel extends from a first end to a second end of the substrate. The first channel has a one or more ridge elements located along a surface thereof. A first port is located in the substrate and in fluid communication with the first end of the channel. A second port is located in the substrate and in fluid communication with the second end of the channel. Systems and methods of use of the microfluidic device for denudation of a cumulus oocyte complex are also disclosed.

There is provided a computer system for evaluating the quality of a fertile ovum. The computer system includes computer processing circuitry configured to receive a plurality of images of a fertile ovum captured in time-series by an imaging apparatus, provide as input to at least one learned model, the plurality of images of the fertile ovum or information based on the plurality of images of the fertile ovum, wherein the at least one learned model has been trained to output, based at least in part, on the plurality of images, fertile ovum analysis information describing characteristics of the fertile ovum used to evaluate a quality of fertile ovum, and provide evaluation support information based, at least in part, on the fertile ovum analysis information, wherein the evaluation support information enables a quality evaluator to interact with the web dashboard to modify at least some of the evaluation support information.