Abstract: Disclosed herein is a method for following up a prognosis of children with autism before and after treatment with different modalities administered by their clinicians, confirming the involvement of infectious agents, dietary proteins, and toxic chemicals in development of autism. The method utilizes detection of increased amounts of antibodies against an antigen based on infectious agent, toxic chemicals, or dietary proteins. Another method utilizes detection of antibodies to a self-tissue or peptide.

Abstract: The present invention relates to a new essential downstream component of the Wnt/Wingless (Wnt/Wg) signaling pathway and therapeutic and diagnostic applications based thereon. The invention relates to nucleotide sequences of the Drosophila melanogaster legless (lgs) gene, of its encoded proteins, as well as derivatives (e.g., fragments) and analogues thereof. The invention further includes vertebrate and invertebrate homologues of the Lgs protein, comprising proteins that contain a contiguous stretch of amino acids with similarity to the Drosophila lgs gene. The invention further relates to the function of the Drosophila and the human Lgs proteins. Methods for producing the Lgs proteins, derivatives and analogs, e.g., by recombinant means and antibodies to Lgs are provided by the present invention. In addition, the invention also relates to the therapeutic and diagnostic methods and compositions based on Lgs proteins and nucleic acids or fragments thereof.

Abstract: The invention concerns a method for the detection of an analyte in a sample using analyte-specific conjugates which have at least one heterologous group for an analyte-independent binding to a control zone. The present invention additionally provides new conjugates and reagent kits.

Abstract: The immunoassay method of this invention measures the content of a subject substance in a sample. The method includes the steps of: (a) preparing a mixed solution by mixing the sample and an antibody solution including a first monoclonal antibody and a second monoclonal antibody capable of specifically binding to the subject substance; and (b) measuring an optical property of the mixed solution. The first monoclonal antibody is capable of binding to a first epitope of the subject substance, and the second monoclonal antibody is capable of binding to a second epitope of the subject substance different from the first epitope. Each of the first and second epitopes exists singly in the subject substance.

Abstract: The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.

Abstract: The current invention discloses nucleic acid and amino acid sequences for novel organic anion transfer proteins (“OATPs”). The invention encompasses the OATPs described herein, together with vectors containing the cDNA sequences, host cells containing the vectors and polypeptides having all or part of an OATP. Also encompasses are uses for OATPs for targeting drugs to specific organs and for modulating the concentration of endogenous substrates.

Abstract: In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/?-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/?-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is ?-synuclein. The aggregation of NACP/?-synuclein is dependent upon the concentration of metal ions in the neuronal cells.

Abstract: The present invention relates to a method to identify substances and a use of such substances which can modulate IL-4 dependent signaling involved in tumor diseases, preferably Hodgkin Lymphomas or inflammatory airway diseases, preferably asthma and a method for determining whether a substance can modulate the interaction of STAT6 with NCoA-1, characterized in that a) STAT6 or fragments or derivatives thereof having the ability to bind to NcoA-1 are brought into contact with NCoA-1 or fragments or derivatives of NCoA-1 having the ability to bind STAT6 under conditions where STAT6 and NCoA-1 or fragments or derivatives thereof are capable of forming a complex, and the complex can be used to induce a measurable readout; b) a readout is measured in the absence or presence of the substance of interest; c) the readout in absence of substance of interest is compared with readout in presence of substance of interest.

Abstract: Bifunctional inhibitor molecules and methods for their use in the inhibition of protein—protein interactions are provided. The subject bifunctional inhibitor molecules are conjugates of a target protein ligand and a blocking protein ligand, where these two moieties are optionally joined by a linking group. In the subject methods, an effective amount of the bifunctional inhibitor molecule is administered to a host in which the inhibition of a protein—protein interaction is desired. The bifunctional inhibitor molecule simultaneously binds to its corresponding target and blocking proteins to produce a tripartite complex that inhibits the target protein—protein interaction. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

Abstract: The present invention is directed to methods and compositions for determining the presence, absence, and/or amounts of one or more membrane-associated analytes in a sample. In accordance with the invention, binding compounds derivatized with releasable molecular tags specifically bind to selected membrane-associated analytes, after which the molecular tags are released upon activation of cleavage moieties, or sensitizers, anchored in the same membrane as the membrane-associated analytes. The released molecular tags are then identified by their distinct separation and detection characteristics.

Abstract: The present invention relates to a screening method/screening kit for screening a compound or its salt that changes the binding properties of (a) a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 19, its partial peptides, or salts thereof, and (b) a ligand capable of binding specifically to the protein; compounds obtained by the screening or salts thereof; pharmaceuticals comprising the compounds or salts thereof; a protein containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 19; etc. The compounds obtained by the screening of the present invention are useful as agents for the prevention/treatment of, for example, neurodegenerative diseases, immunological diseases, edema, acid indigestion, etc.

Abstract: The invention relates to the use of a fluorescent protein chosen in particular from autofluorescent proteins, for the detection of the non-covalent interactions between a target protein labeled with the fluorescent protein and one of its ligands labeled with a label consisting: either of a molecule which is capable of absorbing the light emitted by the fluorescent protein, or of a fluorescent substance, this detection taking place by fluorescence energy transfer: between the fluorescent protein and the above-mentioned fluorescent substance, the fluorescent substance being such that either it is excitable at the emission wavelength of the fluorescent protein, or it emits at the excitation wavelength of the fluorescent protein, or between the fluorescent protein and the above-mentioned molecule which is capable of absorbing the light emitted by the fluorescent protein.

Abstract: Polypeptides derived from vitamin D nuclear receptor, which nuclear receptor comprises a ligand-binding domain, or LBD, which contains a flexible insertion domain. The polypeptides are charactarised in that the LBD flexible insertion domain is modified by substituting or suppressing at least 30 acids. The invention also concerns the use of the polypeptides in particular for screening synthetic vitamin D analogues or for producing tests (double or triple hybrid) for identifying other proteins (activator, repressor, . . . ) interacting with the vitamin D receptor using constructs containing the polypeptide used with Gal4 for example, or for analyzing three dimensional structures of complexes formed between the polypeptides and a particular molecule by crystallography or NMR.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The present invention provides methods for determining a ratio of an amount of a glycated form of a protein to a total amount of the protein in a sample containing the glycated protein, the glycosylated protein, or the glycoprotein. The method incorporates lateral flow test strip or vertical flow test strip devices having negatively charged carboxyl or carboxylate groups and hydroxyboryl groups immobilized and interspersed on a solid support matrix. The solid support matrix may include derivatives of cellulose (e.g., carboxy cellulose) derivatized with carboxylic acid (e.g., carboxylate, carboxyl) groups and hydroxyboryl compounds including phenylboronic acid (e.g., phenylborate), aminophenylboronic acid, boric acid (e.g., borate), or other boronic acid (e.g., boronate) compounds. The present invention is usefi.il for monitoring glycation or glycosylation of hemoglobin or albumin for monitoring glycemic control (e.g., glycemia in diabetes).

Abstract: Method and kits are provided for the detection and diagnosis of metastatic disease. More particularly, the methods and kits employ compounds that can detect EphA2, a specific epithelial cell tyrosine kinase that is overexpressed in metastatic tumor cells. In one embodiment the compound is an antibody capable of binding to an epitope of EphA2.

Abstract: Reagents and methods for detecting target proteins in a sample are provided. The reagents include a replicable genetic package, a protein displayed on an exterior surface of the package that is expressed from a heterologous nucleic acid borne by the package, and one or more antibodies complexed with the expressed protein and which have an open binding site for a target protein. Thus, a segment of the nucleic acid encodes for an epitope that is shared by the expressed polypeptide and the target protein. The reagents can be utilized individually or as part of a library or an array to bind target proteins within protein samples to form one or more complexes. By determining the sequence of the segment of the heterologous nucleic acid of a package within a complex, one can identify the target protein since the segment encodes for an epitope that is shared by the expressed and target proteins.

Abstract: The present invention relates to compositions and methods for assaying homocysteine (Hcy) and thus related moieties, e.g., S-adenosylhomocysteine (SAH) or adenosine. More particularly, assay methods that employ, mutant SAH hydrolase having binding affinity for Hcy, SAH or adenosine but has attenuated catalytic activity, are provided. The modified enzymes and fusion proteins containing the modified enzymes are also provided.

Abstract: The present invention relates to the use of alpha (2) macroglobulin (“?2M”) receptor as a heat shock protein receptor, cells that express the ?2M receptor bound to an HSP, and antibodies and other molecules that bind the ?2M receptor-HSP complex. The invention also relates to screening assays to identify compounds that modulate the interaction of an HSP with the ?2M receptor, and methods for using compositions comprising ?2M-receptor sequences for the diagnosis and treatment of immune disorders, proliferative disorders, and infectious diseases.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: The assay of soluble endothelial protein C receptor (sEPCR) is useful to monitor effective thrombin levels and a hypercoagulable state. An assay for sEPCR is therefore useful to monitor ongoing effectiveness of anticoagulant therapy. A sEPCR ELISA assay is particularly useful for this purpose. A state of hypercoagulability in patients or normal individuals can also be identified by such an assay.

Abstract: Methods for identifying a member of a mass-coded molecular library, which is a ligand for a biomolecule and binds to the biomolecule at the binding site of a known second ligand for the biomolecule are described. The methods includes contacting a mass-coded molecular library with a biomolecule; separating the biomolecule-ligand complexes from the unbound members of the mass-coded molecular library; contacting the biomolecule-ligand complexes with a second ligand to dissociate biomolecule-ligand complexes in which the ligand binds to the biomolecule at the binding site of the second ligand, thereby forming biomolecule-second ligand complexes and dissociated ligands; separating the dissociated ligands and biomolecule-second ligand complexes; and determining the molecular mass of each dissociated ligand.

Abstract: Cells can be labeled with products which they secrete and release in an efficient manner by coupling the cells at their surface to a specific binding partner for the product and allowing the product to be captured by the specific binding partner as it is secreted and released. The product-labeled cells can then be further coupled to suitable labels, if desired, and separated according to the presence, absence, or amount of product.

Abstract: A method for in vitro screening a group of test substances for a ligand using two assay systems, i.e. a cellular or tissue assay system and an enzymatic assay system, is described. First, those test substances are selected which have transcriptional ER-mediated activity measured by an ER-driven reporter gene in the cellular or tissue assay system with an EC50(ER)(half-maximally effective ligand concentration) lower than or equal to 10 nmol/l. Then in an enzymatic assay system the selected test substances having the required transcriptional ER-mediated activity are tested by measuring a physical-chemical interaction (recruitment) of SRC-1 and the ER in the presence of the test substances. The selected ligand activates the ER and induces interaction with the co-present SRC-1 with an E50(ER+SRC) higher than or equal to 100 nmol/l.

Abstract: The invention relates to methods and compositions useful in screening for modulators of IgE synthesis, secretion and switch rearrangement.

Abstract: This invention pertains to the discovery that DPR-1 encodes a putative nuclear hormone receptor (NHR) that, based on gene reporter studies, is expressed in the endoderm throughout the life of the worm. NHR family members are transcriptional regulators that are activated when bound to their small lipophilic ligands such as steroids. While some NHRs are localized to the nucleus, others are cytoplasmic in the absence of ligand and translocate to the nucleus upon ligand binding. Once in the nucleus, they bind target sequences and regulate gene expression.

Abstract: There is provided a method of identifying a PAR cleaving molecule comprising the steps of: (a) providing an immobilized PAR cleavage peptide linked to a reporter molecule; (b) contacting the immobilized PAR cleavage peptide with a PAR cleaving molecule; and (c) detecting release of the reporter molecule.

Abstract: A system and method for detecting mass based on a frequency differential of a resonating micromachined structure, such as a cantilever beam. A high aspect ratio cantilever beam is coated with an immobilized binding partner that couples to a predetermined cell or molecule. A first resonant frequency is determined for the cantilever having the immobilized binding partner. Upon exposure of the cantilever to a solution that binds with the binding partner, the mass of the cantilever beam increases. A second resonant frequency is determined and the differential resonant frequency provides the basis for detecting the target cell or molecule. The cantilever may be driven externally or by ambient noise. The frequency response of the beam can be determined optically using reflected light and two photodetectors or by interference using a single photodetector.

Abstract: A method of designing a new anti-CMV drug is disclosed. In one embodiment, the invention comprises (a) analyzing the binding of glycoprotein O to a glycoprotein O receptor and (b) designing a candidate drug that would competitively interfere with glycoprotein O binding to glycoprotein O receptor and (c) showing that the candidate drug competitively inhibits glycoprotein O binding to glycoprotein O receptor. A method of screening anti-CMV drugs, a vaccine effective to diminish CMV infection, and a method of diminishing CMV infection are also disclosed.

Abstract: Entry of HIV-1 into target cells requires cell surface CD4 as well as additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T cell lines was recently identified and named fusin. Fusin, however, does not promote entry of macrophage-tropic viruses that are believed to be the key pathogenic strains in vivo. It has now been determined that the principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR5, a receptor for the ?-chemokines RANTES, MIP-1?, and MIP-1?.

Abstract: Investigation on the frequency of FLT3/ITD found in various blood cancers has revealed that the frequency is high in acute myeloblastic leukemia in particular. Studies on the effects of FLT3/ITD in the blood cell lines revealed that the tyrosine residues in FLT3/ITD is constitutively phosphorylated in these cell lines and that blood cells into which FLT3/ITD is introduced show IL-3 independent proliferation. Moreover, the blood cells into which FLT3/ITD is introduced are found to be capable of forming tumors and inhibit cell differentiation. The inventors have found that it is possible to screen for pharmaceutical compounds against tumors by using inhibition of these FLT3/ITD functions as an index.

Abstract: The present invention provides compositions and methods for modulating leukocyte activation. Nucleic acids encoding proteins and proteins so encoded which are capable of modulating leukocyte activation are provided. Compositions and methods for the treatment of disorders related to leukocyte dysfunction or dysregulation are also provided. Prophylactics and methods for the prevention of such disorders are also provided. Also provided are compositions and methods for diagnostic and prognostic determination of such disorders. Further provided are assays for the identification of bioactive agents capable of modulating leukocyte activation.

Abstract: Described are methods for identifying targets in RNA molecules based on differences in RNA secondary structure related to sequence variances between different allelic forms. Also described are methods for identifying or developing small molecules which can be used to modulate a target RNA by creation of protein-small-molecule-RNA complexes, as well as compositions which include such small molecules and methods of using those small molecules and compositions.

Abstract: The invention provides methods for identifying compounds suitable for treating a cardiovascular disorder, as well as methods for treating a cardiovascular disorder. The invention also provides methods for determining if a subject is at risk for a cardiovascular disorder.

Abstract: The present invention relates to nine residue peptides (M32-40) from flavivirus M ectodomain able to modulate specifically the apoptotic activity of diverse flavivirus, to pharmaceutical composition comprising the same and their use for the treatment and/or the prevention of flavivirus-linked infections and cancers.

Abstract: A novel receptor-type protein tyrosine phosphatase (RPTP) protein or glycoprotein and the DNA coding therefor is expressed in a wide variety of mammalian tissues. Included in this family of proteins are human RPTP?, human RPTP? and human RPTP?. The RPTP protein or glycoprotein may be produced by recombinant means. Antibodies to the proteins, methods for measuring the quantity of the proteins, methods for screening compounds, such as drugs, which can bind to the proteins and inhibit or stimulate their activity, are provided.

Abstract: Methods for chromatographically separating materials, including the separation of materials in kinase or phosphatase assays, in microfluidic devices under positive or negative fluid pressure. Devices and integrated systems for performing chromatographic separations are also provided.

Abstract: The invention provides a method to screen for a modulator of enzymatic activity comprising the step of monitoring the association or dissociation of a pair of polypeptides which can associate as a dimer. The polypeptide pair comprises a first polypeptide comprising detection means and a site of post-translational modification and a second polypeptide comprising detection means.

Abstract: Methods for identifying modulators of nuclear hormone receptor function comprise the steps of (a) forming a mixture comprising a nuclear hormone receptor, a peptide sensor and a candidate agent, but not a natural coactivator protein of the receptor, wherein the sensor provides direct, in vitro binding to the receptor under assay conditions; (b) measuring an agent-biased binding of the sensor to the receptor; and (c) comparing the agent-biased binding with a corresponding unbiased binding of the sensor to the receptor. In particular embodiments, the sensor comprises an amphipathic alpha helix nuclear hormone interacting domain comprising a recited nuclear hormone transcriptional coactivator motif sequence, the sensor is present at sub-micromolar concentration, the binding reaction occurs in solution, the sensor comprises a fluorescent label and the measuring step comprises detecting fluorescence polarization of the label.

Abstract: A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C?O or a covalent bond; Y is H or O(C1–C4)alkyl, R1 and R2 are individually (C1–C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H or together with R3 is —CH2—CH2— or —S—, R5 is I, O(C1–C4)alkyl or H, and R6 is I, O(C1–C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screetng assays, functional genomics and regulation of traits in transgenic plants and animals.

Abstract: Methods of predicting therapeutic efficacy of treatment of a multiple sclerosis patients with peptides are provided. Multiple sclerosis patients can be screened for the presence of an human leukocyte antigen (HLA)-DR2 haplotype. The presence of the human leukocyte antigen (HLA)-DR2 haplotype in a patient is predictive of therapeutic efficacy of treatment.

Abstract: A method of measuring oestrogen or progesterone receptor (ER or PR) comprises identifying in histopathological specimen image data pixel groups indicating cell nuclei, and deriving image hue and saturation. The image is thresholded using hue and saturation and preferentially stained cells identified. ER or PR status is determined from normalised average saturation and proportion of preferentially stained cells. A method of measuring C-erb-2 comprises correlating window functions with pixel sub-groups to identify cell boundaries, computing measures of cell boundary brightness and sharpness and brightness extent around cell boundaries, and comparing the measures with comparison images associated with different values of C-erb-2. A C-erb-2 value associated with a comparison image having similar brightness-related measures is assigned. A method of measuring vascularity comprises deriving image hue and saturation, producing a segmented image by hue and saturation thresholding and identifying contiguous pixels.

Abstract: This invention relates to the methylation of histones, in particular to a previously uncharacterised group of histone H3 methylases which comprise a SET domain and which methylate either lysine 4 within the amino tail of histone H3 or within the histone H3 core. Methylation by these methylases, in particular trimethylation, is shown to be important for transcriptional activity.

Abstract: Carriers hold remote-acting bodies which can be manipulated by a remote force, and also hold a micro-substance which is a target substance of an assay. The remote-acting bodies are manipulated in order to control the positions of the micro-substances, so as to execute assays for various target substances efficiently, at low cost, easily, and reliably. Various aspects of interest include the carriers which hold the micro-substances, a system suspending the carriers, an apparatus for manipulating the carriers, and a method of controlling the position of the carriers.

Abstract: The invention provides methods and compositions for azide tagging of biomolecules. In one embodiment of the invention, proteins are tagged by metabolic incorporation of prenylated azido-analog substrates. Examples of such analogs are azido farnesyl diphosphate and azido farnesyl alcohol. The azido moiety in the resulting modified proteins provides an affinity tag, which can be chemoselectively captured by an azide-specific conjugation reaction, such as the Staudinger reaction, using a phosphine capture reagent. When the capture agent is biotinylated, the resulting conjugates can be detected and affinity-purified by streptavidin-linked- HRP and streptavidin-conjugated agarose beads, respectively. The invention allows detection and isolation of proteins with high yield, high specificity, and low contamination without harsh treatment of proteins.

Abstract: The invention provides isolated nucleic acids molecules, designated 14094 nucleic acid molecules, which encode a novel trypsin family member. Elevated expression of 14094 mRNA was detected in breast, ovarian, lung, and liver cancers compared to normal cells derived from these tissues. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 14094 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 14094 gene has been introduced or disrupted. The invention still further provides isolated 14094 proteins, fusion proteins, antigenic peptides and anti-14094 antibodies. Therapeutic and diagnostic methods utilizing compositions of the invention to, for example, treat, prevent, and/or diagnose neoplastic conditions, are also provided.

Abstract: The present invention is directed to a novel method of detecting a function or activity of a polypeptide which is related to bone metabolism, in particular, differentiation (maturation) of osteoblast or morphological change (retraction), specifically relating to a polypeptide which comprises an amino acid sequence shown by SEQ ID NO: 2 or SEQ ID NO: 4, an amino acid sequence in which one or several amino acids are deleted, substituted or added in the amino acid sequence shown by SEQ ID NO: 2 or SEQ ID NO: 4, or a polypeptide encoded by a nucleic acid which is capable of hybridizing under stringent condition with a nucleic acid comprising a nucleotide sequence shown by SEQ ID NO: 1 or SEQ ID NO: 3, or a complement sequence thereof.

Abstract: Intracellular translocation of proteins, particularly protein kinase C (PKC) isoenzymes, provides a surrogate test system for determining toxicity of candidate compounds. The profile of translocation with respect to at least one and preferably two or more signal transduction proteins can be correlated with-that of known toxins. In addition, databases of such profiles with respect to toxins of various types provide a useful set of standards for evaluating toxicity of candidate compounds. Moreover, to the extent that a toxin's profile mimics that found in a diseased state, the toxin can be used to construct screens for compounds alleviating the disease.

Abstract: The invention relates to methods and compositions useful for screening for altered cellular phenotypes using an inducible expression system to enrich for and detect the altered phenotypes and, more particularly, relates to screening libraries of candidate bioactive agents, for example, nucleic acids and peptides, in cells using an regulatable expression system to enrich for a subpopulation of cells having an altered phenotype due to the presence of a candidate bioactive agent.