Abstract: Provided herein, in one aspect, is a method of preventing or delaying the onset of clinical type 1 diabetes (T1D), comprising: providing a non-diabetic subject who is at risk for T1D; administering a prophylactically effective amount of an anti-CD3 antibody to the non-diabetic subject; and determining, prior to or after the administering step, that the non-diabetic subject has more than about 5% to more than about 10% TIGIT+KLRG1+CD8+ T-cells in all CD3+ T-cells, which is indicative of successful prevention or delay of the onset of clinical T1D.

Abstract: Provided herein, in one aspect, is a method of preventing or delaying the onset of clinical type 1 diabetes (T1D), comprising: providing a non-diabetic subject who is at risk for T1D; administering a prophylactically effective amount of an anti-CD3 antibody to the non-diabetic subject; and determining, prior to or after the administering step, that the non-diabetic subject has more than about 5% to more than about 10% TIGIT+KLRG1+CD8+ T-cells in all CD3+ T cells, which is indicative of successful prevention or delay of the onset of clinical T1D.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5? end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5?end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.

Abstract: The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.

Abstract: In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Abstract: In one aspect, the invention generally relates to compositions comprising miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Abstract: The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.