Investigating the role of Quaking in antigen uptake and cross-presentation by dendritic cells

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8+ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood. In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have identified QKI as a novel regulator of phagosomes and endolysosomes, and knocking down of QKI significantly downregulates genes involved in phagosome maturation and endosome signaling. Furthermore, we have also shown that QKI interacts with a nuclear receptor, PPARδ, in multiple cell types. The QKI- PPARδ complex induces expression of a large set of genes associated with signaling in phagosome and endolysosome by binding to their promoter regions. Therefore, we hypothesize that in DCs, QKI and PPARδ mediated promotion of phagosome and endolysosome signaling can enhance antigen uptake and cross-presentation function of these cells. Using human monocyte derived DCs, we found QKI and PPARδ to be significantly upregulated upon monocyte differentiation into DC in vitro. Our data have demonstrated that activation of QKI/PPARδ complex by PPARδ receptor agonist increases the phagocytosis activity in DCs while siRNA silencing of QKI or PPARδ impairs it. This suggests that QKI cooperates with PPARδ to enhance the antigen uptake by DCs. Our studies did not establish the role of either QKI or PPARδ in the regulation of exogenous antigen cross-presentation by DCs following uptake. Further investigation aimed at dissecting the mechanisms by which QKI/PPARδ complex enhances antigen uptake will contribute to our current understanding of DC biology and may provide new strategies to improve DC-based immunotherapy

Analysis of dilemma and countermeasures of patent transformation in colleges and universities in Shaanxi Province

To explore and implement the diversifi cation of intellectual property ownership and benefi t distribution is the main theme of the era of knowledge economy. In recent years, Shaanxi colleges and universities have done a lot of work in improving the intellectual property system and promoting the transformation of scientifi c and technological achievements, and have achieved positive results, but there is still a big gap compared with many colleges and universities in advanced areas in China. This paper starts from the current situation of patent transformation in colleges and universities in Shaanxi, analyzes the main problems in patent transformation, namely the diffi culties faced, and puts forward targeted suggestions to improve the patent transformation mechanism in colleges and universities in Shaanxi, and provides reference for promoting the patent transformation work in colleges and universities in Shaanxi by formulating effective countermeasures

Currency crash risk in the carry trade

This thesis provides a systematic study of currency crash risk and funding liquidity risk in carry trade strategy in the foreign exchange (FX) market. Carry trade, which involves longing currencies with high interest rate and shorting currencies with low interest rate, is a popular currency trading strategy in the FX market for obtaining annualized excess return as high as 12%. This thesis studies exchange rates of 9 currencies over 13 years from a microstructure perspective. We identify a global skewness factor and use it to measure the currency crash risk. Applying a portfolio approach in cross-sectional asset pricing, we find that global skewness factor explains more than 80% of carry trade excess returns. On the other hand, funding liquidity is effective in predicting the future currency crash risk. Funding liquidity explains more than 70% of carry trade excess returns. We also use the coefficient of price impact from customer order flows to measure the liquidity, which reveals heterogeneous information content possessed by different types of customers. We find that the order flow implied liquidity risk factor can explain a fraction of carry trade excess returns but with small risk premium on quarterly basis. We provide empirical evidence to show that the excess return and crash risk in carry trade is endogenous; i.e., the crash risk premium is inherent in carry trade process. As the natural condition widely affects all investors, we argue that funding constraints are effective in explaining the excess returns of carry trade. When capital moves smoothly in a liquid condition and investor have sufficient funding supply, carry trade is prosperous in the FX market. When investors hit their funding constraints, market-wide liquidity drop, which force the carry trade positions diminishing. The exchange rates respond as that the low interest rate currencies appreciate and high interest rate currencies depreciate, which exacerbates currency crash risk and induces large loss to carry traders. Our cross-sectional analysis provides empirical evidence to show that funding constraints helps to explain the forward premium puzzle and push the exchange rate shift back to the direction the UIP expects

Navigating Fluid Identities: An Integrative Analysis of the LGBT Experience Through the Prisms of Gender and Sexuality Studies

The intersection of gender and sexuality studies is a dynamic field that delves into the nuanced ways in which these fundamental aspects of identity are constructed and understood within different cultural contexts. This article aims to cast light on the diverse experiences of the LGBT community, focusing on how their stories inform our comprehension of gender and sexuality's fluidity. We delve into the historical evolution of the LGBT movement, tracing its origins and milestones to better understand its impact on contemporary societal norms. Additionally, we explore how cultural forces shape and transform gender and sexuality identities, acknowledging that these influences can both empower and constrain individuals within the LGBT spectrum. In examining the manifold challenges that LGBT individuals encounter, from discrimination to the fight for equal rights and recognition, this study seeks to unearth the intricate ways in which gender, sexuality, and culture are interwoven, and how they collectively influence the lived experiences of LGBT persons. Through this lens, we aspire to contribute to a broader and more inclusive discourse around gender and sexual diversity, emphasizing the importance of understanding and embracing this complexity in the pursuit of a more equitable society

Designer? User? Player! – A Framework of Opportunities to Improve Interpersonal Dynamics During Usability Testing Through Gamification

Usability testing is an important technique in the design process. However, most existing research takes usability testing as a research method, not as the research topic itself. This paper explores the relationships and the interpersonal dynamics between participants and researchers during usability testing. In this study, we use interviews and observations to uncover the interpersonal dynamics that might be hidden in the complex multilevel structure of the testing process. Our findings suggest that interpersonal dynamics impact the testing experience and results: participants in a nervous or tense atmosphere may not perform as in real life or conceal their real thoughts. To improve the usability testing experience and results, we developed a framework of opportunities for improving the interpersonal dynamics through gamification

Entrepreneurial ecosystems and industry knowledge: does the winning region take all?

Entrepreneurial ecosystems (EE) are composed not only of startups but also the organizations that support them. Theory has been ambivalent about whether an EE is spatially bounded or includes distant organizations. This exploratory study uses a time series of all Internet industry initial public offerings (IPO) to explore the locational changes not only of startups but also four key EE service providers: lawyers, investment bankers, venture capitalists, and board directors. We find that while the startups became only slightly more concentrated, the EE service providers concentrated more rapidly, as an industry center in Silicon Valley emerged. Our results suggest that over the industry life cycle, industry knowledge exhibits a tendency to spatially concentrate, and this results in a concentration of industry-specific EE service providers that is even greater than the more gradual concentration of startups. As a result, startups, wherever they are located, increasingly source EE services from the industrial knowledge concentration

Elaborative Simplification as Implicit Questions Under Discussion

Automated text simplification, a technique useful for making text more accessible to people such as children and emergent bilinguals, is often thought of as a monolingual translation task from complex sentences to simplified sentences using encoder-decoder models. This view fails to account for elaborative simplification, where new information is added into the simplified text. This paper proposes to view elaborative simplification through the lens of the Question Under Discussion (QUD) framework, providing a robust way to investigate what writers elaborate upon, how they elaborate, and how elaborations fit into the discourse context by viewing elaborations as explicit answers to implicit questions. We introduce ElabQUD, consisting of 1.3K elaborations accompanied with implicit QUDs, to study these phenomena. We show that explicitly modeling QUD (via question generation) not only provides essential understanding of elaborative simplification and how the elaborations connect with the rest of the discourse, but also substantially improves the quality of elaboration generation.Comment: Equal contribution by Yating Wu and William Sheffield. This the EMNLP 2023 Main camera-ready versio

Preparation and In Vitro Evaluation of Tacrolimus-Loaded Ethosomes

The main objective of the present work was to prepare and assess dermal delivery of tacrolimus-loaded ethosomes versus classic liposomes. Both delivery systems were characterized for particle size, polydispersity index, and entrapment efficiency (EE), by dynamic laser diffraction and ultrafiltration or dialysis methods, respectively. The results indicated that presence of ethanol in the formulations affected the particle size. In addition, ultrafiltration method was selected to determine EE due to relatively short period as compared with dialysis method. Ethosomes exhibited a significant higher EE and amount of drug in dermis in contrast to classic liposomes suggesting that ethosomes with higher entrapment capacity prompted more amount of tacrolimus to permeate through stratum corneum and reach the target of atopic dermatitis (AD). Physical stability was very well for tacrolimus-loaded ethosomes under storage condition (4°C). Our results demonstrated that the ethosomal system might be a promising candidate for dermal delivery of tacrolimus for AD