115 research outputs found
Microstructural Evolution in Chroming Coatings Friction Pairs under Dry Sliding Test Conditions
The microstructures of subsurface layers of 20CrMnTi steel pins against chroming and nonchroming T10 under dry sliding tests were studied by means of OM (optical microscopy), XRD (X-ray diffraction), and SEM (scanning electron microscopy). Results showed that the chroming coating strengthened the disc surface and significantly affected microstructural evolution. Three layers—the matrix, deformation layer (DL), and surface layer (SL)—formed in 20CrMnTi for the chroming T10. The matrix and deformation layer (DL) formed in 20CrMnTi for the nonchroming T10. The formation of the microstructure was considered as a result of the shear deformation
Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck
<p>Abstract</p> <p>Background</p> <p>Cell cycle deregulation is common in human cancer, and alterations of <it>p27 </it>and <it>p21</it>, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that <it>p27 </it>T109G polymorphism individually or in combination with <it>p21 </it>(C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).</p> <p>Methods</p> <p>A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.</p> <p>Results</p> <p>We found that patients with <it>p27 </it>109 TG/GG, <it>p21 </it>98 CA/AA and <it>p21 </it>70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding <it>p27</it>109 TT, <it>p21 </it>98 CC, and <it>p21 </it>70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (<it>P</it><sub>trend </sub>= 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).</p> <p>Conclusions</p> <p>These results suggest that <it>p27 </it>T109G polymorphism individually or in combination with <it>p21 </it>(C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.</p
Identification of RUNX1 and IFNGR2 as prognostic-related biomarkers correlated with immune infiltration and subtype differentiation of low-grade glioma
Immune cell infiltration occurs in the tumor microenvironment (TME) and influences cancer progression through interaction with tumor cells. Runt-related transcription factors (RUNXs), RUNX1-3, are the master regulators of development and differentiation and are all important to the development of immune cells. However, the role of RUNXs in the immune cells of TME remains unclear. In this study, we first used online related databases and related LGG data from TCGA and CGGA to conduct bioinformatics analysis, which confirmed that RUNXs were significantly and positively correlated with immune infiltration in multiple tumors, especially in low-grade glioma (LGG) and there was the highest correlation between RUNXs and the progress and prognosis of LGG. Furthermore, the functional enrichment analysis revealed that RUNXs might be involved in the inflammatory and immune responses of the biological processes, and RUNXs were tightly associated with the multiple immune checkpoint molecules. Subsequent results confirmed that RUNX1, as an independent prognostic factor for LGG, may target interferon-gamma receptor 2 (IFNGR2) to regulate glioma cell proliferation, invasion, and migration. Besides, we also found that the expression levels of RUNX1 and IFNGR2 were significantly reduced, and their correlation was enhanced in the IDH-mutant subtype. Patients with a high expression of RUNX1 and/or IFNGR2 (HH/H) in the IDH-mutant subtype showed poorer prognosis and significantly increased infiltration of M2 macrophages. This finding implied the possible key role of RUNX1 in the differentiation of IDH mutant subtypes as well as in the formation of tumor microenvironment (TME) infiltration signatures by monitoring IFNGR2
Construction of a Medical Micro-Object Cascade Network for Automated Segmentation of Cerebral Microbleeds in Susceptibility Weighted Imaging
Aim: The detection and segmentation of cerebral microbleeds (CMBs) images are the focus of clinical diagnosis and treatment. However, segmentation is difficult in clinical practice, and missed diagnosis may occur. Few related studies on the automated segmentation of CMB images have been performed, and we provide the most effective CMB segmentation to date using an automated segmentation system.Materials and Methods: From a research perspective, we focused on the automated segmentation of CMB targets in susceptibility weighted imaging (SWI) for the first time and then constructed a deep learning network focused on the segmentation of micro-objects. We collected and marked clinical datasets and proposed a new medical micro-object cascade network (MMOC-Net). In the first stage, U-Net was utilized to select the region of interest (ROI). In the second stage, we utilized a full-resolution network (FRN) to complete fine segmentation. We also incorporated residual atrous spatial pyramid pooling (R-ASPP) and a new joint loss function.Results: The most suitable segmentation result was achieved with a ROI size of 32 × 32. To verify the validity of each part of the method, ablation studies were performed, which showed that the best segmentation results were obtained when FRN, R-ASPP and the combined loss function were used simultaneously. Under these conditions, the obtained Dice similarity coefficient (DSC) value was 87.93% and the F2-score (F2) value was 90.69%. We also innovatively developed a visual clinical diagnosis system that can provide effective support for clinical diagnosis and treatment decisions.Conclusions: We created the MMOC-Net method to perform the automated segmentation task of CMBs in an SWI and obtained better segmentation performance; hence, this pioneering method has research significance
Optimization and Lead Selection of Benzothiazole Amide Analogs Toward a Novel Antimycobacterial Agent
Mycobacteria remain an important problem worldwide, especially drug resistant human pathogens. Novel therapeutics are urgently needed to tackle both drug-resistant tuberculosis (TB) and difficult-to-treat infections with nontuberculous mycobacteria (NTM). Benzothiazole adamantyl amide had previously emerged as a high throughput screening hit against M. tuberculosis (Mtb) and was subsequently found to be active against NTM as well. For lead optimization, we applied an iterative process of design, synthesis and screening of several 100 analogs to improve antibacterial potency as well as physicochemical and pharmacological properties to ultimately achieve efficacy. Replacement of the adamantyl group with cyclohexyl derivatives, including bicyclic moieties, resulted in advanced lead compounds that showed excellent potency and a mycobacteria-specific spectrum of activity. MIC values ranged from 0.03 to 0.12 μg/mL against M. abscessus (Mabs) and other rapid- growing NTM, 1–2 μg/mL against M. avium complex (MAC), and 0.12–0.5 μg/mL against Mtb. No pre-existing resistance was found in a collection of n = 54 clinical isolates of rapid-growing NTM. Unlike many antibacterial agents commonly used to treat mycobacterial infections, benzothiazole amides demonstrated bactericidal effects against both Mtb and Mabs. Metabolic labeling provided evidence that the compounds affect the transfer of mycolic acids to their cell envelope acceptors in mycobacteria. Mapping of resistance mutations pointed to the trehalose monomycolate transporter (MmpL3) as the most likely target. In vivo efficacy and tolerability of a benzothiazole amide was demonstrated in a mouse model of chronic NTM lung infection with Mabs. Once daily dosing over 4 weeks by intrapulmonary microspray administration as 5% corn oil/saline emulsion achieved statistically significant CFU reductions compared to vehicle control and non-inferiority compared to azithromycin. The benzothiazole amides hold promise for development of a novel therapeutic agent with broad antimycobacterial activity, though further work is needed to develop drug formulations for direct intrapulmonary delivery via aerosol
Optimization of Resistance Spot Welding with Inserted Strips via FEM and Response Surface Methodology
Resistance spot welding (RSW) with inserted strips, a recent variant of traditional RSW, was usually adopted in joining thin gage steels to lower the temperature developed at the electrode surface and to extend electrode life. In order to understand the influencing mechanism how the inserted strips affect the heat transfer behavior and to optimize the selection of suitable strips, an approach integrated with FEM and response surface methodology (RSM) was employed. FEM results showed that the inserted strips would not only lead to earlier initiation of weld and bigger weld size in both diameter and thickness but also lower the electrode surface temperature. Based on FEM, uniform design and RSM were further employed to build a regression model between the strip properties (i.e., electrical/thermal conductivity, thickness) and the responses (i.e., electrode tip temperature, weld diameter, and temperature at strip/sheet interface). A graphical optimization was conducted to identify a preferable strip, and a Cu55Ni45 strip with a thickness of 0.12 mm was recommended for a 0.4 mm steel sheet
A Cluster-Based Multipath Routing for MANET
(Mobile Ad hoc Networks) is a core issue in the research of MANET. This article proposes a Cluster-Based Multipath Routing in MANET (CBMRP). It distributes traffic among diverse multiple paths to avoid congestion, which optimizes bandwidth using and improves the sharing rate of channel. It uses clustering’s hierarchical structure diverse to decrease routing control overhead and improve the networks scalability. By implementing the algorithm on the OPNET environment, the result shows that this algorithm balances the load of the network and deals with the change effectively of the network topology, and also improves the reliability, throughput and stability of the network efficiently. I
Effect of B2 Precipitation on Hot Ductility of Fe–22Mn–9Al–0.6C Low-Density Steel
Fe–Mn–Al–C low-density steels are regarded as promising materials applied in the automotive industry to achieve the minimization of vehicular emissions and fuel consumption. This study investigates the high-temperature strength and hot ductility of Fe–22Mn–9Al–0.6C low-density steel through high-temperature tensile tests at 800–950 °C. The high-temperature strength decreases with an increasing deformation temperature. This indicates that the precipitation of B2 reduces the hot ductility during the hot deformation of steel, where the results are consistent with those during the solid-solution treatment at 800–950 °C with a holding time of 0.5 h. Furthermore, at 800 °C the γ transforms into a mixture of α + DO3 and κ-carbide precipitates. A transformation of κ + DO3→B2 occurs in the temperature range of 850–900 °C, and at this point the κ-carbide dissolves into the matrix and B2 is generated, resulting in a significant decrease in hot ductility. As the temperature increases up to 950 °C, B2 emerges and transforms into the δ phase, and the κ-carbide precipitates along the γ/γ grain boundaries. The precipitation of B2 during high-temperature treatments in Fe-Mn-Al-C low-density steels is the critical factor affecting hot ductility, leading to crack generation; therefore, it is extremely essential to prevent the temperature interval of B2 precipitation during hot deformation processes
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