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Hefei Advanced Light Facility (HALF) is designed as a fourth-generation light source based on the diffraction-limited storage ring (DLSR). The pre-research for this design is complete. Due to the smaller beam dynamic aperture, about 6 mm, a novel dual-channel kicker has been purposed and designed, with other two traditional kicker, combined the new injection system bump system. This paper presented the principle and layout and the detail of the novel dual-channel kicker.

Hefei Advanced Light Facility (HALF) uses a grid-controlled thermionic cathode gun as its electron source of the linear accelerator. The nanosecond grid-controlled power supply is an important part of the electron gun power supply system, and its performance will affect the quality of the beam. To achieve the requirements of the electron gun for nanosecond pulse power supply, we use the series-parallel multi-stage avalanche transistor scheme to achieve nanosecond fast pulse output. The test results show that the power supply not only can meet the requirements of HALF for its electron gun but also have good waveform repeatability and amplitude stability.

A confining extension of the quark model with nonlocal currents is proposed. The quark propagator is modified by introducing a cut in α -space, which in momentum space corresponds to the subtraction of pole singularities. A two-phase structure is proposed for modeling the confinement-deconfinement phase transition. In the confined phase, the quark propagator does not have any pole singularities, while in the deconfined phase, there is a single quark pole.

In yeast, activation of ATG1/ATG13 kinase complex initiates autophagy. This mechanism of autophagy initiation is conserved, as unc-51-like kinase 1 (ULK1) and unc-51-like kinase 2 (ULK2) are two mammalian functional homologues of ATG1 and form similar complex with mammalian ATG13. Here, we report that both ULK1 and ULK2 are transcriptional targets of tumor suppressor p53. In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. In this context, elevated autophagy contributes to subsequent cell death. These findings suggest that ULK1 and ULK2 may mediate part of tumor suppression activity in mammalian cells and contribute to the efficacy of genotoxic chemotherapeutic drugs.

Advances in embedded systems and low-cost gas sensors are enabling a new wave of low-cost air quality monitoring tools. Our team has been engaged in the development of low-cost, wearable, air quality monitors (M-Pods) using the Arduino platform. These M-Pods house two types of sensors – commercially available metal oxide semiconductor (MOx) sensors used to measure CO, O3, NO2, and total VOCs, and NDIR sensors used to measure CO2. The MOx sensors are low in cost and show high sensitivity near ambient levels; however they display non-linear output signals and have cross-sensitivity effects. Thus, a quantification system was developed to convert the MOx sensor signals into concentrations. We conducted two types of validation studies – first, deployments at a regulatory monitoring station in Denver, Colorado, and second, a user study. In the two deployments (at the regulatory monitoring station), M-Pod concentrations were determined using collocation calibrations and laboratory calibration techniques. M-Pods were placed near regulatory monitors to derive calibration function coefficients using the regulatory monitors as the standard. The form of the calibration function was derived based on laboratory experiments. We discuss various techniques used to estimate measurement uncertainties. The deployments revealed that collocation calibrations provide more accurate concentration estimates than laboratory calibrations. During collocation calibrations, median standard errors ranged between 4.0–6.1 ppb for O3, 6.4–8.4 ppb for NO2, 0.28–0.44 ppm for CO, and 16.8 ppm for CO2. Median signal to noise (S / N) ratios for the M-Pod sensors were higher than the regulatory instruments: for NO2, 3.6 compared to 23.4; for O3, 1.4 compared to 1.6; for CO, 1.1 compared to 10.0; and for CO2, 42.2 compared to 300–500. By contrast, lab calibrations added bias and made it difficult to cover the necessary range of environmental conditions to obtain a good calibration. A separate user study was also conducted to assess uncertainty estimates and sensor variability. In this study, 9 M-Pods were calibrated via collocation multiple times over 4 weeks, and sensor drift was analyzed, with the result being a calibration function that included baseline drift. Three pairs of M-Pods were deployed, while users individually carried the other three. The user study suggested that inter-M-Pod variability between paired units was on the same order as calibration uncertainty; however, it is difficult to make conclusions about the actual personal exposure levels due to the level of user engagement. The user study provided real-world sensor drift data, showing limited CO drift (under −0.05 ppm day−1), and higher for O3 (−2.6 to 2.0 ppb day−1), NO2 (−1.56 to 0.51 ppb day−1), and CO2 (−4.2 to 3.1 ppm day−1). Overall, the user study confirmed the utility of the M-Pod as a low-cost tool to assess personal exposure.

Background:Patients with primary dry syndrome have a disturbed gut microbiota with metabolic dysfunction. The impact of gut microbiota on disease progression in patients with pSS is not yet fully understood, despite a growing body of research suggesting that a healthy gut microbiota is essential for patients with pSS.Objectives:The aim of this study was to investigate the combined effects of gut microbial disorders on disease activity and immune function in patients with pSS and to screen possible biomarkers as potential biomarkers for predicting disease progression.Methods:This study recruited 49 patients with pSS between November 2018 and September 2020 All pSS patients met the 2016 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) joint revised classification and diagnostic criteria. All included cases were not taking systemic antibiotics and probiotics one month before each sample collection. Patients with severe infections, malignant tumors and other autoimmune diseases were excluded. Baseline clinical data and fresh fecal specimens were collected from all subjects, and the subjects’ gut microbiome was assessed using 16S rRNA gene sequencing. Multiple machine learning screens for potential biomarkers.Results:We grouped pSS patients according to the ESSDAI Score and found that patients with pSS in the active group (n=30) had more severe immune imbalances and gut microbiome dysbiosis than patients with pSS in the inactive group (n=19). Moreover, there was a decrease in butyric acid-producing bacteria along with an increase in pro-inflammatory mediator-producing flora in the active pSS patients. Results of correlation analyses showed that butyric acid-producing bacteria (e.g., Prevotella, [Eubacterium]_ruminantium_group, Christensenellaceae_R-7_group, and Butyricoccaceae;_) were negatively correlated with the ESSDAI Score. In particular, Collinsella was positively correlated with the levels of cytokines (e.g., IL-17, IL-2, TNF-a) in peripheral blood, and [Eubacterium]_ruminantium_group and Christensenellaceae_R-7_group were positively correlated with the absolute number of Th17 cells and NK cells, respectively. Next, we screened three significant genera (AUC up to 0.863) as potential biomarkers for assessing disease activity using the machine learning method of Lasso combined logistic regression, which were Prevotella (AUC=0.709), Subdoligranulum (AUC=0.693), Collinsella (AUC=0.6).Conclusion:Dysregulation of the gut microbiome is present in patients with pSS and is particularly significant in patients with active disease. A dysregulated gut microbiome may be involved in immune dysfunction in pSS patients, which in turn promotes disease progression. Therefore, a healthy gut microbiome is essential for patients with pSS, and attention to gut health may help to slow the progression of pSS disease.Figure 1.Microbial communities with significant differences at the genus level in the active group compared to the inactive group.Figure 2.Correlation analysis and potential biomarkers: (A) Correlation between important differential bacterial genera and conventional laboratory indicators; (B) The correlation between important differential bacterial genera and immunological indicators; (C) And (D)Diagnostic efficacy of biomarkers screened by Lasso and logistic regression.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease that can transit to multiple progressive articular and extra-articular damage if left untreated. Short-chain fatty acids (SCFAs) have shown to be associated with onset of arthritis. We hypothesized that SCFAs may associate with polyarthritis (joint swelling) and interstitial lung disease (ILD) that have not been studied.Objectives:To explore the relationship between SCFAs and progression of RA.Methods:We measured the serum SCFA levels in 282 established RA patients undergoing standard treatment though high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) methodologies. Among these patients, 205 were RA with musculo-skeletal pain and no joint deformity, including 91 with positive for anti-citrullinated protein antibodies (ACPA+RA) and 114 with negative for ACPA (ACPA-RA). In addition, of all 282 established RA patients, 40 individuals had ILD (RA-ILD).Results:In ACPA+RA patients, butyrate and propionate in patients progressed to polyarthritis (joint swelling) were significantly reduced compared to individuals not progressed to joint swelling. However, this was not the case in ACPA-RA patients, propionate and butyrate were not associated with the progression of polyarthritis. These findings suggested that SCFAs can affect the risk of RA progression to multiple arthritis, especially in ACPA+RA patients. In addition, serum SCFAs of RA-ILD patients was significantly lower than that of RA-nonILD. Univariate and multivariable logistic regression analysis demonstrated that lower levels of propionate and valerate were significantly correlated with the occurrence of ILD. Further, we found both propionate and valerate were negatively associated with risk of ILD in a nonlinear manner by using the restricted cubic spline nested in logistic regression. The decrease in propionate below 2179 ng/mL and valerate below 172 ng/mL was associated with a rapid increase in the risk of ILD both in univariable and multivariable analyses.Conclusion:We first showed that mean SCFA levels in patients with polyarthritis and RA-ILD were significantly reduced, suggesting that lower SCFAs at a certain level increase the risk of polyarthritis and ILD. SCFAs significantly reduce inflammation, regulate the immune response of intestinal tract and other distal mucosal sites, and delay the clinical progress of RA. Therefore, increasing the level of SCFAs through dietary and restoring immune balance supplement is a potential therapeutic strategy to slow down the progress of RA and reduce mortality.REFERENCES:[1] Tajik N, Frech M, Schulz O, et al. Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis. Nat Commun 2020;11:1995.[2] Martinsson K, Dürholz K, Schett G, et al. Higher serum levels of short-chain fatty acids are associated with non-progression to arthritis in individuals at increased risk of RA. Ann Rheum Dis 2022;81(3):445-7.[3] He J, Chu Y, Li J, et al. Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis. Sci Adv 2022;8(6):eabm1511.[4] Ashique S, De Rubis G, Sirohi E, et al. Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases. Chem Biol Interact 2022;368:110231.Figure 1.Serum level distribution of SCFAs in RA patients. (A) The levels of SCFA in ACPA+RA progressed and not progressed to polyarthritis (joint swelling); (B) The levels of SCFA in ACPA-RA progressed and not progressed to polyarthritis (joint swelling); (C) Difference of serum SCFAs between RA-ILD and RA-nonILD by Mann-Whitney U test; (D) Odds ratio curves of propionate and valerate by using the restricted cubic spline (RCS) for ILD in the RA patients. The red curve was derived from univariable analysis, and the blue curve derived from multivariable analysis after adjusting gender, age, duration of diabetes, BMI, smoking, ESR and CRP levels.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Patients with Primary Sjogren’s syndrome (pSS) have a disturbed gut microbiota with metabolic dysfunction. The impact of gut microbiota on disease progression in patients with pSS is not yet fully understood, despite a growing body of research suggesting that a healthy gut microbiota is essential for patients with pSS.Objectives:The aim of this study was to investigate the combined effects of gut microbial disorders on disease activity and immune function in patients with pSS and to screen possible biomarkers as potential biomarkers for predicting disease progression.Methods:This study recruited 49 patients with pSS between November 2018 and September 2020 All pSS patients met the 2016 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) joint revised classification and diagnostic criteria. All included cases were not taking systemic antibiotics and probiotics one month before each sample collection. Patients with severe infections, malignant tumors and other autoimmune diseases were excluded. Baseline clinical data and fresh fecal specimens were collected from all subjects, and the subjects’ gut microbiome was assessed using 16S rRNA gene sequencing. Multiple machine learning screens for potential biomarkers.Results:We grouped pSS patients according to the ESSDAI Score and found that patients with pSS in the active group (n=30) had more severe immune imbalances and gut microbiome dysbiosis than patients with pSS in the inactive group (n=19). Moreover, there was a decrease in butyric acid-producing bacteria along with an increase in pro-inflammatory mediator-producing flora in the active pSS patients. Results of correlation analyses showed that butyric acid-producing bacteria (e.g., Prevotella, [Eubacterium]_ruminantium_group, Christensenellaceae_R-7_group, and Butyricoccaceae;_) were negatively correlated with the ESSDAI Score. In particular, Collinsella was positively correlated with the levels of cytokines (e.g., IL-17, IL-2, TNF-a) in peripheral blood, and [Eubacterium]_ruminantium_group and Christensenellaceae_R-7_group were positively correlated with the absolute number of Th17 cells and NK cells, respectively. Next, we screened three significant genera (AUC up to 0.863) as potential biomarkers for assessing disease activity using the machine learning method of Lasso combined logistic regression, which were Prevotella (AUC=0.709), Subdoligranulum (AUC=0.693), Collinsella (AUC=0.6).Conclusion:Dysregulation of the gut microbiome is present in patients with pSS and is particularly significant in patients with active disease. A dysregulated gut microbiome may be involved in immune dysfunction in pSS patients, which in turn promotes disease progression. Therefore, a healthy gut microbiome is essential for patients with pSS, and attention to gut health may help to slow the progression of pSS disease.REFERENCES:NIL.Figure 1.Microbial communities with significant differences at the genus level in the active group compared to the inactive group.Figure 2.Correlation analysis and potential biomarkers: (A) Correlation between important differential bacterial genera and conventional laboratory indicators; (B) The correlation between important differential bacterial genera and immunological indicators; (C) And (D)Diagnostic efficacy of biomarkers screened by Lasso and logistic regression.Acknowledgements:NIL.Disclosure of Interests:None declared.

Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on–off ratio of more than 10 8 is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 10 7 cycles under 10-μs pulses, without catastrophic failure of the film. Electric-field-induced cracks are generally detrimental to functionality of ferroelectric ceramics. Liu et al. use an intermetallic alloy and ferroelectric oxide junction to mediate the reversible formation of cracks at nanoscales, resulting in colossal electroresistance modulation for memory applications.

Total gaseous mercury (TGM) was continuously monitored at a remote site (CBS) in Mt. Changbai area, Northeastern China from 24 October 2008 to 31 October 2010. The overall mean TGM concentration was 1.60±0.51 ng m−3, which is lower than those reported from remote sites in Eastern, Southwestern, and Western China, indicating a relatively lower regional anthropogenic mercury (Hg) emission intensity in Northeastern China. Measurements at a site in the vicinity (~1.2 km) of CBS station from August 2005 to July 2006 showed a significantly higher mean TGM concentration of 3.58±1.78 ng m−3. The divergent result was partially attributed to fluctuations in the relatively frequencies of surface winds during the two study periods and moreover an effect of local emission sources. The temporal variation of TGM at CBS was influenced by regional sources as well as long-range transported Hg. Regional sources frequently contributing to episodical high TGM concentrations were pin-pointed as a large iron mining district in Northern North Korea and two large power plants and urban areas to the southwest of the sampling site. Source areas in Beijing, Tianjin, southern Liaoning, Hebei, northwestern Shanxi, and northwestern Shandong were found to contribute to elevated TGM observations at CBS via long-range transport. Diurnal pattern of TGM at CBS was mainly controlled by regional sources, likely as well as intrusion of air masses from the free troposphere during summer season. There are no consistent seasonal pattern of TGM at CBS, and the monthly TGM variations showed links with the patterns of regional air movements and long-range transport.