| Stimulus Sensitive Multi-functional Biomedical Adhesives |
Dr. Hoyong Chung |
17-042 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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> |
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| Pulsed Gliding Arc Electrical Discharge Reactors |
Dr. Bruce Locke |
06-142 |
Garrett Edmunds |
Gedmunds@fsu.edu |
<p>Gliding arc discharges have been investigated as a potential technology for gas phase pollution treatment and for liquid phase pollution treatment. Ultimately, the practical use of gliding arc technology to promote chemical transformations, such as the removal of organic pollutants in water or the generation of hydrogen peroxide, other reactive oxygen species, or reactive nitrogen species for treatment of potentially contaminated foods, depends on the efficiency that can be achieved.</p>
<p>The present invention describes a plasma gliding arc discharge reactor that is useful for chemical transformations in liquids and gases. The reactor may include a housing having a plurality of divergent electrodes, a power supply connected to the electrodes delivering pulsed power to the reactor, and a nozzle that directs a mixture of a carrier gas and a liquid to a region between the divergent electrodes, thereby generating plasma in the region. The nozzle can include a first inlet for receiving the carrier gas, a second inlet for receiving the liquid and a mixing chamber that is configured to mix the carrier gas and the liquid prior to being directed to the region.</p> |
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| MultiSense: A Highly Reliable Wearable-Free Fall Detection System |
Dr. Zhenghao Zhang |
18-015 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p class="lead"><span class="small">Professor Zhang and his team have developed A reliable fall detection system has tremendous value to the well-being of seniors living alone. We design and implement MultiSense, a novel fall detection system, which has the following desirable features. First, it does not require the human to wear any device, therefore convenient to seniors. Second, it has been tested in typical settings including living rooms and bathrooms, and has shown very good accuracy. Third, it is built with inexpensive components, with expected hardware cost around $150 to cover a typical room. Therefore, it has a key advantage over the current commercial fall detection systems which all require the human to wear some device, as well as over academic research prototypes which have various limitations such as lower accuracy. The high accuracy is achieved mainly by combining senses from multiple types of sensors that complement each other, which includes a motion sensor, a heat sensor, and a floor vibration sensor. Roughly speaking, the activities confusing to some sensors are often not confusing to others, and vice versa; therefore, combining multiple types of sensors can bring the performance to a level that can meet the requirements in practice.</span></p> |
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| 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> |
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| 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> |
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| Repurposed Use of the Alkaloids Emetine and Cephaeline to Treat Zika Virus Infection |
Hengli Tang |
18-017 |
Brent Edingtn |
bedington@fsu.edu |
<p>Zika virus (ZIKV), a mosquito-borne flavivirus, has re-emerged and spread across the Western Hemisphere in the past year. A large outbreak started in Brazil in late 2014 and is a growing public health concern. Currently, active transmission has been reported in 58 countries and territories globally. About 20% of ZIKV infected individuals develop symptoms, which mostly resemble symptoms caused by other arboviruses, such as dengue viruses or chikungunya virus. Unlike these viruses, however, ZIKV causes congenital defects, including microcephaly, and is also associated with Guillain-Barré syndrome in infected adults.</p>
<p> </p>
<p>The present invention concerns the novel use of emetine compounds for the treatment or prevention of Flavivirus infections, such as Zika virus infections. Emetine compounds have been FDA approved for use against amoebiasis and has been shown to have some anti-viral activity against other viruses.</p>
<p> </p> |
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| Monoclonal Antibodies for the Detection of Various Species Including Specific Consumed Meats and Bloods. |
Yun-Hwa Hsieh |
15-199 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| 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> |
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| 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> |
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| Antibody Biomarker Specific for Mitotic Cells |
Myra Hurt and Raed Rizkallah |
11-048 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Evaporative Edge Lithography (EEL) of a Liposomal Drug Microarray for Cell Migration Assays |
Dr. Lenhert |
13-035 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Selective Dopamine D4 Receptor Agonists for the Treatment of Working Memory Deficits |
Pradeep G. Bhide |
14-038 |
Brent Edington |
bedington@fsu.edu |
<p>Dopamine is a critical regulator of working memory, a mechanism for short-term information storage. Deficits in working memory occur in diseases with dopamine imbalance such as ADHD, schizophrenia and Parkinson’s Disease. However, a targeted treatment for working memory deficits is not available. In rodent models with working memory deficits, we show that selective activation of the dopamine D4 receptor (D4R) improves working memory. Based on these findings we propose that drugs that selectively activate the D4 receptor are novel class drugs for the treatment for working memory deficits.</p>
<p>D4R is found in abundance in the frontal cortex and hippocampus, brain regions that regulate working memory function. We examined two rodent models with working memory deficits, a prenatal nicotine exposure mouse model and the spontaneously hypertensive rat model. In both the models, activity and expression of the D4R are significantly decreased in the frontal cortex. Although dopamine D2 receptors expression and activity are also decreased in the frontal cortex of these models, improvements in working memory produced by psycho-stimulant administration were accompanied by increases in the activity of only the D4R and not the D2 receptor. Therefore, it can be concluded that selective increase in frontal cortical D4R activity is associated with improvement of deficient working memory.</p>
<p>Dopaminergic drugs that activate or antagonize multiple dopaminergic receptors or that produce global increases in brain dopamine content have failed as effective treatments for working memory deficits because of their pleotropic actions. Our discovery suggests that drugs that selectively target the D4 receptor and improve its function are effective treatments for working memory deficits.</p> |
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| Folding Nucleus Symmetric Expansion |
Michael Blaber |
14-163 |
Brent Edington |
bedington@fsu.edu |
<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> |
|
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| 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> |
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| 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> |
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| Identifying Cell and Disease-Specific Replication Timing Signatures |
David Gilbert |
16-102 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| 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> |
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| 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> |
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| Treatment of Zika Virus Infections Using Alpha-Glucosidase Inhibitors |
Gary Ostrander and Eric Holmes |
16-105 |
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>Castanospermine is an inhibitor of α- and β- glucosidases which catalyze the cleavage of individual glucosyl residues from various glycoconjugates, including complex carbohydrates and glycoproteins. Castanospermine interferes with viral replication and infection that is dependent on glucosidase activity. Evidence of castanospermine antiviral activity has been reported in various Flavivirus and has been demonstrated by our researchers to be an anti-Zika virus drug.</p> |
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| 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> |
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| D-Serine as a Modulator of Epileptic Seizures, Seizures, and Neurological Disorders |
Sanjay Kumar |
13-144 |
Brent Edington |
bedington@fsu.edu |
<p>Researchers at Florida State University Medical School have determined that D-serine can be used to modulate the onset and severity of seizures resulting from epilepsy or other neurological disorders.</p>
<p> </p>
<p>Dr. Kumar and his associates have recently discovered that certain brain cells express receptors to which D-serine is an antagonist. D-serine essentially shuts off the ion channels that these receptors regulate. Because these receptors are located in regions of the brain associated with neurological disorders such as seizures and epilepsy, D-serine may be used to treat such neurological disorders. D-serine can be used to modulate the regulation of ion channels and prevent the onset of and severity of seizures. This technology involves artificially administering a composition of D-serine to select regions of a patient’s brain having epilepsy or other neurological disorders causing seizures and reducing the severity or onset of seizures.</p> |
Epilepsy,Seizures,Neurological Disorders |
|
| Microfluidic Sample Preparation Device for Electron Microscopy |
Dr. Michael Roper and Dr. Scott Stagg |
15-230 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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 of principle paves the way for future added layers of complexity that can be used to uniquely investigate structural biology dynamics.</p>
<p>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.</p>
<h2>Advantages:</h2>
<ul>
<li>User friendly</li>
<li>Reproducibility</li>
<li>Parallel/high throughput</li>
<li>Straightforward manufacturing</li>
</ul>
<p>For further reading, please visit:</p>
<p><a href="http://www.roperlab.com/"><strong>http://www.roperlab.com/</strong></a><strong> <br /></strong></p>
<p><a href="http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b03884"><strong>http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b03884</strong></a></p>
<p><video alt="" width="400" controls="controls">
<source src="/media/4180/rs4-fin.mp4" type="video/mp4" />
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</video></p> |
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| Central Executive Training for ADHD |
Dr. Michael Kofler |
16-106 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>Attention-deficit/hyperactivity disorder (ADHD) is a complex, chronic, and potentially debilitating disorder of brain, behavior, and development that affects approximately 5.4% of school-aged children at an annual U.S. cost of illness of over $42 billion. Medication and behavioral treatment are effective for reducing symptoms, but they are considered maintenance therapies because their benefits disappear within minutes to hours after treatment is stopped. Clearly, novel treatments are needed.</p>
<p> </p>
<p>Central Executive Training (CET) is a novel, evidence-informed, computerized training protocol developed based on recent advancements in clinical and neuropsychological science. It differs fundamentally from existing, capacity-based “working memory training” programs. Each of CET’s 9 training games implement advanced algorithms to adapt based on the child’s performance and build capabilities across three, empirically-identified functions of the midlateral prefrontal cortex. These 3 functions involve dual-processing, continuous updating, and temporal ordering, and are collectively known as the brain’s ‘central executive.’</p>
<p> </p>
<p>Central executive abilities are targeted in CET based on fMRI evidence of significant cortical underdevelopment in these areas in children with ADHD. Importantly, our previous work has shown that hyperactivity and inattentive symptoms are most pronounced in children with ADHD when they are engaged in activities that challenge their underdeveloped central executive abilities. In fact, several studies have found that children with ADHD do not show attention deficits or hyperactivity during conditions with minimal central executive demands.</p>
<p> </p>
<p>Our preliminary data show that CET is superior to the current gold standard psychosocial treatment (behavioral parent training) for improving working memory in children with ADHD. Our data also show that CET is superior to the gold standard for reducing hyperactivity symptoms measured using high-precision actigraphs that sample children’s movement 16 times per second. CET was equivalent to the current gold standard for reducing ADHD symptoms based on parent report. A randomized clinical trial of CET is underway.</p>
<p> </p>
<p><a rel="noopener noreferrer" href="http://news.fsu.edu/news/science-technology/2018/01/24/fsu-psychologist-receives-2m-nih-grant-test-nonmedication-treatment-adhd/" target="_blank" title="http://news.fsu.edu/news/science-technology/2018/01/24/fsu-psychologist-receives-2m-nih-grant-test-nonmedication-treatment-adhd/">More on the NIH Award and a radio interview of Dr. Kofler.</a></p>
<p> </p> |
ADHD |
|
| Frequency-Modulated Continuous Flow Analysis |
Dr. Michael Roper |
18-002 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>Professor Roper and collaborators have developped a new method to multiplex mass spectrometric sample analysis. The purpose of this invention is to be able to analyze multiple samples simultaneously using mass spectrometry. The operation of this method is to pulse the flow of individual samples to the mass spectrometer at unique frequencies. The flow from the individual samples are combined together with a make-up flow that is used to ensure the total flow rate to the mass spectrometer is constant. After mixing of all the streams from the samples and the make-up flow, pulses of each sample are delivered to the mass spectrometer with the pulse frequencies being unique to that particular sample. The mass spectrometer collects the m/z data vs. time. At each m/z there is a time-dependent signal that is the sum of all the pulses from the different samples. For any one particular m/z, a Fourier transform is used to convert the time-based mass spectrometry signal intensity to the frequency domain resulting in a series of peaks at particular frequencies. Each of these frequency peaks corresponding to the different samples. The height of the peaks in the frequency domain is proportional to the concentrations of the samples in the syringes.</p>
<p>The benefit of this new method over the labeling strategy is that the frequency modulated approach allows multiplexing of a theoretically wide number of samples without the need for chemical labeling. Therefore, any problems with chemical labeling (inefficiencies, side products, etc.) are avoided. Also, more than 4-5 samples can be used simultaneously as Jong as their frequencies can be resolved in the frequency domain and the analytes are within the dynamic range of the mass spectrometer. A final advantage is that since all the samples are combined together, any samples that may have different levels of salts (detrimental to mass spectrometry) experience the same salt concentration. This means that they are all affected in the same manner and are much less susceptible to salt effects which hurt mass spectrometry experiments.</p>
<p>This technology was developed in collaboration with Jim Edwards at Saint Louis University</p> |
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| 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> |
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| 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> |
|
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| 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> |
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| 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> |
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| Novel Therapeutic Agent Sequestering Toxic Levels of Hemin in Cardiovascular Injury Events |
Ewa Bienkiewicz |
11-154 16-110 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Polyethylene Glycol Based Oligomers for Coating Nanoparticles |
Dr. Hedi Mattoussi |
12-026 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p id="p-0013" class="style-scope patent-text">We have developed nanoparticle coatings that are water dispersible, have a strong affinity for binding to magnetic nanoparticles, and can be easily modified for attaching the coating to biological materials. The nanoparticle coatings comprise a polyacrylic acid based backbone onto which PEG-based oligomers are appended by modifying the native carboxyl groups of the PAA backbone. The PEG-based oligomers include functional groups on their terminal ends, which are chosen to provide a certain function. Some of the terminal functional groups bind the coatings to the nanoparticle's surface, while others provide reactive sites for binding other compounds to the coating. The method we developed for making these coatings allows one to tune the number and type of PEG-based oligomers appended to the PAA backbone based on the desired properties of the coating.</p>
<p id="p-0014" class="style-scope patent-text">In accordance with a composition aspect of the invention, the nanoparticle coatings comprise repeating polyacrylic acid monomers covalently bound together in an aliphatic chain having a plurality of carboxylic acid functional groups and modified carboxylic acid functional groups extending there from. A first portion of the modified carboxylic acid functional groups are modified by a PEG oligomer having a terminal methoxy functional group and a second portion of the modified carboxylic acid functional groups are modified by a PEG oligomer having at least one terminal catechol group.</p> |
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| 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> |
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| Reusable Colorimetric Fluoride Sensors |
Dr. Sourav Saha |
10-186 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>Fluoridation of drinking water has been effective in preventing tooth decay and improving overall den-tal health; however, overexposure to fluoride poses numerous serious health risks including brittle bone disease and increases in bone cancers. Thus, accurate detection of fluoride levels in water and food sources as well as in body fluids is essential. </p>
<p><a rel="noopener" data-id="7056" href="/media/4156/marketing-document-10-186-saha.pdf" target="_blank" title="Marketing document 10-186 Saha.pdf">Download PDF Version</a> </p>
<h2>Applications:</h2>
<ul>
<li>Medicine and health applications, both commercial and consumer-oriented, to test for the presence of fluoride in tap water, foods, blood and urine</li>
<li>Food industry applications, such as testing toothpaste, bottled water, and food products</li>
<li>Commercial product to enable water purifier manufacturers to test the effectiveness of their products more easily and at a reduced cost</li>
<li>Municipal water-testing applications, particularly field testing</li>
<li>Humanitarian application for use in developing countries with few or non-existent fluoride testing tools or standards</li>
</ul>
<h2>Advantages:</h2>
<ul>
<li>Offers both colorimetric and fluorimetric detection</li>
<li>Can detect fluoride presence and quantity in a variety of environments including water, food, gas/air, and body fluids</li>
<li>The sensors are easy to synthesize, environmentally benign, and can detect a range of fluoride concentration levels, with high sensitivity at extremely low nanomolar concentrations</li>
<li>Dip-stick and spot-test forms are easy to use, effective, and comparatively inexpensive to produce</li>
<li>Tests are reversible, reusable (with power source), and recyclable (disposable), thus reducing waste and costs</li>
</ul> |
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| Advancing Wound Treatment with Saloplastic Dressings |
Dr. Joseph Schlenoff |
10-019 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>The demand for medical wound dressings is universal. Ranging in use from treating minor cuts to traumatic injuries, medical wound dressings prevent infections and save lives. In the case of traumatic injury, current wound dressings often require the application of a variety of materials, such as a combination of wound-filling gels, gauze, tape, and splints. However, Dr. Schlenoff’s research and discovery of saloplastics can decrease the number of necessary materials needed since saloplastic dressings can treat multiple aspects of a wound.</p>
<p>The process of creating saloplastics uses salt instead of heat to melt plastics made from blends of charged polymers. By placing layers of positively and negatively charged electrolytes on top of one another, their electrical charges cancel each other out and create a neutrally charged, ultrathin film. These ultra-thin polymer coatings are useful for producing biocompatible surfaces that can be implanted into the human body for medical purposes.</p>
<p>Approximately 750,000 Americans suffer strokes each year. Worldwide, that number increases to 20 million people. Primary stroke damage occurs from blood clotting and secondary damage occurs when toxic byproducts, including hemin, are produced from the trauma experienced during a stroke. This condition, known as hemin toxicity, leads to cell damage and cell death that in turn may cause irreparable brain damage or death for the individual.</p>
<p>With Dr. Schlenoff’s research, stents used for implantation inside coronary arteries during surgical procedures could be coated with an ultrathin film that prevents cells and proteins from adhering, thus avoiding a narrowing of the arteries and restriction of blood flow.</p>
<p><a rel="noopener" data-id="7055" href="/media/4155/marketing-document-polymer-schlenoff.pdf" target="_blank" title="Marketing document polymer schlenoff.pdf">Download PDF version</a></p>
<h2>Applications:</h2>
<ul>
<li>First responder scenarios</li>
<li>Chronic Wounds</li>
<li>Medical practitioners to consumers</li>
<li>Military</li>
</ul>
<h2>Advantages:</h2>
<ul>
<li>Antibacterial, moldable when wet, and cast-like when dry</li>
<li>Low heating temperatures, 45 – 55 degrees C, are needed to soften the material.</li>
<li>One material can treat multiple aspects of a wound.</li>
<li>Within minutes, the most serious wounds and breaks can be sealed and immobilized.</li>
</ul> |
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| Computer Software that Reduces Known Risk Factors for Anxiety, Depression, and Related Issues |
Dr. Norman B. Schmidt |
15-175 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>According to the World Health Organization anxiety and related issues, including addictions and mood problems as well as suicide, represent some of the most prevalent and disabling conditions across all physical and mental health disorders. As such, there is a clear public health need to more effectively prevent, mitigate and treat these issues.</p>
<p>Despite their prevalence and impairing nature, many of these problems respond remarkably well to treatment. It sounds almost too good to be true, but decades long conditions can be effectively removed in a few weeks with proper treatment. Our computer delivered interventions are even briefer – only about 50 minutes long. Despite their brevity, we have found that these interventions have considerable and long lasting positive benefits. Specifically, these brief treatments reduce the targeted risk factor by about 30% and these reductions are durable for as long as two years. Currently, we have two computer interventions - one focuses on stress sensitivity and the other on social isolation. These constructs have a considerable empirical foundation and are implicated as critical mechanisms involved in anxiety and mood problems.</p>
<p>Our work in this area combines three key tasks: (1) identification of malleable risk factors, (2) developing interventions for these risk factors, and (3) using technology to facilitate delivery of the interventions.</p>
<p>Technology is increasingly used to assist medical professionals. In regard to risk factors, our approach has been to develop interactive computer programs that guide participants through the information and skills needed to correct the problem of interest. These computer programs are brief (under one hour) and are readily disseminated via the web.</p>
<p><a rel="noopener" href="https://psy.fsu.edu/faculty/schmidtb/schmidt.dp.php" target="_blank">More on Dr. Schmidt</a></p>
<p> </p> |
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| Device and Method for Concomitant Ejection and Suction of Perfusate |
Sanjay Kumar |
15-008 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Photodynamic Resolution of Racemic Compounds having Axial Chirality |
Dr. Kenneth Hanson |
17-025 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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> |
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| 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> |
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| Fingerprint for Cell Identity and Pluripotency |
David Gilbert |
12-028 |
Brent Edington |
bedington@my.fsu.edu |
<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> |
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| 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> |
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| Novel Application of Melatonin Antagonists in Obstetrical Practice |
Dr. Olcese |
08-058 |
Brent Edington |
bedington@fsu.edu |
<p>This is a method for the prevention of pre-term labor that will introduce, intravenously, a melatonin antagonist to women who are predisposed to premature birth. Melatonin antagonists are drugs that do not provoke a biological response themselves, but bind to melatonin receptors, and, therefore, prevent endogenous melatonin itself from binding to the receptor. It is believed that the inhibition of melatonin action will prevent women from beginning labor.</p>
<p>Melatonin is a naturally occurring neurohormone found in most animals, including humans. Its role in the body is associated with the maintenance of a biological clock, or circadian rhythm. Besides this function, it is also a powerful antioxidant. Melatonin, or melatonin analogues, are consumed daily by millions of people for sleep induction. However, the application of melatonin in obstetrics represents a completely novel approach to the management of labor.</p>
<p><a href="/media/3989/olcese2.pdf" title="olcese2.pdf" data-id="6638">Download PDF Version</a> </p>
<h2>Applications:</h2>
<ul>
<li>Method for using melatonin to delay pre-term labor by targeting mothers who are at risk for premature labor.</li>
</ul>
<h2>Advantages:</h2>
<ul>
<li>Delay pre-term labor</li>
<li>Save millions of dollars from premature births each year</li>
<li>Prevent thousands of work hours for healthcare providers each year</li>
<li>No expensive new drug development</li>
</ul> |
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| A Prosthetic Socket System with an Unprecedented Degree of Multifunctionality and Integration |
Dr. Chun (Chuck) Zhang |
12-160 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>The proposed prosthetic Socket Optimized for Comfort with Advanced Technologies (SOCAT) integrate advanced materials, nanotechnology, electronics, and manufacturing technologies to achieve a prosthetic socket system with an unprecedented degree of multifunctionality and integration to meet the critical needs for advanced prostheses for patients. Despite the significant advances made in the past decade in the area of prosthetics, discomfort and adverse effects on the skin as a result of poor fit, elevated temperatures and moisture accumulation within the prosthetic socket are still a major problem.</p>
<p>The proposed SOCAT invention utilizes four enabling technologies augmented with a product integration design to form a holistic above-knee socket system to resolve the issues mentioned above:</p>
<ol>
<li>Volume/shape change management will be realized with advanced materials that sense and respond to external stimuli, such as pressure changes due to either volume changes as a result of residual limb swelling or muscle tissue shape changes during a gait cycle</li>
<li>Pistoning control and skin breakdown prevention will be realized via an innovative interface material embedded with nanoparticles</li>
<li>Temperature and sweat control will be achieved by solid state active cooling using an array of miniature thermoelectric devices in combination with nanomaterials and phase change materials; and</li>
<li>Lightweight piezoelectric nanofoam pressure sensors and printed electronic temperature and moisture sensors fully embedded in liners will provide the patient with an early warning of adverse situations, such as abnormal pressure suggesting improper gait or pistoning, and allow the practitioner to remotely collect real-time data for subsequent analysis.</li>
</ol>
<h2>Advantages:</h2>
<ul>
<li>Fully integrated product design that addresses major concerns of current sockets while minimizing parasitic parts and devices</li>
<li>Lightweight, multifunctional material-enabled socket system</li>
<li>Adaptive volume change management with coupled sensing/actuation materials</li>
<li>Biomimetic materials for anti-microbial function and pistoning control</li>
<li>Thermal management and perspiration control with solid state active cooling in conjunction with novel nanomaterials and phase changing materials</li>
<li>Whole-field pressure monitoring by innovative lightweight piezoelectric materials</li>
<li>Embedded printed electronics interconnects for sensing, wireless communication and local data storage</li>
</ul> |
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| Novel Methods to Regulate Uterine Contractions |
Dr. Olcese |
12-239 |
Brent Edington |
bedington@fsu.edu |
<p>The present invention describes a novel method of regulating uterine contractions in pregnant female using light. The method of regulating uterine contractions comprises suppressing a nocturnal endogenous melatonin level of a pregnant female experiencing uterine contractions by exposing the pregnant female during nighttime to a light source emitting visible light. Directing light from a light source positioned about 1 meter from the eyes, emitting predominantly blue light onto the pregnant females eyes between 9 p.m. to 6 a.m., with an intensity of about 10,000 lux of the visible light is sufficient to suppress the pregnant female's endogenous melatonin level.</p>
<p>The results reveal that regular nocturnal contractions are suppressed by bright light exposure under these conditions. This finding supports the proposition that melatonin is a key zeitgeber, regulating the onset of human labor and parturition and that light can be used to regulate melatonin levels and, thereby, regulate uterine contractions. Optionally, the light source is adapted to emit light in discrete on/off cycles or pulses. The duration of the pulses and the separation between successive pulses is adjusted to obtain the desired amount of endogenous melatonin suppression.</p>
<p>This invention will open new avenues for the management of term and preterm labor.</p> |
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| Carbon Nanotube and Polymeric Thin Film Assemblies for Pressure Sensing and Mapping |
Dr. Liang, Dr. Lu, Dr, Whang and Dr. Zhang |
08-132 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>Pressure/force sensing technologies are used in a broad range of applications. Many pressure/force sensors are available, but thin film sensors are limited. Currently, the most common film pressure sensors are either resistive or capacitive, which are both reusable. This new technology utilizes the rupture of microcapsules filled with dyes for pressure sensing to create a disposable thin film mapping.</p>
<p>The sensing assembly is composed of a top and bottom element. The top element is made of elastomer-like polymer with grooves that are filled with polymer gel electrolyte and the bottom is made of patterned conducting material thin film strips on top of flexible polymer film. When pressure is applied, a deformation of the material in the top element causes the gel to come in contact with the film strips, which creates an ionic-conducting path.</p>
<p><a data-id="6119" href="/media/3841/liu2.pdf" title="Liu2.pdf">Download PDF Version</a> </p>
<h2>Applications:</h2>
<ul>
<li>Seat occupancy detection in the automobile industry</li>
<li>Tactile feedback for robots to sense and respond to environments</li>
<li>Rehabilitation progress monitoring in the medical industry</li>
<li>Bite force mapping in dentistry</li>
<li>Measuring force of golf grips</li>
</ul>
<h2>Advantages:</h2>
<ul>
<li>Disposable</li>
<li>Low percolation threshold</li>
<li>Detects low levels of pressure sensing</li>
<li>Utilizes ionic conduction as the major sensing mechanism</li>
</ul> |
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| Liposome Micro- and Nano-Arrays for Molecular Screens in Cell Culture |
Dr. Lenhert |
11-191 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Drug and Protein Design System Based on Advanced Free Energy Simulation Algorithms |
Wei Yang |
11-130 |
Garrett Edmunds |
gedmunds@fsu.edu |
<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 data-id="6090" href="/media/3812/yang.pdf" title="Yang.pdf">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> |
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| An Improved Form of Human Acidic Fibroblast Growth Factor (FGF-1) |
Dr. Blaber |
09-122 |
Brent Edignton |
bedington@fsu.edu |
<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> |
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| Mutants of Human Fibroblast Growth Factor Having Increased Stability and/or Mitogenic Potency |
Dr. Blaber |
04-046 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Mutant Polypeptides of Fibroblast Growth Factor 1 |
Dr. Blaber |
07-055 |
Brent Edington |
bedington@fsu.edu |
<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> |
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| Method to Identify the Molecular Structure of Large Biomolecules via IM/MS |
Christian Bleiholder, Ph.D. |
17-008 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>This method uses data derived from Ion Mobility-Mass Spectroscopy (IM/MS) to computationally decipher molecular structures of proteins, protein assemblies, and protein-small molecules interactions.</p>
<p><span style="text-decoration: underline;"><strong>Advantages</strong></span></p>
<ul>
<li>Enables high-throughput large-scale systematic fragment-based drug discovery</li>
<li>Requires a fraction of the sample amounts and time</li>
<li>Uses systems already available to most pharmaceutical and therapeutics companies.</li>
</ul>
<p><strong><span style="text-decoration: underline;">Introduction and Applications</span></strong></p>
<p>This technology has the potential to revolutionize the field of drug discovery, especially fragment-based drug discovery, by elucidating the molecular structure of biomolecules and any bound ligands with high fidelity. </p>
<p>Currently, structural characterization in drug discovery is often undertaken with techniques such as x-ray crystallography, nuclear magnetic resonance, or cryo-EM. These traditional methods require significant sample amounts, purified samples, and are poorly suited for high-throughput screening assays. Further, many potentail targets are not amenable to structural characterization by these methods, including, for example, the soluble protein assemblies implicated as toxic agents in Alzheimer's or Parkinson's diseases.</p>
<p>In contrast, the current method exhibits sufficient sensitivity, sample-throughput, and dynamic range to enable the high-throughput, large-scale systemic screening of small molecule-target interactions. Additionally, the samples can be studied in a manner that more closely mimics their natural conditions, including flexible branches and glycan moieties that other methods often miss.</p>
<p><span style="text-decoration: underline;"><strong>The Technology</strong></span></p>
<p>The biomolecules of interest are analyzed in a few minutes via IM/MS. The output is then analyzed computationally, providing structural characterization. The program can be modified to work with in-house supercomputers or with cloud-based computing services, such as Amazon's AWS.</p>
<p> </p>
<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="https://www.youtube.com/watch?v=G7etpbzsWtg">https://www.youtube.com/watch?v=G7etpbzsWtg</a></span></p> |
Drug discovery,fragment based drug discovery,computational chemistry |
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| Cessation of Smoking System |
Brigitta Nuccio & Andree Aubrey |
18-055 |
Brent Edington |
bedington@fsu.edu |
<p>This cessation of smoking method is an evidence-based curriculum for delivering both group and individual cessation interventions. It can be used cost-effectively in community based programs and across multiple components of a health system including primary and specialty clinics, behavioral health programs, and hospitals.</p>
<p>The participant workbook contains six sessions or modules and serves as a guide to the tobacco cessation process. The workbook walks participants through the critical steps of making a quit attempt and addresses physical addiction to nicotine, psychological dependence, behavioral habit, and social/cultural influences. In the workbook participants will complete motivational activities, document a specific quit date, outline their quit strategies and have additional information for reference that may not get covered in the counseling sessions. Even participants who attend only one session may use the workbook to make an independent quit attempt. The workbook is designed in a way that it can be used for independent study if a tobacco user wants to quit but is not interested in attending a group. </p> |
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| 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> |
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| 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> |
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| 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> |
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| 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> |
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| 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> |
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| Detection of Shiga Toxin Producing Escherichia Coli Serogroups |
Prashant Singh |
20-032 |
Brent Edington |
bedington@fsu.edu |
<p>Shiga toxin-producing <em>Escherichia coli</em> (STEC) are foodborne pathogens of great concern. In the United States, <em>E. coli</em> O157:H7 and virulent strains of the top six non-O157 STEC serogroups (i.e. O26, O45, O103, O111, O121 and O145) are considered adulterants in non-intact beef and are implicated in major foodborne outbreaks and recalls.</p>
<p>One of the major limitations of official test methods and other commercially available STEC detection assays is their inability to distinguish virulent (disease-causing) strains of <em>E. coli</em> serogroups (i.e. O26, O45, O103, O111, O121, O157 and O145) from avirulent strains, which are more frequently found in beef samples<em>.</em> The USDA-FSIS tested 18,339 beef samples between 2014 and 2020, of which, 1,008 samples tested positive for STEC serogroup screening. However, STEC was confirmed only in 114 samples out of these 1,008 positive samples. The difference of 894 samples (or 89%) that could not be confirmed was most likely due to the detection of interfering avirulent strain of <em>E. coli</em> STEC serogroups by the commercially available assays.</p>
<p>These high positive test results due to the presence of avirulent strains result in product hold up for further investigation and causes safe wholesome meat to be diverted to either thermal treatment steps to destroy the pathogen or forces the establishment to dispose the product. This high false positive rate of commercially available STEC screening methods results in an annual loss of approximately $47 million for the beef industry. Further, this high false positive rate reduces the accuracy of testing laboratories while also increasing their workload.</p>
<p>The present invention is a real-time PCR high resolution melt assay system which can detect four of the STEC serogroups (i.e. O36, O111, O103, and O121). This assay system allows detection of four of the most significant meat foodborne pathogens, saving consumers from illness and the meat industry from significant unnecessary loss.</p> |
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| 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> |
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| 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> |
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| 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> |
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| Flexible and Eco-Friendly X-ray Scintillators |
Dr. Biwu Ma |
20-031 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>Dr. Ma has recently developed highly efficient X-ray scintillators with state-of-the-art performance based on organic metal halide hybrids, which could be prepared using a facile solution growth method at room temperature to form inch-sized single crystals. These organic-inorganic hybrid materials with a zero-dimensional<br />(0D) structure at the molecular level exhibit tunable emissions in the visible spectrum region with high photoluminescence quantum efficiencies (PLQEs) of up to 100%. X-ray imaging tests have showed that scintillators based on powders could provide an excellent visualization tool for X-ray radiography, and<br />flexible scintillators could be fabricated by blending powders with polymer matrix, such as polydimethylsiloxane (PDMS). </p>
<p>These X-ray scintillators have numerous advantages over currently-used materials:</p>
<ol>
<li>The scintillation materials are low cost (~ 1/10 of commercially available products), i.e. room<br />temperature facile synthesis using abundant low cost raw materials;</li>
<li>The scintillation materials are eco-friendly materials, i.e. lead-free, heavy metal-free;</li>
<li>The X-ray scintillation characteristics are exceptional, i.e. higher light yields than most of the<br />conventional commercially available scintillation materials;</li>
<li>It is straightforward to integrate scintillation materials with polymer matrices to make flexible X-ray material</li>
</ol> |
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| Motivational Interviewing |
Sylvie Naar |
19-023 |
Brent Edington |
bedington@fsu.edu |
<p>Motivational Interviewing (MI) is often recommended as an evidence-based approach to behavior change. It is a collaborative, goal-oriented communication with attention to the language of change. MI is designed to strengthen personal motivation and commitment to specific goals by supporting and eliciting the individual’s reasons for change.</p>
<p>MI is:</p>
<ul>
<li>A style of communication that guides the individual and it resides between good listening and providing advice;</li>
<li>Designated to empower people to change by bringing out their own reasons to change;</li>
</ul>
<p>MI is used when:</p>
<ul>
<li>Ambivalence is high;</li>
<li>Confidence is low;</li>
<li>Desire to change is low;</li>
<li>Motivation to change is low.</li>
</ul>
<p>Dr. Sylvie Naar has developed a rating scale for coding interactions for competency in Motivational Interviewing and a method of communication to promote behavior change. This rating scale and method require less time and expense for the client and has been rigorously tested in health care settings. Dr. Naar’s rating scale and guidelines for use provide a straightforward method for the use of Motivational Interviewing. This method has been verified in clinical settings and the guidelines are clear and concise.</p>
<p>The rating scale and guidelines are protected by copyright.</p>
<p> </p> |
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| Lipid Vesicle-Mediated Delivery to Cells |
Zucai Suo |
21-016 |
Brent Edington |
bedington@fsu.edu |
<p>Lipid vesicles (LVs) are vesicles that are enclosed by at least one lipid layer. The present invention relates to the utilization of LVs for delivery of loaded cargo molecules into cells. Any LVs may be utilized, such as liposomes, lipid nanoparticles, lipid droplets, micelles, reverse micelles, and lipid-polymer hybrid nanoparticles.</p>
<p>The invention facilitates the loading of diverse cargo molecules such as drugs, small molecules, nucleic acids, macromolecules, enzymes, proteins, and peptides into LVs. The cargo is then delivered into eukaryotic cells via the loaded LVs without being degraded or modified by extracellular enzymes or neutralized by host immune responses. Moreover, this protection conferred by LV-mediated delivery can be achieved without the need for chemical modification of the cargo molecule as a countermeasure, though chemical modification remains an option. Upon contacting a cell, the LV is internalized by the cell and the cargo is delivered into the cell. The cargo molecule may belong to any class of substance or combination of classes.</p> |
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| Extracellular Vesicle-Mediated Delivery to Cells |
Zucai Suo |
21-010 |
Brent Edington |
bedington@fsu.edu |
<p>Extracellular vesicles (EVs) are membrane-enclosed vesicles released by cells into the extracellular space (“EV” is a collective term encompassing various subtypes of cell-released membranous structures called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names in the literature). The present invention relates to the utilization of EVs for delivery of cargo molecules into cells. The present invention uses unique methods for the loading and delivery of cargo molecules into cells in vitro or in vivo, e.g., for medical, diagnostic, and biological applications.</p>
<p> </p>
<p>The invention allows for the easy and efficient loading of diverse cargo molecules such as drugs, small molecules, nucleic acids, macromolecules, lipids, enzymes, proteins, and peptides into EVs. The cargo is then delivered into eukaryotic cells via the loaded EVs without being degraded or modified by extracellular enzymes or neutralized by host immune responses. Moreover, this protection conferred by EV-mediated delivery can be achieved without the need for chemical modification of the cargo molecule as a countermeasure, though chemical modification remains an option. Upon contacting a cell, the EV is internalized by the cell and the cargo is delivered into the cell.</p> |
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| PCR-based Assay Method for Quantification of Salmonella or Other Microbes in Food Samples |
Prashant Singh |
21-043 |
Brent Edington |
bedington@fsu.edu |
<p><strong>Introduction: </strong><em>Salmonella</em> <em>enterica</em> is a leading cause of bacterial foodborne illnesses worldwide. <em>Salmonella</em> strains cause about 93 million enteric infections annually, which results in 155,000 global deaths. In the U.S., strains of <em>Salmonella</em> are responsible for around 1.35 million cases each year. Despite strong measures by the regulatory agencies (i.e., USDA, FDA) and implementation of various process controls, the <em>Salmonella</em> incidence rate of infection has increased from 15 cases per 100,000 in 2010 to 18.3 cases per 100,000 in 2018.</p>
<p>Knowing a target organism’s concertation range, such as <em>Salmonella,</em> is critical for many industries including the food and diagnostic industry. A food sample with a low level of pathogens may not present a hazard while a higher level of pathogen does. Knowing when the pathogen level approaches the threshold level for safety is important. Current methods of estimating the concertation of microorganisms are based on the most probable number method (MPN). The MPM method is slow, culture-based, laborious, and requires two or more days for completion. Beef or poultry processors who wish to assess a threshold level of <em>Salmonella</em> concentrations of meat currently have to rely on the MPN based method. Some current molecular methods on the market can provide concentration determination, but they rely on external standard curve and regression are required to measure organism concentration. As each sample varies in composition, microbial load and presence of natural inhibitor (i.e., sample matrix effects for each sample type), a separate standard curve is needed. </p>
<p><strong>Working Principle:</strong> Our approach takes advantage of varying PCR amplification efficiencies achieved by the introduction of mismatches in the <em>Salmonella</em>-specific primer sequence. The selected set of primers are used for estimating the initial <em>Salmonella</em> load in the test samples. The primer sequence exactly matching the target gene is amplified at the highest amplification efficiency and can detect the lowest concentration of <em>Salmonella</em>. Whereas primers designed with an increasing number of mismatches result in sequentially lower amplification efficiencies, which in turn enables detection of different log<sub>10</sub>-fold <em>Salmonella</em> concentrations (10-10<sup>4</sup> CFU). As PCR amplification is carried out using primers with mismatches, assay specificity is achieved through a <em>Salmonella</em>-specific dual-labeled probe. Using this approach, a selected set of primer pairs can be used to detect and estimate initial <em>Salmonella</em> concentration in food directly or after enrichment based on the growth dynamics of the pathogen.</p> |
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| Repetitive DNA Elements to Evaluate Genomic Variations |
Alan Lemmon |
20-018 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>A unique combination of steps in laboratory protocol that allow simultaneous enrichment (amplification) of thousands of genomic DNA regions that are sequenced and assessed for genetic variants. Steps include; ligation of a common DNA adapter to fragments of DNA, a Polymerase Chain Reaction, a sequence of computational steps for identifying and profiling sequence data, and a modification of the protocol that utilizes a DNA circularization step to allow larger regions to be enriched that cover upstream and downstream of the repeat motif.</p> |
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| Healthy Living Web Application |
Norman Schmidt |
17-026 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>A web application designed to provide an overview of a variety of healthy living skills including diet and exercise, sleep hygiene, and water consumption using video and audio along with text.</p> |
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| Halide Perovskite-Polymer Composites for High Energy Photon Detection and Protection |
Dr. Zhibin Yu |
18-048 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>An FSU researcher created a novel material comprised of halide perovskite crystals embedded in a polymer matrix for radiation blocking and detection. The material is lightweight and lead free. Other materials require expensive and long manufacturing processes, but this novel material can be manufactured in a variety of ways such as solution-based drop casting, hot pressing, melt extrusion, injection molding, and 3D printing, to save time and money. Electrodes can be embedded in the material for passive and accurate x-ray and gamma-ray detection. </p>
<p>Third party independent testing has shown that the material is 50% more effective than current state of the art radiation blocking technology. These semiconducting nanocrystals are uniformly dispersed in the polymer matrix to not only block radiation but also detect high energy radiation.</p> |
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| Mindfulness-Based Art Therapy (MBAT) |
Theresa Van Lith |
19-040 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>A blend of mindfulness practices like yoga and meditation with art therapy directives into brief modules for college students to habitually address symptoms of anxiety and stress. These modules have been designed for online platforms and mobile apps. There were significant decreases in participants' symptoms of anxiety and perceived stress after the 10-module, 5-week intervention. The virtual platform offers a less stigmatized help-seeking strategy that is more comfortable to digital natives and allows mental health professionals to remotely facilitate mindfulness-based art therapy, an evidence-based mental health practice with positive psychological and neurobiological implications.</p> |
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| 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> |
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| Extracellular Vesical-based Cytokine Storm Therapy |
Zucai Suo |
21-039 |
Brent Edington |
bedington@fsu.edu |
<p>The invention relates to the use of extracellular vesicles (EVs) loaded with CD24, a biological immunomodulator, for treating hypercytokinemia (also named cytokine storm, cytokine storm syndrome, or cytokine release syndrome). Hypercytokinemia can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1, and SARS-CoV-2 (COVID-19 agent). Other causative agents include the Epstein-Barr virus, cytomegalovirus, and group A streptococcus, and non-infectious conditions such as graft-versus-host disease. The present disclosure relates to the application of EVs that are derived from any cells including human mesenchymal stem cells and are loaded with natural or engineered CD24 for therapeutic usages in human and animals.</p>
<p>Our invention allows one to load natural or engineered human or animal CD24 molecules into extracellular vesicles including exosomes without being cleaved or modified by extracellular enzymes, bound by host proteins, or neutralized by host immune responses. Prior to our invention, the N-terminal 56 amino acid residues of human CD24 has to been fused with the Fc region of human IgG1 (CD24Fc) before being used as a protein drug to treat hypercytokinemia.</p>
<p>The invention will allow a very high number of CD24 molecules to be loaded into extracellular vesicles, known as natural nanoparticles. The EVs loaded with CD24 can be directly used as therapeutic agents for treating hypercytokinemia or used in combination with other immuno modulators in order to achieve potential synergy.</p> |
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| Transcranial Stimulation to Treat DMN Dysfunction |
Wen Li |
22-035 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>This technology is directly applied to people with mild cognitive impairment and Alzheimer’s disease to alleviate symptoms and improve life quality. It builds upon non-invasive brain stimulation (NIBS), specifically transcranial alternating current stimulation (tACS) that applies a relatively low-intensity sinusoid current through the scalp to stimulate the brain. It targets a major neural network (the default mode network/DMN), which breaks down with normal aging, precipitously in mild cognitive impairment and severely in Alzheimer’s disease. The application is non-invasive, safe, and user-friendly and has a strong potential to be applied as therapeutics and prophylactics for cognitive impairment and dementia.</p> |
Psychology,Alzheimer's,Aging,Dementia |
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| Topical Oxytocin Treatment with Tactile Stimulation |
Elizabeth Hammock |
22-058 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>Oxytocin is an FDA approved drug (and naturally produced hormone) that is used intravenously for labor induction. Currently, oxytocin is delivered by uncomfortable (intranasal) or invasive (injection) methods. This treatment combines oxytocin receptor modulation with somatosensory stimulation through topical substance delivery. Oxytocin or other oxytocin receptor modulators will be combined with drug delivery vehicles that require somatosensory stimulation as part of their application. Topical application of oxytocin may be delivered in shampoos, soaps, lotions, creams, ointments, massage oils, wipes, chewing gum, toothpastes, personal lubricants, condoms or other mechanisms of substance delivery that involve somatosensory stimulation (e.g., massage, ‘mouthfeel’ of foods/gums/candies, and sexual activity).</p> |
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| Magnetic Levitation Simulator with Large Functional Volume |
Wei Guo |
22-023 |
Michael Tentnowski |
mtentnowski@fsu.edu |
<p>Reduced gravity is known to have important effects on various biological and physical systems. Weightless may prohibit cell culture growth and cause cellular stressors and bone loss that can negatively impact astronauts’ health. In fluid systems, reduced gravity can significantly affect the sloshing dynamics of cryogenic propellants in spacecrafts, surface oscillation of liquid drops, bubble cavitation, and boiling heat transfer in fluids. The positive potential of reduced gravity in the growth of tissue and crystals has been recognized as well.</p> |
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| Rapid and Cost-Effective Isolation and Genotyping of Genomic Regions |
Alan Lemmon |
22-020 |
Michael Tentnowski |
mtentnowksi@fsu.edu |
<p>A method of using a combination of adapter design, hairpinning and exonuclease digestion to enrich samples for target regions of the genome using minimal laboratory effort and produces DNA libraries that can be sequenced. This process allows a rapid and inexpensive way to obtain genotype data in any organism, while avoiding the primary limiting factor of multiplex PCR: primer dimer. This is more flexible in terms of the type of genomic markers that can be evaluated, including SNP, STR (micro satellites), and longer DNA sequence variations.</p>
<p>The technology can be used to obtain randomly distributed (unbiased) markers, or specific genomic regions. The number of regions targeted is also flexible and dramatically reduces upfront development time. Bioinformatic analyses of existing genomes or preliminary DNA sequence data can be conducted quickly to ascertain the most appropriate probes.</p> |
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| Therapeutics for Keloids and Other Fibrotic Disorders |
Akash Gunjan |
23-013 |
Brent Edington |
bedington@fsu.edu |
<p>Keloids are disfiguring, painful, and itchy, but benign fibrotic skin tumors or lesions characterized by excessive dermal fibroblast proliferation and collagen deposition. They occur in susceptible individuals due to abnormal wound healing. Keloids are understudied, difficult to treat, and predominantly affect dark-skinned individuals. Their incidence is estimated to be as high as 1 in 6 among African Americans, compared to around 1 in 1000 among white Americans, suggesting that genetic and/or epigenetic factors contribute strongly to keloid disease. However, the molecular mechanisms involved in driving keloid formation in susceptible individuals are unclear.</p>
<p>Currently there are no standardized treatments available for keloids and they have very high recurrence rates upon surgical resection alone. Intralesional steroids are commonly used, albeit with highly variable responses. Furthermore, although superficial radiation therapy is emerging as one of the most effective post-surgical adjuvant therapies to prevent keloid recurrence, it requires specialized equipment and its association with cancer therapy leads to reluctance among both providers and patients for its use in keloid therapy.</p>
<p>Despite advances in medical research, there is still a scarcity of methods and compositions that are effective in the treatment of keloids that do not require specializedequipment and/or trips to a medical facility, as does radiation therapy. Hence, we have applied a multiplatform approach to identify multiple cellular pathways that can be targeted for keloid therapy using combinations of existing FDA approved or preclinical drugs applied topically. These drugs should greatly expand options for keloid therapy, especially through topical application, leading to a more personalized treatment options.</p> |
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| Generation of Extracellular Vesicles from Human Stem Cells in Dynamic Three-dimensional Cultures |
Yan Li |
23-026 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>A novel stem cell culture method to produce three-dimensional spheroid structures that secrete extracellular vesicles (EVs) with increased yields and cargo capacity. This method unlocks the next-generation of EVs which holds great promise for novel drug delivery methods and cell-free therapeutics.</p> |
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| Control of Multi-Metallic Ratios in Transition Metal Carbides, Phosphides and Nitrides for Electrocatalytic Reactions |
Robert Lazenby |
23-029, 23-052, 23-053 |
Garrett Edmunds |
gedmunds@fsu.edu |
<p>A series of electrocatalysts which efficiently produce Green Hyrdrogen without using costly ruthenium or iridium catalysts. These earth-abundant based materials have carefully controlled syntheses to maximize catalytic efficiency.</p> |
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| Dosing Transcranial Magnetic Brain Stimulation |
Andrew Kozel & Kevin Johnson |
22-046 |
Brent Edington |
bedington@fsu.edu |
<p>Transcranial Magnetic Stimulation (TMS) is a non-invasive method to stimulate the brain, and TMS is FDA cleared for treating depression, OCD and smoking cessation (with many other clinical applications under investigation). Although Transcranial Magnetic Stimulation (TMS) is a highly effective treatment for patients with difficult to treat depression, improvement in remission rates are critically needed. A fundamental problem is that TMS is dosed over the motor cortex which has an observable functional measure (e.g., finger twitch), however, the treatment is performed over the prefrontal cortex (i.e., no observable change). This nonivasive technology uses functional Near-Infrared Spectroscopy (fNIRS) integrated with TMS (TMS-fNIRS) to more accurately personalize treatment dosing of TMS over the prefrontal cortex by <u>more accurately calibrating the dose to the prefrontal cortex</u>. This technology adjusts for coil to cortex distance differences, gyrus orientation differences as well as cortical excitability differences between the motor cortex and dorsolateral prefrontal cortex. The invention involves placement of fNIRS source/detectors under, around, and contralateral to the TMS coil. Thus, a treater can measure the brain effect of TMS and adjust power ("dose&rdquo;) for individual patients to ensure adequate treatment.</p> |
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| RNA Sensors for Detection and Screening of Antifibrotic Drugs |
Branko Stefanovic |
22-042 |
Brent Edington |
bedington@fsu.edu |
<p>5’ stem-loop is unique regulatory element of type I collagen mRNAs which regulates their translation by binding protein LARP6. Drugs that can directly interact with the 5’ stem-loop RNA sequence and interfere with LARP6 recognition can be regarded as truly specific antifibrotic drugs. This invention is to enable screening for such drugs by designing two sensor 5’ stem-loop RNAs which can report drug or protein binding. The sensors are modified by incorporation of a fluorescent nucleotide analog at the critical position in the active site to report the change in fluorescence intensity upon protein or drug binding. Each sensor RNA has only one nucleotide replaced by a fluorescent analog, but they are at different positions in the two sensors so that the sensor RNAs can detect a change in molecular environment at the two positions within the LARP6 recognition site. By measuring the fluorescence intensity of sensors, protein or drug binding to the active site can be detected and quantified. The main application of the sensors is for high throughput screening of compounds that directly interact with 5’ stem-loop RNA, as hits for developing truly specific antifibrotic drugs.</p> |
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| Classical Conditioning of Neuromodulation with Synchronized Musical Stimulation |
Kevin Johnson, Andrew Kozel, and Jayne Standley |
22-027 |
Brent Edington |
bedington@fsu.edu |
<p>Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation treatment method and an FDA-cleared approach to stimulate the brain for treating depression, OCD, and smoking cessation (with many other clinical applications under investigation). A TMS system includes an electric pulse generator or stimulator that is connected to a magnetic coil that is connected to the scalp to generate a varying magnetic field via electromagnetic induction to cause an electric current at a specific area of the brain. TMS over the motor cortex, at sufficient machine power, can cause a thumb/hand movement. TMS treatments are nevertheless cumbersome to perform and are performed by trained technicians in a doctor’s office or clinic. There is a benefit to improving TMS treatments.</p>
<p> </p>
<p>This innovation is a system to evoke or produce neurostimulation effects through music, using the principles of classical (or Pavlovian) conditioning. In classical conditioning the Unconditioned Stimulus (US) inherently produces an Unconditioned Response (UR); when the US is paired with a Conditioning Stimulus (CS), the CS alone subsequently produces a Conditioned Response (CR) that is similar to the UR. This invention involves a system to pair neurostimulation devices (US) with music (CS), for subsequent presentation of music alone. Neurostimulation may be achieved through invasive devices (e.g. peripheral nerve, spinal cord or brain stimulators) or non-invasive devices (e.g. transcutaneous nerve stimulators, transcranial brain stimulation such as electrical or Transcranial Magnetic Stimulation). Music elements may include speakers for audio output, instruments, somatic or tactile sensory outputs, or visual experiences. Music alone may be initiated "on demand”; or on a time or event-based schedule.</p> |
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| Large Scale Purification of Castanospermine |
Gary Ostrander & Eric Holmes |
20-042 |
Brent Edington |
bedington@fsu.edu |
<p>Castanospermine is an alkaloid produced by the <em>Castanospermum australe </em>tree and is enriched in its seeds. Castanospermine is an alpha-glucosidase inhibitor which inhibits glycoprotein processing in mammalian cells by preventing removal of 3-glucose residues linked to a high mannose core structure. This activity of castanospermine has an antiviral effect on many viruses given that many viruses have coat glycoproteins. It has been shown that in many instances misfolded proteins lacking activity occur with castanospermine treatment, thus, castanospermine is apotential anti-viral therapeutic.</p>
<p>The method of the invention is a scalable, large-scale castanospermine preparation method from castanospermine-containing plant sources such as <em>Castanospermum austral</em> seed material. The preparation method differs in significant ways from methods for small-scale analytical isolation of castanospermine and is capable of yielding levels of purity greater than 98%.</p> |
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| Two Phase Indicator Displacement Assay |
Steve Lenhert |
22-048 |
Brent Edington |
bedington@fsu.edu |
<p>Biosensors are developed with the aim of detecting the presence of a target molecule within a certain solution or medium. Within the past few decades, many biosensors revolve around a design involving supramolecular-based molecular sensors, otherwise known as indicator displacement assays (IDAs). These IDAs generally consist of a supramolecular assembly which includes an optical indicator that is reversibly bound to a synthetic receptor. In the presence of an analyte, the optical indicator will be displaced from the synthetic receptor resulting in an optical signal. These IDAs have proven to have many effective applications in the fields of industrial, agriculture, environmental, and biological sciences. Additionally, Indicator displacement can be used to detect binding in biochemical assays. However, there are still many limitations that need to be surmounted if the full capability of this technique is to be recognized. Some of these limitations include low signal-to-noise ratio and sensitivity of IDAs<sup>6</sup>.</p>
<p>Here we describe a new type of displacement assay where the indicator is displaced from one phase into another. We use an organic phase with the indicator dissolved in it and add analyte in a second aqueous phase. This new sensing mechanism is based on analyte partitioning in a two-phased system where the receptor is one of the phases. An indicator what is partitioned into the receptor phase is displaced by an analyte introduced into the aqueous phase leading to label free detection of small molecules. Smaller organic phase droplets allow faster detection, higher sensitivity and lower limits of detection. </p>
<p> The analyte displaces the indicator from the organic phase into the aqueous phase, allowing for analyte detection. We call this new type of displacement assay a partitioning indicator displacement assay (PIDA). The concept of displacement is particularly important in pharmacology, where drug binding proteins in the blood can sequester drugs making them less bioavailable. Understanding displacement is crucial to understanding drug interactions, as taking a second drug can displace the first drug from drug binding proteins leading to toxicity that would not be observed at the dosage of a single drug. This mechanism also has implications in biological systems, where small molecules may be displaced from nonpolar condensates such as lipid bilayers, lipid droplets, or other phase separated compartments.</p>
<p>Example of displacement concept. The blue dye is released as it replaces the red dye associated with a receptor.</p> |
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| Molecular Biomarkers for Predicting Patient Response to Steroid Therapy |
Akash Gunjan |
22-044 |
Brent Edington |
bedington@fsu.edu |
<p>Steroids are commonly prescribed medications in the US and around the world. Topical steroids are used extensively to treat a wide range of skin disorders such as psoriasis, eczema and dermatitis, while local steroid injections are a mainline therapy for benign fibrotic skin tumors know as keloids. Additionally, oral steroids are to treat systemic autoimmune conditions, while inhaled steroids serve as the mainline therapy for long-term control of asthma and nasal allergies. However, there is a wide variation in the response of patients to steroid therapy. For example, only about 34% of keloid patients benefit from steroid therapy, while 49% do not respond to it and the remaining 17% of patients actually see a worsening of their symptoms upon steroid therapy. This variability in patients' responses to steroids is likely due to individual differences in the patients’ genetic or epigenetic makeup, although the genes or epigenetic pathways involved have not yet been identified. The highly variable patient responses to steroid therapy highlight the dire need for a screening test to determine patients’ response to steroids prior to initiating therapy.</p>
<p>Since all our cells reflect our genetic/epigenetic makeup, they are also potentially capable of accurately reporting our response to steroids. Hence, as long as we can obtain a biopsy sample from patients, we can test them for sensitivity to steroids. We have identified six genes whose expression patters correlate well with response to steroids and have developed a simple method for screening patients to determine the effects of steroids. This qRT-PCR based molecular test can provide results in a few hours. In the future it may be possible to use an antibody based lateral flow rapid test that can provide results in minutes.</p> |
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| Area Specific Tissue Analysis (ASTA) |
Sanjay Kumar |
22-024 |
Brent Edington |
bedington@fsu.edu |
<p>ASTA is a methodology for precision harvesting and processing of tissue from acute brain slices for the purposes of cell and molecular biology/analysis. There are currently no known approaches to sampling tissue from hard-to-reach regions of the brain that has been cut acutely into 100 to 500 microns-thick sections for cell biological analysis. Laser dissection is inapplicable/inadequate, laser dissection is more suited for a monolayer of cells. ASTA solves this problem by incorporating 1) visually guided core sampling component and 2) a tissue processing component. Together, this methodology enables precision analysis and tracking of cellular and molecular changes across juxtaposed brain regions (nuclei) and lamina allowing for detailed characterization of disease-related pathology.</p> |
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| Tailored Motivational Interviewing Training |
Sylvie Naar |
21-048 |
Brent Edington |
bedington@fsu.edu |
<p>An evidence-based training program for a front-line behavioral intervention targeting adolescents and young adults. Includes video examples. Can be used by organizations working with young people around health behaviors (managing medical conditions, substance use, smoking, sexual risk), especially members of ethnic, sexual and gender minorities.</p> |
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| Assays for On-Site Identification of Seafood |
Prashant Singh |
22-053 |
Brent Edington |
bedignton@fsu.edu |
<p>The FDA's DNA barcoding method is the gold standard method for identifying seafood species. This method involves shipping samples to testing laboratories. The testing can take from 5 – 10 days and cost $100 - $200 per sample. This method is expensive, time-consuming, highly susceptible to tissue contamination during sample collection and provides detailed information regarding fish species. However, those in the wholesale/retail fish market don’t necessarily wants all the information generated by the DNA barcoding, they only care about whether or not the particular seafood species they’ve purchased or are interested in purchasing is the same species as mentioned on the label (a simple yes/ no answer). There is a need in the industry for a low-cost, rapid assay to discern whether a certain sample is the same seafood species as mentioned on the label or not. Furthermore, there is a need for a method that can be performed onsite, at an in-house food processing facility, in a resource limited setting, using a minimally trained labor.</p>
<p>Our assay is a method that rapidly determines if a specific food product is present or not, the method comprising: providing a sample comprising at least one target sequence; placing the sample into at least one container; using reagents to amplify a sample; amplifying a sample using a small footprint nucleic acid amplification device, wherein the sample is amplified by exposing it to different sets and types of primers (conventional and rhPCR primers) in conditions suitable for nucleic acid amplification, where each set of primers comprises of a forward and reverse primers; exposing the amplified sequence to a means of detection, wherein the means of detection provides a present/not present result; and identifying whether the food or ingredient is present or not, based on the results.</p> |
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