Abstract: ?-cell loss in In Type 1 diabetes is typically undetected until the development of hyperglycemia, at which point ?-cell mass is significantly reduced. Methylation sensitive quantitative real time PCR (qRTPCR) of demethylated circulating free ?-cell specific DNA can be used as a biomarker of ?-cell death. Such DNA includes insulin gene and amylin gene DNA. Detection may be by determination of a gene demethylation index. Methylated and demethylated DNA may be distinguished by bisulfite treatment and use of specific PCR primers or probes to detect the different bisulfite treatment products. Detection of demethylated circulating free amylin DNA is useful in identifying ?-cell death. The amylin DNA may be used in conjunction with other ?-cell specific genes, such as insulin, to provide a multi-gene approach towards the detection of ?-cell loss.

Abstract: The present invention relates to compositions and methods for detecting cell death by detecting cell DNA in a biological sample. The invention relates the discovery that the presence of hypomethylated ? cell DNA outside of the pancreas of a subject is indicative of ? cell death. Thus, in one embodiment, the invention is a method of detecting hypomethylated ? cell insulin DNA in a biological sample of a subject including the steps of: obtaining a biological sample from the subject, where the biological sample is obtained from outside of the subject's pancreas and where the biological sample contains ? cell insulin DNA; determining the methylation status of at least one of the CpG dinucleotides in the ? cell insulin DNA, where when at least one of the CpG dinucleotides in the ? cell insulin DNA is determined to be unmethylated, the hypomethylated ? cell insulin DNA is detected.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.

Abstract: A method of data mining based on microarray data and a document database, comprising: receiving microarray data; generating a search of a microarray data database for information interpreting the microarray data; analyzing the microarray data based on the first search, to determine sequences of interest; receiving a topical; generating a second search of a document database for documents corresponding to the sequences of interest and a conjunction of the sequences of interest and the annotation; performing at least one quantitative comparative analysis between a first quantity of citations of the document database for documents corresponding to the sequences of interest versus a second quantity of citations for documents corresponding to a conjunction of the sequences of interest and the annotation; and ranking the sequences of interest based on the comparative quantitative analysis.

Abstract: The present invention relates to compositions and methods for detecting cell death by detecting cell DNA in a biological sample. The invention relates the discovery that the presence of hypomethylated ? cell DNA outside of the pancreas of a subject is indicative of ? cell death. Thus, in one embodiment, the invention is a method of detecting hypomethylated ? cell insulin DNA in a biological sample of a subject including the steps of: obtaining a biological sample from the subject, where the biological sample is obtained from outside of the subject's pancreas and where the biological sample contains ? cell insulin DNA; determining the methylation status of at least one of the CpG dinucleotides in the ? cell insulin DNA, where when at least one of the CpG dinucleotides in the ? cell insulin DNA is determined to be unmethylated, the hypomethylated ? cell insulin DNA is detected.

Abstract: ?-cell loss in In Type 1 diabetes is typically undetected until the development of hyperglycemia, at which point ?-cell mass is significantly reduced. Methylation sensitive quantitative real time PCR (qRTPCR) of demethylated circulating free ?-cell specific DNA can be used as a biomarker of ?-cell death. Such DNA includes insulin gene and amylin gene DNA. Detection may be by determination of a gene demethylation index. Methylated and demethylated DNA may be distinguished by bisulfite treatment and use of specific PCR primers or probes to detect the different bisulfite treatment products. Detection of demethylated circulating free amylin DNA is useful in identifying ?-cell death. The amylin DNA may be used in conjunction with other ?-cell specific genes, such as insulin, to provide a multi-gene approach towards the detection of ?-cell loss.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.

Abstract: A method for measuring blood levels of DNA that is released upon death from specialized cells in the body, by using PCR or a quantitative probe technology to detect amplified methylated and demethylated forms of cell-specific gene DNA, representing normal tissue and cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated cell-specific DNA patterns that are present only in the dying cells. The method offers a bioassay for detecting ? cell loss in diabetes based on circulating demethylated insulin gene DNA, and circulating demethylated myelin oligodendrocyte protein (MOG) genes of oligodendrocytes in multiple sclerosis, for example, and may be useful for screening, monitoring of disease progression, and selection and monitoring of therapies.

Abstract: Insulin producing ? cells are found in three dimensional (3D) structures, the Islet of Langerhans. The 3D structure is required for normal ? cell function and survival. ? cell pseudoislets (PIs) are useful for study of ? cell physiology. Co-culturing of primary human islets and ? cell lines together with islet-derived epithelial cells can improve ? cell function and survival and maintain the cells' 3D structure, resulting a rapid and spontaneous formation of free-floating PIs. ? cells in PIs were similar in size to native islets and showed increased percentage of pro-insulin-positive cells, increased insulin gene expression in response to glucose stimulation, improved glucose-stimulated insulin secretion, and reduced ? cell death. Key ECM proteins, absent in monolayer ? cells, are deposited by iECs in and round the PIs. iEC induced PIs are a useful tool for examining ?-cell/iEC interactions and studying ?-cell function in a native 3D configuration.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.

Abstract: The present invention relates to compositions and methods for detecting cell death by detecting cell DNA in a biological sample. The invention relates the discovery that the presence of hypomethylated ? cell DNA outside of the pancreas of a subject is indicative of ? cell death. Thus, in one embodiment, the invention is a method of detecting hypomethylated ? cell insulin DNA in a biological sample of a subject including the steps of: obtaining a biological sample from the subject, where the biological sample is obtained from outside of the subject's pancreas and where the biological sample contains ? cell insulin DNA; determining the methylation status of at least one of the CpG dinucleotides in the ? cell insulin DNA, where when at least one of the CpG dinucleotides in the ? cell insulin DNA is determined to be unmethylated, the hypomethylated ? cell insulin DNA is detected.

Abstract: A method for measuring blood levels of ? cell DNA that is released upon ? cell death by using a quantitative probe technology to detect amplified methylated and demethylated forms of the insulin gene DNA, representing normal tissue and ? cell specific origin, respectively. Using probes permits the sensitive and specific identification of demethylated insulin DNA patterns that are present only in ? cells. The method offers a bioassay for detecting ? cell loss in diabetes, useful for screening of prediabetes, monitoring of disease progression, and selection and monitoring of therapies. The technique finds potential use in both Type I and Type II diabetes, as well as gestational diabetes.