Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.     

Gap Junctional Communication via Connexin43 between Purkinje Fibers and Working Myocytes Explains the Epicardial Activation Pattern in the Postnatal Mouse Left Ventricle

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.     

Hybrid Solar Cells Based in Silicon Nanowires: Electronic Simulation and Optimization

Silicon - This paper presents recent progress in computational modeling on blend morphology of silicon nanowires (SiNWs) dispersed in a conjugated polymer poly(3-hexylthiophene) P3HT hybrid solar...     

A large-displacement 65Pb(Mg1/3Nb2/3)O3–35PbTiO3/Pt bimorph actuator prepared by screen printing

In this paper we present a novel approach to preparing large-displacement 65Pb(Mg_1/3Nb_2/3)O₃–35PbTiO₃/Pt (65/35 PMN–PT/Pt) bimorph actuators. These “substrate-free”, bending-type actuators were prepared by screen-printing the 65/35 PMN–PT and Pt thick-film pastes as the electrodes on alumina substrates. After this screen printing and the subsequent firing the 65/35 PMN–PT/Pt composites were peeled off from the substrates. Displacements of nearly 100 μm at 18 V were achieved for actuators with dimensions of 1.8 cm × 2.5 mm × 50 μm for the 65/35 PMN–PT layer. The normalized displacement (the displacement per unit length) was 40 μm/cm at 18 V. The experimental results together with a computation procedure were used to obtain the material parameters for a finite-element analysis of the 65/35 PMN–PT/Pt bimorph actuators.     

融合颜色相关性和纹理差异的阴影检测方法

在雨天交通视频中,车辆同时受阴影和水汽拖尾的干扰。为此,在分析目标车辆、路面、阴影和水汽拖尾区域特性的基础上,提出一种融合颜色相关性和纹理差异的阴影检测方法。由当前点与背景点的HIS向量点积测量颜色相关程度,检测出车辆目标和水汽拖尾区域,利用当前区域和背景区域的纹理差异区分深色车辆和阴影。实验结果表明,该方法能较好地检测雨天交通视频中运动车辆的投射阴影,且能有效去除水汽拖尾,从而保证车辆的正确分割。     

Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.