Probabilistic matching systems: stability, fluid and diffusion approximations and optimal control

In this work we introduce a novel queueing model with two classes of users in which, instead of accessing a resource, users wait in the system to match with a candidate from the other class. The users are selective and the matchings occur probabilistically. This new model is useful for analysing the traffic in web portals that match people who provide a service with people who demand the same service, e.g. employment portals, matrimonial and dating sites and rental portals. We first provide a Markov chain model for these systems and derive the probability distribution of the number of matches up to some finite time given the number of arrivals. We then prove that if no control mechanism is employed these systems are unstable for any set of parameters. We suggest four different classes of control policies to assure stability and conduct analysis on performance measures under the control policies. Contrary to the intuition that the rejection rate should decrease as the users become more likely to be matched, we show that for certain control policies the rejection rate is insensitive to the matching probability. Even more surprisingly, we show that for reasonable policies the rejection rate may be an increasing function of the matching probability. We also prove insensitivity results related to the average queue lengths and waiting times. Further, to gain more insight into the behaviour of probabilistic matching systems, we propose approximation methods based on fluid and diffusion limits using different scalings. We analyse the basic properties of these approximations and show that some performance measures are insensitive to the matching probability agreeing with the results found by the exact analysis. Finally we study the optimal control and revenue management for the systems with the objective of profit maximization. We formulate mathematical models for both unobservable and observable systems. For an unobservable system we suggest a deterministic optimal control, while for an observable system we develop an optimal myopic state dependent pricing

Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

Authors thank the Chinese Scholarship Council for funding a Studentship (No. 202008060063) at the University of St. Andrews, U.K.C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.Publisher PDFPeer reviewe

Fictional Worlds, Real Connections: Developing Community Storytelling Social Chatbots through LLMs

We address the integration of storytelling and Large Language Models (LLMs) to develop engaging and believable Social Chatbots (SCs) in community settings. Motivated by the potential of fictional characters to enhance social interactions, we introduce Storytelling Social Chatbots (SSCs) and the concept of story engineering to transform fictional game characters into "live" social entities within player communities. Our story engineering process includes three steps: (1) Character and story creation, defining the SC's personality and worldview, (2) Presenting Live Stories to the Community, allowing the SC to recount challenges and seek suggestions, and (3) Communication with community members, enabling interaction between the SC and users. We employed the LLM GPT-3 to drive our SSC prototypes, "David" and "Catherine," and evaluated their performance in an online gaming community, "DE (Alias)," on Discord. Our mixed-method analysis, based on questionnaires (N=15) and interviews (N=8) with community members, reveals that storytelling significantly enhances the engagement and believability of SCs in community settings

HECT, UBA and WWE domain containing 1 represses cholesterol efflux during CD4+ T cell activation in Sjögren’s syndrome

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology.Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy.Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice.Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment

RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis

Knockdown of MALAT1 Inhibits the Progression of Chronic Periodontitis via Targeting miR-769-5p/HIF3A Axis

Purpose. Chronic periodontitis (CP) is a long-lasting inflammatory disease that seriously affects oral health. This study is aimed at investigating the regulatory mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in CP. Methods. Primary human periodontal ligament cells (PDLCs) were treated with P. gingivalis lipopolysaccharide (LPS) to establish a CP model. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of MALAT1 and miR-769-5p in gingival tissues of patients with CP and LPS-treated PDLCs. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines. The protein levels of caspase-3, Bax, Bcl-2, and hypoxia-inducible factor (HIF) 3A were determined by western blot assay. Dual-luciferase reporter (DLR) assay was applied to validate the target relationships between miR-769-5p and MALAT1/HIF3A. Results. The expression of MALAT1 and HIF3A was enhanced, and the expression of miR-769-5p was reduced in gingival tissues of patients with CP and LPS-treated PDLCs. MALAT1 knockdown promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. MALAT1 targeted miR-769-5p and negatively regulated miR-769-5p expression. miR-769-5p overexpression promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. Besides, miR-769-5p targeted HIF3A and negatively modulated HIF3A expression. Both miR-769-5p inhibition and HIF3A overexpression reversed the inhibitory effects of MALAT1 silencing on LPS-induced PDLC injury in vitro. Conclusion. MALAT1 knockdown attenuated LPS-induced PDLC injury via regulating the miR-769-5p/HIF3A axis, which may supply a new target for CP treatment