The role of aryl hydrocarbon receptor (AHR) in drug-drug interaction and the expression of AHR in Pichia Pastoris

The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear translocator) in sufficient amount with reasonable cost. Codon optimized human AHR and ARNT genes were separately transformed into the Pichia pastoris genome and expressed. Co-immunoprecipitation, gel-shift assay and western analysis indicate Pichia pastoris was able to stably overexpress functional AHR and ARNT proteins in comparable yield and lower cost compared to baculovirus insect expression system and the expressed proteins were used to develop a new in vitro method to study AHR and ARNT binding. Pharmacokinetic studies were performed to investigate the role of AHR in rutacarpine-caffeine interactions. Oral RUT pretreatment was shown to reduce oral caffeine area under the curve (AUC) in rats, due to an increase in caffeine clearance (CL) and a decrease in oral bioavailability (F). RUT, an AHR ligand, increases caffeine CL by inducing Cyp1A2 enzyme, but the mechanism by which RUT reduces caffeine F is not understood. We hypothesize that it is also mediated via AHR pathway. To test the hypothesis, wild type (WT) and AHR knock out (KO) mice were administered caffeine IV and orally, with and without VEH or RUT pretreatment. As expected, PK data show higher caffeine CL and lower F values in WT, but similar CL and F values in AHR KO mice, upon RUT co-administration. Rats study, in which with pretreatment of vehicle, AHR ligands: RUT, beta-naphthoflavone or indole-3-carbinol before caffeine was dosed orally is consistent with mice study, that all three AHR agonists tested were able to reduce oral caffeine AUCs in rats. RUT reduces caffeine’s oral bioavailability is through AHR signaling pathway, however, However, the mechanism by which AHR mediates the reduced caffeine F is not known

Speed Control and Optimization of Variable Speed Diesel Generator Set

The fuel consumption rate of a diesel engine is closely related to its operating speed. In order to minimize the fuel consumption rate of the diesel engine, this paper studies the optimal operating speed of the diesel generator set, and designs the optimal operating speed curve of the diesel generator based on the actual situation. Aiming at the phenomenon that the load changes at any time in the actual working condition of the diesel generator set, this paper designs a fuzzy adaptive PID control algorithm for the diesel engine governor and realizes algorithm optimization. Using MATLAB platform simulation analysis, it is verified that the fuzzy adaptive PID controller after algorithm optimization has better dynamic response and stability performance in diesel generator system

HOW DOES ENTERPRISE SOCIAL MEDIA (ESM) INFLUENCE NEWCOMERS’ SOCIALIZATION: A MULTILEVEL PERSPECTIVE

Socialization plays an essential role in ensuring that newcomers to an organization enjoy greater productivity and also integrate well into their workgroups. Since the COVID-19 pandemic, enterprise social media (ESM) is increasingly being used in organizations as an informal socialization tool. However, the effectiveness of these tools in affording the necessary socialization opportunities and enabling the newcomers to better integrate within their organizational settings remains both unclear and understudied. Drawing on the extant literature on newcomer socialization within organizational behavior and the IT affordances research, this study proposes a multilevel research model to explain how various ESM affordances affect newcomers’ socialization effectiveness (i.e., performance proficiency at the individual level and group cohesion at the group level). Plans for verifying the model using two quantitative sub-studies based on the multi-source and multi-wave research design are also presented. Research implications and future research plans are also discussed

AN EMPIRICAL INVESTIGATION INTO THE EFFECT OF TECHNOSTRESS OF PHYSICIANS ON ADOPTION OF ELECTRONIC HEALTHCARE SYSTEMS

Information technology systems in healthcare have existed for several years and gained relatively widespread usage. Therefore, factors of IT adoption have largely been discussed in literatures in order to improve the efficiency and effectiveness of using systems. However, existing frameworks are failing to include an important aspect, the technostress undertaken by physicians. Our research idea is that IT adoption in a clinical environment depends on five different dimensions of technostress (e.g. work overload, techno-invasion and etc. al) of physicians through PU and PEOU based on TAM model. This paper first made comprehensive literature review to the content about technostress and different theories related to adoption, then put forward five hypotheses based on the TAM Model, which has been widely perceived by scholars. As for the model construction and data collection, the research intends to use a 5-point Likert scale and select physicians at different levels from 7 representative hospitals’ basic units located in Shaanxi province. Based on all above, we expect the research could offer a subtle theoretical understanding about the nature of technostress and their impact on adoption by physicians. On the practical front, the research has implications for managers intending to design managerial procedures or rules for the purpose of improving the adoption

Impacts of Users’ Extra-Role Behaviors on Bright Internet Policy Adoption

Cyberspace security has been one top issue for a society. The Bright Internet (BI) based on the five principles offers a viable solution. The adoption of BI is important to the implementation of BI. A majority of the previous studies have mainly focused on access-policy violations and compliance in the past decades, while the extra-role behaviors have obtained insufficient attentions. Based on the theories of social control and accountability, this study examines the impacts of extra-role behaviors on BI policy adoption. The research findings have implications for future research and practice

Arylsulfonyl indoline-enzamide exhibits inhibitory effect on nasopharyngeal carcinoma

Purpose: To investigate the effect of arylsulfonyl indoline-benzamide (ASIB) on the viability of nasopharyngeal carcinoma (NPC) cells, and the underlying mechanism of action. Methods: The viability of C666 and NPC 039 cells was determined using 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay. Cell migration was analysed by wound healing assay, while protein expression levels of matrix metalloproteinases (MMPs), p50, p65 and NF κB were assayed using western blotting. Results: MTT assay results showed that ASIB treatment led to significant and dose-dependent reductions in the viability of C666 and NPC 039 (p ˂ 0.05). The migration and invasive potential of C666 cells were decreased on incubation with ASIB for 48 h. Western blotting data showed significant decrease in MMP 2/9 expressions in C666 cells on treatment with ASIB (p ˂ 0.05). The levels of p65 and p50 in the nuclear fraction of C666 cells were markedly lower than those in the negative control group. Arylsulfonyl indoline-benzamide (ASIB) treatment for 48 h decreased the level of NF κB expression in C666 cells (p ˂ 0.05). The volume of tumor excised from ASIB-treated NPC mice was lower than that of the untreated group. Conclusion: Arylsulfonyl indoline-benzamide (ASIB) exhibits inhibitory effects on the viability and metastasis potential of NPC cells. Thus, it may be beneficial in the treatment of nasopharyngeal carcinoma but this has to be further investigated

Business Cycle Asymmetry in China: Evidence from Friedman’s Plucking Model

Friedman’s plucking model of business fluctuations suggests that output cannot exceed an upper limit, or ceiling level, but it is occasionally plucked downward, with depth and steepness, due to recessions. This paper investigates China’s business fluctuations using the quarterly real GDP data over the period 1978-2009. Our results provide some support for the plucking model. We find that there exists the ceiling effect of real output, and the negative asymmetric  shocks affect the transitory component significantly, which therefore captures the plucking downward behavior during the recession from the idea of Friedman. In addition, it is also suggested by the results that the basic asymmetric UC model is not appropriate for directly modeling China’s real output since the business cycle is inaccurately measured, but it works quite well when considering a structural break at 1992:Q2.This paper has been accepted for publication to China & World Economy