Try Anything

Conference Review “Anxiety, Urgency, Outrage, Hope . . . A Conference on Political Feeling.” Franke Institute for the Humanities, University of Chicago, October 19–20, 200

Reflections 1995

The 1995 issue of Reflections is edited by Mandy Moonyham and Heather Love with Kevin Binfield serving as faculty adviser. Cover art is by Sabrina Barnes. Award winners of the student poetry contest include: Karne Brower and Charles Freeman. Award winners of the student art contest include: Sabrina Barnes, Mickie Norman, and Yasuhiro Mori. This year the Communications Department has sponsored a photography contest; winners include: Jason Kerr, Brenda Ledford, and Shawn Childress.https://digitalcommons.gardner-webb.edu/reflections/1020/thumbnail.jp

Building a Better Description

Universally practiced across the disciplines, description is also consistently devalued or overlooked. In this introduction to the special issue "Description Across Disciplines," Sharon Marcus, Heather Love, and Stephen Best propose that description is a critical practice more complex (and less contradictory) than its detractors have taken it to be. They argue that turning critical attention toward description’s nuances gives us access to the ways that scholars conventionally assign and withhold value and prestige. The authors set forth a number of principles (using their contributors’ essays as a guide) toward the end of "building a better description.

A designed protein interface that blocks fibril formation

Protein fibril formation is implicated in many diseases, and therefore much effort has been focused toward the development of inhibitors of this process. In a previous project, a monomeric protein was computationally engineered to bind itself and form a heterodimer complex following interfacial redesign. One of the protein monomers, termed monomer-B, was unintentionally destabilized and shown to form macroscopic fibrils. Interestingly, in the presence of the designed binding partner, fibril formation was blocked. Here we describe the complete characterization of the amyloid properties of monomer-B and the inhibition of fiber formation by the designed binding partner, monomer-A. Both proteins are mutants of the betal domain of streptococcal protein-G. The free monomer-B protein forms amyloid-type fibrils, as determined by transmission electron microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific dye. Fibril formation kinetics are influenced by pH, protein concentration, and seeding with preformed fibrils. Under all conditions tested, monomer-A was able to inhibit the formation of monomer-B fibrils. This inhibition is specific to the engineered interaction, as incubation of monomer-B with wild-type protein-G (a structural homologue) did not result in inhibition under the same conditions. Thus, this de novo-designed heterodimeric complex is an excellent model system for the study of protein-based fibril formation and inhibition. This system provides additional insight into the development of pharmaceuticals for amyloid disorders, as well as the potential use of amyloid fibrils for self-assembling nanostructures

Ethical Tech Innovation: Uniting Educational Initiatives and Professional Practice

This Knowledge Synthesis Report, “Ethical Tech Innovation: Uniting Educational Initiatives and Professional Practice,” is co-funded by the Social Sciences and Humanities Research Council and the Government of Canada’s Future Skills program.Engineers and other workers at the forefront of technological innovation play a central role in shaping the future of our digital economy, and the COVID-19 pandemic has revealed with stark clarity the urgent need for ethical conversations about the ways technologies are developed and integrated into society. However, there is inadequate understanding about effective methods for integrating ethical training in engineering academia, both in terms of the types of training required and how best to implement this training within existing engineering programs. This neglect poses significant challenges for the engineering profession, particularly since it makes it difficult for educators to effectively deliver and assess ethical training. Going beyond engineering, the consequences of this lack are significant: perpetuating technological bias and inequities, environmental degradation, and a culture that is apathetic to the impacts of technological innovation. This Knowledge Synthesis report, funded by the Social Sciences and Humanities Research Council (SSHRC), responds to this gap in two ways: summarising preliminary findings of a literature review from the past ten years to identify recent knowledge and gaps on effective approaches to embedding ethics in the tech industry; and, synthesizing results of semi-structured interviews with 10 key industry leaders and experts about the need for and barriers of ethics training in engineering. Recommendations for academia, industry, and government are provided to cultivate ethical interventions in academia and industry teaching and training. While the literature presents a great deal of exemplary efforts to grow and embed ethics training, our analysis finds that the status of these efforts in engineering disciplines remain sporadic, transitory, and idiosyncratic. This report therefore aims to empower engineers, engineering educators, administrators, industry professionals, policymakers, and even members of the public to develop new ways to prioritize and embed robust frameworks for ethical thinking in tech sector and engineering culture more broadly.Social Sciences and Humanities Research Council of Canada || Canada's Future Skills Progra

Moving Beyond CHO: Alternative host systems may be the future of biotherapeutics

CHO cells are the primary expression system for recombinant proteins with significant investment over the last three decades resulting in robust cell lines and processes. The flexible nature of CHO has lent itself to multiple process formats, such as fed batch, perfusion and continuous cultures, and advances in omics technology has enabled customization of media formulations and targeted engineering of CHO cells. This knowledge has led to large gains in protein productivity that can be captured with culture duration and/or scale. Despite this, constant pressure exists to reduce cost of manufacturing and improve per batch productivity to meet the needs of increased patient populations and increase accessibility of these therapeutics. Biogen has partnered with MIT to take a holistic view of the potential future of biomanufacturing to identify technologies that can make step changes in productivity and cost reduction. This effort has identified the host system as the most important factor to enabling this vision. Specifically, a non-mammalian host could be the key to realizing the most significant gains in productivity and reduction in cost of manufacturing. Through this initiative, we sought to take a more comprehensive approach to investigate alternative hosts for recombinant antibody production. Eight non-mammalian hosts were selected based on several properties, including proven secretion of recombinant protein products, ability to glycosylate proteins, established genome or molecular biology toolkit, amongst others. The final panel of organisms included yeast, filamentous fungi, a diatom, and a trypanosome. In collaboration with Amyris, we evaluated these eight non-mammalian host cell lines to compare their suitability as a potential primary host for the biotechnology industry. Only non-engineered, wild-type strains were used as a starting point for this evaluation, which assessed the ability of each host to express the same IgG1 model antibody. The outcome of this comparative analysis demonstrated that several of the alternative hosts could express full length antibody with acceptable glycoforms. Additionally, the ease of culture, ability to engineer the genome, and flexibility of carbon source were assessed. As an output of this work, the most productive strains will be made available for use without restrictions to allow others in the community to freely work with these hosts. Based on this initial assessment, a strategy to further investigate the potential of the most promising hosts will be shared

Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota.

Daily PrEP is highly effective at preventing HIV-1 acquisition, but risks of long-term tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC) include renal decline and bone mineral density decrease in addition to initial gastrointestinal side effects. We investigated the impact of TDF-FTC on the enteric microbiome using rectal swabs collected from healthy MSM before PrEP initiation and after 48 to 72 weeks of adherent PrEP use. The V4 region of the 16S ribosomal RNA gene sequencing showed that Streptococcus was significantly reduced from 12.0% to 1.2% (p = 0.036) and Erysipelotrichaceae family was significantly increased from 0.79% to 3.3% (p = 0.028) after 48-72 weeks of daily PrEP. Catenibacterium mitsuokai, Holdemanella biformis and Turicibacter sanguinis were increased within the Erysipelotrichaceae family and Streptococcus agalactiae, Streptococcus oralis, Streptococcus mitis were reduced. These changes were not associated with host factors including PrEP duration, age, race, tenofovir diphosphate blood level, any drug use and drug abuse, suggesting that the observed microbiome shifts were likely induced by daily PrEP use. Long-term PrEP resulted in increases of Catenibacterium mitsuokai and Holdemanella biformis, which have been associated with gut microbiome dysbiosis. Our observations can aid in characterizing PrEP's side effects, which is likely to improve PrEP adherence, and thus HIV-1 prevention

Beyond CHO – Non-mammalian hosts could be the future expression systems of choice for recombinant biotherapeutics

Over the last 30 years there have been tremendous advances in CHO cell culture process engineering. Novel process concepts, such as fed batch, perfusion and continuous cultures, evolved from a deep understand of CHO metabolic needs and extensive media/feed formulation development. This knowledge has led to large gains in protein productivity that can be captured with culture duration and/or scale. The biotechnology industry is consistently pressured to reduce cost of manufacturing and improve per batch productivity. Independent, but related to this burden, is the ability to support an ever growing patient population with high doses of therapeutic protein. As such, Biogen partnered with MIT to take a holistic view of the potential future of biomanufacturing to identify technologies that can make step changes in productivity and cost reduction. These efforts have cast doubt that CHO would be the optimal host in the future, whereas a non-mammalian host could be a key to realizing the most significant gains in productivity and reduction in cost of manufacturing. Recombinant antibody production from non-mammalian hosts has been reported in the past, for example from the yeast pichia and filamentous fungi Trichoderma, and antibody material produced from pichia has been used in clinical trials. In the next phase of this initiative, we sought to take a more comprehensive approach to investigate alternative hosts in recombinant antibody production. Eight non-mammalian hosts were selected based on a number of properties, including proven secretion of recombinant protein products, ability to glycosylate proteins, established genome or molecular biology toolkit, amongst other characteristics. We designed an experimental plan that would enable more straightforward comparative analysis between hosts and included two main criteria to maintain a level playing field. First, only non-engineered, wild-type strains would be used as a starting point for all eight hosts of interest. Second, a single IgG1 model antibody was selected to be expressed by all hosts. In this presentation, the outcome of this comparative analysis will be discussed, including productivity values and details of the model antibody product quality. Based on this data the most productive strains will be made available for use without restrictions to allow others in the community to freely work with these hosts