I Rest My Case! The Possibilities and Limitations of Blockchain-Based IP Protection

We have identified, mapped and discussed existing research on Blockchain-based solutions for intellectual property (IP) protection, an investigation that emerged from a case in antibody production for scientific and medical applications. To that end, we have performed a systematic literature review and created an instrument that classifies the contributions according to the materiality of the object they protect (from immaterial to physical), the type of protection (authorship notarization or prevention of illegal use) and the type of research (conceptual or empirical). Our results can be used to understand which avenues to pursue in the effort to create a new generation of more effective technology-assisted IP protection systems, a priority for 152 signatory countries of the patent cooperation treaty

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution

Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems. Advisers: Myra B. Cohen and Brittany A. Dunca

Genome-Driven Targeted Cancer Therapy

abstract: Cancer is a heterogeneous disease with discrete oncogenic mechanisms. P53 mutation is the most common oncogenic mutation in many cancers including breast cancer. This dissertation focuses on fundamental genetic alterations enforced by p53 mutation as an indirect target. p53 mutation upregulates the mevalonate pathway genes altering cholesterol biosynthesis and prenylation. Prenylation, a lipid modification, is required for small GTPases signaling cascades. Project 1 demonstrates that prenylation inhibition can specifically target cells harboring p53 mutation resulting in reduced tumor proliferation and migration. Mutating p53 is associated with Ras and RhoA activation and statin prevents this activity by inhibiting prenylation. Ras-related pathway genes were selected from the transcriptomic analysis for evaluating correlation to statin sensitivity. A gene signature of seventeen genes and TP53 genotype (referred to as MPR signature) is generated to predict response to statins. MPR signature is validated through two datasets of drug screening in cell lines. As advancements in targeted gene modification are rising, the CRISPR-Cas9 technology has emerged as a new cancer therapeutic strategy. One of the important risk factors in gene therapy is the immune recognition of the exogenous therapeutic tool, resulting in obstruction of treatment and possibly serious health consequences. Project 2 describes a method development that can potentially improve the safety and efficacy of gene-targeting proteins. A cohort of 155 healthy individuals was screened for pre-existing B cell and T cell immune response to the S. pyogenes Cas9 protein. We detected antibodies against Cas9 in more than 10% of the healthy population and identified two immunodominant T cell epitopes of this protein. A de-immunized Cas9 that maintains the wild-type functionality was engineered by mutating the identified T cell epitopes. The gene signature and method described here have the potential to improve strategies for genome-driven tumor targeting.Dissertation/ThesisDoctoral Dissertation Chemistry 201

Terrified by Technology: How Systemic Bias Distorts U.S. Legal and Regulatory Responses to Emerging Technology

Americans are becoming increasingly aware of the systemic biases we possess and how those biases preclude us from collectively living out the true meaning of our national creed. But to fully understand systemic bias we must acknowledge that it is pervasive and extends beyond the contexts of race, privilege, and economic status. Understanding all forms of systemic bias helps us to better understand ourselves and our shortcomings. At first glance, a human bias against emerging technology caused by systemic risk misperception might seem uninteresting or unimportant. But this Article demonstrates how the presence of systemic bias anywhere, even in an area as unexpected as technology regulation, creates inefficiencies and inequalities that exact heavy costs in the form of human lives, standards of living, and lost economic opportunities. The decision to regulate or implement an emerging technology, like any other complex decision, naturally involves some form of cost-benefit or risk-reward analysis. However, in the context of emerging technology, that analysis is biased by systemic risk misperception. Immutable characteristics existing in emerging technology combine with interrelated characteristics in human decisionmakers and regulators to inflate perceptions of risks and depress perceptions of benefits. This artificial shifting of cost-benefit curves results in suboptimal legislative and regulatory responses to emerging technology, and ultimately, in the loss of American lives

Expression of O-linked N-acetylglucosamine modified proteins and production and characterization of chlamydia trachomatis CT663

O-linked â-N-acetylglucosamine is a regulatory post translational modification. This modification occurs on nearly all functional classes of proteins, in the nucleus and cytoplasm. O-GlcNAc is added to serine or threonine by O-GlcNAc transferase and removed by O-GlcNAcase. Previous attempts to study O-GlcNAc-modified proteins have resulted in low yields, making 3-dimensional structure determination impossible. In this dissertation O-GlcNAc transferase will be co-expressed with domains of human cAMP responsive element-binding protein (CREB1) and Abelson tyrosine-kinase 2 (ABL2) in E. coli, to produce O-GlcNAc-modified protein. The O-GlcNAc-modified protein was expressed in a variety of E. coli cell lines at a variety of conditions, but only small quantities of insoluble protein were produced. A glycosidase was suspected due to the disappearance of the O-GlcNAc modification from the protein. O-(2-acetamido-2-dexoy-dglucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), a â-N-acetylglucosaminidase inhibitor, was added to the culture media and increased the production of O-GlcNAc-modified protein. This was the first evidence that â-N-acetylglucosaminidase (NagZ), an E. coli enzyme, cleaves O-GlcNAc from proteins in vivo. NagZ was isolated and shown to cleave O-GlcNAc from a synthetic O-GlcNAc-peptide in vitro. In E. coli, NagZ cleaves the GlcNAc-â1,4-N-acetylmuramic acid linkage to recycle peptidoglycan in the cytoplasm. A NagZ knockout showed no activity towards the O-GlcNAc-peptide, confirming NagZ as the enzyme responsible for cleaving O-GlcNAc from our glycoprotein expressed in vivo. O-GlcNAc-modified protein produced by the NagZ knockout (∆NagZ) co-expression system is highly glycosylated and can be resolubilized from the pellet. The ∆NagZ is a step closer to production of milligram quantities of O-GlcNAc-modified protein for structure determination

Business Model Innovation For Potentially Disruptive Technologies: The Case Of Big Pharmaceutical Firms Accommodating Biotechnologies

Potenziell disruptive Technologien sind schwer zu vermarkten, weil sie mit Werten verbunden sind, die für etablierte Unternehmen neu sind. Ohne geeignete Geschäftsmodellinnovation gelingt es den etablierten Unternehmen nicht, neue, potenziell disruptive Technologien auf den Markt zu bringen. Die aufkeimende Literatur über disruptive Innovationen bietet nur begrenzte Empfehlungen zu spezifischen Geschäftsmodellelementen, die dazu dienen können, potenziell disruptive Technologien zu integrieren. Um diese Forschungslücke zu schließen, wird in dieser Arbeit untersucht, wie große Pharmaunternehmen Biotechnologien in die Gestaltung ihrer Geschäftsmodellinnovation einbezogen haben, um erfolgreiche Elemente der Geschäftsmodellgestaltung zu ermitteln. Es wird ein qualitativer Forschungsansatz gewählt, der aus drei Studien besteht. Zunächst werden nach einer systematischen Literaturrecherche zur Geschäftsmodellforschung in der pharmazeutischen Industrie 45 Arbeiten ausgewählt und qualitativ ausgewertet. Zweitens werden qualitative halbstrukturierte Interviews mit 16 Experten in großen Pharmaunternehmen geführt. Die Transkripte werden mit der Methode der Qualitativen Inhaltsanalyse ausgewertet. Schließlich wird eine Clusteranalyse durchgeführt, um den von allen digitalen Angeboten großer Pharmaunternehmen vorgeschlagenen und gelieferten Wert zu ermitteln. In dieser Arbeit werden erstmals zwei Geschäftsmodelle großer Pharmaunternehmen aus der Zeit vor und nach der Einführung der Biotechnologien beschrieben. In dieser Arbeit wird argumentiert, dass für die Anpassung an potenziell disruptive Technologien folgende Geschäftsmodellelemente empfohlen werden: Kollaborationsportfolios und digitale Servitisierung. Erstens sollten etablierte Unternehmen ein Portfolio von Kooperationsformaten entwickeln, indem sie die Breite der Partner (einschließlich der Wettbewerber) diversifizieren und alle Aktivitäten in ihrer Wertschöpfungskette abdecken. Zweitens sollten die etablierten Unternehmen den Wert, den sie anbieten, und die Art und Weise, wie sie diesen Wert für etablierte und neue Kundensegmente bereitstellen, innovativ gestalten, indem sie ihre Produkte mit ergänzenden Dienstleistungen bündeln, insbesondere mit solchen, die digital ermöglicht werden. Digitale Dienstleistungen dienen dazu, die Bedürfnisse der Kunden mit denen des Herstellers zu verknüpfen. Neben der Weiterentwicklung der Theorie über disruptive Innovationen können die empfohlenen Elemente des Geschäftsmodells von führenden mittelständischen Pharmaunternehmen (z. B. Fresenius oder Servier) und Unternehmen aus anderen Branchen direkt genutzt werden, um andere potenziell disruptive Technologien zu vermarkten. Diese Forschung unterstützt politische Entscheidungsträger bei der Entwicklung von Strategien zur Förderung der Kommerzialisierung potenziell disruptiver Innovationen in ihrem spezifischen Kontext.Potentially disruptive technologies are challenging to commercialize because they are associated with values new to established firms. Without fitting business model innovation, incumbent firms fail to bring new potentially disruptive technologies to the market. The burgeoning literature on disruptive innovation provides only limited recommendations on specific business model elements that can serve to accommodate potentially disruptive technologies. To close this research gap, this thesis explores how big pharmaceutical firms accommodated biotechnologies in the design of their business model innovation to discover successful business model design elements. A qualitative research approach consisting in three studies is adopted. First, following a systematic literature review on business model research in the pharmaceutical industry, 45 papers are selected and qualitatively analyzed. Second, qualitative semi-structured interviews are conducted with 16 experts in big pharmaceutical firms. The transcripts are analyzed using the qualitative content analysis method. Finally, a cluster analysis is conducted to identify value proposed and delivered by all digital offers of big pharmaceutical firms. This thesis is the first to describe two business model designs of big pharmaceutical firms from before and since the accommodation of biotechnologies. This research argues that business model designs recommended for the accommodation of potentially disruptive technologies are collaboration portfolios and digital servitization. First, established firms should devise a portfolio of collaboration formats by diversifying breadth of partners (including competitors), and by covering all activities in their value chain. Second, incumbent firms should innovate in the value they offer and how they deliver it to mainstream and new customer segments though bundling their products with complementary services, especially those that are digitally enabled. Digital services serve for back-coupling customers’ needs with the producer. Besides advancing theory on disruptive innovation, the recommended business model design elements can be directly used by top midsize pharmaceutical firms (e.g., Fresenius or Servier) and firms from other industries to commercialize other potentially disruptive technologies. This research supports policy makers in devising strategies for the promotion of the commercialization of potentially disruptive innovations in their specific contexts

Winthrop University Undergraduate Scholarship & Creative Activity 2022

University College and Winthrop University proudly present Undergraduate Scholarship and Creative Activity 2022. This eleventh annual University-wide compilation of undergraduate work chronicles the efforts and accomplishments of students and faculty mentors campus wide. The remarkable work summarized in these pages represents nearly every academic department and spans all five colleges of the university: College of Arts and Sciences (CAS), College of Business Administration (CBA), College of Education (COE), College of Visual and Performing Arts (CVPA) and University College (UC).https://digitalcommons.winthrop.edu/undergradresearch_abstractbooks/1020/thumbnail.jp

12th Annual Focus on Creative Inquiry Poster Forum Program

The 2017 Focus on Creative Inquiry Poster Forum displays a selection of the projects accomplished by Clemson University students in their Creative Inquiry teams. What is Creative Inquiry? It is small-group learning for all students, in all disciplines. It is the imaginative combination of engaged learning and undergraduate research – and it is unique to Clemson University. In Creative Inquiry, small teams of undergraduate students work with faculty mentors to take on problems that spring from their own curiosity, a professor’s challenge, or the pressing needs of the world around them. Students take ownership of their projects. They ask questions, they take risks, and they get answers