Current Status on Stem Cells and Cancers of the Gastric Epithelium

Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.     

Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

基于WiMAX通信网络的电源监控系统的构建

分析了全球微波接入互存(WiMAX)的技术特点和算法复杂度,探讨了其在电源监控系统中的应用,提出了基于Inter WiMAX Connection 2250技术的远程电源监控系统。在讨论WiMAX物理层算法的基础上,确定了以正交频分多址(OFDMA)模式为主体的物理层通信协议,提高了信道的利用率,抑制了码间干扰,为构建电源监控系统打下了良好的基础。     

Distributed wireless power transfer in sensor networks with multiple Mobile Chargers

We investigate the problem of efficient wireless power transfer in wireless sensor networks. In our approach, special mobile entities (called the Mobile Chargers) traverse the network and wirelessly replenish the energy of sensor nodes. In contrast to most current approaches, we envision methods that are distributed and use limited network information. We propose four new protocols for efficient charging, addressing key issues which we identify, most notably (i) what are good coordination procedures for the Mobile Chargers and (ii) what are good trajectories for the Mobile Chargers. Two of our protocols (DC, DCLK) perform distributed, limited network knowledge coordination and charging, while two others (CC, CCGK) perform centralized, global network knowledge coordination and charging. As detailed simulations demonstrate, one of our distributed protocols outperforms a known state of the art method, while its performance gets quite close to the performance of the powerful centralized global knowledge method.     

泛在电力物联网在北京经济技术开发区的应用探索

泛在电力物联网是物联网在电力领域的具体体现，建设泛在电力物联网是推进"三型两网"建设的关键环节，也是实现能源转型的必要手段。阐述了泛在电力物联网的定义，从供电公司角度出发，根据北京经济技术开发区实际情况，讨论了依托地区特点的泛在电力物联网实施策略和实际应用场景，分析了可能遇到的问题。得出结论：随着泛在电力物联网的深入建设，供电公司能够为电力客户提供多元化服务，提高客户满意度；地市供电公司能够依托泛在电力物联网开展更多电力相关业务；泛在电力物联网的安全性、实用性、有效性是发展面临的首要问题。     

摇摆运动下多环路主冷却剂系统自然循环流量的稳定性分析

海洋核动力平台因其突出的安全性已成为当今核能领域热点研究问题之一，但在海洋等非惯性条件下会使一回路系统的热工特性发生变化。针对此问题，本文对几种典型的一回路系统在摇摆条件下的自然循环流量波动特性进行计算分析。分别建立典型的双环路、三环路、四环路的一回路系统模型布置方案，并同时考虑摇摆中心的位置，根据流体动量守恒方程，得到不同状态下一回路系统内的流量变化规律。对于单堆双环路系统，摇摆中心在船上/中/下部位置时，环路流量波动幅度分别为13.2%/11.2%/9.5%，堆芯流量波动幅度分别为0.9%/0.8%/0.6%；对于单堆三环路系统，摇摆中心在船下部时，环路流量和堆芯流量波动幅度分别为9.2%和0.8%；对于单堆四环路系统，摇摆中心在船下部时，布置方案1和方案2的环路流量波动幅度分别为9.5%和9.2%，堆芯流量波动幅度分别为0.9%和0.7%。计算结果表明：采用单堆双环路的设计布置方案是最有利于系统稳定性的。     

The Interplay of Modulus,Strength, and Ductility in Adhesive Design Using Biomimetic Polymer Chemistry

High‐performance adhesives require mechanical properties tuned to demands of the surroundings. A mismatch in stiffness between substrate and adhesive leads to stress concentrations and fracture when the bonding is subjected to mechanical load. Balancing material strength versus ductility, as well as considering the relationship between adhesive modulus and substrate modulus, creates stronger joints. However, a detailed understanding of how these properties interplay is lacking. Here, a biomimetic terpolymer is altered systematically to identify regions of optimal bonding. Mechanical properties of these terpolymers are tailored by controlling the amount of a methyl methacrylate stiff monomer versus a similar monomer containing flexible poly(ethylene glycol) chains. Dopamine methacrylamide, the cross‐linking monomer, is a catechol moiety analogous to 3,4‐dihydroxyphenylalanine, a key component in the adhesive proteins of marine mussels. Bulk adhesion of this family of terpolymers is tested on metal and plastic substrates. Incorporating higher amounts of poly(ethylene glycol) into the terpolymer introduces flexibility and ductility. By taking a systematic approach to polymer design, the region in which material strength and ductility are balanced in relation to the substrate modulus is found, thereby yielding the most robust joints.     

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.     

The control of sea lice in Atlantic salmon by selective breeding

Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production.