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A mathematical model for predicting the attenuation of measurement while drilling (MWD) pressure pulses in aerated drilling was proposed using the two-phase flow model and considering the momentum and energy exchange at the phase interface, gravity of each phase, viscous pipe shear and other closing conditions. The small perturbation theory was used to solve the mathematical model; then, a model was established to compute the velocity and attenuation coefficient of mud pulse signal, and the simulated result of the model is in line with the measured attenuation in field test. With the mathematical model, the influencing factors for mud pulse attenuation were simulated and analyzed. The results reveal that the gas holdup, system pressure and pulse frequency are the major influencing factors. In case of low gas holdup (0–5%), as the gas holdup increases, the pulse velocity decreases drastically, and as it further increases, the pulse velocity tends to be flattened; whereas the attenuation coefficient increases gradually with the increase of gas holdup and begins to decline when it reaches maximum. At the same gas holdup, the mud pulse signal shows higher velocity under a high system pressure, and the attenuation coefficient increases faster with increase of the gas holdup under a low system pressure. Both pulse velocity and attenuation coefficient increase gradually with the increase of pulse frequency, and tend to be a stable high value when the frequency exceeds 100 Hz. Key words: mud pulse attenuation, gas-liquid (two-phase) flow, mathematical model, influencing factor

The drilling fluid loss or lost circulation via fractures is one of the critical engineering problems in the development of deep oil and gas resources. The conventional treatment is to introduce granular lost circulation material (LCM) into the drilling fluid system to plug fractures. In this work, a method incorporating the fracture surface scanning technique and coupled Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) numerical simulation is proposed for the first time to investigate how the LCM particles plug rough fractures. The rough fracture model is built utilizing a high resolution and high precision measurement system. The LCM particle transport and plugging process in rough fractures are captured in the CFD-DEM numerical simulations. The results show that the local fracture aperture has a significant influence on LCM particle transport and the distribution of the plugging zone. The drilling fluid loss rate will decrease, and the drilling fluid pressure will redistribute during the accumulation of LCM particles in the fracture. The fracture plugging efficiency of nonspherical LCM is improved as a result of formation of multi-particle bridges. This study provides a novel approach and important theoretical guidance to the investigation of LCM particle transport in rough fractures.

Kinsenoside (KD), an active compound isolated from Anoectochilus roxburghii, has demonstrated multiple pharmacological activities including hepatoprotection, antihyperliposis, antihyperglycemia, and antiosteoporosis. To the best of our knowledge, there are no available data concerning its preclinical pharmacokinetics and bioavailability in beagle dogs. To support preclinical pharmacokinetic and bioavailability study, a reliable LC-MS/MS method was developed for KD concentration measurements in beagle dog plasma. The chromatographic separation was achieved on a Waters Atlantis® Hilic Silica column with an optimum mobile phase consisting of 5 mM ammonium acetate in water (pH 3.0 adjusted with acetic acid) and acetonitrile at a flow rate of 0.2 mL/min. Mass spectrometric analyses were carried out by monitoring multiple reaction monitoring transitions at m/z 265.2→102.9 for KD and m/z 174.0→128.0 for l-phenyl-d5-alanine-2,3,3-d3 (IS). The stability of KD in beagle dog whole blood and plasma was systematically evaluated. Lowering the temperature played a more critical role in stabilizing KD than decreasing the pH and adding esterase inhibitors, indicating that the major reason for instability of KD was probably due to chemical hydrolysis rather than esterase-mediated degradation. The currently developed method was validated and applied to a pharmacokinetic and bioavailability study of KD in beagle dogs following oral administration at a dose of 3 mg/kg. The absolute oral bioavailability for KD was determined to be 27.6%. Compared with typical glycosides, KD has a better bioavailability and is suitable for developing an oral dosage form.

Electric propulsion is an important technology in the future space missions. The verification and testing system is mainly used for the manufacturers to fully understand the propulsion behavior in the most diverse conditions, and to indentify and eliminate potential failure modes to advance its validity and reliability, explore the applied potential for space missions. The paper presents a new verification and testing system for spacecraft propulsion and the key technologies needed to be developed are studied. The debugging data and research indicate that ultimate pressure of system is better than the 5.0×10-6Pa. Both the cold plate used for xenon pumping and sputtering protective system get an excellent performance in system. The DSMC numerical simulation method is verified that is beneficial to the research of optimization design and plume effect of electric propulsion in future.

A new intrusion detection method was presented based on machine learning for intrusion detection systems using shell commands as audit data.In the method,multiple dictionaries of shell command sequences of different lengths were constructed to represent the normal behavior profile of a network user.During the detection stage,the similarities between the command sequences generated by the monitored user and the sequence dictionaries were calculated.These similarities were then smoothed with sliding windows,and the smoothed similarities were used to determine whether the monitored user’s behaviors were normal or anomalous.The results of the experience show the method can achieve higher detection accuracy and shorter detection time than the instance-based method presented by Lane T.

Global wind power expansion raises concerns about its potential impact on plant biomass production (PBP). Using a high-dimensional fixed effects model, this study reveals significant PBP reduction due to wind farm construction based on 2404 wind farms, 108,361 wind turbines, and 7,904,352 PBP observations during 2000-2022 in China. Within a 1-10 km buffer, the normalized differential vegetation and enhanced vegetation indices decrease from 0.0097 to 0.0045 and 0.0075 to 0.0028, respectively. Similarly, absorbed photosynthetically active radiation and gross primary productivity decline from 0.0094 to 0.0034% and 0.0003-0.0002 g*C/m2 within a 1-7 km buffer. Adverse effects last over three years, magnified in summer and autumn, and are more pronounced at lower altitudes and in plains. Forest carbon sinks decrease by 12,034 tons within a 0-20 km radius, causing an average economic loss of $1.81 million per wind farm. Our findings underscore the balanced mitigation strategies for renewable energy transition when transiting from fossil fuels.

IntroductionPeriodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis.MethodsA polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer's-related changes, and nisin's therapeutic potential in this context.Results16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1β/IL-1 β, Interleukin 6/IL-6, and Tumor Necrosis Factor α/TNF-α) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-β 42 (Aβ42), total Tau, and Tau (pS199) (445.69 ± 120.03, 1420.85 ± 331.40, 137.20 ± 36.01) were significantly higher in the infection group compared to the control group (193.01 ± 31.82, 384.27 ± 363.93, 6.09 ± 10.85), respectively. Nisin treatment markedly reduced the Aβ42 (261.80 ± 52.50), total Tau (865.37 ± 304.93), and phosphorylated Tau (82.53 ± 15.77) deposition in the brain of the infection group.DiscussionNisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal-dysbiosis-related AD.

Background: Chimeric antigen receptor (CAR) T-cell therapy is practical in treating cancers of hematopoietic origin, but of that in solid tumors compromises efficacy for the loss of the antigen recognized by the CAR. However, dendritic cell (DC)/tumor fusion vaccines present a spectrum of known or unknown tumor antigens to stimulate T cell expansion and enhanced T cell response. Developing a new strategy of enhanced nanobody-based CAR-T (Nb-CAR-T) cells antitumor activity by DC/tumor fusion vaccines stimulation would provide guidance for more effective CAR-T cell therapies. Methods: Considering the therapeutic potential of nanobody (Nb), we first screened EGFRvIII Nb, then constructed and verified the function of EGFRvIII Nb-CAR-T cells in vitro and in vivo. We further combined DC/tumor fusion vaccines to boost EGFRvIII Nb-CAR-T cells antitumor effect, which was evaluated in vitro Nb-CAR-T cell function and in the tumor-bearing xenograft mouse models. Results: We had for the first time successfully selected EGFRvIII Nb for the generation of the novel EGFRvIII Nb-CAR-T cells. Importantly, our results suggested that DC/tumor fusion vaccines stimulate Nb-CAR-T cells response not only in improving T cell proliferation, T cell activation, cytokine secretion and tumor-specific cytotoxicity in vitro, but also significantly reducing tumor burden, prolonging survival and improving Nb-CAR-T cells infiltration. Conclusions: We have innovatively shown that DC/tumor fusion vaccines significantly enhance the efficacy of Nb-CAR-T cells against solid tumors. This new strategy has provided a promising therapeutic platform for promoting the clinical treatment of CAR-T cells therapy.

In this work, a methodology for characterizing reservoir pore pressure and permeability during underbalanced drilling of horizontal wells was presented. The methodology utilizes a transient multiphase wellbore flow model that is extended with a transient well influx analytical model during underbalanced drilling of horizontal wells. The effects of the density behavior of drilling fluid and wellbore heat transfer are considered in our wellbore flow model. Based on Kneissl’s methodology, an improved method with a different testing procedure was used to estimate the reservoir pore pressure by introducing fluctuations in the bottom hole pressure. To acquire timely basic data for reservoir characterization, a dedicated fully automated control real-time data monitoring system was established. The methodology is applied to a realistic case, and the results indicate that the estimated reservoir pore pressure and permeability fit well to the truth values from well test after drilling. The results also show that the real-time data monitoring system is operational and can provide accurate and complete data set in real time for reservoir characterization. The methodology can handle reservoir characterization during underbalanced drilling of horizontal wells.

Reading is one of the crucial aspects of the learning process. The learning efficiency depends on the motivation and involvement of students. The paper aims to determine whether the developed online course enhances student motivation and engagement in contemporary American literature. For this purpose, questionnaires were used. The sample consisted of 126 students enrolled in Yulin Gaoxin Secondary School, who had English proficiency at a high enough level to read English literature in the original language. Before and after the course, the Reading Motivation Questionnaires test was administered, with its scores validated using Student's t-test for dependent samples. Significant progress is observed in the internal and social components of motivation (23-25%), as well as in the Engagement category (31%). The course also positively affected learning effectiveness. None of the participants scored less than half of the possible points for the course assignments. Most children obtained high (95-119 points) and very high scores (120-140 points). This finding demonstrates the suitability of the tools used (videoconferencing, learning management systems, discussion forums, and interactive exercises) in online learning when studying modern literature. The research findings are of interest, first of all, to instructors who adopt technological innovations in their lessons or want to motivate students to read. Second, school administrators and education sector officials can draw information from the findings for corrective action. Third, software developers may be inspired by the data and create new technology solutions.