Traction drive is a mechanism that transmits power by a rotor and lubricating oil. To evaluate the characteristics of the fluid molecules in the traction drive, we construct a simulation method to apply shear to the fluid confined between solids using LAMMPS, a molecular dynamics simulator. In this simulation, conditions are set as follows. Fluid is composed of a single hydrocarbon compound and the number of atoms is about ten thousand. The solids are a model metal surface imitating (100) plane of α-iron, and their atomic motion is frozen. Apply a pressure of 1.24 GPa in the direction perpendicular to the solid atoms. Furthermore, a constant slip of relative sliding speed 50 m/s is applied. Then, the simulation time on the order of nanoseconds is passed and the steady state is set. The temperature dependency of the coefficient of traction is evaluated by changing the temperature of the fluid from -20 oC to 140 oC. The coefficient of traction also changes with the change of temperature, and the tendency is at least qualitatively consistent with the experimental values.
Growing evidence reveals a pathological role of somatic mutations in various autoimmune diseases, such as the mutation in UBA1 in VEXAS syndrome, CARD11 and KLHL6 in cryoglobulinemic vasculitis, or STAT3 in Felty's syndrome[1]. Somatic mutations might also be involved in the pathogenesis of ANCA-associated vasculitis (AAV), which typically manifests in middle-aged and elderly individuals.
Objectives
We aimed to identify somatic mutations in patients with AAV.
Methods
We collected whole blood and obtained peripheral blood mononuclear cells (PBMCs) and neutrophils from patients with AAV in active-disease status (n=16), as well as from patients with other autoimmune diseases (n=8) as disease controls, and healthy subjects (n=10). In addition, we collected these specimens from 12 out of the 16 patients with AAV after remission induction. We performed RNA sequencing (RNA-seq) on the obtained cells and whole genome sequencing (WGS) on DNA extracted from the whole blood. Somatic mutations were detected by comparing the RNA and DNA sequences[2].
Results
After stringent quality control, we identified 108 somatic mutations across 16 patients in active-disease status. The mean coverage of RNA-Seq at the mutation site was 100.9 ± 367.8 ×, and that of WGS was 14.4 ± 4.3 ×, while the mean allele fraction was 22.9 ± 20.5%. One or more mutations were detected in each of the 15 (93.8%) patients. The median mutation count of each patient was 4.0, which was not significantly different from disease controls or samples after remission induction. We mapped one gene to each of the 108 mutations, resulting in 95 genes in total. Mutations for six of the 95 genes were observed in two or more patients, and two of them were related to the ubiquitin system. Of the 108 mutations, 37 were missense, and 20 were predicted to be deleterious (combined annotation-dependent depletion Phred score > 20). Among the 20 mutations, the HIST2H2AC mutation (NM_003517: p.L86P) in neutrophils was observed in two patients. To evaluate the functional outcome of the 20 mutations, we analysed the data on knocking out the corresponding genes using CRISPR in K562 cells[3]. The results showed that the expression of genes related to antigen presentation was increased in HEATR1 and RPL18 knockouts. When we followed up with 12 of the 16 patients after remission induction, 81.4% of the somatic mutations were no longer detected. Additionally, 91.7% of the deleterious mutations disappeared.
Conclusion
We found somatic mutations with potential pathological effects in some patients with AAV exhibiting active-disease status. Notably, the majority of these mutations were not detected after remission induction.
References
[1]Mustjoki, S. & Young, N. S. Somatic Mutations in 'Benign' Disease. N. Engl. J. Med. 384, 2039–2052 (2021). [2]Yizhak, K. et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364, (2019). [3]Replogle, J. M. et al. Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq. Cell 185, 2559-2575.e28 (2022).
Acknowledgements
The present study was supported in part by JSPS KAKENHI. (Grant No. 19H03209).
Abstract Background The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA. Methods Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results. Results Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway. Conclusions Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.
The present study aimed to clarify comprehensive relationships among the clinical variables of systemic lupus erythematosus (SLE).We retrospectively surveyed 32 clinical variables in 581 patients and conducted comprehensive association studies among SLE clinical phenotypes. A univariate analysis of all possible combinations was performed, and the results of phenotypic correlations were reduced into two dimensions. We also created a regression formula using L1 regularisation (LASSO) to calculate the probability of exhibiting each phenotype.The univariate analysis identified 26 correlations, including multiple phenotypes with low complement. Some unpredicted correlations were identified, including fever and the anti-Sm antibody (odds ratio; OR = 2.3, p = 1.6 × 10-5) or thrombocytopenia and psychosis (OR = 3.7, p = 3.2 × 10-5). The multivariate analysis accurately estimated the probability of exhibiting each phenotype (area under the curve > 0.7) in 10 out of 20 phenotypes.The present results show the phenotypic architecture of SLE and represent a model for estimating the probability of exhibiting each phenotype. They also offer insights into the pathology of SLE and estimating the probability of the onset of new phenotypes in clinical practice.
Prepared by the Case Histories Committee for the Engineering Geology Division of the Geological Society of America, these histories are intended as reference material for the practicing geologist and for the college student. This volume, the ninth in the series, contains the following papers: Rapid excavation and the role of engineering geology; The engineering geologist's role in hard rock tunnel machine selection; Some geological structural influences in quarrying limestone and dolomite; Geologic factors in rapid excavation with nuclear explosives; Theory of spacing of extension fracture; Experimental investigation of sliding friction in multilithologic specimens; Total systems approach to rapid excavation and its geological requirements; and more.
Abstract CF 3 SO 3 H was found to serve as a more superior initiator for the polymerization of diisopropenylbenzenes than the conventionally used acids such as H 2 SO 4 . Much faster polymerization at lower temperatures seems to be ascribed to the higher acidity of CF 3 SO 3 H. The use of microflow systems was also found to be effective in increasing the indane unit content, especially for 1,4‐DPB. Fast mixing and uniformity of the temperature seem to be responsible. The thus‐obtained polymers of high indane unit content serve as useful materials having high thermal resistance and low dielectric constants. magnified image
The IP session highlights three innovative test practices in Asia, which include a testing solution for the millimeterwave (76- to 81- GHz) without expensive instruments, an on-chip delay measurement method for in-field test and a power control method of at-speed scan test for IR violation reduction. These would be useful for automotive and IoT application device testing.
The thermal decomposition of a radical initiator, AIBN in a microreactor was examined. The plots of unchanged AIBN against the residence time fitted well to the calculated one based on the bath temperature, indicating the efficient heat transfer through the wall of the microreactor by virtue of a high surface-to-volume ratio. The effectiveness of the microreactor on the molecular weight distribution control was then examined. For the polymerization of butyl acrylate (BA), the polydispersity index (PDI) of the polymer obtained using the microreactor was much smaller than that obtained with a macroscale batch reactor. The result can be explained in terms of much higher heat removal efficiency of the microreactor compared with the macroscale batch reactor. For the polymerization of benzyl methacrylate (BMA) and methyl methacrylate (MMA), the effect of the microreactor on PDI was smaller than in the case of BA. For the polymerization of vinyl benzoate (VBz) and styrene (St), no appreciable effect of microreactor on PDI was observed. These experimental results indicate that the microreactor is quite effective to the molecular weight distribution control for highly exothermic free radical polymerizations (BA, BMA, and MMA) but that it is not so effective for less exothermic polymerizations (VBz and St).
Recent advances in imaging revealed that giant cell arteritis (GCA) is frequently associated with large vessel involvement (LVI), but they may also contribute to earlier diagnosis and treatment of LV-GCA. We aimed to compare the clinical characteristics of GCA with or without LVI and evaluate its association with clinical outcomes.We retrospectively reviewed the medical records of 36 patients with GCA in Kyoto University Hospital.Eighteen patients each were assigned to the LVI(+) and LVI(-) groups. Five-year survival rates in the LVI(+) group were better than in the LVI(-) group (p = .034), while five-year relapse-free survival rates were similar between the groups (p = .75). The LVI(+) group required lower doses of glucocorticoid at month 6 (p = .036). Disease activity evaluated with the Birmingham Vasculitis Activity Score at disease onset was higher in the LVI(-) group (p = .014), and the Vasculitis Damage Index score examined at the last visit was higher in the LVI(-) group (p = .011).GCA without LVI had more active disease, severer vascular damage, and worse survival, possibly because of ophthalmic complications and their greater glucocorticoid requirement. Our results revisit the impact of cranial manifestations on disease severity and morbidity.
