Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.     

RESERVOIR PROPERTIES OF BARREMIAN – APTIAN URGONIAN LIMESTONES,SE FRANCE,PART 1: INFLUENCE OF STRUCTURAL HISTORY ON POROSITY-PERMEABILITY VARIATIONS

Upper Barremian – Lower Aptian inner platform “Urgonian” limestones in the Mont de Vaucluse region, SE France, consist of alternating metre-scale microporous and tight intervals. This paper focuses on the influence of structural deformation on the reservoir properties of the Urgonian limestone succession in a study area near the town of Rustrel. Petrographic, petrophysical and structural data were recovered from five fully-cored boreholes, from the walls of a 100 m long underground tunnel, and from a 50 m long transect at a nearby outcrop. The data allowed reservoir property variations in the Urgonian limestones to be studied from core to reservoir scale. Eleven Reservoir Rock Types (RRTs) were identified based on petrographic features (texture, grain size), reservoir properties (porosity, permeability), and the frequency of structural discontinuities such as fractures, faults and stylolites. Tight and microporous reservoir rock types were distinguished. Tight reservoir rock types were characterised by early cementation of intergranular pore spaces and by the presence of frequent structural discontinuities. By contrast microporous reservoir rock types contained preserved intragranular microporosity and matrix permeability, but had very few structural discontinuities. Observed vertical alternations of microporous and tight rock types are interpreted to have been controlled by the early diagenesis of the Urgonian carbonates. Deformation associated with regional-scale tectonic phases, including Albian – Cenomanian “Durancian” uplift (∼105 to 96 Ma) and Pyrenean compression (∼55 to 25 Ma), resulted in the modification of the initial petrophysical properties of the Urgonian limestones. An early diagenetic imprint conditioned both the intensity of structural deformations and the associated circulations of diagenetic and meteoric fluids. Evolution of the Reservoir Rock Types is therefore linked both to the depositional conditions and to subsequent phases of structural deformation.     

Household endotoxin reduction in the Louisa Environmental Intervention Project for rural childhood asthma

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.     

川西彭州地区雷口坡组潮坪相薄储层辨识机理研究

川西彭州地区三叠系雷口坡组雷四上亚段潮坪相薄储层识别难度极大。围绕如何从复合地震强反射中区分并识别上、下两套储层面临的地球物理难题,采用先“分”后“合”的研究思路,基于实际地层结构及不同储层叠加样式建立正演模型,利用全波场波动方程正演模拟技术,剖析了不同主频条件下薄储层的地震响应特征,通过波形差异化分析,从复合地震响应中“剥离”出了两套储层所引起的地震响应特征及变化规律,明确了两套储层在不同频带下的地震识别标志和识别方法,为该区强反射界面干扰下两套薄互层储层辨识机理分析及精准预测奠定了基础。基于不同频带下薄储层辨识机理的分析结果,定性预测了薄储层平面展布,提出了深层潮坪相薄储层识别和预测难题的解决方案,为该区地震资料品质评价、面向薄储层的地震采集技术设计、地震资料处理及薄储层预测提供了依据和指导。     

Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells

In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism’s ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells.     

Enhanced photoreactivity of MOFs by intercalating interlayer bands via simultaneous ?NCO and ?SCu modification

Herein, we propose a novel method to enhance the photoreactivity of an MOF catalyst by grafting isocyanate bonds ( NCO) and sulfhydryl-complexed copper ( SCu) onto ZIF-8 (NIF-SCu). The grafting process intercalated interlayer bands between the conduction and valence bands of ZIF-8, thereby providing a “ladder” for facile electron transition. The extreme improvement in the photoreactivity of NIF-SCu could be attributed to the enhancement in light responses in the range of 350–450 nm by  NCO groups and the widening of the visible light range of the MOF by  SCu groups. The formation of staggered energy levels in NIF-SCu could also narrow the band gap, lower the resistance, and facilitate the transfer of photogenerated carriers, thereby generating electrons with strong reduction potential in the  SCu conduction band. This study provides a new strategy for improving or even endowing the photoactivity of environmental functional materials with wide bandgaps.     

基于局部分型面的电器外壳注塑模具设计

电器外壳制品形状结构复杂,有两处侧凸(孔)较难处理。通过对矩形孔内侧凸的结构分析,在其局部设计了分型面,避免了使用侧向抽芯机构;对侧孔部位设计了斜顶杆侧向抽芯机构,其结构简单、紧凑。模具采用一模二腔、平衡式布局,采用经扁推杆由制品内部进料的潜伏式浇口,S型流道。在NX 8.0中完成了模具结构设计。经实践证明,该模具结构合理,产品合格。     

基于“天空地”一体化技术的安全监测系统建设与应用

西藏江达县白格村金沙江右岸于2018年10月11日和2018年11月3日先后发生2次大规模滑坡—堰塞湖堵江事件,溃堰洪水对下游拉哇库区不良地质体的稳定性造成不同程度的影响。为保障下游水电站建设安全,对拉哇库区主要不良地质体建立了基于星载InSAR技术、无人机技术和地面传感器实时监测的“天空地”一体化监测预警体系,以多维空间采集技术获取变形信息,通过智能监控平台对信息及时进行处理、分析和可视化呈现,利用平台、短信等方式向相关人员进行分级告警,取得了较好的应用效果。     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Compiler compatible 5.66 Mb/mm2 8T 1R1W register file in 14 nm FinFET technology

1-read/1-write (1R1W) register file (RF) is a popular memory configuration in modern feature rich SoCs requiring significant amount of embedded memory. A memory compiler is constructed using the 8T RF bitcell spanning a range of instances from 32 b to 72 Kb. An 8T low-leakage bitcell of 0.106 μm² is used in a 14 nm FinFET technology with a 70 nm contacted gate pitch for high-density (HD) two-port (TP) RF memory compiler which achieves 5.66 Mb/mm² array density for a 72 Kb array which is the highest reported density in 14 nm FinFET technology. The density improvement is achieved by using techniques such as leaf-cell optimization (eliminating transistors), better architectural planning, top level connectivity through leaf-cell abutment and minimizing the number of unique leaf-cells. These techniques are fully compatible with memory compiler usage over the required span. Leakage power is minimized by using power-switches without degrading the density mentioned above. Self-induced supply voltage collapse technique is applied for write and a four stack static keeper is used for read Vmin improvement. Fabricated test chips using 14 nm process have demonstrated 2.33 GHz performance at 1.1 V/25 °C operation. Overall V_min of 550 mV is achieved with this design at 25 °C. The inbuilt power-switch improves leakage power by 12x in simulation. Approximately 8% die area of a leading 14 nm SoC in commercialization is occupied by these compiled RF instances.