The Role of Tra1 in Cellular Stress Responses in Yeast: Implications for Human Diseases

Regulation of gene expression under stress conditions involves chromatin remodeling through post-translational modification of histones. One of these modifications, acetylation of lysine residues, regulates transcription initiation and is linked to a variety of essential cellular processes including cell cycle control, DNA repair, and importantly, activation of cellular stress response pathways. Dysregulation of histone acetylation has been observed in many stress-related diseases such as inflammatory diseases, cancer, neurodegenerative disorders, and fungal infections. Tra1 is the only essential component of both the highly conserved SAGA and NuA4 histone acetyltransferase (HAT) complexes that are responsible for acetylation of histones and other proteins. Tra1 has been shown to be involved in the regulation of stress response pathways; however, the underlying mechanisms remain unclear. Huntington’s disease (HD) is a neurodegenerative disease caused by the aberrantly expanded polyglutamine (polyQ) repeats within the gene encoding the Huntingtin protein (Htt), leading to misfolding and aggregation of the mutant Htt. Defect in misfolded protein stress responses is a hallmark of HD. Thus, I sought to investigate how Tra1 orchestrates the transcriptional responses to toxic misfolded polyQ expansions. First, I developed an optimized yeast model of HD to study the effects of Tra1 on polyQ toxicity. I found that polyQ expansions impair the assembly of the Tra1-containing SAGA HAT complex. This correlates with loss of Tra1/SAGA function that exacerbates polyQ toxicity. Furthermore, polyQ expansions lead to increased expression of TRA1, revealing a compensatory feedback mechanism. Interestingly, deletion of SFP1, a transcription regulator downstream of TORC1, abolished TRA1 upregulation upon polyQ expression. Thus, I identified a novel link between Tra1 and TORC1 signaling. Moreover, I showed that the increased sensitivity to heat stress in cells expressing expanded polyQ is rescued by an osmotic stabilizer sorbitol, suggesting that the defect can be traced back to the cell wall integrity. Considering that Tra1 is vital to maintain cell wall integrity and activation of the heat shock response, it appears that impaired Tra1/SAGA functions could underlie the dysregulation of these stress responses in the yeast model of HD. Finally, because of its essential role in cell wall maintenance and calcium homeostasis (two targets of antifungal drugs), Tra1 emerges as a rationale target for pathological yeast infections. Indeed, I found that cells expressing a mutant tra1 allele showed increased sensitivity to antifungal drugs. Overall, my graduate work helps characterize the global role of Tra1 in protein homeostasis and define its potential as a therapeutic target for stress-related human diseases

Attitudes Towards Occupy Central and Factors That Influence Attitudes

This paper quantitatively and qualitatively analyzes people’s attitudes towards Occupy Central and what factors influenced their attitudes. The data was collected by using questionnaires sent out by investigators in Hong Kong, mainland China and through the Internet, using Qualtrics, provided by the Teachers College of Columbia University. At the beginning, information about Hong Kong Special Administrative Region (HKSAR) and Occupy Central is given, followed by an introduction of purpose and methodology. Then, data analysis, both quantitative and qualitative, is shown, followed by a discussion about the results of the analysis and conclusions. The key research questions were about how people’s attitudes towards Occupy Central were influenced by eleven factors: gender, age, occupation, residency, travel experience, whether they have children under the age of eighteen, their knowledge about Occupy Central, their accessibility to Occupy Central, the influence Occupy Central had on them, their ideas about a region’s development and their ideas about a country’s development. An analysis of statistical data, with tests of mean scores and t-tests, suggested some factors that influence people’s attitude. People’s occupations played a role in influencing their attitudes, especially between government officers and people from other sectors. How people were influenced significantly affected their attitudes with a more negative attitude related to negative influences. People’s residency also influenced people’s attitudes with people from the mainland China holding more negative attitudes towards Occupy Central than Hong Kong residents and with people from other places holding the most positive attitudes. The ideological difference in development of a region and a country also played an important role in influencing people’s attitudes

Enhanced coherent light-matter interaction and room-temperature quantum yield of plasmonic resonances engineered by a chiral exceptional point

Strong dissipation of plasmonic resonances is detrimental to quantum manipulation. To enhance the quantum coherence, we propose to tailor the local density of states (LDOS) of plasmonic resonances by integrating with a photonic cavity operating at a chiral exceptional point (CEP), where the phase of light field can offer a new degree of freedom to flexibly manipulate the quantum states. A quantized few-mode theory is employed to reveal that the LDOS of the proposed hybrid cavity can evolve into sub-Lorentzian lineshape, with order-of-magnitude linewidth narrowing and additionally a maximum of eightfold enhancement compared to the usual plasmonic-photonic cavity without CEP. This results in the enhanced coherent light-matter interaction accompanied by the reduced dissipation of polaritonic states. Furthermore, a scattering theory based on eigenmode decomposition is present to elucidate two mechanisms responsible for the significant improvement of quantum yield at CEP, the reduction of plasmonic absorption by the Fano interference and the enhancement of cavity radiation through the superscattering. Importantly, we find the latter allows achieving a near-unity quantum yield at room temperature; in return, high quantum yield is beneficial to experimentally verify the enhanced LDOS at CEP by measuring the fluorescence lifetime of a quantum emitter. Therefore, our work demonstrates that the plasmonic resonances in CEP-engineered environment can serve as a promising platform for exploring the quantum states control by virtue of the non-Hermiticity of open optical resonators and building the high-performance quantum devices for sensing, spectroscopy, quantum information processing and quantum computing.Comment: 20 pages,9 figure

ENGINEERED BONE-LIGAMENT INTERFACE FOR ANTERIOR CRUCIATE LIGAMENT REGENERATION: IN-VITRO STUDY

Ph.DDOCTOR OF PHILOSOPH

Topologically protected subradiant cavity polaritons through linewidth narrowing enabled by dissipationless edge states

Cavity polaritons derived from the strong light-matter interaction at the quantum level provide a basis for efficient manipulation of quantum states via cavity field. Polaritons with narrow linewidth and long lifetime are appealing in applications such as quantum sensing and storage. Here, we propose a prototypical arrangement to implement a whispering-gallery-mode resonator with topological mirror moulded by one-dimensional atom array, which allows to boost the lifetime of cavity polaritons over an order of magnitude. This considerable enhancement attributes to the coupling of polaritonic states to dissipationless edge states protected by the topological bandgap of atom array that suppresses the leakage of cavity modes. When exceeding the width of Rabi splitting, topological bandgap can further reduce the dissipation from polaritonic states to bulk states of atom array, giving arise to subradiant cavity polaritons with extremely sharp linewidth. The resultant Rabi oscillation decays with a rate even below the free-space decay of a single quantum emitter. Inheriting from the topologically protected properties of edge states, the subradiance of cavity polaritons can be preserved in the disordered atom mirror with moderate perturbations involving the atomic frequency, interaction strengths and location. Our work opens up a new paradigm of topology-engineered quantum states with robust quantum coherence for future applications in quantum computing and network.Comment: 19 pages,8 figure

FedBIAD: Communication-Efficient and Accuracy-Guaranteed Federated Learning with Bayesian Inference-Based Adaptive Dropout

Federated Learning (FL) emerges as a distributed machine learning paradigm without end-user data transmission, effectively avoiding privacy leakage. Participating devices in FL are usually bandwidth-constrained, and the uplink is much slower than the downlink in wireless networks, which causes a severe uplink communication bottleneck. A prominent direction to alleviate this problem is federated dropout, which drops fractional weights of local models. However, existing federated dropout studies focus on random or ordered dropout and lack theoretical support, resulting in unguaranteed performance. In this paper, we propose Federated learning with Bayesian Inference-based Adaptive Dropout (FedBIAD), which regards weight rows of local models as probability distributions and adaptively drops partial weight rows based on importance indicators correlated with the trend of local training loss. By applying FedBIAD, each client adaptively selects a high-quality dropping pattern with accurate approximations and only transmits parameters of non-dropped weight rows to mitigate uplink costs while improving accuracy. Theoretical analysis demonstrates that the convergence rate of the average generalization error of FedBIAD is minimax optimal up to a squared logarithmic factor. Extensive experiments on image classification and next-word prediction show that compared with status quo approaches, FedBIAD provides 2x uplink reduction with an accuracy increase of up to 2.41% even on non-Independent and Identically Distributed (non-IID) data, which brings up to 72% decrease in training time

Contrast and assimilation effects of processing fluency

When perceptually difficult-to-read information (e.g., a magazine article in difficult font) precedes easy-to-read information about a product, the subjective ease of processing experienced in reading the product's information increases. This change in subjective ease leads to more favorable evaluations of it. Three experiments identify whether this contrast effect on judgment of the second product occurs because evaluations of the content described by the difficult-to-read material are used as a basis for evaluation. Or, if the effect is perceptual in nature and participants are unaware of the influence that fluency of previously encountered information has on subsequent evaluations