The 3D abstract Tile Assembly Model is Intrinsically Universal

In this paper, we prove that the three-dimensional abstract Tile Assembly Model (3DaTAM) is intrinsically universal. This means that there is a universal tile set in the 3DaTAM which can be used to simulate any 3DaTAM system. This result adds to a body of work on the intrinsic universality of models of self-assembly, and is specifically motivated by a result in FOCS 2016 showing that any intrinsically universal tile set for the 2DaTAM requires nondeterminism (i.e. undirectedness) even when simulating directed systems. To prove our result we have not only designed, but also fully implemented what we believe to be the first intrinsically universal tile set which has been implemented and simulated in any tile assembly model, and have made it and a simulator which can display it freely available

Investigations into the Stucture and Function of Type I Polyketide Synthases

The polyketide (PK) class of natural products constitutes an abundant array of secondary metabolites produced in microorganisms, many of which possess potential medicinal value, especially in the area of oncology. Polyketides are assembled biosynthetically via the megaenzymes polyketide synthases (PKSs) through an assembly line process of stepwise condensations of simple malonic acid building blocks derived from primary metabolism. Despite the usefulness of natural products in medicine, the development of polyketide natural products into new drugs is often hindered by their suboptimal pharmacological properties, highlighting the need for their modification by medicinal chemistry. However, low natural abundance and high structural complexity often necessitates lengthy and expensive synthetic routes to natural product analogs, thus impeding their clinical development. A promising method for expanding the chemical diversity within polyketide natural products is PKS bioengineering, whereby natural product analogs are generated by engineering new functionality into the enzymes responsible for their production instead of through synthetic derivatization. While notable successes in PKS engineering have been achieved, many attempts result in decreased product yields or fail to produce the predicted molecules entirely. The studies in this thesis focus on investigating the structural and mechanistic parameters that govern PKS catalysis in order to increase the potential of harnessing these enzymes as biocatalysts for the production of new polyketide analogs. First, a series of engineered PKS modules was generated by combining modules from the pikromycin, erythromycin, and juvenimycin biosynthetic pathways with non-native TE domains and analyzed for substrate flexibility in vitro. The results from this study implicated the TE domain as the dominant catalytic bottleneck in the full-module processing of unnatural substrates. We next focused our investigations on probing the TE directly as an excised domain, subsequently confirming the previously observed catalytic bottleneck. Mutational analysis of the Pik TE domain resulted in an engineered variant (S148C) with improved substrate flexibility and catalytic efficiency, which eliminated the aforementioned bottleneck and allowed for the production of diastereomeric macrolactone analogs. Finally, we performed molecular dynamics (MD) simulations coupled with quantum mechanical (QM) calculations of the native and engineered TE domains to provide a mechanistic rational for our experimental observations. Taken together, the results herein provide further insight into the catalytic and mechanistic parameters that govern the productive functioning of engineered PKSs. Our identification of the thioesterase domain as a key catalytic bottleneck in the processing of unnatural substrates builds the groundwork for future engineering of PKS TE domains in order to generate more flexible catalysts for the production of novel natural product analogs.PHDCancer BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/140831/1/aakoch_1.pd

Project iCAN: A STEM Learning and Persistence Model for Postsecondary Students with Disabilities

Education and work in Science, Technology, Engineering, & Math (STEM) are of utmost importance in a post-modern society. Yet American performance in the STEM disciplines has waned over recent years. In order to recapture a global advantage in STEM, efforts are being made by educators and policy makers to compile and implement instructional supports. Of particular interest to this study are post-secondary students with disabilities (SWDs) who persist and learn in STEM degree paths. This population is an untapped resource with limitless potential for contribution to the collective fields of STEM (Leddy, 2010, p. 3; Alston, Hampton, Bell, & Strauss, 1998, p. 5). The National Science Foundation (NSF) has funded Project Interdisciplinary Coaching as a Nexus for Transforming How Institutions Support Undergraduates in STEM (Project iCAN) at Landmark College as a model to develop a successful STEM support model. Post hoc interview data from students and staff at Landmark revealed themes pertaining to educational and vocational-training supports that may generalize to larger, urban institutions of higher education for further development of STEM persistence and learning models

Submarine mass movements and their consequences

Submarine spreading is a type of mass movement that involves the extension and fracturing of a thin surficial layer of sediment into coherent blocks and their finite displacement on a gently sloping slip surface. Its characteristic seafloor signature is a repetitive pattern of parallel ridges and troughs oriented perpendicular to the direction of mass movement. We map ~30 km2 of submarine spreads on the upper slope of the Hikurangi margin, east of Poverty Bay, North Island, New Zealand, using multibeam echosounder and 2D multichannel seismic data. These data show that spreading occurs in thin, gently-dipping, parallel-bedded clay, silt and sandy sedimentary units deposited as lowstand clinoforms. More importantly, high-amplitude and reverse polarity seismic reflectors, which we interpret as evidence of shallow gas accumulations, occur extensively in the fine sediments of the upper continental slope, but are either significantly weaker or entirely absent where the spreads are located. We use this evidence to propose that shallow gas, through the generation of pore pressure, has played a key role in establishing the failure surface above which submarine spreading occurred. Additional dynamic changes in pore pressure could have been triggered by a drop in sea level during the Last Glacial Maximum and seismic loading.peer-reviewe

A Second-Site Noncomplementation Screen for Modifiers of Rho1 Signaling during Imaginal Disc Morphogenesis in Drosophila

Rho1 is a small GTPase of the Ras superfamily that serves as the central component in a highly conserved signaling pathway that regulates tissue morphogenesis during development in all animals. Since there is tremendous diversity in the upstream signals that can activate Rho1 as well as the effector molecules that carry out its functions, it is important to define relevant Rho1-interacting genes for each morphogenetic event regulated by this signaling pathway. Previous work from our lab and others has shown that Rho signaling is necessary for the morphogenesis of leg imaginal discs during metamorphosis in Drosophila, although a comprehensive identification of Rho1-interacting genes has not been attempted for this process.We characterized an amorphic allele of Rho1 that displays a poorly penetrant dominant malformed leg phenotype and is capable of being strongly enhanced by Rho1-interacting heterozygous mutations. We then used this allele in a second-site noncomplementation screen with the Exelixis collection of molecularly defined deficiencies to identify Rho1-interacting genes necessary for leg morphogenesis. In a primary screen of 461 deficiencies collectively uncovering approximately 50% of the Drosophila genome, we identified twelve intervals harboring Rho1-interacting genes. Through secondary screening we identified six Rho1-interacting genes including three that were previously identified (RhoGEF2, broad, and stubbloid), thereby validating the screen. In addition, we identified Cdc42, Rheb and Sc2 as novel Rho1-interacting genes involved in adult leg development.This screen identified well-known and novel Rho1-interacting genes necessary for leg morphogenesis, thereby increasing our knowledge of this important signaling pathway. We additionally found that Rheb may have a unique function in leg morphogenesis that is independent of its regulation of Tor

Data Models for the Probabilistic Design of the Thermal Protection System of a Reusable Launch Vehicle Stage

Early design phases significantly impact a system’s life-cycle costs, yet they are fraught with large uncertainties. Hence, it is important to incorporate uncertainties in preliminary design activities. However, sampling the uncertain design space instead of analyzing a single system entails a considerable computational cost. It also demands a high degree of automation, with data models being a crucial component. Consolidating all data describing a system in a structured way in a single source helps to streamline processes. This applies to the technical system itself as well as the description of the probabilistic study. The use of the Extensible Markup Language (XML) along with XML Schema Definition (XSD) , complemented by libraries written in C++ with Python bindings via Boost.Python, has proven to be effective for implementing data models. This paper demonstrates the application of such data models through the sizing of a thermal protection system (TPS) of a reusable launch vehicle stage. The results indicate that a probabilistic design of a TPS can lead to a reduction in the required material thickness compared to a worst-case scenario

Food Insecurity in Bloomington-Normal: How a Grocery Cooperative Might Help Meet the Needs of Low-Income Residents

The purpose of this report is to understand the current food needs of marginalized community-members in the Bloomington-Normal area, to learn how Green Top Grocery may help improve food security among these residents, and to ascertain viable mechanisms to encourage involvement in the cooperative among a diversity of local residents. The findings are based on data from three focus groups and nine key-informant interviews conducted in the Bloomington-Normal community. Key findings most relevant to Green Top’s goal of encouraging a diverse membership include the following: Green Top may wish to use existing networks to build trust in the Bloomington-Normal community, keeping in mind they will need communicate in multiple languages; Green Top could educate the public about what a grocery cooperative is; Green Top could consider the needs of marginalized community members when making infrastructure decisions such was where to locate their store. A number of other findings are discussed. In conclusion, additional research is highly recommended for Green Top to move forward with their goals