The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in \u3cem\u3eC. elegans\u3c/em\u3e

The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease

Uniformly bounded components of normality

Suppose that $f(z)$ is a transcendental entire function and that the Fatou set $F(f)\neq\emptyset$. Set $$B_1(f):=\sup_{U}\frac{\sup_{z\in U}\log(|z|+3)}{\inf_{w\in U}\log(|w|+3)}$$ and $$B_2(f):=\sup_{U}\frac{\sup_{z\in U}\log\log(|z|+30)}{\inf_{w\in U}\log(|w|+3)},$$ where the supremum $\sup_{U}$ is taken over all components of $F(f)$. If $B_1(f)<\infty$ or $B_2(f)<\infty$, then we say $F(f)$ is strongly uniformly bounded or uniformly bounded respectively. In this article, we will show that, under some conditions, $F(f)$ is (strongly) uniformly bounded.Comment: 17 pages, a revised version, to appear in Mathematical Proceedings Cambridge Philosophical Societ

Delay Learning Architectures for Memory and Classification

We present a neuromorphic spiking neural network, the DELTRON, that can remember and store patterns by changing the delays of every connection as opposed to modifying the weights. The advantage of this architecture over traditional weight based ones is simpler hardware implementation without multipliers or digital-analog converters (DACs) as well as being suited to time-based computing. The name is derived due to similarity in the learning rule with an earlier architecture called Tempotron. The DELTRON can remember more patterns than other delay-based networks by modifying a few delays to remember the most 'salient' or synchronous part of every spike pattern. We present simulations of memory capacity and classification ability of the DELTRON for different random spatio-temporal spike patterns. The memory capacity for noisy spike patterns and missing spikes are also shown. Finally, we present SPICE simulation results of the core circuits involved in a reconfigurable mixed signal implementation of this architecture.Comment: 27 pages, 20 figure

Finalist - 999 Park

999 Park by Julia wang was one of the five finalists in the 2018 Yale Law Library short story contest

Mechanoresponsive drug delivery: harnessing forces for controlled release

Mechanically-activated delivery systems harness existing physiological and/or externally-applied forces to provide spatiotemporal control over the release of active agents. The presence and necessity of these forces in the human body and in the increasing use of mechanically-driven medical devices (e.g., stents, balloon catheters, gastric bands, tissue expanders) can serve as functional dynamic triggers. Therefore, this dissertation investigates the use of applied tensile strain and cyclic loading to control release of entrapped agents, and further translates the concept towards clinical applications by integrating the system with commercial medical devices that provide precise forces to trigger release. As an initial proof-of-concept, mechanoresponsive composites, consisting of highly-textured superhydrophobic barrier coatings over a hydrophilic substrate, are fabricated. The release of entrapped agents, controlled by the magnitude of applied strain, results in a graded response due to water infiltration through propagating patterned cracks in the coating. The strain-dependent delivery of anticancer agents with in vitro efficacy as well as the ex vivo delivery to esophageal tissue with an integrated stent system are demonstrated. Release is further modulated by barrier coating properties. Thicker coatings afford slower release rates with preserved in vitro activity for both a chemotherapeutic and an enzyme. Localizing coating crack patterns based on different geometric stress concentration factors further controls the selective sequential release of multiple agents. Finally, the development of a reversible mechanoresponsive system is investigated to provide cycle-mediated pulsatile release. Optimization of mechanical parameters results in delivery of multiple doses. To translate this concept towards the clinic, the system is integrated with commercial balloon catheters to provide multidose delivery of small molecules to ex vivo vessels. Using the inherent inflation and deflation of the catheter to trigger release, the system enhances existing capabilities to treat cardiovascular and peripheral artery diseases. In summary, the development of mechanoresponsive systems that respond to tensile strain and cycle number are described for the delivery of a wide-range of active agents (hydrophilic and hydrophobic small molecules as well as an enzyme), and their integration with existing medical devices. Furthermore, the comprehensive range of specific kinetic profiles, including triggered release, pulsatile delivery, and the sequential delivery of multiple agents, showcases the capabilities and versatility of these dynamic mechanoresponsive systems to modulate release for the treatment of various clinical diseases.2019-02-20T00:00:00

Void in Silhouette: On Three Paintings by Tseng Yu-ho

HonorsHistory of ArtUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/162681/1/wanqingy.pd

Visible effects of affirmative action: An analysis of print media in Brazil

In 2004, University of Brasília was the first federal university to enact racial quotas into their admissions policy. This was a significant and progressive move by Brazil, after it had labeled itself a racial democracy for over forty years. This study focuses on investigating the sources of change and social effects resulting from the enactment of racial policies through the analysis of models’ skin tone in advertisements of Brazilian print media. Advertisements serve as a measure of the Brazilian public’s attitudes regarding the inclusion of Afro-Brazilians. Key questions of analysis include: Are policy changes the result of attitude changes? Or are attitude changes the result of policy changes? Is change due to a direct causal impact of the affirmative action policies or is the enactment of race-conscious policies and the change in models’ skin tones the result of a shift in attitudes to begin with? Advertisements from 1998 to 2010 in three widely read Brazilian magazines are evaluated to see whether there is a relationship between the affirmative action policies enacted in Brazil in 2004 and the acceptance of racial inclusion (seen through the complexion of Brazilians represented in the media). Results show an increase in the representation of non-White Brazilians from 1998-2006. Following 2006 and the enactment of affirmative action policies, there is a decline in non-White representation, suggesting a public backlash against racial inclusion. These findings suggest that before 2004-2006, elite actions from social movements and the Executive produced a shift in public’s attitudes and, after 2006, public attitudes affected policy change. These two entities did not exhibit a mutually reinforcing relationship, but at least in the short term, a negative relationship.Governmen