Direct and controlled device integration of graphene oxide on Quartz Crystal Microbalance via electrospray deposition for stable humidity sensing

Integration of advanced and functional materials onto conventional sensing platforms can improve the device performances and even discover new applications. For piezoelectric resonant sensors, an addition of sensing materials can induce damping and hinder a stable device operation. Hence, the development of efficient method for materials integration is important to ensure high-performance and reliable sensor operation. This work presents a direct and precisely controlled integration of graphene oxide (GO) using the electrospray deposition (ESD) onto a 10 MHz Quartz Crystal Microbalance (QCM) for humidity sensing. The proposed ESD method achieves a high mass resolution of a few nanograms. Moreover, the GO uniformly coats across the sensing electrode region as it acts as a ground electrode during ESD. The proposed ESD method also works for a wide range of nanomaterials, such as carbon nanotubes, tin oxide, and silicon carbide micro-and nano-powders. Compared to the conventional drop-casting and dip coating approaches, our method ensures minimal GO agglomeration, resulting in a stable QCM-oscillator operation in a wide range of relative humidity from 11% to 97%. The measurement sensitivity increases with an amount of GO, but less GO results in better noise and detection limit performances. The results shed light on the importance of selecting an optimal amount of sensing materials for stable sensor operations.     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

The Impact of the ‘Mis-Peptidome’ on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response

The strong association with the Major Histocompatibility Complex (MHC) class I genes represents a shared trait for a group of autoimmune/autoinflammatory disorders having in common immunopathogenetic basis as well as clinical features. Accordingly, the main risk factors for Ankylosing Spondylitis (AS), prototype of the Spondyloarthropathies (SpA), the Behçet’s disease (BD), the Psoriasis (Ps) and the Birdshot Chorioretinopathy (BSCR) are HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02, respectively. Despite the strength of the association, the HLA pathogenetic role in these diseases is far from being thoroughly understood. Furthermore, Genome-Wide Association Studies (GWAS) have highlighted other important susceptibility factors such as Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and, less frequently, ERAP2 that refine the peptidome presented by HLA class I molecules to CD8⁺ T cells. Mass spectrometry analysis provided considerable knowledge of HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02 immunopeptidome. However, the combined effect of several ERAP1 and ERAP2 allelic variants could generate an altered pool of peptides accounting for the “mis-immunopeptidome” that ranges from suboptimal to pathogenetic/harmful peptides able to induce non-canonical or autoreactive CD8⁺ T responses, activation of NK cells and/or garbling the classical functions of the HLA class I molecules. This review will focus on this class of epitopes as possible elicitors of atypical/harmful immune responses which can contribute to the pathogenesis of chronic inflammatory diseases.     

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.     

Design,Synthesis, and in vitro Evaluation of P2X7 Antagonists

The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide ( 56 ) exhibiting the best potency with an IC₅₀ value of 0.39 μM.     

大数据环境下基于K中心点优化算法的Web服务组合

在当前Web服务海量增加、现有Web服务选择算法低效、用户匹配度差的基础上，针对K中心点算法存在的质点偏移、准确率低和容易发生畸变等问题，提出一种大数据环境下基于K中心点优化算法的Web服务组合方法。该方法是在大数据环境下，根据不同用户需求满意度及Web服务QoS参数，对基于优化初始聚类中心的K中心点算法的Web服务选择及最优Web服务组合进行研究。同时针对不同的选择方法对服务动态选择及组合的准确度、迭代更新次数、候选集选择时间及选择总时间进行实验分析，验证了本文研究方法的有效性和可靠性。     

面向连续查询的敏感语义位置隐私保护方案

针对连续查询位置服务中构造匿名区域未考虑语义位置信息导致敏感隐私泄露问题，通过设计[(K,θ)]-隐私模型，提出一种路网环境下面向连续查询的敏感语义位置隐私保护方案。该方案利用Voronoi图将城市路网预先划分为独立的Voronoi单元，依据用户的移动路径和移动速度，选择具有相似特性的其他[K-1]个用户，构建匿名用户集；利用匿名用户集用户设定的敏感语义位置类型和语义安全阈值，以及用户所处语义位置的Voronoi单元，构建满足[(K,θ)]-隐私模型的语义安全匿名区域，可以同时防止连续查询追踪攻击和语义推断攻击。实验结果表明，与SCPA算法相比，该方案在隐私保护程度上提升约15%，系统开销上降低约20%。     

2种灰色模型在矿区地表沉陷预计中的适用性

目前矿区地表单点沉陷动态预计方法主要基于传统的水准测量数据,监测方法单一,成本高,观测点易破坏,不能保证地表形变信息的实时性,且采用灰色模型进行地表沉陷预计时只针对单一模型的应用,没有结合模型自身特点分析其适用性。以袁店二矿7221工作面为试验区域,采用合成孔径雷达差分干涉测量技术监测矿区地表沉陷量,分别建立了描述沉陷量与时间关系的GM(1,1)与灰色Verhulst模型进行地表沉陷量预计,实现了矿区地表沉陷监测与动态预计一体化。通过比较、分析GM(1,1)与灰色Verhulst模型对地表沉陷量的拟合及预计结果,得出了2种灰色模型在矿区地表沉陷预计中的适用性:在矿区开采沉陷开始至活跃前期,若地表单点沉陷量曲线呈近似单峰型,则宜采用GM(1,1)进行短期预计;当矿区地表沉陷进入衰退阶段,单点沉陷量曲线呈平底饱和状态,则宜采用灰色Verhulst模型进行中长期预计。     

异螺距万分尺设计

介绍了一种螺旋万分尺的结构设计。该万分尺的微分筒采用双螺纹,两螺纹的螺旋方向相同,螺距不同。采用V型槽和V型块精确定位来增加量程。测量最小刻度可达0.001 mm,读数精度达0.0001 mm。万分尺采用纯机械结构,结构原理简单,制造安装方便。