{"title":"Re-Invigorating HIBAR Research for the 21st Century : Enhancing Fundamental Research Excellence in Service to Society","authors":"L. Whitehead, S. Slovic, Janet E. Nelson","doi":"10.14288/1.0379895","DOIUrl":"https://doi.org/10.14288/1.0379895","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"46 1","pages":"153-167"},"PeriodicalIF":0.5,"publicationDate":"2020-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84098351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Supercoiling affects every aspect of DNA function (replication, transcription, repair, recombination, etc.), yet the vast majority of studies on DNA and crystal structures of the molecule utilize short linear duplex DNA, which cannot be supercoiled. To study how supercoiling drives DNA biology, we developed and patented methods to make milligram quantities of tiny supercoiled circles of DNA called minicircles. We used a collaborative and multidisciplinary approach, including computational simulations (both atomistic and coarse-grained), biochemical experimentation, and biophysical methods to study these minicircles. By determining the three-dimensional conformations of individual supercoiled DNA minicircles, we revealed the structural diversity of supercoiled DNA and its highly dynamic nature. We uncovered profound structural changes, including sequence-specific base-flipping (where the DNA base flips out into the solvent), bending, and denaturing in negatively supercoiled minicircles. Counterintuitively, exposed DNA bases emerged in the positively supercoiled minicircles, which may result from inside-out DNA (Pauling-like, or "P-DNA"). These structural changes strongly influence how enzymes interact with or act on DNA. We hypothesized that, because of their small size and lack of bacterial sequences, these small supercoiled DNA circles may be efficient at delivering DNA into cells for gene therapy applications. "Minivectors," as we named them for this application, have proven to have therapeutic potential. We discovered that minivectors efficiently transfect a wide range of cell types, including many clinically important cell lines that are refractory to transfection with conventional plasmid vectors. Minivectors can be aerosolized for delivery to lungs and transfect human cells in culture to express RNA or genes. Importantly, minivectors demonstrate no obvious vector-associated toxicity. Minivectors can be repeatedly delivered and are long-lasting without integrating into the genome. Requests from colleagues around the world for minicircle and minivector DNA revealed a demand for our invention. We successfully obtained start-up funding for Twister Biotech, Inc. to help fulfill this demand, providing DNA for those who needed it, with a long-term goal of developing human therapeutics. In summary, what started as a tool for studying DNA structure has taken us in new and unanticipated directions.
{"title":"BIOPHYSICS MEETS GENE THERAPY: HOW EXPLORING SUPERCOILING-DEPENDENT STRUCTURAL CHANGES IN DNA LED TO THE DEVELOPMENT OF MINIVECTOR DNA.","authors":"Lynn Zechiedrich, Jonathan M Fogg","doi":"10.21300/20.4.2019.427","DOIUrl":"https://doi.org/10.21300/20.4.2019.427","url":null,"abstract":"<p><p>Supercoiling affects every aspect of DNA function (replication, transcription, repair, recombination, etc.), yet the vast majority of studies on DNA and crystal structures of the molecule utilize short linear duplex DNA, which cannot be supercoiled. To study how supercoiling drives DNA biology, we developed and patented methods to make milligram quantities of tiny supercoiled circles of DNA called minicircles. We used a collaborative and multidisciplinary approach, including computational simulations (both atomistic and coarse-grained), biochemical experimentation, and biophysical methods to study these minicircles. By determining the three-dimensional conformations of individual supercoiled DNA minicircles, we revealed the structural diversity of supercoiled DNA and its highly dynamic nature. We uncovered profound structural changes, including sequence-specific base-flipping (where the DNA base flips out into the solvent), bending, and denaturing in negatively supercoiled minicircles. Counterintuitively, exposed DNA bases emerged in the positively supercoiled minicircles, which may result from inside-out DNA (Pauling-like, or \"P-DNA\"). These structural changes strongly influence how enzymes interact with or act on DNA. We hypothesized that, because of their small size and lack of bacterial sequences, these small supercoiled DNA circles may be efficient at delivering DNA into cells for gene therapy applications. \"Minivectors,\" as we named them for this application, have proven to have therapeutic potential. We discovered that minivectors efficiently transfect a wide range of cell types, including many clinically important cell lines that are refractory to transfection with conventional plasmid vectors. Minivectors can be aerosolized for delivery to lungs and transfect human cells in culture to express RNA or genes. Importantly, minivectors demonstrate no obvious vector-associated toxicity. Minivectors can be repeatedly delivered and are long-lasting without integrating into the genome. Requests from colleagues around the world for minicircle and minivector DNA revealed a demand for our invention. We successfully obtained start-up funding for Twister Biotech, Inc. to help fulfill this demand, providing DNA for those who needed it, with a long-term goal of developing human therapeutics. In summary, what started as a tool for studying DNA structure has taken us in new and unanticipated directions.</p>","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"20 4","pages":"427-439"},"PeriodicalIF":0.5,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21300/20.4.2019.427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael K. Carroll, K. Carroll, J. Rheinstein, M. Jason Highsmith
Many unilateral amputations are followed by a contralateral amputation within three years, sometimes presenting as bilateral transfemoral amputations. Bilateral transfemoral amputees that successfully use prostheses are an understudied patient population. This study establishes reference values for this population in users of short non-articulating (stubby) or full-length articulating prostheses. Anthropometric and demographic information was collected from participants. Additionally, participants completed a self-reported Prosthesis Evaluation Questionnaire-Mobility Subscale 12/5 (PEQ-MS) and performed multiple physical mobility tests, including walking tests and the multi-directional Four Square Step Test (FSST). Full-length users rated their abilities to complete the PEQ-MS tasks as less difficult than stubby users in eight of the 12 items. Gait analysis revealed a greater amount of time is spent in stance phase with a greater portion in double limb support for both user groups, and a greater percentage in stance phase for the subject-reported dominant limb. Stubby users' gait velocity had a significant reduction from that of their full-length peers; however, cadence was similar between groups. Both user groups completed the FSST at comparable times. These outcomes may be of benefit for identifying tasks bilateral transfemoral prosthetic users may find to be most difficult as well as for identifying normal ambulation patterns within this population. Future studies with a greater number of subjects would enable these results to be further generalized.
{"title":"FUNCTIONAL DIFFERENCES OF BILATERAL TRANSFEMORAL AMPUTEES USING FULL-LENGTH AND STUBBY-LENGTH PROSTHESES.","authors":"Michael K. Carroll, K. Carroll, J. Rheinstein, M. Jason Highsmith","doi":"10.21300/20.1-2.2018.75","DOIUrl":"https://doi.org/10.21300/20.1-2.2018.75","url":null,"abstract":"Many unilateral amputations are followed by a contralateral amputation within three years, sometimes presenting as bilateral transfemoral amputations. Bilateral transfemoral amputees that successfully use prostheses are an understudied patient population. This study establishes reference values for this population in users of short non-articulating (stubby) or full-length articulating prostheses. Anthropometric and demographic information was collected from participants. Additionally, participants completed a self-reported Prosthesis Evaluation Questionnaire-Mobility Subscale 12/5 (PEQ-MS) and performed multiple physical mobility tests, including walking tests and the multi-directional Four Square Step Test (FSST). Full-length users rated their abilities to complete the PEQ-MS tasks as less difficult than stubby users in eight of the 12 items. Gait analysis revealed a greater amount of time is spent in stance phase with a greater portion in double limb support for both user groups, and a greater percentage in stance phase for the subject-reported dominant limb. Stubby users' gait velocity had a significant reduction from that of their full-length peers; however, cadence was similar between groups. Both user groups completed the FSST at comparable times. These outcomes may be of benefit for identifying tasks bilateral transfemoral prosthetic users may find to be most difficult as well as for identifying normal ambulation patterns within this population. Future studies with a greater number of subjects would enable these results to be further generalized.","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"75 1","pages":"75-83"},"PeriodicalIF":0.5,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90848504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Building Impactful National Academy of Inventors (NAI) Chapters","authors":"K. Burg","doi":"10.21300/19.3.2018.631","DOIUrl":"https://doi.org/10.21300/19.3.2018.631","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"73 1","pages":"631-634"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86809502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pillars of Academic Innovation: The Sixth Annual Conference of the NAI","authors":"T. Keiller, E. Mathiowitz","doi":"10.21300/19.3.2018.567","DOIUrl":"https://doi.org/10.21300/19.3.2018.567","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"518 1","pages":"567-568"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77476604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
593 Online platforms today are being used in deplorably diverse ways: recruiting and radicalizing terrorists; exploiting children; buying and selling illegal weapons and underage prostitutes; bullying, stalking, and trolling on social media; distributing revenge porn; stealing personal and financial data; propagating fake and hateful news; and more. Technology companies have been and continue to be frustratingly slow in responding to these real threats with real consequences. I advocate for the development and deployment of new technologies that allow for the free flow of ideas while reining in abuses. As a case study, I will describe the development and deployment of two such technologies—photoDNA and eGlyph—that are currently being used in the global fight against child exploitation and extremism.
{"title":"Reining in Online Abuses","authors":"H. Farid","doi":"10.21300/19.3.2018.593","DOIUrl":"https://doi.org/10.21300/19.3.2018.593","url":null,"abstract":"593 Online platforms today are being used in deplorably diverse ways: recruiting and radicalizing terrorists; exploiting children; buying and selling illegal weapons and underage prostitutes; bullying, stalking, and trolling on social media; distributing revenge porn; stealing personal and financial data; propagating fake and hateful news; and more. Technology companies have been and continue to be frustratingly slow in responding to these real threats with real consequences. I advocate for the development and deployment of new technologies that allow for the free flow of ideas while reining in abuses. As a case study, I will describe the development and deployment of two such technologies—photoDNA and eGlyph—that are currently being used in the global fight against child exploitation and extremism.","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"35 1","pages":"593-599"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90532470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa B. Crawford, Zakiya S. Wilson-Kennedy, Gloria A. Thomas, Samuel D. Gilman, I. Warner
{"title":"LA-STEM Research Scholars Program: A Model for Broadening Diversity in STEM Education","authors":"Melissa B. Crawford, Zakiya S. Wilson-Kennedy, Gloria A. Thomas, Samuel D. Gilman, I. Warner","doi":"10.21300/19.3.2018.577","DOIUrl":"https://doi.org/10.21300/19.3.2018.577","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"73 1","pages":"577-592"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85533719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Entrepreneurship and Commercialization At Universities: A Faculty Perspective","authors":"Amy Phillips, Paul Tumarkin, N. Peyghambarian","doi":"10.21300/19.3.2018.601","DOIUrl":"https://doi.org/10.21300/19.3.2018.601","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"94 2 1","pages":"601-603"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86174747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The United States Patent and Trademark Office's Partnership with the National Inventors Hall of Fame","authors":"Philippa Olsen, Linda Hosler","doi":"10.21300/19.3.2018.639","DOIUrl":"https://doi.org/10.21300/19.3.2018.639","url":null,"abstract":"","PeriodicalId":44009,"journal":{"name":"Technology and Innovation","volume":"45 1","pages":"639-643"},"PeriodicalIF":0.5,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77237945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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