Reducing facet nucleation during algorithmic self-assembly

Algorithmic self-assembly, a generalization of crystal growth, has been proposed as a mechanism for bottom-up fabrication of complex nanostructures and autonomous DNA computation. In principle, growth can be programmed by designing a set of molecular tiles with binding interactions that enforce assembly rules. In practice, however, errors during assembly cause undesired products, drastically reducing yields. Here we provide experimental evidence that assembly can be made more robust to errors by adding redundant tiles that "proofread" assembly. We construct DNA tile sets for two methods, uniform and snaked proofreading. While both tile sets are predicted to reduce errors during growth, the snaked proofreading tile set is also designed to reduce nucleation errors on crystal facets. Using atomic force microscopy to image growth of proofreading tiles on ribbon-like crystals presenting long facets, we show that under the physical conditions we studied the rate of facet nucleation is 4-fold smaller for snaked proofreading tile sets than for uniform proofreading tile sets

Cross-Cultural Differences in Work-Life Integration

The dramatic change in the career and family aspirations of Penn graduates over the past twenty years is illustrative of a general trend towards reduced choice regarding work and children. Professor Friedman, founder of the Work/Life Integration Project (W/LIP), discovered that the number of Penn graduates who intend to have children has nearly halved from 1992 to 2012. A greater understanding of work-life balance in Western European countries such as Germany will highlight the cultural changes that need to occur in order to achieve a greater work-life balance in the United States. Through student-led discussions at German universities similar to those of the Work/Life Integration Project Student Advisory Board at Penn, this paper aims to shed light on student attitudes and aspirations that are instrumental in institutional and cultural reform here at Penn and other universities. This study aims to understand how much of the change in career and family aspirations can be attributed to the pre-professional environment at universities in the United States. A cross-cultural comparison between work-life balance in Germany and the United States will be provided through student-led discussions and interviews. This study will highlight institutional mechanisms that facilitate work-family balance and provide policy-relevant recommendations that affect men and women everywhere

Utilizing logic-gated DNA strand displacement to induce cancer prodrug activation

Highly selective cancer therapeutics with minimal off target effects that preserve patient quality of life are in high demand. Towards creating more targeted therapies, advances in bioinformatics and systems biology reinforce that cancer is an extremely complex disease, and multiple biomarkers must be considered to exclusively identify cancer cells. Furthermore, unique multi-input cancer signatures can vary between cancer subtypes, individual patients, and even over time within an individual. To address this, we have developed a flexible platform based on synthetic nucleic acid computation for a “smart drug” that can match the complex and dynamic nature of cancer. Harnessing the powerful properties of toehold-mediated strand displacement, our technology has the ability to control protein assembly through input-triggered nucleic acid circuits. By conjugating DNA to fluorescent proteins or a split version of yeast cytosine deaminase, a cancer prodrug activating enzyme, we can use nucleic acid computation to control protein behavior for sensing or therapeutic applications, respectively. We first created multi-input logic-gated circuits controlled by various cancer-specific miRNA inputs. Realizing the limitations that low input concentrations inside cells could place on our protein-DNA devices, we utilized catalytic hairpin assembly (CHA) for signal amplification. Next, we integrated both Boolean-logic and amplification architectures into a programmable and streamlined design. Moving beyond an in vitro demonstration, we executed our protein-DNA computation device in various cancer cells lines that endogenously express cancer-specific RNA. To our knowledge, this is the first time protein assembly/activity controlled by strand displacement computation has been executed inside live mammalian cells, a significant step in realizing the power of nucleic acid nanotechnology for future applications

Brazilian piano through the ages: A look at the development in style through the context of social issues and historical influences

This project seeks to explore the development of piano music in Brazil, through the historical and social context of five different composers: Chiquinha Gonzaga, Ernesto Nazareth, Heitor Villa-Lobos, Francisco Mignone, and Edmundo Villani-Côrtes. By studying representative pieces of these composers, main influences are revealed, such as avoidance of or defying social stigmas, the impact of choro music, the influence of folklore and folk tunes, and the European and Romantic piano tradition. Furthermore, through the work of a composer still living today, we can trace these historical aspects into the modern day

The Impact of Social Media on Intercultural Adaptation

Social media has become increasingly popular components of our everyday life in today’s globalizing society. It provides a context where people across the world can communicate, exchange messages, share knowledge, and interact with each other regardless of the distance that separates them. Intercultural adaptation involves the process of promoting understanding through interaction to increase the level of fitness so that the demands of a new cultural environment can be met. Research shows that people tend to use social media to become more integrated into the host culture during their adaptation and to maintain connections to their home countries. This paper attempts to investigate the impact of using social media on the intercultural adaptation process. In-depth interviews of international students of a U.S. university are conducted. Based on the results of the analysis, directions for future studies in this line of research are also discussed

Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution.

The Hippo pathway is a central regulator of organ size and a key tumor suppressor via coordinating cell proliferation and death. Initially discovered in Drosophila, the Hippo pathway has been implicated as an evolutionarily conserved pathway in mammals; however, how this pathway was evolved to be functional from its origin is still largely unknown. In this study, we traced the Hippo pathway in premetazoan species, characterized the intrinsic functions of its ancestor components, and unveiled the evolutionary history of this key signaling pathway from its unicellular origin. In addition, we elucidated the paralogous gene history for the mammalian Hippo pathway components and characterized their cancer-derived somatic mutations from an evolutionary perspective. Taken together, our findings not only traced the conserved function of the Hippo pathway to its unicellular ancestor components, but also provided novel evolutionary insights into the Hippo pathway organization and oncogenic alteration

Lamina Cribrosa and Choroid Features and Their Relationship to Stage of Pseudoexfoliation Glaucoma.

PurposeTo better understand the relationship of lamina cribrosa (LC) and choroid features to the severity of pseudoexfoliation glaucoma (PXG).MethodsIn this cross-sectional study, 137 eyes of 122 subjects (47 eyes with moderate/advanced PXG [mean deviation (MD), -15.0 ± 7.7 dB], 34 eyes with mild PXG [MD, -2.7 ± 1.5 dB], 32 aged-matched pseudoexfoliation syndrome [PXS] eyes, and 24 aged-matched control eyes) were investigated. Optic discs, LC thickness, and anterior LC depth (ALD; midsuperior, center, and midinferior) as well as peripapillary choroidal thickness were determined. Linear mixed modeling was used to adjust for age, sex, and axial length.ResultsA progressive decrease in LC thickness was found when comparing controls (271.9 ± 61.3 μm), PXS (212.6 ± 51.5 μm), mild PXG (180.8 ± 24.6 μm), and moderate/advance PXG (138.9 ± 37.5 μm) (P < 0.001). ALD was greater (P < 0.001) in moderate/advance glaucoma (306.7 ± 105.3 μm) and mild PXG (209.5 ± 79.7 μm) compared with PXS (155 ± 86.7 μm) and healthy controls (149.2 ± 103 μm). Although eyes with moderate/advance PXG had the thinnest choroid (117.2 ± 36.6 μm), choroidal thickness was comparable in mild PXG, PXS, and controls (150.0 ± 46.1, 159.7 ± 65.5, and 157.5 ± 51.1 μm, respectively; P = 0.002). Worse MD was the only factor associated with thinner LC (β = 2.344, P < 0.001) and choroid (β = 1.717, P = 0.009 μm) in PXG eyes. Higher IOP (β = 4.305, P = 0.013) and worse MD (β = -6.390, P < 0.001) were associated with deeper ALD in PXG.ConclusionsIn pseudoexfoliation, LC thinning is an early sign, and there is progressive thinning with advancing glaucoma. Choroidal thinning is observable only with moderate/advanced glaucoma. In PXG eyes, LC thickness, depth, and peripapillary choroidal thickness are associated with glaucoma severity