江西省水系连通及水美乡村建设试点县实施方案编制存在的问题及对策

为提高水系连通及水美乡村建设试点县实施方案编制质量，更好地参加全国竞争性立项，本文分析研究了江西省55个水系连通及水美乡村建设试点县实施方案和相应的专家评审意见，对实施方案编制过程中存在的符合性、完整性不够，实施范围情况调查不准等七个方面突出问题进行梳理剖析，并提出相应对策，可为实施方案编制提供参考。     

Development of a stakeholder identification and analysis method for human factors integration in work system design interventions – Change Agent Infrastructure

In any work system design intervention—for example, a physical workplace re-design, a work process change, or an equipment upgrade—it is often emphasized how important it is to involve stakeholders in the process of analysis and design, to gain their perspectives as input to the development, and ensure their future acceptance of the solution. While the users of an artifact or workplace are most often regarded as being the most important stakeholders in a design intervention, in a work-system context there may be additional influential stakeholders who influence and negotiate the design intervention's outcomes, resource allocation, requirements, and implementation. Literature shows that it is uncommon for empirical ergonomics and human factors (EHF) research to apply and report the use of any structured stakeholder identification method at all, leading to ad-hoc selections of whom to consider important. Conversely, other research fields offer a plethora of stakeholder identification and analysis methods, few of which seem to have been adopted in the EHF context. This article presents the development of a structured method for identification, classification, and qualitative analysis of stakeholders in EHF-related work system design intervention. It describes the method's EHF-related theoretical underpinnings, lessons learned from four use cases, and the incremental development of the method that has resulted in the current method procedure and visualization aids. The method, called Change Agent Infrastructure (abbreviated CHAI), has a mainly macroergonomic purpose, set on increasing the understanding of sociotechnical interactions that create the conditions for work system design intervention, and facilitating participative efforts.     

Thermal shock effects on the impact resistance,tolerance and flexural strength of alumina based oxide/oxide ceramic matrix composites

In this study the effects of thermal shock on the impact damage resistance, damage tolerance and flexural strength of Nextel 610/alumina silicate ceramic matrix composites were experimentally evaluated. Composite laminates with balanced and symmetric layup were gradually heated to 1200°C in an air-based furnace and held for at least 30 min before being removed and immersed in water at room temperature. The laminates were then subjected to low velocity impacts via a hemispherical steel impactor. The resultant damage was characterized non-destructively, following which the laminates were subjected to compression tests. Three-point bend tests were also performed to evaluate the effect of thermal shock on the flexural strength and related failure modes of the laminates. Thermally shocked laminates showed smaller internal damage and larger external damage areas in comparison to their pristine counterparts. For the impact energy and resultant damage size considered, the residual compressive strengths for the thermally shocked and pristine laminates were similar.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Radiation- and Photo-Induced Oxidation Pathways of Methionine in Model Peptide Backbone under Anoxic Conditions

Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO^•) play an important role, being the most aggressive towards biomolecules. The reactions of HO^• with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO^•, and by CB triplets allowed for assigning transient species to the pathways of products formation.     

In Vivo Simultaneous Analysis of Gene Expression by Dual-Color Luciferases in Caenorhabditis elegans

Both fluorescent and luminescent observation are widely used to examine real-time gene expression patterns in living organisms. Several fluuorescent and luminescent proteins with specific optical properties have been developed and applied for simultaneous, multi-color observation of more than two gene expression profiles. Compared to fluorescent proteins, however, the application of multi-color luminescent imaging in living organisms is still limited. In this study, we introduced two-color luciferases into the soil nematode C. elegans and performed simultaneous analysis of two gene expression profiles. Using a green-emitting luciferase Eluc (emerald luciferase) and red-emitting luciferase SLR (stable luciferase red), the expression patterns of two genes were simultaneously observed in single animals from embryonic to adult stages over its whole life span. In addition, dual gene activities were observed at the single embryo level, with the simultaneous observation of morphological changes. These are the first application of a two-color luciferase system into a whole animal and suggest that precise relationship of expression patterns of multiple genes of interest can be analyzed over the whole life of the animal, dependent on the changes in genetic and/or environmental conditions.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.