Substrate Selectivity APPLies to Akt

The protein kinase Akt occupies a central position in multiple signaling pathways. Although numerous Akt substrates have been identified, less is known about the factors that regulate specific cellular responses to Akt signaling. In this issue, Schenck et al. (2008) demonstrate that the endosomal protein Appl1 modulates Akt's substrate selectivity to promote cell survival during zebrafish development

Numerical simulation and thermo-hydro-mechanical coupling model of in situ mining of low-mature organic-rich shale by convection heating

The in situ efficient exploitation of low-mature organic-rich shale resources is critical for alleviating the current oil shortage. Convection heating is the most critical and feasible method for in situ retortion of shale. In this study, a thermo-hydro-mechanical coupling mathematical model for in situ exploitation of shale by convection heating is developed. The dynamic distribution of the temperature, seepage, and stress fields during the in situ heat injection of shale and the coupling effect between multiple physical fields are studied. When the operation time increases from 1 to 2.5 years, the temperature of most shale formations between heat injection and production wells increases significantly (from less than 400 to 500 °C), which is a period of significant production of shale oil and pyrolysis gas. The fluid pore pressure gradually decreases from the peak point of the heat injection well to the surrounding. Compared with shale formation, bedrock permeability is poor, pore pressure increases slowly, and a lag phenomenon exists. The pore pressure difference between bedrock and shale is minimal by 1 year. When the heat injection time is 2.5 years, the permeability coefficient of shale formation in the area from the heat injection well to the production wells increases nearly 100 times the initial permeability coefficient. With increasing formation temperature, the vertical stress gradually evolves from compressive stress to tensile stress. Meanwhile, the action area of tensile stress expands outward with time with the heat injection well as the center. In general, increasing tensile stress enlarges the pore volume. It extends the fracture width, creating favorable conditions for the injection of high-temperature fluids and the production of oil and gas.Cited as: Zhao, J., Wang, L., Liu, S., Kang, Z., Yang, D., Zhao, Y. Numerical simulation and thermo-hydro-mechanical coupling model of in situ mining of low-mature organic-rich shale by convection heating. Advances in Geo-Energy Research, 2022, 6(6): 502-514. https://doi.org/10.46690/ager.2022.06.0

Measuring Access to Medicines: A Survey of Prices, Availability and Affordability in Shaanxi Province of China

Objective: To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009. Methods: Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days’ wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. Findings: The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day’s wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days’ wages for losartan. For originator brands, the costs rise to 1.2 days’ wages for salbutamol inhaler and 15.6 days’ wages for omeprazole. Conclusions: The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor. This requires multi-faceted interventions, as well as the review and refocusing of policies, regulations and educational interventions

Planning Model for Integrated Energy Supply System in Park Level Regions Under the Energy Internet

With the reduction of traditional fossil fuels and the increasing severity of environmental issues, it is of great significance to study energy system planning and optimization models that complement and integrate multiple energy utilization methods in the context of the energy internet for building an integrated energy supply system. Firstly, this article divides the planning indicators of the regional integrated energy supply system into four categories based on the goal of “two highs and three lows”; Secondly, analyze the three key issues of exergy efficiency, economy, and multi energy coupling in regional integrated energy planning; Finally, a multi-objective planning model for regional integrated energy systems that takes into account equipment capacity planning and operation scheduling optimization is proposed, with the optimization objectives of minimizing the annual value of full life cycle cost and maximizing efficiency, and a double-layer optimization structure is designed for efficient solution

Antibacterial effects of platelet-rich fibrin produced by horizontal centrifugation.

Platelet-rich fibrin (PRF) has been widely used owing to its ability to stimulate tissue regeneration. To date, few studies have described the antibacterial properties of PRF. Previously, PRF prepared by horizontal centrifugation (H-PRF) was shown to contain more immune cells than leukocyte- and platelet-rich fibrin (L-PRF). This study aimed to compare the antimicrobial effects of PRFs against Staphylococcus aureus and Escherichia coli in vitro and to determine whether the antibacterial effects correlated with the number of immune cells. Blood samples were obtained from eight healthy donors to prepare L-PRF and H-PRF. The sizes and weights of L-PRF and H-PRF were first evaluated, and their antibacterial effects against S. aureus and E. coli were then tested in vitro using the inhibition ring and plate-counting test methods. Flow-cytometric analysis of the cell components of L-PRF and H-PRF was also performed. No significant differences in size or weight were observed between the L-PRF and H-PRF groups. The H-PRF group contained more leukocytes than the L-PRF group. While both PRFs had notable antimicrobial activity against S. aureus and E. coli, H-PRF demonstrated a significantly better antibacterial effect than L-PRF. Furthermore, the antimicrobial ability of the PRF solid was less efficient than that of wet PRF. In conclusion, H-PRF exhibited better antibacterial activity than L-PRF, which might have been attributed to having more immune cells

Mild Moxibustion Decreases the Expression of Prokineticin 2 and Prokineticin Receptor 2 in the Colon and Spinal Cord of Rats with Irritable Bowel Syndrome

It has been proven that prokineticin 2 (PK2) and its receptor PKR2 play an important role in hyperalgesia, while mild moxibustion can relieve visceral hypersensitivity in a rat model of irritable bowel syndrome (IBS). The goal of the present study was to determine the effects of mild moxibustion on the expression of PK2 and PKR2 in colon and spinal cord in IBS rat model, which was induced by colorectal distension using inflatable balloons. After mild moxibustion treatment, abdominal withdrawal reflex (AWR) scores were assessed by colorectal distension; protein and mRNA expression of PK2 and PKR2 in rat colon and spinal cord was determined by immunohistochemistry and fluorescence quantitative PCR. Compared with normal rats, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly increased in the model group; compared with the model group, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly decreased in the mild moxibustion group. These findings suggest that the analgesia effect of mild moxibustion may be associated with the reduction of the abnormally increased expression of the PK2/PKR2 proteins and mRNAs in the colon and spinal cord

LogPrompt: Prompt Engineering Towards Zero-Shot and Interpretable Log Analysis

Automated log analysis is crucial in modern software-intensive systems for ensuring reliability and resilience throughout software maintenance and engineering life cycles. Existing methods perform tasks such as log parsing and log anomaly detection by providing a single prediction value without interpretation. However, given the increasing volume of system events, the limited interpretability of analysis results hinders analysts' trust and their ability to take appropriate actions. Moreover, these methods require substantial in-domain training data, and their performance declines sharply (by up to 62.5%) in online scenarios involving unseen logs from new domains, a common occurrence due to rapid software updates. In this paper, we propose LogPrompt, a novel zero-shot and interpretable log analysis approach. LogPrompt employs large language models (LLMs) to perform zero-shot log analysis tasks via a suite of advanced prompt strategies tailored for log tasks, which enhances LLMs' performance by up to 107.5% compared with simple prompts. Experiments on nine publicly available evaluation datasets across two tasks demonstrate that LogPrompt, despite using no training data, outperforms existing approaches trained on thousands of logs by up to around 50%. We also conduct a human evaluation of LogPrompt's interpretability, with six practitioners possessing over 10 years of experience, who highly rated the generated content in terms of usefulness and readability (averagely 4.42/5). LogPrompt also exhibits remarkable compatibility with open-source and smaller-scale LLMs, making it flexible for practical deployment

Generation of acetyllysine antibodies and affinity enrichment of acetylated peptides

Lysine acetylation has emerged as one of the major post-translational modifications, as indicated by its roles in chromatin remodeling, activation of transcription factors and, most recently, regulation of metabolic enzymes. Identification of acetylation sites in a protein is the first essential step for functional characterization of acetylation in physiological regulation. However, the study of the acetylome is hindered by the lack of suitable physical and biochemical properties of the acetyl group and existence of high-abundance acetylated histones in the cell, and needs a robust method to overcome these problems. Here we present protocols for (i) using chemically acetylated ovalbumin and synthetic acetylated peptide to generate a pan-acetyllysine antibody and a site-specific antibody to Lys288-acetylated argininosuccinate lyase, respectively; (ii) using subcellular fractionation to reduce highly abundant acetylated histones; and (iii) using acetyllysine antibody affinity purification and mass spectrometry to characterize acetylome of human liver tissue. The entire characterization procedure takes ~2–3 d to complete