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关键词： Diesel   Fuel cell   Auxiliary power unit   Autothermal reforming   Kinetic modeling  

摘要： Fuel cell auxiliary power unit (FC-APU) system for heavy-duty trucks has been attracting much attention as an alternative to engine idling to reduce pollutant emissions. In this system, a reformer, which converts diesel, the main fuel of heavy-duty trucks, into syngas suitable for the fuel cell, is essential. A kinetic model of the reforming can be helpful in tasks such as the reactor design and system operation, but it is highly challenging to develop such a model due to the complexity of the reforming reaction network. Thus, in this study, we propose a systematic approach to build a reduced kinetic model of the diesel autothermal reformer. Specifically, microreactor experiments are conducted using a commercial diesel fuel, where the temperature, oxygen-to-carbon ratio (OCR), and steam-to-carbon ratio (SCR) are varied. Then, based on the composition measurements of the exit gas, optimal kinetic models are constructed by iteratively solving a parameter estimation problem for the candidate kinetic models with varying number of reactions. To reduce the number of candidates significantly, lumping techniques are used to generate reduced kinetic models. A stochastic optimization method is employed for the parameter estimation in which the concept of cross-entropy is used. The optimal reduced kinetic models with 3 and 4 reactions showed a consistency with the literature in terms of the reactions included. The accuracy of optimal reduced kinetic models increased, showing 21% improvement as the number of reactions increased from 3 to 4.

关键词： replicative senescence   aging   breast cancer   mammary epithelial cell   proteomics   data integration  

摘要： Senescence is a permanent cell cycle arrest that occurs in response to cellular stress and promotes age-related disease. Because senescence differs greatly depending on cell type and senescence inducer, continued progress in the characterization of senescent cells is needed. Here, we analyzed primary human mammary epithelial cells (HMECs), a model system for aging and cancer, using mass spectrometry-based proteomics. By integrating data from replicative senescence, immortalization by telomerase reactivation, and quiescence, we identified a robust proteomic signature of HMEC senescence consisting of 34 upregulated and 10 downregulated proteins. This approach identified known senescence biomarkers including beta-galactosidase (GLB1) as well as novel senescence biomarkers including catechol O-methyltransferase (COMT), synaptic vesicle membrane protein VAT-1 homolog (VAT1), and plastin-1/3 (PLS1/PLS3). Gene ontology enrichment analysis demonstrated that senescent HMECs upregulated lysosomal proteins and downregulated RNA metabolic processes. In addition, a classification model based on our proteomic signature successfully discriminated proliferating and senescent HMECs at the transcriptional level. Finally, we found that the HMEC senescence signature was positively and negatively correlated with proteomic alterations in HMEC aging and breast cancer, respectively. Taken together, our results demonstrate the power of proteomics to identify cell type-specific signatures of senescence and advance the understanding of senescence in HMECs.

关键词： Mannich bases   Imidazole   Benzimidazole   Chagas disease   Neglected tropical diseases   Trypanosoma cruzi  

摘要： The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline. (C) 2021 Elsevier Masson SAS. All rights reserved.

关键词： 公路桥梁   伸缩缝   设计   施工应用  

摘要： 随着社会经济的发展,人们的日常出行和城市建设都离不开公路桥梁的支持,在现代的公路桥梁施工过程中,桥梁伸缩缝技术得到了较广的应用,公路桥梁的伸缩缝施工质量将会对公路桥梁的使用质量起到关键的影响。在公路桥梁伸缩缝施工中,对施工的技术和质量一直以来都是施工技术人员所关心的问题。本文主要针对公路桥梁的伸缩缝施工质量控制展开讨论。

摘要： Purpose/Objective(s) To investigate the timing and pattern of recurrence in stage IIIA-N2 non-small cell lung cancer (NSCLC) patients after complete resection and adjuvant chemotherapy. Materials/Methods The study cohort included pathologically confirmed stage IIIA-N2 NSCLC patients treated with complete resection and adjuvant chemotherapy from 2003 to 2015 in our single institution. Recurrence was categorized as local-regional recurrence (LRR), distant metastasis (DM) and both LRR and DM. The risk distribution was assessed by using clinical and pathological factors. The hazard rate function and competing risk analysis were used to evaluate the recurrence dynamics. The Gray's test was employed to estimate the cumulative recurrence rates and compare the differences between groups. Results Among 854 patients, 61.9% had multiple station N2 involvement. The 1, 3 and 5-year cumulative incidence rates of recurrence was 16.85%, 50.74% and 67.37%, respectively. Of the 510 patients who experienced recurrence, 95 (18.6%) experienced LRR, 285 (55.9%) experienced DM, whereas 130 (25.5%) had both LRR and DM. The hazard rate function for overall recurrence revealed a continuous increase between 0-18 months after surgery, consistent high level during 8-48 months and marked decline thereafter. And the DM displayed a hazard rate curve similar to that of overall recurrence. However, a double-peaked pattern of hazard rate was present in LRR and both LRR and DM. What's more, the peak recurrence frequency of DM differed by organs. A comparison of clinical and pathological factors revealed that patients with lower pT stage, single pN2 station and postoperative radiotherapy had a lower recurrence risk but similar pattern of recurrence. Conclusion The recurrence risk of IIIA-N2 NSCLC after complete resection and adjuvant chemotherapy increased to a high level in 18 months and maintained continuously high till 48 months after surgery, which hinted necessity of intensive follow-up during thi

摘要： Purpose/Objective(s) We previously reported the two-year results of MC1273, a phase II trial evaluating 30-36 Gy of adjuvant radiation therapy (RT) for selected patients (pts) with HPV+ OPSCC. Herein we report the long-term disease control and toxicity rates for this de-escalated regimen. Materials/Methods Details for the MC1273 regimen have previously been published. All pts received surgery & neck dissection for a margin negative resection. Eligibility criteria included pts with HPV+OPSCC, ≤10 pack-year smoking history, and negative margins. Cohort A (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) received 30 Gy delivered in 1.5 Gy b.i.d. over 12 days along with weekly docetaxel (15 mg/m2, days 1 & 8). Pts with +ECE were enrolled in Cohort B and received the same treatment plus a simultaneous integrated boost to nodal levels with ECE to 36 Gy in 1.8 Gy b.i.d. The primary endpoint was local/regional control (LRC) at 2 years with each cohort powered to detect a 10% locoregional failure rate with 85% confidence. Secondary endpoints included 2-yr progression free survival (PFS), overall survival (OS), toxicity, swallow function, and pt reported QOL. Follow-up was q3 mos for the first 2 years, q6 mo for year 3, and yearly until year 5. Based upon the 2-year MC1273 data, pts with pT4 disease were excluded from MC1675, the follow-up phase III trial randomizing pts to the 30-36 Gy regimen versus a standard 60 Gy regimen. Results Accrual was from September 2013 to June 2016 (n = 80, 1 ineligible, Cohort A: 37, Cohort B: 43, median (range) age 61 years (25 - 77), male n = 71 (89.9%). Median follow-up for alive pts as of 2/22/21 was 52 mos (30 – 67). Late grade 2 or higher toxicity rates at 2, 3, and 5 years were 6.7%, 6.8%, and 5.0%, respectively, with the most common being dry mouth (1.7%, 3.4%, and 0.0% at years 2, 3, and 5) and dysphagia (3.3%, 0.0%, and 5.0% at years 2, 3, and 5). Grade 3 rates were 0.0%, 0.0%, and 1.2% at years 2, 3, and 5, respectively, wi