The objective of this project is to establish methods for conjugating the potent marine toxin, palytoxin to antibodies in such a way that specific cytotoxicity of target cells is possible. the product, immunopalytoxin (ipt), should be easily prepared, have high specific cytotoxic activity and be… More

We propose to develop an immunoassay for the pesticide, carbofuran. phase i will consist of synthesizing suitable haptens, conjugating these haptens to an immunogenic carrier, preparing and screening rabbit antisera, and conducting preliminary competitive elisa tests to demonstrate the feasibility… More

The objective of this project is to use immunological methods to purify and characterize the 50 kda anorexigen isolated previously in low yields using conventional procedures. a small amount of the purified anorexigen is presently available and will be used to generate a set of monoclonal… More

The saxitoxins are neurotoxins and are among the most potent nonprotein toxins known. several thousand cases of paralytic shellfish poisoning occur worldwide each year, with a case-fatality rate approaching 10 percent. since there is no antidote for such poisoning, avoidance of contaminated material… More

The ultimate objective of this project is the production of a dengue vaccine. the four dengue viruses (serotypes) as a group are by far the most important viruses transmitted to man by arthropods and in terms of global morbidity are responsible for several hundred thousand to several million cases… More

Tetrodotoxin is a highly potent low molecular weight neurotoxin found in some species of pufferfish and a few other widely divergent organisms. currently, tetrodotoxin is measured by mouse bioassay or with sophisticated chromatographic methods. a simple, specific, easy to use assay method for… More

The overall goal of this project is to develop immunoassays capable of detecting avarol and avarone at the nanogram level in biological samples. avarol is a marine natural product with potent anti-tumor and anti-aids activity. thiscompound is undergoing evaluation as an anti-aids drug and an… More

The overall goal of this project is to develop immunoassays capable of detecting didemnins at the nanogram level. didemnin b is the most potent antitumor, antiviral, and cytotoxic member of a family of five cyclic depsipeptides isolated from marine tunicates. this compound is currently in clinical… More

Immunochemical techniques have many diverse applications. however, they are restricted to use only in aqueous media. economical techniques for direct organic phase analysis and immunoaffinity isolation would significantly broaden the usefulness of antibody-based technology. the purpose of this… More

The proposed research will investigate the ability of neurospora crassa to express and secrete biologically-activemammalian proteins. the ability to genetically engineer bacteria and yeasts for these tasks is well documented. however, recombinant products from these organisms often require costly… More

The four serotypes of dengue viruses are a leading cause of morbidity throughout the tropics and subtropics. for the development of diagnostics for and subunit vaccines against dengue virus, a reliable and inexpensive source of dengue proteins is needed. the expression of recombinant proteins in… More

Human t-lymphotropic virus type ii (htlv-ii) is a human retrovirus related to, but distinct from, other retrovirusesthat are identified causative agents of disease. little is known about htlv-ii prevalence in the population or its disease associations because the study of htlv-ii has lagged, in part… More

The four serotypes of dengue viruses are a leading cause of morbidity throughout the tropics and subtropics. for use in diagnostics and in subunit vaccines against dengue, a reliable and inexpensive source of dengue antigens is required. for these purposes, expression of recombinant antigens in… More

Taxol is a promising new anticancer drug, isolated from the bark of the western yew (taxus brevefolia), and is currentlyin phase ii clinical trials. development of this drug is impeded by a supply shortage. identification of new taxol sources is hampered by the lack of suitable assays for detecting… More

Considerable interest has been focussed on the production and characterization of therapeutic immunoconjugates. such hybrid molecules usually consist of a monoclonal antibody with covalently attached toxin, drug, or radioisotope. some of these agents have been shown to be clinically useful for… More

It has been demonstrated that alpha-galactosidase and alpha-n-acetyl galactosaminidase have the ability to enzymatically convert type b and a human erythrocytes, respectively, to serotypically type o erythrocytes. this ability would obviate the need for typing or crossmatching, would simplify… More

Palytoxin is an extremely cytotoxic low molecular weight natural product isolated from soft corals of the genus, palythoa. n-acylated derivatives of palytoxin have been reported to be up to 100-fold less cytotoxic than the unmodified toxin. palytoxin n-acyl derivatives which can be converted to the… More

Urease offers distinct advantages over other enzymes for preparation of conjugates used in enzyme-linked immuno-sorbent assay systems. molecular devices corporation (menlo park, ca) has capitalized on these advantages in their threshold system. this impressive system utilizes avidin-biotin to… More

Production of recombinant products of pharmaceutical and industrial importance in a variety of microorganisms has yielded a wide variety of biologically active proteins. fungi offer the advantage of reduced culturing and downstream processing costs because they are capable of secreting prodigious… More

Dengue viruses are a leading cause of morbidity throughout the tropics and subtropics. attempts to develop live attenuated dengue vaccines analogous to the yellow fever vacine have been unsuccessful. in an effort to contrubite to the development of a recombinant subunit dengue vaccine, we will… More

Transition state analog haptens will be prepared for the elicitation of antibodies which can catalyze the conversion of palytoxin prodrugs to palytoxin.

We will construct hybrid polio/dengue virus genomes in order to develop a vaccine for dengue virus. in the chimeric genomes, one of two dengue virus envelope gene fragments will replace segment of the polio virus structural protein genes. such chimerae would have the ability to replicate in the gut… More

We will achieve the selective delivery of cytotoxic agents through the use of bispecific antibodies. taxol is a promising new anticancer agent isolated in low yield from the bark of the pacific yew tree, taxus brevifolia. the applicant will prepare a thioether-linked bispecific antibody with dial… More

High affinity antigen-antibody binding is essentially anhydrous hydrophobic organic solvents has been demonstrated in our laboratory. using an estradiol-antiestradiol system, a prototype organic phase radioimmunoassay (opria) has been developed which detects 200 pg/ml or estradiol in a hexane medium… More

A palytoxin produrg derivative will be prepared. this compound will be tested for its differential cytotoxicity compared to palytoxin; and for its ability to be enzymatically activated.

This phase i project is designed to test the feasibility of purifying taxol by immunoaffinity chromatography. the use of this technique for purification of a low molecular weight compound with low aqueous solubility has not been reported to date. taxol-specific monoclonal antibodies will be selected… More

A Taxol prodrug derivative will be prepared. This compound will be tested for its differential cytotoxicity compared to Taxol and for its ability to be enzymatically activated. The cytotoxicity of the prodrug in combination with a monoclonal-antibody enzyme conjugate in the presence of targeted and… More

The development of microbial systems for expression of heterologous proteins has enabled the isolation of greater amounts of source proteins, often in greater purity than is posible from the original source. proteins so expressed have applications ranging from industrial use, through protein… More

Regulation of gene expression is critical for cellular and organismal development, and it often plays an important role in expression of heterologous recombinant proteins. Toward development of regulated expression vectors for filamentous fungi that will minimize materials cost and manipulation of… More

The filamentous fungi, owing to their ability to secrete high levels of proteins, are attractive organisms for the expression and secretion of heterologous proteins of commercial and medical value. Secretion is a key element in their attraction; secretion provides the opportunity for complex… More

The overall goals of this project are to develop immunoassays for the detection of bryostatin 1 and its analogues in a variety of biological matrices. the bryostatins have exhibited strong antineoplastic activity in preclinical studies and are scheduled to enter phase i clinical trials later this… More

Murine monoclonal antibodies which neutralize maitotoxin will be selected using a functionalassay that exploits the hemolytic action of maitotoxin. The resulting antibodies should be useful forseveral purposes. They will provide a means to measure the toxin content in crude extracts of fishtissues… More

Dengue viruses are a leading cause of morbidity and mortality throughout the tropics andsubtropics. It is estimated that more than 100 million people in the tropics are infected annually by thisvirus. This threat has now reached the southern United States with the arrival of the Aedes… More

Several fundamental parameters need to be addressed with regard to the development of biosensors. Protein stability is a major criteria for sensors devoted to long-term monitoring. The enzyme label is typically the most unstable componenet in biosensors. Additional problems encountered with… More

The filamentous fungi, owing to their ability to secrete high levels of proteins, are attractive organisms for the expression and secretion of heterologous proteins of commercial and medical value. Secretion is a key element in their attraction, for secretion enables proper folding and processing of… More

We will develop a specific binding protein that has antibody-like diversity but is suitable for higexpression and use in extreme environments. Production of recombinant antibodies in E. coli providessource of active protein for antibody-based technologies, and the small size of the recombinant… More

We will develop high affinity, highly selective, synthetic receptors for small organic molecules. Achemistry approach will be used to produce an encoded, highly diverse, novel type of receptor librarconsists of three peptide arms symmetrically arranged about a rigid hydrophobic pocket. This… More

Dengue virus causes dengue fever, a debilitating illness marked by high fever, headache, muscleand joint pain, and rash. The more severe forms of the illness, dengue hemorrhagic fever and dengueshock syndrome, are life threatening and are a principal cause of hospitalization among children… More

The department of Defense is currently engaged in extensive biosensor research and development efforts. A major goal of these efforts id the development of automated field-usable systems for the detection of a variety of analytes including toxins, infectious organisms, and chemical agents in either… More

The neurotoxins of Clostridium botulinum are the most lethal proteins known. The bacterium is ubiquitous, and thus rapid, reliable, sensitive, and cost-effective assays are needed to detect the toxin. Current immunoassays provide a rapid means to detect the neurotoxin. Their sensitivity, however,… More

Campylobacter jefjuni and Campylobacter coli are significant pathogens of humans. In the United States, the estimated annual incidence of the disease 1-2 million cases costing almost one billion dollars in health care costs and lost productivity. Currently, effective vaccines for do not exist;… More

To ensure safety, it is essential to monitor foods for microbial pathogens. Campylobacter jejuni ancoli are significant food-borne pathogens of humans. In the United States, the estimated annual inci2 million cases costing almost one billion dollars in health care cost and lost productivity.… More

Botulism is a debilitating and often fatal intoxication for which there is no approved pharmacological treatment. The intent of Phase I research is threefold. First, to demonstrate that a combinatorial strategy can be used to identify novel, peptide-based inhibitors of BoNT/A light chain activity.… More

Not Available Impact Technologies in cooperation with the Applied Research Laboratory (ARL) at Penn State University proposes the development and implementation of metric strategies and algorithms to impartially evaluate the performance and effectiveness of diagnostic and prognostic technologies.… More

Not Available The Air Force needs an autonomous service vehicle to inspect, repair, upgrade, or refuel future satellites configured for on-orbit servicing. Such a vehicle must be very low mass, with a high power output for electric propulsion. Conventional ion rockets or arcjets may not have the… More

There are an estimated 76 million cases of foodborne illness in the United States annually, resulting in 325,000 hospitalizations and 5,000 deaths. The financial impact has been estimated at $35 billion. Bacterial pathogens account for 14 million of the total cases. To assure food safety, monitoring… More

DESCRIPTION (provided by the applicant): Malaria is a tropical parasitic disease that poses a significant health threat to much of the world. Each year, approximately 500 million people become infected and more than 2 million die. There is a great need to control the spread… More

DESCRIPTION (provided by the applicant): Malaria is a tropical parasitic disease that poses a significant health threat to much of the world. Each year, approximately 500 million people become infected and more than 2 million die. There is a great need to control the spread… More

DESCRIPTION (Adapted from the application): The goal of this project is to produce a water-soluble anticancer prodrug and an antibody-enzyme conjugate for use in Antibody-Directed Enzyme Prodrug Therapy (ADEPT). The prodrug will be a derivative of 9-aminocamptothecin (9AC), a… More

DESCRIPTION (applicant's abstract): The detection of pesticide residue in foods is a significant issue in food safety. Current analytical methods, however, involve complicated and expensive equipment that requires skilled operators and cannot be readily applied to field… More

DESCRIPTION (provided by applicant): An estimated 150 million people world-wide are infected with the hepatitis C virus (HCV), a major cause of chronic liver disease. The nonstructural protein 3 (NS3) of HCV is a multi-functional enzyme in the replication cycle of the virus and… More

DESCRIPTION: (Adapted from Applicant's Abstract) Malaria is a tropical parasitic disease that is a significant health threat. Each year, approximately 500 million people become infected and 2 to 3 million die worldwide. There is a great need to control the spread of this… More

DESCRIPTION (provided by the applicant): There are 100 million cases of dengue infection each year with 250,000 cases of the life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHS/DSS). Treatment options are limited to symptoms management. Passive… More

DESCRIPTION (provided by applicant): This proposal outlines a novel approach towards the development of a therapeutic agent to treat anthrax infection by inhibiting the intracellular actions of lethal factor, the main virulence factor expressed in Bacillus anthracis infected organisms. While… More

Malaria is a tropical parasitic disease that poses a significant health threat to much of the world. Each year, approximately 500 million become infected and more them 2 million die. There is great need to control the spread of the disease. One of the main focuses of malaria vaccine development has… More

DESCRIPTION (Provided by applicant): The proposed research will investigate the feasibility of utilizing inherent properties of the infection site as a means to activate antifungal prodrugs selectively. Prodrug derivatives of an antifungal agent will be prepared and tested for their susceptibility… More

DESCRIPTION (provided by applicant): West Nile virus infection has become an emerging infectious disease in the United States. The virus infects birds, the natural reservoir of the virus, and is transmitted to humans by the bite of the Culex mosquito. The virus has been found in bird populations… More

DESCRIPTION (provided by applicant): West Nile virus infection is an emerging infectious disease in the United States. The virus infects birds, which serve as the natural reservoir for the virus, in addition to humans and horses which are incidental hosts. It is an arthropod-borne virus, being… More

DESCRIPTION (provided by applicant): Tick-borne encephalitis (TBE) is a neurological disease caused by Flaviviruses of the tick-borne encephalitis group and causes death in up to 60% of the individuals developing clinical symptoms. Survivors often show severe long-term neurological sequelae. In… More

DESCRIPTION (provided by applicant): Current influenza vaccine production procedures (use of embryonated chicken eggs) inherently limit the amount of influenza vaccine that can be produced prior to each year's flu season. Most of the influenza vaccine sold is inactivated. Inactivation of the virus… More

DESCRIPTION (provided by applicant): The strain of West Nile virus now endemic in the continental United States is more virulent than the virus originally isolated in Africa and is classified as a category B priority pathogen by the NIAID. In only six years, it has spread throughout the continental… More

DESCRIPTION (provided by applicant): Over half of the world population is at risk for infection by dengue virus, a mosquito borne member of the Flavivirus family that consists of four distinct serotypes. Approximately 50 to 100 million infections occur annually resulting in an estimated 500,000… More

DESCRIPTION (provided by applicant): Medicinal and computational chemistry methods will be used to optimize validated hit compounds found to inhibit botulinum neurotoxin. These inhibitors, discovered through in silico docking and confirmed with an in vitro fluorescence resonance energy transfer… More

DESCRIPTION (provided by applicant): Tick-borne encephalitis (TBE) is a neurological disease caused by Flaviviruses of the tick-borne encephalitis group and causes death in up to 60% of the individuals developing clinical symptoms. Survivors often show se vere long-term neurological sequelae. In… More

DESCRIPTION (provided by applicant): Emerging and reemerging infectious diseases continue to pose serious health threats world-wide. Consequently, the development of measures to mitigate the natural, as well as potential bioterrorist threats of these infectious diseases is an important endeavor. The… More