Lignin-Based Nanoparticles and Smart Polymers |
Dr. Hoyong Chung |
15-122 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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 |
gedmunds@fsu.edu |
<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 |
gedmunds@fsu.edu |
<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> |
|
|
Drugs for the Treatment of Zika Virus Infections |
Hengli Tang |
16-114 |
Brent Edington |
bedington@fsu.edu |
<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 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<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 |
gedmunds@fsu.edu |
<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> |
|
|
Comprehensive, Genome-Wide Epigenetic Fingerprinting by Replication Profiling |
David Gilbert |
07-106 |
Brent Edington |
bedington@fsu.edu |
<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 |
bedington@fsu.edu |
<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> |
|
|
TrkB Receptor Antagonist for Treatment of Cognitive Inflexibility |
Pradeep G. Bhide |
15-137 |
Brent Edington |
bedington@fsu.edu |
<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/ 18-016 |
Brent Edington |
bedington@fsu.edu |
<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 seems 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> |
|
|
Fusicoccane Derivatives and Methods |
Prof. James Frederich |
17-039 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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="https://www.chemistryworld.com/news/four-step-route-to-carbotricycles/3009180.article">https://www.chemistryworld.com/news/four-step-route-to-carbotricycles/3009180.article</a></p>
<p><span><a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__app.meltwater.com_mwTransition_-3Furl-3Dhttps-253A-252F-252Fwww.sciencedaily.com-252Freleases-252F2018-252F07-252F180703143810.htm-26uId-3D56547ed34c07ddc0670b7c8f-26cId-3D55f84f24ab7e72fa1a4861aa-26dId-3DmaVnLQrhuPt1NOfjrR9BF-5FfEgpo-26contextId-3D5b3dfda3050a7ecb4ce1448b-26op-3Dopen-26sentiment-3DN-26isHosted-3Dfalse-26publishTime-3D1530653142450-26id-3D-26name-3D-26type-3D-26transitionToken-3DeyJ0eXAiOiJKV1QiLCJhbGciOiJIUzUxMiJ9.eyJob3N0bmFtZSI6Ind3dy5zY2llbmNlZGFpbHkuY29tIn0.Ki-5FMhVIfMfUk7falEvFecn0pLyO2IbwTRz0pkC5PQ1uOxwTzEl1gaKsfWOGSIrAp9s-5FbATcjZQWi29WHH6Kuzg-26s-3Dmail-2Dnewsletter&d=DwMFaQ&c=HPMtquzZjKY31rtkyGRFnQ&r=WPBE5mf0vyLaRUqjuwH1sg&m=gds5bbavh_mOdw_HPOAn-28dTWw1TVDSjNLAhAIdhfg&s=YwFs1A7P4BnsXk0ndHmTkrtzEkJGOnu34P3vz9tJhDg&e=">Breakthrough synthesis strategy could mean a wave of new medicinal compounds</a></span></p>
<p><span><a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__app.meltwater.com_mwTransition_-3Furl-3Dhttps-253A-252F-252Fwww.news-2Dmedical.net-252Fnews-252F20180704-252FInnovative-2Dsynthetic-2Dtechnique-2Dopens-2Ddoor-2Dto-2Dnew-2Dworld-2Dof-2Dcutting-2Dedge-2Dmedicinal-2Dcompounds.aspx-26uId-3D56547ed34c07ddc0670b7c8f-26cId-3D55f84f24ab7e72fa1a4861aa-26dId-3Dgj8XzuoC5zJ0WF3if4FF53pkkc0-26contextId-3D5b3dfda3050a7ecb4ce1448b-26op-3Dopen-26sentiment-3DN-26isHosted-3Dfalse-26publishTime-3D1530640920639-26id-3D-26name-3D-26type-3D-26transitionToken-3DeyJ0eXAiOiJKV1QiLCJhbGciOiJIUzUxMiJ9.eyJob3N0bmFtZSI6Ind3dy5uZXdzLW1lZGljYWwubmV0In0.rU0GULKC-5F2ZAVA6OU89-2DA2RYgAPyGPGO2xWgL4m-2Dsmlcv-5Fz0gkYGgmtgFPcp5l-2Dzw5agpVVczbF7idNkIMwIsA-26s-3Dmail-2Dnewsletter&d=DwMFaQ&c=HPMtquzZjKY31rtkyGRFnQ&r=WPBE5mf0vyLaRUqjuwH1sg&m=gds5bbavh_mOdw_HPOAn-28dTWw1TVDSjNLAhAIdhfg&s=wihplsHAdfgWkE8eGtsvfmv-mG2oqhmU0B6p4xbHTlQ&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 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<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 |
gedmunds@fsu.edu |
<p>For optical applications in general and eyewear in particular, the synthesis of new polymers with refractive indices >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> |
|
|
Mutations of the Rhodopsin Gene in Zebrafish and uses of the Mutations |
James Fadool |
17-038 |
Brent Edington |
bedington@fsu.edu |
<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/ 20-008 |
Brent Edington |
bedington@fsu.edu |
<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 and painful for frail patients such as the elderly. Although, stretching of calf muscles improves vascular function in the lower leg and walking is the best therapy. 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>
<p> </p>
<p>The splint allow the patient to walk without a high level of pain and thus able to walk as a useful therapy.</p> |
|
|
Personalized immunotherapy selection for breast cancer |
Professor Qing-Xiang Amy Sang and Professor Jinfeng Zhang |
17-046 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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 |
bedington@fsu.edu |
<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> |
|
|
Modified Fibroblast Growth Factor 1 (FGF-1) Polypeptides with Increased Binding Affinity for Heparin and Associated Methods |
Michael Blaber |
15-039 |
Brent Edington |
bedington@fsu.edu |
<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> |
|
|
Quantitative Analysis of Metabolic Mixtures by 2D 13C-Constant-Time TOCSY NMR Spectroscopy |
Rafael Bruschweiler |
13-204 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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> |
|
|
Genome Capture and Sequencing to Comprehensively Map Chromatin Structure in Complex Genomes |
Dr. Jonathan Dennis |
14-044 |
Brent Edington |
bedington@fsu.edu |
<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> |
|
|
Anti-Flavivirus Compounds for Zika Virus and Dengue Virus Infections |
Hengli Tang |
19-003 |
Brent Edington |
bedington@fsu.edu |
<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 |
bedington@fsu.edu |
<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 |
bedington@fsu.edu |
<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> |
|
|
Inhibition of Vascular Endothelial Cell-Mediated Phagocytic Processes for Treatment of Demyelinating Conditions |
Yen Ri |
19-006 |
Brent Edington |
bedington@fsu.edu |
<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> |
|
|
Anti-fibrotic Drugs Targeting Synthesis of Type 1 Collagen |
Branko Stefanovi |
10-042, 12-047, 17-024, 19-034, and 20-047 |
Brent Edington |
bedington@fsu.edu |
<p>Fibrosis affects 45% of the population in the USA. It is characterized by excessive synthesis of type 1 collagen and scarring of various organs. This leads to organ insufficiency and death. The process is chronic and progressive and there are no approved drugs that can inhibit collagen synthesis. Aspects of the regulation of type 1 collagen production have been delineated and a drug screening procedure based on disruption of the regulatory pathway has been devised. Using this screening procedure a library of chemicals compounds has been screened and nine compounds that can inhibit collagen synthesis in cultured cells between 50-90% have been found.</p>
<p>This is a completely novel approach to finding antifibrotic drugs. If these compounds prove to be effective in humans, they will be the first chemicals that can directly inhibit collagen production. Since there is no cure for fibrosis, they may represent the first specific antifibrotic drugs.</p>
<p>This technology consists of two novel assay systems and three potential antifibrosis drugs.</p> |
|
|
Treatment of Human Coronavirus Infections using Alpha Glucosidase Glycoprotein Processing Inhibitors |
Eric Holmes & Gary Ostrander |
20-037 |
Brent Edington |
bedington@fsu.edu |
<p>Coronaviruses cause illness in adults and children ranging from the common cold to more severe diseases. Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, coronavirus infection can cause pneumonia, severe acute respiratory syndrome (SARS), kidney failure, and even death.</p>
<p>Coronaviruses are zoonotic, meaning they are transmitted between animals and humans. Several known coronaviruses are circulating in animals that have not yet infected humans. A novel coronavirus (nCo V) is a new strain that has not been previously identified in humans. There are currently no vaccines or antiviral drugs to prevent or treat human coronavirus infections.</p>
<p>The present invention concerns the use of alpha-glucosidase glycoprotein processing inhibitors for the treatment or prevention of human coronavirus infections.</p>
<p> </p> |
|
|
Niclosamide Formulations and Methods of Use |
Eric Holmes & Gary Ostrander |
20-051 |
Brent Edington |
bedington@fsu.edu |
<p>Niclosamide is widely used as an oral medication for various tapeworm infections and has also been shown to be effective inhibitor of viral replication and infection. The invention involves a Niclosamide formulation utilizing permeability enhancers used to increase the amount of Niclosamide capable of being taken up by cells. The Niclosamide formulation has been shown to increase cellular uptake by as much as 150%. This Niclosamide formulation may be used to enhance delivery of Niclosamide in the treatment of human coronavirus or flavivirus infections.</p> |
|
|
Selective Treatment of Cancers Having Histone H3 Mutations and Aberrant Levels of DNA or Histone Methylation or Acetylation, or Defects in Homologous Recombination |
Akash Gunjan |
16-092 |
Brent Edington |
bedington@fsu.edu |
<p>Mutations in the DNA packaging and regulatory protein histone H3 and its primary sequence variants drive specific types of predominantly pediatric cancers, including the 10 incurable high-grade brain stem gliomas known as Diffuse Intrinsic Pontine Gliomas (DIPG). Up to 90% of DIPG tumors carry the lysine 27 to methionine (K27M) mutation in histone H3 variants, usually the histone H3.3 variant. H3 K27M mutant high-grade pediatric gliomas such as DIPG do not currently have any approved therapies and are 100% fatal. The present invention is a therapeutic approach which targets specific molecular pathways that are aberrant only in the mutant tumor cells but not the wild type cells, i.e., a therapy in which only the H3 mutant tumor cells would be eliminated specifically, while the normal cells carrying wild type H3 would be largely spared.</p>
<p>This targeted approach can be pursued is a few different ways that are the focus of this invention. </p>
<p> </p> |
|
|
MORIARTY: A Rapid, Highly Sensitive, Nucleic Acid Detection Method |
Dr. Hong Li |
21-044 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>The COVID-19 Pandemic demonstrated the need for rapid, affordable, and accurate virus testing methods. While the standard Polymerase Chain Reaction (PCR)-based methods remain effective and widely used, they require hours to complete and are unable to directly detect virus variants and other subtle changes to genetic material. Additionally, PCR lacks the possibility for testing under limited resources.</p>
<p>MORIARTY (an acronym for <u>M</u>ultipronged, <u>O</u>ne-pot, <u>R</u>NA-<u>I</u>nduced, <u>A</u>ffordable, <u>R</u>apid, <u>T</u>est s<u>Y</u>stem) is an enzyme-based method that can detect nucleic acids from a variety of sources, including the SARS-CoV2 coronavirus, seasonal flu varieties, and circulating tumor DNA for early cancer detection. This detection method is consistent with the accuracy of PCR methods but is considerably faster does not require costly equipment, with results available in as little as 15 minutes.</p>
<p>The technology utilizes CRISPR-Cas enzymes to detect genetic material and induce a fluorescent signal. The system can be easily repurposed and reprogramed for any genetic material detection, including viral RNA, viral DNA, and ctDNA, and can be used to detect variants with single-nucleotide resolution. This fidelity, for example, can detect the difference between the various coronavirus variants with the same point-of-care test. It can also be used for liquid biopsies to test for ctDNA for various cancers.</p> |
|
|