Biologically Inspired Design of Protein-Silica Hybrid Nanoparticles for Drug Delivery Applications

The design and application of effective drug carriers is a fundamental concern in the delivery of therapeutics for the treatment of cancer and other vexing health problems. Traditionally utilized chemotherapeutics are limited in efficacy due to poor bioavailability as a result of their size and solubility as well as significant deleterious effects to healthy tissue through their inability to preferentially target pathological cells and tissues, especially in treatment of cancer. Thus, a major effort in the development of nanoscopic drug delivery vehicles for cancer treatment has focused on exploiting the inherent differences in tumor physiology and limiting the exposure of drugs to non-tumorous tissue, which is commonly achieved by encapsulation of chemotherapeutics within macromolecular or supramolecular carriers that incorporate targeting ligands and that enable controlled release. The overall aim of this work is to engineer a hybrid nanomaterial system comprised of protein and silica and to characterize its potential as an encapsulating drug carrier. The synthesis of silica, an attractive nanomaterial component because it is both biocompatible as well as structurally and chemically stable, within this system is catalyzed by self-assembled elastin-like polypeptide (ELP) micelles that incorporate of a class of biologically-inspired, silica-promoting peptides, silaffins. Furthermore, this methodology produces near-monodisperse, hybrid inorganic/micellar materials under mild reaction conditions such as temperature, pH and solvent. This work studies this material system along three avenues: 1) proof-of-concept silicification (i.e. the formation and deposition of silica upon organic materials) of ELP micellar templates, 2) encapsulation and pH-triggered release of small, hydrophobic chemotherapeutics, and 3) selective silicification of templates to potentiate retention of peptide targeting ability.

I Stood Up: Social Design in Practice

Through practice-based research, we explore how interdisciplinary design projects can function to address social issues concerning environmental and social problems. Using two case studies developed between London in the United Kingdom, and Delhi and Ahmedabad in India, we discuss the importance of engagement with the people who the design ultimately serves. Finally, we argue that design concerned with complex social problems require equally complex, multidimensional responses, informed by bodies of knowledge, practices and approaches that lie outside of traditional design approaches.

GRASP and statistical bounds for heuristic solutions to combinatorial problems

The quality of a heuristic solution to a NP-hard combinatorial problem is hard to assess. A few studies have advocated and tested statistical bounds as a method for assessment. These studies indicate that statistical bounds are superior to the more widely known and used deterministic bounds. However, the previous studies have been limited to a few metaheuristics and combinatorial problems and, hence, the general performance of statistical bounds in combinatorial optimization remains an open question. This work complements the existing literature on statistical bounds by testing them on the metaheuristic Greedy Randomized Adaptive Search Procedures (GRASP) and four combinatorial problems. Our findings confirm previous results that statistical bounds are reliable for the p-median problem, while we note that they also seem reliable for the set covering problem. For the quadratic assignment problem, the statistical bounds has previously been found reliable when obtained from the Genetic algorithm whereas in this work they found less reliable. Finally, we provide statistical bounds to four 2-path network design problem instances for which the optimum is currently unknown.

Web-based museum trails on PDAs for university-level design students: Design and evaluation

This paper describes the development and evaluation of web-based museum trails for university-level design students to access on handheld devices in the Victoria and Albert Museum (V&A) in London. The trails offered students a range of ways of exploring the museum environment and collections, some encouraging students to interpret objects and museum spaces in lateral and imaginative ways, others more straightforwardly providing context and extra information. In a three-stage qualitative evaluation programme, student feedback showed that overall the trails enhanced students’ knowledge of, interest in, and closeness to the objects. However, the trails were only partially successful from a technological standpoint due to device and network problems. Broader findings suggest that technology has a key role to play in helping to maintain the museum as a learning space which complements that of universities as well as schools. This research informed my other work in visitor-constructed learning trails in museums, specifically in the theoretical approach to data analysis used, in the research design, and in informing ways to structure visitor experiences in museums. It resulted in a conference presentation, and more broadly informed my subsequent teaching practice.

Exploring design patterns for sustainable behaviour

Products and services explicitly intended to influence users’ behaviour are increasingly being proposed to reduce environmental impact and for other areas of social benefit. Designing such interventions often involves adopting and adapting principles from other contexts where behaviour change has been studied. The ‘design pattern’ form, used in software engineering and HCI, and originally developed in architecture, offers benefits for this transposition process. This article introduces the Design with Intent toolkit, an idea generation method using a design pattern form to help designers address sustainable behaviour problems. The article also reports on exploratory workshops in which participants used the toolkit to generate concepts for redesigning everyday products—kettles, curtains, printers and bathroom sinks/taps—to reduce the environmental impact of use. The concepts are discussed, along with observations of how the toolkit was used by participants, suggesting usability improvements to incorporate in future versions.

Digital Humanities Research Through Design

Humanities Computing gave rise to the Digital Humanities, which brought considerations of a wider scope of the digital turn to humanities research. Increasingly, the area is understood to include the field of design, exemplified by definitions that describe the Digital Humanities as a “generative enterprise”. We suggest that design contributes not only to the making of digital artefacts. Design practiced with the aim to generate new knowledge constitues a research method. Design research contributes to the Digital Humanities expertise in addressing complex problems and methods for making the knowledge that is generated during a design process explicit.

Adaptive Crowd Algorithms for Open-Ended Problems

Thesis (Ph.D.)--University of Washington, 2016-06

Citizen science and natural resource governance: program design for vernal pool policy innovation

Effective natural resource policy depends on knowing what is needed to sustain a resource and building the capacity to identify, develop, and implement flexible policies. This retrospective case study applies resilience concepts to a 16-year citizen science program and vernal pool regulatory development process in Maine, USA. We describe how citizen science improved adaptive capacities for innovative and effective policies to regulate vernal pools. We identified two core program elements that allowed people to act within narrow windows of opportunity for policy transformation, including (1) the simultaneous generation of useful, credible scientific knowledge and construction of networks among diverse institutions, and (2) the formation of diverse leadership that promoted individual and collective abilities to identify problems and propose policy solutions. If citizen science program leaders want to promote social-ecological systems resilience and natural resource policies as outcomes, we recommend they create a system for internal project evaluation, publish scientific studies using citizen science data, pursue resources for program sustainability, and plan for leadership diversity and informal networks to foster adaptive governance.

It's Not Rocket Library Science: Design Epistemology and American Librarianship

Thesis (Ph.D.)--University of Washington, 2016-06

A domain decomposition based algorithm for non-linear 2D inverse heat conduction problems

Inverse heat conduction problems (IHCPs) appear in many important scientific and technological fields. Hence analysis, design, implementation and testing of inverse algorithms are also of great scientific and technological interest. The numerical simulation of 2-D and –D inverse (or even direct) problems involves a considerable amount of computation. Therefore, the investigation and exploitation of parallel properties of such algorithms are equally becoming very important. Domain decomposition (DD) methods are widely used to solve large scale engineering problems and to exploit their inherent ability for the solution of such problems.

Conceptual Design of a Circulating Fluidized Bed Reactor as a Thermochemical Thermal Energy Storage System for Applications in Concentrated Solar Thermal Power Plants

Thesis (Master's)--University of Washington, 2016-08

The strategic role of design in supporting knowledge exchange

Within the last decade design has had a strategic role in tackling escalating environmental, social and economic problems. Through design thinking, creative methods have been applied to problem solving in a process of collaboration and designers working in new territories and knowledge domains. As the designer has moved further afield the method of Knowledge Exchange (KE) has become more recognised as a democratic approach to collaboration with the ethos that everyone has something creative and productive to offer. This paper provides reflections on early stage findings from a strategic design innovation process in which collaborative partnerships between academics, SMEs and designers emerged through KE and suggests that there is value to be had from using design strategically for not only those from a business or academic background but also for those from the design community and points to a need for more training for designers from all disciplines in how to use design strategically

Design of advanced reverse osmosis and nanofiltration membranes for water purification

Most commercially available reverse osmosis (RO) and nanofiltration (NF) membranes are based on the thin film composite (TFC) aromatic polyamide membranes. However, they have several disadvantages including low resistance to fouling, low chemical and thermal stabilities and limited chlorine tolerance. To address these problems, advanced RO/NF membranes are being developed from polyimides for water and wastewater treatments. The following three projects have resulted from my research. (1) Positively charged and solvent resistant NF membranes. The use of solvent resistant membranes to facilitate small molecule separations has been a long standing industry goal of the chemical and pharmaceutical industries. We developed a solvent resistant membrane by chemically cross-linking of polyimide membrane using polyethylenimine. This membrane showed excellent stability in almost all organic solvents. In addition, this membrane was positively charged due to the amine groups remaining on the surface. As a result, high efficiency (> 95%) and selectivity for multivalent heavy metal removal was achieved. (2) Fouling resistant NF membranes. Antifouling membranes are highly desired for “all” applications because fouling will lead to higher energy demand, increase of cleaning and corresponding down time and reduced life-time of the membrane elements. For fouling prevention, we designed a new membrane system using a coating technique to modify membrane surface properties to avoid adsorption of foulants like humic acid. A layer of water-soluble polymer such as polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyvinyl sulfate (PVS) or sulfonated poly(ether ether ketone) (SPEEK), was adsorbed onto the surface of a positively charged membrane. The resultant membranes have a smooth and almost neutrally charged surface which showed better fouling resistance than both the positively charged NF membranes and commercially available negatively charged NTR-7450 membrane. In addition, these membranes showed high efficiency for removal of multivalent ions (> 95% for both cations and anions). Therefore, these antifouling surfaces can be potentially used for water softening, water desalination and wastewater treatment in a membrane bioreactor (MBR) process. (3) Thermally stable RO membranes. Commercial RO membranes cannot be used at temperature higher than 45°C due to the use of polysulfone substrate, which often limits their applications in industries. We successfully developed polyimides as the membrane substrate for thermally stable RO membranes due to their high thermal resistance. The polyimide-based composite polyamide membranes showed desalination performance comparable to the commercial TFC membrane. However, the key advantage of the polyimide-based membrane is its high thermal stability. As the feed temperature increased from 25oC to 95oC, the water flux increased 5 - 6 times while the salt rejection almost kept constant. This membrane appears to provide a unique solution for hot water desalination and also a feasible way to improve the water productivity by increasing the operating temperature without any drop in salt rejection.

Discontinuous Galerkin Methods for Advection-Diffusion-Reaction Problems on Anisotropically Refined Meshes

In this paper we consider the a posteriori and a priori error analysis of discontinuous Galerkin interior penalty methods for second-order partial differential equations with nonnegative characteristic form on anisotropically refined computational meshes. In particular, we discuss the question of error estimation for linear target functionals, such as the outflow flux and the local average of the solution. Based on our a posteriori error bound we design and implement the corresponding adaptive algorithm to ensure reliable and efficient control of the error in the prescribed functional to within a given tolerance. This involves exploiting both local isotropic and anisotropic mesh refinement. The theoretical results are illustrated by a series of numerical experiments.