Abstract: The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), Ra is a benzyl group with alkyl and/or alkoxy; Rb is selected from H and alkyl groups; Rf is an alkyl; and R3 is selected from a substituted phenyl, a heterocyclic group, and wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group.

Abstract: Diagnostic tests for characterizing a test subject's risk of developing or having cancer, based on determining the level of LRG1 and/or CD13 in a bodily sample obtained from a test subject are described. Levels of LRG1 and/or CD13 are then compared to a predetermined value that is derived from measurements of the levels of LRG1 and/or CD13 in comparable bodily samples obtained from control subjects. Such comparison characterizes the test subject's risk of developing or having cancer.

Abstract: The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), Ra is a benzyl group with alkyl and/or alkoxy; Rb is selected from H and alkyl groups; Rf is an alkyl; and R3 is selected from a substituted phenyl, a heterocyclic group, and wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group.

Abstract: A system and method for combining the model-based and genetics-based methods are combined according to a convergence criterion. When the population is not converged, the genetics-based approach is used, and when the population is converged, the model-based method is used to generate offspring. The algorithm benefits from using a model-based offspring generation only when the population shows a certain degree of regularity, i.e., converged in a stochastic sense. In addition, a more sophisticated method to construct the stochastic part of the model can be used. Also a biased Gaussian noise (the mean of the noise is not zero), as well as a white Gaussian noise (the mean of the noise is zero) can be preferably used for the stochastic part of the model.

Abstract: A system and method for combining the model-based and genetics-based methods are combined according to a convergence criterion. When the population is not converged, the genetics-based approach is used, and when the population is converged, the model-based method is used to generate offspring. The algorithm benefits from using a model-based offspring generation only when the population shows a certain degree of regularity, i.e., converged in a stochastic sense. In addition, a more sophisticated method to construct the stochastic part of the model can be used. Also a biased Gaussian noise (the mean of the noise is not zero), as well as a white Gaussian noise (the mean of the noise is zero) can be preferably used for the stochastic part of the model.

Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endonbonuclease RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase PKR are provided. Methods for producing enhanced levels of recombinant proteins in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption in the PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein. In another aspect the methods employ mutant cells hating a homozygous disruption in the PKR gene, i.e. PKR null cells.

Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endoribonuclease known as RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase known as PKR. Methods for producing enhanced levels of recombinant proteins, or polypeptides, in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein, or polypeptide; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein.

Abstract: The present invention provides a mutant, non-human mammal, particularly a mutant mouse, having a homozygous disruption in the RNase L gene thereof. Since the homozygous disruption in the RNase L gene leads to minimal if any production of RNase L in the mutant mammals, such mutant mammals are useful for assessing the effect of antiviral drugs on the induction, synthesis, or activation of RNase L. The present invention also relates to mutant, non-human, embryonic stem cell lines having a heterozygous disruption of the RNase L gene thereof, to isolated mammalian cells having a homozygous disruption in the RNase L gene thereof, and to a DNA construct comprising a DNA sequence of a disrupted coding exon of a RNase L gene.

Abstract: Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide.

Abstract: 2-5A-dependent RNase, an endoribonuclease that requires 5'-phosphorylated 2',5'-linked oligoadenylates (2-5A), functions in the molecular mechanism of interferon action. Recombinant, 2-5A-dependent RNase was expressed to high levels (at least 10% of the soluble protein) in insect cells by infecting with baculovirus containing human cDNA to 2-5A-dependent RNase. In contrast, there was no 2-5A-dependent RNase present in control insect cells infected with nonrecombinant baculovirus. The purified, recombinant enzyme eluted from a gel-filtration column as a monomer that showed potent and highly specific, 2-5A-dependent RNase activity. Precise activitor requirements were determined using the purified enzyme of a variety of 2',5'-linked oligonucleotides. The activated enzyme was capable of cleaving both poly(rU) and, to a lesser extent, poly(rA) but not poly(rC), poly(rG), or poly(dT. Interestingly, poly(rU) was cleaved to a series of discrete products ranging between 5 and 22 nucleotides in length.

Abstract: Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide.