基于突变级数法的青海木里矿区冻土环境评价

为探索矿区冻土环境评价的方法和理论,应用突变理论对冻土环境进行了分析.基于由冻土冻融侵蚀敏感性、冻土热稳定性和冻土生态脆弱性3个子系统组成的青海木里矿区冻土环境评价指标体系,建立了木里矿区冻土环境评价突变模型.利用文献资料和野外考察资料,采用突变级数法,通过突变模型的归一公式建立了评价等级标准（理想状态、良好状态、一般状态、较差状态、恶劣状态),并对木里矿区冻土环境进行了综合评价.研究结果表明：木里矿区冻土环境质量为一般状态;与其他环境评价方法相比,突变级数法只需对评价因子进行重要性排序,在一定程度上避免了权重赋值的主观性.由于冻土环境的特殊性,应用突变级数法对矿区冻土环境进行评价更加地科学和有效.     

基于分形理论的超特高压线路绕击耐雷性能评估

超特高压输电线路雷电屏蔽模型对线路的防雷设计有着重要的指导意义。为此研究了一种基于分形理论的输电线路绕击先导发展模型,首先从雷云电荷分布、上行先导起始、上下行先导发展和最终判据等方面研究了分形先导发展模型计算流程中的关键问题。并根据分形理论研究了上下行先导发展的电介质击穿模型DBM以及实现方式,通过雷电先导发展过程中空间电场的计算,得出了先导向空间各可能击穿点发展的概率分布,实现了雷电先导发展过程的分形生长。基于分形先导发展模型,还给出了超特高压输电线路绕击耐雷性能的评估方法,结合雷电流空间概率分布和由分形先导模型计算得出的绕击概率分布,可计算得出输电线路的绕击率。此方法在±800kV特高压输电线路上的绕击耐雷性能评估中的应用表明,该方法不仅能获得较精确的绕击率,同时使先导发展过程中既保持了沿最大场强发展的概率最大这一确定性因素,也呈现了先导发展的随机性因素。     

均质粘性土坝漫顶溃决过程试验研究

为研究均质粘性土坝不同几何断面对溃坝过程的影响,设计了四组物理模型试验,对比研究了不同坝坡比、坝高、坝顶宽度情况下均质粘性土坝溃坝的流量过程与溃口宽度的变化过程,同时通过理论计算验证模型的准确性。试验结果表明,整个溃决过程大致可分为冲刷沟形成阶段、冲刷沟扩展阶段、溃口坍塌阶段、溃口趋于稳定阶段4个阶段;坝坡比、坝体高度分别对下游坝坡的中下部和顶部的溃口宽度起主要作用,而坝顶宽度对溃口形状的影响不大。     

DATA BREACH MANAGEMENT: AN INTEGRATED RISK MODEL

In response to organizations’ increasing vulnerability to data breaches, we present an integrated risk model for data breach management based on a systematic review of the literature. Theoretically, the study extends the body of knowledge on data breach management by identifying and updating conceptualizations of data breach risks (items) and resolutions (actions) and by providing a foundation for organizational responses to emerging data breach incidents (heuristics). Practically, the study provides key insights that practitioners can use to organize and orchestrate effective data breach management based on comprehensive profiles of risk items and resolution techniques.     

Long Non-Coding RNAs as Functional Codes for Oral Cancer: Translational Potential,Progress and Promises

Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection and effective therapies. Long non-coding RNAs (lncRNAs) are recognized as key elements of gene regulation, with pivotal roles in various physiological and pathological processes, including cancer. Over the past few years, an exponentially growing number of lncRNAs have been identified and linked to tumorigenesis and prognosis outcomes in oral cancer, illustrating their emerging roles in oral cancer progression and the associated signaling pathways. Herein, we aim to summarize the most recent advances made concerning oral cancer-associated lncRNA, and their expression, involvement, and potential clinical impact, reported to date, with a specific focus on the lncRNA-mediated molecular regulation in oncogenic signaling cascades and oral malignant progression, while exploring their potential, and challenges, for clinical applications as biomarkers or therapeutic targets for oral cancer.     

Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy

Teneurins have been identified in vertebrates as four different genes (TENM1-4), coding for membrane proteins that are mainly involved in embryonic and neuronal development. Genetic studies have correlated them with various diseases, including developmental problems, neurological disorders and congenital general anosmia. There is some evidence to suggest their possible involvement in cancer initiation and progression, and drug resistance. Indeed, mutations, chromosomal alterations and the deregulation of teneurins expression have been associated with several tumor types and patient survival. However, the role of teneurins in cancer-related regulatory networks is not fully understood, as both a tumor-suppressor role and pro-tumoral functions have been proposed, depending on tumor histotype. Here, we summarize and discuss the literature data on teneurins expression and their potential role in different tumor types, while highlighting the possibility of using teneurins as novel molecular diagnostic and prognostic biomarkers and as targets for cancer treatments, such as immunotherapy, in some tumors.     

Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini

Local basement membrane (BM) disruption marks the initial step of breast cancer invasion. The activation mechanisms of force-driven BM-weakening remain elusive. We studied the mechanical response of MCF10A-derived human breast cell acini with BMs of tuneable maturation to physical and soluble tumour-like extracellular matrix (ECM) cues. Traction force microscopy (TFM) and elastic resonator interference stress microscopy (ERISM) were used to quantify pro-invasive BM stress and protrusive forces. Substrate stiffening and mechanically impaired BM scaffolds induced the invasive transition of benign acini synergistically. Robust BM scaffolds attenuated this invasive response. Additional oncogenic EGFR activation compromised the BMs’ barrier function, fuelling invasion speed and incidence. Mechanistically, EGFR-PI3-Kinase downstream signalling modulated both MMP- and force-driven BM-weakening processes. We show that breast acini form non-proteolytic and BM-piercing filopodia for continuous matrix mechanosensation, which significantly push and pull on the BM and ECM under pro-invasive conditions. Invasion-triggered acini further shear and compress their BM by contractility-based stresses that were significantly increased (3.7-fold) compared to non-invasive conditions. Overall, the highest amplitudes of protrusive and contractile forces accompanied the highest invasiveness. This work provides a mechanistic concept for tumour ECM-induced mechanically misbalanced breast glands fuelling force-driven BM disruption. Finally, this could facilitate early cell dissemination from pre-invasive lesions to metastasize eventually.     

Multi-compartment tumor organoids

Organoid cultures are widely used for tumor modeling because they preserve many phenotypic features of cancer cells in vivo. However, current organoids present issues of consistency, efficiency, mimicry, and cell-seeding control. More importantly, they can only contain only one extracellular matrix (ECM) compartment at a time, while solid tumors feature two main ECM compartments: the basement membrane and the stromal matrix. Here, we develop, test, and validate a high-throughput oil-in-water droplet microtechnology to generate highly uniform, small-volume, multi-compartment organoids. Each organoid culture features microenvironmental architectures that mimic both the basement membrane and stromal barriers. This matrix architecture, which allows us to simultaneously take into account and assess the proliferative and invasive properties of cancer cells in a single platform, has profound effect on observed drug responsiveness and tumor progression that correlate well with in vivo and clinical outcomes. Our method was tested on multiple types of cells including primary breast and ovarian cancer cells and immortalized cell lines, and we determined our platform is suitable even for cancer cells of poor standard organoid-forming ability such as primary patient samples. These new organoids also allow for direct orthotopic mouse implantation of cancer cells with unprecedented success.