Abstract: Described herein is a gene regulatory network based focused approach to cell transformation. The methods described herein allow for identification of circuit and sub-circuit repertoires for which modification in a starting cell type can result in generation of a transformed cell type in a durable and persistent manner, without requiring potentially deleterious genome modification. The described methods and compositions produced by the methods find widespread application in regenerative medicine applications.

Abstract: The invention provides a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cell, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell. Also provided is a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cellular state, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell.

Abstract: A computational method is described which uses the process of cis-regulatory module evolution to identify conserved sequence patches which exhibit suppression of change by snp/indel occurrence, including determining sequence similarities significantly greater than random expectation on selected genome sequences from two or more species in sequences that lie outside of protein coding regions, sorting the similarities for conserved patches of single nucleotide polymorphisms (SNPs) and insertion/deletions (indels). and selecting such patches to identify cis-regulatory modules. Further, the disclosed method is practiced in the absence of having to execute multiple interspecific sequence comparison analysis, where such identified cis-regulatory modules are used to produce libraries and arrays containing such cis-regulatory modules.

Abstract: The present invention relates to compositions and methods for detection and quantification of individual target molecules in biomolecular samples. In particular, the invention relates to coded, labeled probes that are capable of binding to and identifying target molecules based on the probes' label codes. Methods, computers, and computer program products for identifying target-specific sequences for inclusion in the probes are also provided, as are methods of making and using such probes. The probes can be used in diagnostic, prognostic, quality control and screening applications.

Abstract: The invention provides a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cell, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell. Also provided is a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cellular state, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell.

Abstract: The invention provides a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cell, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell. Also provided is a method of modulating a regulatory state of a cell. The method consists of: (a) identifying a point of interdiction within a cis regulatory network specifying a genetic regulatory architecture of a cellular state, and (b) introducing into a progenitor cell two or more network elements within said network to induce a predetermined series of cis regulatory network interactions resulting in a specified regulatory state of said progenitor cell.

Abstract: The present invention is directed to methods and compositions useful for altering the transcriptional expression of genes in eukaryotic cells. The invention employs novel antibody derivative molecules which function to recognize and bind to specific cis-regulatory DNA sequence elements of a eukaryotic gene. When two antibody derivative molecules are bound to adjacent cis-regulatory DNA sequence elements of a gene, those molecules may interact to form an antibody binding site which is capable of recognizing and binding to a transcription factor protein for the target gene, thereby affecting the functionality of that transcription factor protein and, in turn, the transcriptional activity of the gene. Also provided herein are isolated nucleic acids encoding the novel antibody derivative molecules of the present invention and expression vectors comprising those nucleic acids.

Abstract: The present invention is directed to methods and compositions useful for altering the transcriptional expression of genes in eukaryotic cells. The invention employs novel antibody derivative molecules which function to recognize and bind to specific cis-regulatory DNA sequence elements of a eukaryotic gene. When two antibody derivative molecules are bound to adjacent cis-regulatory DNA sequence elements of a gene, those molecules may interact to form an antibody binding site which is capable of recognizing and binding to a transcription factor protein for the target gene, thereby affecting the functionality of that transcription factor protein and, in turn, the transcriptional activity of the gene. Also provided herein are isolated nucleic acids encoding the novel antibody derivative molecules of the present invention and expression vectors comprising those nucleic acids.

Abstract: The present invention is directed to methods and compositions useful for altering the transcriptional expression of genes in eukaryotic cells. The invention employs novel antibody derivative molecules which function to recognize and bind to specific cis-regulatory DNA sequence elements of a eukaryotic gene. When two antibody derivative molecules are bound to adjacent cis-regulatory DNA sequence elements of a gene, those molecules may interact to form an antibody binding site which is capable of recognizing and binding to a transcription factor protein for the target gene, thereby affecting the functionality of that transcription factor protein and, in turn, the transcriptional activity of the gene. Also provided herein are isolated nucleic acids encoding the novel antibody derivative molecules of the present invention and expression vectors comprising those nucleic acids.

Abstract: A system for mapping radioactive specimens comprises an avalanche counter, an encoder, pre-amplifier circuits, sample and hold circuits and a programmed computer. The parallel plate counter utilizes avalanche event counting over a large area with the ability to locate radioactive sources in two dimensions. When a beta ray, for example, enters a chamber, an ionization event occurs and the avalanche effect multiplies the event and results in charge collection on the anode surface for a limited period of time before the charge leaks away. The encoder comprises a symmetrical array of planar conductive surfaces separated from the anode by a dielectric material. The encoder couples charge currents, the amplitudes of which define the relative position of the ionization event. The amplitude of coupled current, delivered to pre-amplifiers, defines the location of the event.

Abstract: A system for the production and maintenance of genomic libraries of recombinant DNA in a fixed geometric array arranged so that such libraries may be accurately replicated and maintained with the same set of individual DNA inserts occupying reproducible locations and comprising,(a) sets of individual bacterial colonies or plaques of bacteriophage which contain inserts of animal or plant DNA and are present in so large a number that there will be a high probability that the complete library will contain each DNA sequence of all of the sequences present in an animal or plant genome; to be established in subarrays which can individually be replicated,(b) a subsystem for picking up inocula from each of a geometric array simultaneously and transferring them to a second similar geometric array, including carrying and aligning means for maintaining a transfer means in superposed relationship with respect and for raising and lowering the transfer means into and out of proximity to said colonies or plaques, and(c) a s

Abstract: Novel large area spark chamber having a support for carrying a generally planar, radioactive work piece. The spark chamber has a thin window which is either a rigid plastic sheet carrying a thin layer of an electrically conductive material on the surface thereof, or a thin planar piece or film of electrically conductive metal. There is positioned in superposed relationship to the thin window, a layer of semi-conducting glass in spaced-apart relationship from the thin window by a resilient insulating seal to form an enclosed gas retaining chamber. An electrically conducting surface is adhered to the upper surface of the layer of semi-conducting glass. An electrically conductive path is provided between the thin layer of electrically conductive material on the thin window and the electrically conducting surface on said semi-conducting glass. The electrically conductive path includes a high voltage supply and TDCs and ADCs.