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Stimulus Sensitive Multi-functional Biomedical Adhesives Dr. Hoyong Chung 17-042 Garrett Edmunds <p>Functional polymers can be synthesized to have different useful properties through the designed placement of various organic functional groups. Bottlebrush polymers are a type of functional polymer with multiple applications such as replacements for hydrogels, templates for carbon nanotubes, and medical applications.</p> <p>Currently biocompatible polymers are used as coatings on biomedical devices, as micro- and nanoparticles, and even for targeted drug delivery. These polymers can respond to different stimuli but even with various polymers available, it can be difficult to find one polymer that meets multiple requirements in a cost effective manner.</p> <p>An FSU inventor synthesized novel biocompatible polymers. These materials are highly functional and hydrophilic and have tunable properties. They are strong adhesives on multiple surfaces but can also be easily detached. The biomedical adhesives have the potential to greatly improve the medical industry.</p> <h2><strong>Advantages and Applications</strong></h2> <ul> <li>Tunable properties such as stiffness</li> <li>Enhanced adhesion properties on universal surfaces</li> <li>Easily cleaved to decrease adhesion</li> <li>Highly hydrophilic</li> <li>Biocompatible</li> <li>Can be used for</li> <ul> <li>localized drug delivery</li> <li>coatings on biomedical devices</li> <li>biomedical adhesive</li> </ul> </ul>
Lignin-Based Nanoparticles and Smart Polymers Dr. Hoyong Chung 15-122 Garrett Edmunds <p>Smart polymers are materials that are designed to have advanced functionality, enabling a host of new applications. The next challenge in this field is to develop classes of smart polymers that possess multiple complementary functions. Examples include stimulus-responsive materials that are self-healing and pressure-sensitive adhesives that form the basis for nanolithography.</p> <p>Dr. Chung created numerous approaches to developing these materials while incorporating natural, renewable resources, such as lignin, and leveraging advances in polymer chemistry, such as ruthenium metathesis catalysts. These novel materials can offer significant improvements over current production methods of smart polymers and the application of lignin-based materials.  Applications are nearly limitless with properties such as self-healing, shape-memory functionality, and responsiveness to external stimuli while taking advantage of biodegradable, readily available resources.</p>
Combined Gas-Liquid Plasma and Bioreactor Remediation of Liquids and Gases Bruce Locke and Youneng Tang 17-018 Garrett Edmunds <p>An increasing number of types and vast amounts of different complex organic compounds into the natural environment. Of these compounds, the emerging contaminants, those typically not regulated or routinely monitored by government agencies, include a wide range of pharmaceuticals and personal care products (PPCPs), and other compounds that cannot be degraded or removed in conventional drinking water and wastewater treatment processes. Many of these compounds can have adverse effects on the environment, animal, and human health (e.g., endocrine disruption), even at low concentrations. For example, widespread release of antibiotics has led to the evolution of antibiotic resistant bacteria which reduce our capability to manage infectious diseases. Such compounds are released into drinking water, ground water, and wastewater from hospitals, water treatment plants, and distributed sources such as septic field and edge agricultural runoff. Many of these compounds are not readily biodegradable, some are highly persistent in the environment, some may accumulate in the food chain, and some may degrade into more hazardous compounds causing further environmental and health issues. Approximately 700 emerging pollutants, including their metabolic and degradation products, are listed in Europe.</p> <p>Biological reactors offer significant energy efficiency, but require significant residence times, on the order of days or weeks, in order to fully degrade some contaminants. Also, biological reactors are incapable of degrading some toxic organic compounds, or are incapable of completely degrading some organic contaminants to mineralized products. Plasma reactors that only treat liquid contaminants combined with biological reactors are incapable of degrading gas phase contaminants. Such combined systems also are not readily adaptable to changing contaminant composition streams.</p> <p>In order to solve these issues, this novel technology uses a mixture comprising liquid water, a gas and organic compounds, which are injected into a non-thermal gas-liquid plasma discharge reactor to generate a flowing liquid film region with a gas stream flowing alongside. A plasma discharge is propagated along the flowing liquid film region. During this process, water is<br />dissociated and reactive species such as hydroxyl radicals, hydrogen peroxide, and nitrogen oxides are formed. The organic compound reacts with the reactive species such as hydroxyl radicals and hydrogen peroxide present in the flowing liquid film region and in the flowing gas stream to produce organic compound dissociation products. Some of the organic compound dissociation products and nitrogen oxides are transferred to a bioreactor for further degradation. The nitrogen oxides are used as nutrients for bacteria in the bioreactor. The combination of the two reactors saves energy and time on the process of degrading the compounds, thereby cutting costs. Additionally, the increased efficiency of the system is far greater than the addition of the two individual reactors.</p>
Alkylamine-Gold Nanoparticle Monolayers having Tunable Electrical and Optical Properties Daniel Hallinan 16-068 Garrett Edmunds <p>The unique physical and chemical properties of most traditional materials are largely determined by the spatial arrangement of the constituent building blocks (i.e. atoms) relative to one another.  When the scale of the building blocks extend to the range outside that of atomic elements (e.g. nanoparticles), the 'artificial solids' composed of such nanoparticles exhibit unique properties different from their bulk counterparts. In particular, monolayer two-dimensional (2D) artificial solids, serving as the structural basis for more complicated nanostructures, display distinct collective optical, electrical, and catalytic properties, thus finding vast prospective applications in high-performance solar cells, electrogenerated chemilumines, chemical sensors, transistors, integrated microcircuitry, batteries, capacitors, and thermolectrics. Akin to traditional materials, the physical and chemical properties of artificial solids are not only dependent on the elementary nanoparticle size and shape, but as importantly on the interparticle separation and the periodic arrangement of the constituents.</p> <p>FSU researchers have successfully prepared monolayer gold nanoparticle (Au NP) films using a water/organic solvent self-assembly strategy. A new approach, “drain to deposit”, is demonstrated most effective to transfer the Au NP films from a liquid/liquid interface to various solid substrates while maintaining their integrity. The interparticle spacing was tuned from 1.4 nm to 3.1 nm using different length alkylamine ligands. The ordering of the films increased with increasing ligand length. The surface plasmon resonance and the in-plane conductivity of the Au NP films both exhibit an exponential dependence on the particle spacing. These findings show great potential in scaling up the fabrication of high-performance optical and electronic devices based on metallic nanoparticle superlattices.</p> <p>In addition, these FSU researchers have developed a three phase system for depositing monolayer gold nanoparticle films. Using this three-phase system, centimeter-scale monolayer gold nanoparticle (Au NP) films have been prepared that have long-range order and hydrophobic ligands. The system contains an interface between an aqueous phase containing Au NPs and an oil phase containing one of various types of amine ligands, and a water/air interface. As the Au NPs diffuse to the water/oil interface, ligand exchange takes place which temporarily traps them at the water/oil interface. The ligand exchanged particles then spontaneously migrate to the air/water interface, where they self-assemble, forming a monolayer under certain conditions. The spontaneous formation of the NP film at the air/water interface was due to the minimization of the system Helmholtz free energy. However, the extent of surface functionalization was dictated by kinetics. This decouples interfacial ligand exchange  from interfacial self-assembly, while maintaining the simplicity of a single system. The interparticle center-to-center distance was dictated by the amine ligand length. The Au NP monolayers exhibit tunable surface plasma resonance and excellent spatial homogeneity, which is useful for surface-enhanced Raman scattering. The “air/water/oil” self-assembly method developed here not only benefits the fundamental understanding of NP ligand conformations, but is also applicable to the manufacture of plasmonic nanoparticle devices with precisely designed optical properties.</p> <h1>Applications and Advantages</h1> <ul> <li>Batteries <ul> <li>Electric car</li> <li>Laptop</li> <li>Mobile device</li> <li>Other electric vehicles and locomotion devices</li> </ul> </li> <li>Extremely precise detection of compounds</li> <li>Increases reliability of batteries</li> <li>Increases the performances of batteries</li> <li>Reduces the possibility of catastrophic failure of devices due to battery failure</li> </ul> <p> </p> <p> </p>
A Method of Producing Extracellular Metal or Metalloid Nanoparticles Using a Bioreactor Youneng Tang 18-031 Brittany Ferraro <p>Metals and metal ions are essential trace elements for humans and animals. However, when presenting in water at high concentrations, they are often toxic and can cause diseases such as hair loss and reproductive failure. Consequently, metal and metal ion contamination represent a potential health hazard. A major cause of contamination in water is the disposal of agricultural drainage. Selenium (Se) is one such element, and can be used to exemplify the hazards of metal and metal ion contamination. The maximum contaminant level set by U.S. Environmental Protection Agency for Se in drinking water is 50 μg Se/L.</p> <p>Thus, this technology is directed to bio-electrochemical reactors, methods of reducing metal ions in contaminated medium to extracellular metal or metalloid nanoparticles, and methods and devices for separating the extracellular metal or metalloid nanoparticles from the bacteria. For example, the bio-electrochemical reactor is used as a selector to select only bacteria that<br />produce extracellular metal or metalloid nanoparticles from an electrode inoculum comprising a highly diverse mixed culture. As a result, the bio-electrochemical reactors described serve as an effective means for removing and separating metal ions from contaminated water.</p>
Drugs for the Treatment of Zika Virus Infections Hengli Tang 16-114 Brent Edington <p>The Zika virus is a Flavivirus that is spread to humans through mosquito bites. It is presently a major human health concern. When pregnant women are infected the virus can be transferred to the baby and result in microcephaly and other sever brain problems. Infections can also result in Guillain-Barre syndrome in adults and children, a neurological syndrome that can cause temporary paralysis. There are presently no vaccines or medications capable of preventing or treating Zika virus infections.</p> <p>Various libraries of known compounds have been screened for their ability to inhibit Zika virus infections. A collection of compounds has been identified which have activity against Zikda virus replication and growth. These compounds have been assessed and ranked according to efficacy in test assays and suitability as therapeutic compounds.</p>
Space Efficient Photobioreactor System Jose Vargas 10-090 Brittany Ferraro <p>The continued use of petroleum-derived fuels is now widely seen as unsustainable. Presently available biofuels can be substituted for petroleum-derived fuels without the need for extensively modifying existing internal combustion engines.</p> <p>The present invention describes a microalgae-based bio-fuels production system in a space efficient photo-bioreactor. The bioreactor grows microalgae in a tall array of transparent flooded tubes. A nutrient media is circulated through the tubes. The array is configured to maximize the amount of sunlight falling upon each tube so that growth of the microalgae is as uniform as possible. Gassing/degassing systems are attached to the array of tubes at appropriate locations. These introduce carbon dioxide and remove oxygen. Cooling systems are preferably also provided so that the circulating media can be maintained at a desired temperature. Microalgae are harvested from the photo-bioreactor. The microalgae are filtered and dried. Lipids are then extracted from the microalgae. These lipids are made into biodiesel through a trans-esterification process and can be used to make other products as well.</p> <h2>Advantages:</h2> <ul> <li>Compact microalgae cultivation in a high productive manner</li> <li>Reduces the need for land since it has the potential to provide higher biomass production density than traditional systems of microalgae biomass production</li> <li>The modular conception allows for the gradual implementation of the system for in situ biofuel production wherever it is needed</li> </ul>
Organic Chemical Synthesis using Plasma Reactors with Liquid Organic and Liquid Water Bruce Locke 13-153 Garrett Edmunds <p>Electrical discharge plasma contacting liquid phases has been studied for a wide range of chemical, biomedical, environmental, and Materials synthesis applications.  The present invention utilizes a gas-water-organic plasma reactor for the conversion of alkanes into functionalized products (alcohols, aldehydes, etc.) using a pulsed plasma reactor with liquid water and flowing carrier gas. Hydrogen peroxide is also generated conjunction with the functionalized products.</p> <h1>Applications</h1> <ul> <li>Agriculture</li> <li>Healthcare</li> <li>Sanitization</li> <li>Waste water degradation</li> </ul>
Mesenchymal Stem Cells (MSC) Expansion Teng Ma 11-054 Brittany Ferraro <p>The present invention describes materials and methods for growing and expanding mammalian mesenchymal stem cells (MSC) while maintaining their undifferentiated phenotype, self-renewal ability, therapeutic potency, and/or multi-lineage potential. The method describes i) the seeding of freshly isolated MSC on a 3-D scaffold and their growth under physiological or low O2 tension for a period of time sufficient to support formation of 3-D extracellular matrix (ECM) network; ii) the decellularizing of the 3-D scaffold; and iii) the reseeding of the decellularized 3-D scaffold with MSCs, whereby the reseeded MSCs grow on the scaffold and maintain an undifferentiated phenotype. The 3-D scaffold comprises or is composed of poly(ethylene terephthalate) (PET).</p> <p>A faster production of highly potent human MSC is obtained using our methodology based on combining hypoxia and cell-derived ECM compared with the traditional culture methods utilizing growth factor supplements and a high concentration of serum.</p> <h2>Advantages:</h2> <ul> <li>Expands hMSC faster than the conventional methods</li> <li>Better presses hMSC's therapeutic potency compared with the traditional culture methods</li> <li>Requires a low concentration of serum and requires no exogenous factors to be added to expand the cells</li> </ul>
Materials and Methods for Cryopreserved Bone Contstructs Teng Ma 11-011 Garrett Edmunds <p>The technology developed includes materials and methods for cryo-preservation of HCG-cell constructs. In one embodiment, porous HCG scaffolds are provided in a perfusion bioreactor having perfusion chambers that can contain the HCG scaffolds, cells are then seeded in the HCG scaffolds in the perfusion bioreactor, cell culture media is perfused through and the bioreactor operated so as to allow for cell seeding and growth in the HCG scaffold. After a suitable period of time, the cell culture media is removed and the HCG containing cells (HCG-cell constructs) can be washed with a suitable buffer, such as phosphate-buffered saline (PBS). The HCG-cell constructs are then perfused with a suitable cryo-preservation fluid transversely across the HCG-cell constructs in the bioreactor. The cryo-preservant can comprise one or more of the following: DMSO, trehalose, glycerol, ethylene glycol, and serum for cell culture (e. g., fetal bovine serum (FBS)). In one embodiment, the HCG-cell constructs are perfused for a suitable period of time with cryo-preservant fluid using transverse flow of the fluid in the bioreactor at a suitable flow rate. The HCG-cell constructs (or the perfusion chambers containing them) are then removed from the bioreactor and placed in a cryo-preservant media and maintained at increasingly colder temperatures until temperatures reach about  -80° C. The frozen HCG-cell constructs (or the chambers containing them) can then be stored at a suitable cryogenic temperature (e.g., in liquid nitrogen) until needed. When needed, frozen HCG-cell constructs can be removed from cold storage and thawed using suitable means (e. g., 37°C. water bath). Cells contemplated for use in the presentinvention include stem cells, such mesenchymal stem cells.Cells can be animal cells, such as mammalian cells or human cells.</p>
Bioreactor for Stem Cell Cultivation Teng Ma 03-001 Brittany Ferraro <p>Maintaining adult stem cell lines is an important aspect of future research and development. The perfusion bioreactor mimics conditions encountered by adult stem cells within the human body by bathing stem cells in a protein-rich liquid and simulating the flow of the human body’s circulatory system. The reactor creates the ability to control what type of cells the stem cells become.</p> <p>The present technology enables automated seeding, harvesting, and transport, while sustaining high density human hematopoietic stem/progenitor cell expansion and RBC differentiation.</p> <h2>Advantages:</h2> <ul> <li>Allows for greater cell viability due to the lack of enzymatic treatment of the cells when harvesting</li> <li>Allows for significantly greater cell densities to be achieved than previously available technology</li> <li>Ability to direct differentiation and therefore control the type of cells ultimately produced</li> <li>Uses a “smart” coating that enables on-off affinity control between the cells and the scaffolds to achieve automated cell harvesting and transport. This feature eliminates the need for enzymatic treatment which simplifies large scale growth and increases the viable cell yield</li> <li>Modular design allows for the removal of individual flow chambers without interrupting the system. This is an attractive feature for research use where multiple samples are needed at various times</li> </ul>
Monoclonal Antibodies for the Detection of Various Species Including Specific Consumed Meats and Bloods. Yun-Hwa Hsieh 15-199, 16-083 Brent Edington <p>The monoclonal antibodies developed by Dr. Hsieh detect various species of fish, bovine, equine, chicken, sheep, porcine, bovine blood, porcine blood, chicken blood, turkey blood, bovine spinal column. These can be used in immunoassays to differentiate the source of protein and blood protein.</p>
Comprehensive, Genome-Wide Epigenetic Fingerprinting by Replication Profiling David Gilbert 07-106 Brent Edington <p>This is a procedure for typing cells (cancer cells, stem cells, any kind of cells) based upon the order of replication of chromosome segments. In brief, cells from any source are pulse-labeled with 5-bromo-2deoxyuridine, sorted into early and late S-phase of the cell cycle by flow cytometry and the DNA replicated in each temporal compartment of S-phase is differentially labeled and hybridized to a DNA array consisting of evenly spaced probes from the entire genome. Using customized algorithms, the resulting data (ratio of each probe sequence replicated in early vs. late S-phase) can be converted into a form that can segment the genome and identify the order of replication of chromosome segments characteristic for a cell type. An alternative, if the cell line is difficult to label metabolically, is to sort cells into S-phase and G1-phase populations, hybridize differential labeled DNA from these sorted populations, and determine the ratio of each probe sequence in S vs G1. This provides similar data that can be evaluated by the same computational conversion.</p> <h2>Advantages:</h2> <ul> <li>More comprehensive (covers the entire genome)</li> <li>Less expensive (covers the entire genome for less than 1/20th what is needed for existing profiling methods)</li> <li>Much easier to interpret- the informative data for each cell line is distilled down to combinations of only about 1,000-2,000 segments of the genome that uniformly identify each cell type</li> <li>Measures very different properties of cells than any other method</li> <li>Focuses the analysis on the proliferating population of cells, which is particularly useful for stem cell and cancer technologies.</li> </ul>
A Peptide Building Block for P-trefoil Protein Architecture Dr. Blaber 10-114 Brent Edington <p>Protein folding is a poorly understood science, and therefore, protein engineering has yet to realize the functional potential inherent in proteins. Development of a useful "structural toolkit" for de novo protein design is a highly desirable, yet unrealized goal of the field.</p> <p>A novel 42 amino acid polypeptide sequence has been designed that spontaneously assembles into a homo-trimer, forming a thermostable P-trefoil protein architecture. The polypeptide can also be ligated, to form three identical repeating sequences within a single polypeptide, which also spontaneously folds into a thermostable P-trefoil protein architecture. The peptide is thus useful for either de novo design, rational design, or directed evolution of novel proteins based upon the P-trefoil architecture. The Invention represents an initial successful example of the development of a useful peptide building block for a common protein architecture (the P-trefoil).</p> <p>The peptide sequence was designed using a novel approach, and as a consequence there are an extremely limited number of useful related "building blocks" in protein design. The idea of a "structural toolkit" for protein design is largely conceptual; the current Invention is arguably one of the first successful examples.</p>
Antibody Biomarker Specific for Mitotic Cells Myra Hurt and Raed Rizkallah 11-048 Brent Edington <p>An isolated monoclonal antibody that has a specific binding affinity to a polypeptide comprising the amino acid sequence HTEGKP phosphorylated at the threonine residue. The antibody may be used as a biomarker for mitotic cells. Proliferation biomarkers are of indispensable value in cell cycle research. More importantly, many of these markers have been translated into valuable cancer prognostic and diagnostic tools, particularly those used to assess the mitotic index of a cellular mixture.</p>
Evaporative Edge Lithography (EEL) of a Liposomal Drug Microarray for Cell Migration Assays Dr. Lenhert 13-035 Brent Edington <p>The proposed invention is capable of producing linear lipid multilayer nanostructures along the edge of a stencil. The thickness of these lipid films is controlled that results in controlling dosage of material that is taken up by cells cultured over these areas. Unlike other migration assays, this approach makes it possible to screen different compounds and dosages on the same surface, with scalability for high throughput screening microarrays to assay for cell migration. Additionally, the drug or small molecules encapsulated will only be delivered to cells at the edge of the stencil because of the precipitation properties which can be important to selectively affect the migrating cells at the edge from non-migratory cells. This invention utilizes lipids as the bio compatible patterning materials, which have been used previously to create surface supported monolayers mainly to detect functionality in reconstituted proteins and to measure membrane diffusion. </p> <p>Creating bio-compatible films with defined features is important for materials research as these patterned surfaces can give rise to cellular responses such as differentiation, migration, alignment, and other cellular mechanisms. This research is important for biomedical applications such as implants, stents, and other devices surgically implanted in humans.</p>
Folding Nucleus Symmetric Expansion Michael Blaber 14-163 Brent Edington <p>The present technology is a novel method and design strategy for the efficient design of de novo proteins. This invention uses experimental or computation methods to identify an amino acid sequence that defines a folding nucleus of a protein that belongs to a symmetric protein architecture. Next, a complete amino acid sequence for the target architecture is generated by expanding the folding nucleus sequence by the intrinsic symmetry. The resulting protein will have robust folding properties that can tolerate subsequent mutational introduction of novel function. This process is an efficient means to create novel protein scaffolds with robust folding properties.</p> <h2>Advantages:</h2> <ul> <li>Leverages knowledge of naturally-evolved proteins for application in the design of novel proteins</li> <li>Uses a simple algorithm that permits design of the complete protein</li> <li>Produces a protein with highly-redundant folding potential- a protein that can therefore tolerate substantial mutational change and still yield a foldable protein.</li> </ul>
TrkB Receptor Antagonist for Treatment of Cognitive Inflexibility Pradeep G. Bhide 15-137 Brent Edington <p>Cognitive flexibility is the ability to execute multiple mental tasks simultaneously, to switch from one task to the next easily, and to restructure knowledge and strategy to tackle changing tasks. Deficits in cognitive flexibility are associated with multiple psychiatric conditions including schizophrenia, autism spectrum disorder and ADHD. Despite its critical role in normal mental function, and despite its well documented associated impairment, drugs that selectively target and improve cognitive flexibility are not available.</p> <p>The present technology shows that excess brain derived growth factor (BDGF) is associated with deficits in cognitive flexibility and that ANA-12 is an effective treatment for cognitive ability.</p>
Monoclonal Antibodies Specific for 4,6-Diamino-5-(Formylamino) Pyrimidine Gary Ostrander and Eric Holmes 16-019 Brent Edington <p>The present invention describes monoclonal antibodies that are specific for 4,6-Diamino-5-(formylamino)pyrimidine. This structure, also known as FAPY-A, is formed in DNA bases by single electron oxidation reactions caused primarily by oxygen free radicals. Damage to DNA of this sort, along with its alternate product 8-hytdroxy-pyrimidine derivatives, can result in mutations from misreading if not first repaired. In the case of free radical oxidations of the DNA base Adenine, FAPY-A and 8-OH-A formed under more oxidative redox conditions. These different reaction products and their expression in biological tissues to correlate well with precancerous and cancerous changes in tissues. Thus, detection of FAPY-A and 8-OH-A via immunoassay may provide important future cancer risk information to individuals. Detection of FAPY-A in populations of various species can also act as an indicator of environmental damage.  </p>
Identifying Cell and Disease-Specific Replication Timing Signatures David Gilbert 16-102 Brent Edington <p>Methods for identifying and classifying differences between biological samples are based on replication timing data. By comparing replication timing data for a test sample(s) to replication timing data for already characterized samples, one can identify differences and profile any new cell type or disease including various cancers. These new methods allow for detection of all the changes between distinct samples, many of which would escape detection by previous methods that discard any features showing any intra-sample variation. This method also has the ability to use replication timing to identify novel biomarkers not detected by other methods.</p>
Treatment of Lipid Encapsulated Surface Supported Drug Multilayers for In Vitro Delivery to Cells Steven Lenhert 18-006 Brent Edington <p>Fluid Phospholipids have demonstrated their usefulness in biotechnology and biomimetic applications such as cell modeling and drug delivery. However, their exploitation has been limited to low throughput applications due to the instability of supported lipid multilayers to aqueous immersion. Our researchers have been successful in the immersion of supported lipid multilayers in simple buffers, immersion under high-protein-content media has remained a challenge.</p> <p>Screening the effects of small molecules on cells grown in culture is a well-established method for drug discovery and testing, and faster throughput at lower cost is needed. Small molecule arrays and microfluidics are promising approaches. This technology consists of devices involving a microarray of lipid multilayers combined with silicon containing compounds to form a hybrid silicon based assembly on the surface of the lipid multilayer dot.</p> <p>The devices can provide a surface mediated delivery of drugs to cells from the microarray of lipid multilayers encapsulating drug. The multilayer patterns can be of sub-cellular dimensions and controllable thickness and can be formed by dip-pen nanolithography. The patterns can successfully deliver a small molecule only to the cells directly over them, resulting in no cross-contamination to cells grown next to the patterns.</p> <p>There is a need for lipid multilayer arrays that are stable in cell-based applications, stability of lipid multilayer arrays under high protein cell culture media, and for lipid multilayer arrays that allow for viable cell adhesion. Our researchers have developed lipid multilayer array devices which exhibit increased stability in cell-based applications such as high protein cull culture media, as well as allow for viable cell adhesion.</p>
Fusicoccane Derivatives and Methods Prof. James Frederich 17-039 Garrett Edmunds <p>Fusicoccanes are a family of natural products containing a characteristic 5-8-5 carbocyclic nucleus. Certain of these natural products, namely fusicoccin (FC) and cotylenin (CN), have attracted considerable interest for their anticancer activity. These molecules cooperate with the cytokine interferon-alpha to induce apoptosis in cancer cells with negligible toxicity to healthy cells.</p> <p>Professor Frederich and his team have developed a short and flexible photochemical process to prepare the core of these diterpenes and a range of non-natural variants. This synthetic chemistry provides direct access to functional structures with valuable applications in biomedical research and drug development.</p> <p>In the news:</p> <p><a href=""></a></p> <p><span><a href=";d=DwMFaQ&amp;c=HPMtquzZjKY31rtkyGRFnQ&amp;r=WPBE5mf0vyLaRUqjuwH1sg&amp;m=gds5bbavh_mOdw_HPOAn-28dTWw1TVDSjNLAhAIdhfg&amp;s=YwFs1A7P4BnsXk0ndHmTkrtzEkJGOnu34P3vz9tJhDg&amp;e=">Breakthrough synthesis strategy could mean a wave of new medicinal compounds</a></span></p> <p><span><a href=";d=DwMFaQ&amp;c=HPMtquzZjKY31rtkyGRFnQ&amp;r=WPBE5mf0vyLaRUqjuwH1sg&amp;m=gds5bbavh_mOdw_HPOAn-28dTWw1TVDSjNLAhAIdhfg&amp;s=wihplsHAdfgWkE8eGtsvfmv-mG2oqhmU0B6p4xbHTlQ&amp;e=">Innovative synthetic technique opens door to a new world of cutting-edge medicinal compounds</a></span></p> <p> </p>
Tumor Drug Resistance Measured by Sodium Diffusion Dr. Schepkin 12-106 Matthieu Dumont <p>This invention is a non-invasive, comprehensive and individualized evaluation of tumor resistance using sodium and/or diffusion magnetic resonance imaging (MRI). The method includes conducting a sodium and/or diffusion MRI on a tumor of a subject and on a normal region of the subject- for example, the normal region in brain being contralateral to the tumor. When the images of the MRI procedures have been obtained, the indicias (i.e., sodium and/or diffusion) are measured and analyzed. These indicias are compared between the tumor region and normal region. A low level of the indicia in the tumor region, relative to the level of indicia in the normal region, indicates a higher/increased tumor resistance to a drug.</p> <p>Currently, a biopsy and Positron emission tomography (PET) are the conventional technologies used to deliver information on tumor resistance prior to therapy. The evaluation can be performed prior to therapy and can help select a strategy of treatment but also help in evaluating the efficacy of an agent for the treatment of cancer in a subject. The invention can be used in the brain glioma model but is contemplated for use in different types of tumors in most parts of the human body in addition the agent may be carmustine, though other tumor types and agents are contemplated by the invention. The level of tumor resistance can be determined reproducibly in a relatively short amount of time, for example less than thirty minutes, and the results can be used immediately to create individualized therapy.</p> <p>The invention allows clinicians to avoid ineffective therapies, which may be more harmful than useful or come up with the other more appropriate alternatives. It can facilitate a separation of the effects due to metabolic changes in the tumor at the beginning of therapy from the effects introduced by drug intervention.</p>
Thiol-ene polymer metal oxide nanoparticle high refractive index composites Dr. Albert Stiegman 12-228 Garrett Edmunds <p>For optical applications in general and eyewear in particular, the synthesis of new polymers with refractive indices &gt;1.65 and acceptable Abbe numbers is of considerable importance. Higher refractive index materials will permit smaller, lighter weight lenses to be used and provide a much broader graded index for progressive lenses. The material modification that leads to higher refractive indices is the incorporation of highly polarizable atoms and ions. Incorporating such polarizable groups has been the standard protocol used to develop new high R.I. polymers. The electronic polarizability is a tensor property of an atom or molecule that measures the distortion of the electron cloud in the presence of an applied electric field (which can be an optical field). The more the electron cloud can be distorted, the higher the refractive index. The characteristics of atomic and molecular electronic structure that yield large polarizabilities are well understood and can be predicted from basic chemical principles. In particular, the more electronegative an atom is the less polarizable it will be, hence late first-row elements such as F, O and N tend to yield lower refractive index materials. Better choices are 2<sup class="style-scope patent-text">nd</sup>, 3<sup class="style-scope patent-text">rd </sup>or 4<sup class="style-scope patent-text">th </sup>row main group elements such as S (which is currently used in order to increase the refractive index in many polymeric materials), P, and Sn. From a molecular standpoint, the higher electronegativity of the first row can be overcome by delocalization of the electrons across several atoms. Aromatics are more polarizable than saturated hydrocarbons and compounds such as propylene carbonate and dimethylformamide have high dielectric constants.</p> <p>the present invention comprises a bulk polymer composite comprising a thiol-ene polymer matrix, or a matrix comprising a corresponding polymer derived from a phosphinyl, selenol, or arsinyl monomer, and metal oxide nanoparticles dispersed within the matrix, said nanoparticles being bonded to polymer molecules contained in the matrix. In certain preferred embodiments, the polymer matrix comprises a matrix corresponding to the structure.</p>
Antifouling Coatings Professor Joseph Schlenoff 17-053 Garrett Edmunds <p>Professor Schlenoff and his team have developed an ion exchange resin associated with a polyelectrolyte that <span>reduces the fouling of the ion exchange resins or renders it nonfouling. This without impacting the ion exchange capacity of resin, even when applied with an anion exchange resin.  </span></p> <p>Ion exchange resins (IERs) and membranes have been widely used for water treatment and purification processes.  Anion exchange resins (AER) may be employed for the removal of natural organic matter (NOM), which typically is mostly anionic. However, the use of AERs has been limited, at least in part, by fouling.  Typically, fouling is caused at least in part by organic substances, such as humic and fulvic acids, Resin fouling has been reported to cause capacity and performance losses especially during repeated uses in cyclic and long-term operations. A component of NOM in raw waters include algal cells and algae-derived precursors, which can cause water contamination by the formation of disinfection byproducts (DBPs).  Resins are also used for water softening and demineralization. In these applications, the adsorption of pollutants and organic substances typically is unfavorable for the optimum performance of the deionizer. Ion exchange resins are usually continuously submerged in water, and thus subjected to the settlement of marine organisms, e.g. algal cells.</p> <p> </p> water,filter,water purification,potable water,ion exchange resin
Microfluidic Sample Preparation Device for Electron Microscopy Dr. Michael Roper and Dr. Scott Stagg 15-230 Garrett Edmunds <p>Cryogenic electron microscopy (cryoEM) is quickly becoming a routine method in the determination of high-resolution structures of biological molecules. However, for most samples before cryoEM data can be collected, the sample quality and heterogeneity must first be characterized using negative staining. Conventionally, EM grids are prepared by hand and, as such, variability is introduced due to user-to-user differences. The variability of the staining can have large effects on the final stained sample, ultimately hindering the resolution, image processing, and data analysis.</p> <p>A microfluidic platform is presented for preparing negatively stained grids for use in transmission electron microscopy (EM). The microfluidic device is composed of glass etched with readily fabricated features that facilitate the extraction of the grid post staining and maintains the integrity of the sample. The device allows for sealing of an electron microscopy grid, facile and reproducible delivery of a sample, followed by delivery of subsequent solutions that could be negative stains or other biological samples. The device houses the EM grid in an outlined chamber with an access point below the grid for gentle and easy recovery of the EM grid. The fluid is directed to the grid using the integrated channels of the microfluidic system.</p> <p>Utilization of this device simultaneously reduced environmental contamination on the grids and improved the homogeneity of the heavy metal stain needed to enhance visualization of biological specimens as compared to conventionally prepared EM grids.</p> <p>High-magnification images from grids prepared by the microfluidic system showed similar image qualities as those prepared by hand. With this methodology for housing the grid, opportunities are abound for more integrated systems using elastomeric materials for incorporation of valving and other microfluidic features. For example, this system can subsequently be complemented with gradient generators or multianalyte perfusion and reaction timers to study both multivariable interactions as well as reaction kinetics. This proof</p> <p>of principle paves the way for future added layers of complexity that can be used to uniquely investigate structural biology dynamics.</p> <h2>Advantages:</h2> <ul> <li>User friendly</li> <li>Reproducibility</li> <li>Parallel/high throughput</li> <li>Results have been published in Analytical Chemistry (Roper, 2016, American Chemical Society Publications) and led to multiple requests by research groups offering to beta test the prototype.</li> <li>Straightforward manufacturing</li> </ul> <p>For further reading, please visit:</p> <p><a href=""><strong></strong></a><strong> <br /></strong></p> <p><a href=""><strong></strong></a></p> <p><video alt="" width="400" controls="controls"> <source src="/media/4180/rs4-fin.mp4" type="video/mp4" /> Your browser does not support HTML5 video. </video></p>
Mutations of the Rhodopsin Gene in Zebrafish and uses of the Mutations James Fadool 17-038 Brent Edington <p>The invention involves isolation and use of zebrafish having novel genetic mutations in the rhodopsin genes dealing with retinal disease to serve as a model for human retinal disease. Rhodopsin is a protein receptor expressed in the light sensitive cells of the retina responsible for initiation of vision. Nearly 100 spontaneous mutations in the human rhodopsin genes are associated with inherited photoreceptor degeneration, retinitis pigmentosa, progressive retinal degeneration, low vision and blindness for which there are currently no cures. The novel zebrafish models were generated to produce known disease causing mutations in the zebrafish rhodopsin genes. DNA sequencing revealed the novelty of the isolated zebrafish mutations. Analysis of the retinal phenotypes associated with the novel alleles of zebrafish rhodopsin genes revealed that specific mutations were associated with phenotypes that mimic photoreceptor defects and degeneration observed in humans. These zebrafish models provide novel tools for investigating the cellular consequences of expression of mutated forms of rhodopsin, and are useful for genetic, small molecule, and chemical screens, or molecular manipulations with the goal of discovering compounds, genes, or treatments that may alter, slow, reverse or prevent the photoreceptor defects.  </p>
Dorsiflexion Splinting for Treatment of Peripheral Artery Disease Judy Delp 18-013 Brent Edington <p>Patients with peripheral arterial disease (PAD) often have walking impairment and pain during walking due to insufficient oxygen supply to the leg muscles. Existing clinical treatment of PAD involves walking programs or revascularization. Surgery can carry significant costs and risks of acute complications from, for instance, recurrences due to restenosis or graft occlusion. Adherence to long-term walking programs can be difficult for frail patients such as the elderly. Although, stretching of calf muscles improves vascular function in the lower leg. Use of a splint developed by researchers at Florida State University can enhance a patient’s vascular function by improving blood flow to the leg and decrease in pain during walking. The splint positions the leg and stretches muscles in a way that improves blood flow and/or oxygenation while resting. This device will be automated to easily adjust to the correct position for optimum therapeutic value for each patient.</p>
Personalized immunotherapy selection for breast cancer Professor Qing-Xiang Amy Sang and Professor Jinfeng Zhang 17-046 Garrett Edmunds <p>Professors Sang and Zhang  have identified biomarkers that define subgroups of breast cancer and clinically useful classifiers for distinguishing breast cancer subtypes.  The present invention provides methods for selecting a therapy for a patient suffering from breast cancer based on expression levels of biomarkers.  The present invention also provides methods for treating breast cancer. </p>
CHIMERIC HUMAN PROTEINS AND THEIR USE IN IDENTIFYING NOVEL ANTI-DEUBIQUITINASE COMPOUNDS Robert Tomko 18-005 Brent Edington <p>This technology involves chimeric proteins having deubiquitinase activity and methods of identifying anti-deubiquitinase compounds using the chimeric proteins. These methods and assays can be adapted to high throughput screening procedures to assay for anti-cancer drugs effecting deubiquitinase activity. Disrupting the Rpn11 deubiquitinase function is a validated strategy for treatment of human cancers.</p> <p>The assay utilizes a collection of genetically modified yeast strains producing a chimeric human proteasomal Rpn11 deubiquitinase. In baker’s yeast, deletion of the endogenous yeast Rpn11 gene is lethal, but inhibition of Rpn11 deubiquitinating activity is not. Inhibition of Rpn11 activity is lethal only when a second deubiquitinase, UBP6 (USP14 in humans), is deleted. Importantly, this synthetic lethal relationship is maintained in yeast harboring hRpn11. Thus, a selective inhibitor of human Rpn11 would be lethal in the hRpn11 strain lacking UBP6, but nontoxic in a strain containing UBP6 and harboring inactivating point mutations in hRpn11.By measuring cell growth in the presence of potential inhibitors using any commercially available plate reader, a high throughput cell-based screen for compounds selectively inhibiting hRpn11 can be enacted.</p>
Novel Therapeutic Agent Sequestering Toxic Levels of Hemin in Cardiovascular Injury Events Ewa Bienkiewicz 11-154 16-110 Brent Edington <p>In vascular injury, one of the key damage-inflicting events is the release of toxic levels of free hemin that leads to cell and tissue death.  Currently, there is no direct treatment to alleviate hemin toxicity that exacerbates tissue damage during injury events. Our technology offers a solution to this damage with a peptide therapeutic agent that would serve as a high-capacity scavenger of the toxic hemin released during vascular trauma. This technology proposes the use of a peptide to sequester excess hemin and alleviate the extent of injury.</p> <p>We have shown that peptide fragments derived from the N-terminal domain of the normal, non-pathological prion protein, bind hemin.  Each peptide can bind more than one hemin molecule.  The hemin binding capacity of these peptides increases in an acidic environment, which is characteristic of vascular injury, including stroke.  These findings make the prion protein fragments, or their analogs, strong candidates for a therapeutic agent that would act as a “hemin sponge” sequestering the toxic hemin molecules. </p> <p>An important aspect of the developed product is that our peptide fragments originate from a naturally occurring protein that is essential in maintaining hemin equilibrium in our bodies, and has been shown to be a part of a cell rescue response in vascular trauma. Delivery of this high-capacity, hemin-sequestering peptide as a therapeutic agent would effectively amount to a boost of the natural defense mechanism against excess of hemin.  Overall, this therapeutic agent would diminish the damaging effects of the vascular injury, including stroke, significantly improving patients’ chances for survival and full recovery.</p>
Modified Fibroblast Growth Factor 1 (FGF-1) Polypeptides with Increased Binding Affinity for Heparin and Associated Methods Michael Blaber 15-039 Brent Edington <p>A Mutant FGF-1 was designed so as to increase the intrinsic affinity for heparin sulfate glycosaminoglycan; involving a point mutation that introduces a basic amino acid (i.e. Arg or Lys) at position Ser116. Characterization of this mutant (S116R) shows reduction in mitogenic stimulation, increase in growth factor receptor-1c activation, and prolonged duration of glucose lowering in hyperglycemic mice. Such a mutant form can be advantageous in reducing blood glucose and as a novel insulin sensitizer to treat metabolic disorder.   </p>
Method of Treating Multiple Sclerosis with Anti-K6 Antibody Michael Blaber 03-013 Brent Edington <p>This invention is based on the discovery that modulators of kallikrein 6 can alter pathogenesis of inflammatory cell mediated diseases both within the central nervous system and in the periphery. As a result, modulators of kallikrein 6 can aid in the treatment and prevention of inflammatory conditions such as MS, rheumatoid arthritis, lupus, and asthma. An antibody having specific binding affinity for kallikrein 6 reduced the degree of demyelination and reduced behavioral defects in animal models of multiple sclerosis.</p> multiple sclerosis,rheumatoid arthritis,lupus,and asthma
Device and Method for Concomitant Ejection and Suction of Perfusate Sanjay Kumar 15-008 Brent Edington <p>CESOP is a microfluidic device that enables focal application and clearance of drugs/compounds to nuclei or regions within acute brain slices submerged in artificial cerebrospinal fluid or other bathing media under non-laminar/turbulent flow conditions. The CESOP technique has distinct advantages over either both perfusion or local perfusion for studying how drug application to one region of the brain affects a neighboring/juxtaposed region. The CESOP device/method enables rapid focal application of drugs/compounds while restricting their spillover to neighboring regions. Turbulent/non-laminar flow conditions that manifest in slice recording chambers exacerbate spillover thereby hindering electrophysiological recordings and the study of region-specific drug effects. CESOP solves this problem through concomitant ejection and suction of perfusate, even under moderately turbulent conditions.</p> <h2>Advantages:</h2> <ul> <li>Rapid and focal delivery of drugs/compounds to regions of interest within the tissue with minimal or no spillover</li> <li>Fine control of application area</li> <li>Mobility within the restricted environs of the recording chamber/scope</li> <li>Savings in precious drug volumes while assaying drug effects</li> <li>Feasibility for assaying reversibility of drug effects</li> <li>Cost-effective</li> </ul>
Device and Method for Concomitant Ejection and Suction of Perfusate Sanjay Kumar 15-008 Brent Edington <p>CESOP is a microfluidic device that enables  focal application and clearance of drugs/compounds  (perfusate) to nuclei or regions within acute brain slices submerged in artificial cerebrospinal  fluid or other bathing media under non-laminar/ turbulent now conditions. The CESOP technique has distinct advantages over either bath perfusion or local perfusion which prove cumbersome and/or inadequate for studying how drug application to one region or the brain affects a neighboring (juxtaposed) region.  The CESOP device/method enables rapid  focal application of drugs/compounds while restricting their "spillover" to neighboring regions. Turbulent/non-laminar flow conditions that manifest in slice recording chambers exacerbate spillover thereby hindering/disrupting electrophysiological recordings and the study of region-specific drug effects. The CESOP device/method solves this problem through concomitant ejection and suction or perfusate, even under moderately turbulent conditions.</p> <p> </p> <p> </p> <p> </p> <p> </p>
Solid State NMR Method for Screening Cell Membrane Protein Binding Drug Candidates Dr. Cross 07-043 Matthieu Dumont <p>The present invention describes a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The possible shift in solid-state NMR spectrums between treated and untreated membrane protein is indicative of protein binding by the candidate ligand.</p> <p>This new way to undertake structure-function studies of proteins provides atomic-scale structural data with minimal perturbation to the system and allows the protein to be maintained in a functionally relevant conformational state. Ideally, it possibly will allow to observe detailed molecular structure while the protein progresses through conformational states associated with normal function.<span class="patent-number"></span></p>
Diagnostic Test for Detecting Anti-Cashew IgE in Patients Dr. Roux 01-030 Brent Edington <p>Approximately 0.5% of the US population is believed to be allergic to tree nuts. Additionally, the data from a voluntary registry of peanut and tree nut allergic US patients shows 20% of those reporting allergy to tree nuts list sensitivity to cashews, the highest percentage for any tree nut.</p> <p>The proposed invention discloses major allergenic proteins in cashew nut, which are legumin-like proteins and 2S albumins. Also disclosed is a polypeptide allergen in the 7S superfamily, which includes vicilin-like and sucrose binding proteins. Several linear epitopes of the cashew nut are identified and characterized.</p> <p>The invention further discloses the sequence of cDNA encoding the allergenic polypeptide, the allergen being designated Ana o 1, and also describes the characterization of the expressed recombinant polypeptide and associated methods employing the polypeptide. A diagnostic test for detecting anti-cashew IgE in a patient to thereby indicate an allergy to cashews comprises of: reacting patient's serum with a composition comprising at least one of the above mentioned purified polypeptide; separating the polypeptide from unreacted patient serum; reacting the polypeptide with a labeled human IgE-reactive agent after separating from unreacted patient serum; separating the polypeptide from unreacted labeled human IgE-reactive agent; and directly or indirectly detecting the labeled human IgE-reactive agent bound to the polypeptide after separating from unreacted agent to thereby indicate presence in the patient's serum of anti-cashew IgE.</p>
Major Allergenic Proteins in Cashew Nut Dr. Roux 01-030 Brent Edington <p>It is estimated that up to 8% of children less than 3 years of age and 2% of adults are affected by food allergies. While food-induced allergic reactions are the most common cause of outpatient anaphylaxis, the majority of severe reactions of this kind are caused by peanuts and tree nuts. Cashew nuts have been associated with contact or systemic dermatitis, atopic dermatitis, and IgE-mediated systemic allergic reactions. Cashew nuts are widely used in snack foods and as an ingredient in a variety of processed foods such as bakery and confectionery products.</p> <p>The present invention discloses major allergenic proteins in cashew nut, which are legumin-like proteins and 2S albumins. Also disclosed is a polypeptide allergen in the 7S superfamily, which includes vicilin-like and sucrose binding proteins. Several linear epitopes of the cashew nut are identified and characterized. The invention further discloses the sequence of cDNA encoding the allergenic polypeptide, the allergen being designated Ana o 1, and also describes the characterization of the expressed recombinant polypeptide and associated methods employing the polypeptide.</p> <p>The skilled will recognize that the isolated nucleic acids will be useful at least when expressed in a suitable cell or organism to produce the encoded polypeptides, which in turn may be employed in testing to identify patients allergic to cashew nuts. Furthermore, expression of the nucleic acid sequences of the present invention in a suitable cell may be useful in studying and characterizing gene function.</p>
Photodynamic Resolution of Racemic Compounds having Axial Chirality Dr. Kenneth Hanson 17-025 Garrett Edmunds <p><span>Enantioselective synthesis is the cornerstone of modern synthetic chemistry and a crucial step in the production of fine chemicals like food additives, fragrances, natural products, and pharmaceuticals. </span></p> <p><span>One of the most utilized ligands/ catalysts for these enantioselective reactions is 1,1' - bi-2-napthol ("BINOL"). The most common methods to synthesize these complexes, however, result in the formation of a racemic mixture of R and S isomers. Unfortunately, since only a single isomer of BINOL is needed, the racemic mixture is typically purified through chromatography or recrystallization to achieve the desired isomer, while the other half of the reaction mass is discarded. </span></p> <p><span>The present invention proposes the use of photoisomerization as an alternative strategy to generate enantiomerically pure BINOL. Due to excited state proton transfer (ESPT) BINOL can planarize and isomerize upon photoexcitation. We have invented the use of bulky chiral auxialiary groups to increase the rotational barrier of relaztion selectively for one BINOL atropisomer as a means of preferentially generating one of the BINOL isomers. The identity of the auxiliary group determined both the direction of rotation and the extent of enantiomeric excess observed. </span></p> <h2><span>Advantages:</span></h2> <ul> <li><span>Photoisomerization can generate a racemic mixture and then preferentially photoconvert to only one of the isomers</span></li> <li><span>This strategy does not waste 50 percent of the product</span></li> <li><span>Can be done on large scale with minimal solvent</span></li> </ul> <h2><span>Applications:</span></h2> <ul> <li><span>Chemical companies that sell or use BINOL (Sigma, VWR, Merck, etc.)</span></li> </ul>
Analysis of Mixtures with High Complexity by NMR Drs. Bruschweiler and Bingol 12-012 Matthieu Dumont <p>Identification and quantification of analytes in complex solution-state mixtures are critical procedures in many areas of Chemistry, Biology and Molecular Medicine. Nuclear magnetic resonance (NMR) is a unique tool for this purpose providing a wealth of atomic-detail information without requiring extensive fractionation of the samples. Our technology involves three new12-19 multidimensional-NMR based approaches that are geared toward the analysis of mixtures with high complexity at natural 13C abundance, including ones encountered into metabolomics. Common to all three approaches is the concept of the extraction of consensus 1D spectral traces or consensus 2D planes followed by clustering, which significantly improves the capability to identify mixture components that are affected by strong spectral overlap.</p> <p> </p>
Quantitative Analysis of Metabolic Mixtures by 2D 13C-Constant-Time TOCSY NMR Spectroscopy Rafael Bruschweiler 13-204 Garrett Edmunds <p>Quantification of metabolite concentrations is a key task in metabolomics studies.</p> <p>Significant peak overlaps in 1D NMR spectra of metabolomics samples prevent straightforward quantification through 1D peak integrals.Using uniformly 13C-labeled organisms, the 2D NMR 13C-13C constant-time (CT) TOCSY experiment provides high-resolution information about individual metabolites that allows their identification via database searching or, in the case of novel compounds, through the reconstruction of their backbone-carbon topology.</p> <p>FSU researchers demonstrated how CT-TOCSY spectra can also be utilized for quantification purposes. The methods are demonstrated for carbohydrate and amino-acid mixtures.</p>
Fingerprint for Cell Identity and Pluripotency David Gilbert 12-028 Brent Edington <p>At Florida State University, we have developed a method to identify sets of regions that replicate at unique times in any given cell type (replication timing fingerprints) using pluripotent stem cells as an example, and show that genes in the pluripotency fingerprint belong to a class previously shown to be resistant to reprogramming in induced pluripotent stem cells (iPSCs), identifying potential new target genes for more efficient iPSC production. We propose that the order in which DNA is replicated (replication timing) provides a novel means for classifying cell types, and can reveal cell type specific features of genome organization.</p> <p>A major advantage of our fingerprinting method is in selection of a minimal set of regions that allow for classification with a straightforward PCR-based timing assay and a reasonably small set of primers, particularly if only cell-type specific regions are examined. Our results suggest that a standard set of 20 fingerprint loci can be effective for classification, but the number of regions queried can be adjusted based on the confidence level required. The sole requirement for replication profiling is the collection of a sufficient number of proliferating cells for sorting on a flow cytometer. Consistently, just as replication fingerprints can be generated for particular cell types or general categories of cells, features of replication profiles allow for the creation of disease-specific fingerprints, which may be valuable for prognosis. We have also identified regions that may undergo important organizational changes upon differentiation.</p>
Detecting Interaction of CFTR Polypeptides Dr. Teem 08-009 Brent Edington <p>Cystic fibrosis (CF) is the most common genetic disease of Caucasians in North America, occurring at a frequency of approximately 1 in 2500 births. The disease results from defective function of the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein in a variety of tissues, including the pancreas and the lung epithelium.</p> <p>The present invention describes materials and methods for detecting the interaction of CFTR proteins. The method can be used to determine whether one CFTR NBD1 polypeptide interacts with a second CFTR NBD1 polypeptide using a yeast dual hybrid assay. The subject methods can be used to determine whether mutations to the CFTR polypeptide reduce or eliminate dimerization of the CFTR polypeptides. The present methods can also be used to screen and identify revertant mutations that restore dimerization of a mutant CFTR polypeptide, as well as mutations that enhance dimerization and CFTR activity greater than that of wildtype protein.The subject invention also provides materials and methods for efficiently identifying and screening for compounds, drugs and other such compositions that facilitate proper dimerization of the CFTR polypeptides and would be candidate agents for use in treating patients having CF. </p> <h2>Advantages:</h2> <ul> <li>The use of a yeast growth bioassay is fast and inexpensive in comparison to current screening procedures that involve mammalian cells and assays for CFTR channel activity</li> <li>Can be used to evaluate a large number of compounds in a high throughput format</li> </ul>
Genome Capture and Sequencing to Comprehensively Map Chromatin Structure in Complex Genomes Dr. Jonathan Dennis 14-044 Brent Edington <p>This invention brings significant improvement to our ability to query the chromatin structure of select important regions of the entire human genome. Utilizing a unique sequencing strategy, the invention offers a solution-based sequence capture method enabling the enrichment of the 2000 bp surrounding the transcription start site of 25,464 human open reading frames. This enrichment reduces the sequence space of the human genome from 3.4 Gb in total to 50 Mb of transcription start sites, a 98.5% reduction. Additionally, the enrichment is analogous to that achieved for well-documented exome sequencing experiments. This sequence capture approach will allow researchers to multiplex chromatin structure analyses in Illumina HiSeq2500 lanes, thereby opening this strategy for a wide range of diagnostic and prognostic indicators in human disease.</p> <h2>Applications:</h2> <ul> <li>Identify stages in the progression of cancer</li> <li>Identify host response in viral infection (HIV and KSHV)</li> <li>Define cryptic effects of drugs of abuse (amphetamines, cocaine, and nicotine)</li> </ul> <h2>Advantages:</h2> <ul> <li><span>Allows for the targeted analysis of specific areas of interest in complex genomes</span></li> <li><span>Provides a cost effective strategy for querying multiple samples in a single reaction</span></li> <li><span>Provides an extremely cost effective way to screen patient samples </span></li> <li><span>Opens a new field of biomarker development: distribution of nucleosomes</span></li> <li><span>Nucleosome distribution mapping is independent of genotype and gene expression</span></li> </ul>
Substituted Heterocyclic Mercaptosulfonamide Metalloprotease Inhibitors Dr. Qing-Xiang (Amy) Sang 08-144 Garrett Edmunds <p>Dr. Sang's team developed a series of substituted heterocyclic mercaptosulfonamide compounds, precursors, and derivatives as well as methods for the preparation of and pharmaceutical compositions comprising these compounds. These compounds are designed to be potent selective inhibitors of matrix metalloproteinases (MMPs), including, for example, gelatinases, collagenases, matrilysins, metalloelastase, stromelysin, and membrane-type 1 matrix metalloproteinase. These inhibitors may be used for the control of physiological and pathological processes and disease conditions in which MMPs are believed to play significant functions.</p>
A Reliable Assay for the Detection of Pork and Blood Components for Halal, Kosher, and Other Dietary Needs and Applications Yun-Hwa Hsieh 06-097, 12-194 Brent Edington <p>Nearly half of the world’s total population is strictly prohibited to consume pork and any substances derived from animal blood. However, food ingredients derived from pork and blood are widely used and present in various forms of dietary products without the awareness of consumers and even regulators.</p> <p>Analytical tools for monitoring these materials are lacking. Our laboratory at FSU possesses the only reliable technology to protect consumers who avoid eating products containing pork and blood, and such technology has been frequently sought for commercialization by a number of domestic and international companies for consumer protection in the markets of Kosher food for 13.8- million Jews; Halal foods for 1.6-billion Muslims; 1 billion of Hindus and non-religious vegans/vegetarians.</p> <p>The most desirable detection method is enzyme-linked immunosorbent assays (ELISA) which, coupled with our panel of monoclonal antibodies (mAbs) is able to detect protein ingredients derived from pork and blood components. These unique monoclonal antibodies are able to detect pork and blood from processed and cooked samples.</p>
Method of Using RNA as an Inhibitor of HCV Dr. Hengli Tang 07-073 Brent Edington <p>The NIH estimates that four million Americans are infected with Hepatitis C Virus (HCV) and an estimated 8,000 to 10,000 Americans die annually of HCV related complications. This figure is expected to triple in the next 10 to 20 years. FSU researchers have utilized siRNA HT-161 to effectively block HCV replication and infection in cell culture. The replication is inhibited by clearing human cells of a protein essential for HCV replication. HT-161 inhibits diverse HCV strains including the genotype 1a and 1b that are prevalent and resistant to interferon therapy.</p> <p><a href="/media/3808/tang1_2.pdf" title="Tang1_2.pdf" data-id="6086">Download PDF Version</a> </p> <h2>Applications:</h2> <ul> <li>The method has been shown to prevent new infection and eliminates replicating HCV RNA from infected cells</li> <li>Can be utilized against a diverse selection of HCV</li> </ul> <h2>Advantages:</h2> <ul> <li>HT-161 targets a cellular gene necessary for viral replication thereby significantly reducing the likelihood of viral escape and resistance due to mutation</li> <li>Current therapies, such as interferon (IFN), have significant adverse side effects and HCV strains develop resistance to IFN treatment</li> <li>Unlike other siRNAs, the treatment does not target the viral genome, which, when targeted, increases the risk of mutations conveying resistances to treatment</li> </ul>
Fibroblast Growth Factor (FGF) 1 with Mutation in the Heparin Binding Domain and Methods of Use to Reduce Blood Glucose Michael Blaber 15-211 Brent Edington <p>Type 2 diabietes and obesity are leading causes of mortality and are associated with the Western lifestyle, which is characterized by excessive nutritional intake and lack of exercise.</p> <p>The present technology provides mutated FGF1 proteins and methods of their use to reduce blood glucose and/or to treat a metabolic disease.</p>
Pressure Sensors including an Ionic Conduction Sensing Mechanism Dr. Liu 08-132 Brittany Ferraro <p>The present invention describes thin film sensors for detecting the presence, intensity, and/or location of a compressive force, or pressure based on ionic conduction variation as the sensing principle. Upon wisely choosing soft materials-- elastomer-like polymer and polymeric gel electrolytes/polymer electrolytes in combination with appropriate patterning, the present invention offers low pressure level sensing and mapping capability with enhanced sensitivity. The sensor includes a plurality of conducting elements spaced apart from each other and at least one deformable electrolyte bridge contacting each of the conducting elements at one or more contact points having an aggregate contact area. Upon formation of an ionic circuit between two of the conducting elements, a first resistivity between the two conducting element exists. Upon application of a compressive force on the at least one deformable electrolyte bridge directed toward at least one of the conducting elements, the aggregate contact area increases such that a second resistivity between the two conducting elements exists. The difference between the first and second resistivity can be correlated with the pressure or mechanical displacement to be measured.</p> <h2>Applications:</h2> <ul> <li>This invention has numerous potential application in pressure sensing and mapping, e.g., seat occupancy detection for the automobile industry, tactile feedback for robots to sense and respond to environments, rehabilitation progress monitoring of a patient for the medical industry, biting force mapping in dentistry application, or measuring force on golf club grips.</li> </ul>
Liposome Micro- and Nano-Arrays for Molecular Screens in Cell Culture Dr. Lenhert 11-191 Brent Edington <p>The proposed invention describes the use of surface supported liposome arrays as a platform for screening of molecular libraries in cell culture models. Drug candidates encapsulated into surface supported liposomes are arrayed on a surface to form lipid multilayer arrays. The surface has been functionalized to ensure liposome uptake by the cells. Cells are cultured on these arrays and their response to the liposomes are monitored optically. Multiple liposome compositions and different lipids or other additives printed onto the same surface can be simultaneously screened. The drugs that are and are not working can be determined by their position on the surface.</p> <p>Contrarily to actual small molecule microarrays for drug screening strategies our invention does not require to covalently attach to a surface, and cells can be grown on the surface. Covalent attachment of the small molecule on the surface prevents internalization of the compounds, limiting the types of tests that can be carried out. Furthermore, the number of molecules that a single cell can see is limited by the surface it contacts. Diffusion of small molecules from array sources, such as gels has also been used for screening, although molecular diffusion limits applicability of those methods. Using surface supported lipid multilayers encapsulating drug candidates solves these problems.</p> <h2>Applications:</h2> <ul> <li>Screening of delivery systems, particularly for lipophilic drug candidates</li> <li>Drug resistance cell screening, where cells from biopsies are cultured ex situ</li> </ul>
Drug and Protein Design System Based on Advanced Free Energy Simulation Algorithms Wei Yang 11-130 Matthieu Dumont <p>Free energy simulation algorithms are designed to solve problems in protein and drug design. This software is more accurate than any other method at predicting binding free energy changes upon the modifications of ligands to allow for more efficient, accurate, and reliable samples for pharmaceutical and bio-technology research.The proposed invention has demonstrated the ability to efficiently and accurately predict protein ligand interactions that have the potential to be effective drugs. </p> <p>The fundamentals of this algorithm are based on physical principles, various conformations of trial small molecules, or proteins are docked into the target proteins. Then binding affinity changes (scoring) are evaluated on each obtained docking mode. The combination of these two centerpieces in structure based rational drug/protein design can facilitate the drug discovery and protein engineering processes dramatically.</p> <p>This software has the potential to significantly reduce the time and cost of drug discovery by enabling unprecedented prediction accuracy within industry tractable computing resources and timescales.</p> <p><a href="/media/3812/yang.pdf" title="Yang.pdf" data-id="6090">Download PDF Version</a> </p> <h2>Applications:</h2> <p>This software will allow pharmaceutical and bio-technology companies to create new drugs and products with more efficiency and accuracy</p> <h2>Advantages:</h2> <ul> <li>Reduces cost and time spent discovering new medicines</li> <li>Helps identify lead ligands, the initial bottleneck step in research and development for new pharmaceuticals</li> </ul>
Assay for Screening HCV Drugs Hengli Tang 06-028 Brent Edington <p>More than 170 million people worldwide are infected with the Hepatitis C Virus (HCV), which can lead to acute and chronic liver diseases. Since the virus will not reproduce in test tubes for more than a few hours it is very difficult to perform experimental research on it. This novel assay uses a reporter cell line, causing the cells to send out a detectable signal when certain events happen internally. Whenever HCV is replicating, the cell will emit green fluorescence. The fluorescence is then tracked in the cell culture through flow cytometry.</p> <p><a href="/media/3810/tang2_2.pdf">Download PDF Version</a></p> <h2>Applications:</h2> <ul> <li>HCV testing</li> <li>Rapidly identify and isolate antiviral drug candidates</li> </ul> <h2>Advantages:</h2> <ul> <li>Easy to use</li> <li>Identifies HCV quickly relative to other assays</li> </ul>
An Improved Form of Human Acidic Fibroblast Growth Factor (FGF-1) Dr. Blaber 09-122 Brent Edignton <p>The creation of a mutant form of human acidic fibroblast growth factor (FGF-1) with improved stability and functional properties is a unique discovery with a very large potential target market. Angiogenesis therapy can be greatly enhanced by this new technology. The growth factor is formulated without heparin, which reduces cost and eliminates the potential for introducing other disease, such as BSE (Mad Cow Disease). Additionally, improvements in potency and functional half-life may significantly reduce the effective dosage</p> <p>This is a cutting-edge “hidden design” protein engineering technique to enhance protein function while minimizing immunogenic potential.</p> <p><a href="/media/3803/blaber2.pdf">Download PDF Version</a></p> <h2>Applications:</h2> <ul> <li>Can be injected at the site of a vascular blockage to cause the development of new vasculature to supply blood to previously hypoxic tissue</li> <li>Treatment of patients with coronary artery disease</li> <li>Therapy of ischemic limbs where there is a potential for both tissue and nerve regeneration</li> <li>Enhanced wound-healing</li> </ul> <h2>Advantages:</h2> <ul> <li>More stable, has a longer half-life, and is 100 times more reactive than wild-type FGF-1</li> <li>Because heparin is not used in the formulation, cost is reduced and safety is increased</li> <li>Less dosage is required than FGF-1</li> <li>Better controlled than FGF-1</li> <li>Patent protection (unlike wild-type FGF-1)</li> </ul>
Nucleic Acid and Allergenic Polypeptides Encoded Thereby in Cashew Nuts Dr. Roux 03-035 Brent Edington <p>Approximately 0.5% of the US population is believed to be allergic to tree nuts and the data from a voluntary registry of peanut and tree nut allergic US patients shows 20% of those reporting allergy to tree nuts list sensitivity to cashews, the highest percentage for any tree nut.</p> <p>The present invention describes isolated nucleic acid sequences and degenerate variants encoding an Ig-E binding immunogenic polypeptide of cashew. The invention additionally provides an in vitro diagnostic test for detecting anti-cashew IgE in a patient.</p> <p>The test comprises of reacting the patient's serum with a purified polypeptide, the amino acid sequence of which comprises at least one sequence selected from the isolated nucleic acid sequences; separating the polypeptide from unreacted patient serum; reacting the polypeptide with a labeled human IgE-reactive agent after separating from unreacted patient serum; separating the polypeptide from unreacted labeled human IgE-reactive agent; and detecting labeled human IgE-reactive agent bound to the polypeptide after separating from unreacted agent to thereby indicate presence in the patient's serum of anti-cashew IgE. The present invention thus discloses isolated nucleic acid sequences, polypeptide products thereof, and associated methods. The skilled will recognize that the isolated nucleic acids will be useful at least when expressed in a suitable cell or organism to produce the encoded polypeptides, which in turn may be employed in testing to identify patients allergic to cashew nuts. Furthermore, expression of the nucleic acid sequences of the present invention in a suitable cell may be useful in studying and characterizing gene function.</p>
Mutants of Human Fibroblast Growth Factor Having Increased Stability and/or Mitogenic Potency Dr. Blaber 04-046 Brent Edington <p>Human fibroblast growth factor-1 (FGF-1) is a potent human mitogen for a variety of cell types, including vascular endothelial cells, and can stimulate such cells to develop neovasculature capable of relieving ischemia. For this reason, FGF-1 is an angiogenic factor with potential applicability in "angiogenic therapy."</p> <p>The present invention describes engineered mutant polypeptides of human fibroblast growth factor 1 (FGF-1) having improved thermal stability and/or improved mitogenic activity. In comparison to wild-type FGF1, polypeptides having mutations at positions 12 and 134 exhibit enhanced properties of stability and/or mitogenic activity. Enhanced stability may preclude the need for added heparin in formulations of FGF1 for therapeutic use. Additionally, the enhanced thermal stability may translate to a longer shelf-life and minimization of aggregation during storage. The enhanced mitogenicity, which is possibly related to enhanced stability, may provide for use of smaller dosages for equivalent efficacy.</p>
Mutant Polypeptides of Fibroblast Growth Factor 1 Dr. Blaber 07-055 Brent Edington <p>Human fibroblast growth factor-1 (FGF-1) is a potent human mitogen for a variety of cell types including vascular endothelial cells, and can stimulate such cells to develop neovasculature capable of relieving ischemia. For this reason, FGF-1 is an angiogenic factor with potential applicability in "angiogenic therapy”.</p> <p>The present inventions describe several mutant polypeptides of the β-trefoil protein human fibroblast growth factor-1 (FGF-1) which greatly exceed the wild-type polypeptide in ability to stimulate human fibroblasts to proliferate. The amino acid sequence of the FGF-1 mutants, as well as the methods of treating fibroblasts and of stimulating mitogenesis of the fibroblast leading to tissue healing are described. The purified polypeptides of the present invention exhibit from approximately fifteen to one thousand times more mitogenic activity than wild-type FGF-1 in stimulating fibroblasts to proliferate.</p> <p>These mutants of human FGF-1 with enhanced stability and mitogenic potency can be used as second generation forms of FGF-1 in angiogenic therapy. Enhanced stability may preclude the need for added heparin in the formulation of FGF-1 for therapeutic use. Additionally, the enhanced thermal stability may translate to longer shelf-life and minimization of aggregation during storage. The enhanced mitogenicity (possibly related to enhanced stability) may provide for smaller dosages for equivalent efficacy.</p>
Method to Elucidate Molecular Structure from Momentum Transfer Cross Section Christian Bleiholder 17-008 Garrett Edmunds <p>Ion mobility spectrometry-mass spectrometry (IMS-MS) is ideally suited to study co-existing, transient conformations of proteins and their complexes related to diseases because of its high sensitivity and speed of MS analysis.</p> <p>Many existing results suggest that IMS-MS could accurately elucidate structures for these protein conformations in a high-throughput manner.</p> <p>The present technology identifies how protein tertiary structures can be determined from IMS-MS data in an automated manner.</p> <h2>Advantages:</h2> <ul> <li>IMS-MS requires a fraction of sample amounts and time</li> <li>Does not suffer from charge-state dependent protein dynamics in the gas phase</li> <li>Computationally efficient</li> <li>Automatized</li> </ul> <p><span>Click here to watch an interview with Dr. Bleiholder: <span class="fa fa-caret-square-o-right"></span><span class="fa fa-blind"></span><span class="fa fa-check-circle"></span><span class="fa fa-hand-o-right"></span><a href=""></a></span></p>
Anti-Flavivirus Compounds for Zika Virus and Dengue Virus Infections Hengli Tang 19-003 Brent Edington <p>Zika virus, a mosquito-borne flavivirus, has recently re-emerged and spread across the Western Hemisphere after it had remained in relative obscurity for many years. Zika virial infection causes many of the same symptoms caused by dengue viruses or chikungunya virus. Unlike these viruses Zika virus causes congenital defects, including microcephaly, and is also associated with Guillain-Barre syndrome in infected adults.</p> <p>Through a combination of computational modeling and screening, a portfolio of 19 compounds has been identified which have antiviral activity against Zika virus. In some cases, these drugs have activity against Zika virus and dengue viral infections. These compounds may be used in new therapies for the treatment of infection with flaviviruses, such as Zika virus and dengue virus.</p>
Monoclonal Antibodies Targeting Zika Viris Envelope Proteins Hengli Tang 17-037 Brent Edington <p> </p> <p>Due to the nascent nature of Zika Virus research reagents specific for the Zika Virus such as monoclonal antibodies are not widely available. FSU researchers have produced monoclonal antibodies to the Zika virus. These monoclonal antibodies are targeted to the envelope proteins NS1 and NS5. They enable detection of Zika infection, development of diagnostics, and can also be used as control reagents in research.</p>
Inhibiting Neuroinflammation Due to a Brain Injury with D-Serine Sanjay Kumar 19-037 Brent Edington <p>D-serine is an antagonist of GluN2 containing triheteromeric NMDA receptors found in the temporal lobe of the brain. It has been shown that D-serine may be used to treat neurological disorders, such as epilepsy, that cause seizures.</p> <p>Unexpectedly, it was recently discovered that D-serine inhibits neuroinflammation of brain cells after a brain injury by reducing the neurotoxic immune response of glial cells after the injury. Accordingly, D-serine may be used in the treatment of brain injuries to help prevent neural cell loss caused by harmful immune responses. Following brain injury an immune response is triggered and immune cells are directed to and sequestered to the site of injury. These immune cells release cytokines that exasperate the survivability of healthy neurons. Application of D-serine stopes the infiltration of these immune response cells to the site of injury, thereby preventing loss of healthy neurons by reducing the neuroinflammation response.</p>
Universal Insulin Pump Leakage Detection System John Wilcox 17-014 Garrett Edmunds <p>Insulin pump technology is a commonly implemented form of treatment for patients who suffer complications from diabetes mellitus. Mechanical malfunctions associated with the infusion site are a common source of failure and frustration experienced by many patients with these devices. Cannula dislodgement, lipohypotophy, and internal pump occlusions may result in leakage of insulin from the infusion site onto the surrounding adhesive material. For many, the only form of detection are the symptoms associated with hyperglycemia.</p> <p>This technology is a practical method for detecting these leaks as they occur. A mixture of 4-aminoantipyrine and potassium persulfate is deposited onto the surface of the adhesive holding the cannula. When exposed to the insulin solution, these compounds react to turn a bright blue color, indicating to the wearer that a leak is occurring and prompting them to change out their injection site. This allows people with diabetes to better control their blood glucose levels and avoid leakages.</p>
Inhibition of Vascular Endothelial Cell-Mediated Phagocytic Processes for Treatment of Demyelinating Conditions Yen Ri 19-006 Brent Edington <p>The present invention concerns a method for treating a demyelinating condition by administering an agent that inhibits vascular endothelial cell phagocytosis. The method of the invention is useful in treating demyelinating conditions associated with an injury such as a spinal cord injury or traumatic brain injury as well as other demyelinating conditions such as multiple sclerosis.</p> <p>The inventor has established a previously unidentified role for microvascular endothelial cells (EC) which have been shown to engulf and clear myelin debris in spinal cord injury and multiple sclerosis animal model systems. The inventor also discovered a novel pathway for myelin debris degradation through the autophagy-lysosome system. Importantly, the inventor demonstrated for the first time that microvascular EC uptake exerts critical functions beyond myelin debris clearance. Engulfment and autophagic processing of myelin debris by microvascular ECs have sequential consequences in promoting chronic inflammation and pathological healing (angiogenesis and fibrotic scar formation) during the progression of demyelinating disorders. Therefore, this research reveals how myelin debris engulfment and processing by microvascular ECs contribute to pathological progression in demyelinating disorders.</p>