Hope College and Ready for Life: Kate\u27s Story

In an effort to merge social science and humanities methodology, I undertook an ethnographic case study of Ms. Kate Veldink, a student in the Ready for Life (RFL) program at Hope College. My research question is: What are the day-to-day experiences of a RFL student on Hope College’s campus? I obtained consent from Ms. Veldink and her family, enabling us to embark as research partners in this query. Through the Mellon Scholars Program of Hope College, we created an inquiry-into-research project as an extension to the class Human Behavior and the Social Environment in the Department of Sociology and Social Work. We investigated accessibility and awareness for students with disabilities on-campus in the RFL program. Under the mentorship of advisor Dr. Dennis Feaster, we developed a project to showcase Ms. Veldink’s vision for greater integration between Hope College and RFL. We used oral history methodology to conduct a series of interviews with Ms. Veldink and her family, friends, and community supports. Both the Grounded Theory and Cooley’s looking-glass self concept further informed our process as these interviews were then analyzed and compiled into a short documentary that brings to light the story of Ms. Veldink and her peers as they navigate Hope College through the RFL program, and calls to action the administration of Hope College to recognize and react to these students’ realities. A central theme that emerged from this process is the paradox between accessibility and barriers for RFL students. Hope College welcomes RFL students into the campus community, but inviting these students into our daytime routine is not enough. Rather, we must embrace the challenge of Hope College’s core values of “being a caring community” that “fosters the development of the whole person - intellectually, spiritually, socially, and physically.

Compression and communication in the cultural evolution of linguistic structure

Language exhibits striking systematic structure. Words are composed of combinations of reusable sounds, and those words in turn are combined to form complex sentences. These properties make language unique among natural communication systems and enable our species to convey an open-ended set of messages. We provide a cultural evolutionary account of the origins of this structure. We show, using simulations of rational learners and laboratory experiments, that structure arises from a trade-off between pressures for compressibility (imposed during learning) and expressivity (imposed during communication). We further demonstrate that the relative strength of these two pressures can be varied in different social contexts, leading to novel predictions about the emergence of structured behaviour in the wild

Venice: Behind the mask, an architectural study

This study will illustrate and explore the conservation policies and procedures adopted by the authorities in Venice and investigate the legalities of restoration practice employed by the state. As well as this, Venice's struggle for a new sense of identity is a premise for this study. The role of modern architecture in Venice and the type of design that could find a sympathetic home here is explored. Essentially, the question of the future of the architectural fabric of Venice, both prospective development and the conservation of what already exists, is the theme of this work. Chapter one outlines the designs for the Biennale competition of 1991, Una Porta per Venezia and uses it as an opportunity to highlight the particular difficulties for the architect in creating an architecture for Venice. Issues such as the essential tension between the traditional and the modern, and the relationship between a building and its site are explored in this chapter. An assessment of the competition entries, and specifically the winning design by Dixon Jones, is used as an attempt to establish the preferences and priorities of the Biennale panel, many of which are directly responsible for any future development of the built environment in Venice. Chapter two seeks to set the Dixon Jones project in its wider context and underlines the ambiguities and inconsistencies in which new development in Venice is managed. It attempts to determine possible motivations behind the inclusion of certain designs into the historic fabric and the omission of others. In Illustrating recent admissions to the built environment, Chapter two explores the theory that modern architecture in Venice has been a slave to traditional typologies and that this has impeded the formulation of an appropriately modern architectural language for Venice. Chapter three outlines and examines restoration practice in Venice. It proposes that the interventions have, as a whole, been destructive and investigates where the system of management and the laws that govern conservation in Venice are inadequate. Specific instances of the harsh restoration techniques employed by the state are illustrated and examples of conservation projects carried out by international agencies, as an alternative to those of the Venetian authorities, are also outlined. This chapter argues that the working methods of the state and those of the international funding bodies represent two different philosophies, and essentially, distinct interpretations of the future of Venice. It suggests the city council in Venice perceives the city's future as transformation and the International funding bodies as conservation

Challenges and solutions for allogeneic cell therapy manufacturing

Development of a scalable and robust manufacturing process will be critical for successful commercialization of an allogeneic cell therapy product. However, the biological characteristics of anchorage-dependent cells and the process requirements for mass production of living human cells as a final product create different challenges compared to traditional biotech manufacturing. This presentation will discuss some of these challenges and potential solutions, particularly those that relate to manufacturing of allogeneic cell therapy products at larger volumetric scales. Single-use bioreactors have the potential to be the optimal technology for scalable and costeffective manufacturing of therapeutic cells. However, cell expansion and differentiation processes involving large suspended particles, such as cell aggregates or microcarriers with attached cells, are significantly affected by a bioreactor’s hydrodynamic conditions. The intensity and distribution of conditions such as fluid flow, turbulent energy dissipation rate, and shear forces will influence the quality and quantity of cells. A bioreactor that is capable of creating optimal conditions at small scale during process development and then consistently replicating those conditions at larger scales will be a key enabling technology. Maintaining optimal growth parameters for therapeutic cells during scale up in bioreactors is another critical challenge. In particular, providing sufficient dissolved oxygen and maintaining optimal pH for large-scale cell culture processes will be essential to maximizing cell yield and quality. For recombinant protein manufacturing processes, gas is sparged directly into fluid and anti-foaming agents are added, as such chemicals can be removed during extensive downstream purification steps. In contrast, therapeutic cells are the final product and are more susceptible to shear damage from bursting bubbles, and it would be difficult to remove hydrophobic anti-foaming chemicals from cell membranes through simple buffer washes. Any potential solution for large-scale oxygenation and removal of pCO2 from a bioreactor will likely seek to avoid exposing cells to sparging or foreign chemical contaminants. The process duration and conditions of exchanging spent medium in a bioreactor at larger scales is another potential bottleneck for allogeneic cell therapy manufacturing. Complete and rapid medium exchange is especially crucial for differentiation processes in order to minimize unwanted heterogeneous differentiation of cells. Pausing agitation and allowing cell aggregates or microcarriers to settle in order to remove supernatant and replenish new medium becomes a less desirable option at larger scales due to prolonged processing times and undesirable conditions which can negatively impact cell viability, yield, and quality. The optimal solution will minimize the amount of leftover medium and the time for cells to be transferred into new medium. A final challenge to consider is large scale dissociation of cell aggregates into single cells, or cells from surfaces of microcarriers, for serial passaging or harvesting. Addition of enzymes along with a temporary increase in impeller agitation speed are typically performed to facilitate separation. Depending on a bioreactor’s mixing characteristics, the agitation required to efficiently dissociate considerable quantities of cells at larger volumes may also increase the likelihood of damage to cells. A bioreactor and methodology that can minimize potential harm to cells during dissociation processes are desirable solutions. Ultimately, all of these presented manufacturing process challenges will need to be addressed in order to scale up allogeneic cell therapy products from research and development to clinical and commercial production

Challenges and solutions for allogeneic cell therapy manufacturing

Development of a scalable and robust manufacturing process will be critical for successful commercialization of an allogeneic cell therapy product. However, the biological characteristics of anchorage-dependent cells and the process requirements for mass production of living human cells as a final product create different challenges compared to traditional biotech manufacturing. This presentation will discuss some of these challenges and potential solutions, particularly those that relate to manufacturing of allogeneic cell therapy products at larger volumetric scales. Single-use bioreactors have the potential to be the optimal technology for scalable and cost-effective manufacturing of therapeutic cells. However, cell expansion and differentiation processes involving large suspended particles, such as cell aggregates or microcarriers with attached cells, are significantly affected by a bioreactor’s hydrodynamic conditions. The intensity and distribution of conditions such as fluid flow, turbulent energy dissipation rate, and shear forces will influence the quality and quantity of cells. A bioreactor that is capable of creating optimal conditions at small scale during process development and then consistently replicating those conditions at larger scales will be a key enabling technology. Maintaining optimal growth parameters for therapeutic cells during scale up in bioreactors is another critical challenge. In particular, providing sufficient dissolved oxygen and maintaining optimal pH for large-scale cell culture processes will be essential to maximizing cell yield and quality. For recombinant protein manufacturing processes, gas is sparged directly into fluid and anti-foaming agents are added, as such chemicals can be removed during extensive downstream purification steps. In contrast, therapeutic cells are the final product and are more susceptible to shear damage from bursting bubbles, and it would be difficult to remove hydrophobic anti-foaming chemicals from cell membranes through simple buffer washes. Any potential solution for large-scale oxygenation and removal of pCO2 from a bioreactor will likely seek to avoid exposing cells to sparging or foreign chemical contaminants. The process duration and conditions of exchanging spent medium in a bioreactor at larger scales is another potential bottleneck for allogeneic cell therapy manufacturing. Complete and rapid medium exchange is especially crucial for differentiation processes in order to minimize unwanted heterogeneous differentiation of cells. Pausing agitation and allowing cell aggregates or microcarriers to settle in order to remove supernatant and replenish new medium becomes a less desirable option at larger scales due to prolonged processing times and undesirable conditions which can negatively impact cell viability, yield, and quality. The optimal solution will minimize the amount of leftover medium and the time for cells to be transferred into new medium. A final challenge to consider is large scale dissociation of cell aggregates into single cells, or cells from surfaces of microcarriers, for serial passaging or harvesting. Addition of enzymes along with a temporary increase in impeller agitation speed are typically performed to facilitate separation. Depending on a bioreactor’s mixing characteristics, the agitation required to efficiently dissociate considerable quantities of cells at larger volumes may also increase the likelihood of damage to cells. A bioreactor and methodology that can minimize potential harm to cells during dissociation processes are desirable solutions. Ultimately, all of these presented manufacturing process challenges will need to be addressed in order to scale up allogeneic cell therapy products from research and development to clinical and commercial production

Postoperative Radiotherapy and Facial Nerve Outcomes Following Nerve Repair: A Systematic Review

OBJECTIVE: To compare outcomes of facial nerve repair or grafting following facial nerve-sacrificing procedures among patients treated with and without postoperative radiotherapy (RT). DATA SOURCES: PubMed, OVID, Conference Papers Index, Cochrane Library, ClinicalTrials.gov. REVIEW METHODS: Databases were searched using terms including facial nerve, graft, repair, and radiotherapy. Abstracts mentioning facial nerve repair and evaluation of facial nerve function were included for full-text review. Studies that utilized the House-Brackmann or similar validated scale for evaluation of postoperative facial nerve function were selected for review. All identified studies were included in a pooled t test analysis. RESULTS: Twelve studies with 142 patients were included in the systematic review. All 12 studies individually demonstrated no significant difference in facial nerve outcomes between patients who received postoperative radiation and patients who did not. A pooled t test of data from all studies also demonstrated no significant difference in postoperative facial nerve function between the postoperative RT and non-RT groups (t stat = 0.92, p = .36). CONCLUSION: This analysis, including 12 studies, demonstrated that among patients undergoing facial nerve grafting or repair, there was no significant difference in postoperative facial nerve function between postoperative RT and non-RT patients. Due to the small sample size and variability in study methods, further studies directly comparing outcomes between patients with and without postoperative RT would be beneficial

Computational Tracking of Shear-Mediated Platelet Interactions with von Willebrand Factor

The imaging of shear-mediated dynamic platelet behavior interacting with surface-immobilized von Willebrand factor (vWF) has tremendous potential in characterizing changes in platelet function for clinical diagnostics purposes. However, the imaging output, a series of images representing platelets adhering and rolling on the surface, poses unique, non-trivial challenges for software algorithms that reconstruct the positional trajectories of platelets. We report on an algorithm that tracks platelets using the output of such flow run experiments, taking into account common artifacts encountered by previously-published methods, and we derive seven key metrics of platelet dynamics that can be used to characterize platelet function. Extensive testing of our method using simulated platelet flow run data was carried out to validate our tracking method and derived metrics in capturing key platelet-vWF interaction-dynamics properties. Our results show that while the number of platelets present on the imaged area is the leading cause of errors, flow run data from two experiments using whole blood samples showed that our method and metrics can detect platelet property changes/differences that are concordant with the expected biological outcome, such as inhibiting key platelet receptors such as P2Y1, glycoprotein (GP)Ib and GPIIb/IIIa. These findings support the use of our methodologies to characterize platelet function among a wide range of healthy and disease cohorts

PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes

Non-viral vector formulations comprise typically complexes of nucleic acids with cationic polymers or lipids. However, for in vivo applications cationic formulations suffer from problems of poor tissue penetration, non-specific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic formulations may provide a solution to these problems but they have not been developed to the same extent as cationic formulations due to difficulties of nucleic acid packaging and poor transfection efficiency. We have developed novel PEGylated, anionic nanocomplexes containing cationic targeting peptides that act as a bridge between PEGylated anionic liposomes and plasmid DNA. At optimized ratios, the components self-assemble into anionic nanocomplexes with a high packaging efficiency of plasmid DNA. Anionic PEGylated nanocomplexes were resistant to aggregation in serum and transfected cells with a far higher degree of receptor-targeted specificity than their homologous non-PEGylated anionic and cationic counterparts. Gadolinium-labeled, anionic nanoparticles, administered directly to the brain by convection-enhanced delivery displayed improved tissue penetration and dispersal as well as more widespread cellular transfection than cationic formulations. Anionic PEGylated nanocomplexes have widespread potential for in vivo gene therapy due to their targeted transfection efficiency and ability to penetrate tissues