Nonlinear behavior evolution and squeal analysis of disc brake based on different friction models

A four-degree-of-freedom model of disc brake with friction and contact loss nonlinearities is developed to investigate the mechanism and dynamic characteristics of brake squeal. The nonlinear equations of motion are presented, and Coulomb and Stribeck friction models are applied and compared in the analysis. The effects of key parameters on system stability are investigated based on the linear equations around the equilibrium point using the complex eigenvalue analysis method. Mode-coupling motion is found to be one significant mechanism to initiate the system instability and lead to brake squeal, and is exceptionally reliant on the parameter configurations of brake system. Numerical solutions of the nonlinear equations of motion are obtained to examine the dynamic behaviors and find the routes to squeal of the brake system with nonlinearities. Results demonstrate that the tangential stiffness of the pad and the rotating velocity of the disc play important roles on the occurrence of stick-slip vibration resulting from the falling characteristic of friction coefficient, and contact loss nonlinearity may make system become unstable even for constant friction coefficient. The separation between the brake pad and disc is dependent on the ratio of normal stiffness of pad/disc and contact stiffness. Strong nonlinear items of the brake system may lead to complicated quasi-periodic and chaotic motions, resulting in squeal problem

Dominant factor affecting Pb speciation and the leaching risk among land- use types around Pb-Zn mine

Soil lead (Pb) pollution around the mining area has severely threaten human health. However, Pb leaching risk in soils with different land uses and which is the proper land use are still unknown. In this work, Pb speciation characteristics and the dominant soil factors affecting Pb speciation in three land uses (farmland, woodland, and grassland) surrounding the Pb-Zn mine in Feng Country, Shaanxi province were investigated. Moreover, the Pb leaching risk and associated determining factors were evaluated by the combination of leached Pb concentration and structural equation model (SEM). The results showed that farmland presented the highest total Pb content (410.1 mg kg(-1)) among three land use types. The reducible fraction of Pb (Fe-Mn oxides bound) was the major speciation ( > 50%) in all tested soils of three land-use types. Soil total phosphorus (TP), water content (WC), and pH play major role in regulating Pb speciation. Though soil biological properties, like microbial communities, catalase, and microbial biomass nitrogen (MBN) exhibited distinct responses to three different land uses, they showed minor influence on Pb speciation. More interestingly, SEM analysis indicated that Pb leaching risk was directly linked with bacteria abundance, total Pb content, clay content, and C/N. Grassland presented the higher predicted Pb leaching concentration (85.03 mg kg(-1)), compared with that in woodland, suggesting that grassland was the worst land-use type to buffer the Pb toxicity. Woodland could be recommended as the proper native land use to alleviate environmental risk. Overall, our results demonstrated the dominant factor to regulate Pb speciation and pointed out the proper land-use in relieving Pb leaching risk around Pb-Zn mine. These finding provides the new strategies to the remediation and management of metal-contaminated soil

Spatial and temporal distribution of falciparum malaria in China

Background: Falciparum malaria is the most deadly among the four main types of human malaria. Although great success has been achieved since the launch of the National Malaria Control Programme in 1955, malaria remains a serious public health problem in China. This paper aimed to analyse the geographic distribution, demographic patterns and time trends of falciparum malaria in China. Methods: The annual numbers of falciparum malaria cases during 1992–2003 and the individual case reports of each clinical falciparum malaria during 2004–2005 were extracted from communicable disease information systems in China Center for Diseases Control and Prevention. The annual number of cases and the annual incidence were mapped by matching them to corresponding province- and county-level administrative units in a geographic information system. The distribution of falciparum malaria by age, gender and origin of infection was analysed. Time-series analysis was conducted to investigate the relationship between the falciparum malaria in the endemic provinces and the imported falciparum malaria in non-endemic provinces. Results: Falciparum malaria was endemic in two provinces of China during 2004–05. Imported malaria was reported in 26 non-endemic provinces. Annual incidence of falciparum malaria was mapped at county level in the two endemic provinces of China: Yunnan and Hainan. The sex ratio (male vs. female) for the number of cases in Yunnan was 1.6 in the children of 0–15 years and it reached 5.7 in the adults over 15 years of age. The number of malaria cases in Yunnan was positively correlated with the imported malaria of concurrent months in the non-endemic provinces. Conclusion: The endemic area of falciparum malaria in China has remained restricted to two provinces, Yunnan and Hainan. Stable transmission occurs in the bordering region of Yunnan and the hilly-forested south of Hainan. The age and gender distribution in the endemic area is characterized by the predominance of adult men cases. Imported falciparum malaria in the non-endemic area of China, affected mainly by the malaria transmission in Yunnan, has increased both spatially and temporally. Specific intervention measures targeted at the mobile population groups are warranted

The prognostic biological markers of immunotherapy for non-small cell lung cancer: current landscape and future perspective

The emergence of immunotherapy, particularly programmed cell death 1 (PD-1) and programmed cell death ligand-1 (PD-L1) produced profound transformations for treating non-small cell lung cancer (NSCLC). Nevertheless, not all NSCLC patients can benefit from immunotherapy in clinical practice. In addition to limited response rates, exorbitant treatment costs, and the substantial threats involved with immune-related adverse events, the intricate interplay between long-term survival outcomes and early disease progression, including early immune hyperprogression, remains unclear. Consequently, there is an urgent imperative to identify robust predictive and prognostic biological markers, which not only possess the potential to accurately forecast the therapeutic efficacy of immunotherapy in NSCLC but also facilitate the identification of patient subgroups amenable to personalized treatment approaches. Furthermore, this advancement in patient stratification based on certain biological markers can also provide invaluable support for the management of immunotherapy in NSCLC patients. Hence, in this review, we comprehensively examine the current landscape of individual biological markers, including PD-L1 expression, tumor mutational burden, hematological biological markers, and gene mutations, while also exploring the potential of combined biological markers encompassing radiological and radiomic markers, as well as prediction models that have the potential to better predict responders to immunotherapy in NSCLC with an emphasis on some directions that warrant further investigation which can also deepen the understanding of clinicians and provide a reference for clinical practice

Evolutionarily distinct Resistance proteins detect a pathogen effector through its association with different host targets

Knowledge of the evolutionary processes which govern pathogen recognition is critical to understanding durable disease resistance. We determined how Phytophthora infestans effector PiAVR2 is recognised by evolutionarily distinct resistance proteins R2 and Rpi-mcq1. We employed yeast two-hybrid, co-immunoprecipitation, virus-induced gene silencing, transient overexpression, and phosphatase activity assays to investigate the contributions of BSL phosphatases to R2- and Rpi-mcq1-mediated hypersensitive response (R2 HR and Rpi-mcq1 HR, respectively). Silencing PiAVR2 target BSL1 compromises R2 HR. Rpi-mcq1 HR is compromised only when BSL2 and BSL3 are silenced. BSL1 overexpression increases R2 HR and compromises Rpi-mcq1. However, overexpression of BSL2 or BSL3 enhances Rpi-mcq1 and compromises R2 HR. Okadaic acid, which inhibits BSL phosphatase activity, suppresses both recognition events. Moreover, expression of a BSL1 phosphatase-dead (PD) mutant suppresses R2 HR, whereas BSL2-PD and BSL3-PD mutants suppress Rpi-mcq1 HR. R2 interacts with BSL1 in the presence of PiAVR2, but not with BSL2 and BSL3, whereas no interactions were detected between Rpi-mcq1 and BSLs. Thus, BSL1 activity and association with R2 determine recognition of PiAVR2 by R2, whereas BSL2 and BSL3 mediate Rpi-mcq1 perception of PiAVR2. R2 and Rpi-mcq1 utilise distinct mechanisms to detect PiAVR2 based on association with different BSLs, highlighting central roles of these effector targets for both disease and disease resistance

Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy

BackgroundThe aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model.MethodsThe Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7–14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein–protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI.ResultsForty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467–0.699, p < 0.05), and all with optimal AUC values (0.7344–1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669–0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI.ConclusionIL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers

Phytophthora infestans RXLR effectors act in concert at diverse subcellular locations to enhance host colonization

Oomycetes such as the potato blight pathogen Phytophthora infestans deliver RXLR effectors into plant cells to manipulate host processes and promote disease. Knowledge of where they localize inside host cells is important in understanding their function. Fifty-two P. infestans RXLR effectors (PiRXLRs) up-regulated during early stages of infection were expressed as fluorescent protein (FP) fusions inside cells of the model host Nicotiana benthamiana. FP-PiRXLR fusions were predominantly nucleo-cytoplasmic, nuclear, or plasma membrane-associated. Some also localized to the endoplasmic reticulum, mitochondria, peroxisomes, or microtubules, suggesting diverse sites of subcellular activity. Seven of the 25 PiRXLRs examined during infection accumulated at sites of haustorium penetration, probably due to co-localization with host target processes; Pi16663 (Avr1), for example, localized to Sec5-associated mobile bodies which showed perihaustorial accumulation. Forty-five FP-RXLR fusions enhanced pathogen leaf colonization when expressed in Nicotiana benthamiana, revealing that their presence was beneficial to infection. Co-expression of PiRXLRs that target and suppress different immune pathways resulted in an additive enhancement of colonization, indicating the potential to study effector combinations using transient expression assays. We provide a broad platform of high confidence P. infestans effector candidates from which to investigate the mechanisms, singly and in combination, by which this pathogen causes disease.</p