An Adaptive Maintenance Model Oriented to Process Environment of the Manufacturing Systems

We explored an adaptive maintenance model of the process environment to diagnose progressive faults in manufacturing systems. Progressive faults are usually caused by deterioration of the operating environment or aging and show stochastic properties. Many researchers have reported how to detect faults on the machine body in manufacturing systems. However, little research has been conducted on the process environment which causes progressive faults. To tackle this problem, we explored an adaptive maintenance model to detect progressive faults and repair the process environment on the E-repair location. When a difference of the environmental factor state is detected, it will combine the transcription factor and the state enzyme to locate fault source. Then the comprehensive maintenance program is derived to repair the operating environment while eliminating progressive faults. For the purpose of validation, this model was implemented on the process environment of the air separation plant. And the simulation experiments validated the feasibility and effectiveness of this method

l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.</p

Reinforced Lin-Kernighan-Helsgaun Algorithms for the Traveling Salesman Problems

TSP is a classical NP-hard combinatorial optimization problem with many practical variants. LKH is one of the state-of-the-art local search algorithms for the TSP. LKH-3 is a powerful extension of LKH that can solve many TSP variants. Both LKH and LKH-3 associate a candidate set to each city to improve the efficiency, and have two different methods, $\alpha$-measure and POPMUSIC, to decide the candidate sets. In this work, we first propose a Variable Strategy Reinforced LKH (VSR-LKH) algorithm, which incorporates three reinforcement learning methods (Q-learning, Sarsa, Monte Carlo) with LKH, for the TSP. We further propose a new algorithm called VSR-LKH-3 that combines the variable strategy reinforcement learning method with LKH-3 for typical TSP variants, including the TSP with time windows (TSPTW) and Colored TSP (CTSP). The proposed algorithms replace the inflexible traversal operations in LKH and LKH-3 and let the algorithms learn to make a choice at each search step by reinforcement learning. Both LKH and LKH-3, with either $\alpha$-measure or POPMUSIC, can be significantly improved by our methods. Extensive experiments on 236 widely-used TSP benchmarks with up to 85,900 cities demonstrate the excellent performance of VSR-LKH. VSR-LKH-3 also significantly outperforms the state-of-the-art heuristics for TSPTW and CTSP.Comment: arXiv admin note: text overlap with arXiv:2107.0687

The correlation between intracranial arterial calcification and the outcome of reperfusion therapy

Objective: Intracranial arterial calcification (IAC) is a risk factor of ischemic stroke. However, the relationship between IAC patterns and clinical outcome of ischemic stroke remains controversial. We aimed to investigate the correlation between IAC patterns and the effects of reperfusion therapy among acute stroke patients. Methods: Consecutive acute ischemic stroke patients who underwent reperfusion therapy were included. IAC was categorized as intimal or medial. Based on its involvement, IAC was further classified as diffuse or focal. Neurologic dysfunction was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed. Results: Of 130 patients, 117 had IAC. Intimal IAC was identified in 74.6% of patients and medial IAC was present in 64.6% of patients. Diffuse IAC was present in 31.5% of patients. All diffuse IACs were medial pattern. Diffuse IAC was associated with higher baseline NIHSS (p = 0.011) and less FNO (p = 0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p = 0.002) and less FNO (p = 0.024). Multivariable linear regression (p &lt; 0.001) and logistic regression (p = 0.027) suggested that multiple diffuse IAC was associated with higher baseline NIHSS and less FNO. No significant association was found between END and different IAC patterns. Interpretation: Multiple diffuse medial IAC may predict severer neurologic dysfunction and less favorable neurologic outcome after reperfusion therapy in acute stroke patients.</p

Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P &lt; 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).ConclusionsOur findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children

Association between IL-6 polymorphisms and Atopic Dermatitis in Chinese Han children

IntroductionAtopic Dermatitis (AD) is a chronic inflammatory skin disease that affects almost 20% of children and 2 -10% of adults worldwide. Previous studies revealed that Interleukin-6 (IL-6) plays an essential role in autoimmune and chronic inflammatory diseases. This study aims to investigate the associations between IL-6 polymorphisms and AD.MethodsBlood samples were collected from 132 AD patients and 100 controls, and single nucleotide polymorphisms (SNPs) in IL-6 (rs2069840 (C/G), rs2066992 (G/T), rs2069837 (A/G) and rs1800796 (G/C)) were analyzed using Multiplex PCR-Based Next Generation Sequencing (NGS).ResultsResults showed that the A/G genotype of IL-6/rs2069837 was significantly associated with a 1.933-fold increased risk of AD compared to those patients with A/A genotype (OR 1.933; 95%CI 1.086-3.438; p=0.024). The combined A/G-G/G genotype raised AD risk by 1.856 times compared to patients with the A/A genotype in dominant model (OR: 1.856; 95% CI: 1.056-3.261; p=0.030). No association was observed for 3 other SNPs and 4 haplotypes.DiscussionThese findings suggested that the A/G genotype of IL-6/rs2069837 was more susceptible to AD than A/A genotype in Chinese Han children, indicating the risk role of IL-6/rs2069837 in the occurrence of AD

Verification of thermoelectric magnetohydrodynamic flow effects on dendritic tip kinetics by in-situ observations

Magnetohydrodynamic flows can be driven by Lorentz forces acting on thermoelectric currents. Their effects on tip velocities of Pd dendrites solidifying from an undercooled melt under magnetic field intensities of up to 6 T were investigated by in-situ observations using a high-speed camera. At low undercoolings, the tip velocities are depressed by magnetic fields of low and high intensities, but recover under an intermediate magnetic field intensity. At high undercoolings, the tip velocities are also depressed, but their recovery is shifted to a higher magnetic field intensity. These observations on Pd dendrites support and extend the findings obtained in previous studies on Ni and Fe dendrites, and fully verify the convection effects on dendritic growth due to three thermoelectric magnetohydrodynamic flow patterns as predicted in recent numerical simulations

Effect of FTY720 on Some Physiological Indexes of Non-Obese Diabetic (NOD) Mice

The studies were performed to investigate the physiological characteristics of non-obese diabetic (NOD) mice treated with FTY720. At the age of 12 weeks, each mouse was fed with FTY720 or physiological saline once a day for 10 weeks running, and their blood glucose, weight, anti-GAD antibody and organ indexes were determined. No mouse in group FTY720 (NOD mice treated with FTY720) showed diabetic symptoms. The average content of serum anti-GAD antibody in group FTY720 decreased 48.75% (P < 0.01). It was concluded that the spleen, kidney and liver of NOD mice treated with FTY720 shriveled significantly in the progression of diabetes (P < 0.01 or P < 0.05). The body weight of group FTY720 mice was slightly lower than that of the model control (MC) group and these two groups both had less body weight than the normal control (NC) group (P < 0.01). The result of tests of anti-GAD antibody suggested that FTY720 treatment could suppress the anti-GAD response

Targeting glutamine metabolic reprogramming of SLC7A5 enhances the efficacy of anti-PD-1 in triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is a heterogeneous disease that is characterized by metabolic disruption. Metabolic reprogramming and tumor cell immune escape play indispensable roles in the tumorigenesis that leads to TNBC.MethodsIn this study, we constructed and validated two prognostic glutamine metabolic gene models, Clusters A and B, to better discriminate between groups of TNBC patients based on risk. Compared with the risk Cluster A patients, the Cluster B patients tended to exhibit better survival outcomes and higher immune cell infiltration. In addition, we established a scoring system, the glutamine metabolism score (GMS), to assess the pattern of glutamine metabolic modification.ResultsWe found that solute carrier family 7 member 5 (SLC7A5), an amino acid transporter, was the most important gene and plays a vital role in glutamine metabolism reprogramming in TNBC cells. Knocking down SLC7A5 significantly inhibited human and mouse TNBC cell proliferation, migration, and invasion. In addition, downregulation of SLC7A5 increased CD8+ T-cell infiltration. The combination of a SLC7A5 blockade mediated via JPH203 treatment and an anti-programmed cell death 1 (PD-1) antibody synergistically increased the immune cell infiltration rate and inhibited tumor progression.ConclusionsHence, our results highlight the molecular mechanisms underlying SLC7A5 effects and lead to a better understanding of the potential benefit of targeting glutamine metabolism in combination with immunotherapy as a new therapy for TNBC