Criteria for assessing the quality of nuclear probabilistic risk assessments

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 2004.Includes bibliographical references (p. 194-200).The final outcome of a nuclear Probabilistic Risk Assessment (PRA) is generally inaccurate and imprecise. This is primarily because not all risk contributors are addressed in the analysis, and there are state-of-knowledge uncertainties about input parameters and how models should be constructed. In this thesis, we formulate two measures, risk significance (RS) and risk change significance (RCS) to examine these drawbacks and assess the adequacy of PRA results used for risk-informed decision making. The significance of an event within a PRA is defined as the impact of its exclusion from the analysis on the final outcome of the PRA. When the baseline risk is the final outcome of interest, we define the significance of an event as risk significance, measured in terms of the resulting percentage change in the baseline risk. When there is a proposed change in plant design or activities and risk change is the final outcome of interest, we define the significance of an event as risk change significance, measured in terms of the resulting percentage change in risk change. These measures allow us to rank initiating events and basic events in terms of relative importance to the accuracy of the baseline risk and risk change.(cont.) This thesis presents general approaches to computing the RS and RCS of any event within the PRA. Our significance measures are compared to traditional importance measures such as Fussell-Vesley (FV), Risk Achievement Worth (RAW), and Risk Reduction Worth (RRW) to gauge their effectiveness. We investigate the use of RS and RCS to identify events that are important to meet the decision maker's desired degree of accuracy of the baseline risk and risk change. We also examine the use of 95th confidence level acceptance guideline for assessing the adequacy of the uncertainty treatment of a PRA. By comparing PRA results with the desired accuracy and precision level of risk and risk change, one can assess whether PRA results are adequate enough to support risk-informed decisions. Several examples are presented to illustrate the application and advantages of using RS and RCS measures in risk-informed decision making. We apply our frame- work to the analysis of the component cooling water (CCW) system in a pressurized water nuclear reactor. This analysis is based upon the fault tree for the CCW system presented in the plant's PRA analysis.(cont.) One result of our analysis is an estimate of the importance of common cause failures of the CCW pumps to the accuracy of plant core damage frequency (CDF) and change in CDF.by Yingli Zhu.Ph.D

Study on Effect of Product Liability to Inherent Safety

AbstractMany industry accidents and product liability problems occur in China in recent years. The safety of products not only influents public daily life, also affects industrial production. Product safety concept reflects the attitude of people to product safety, and is reflected in product liability system. The influences of different product liability system to the status of inherent safety were studied based on the analysis of the doctrine of liability fixation in different technology development period. It can be seen that there were still many problems in the product liability acts such as the standard and identification of product defects, compensation liability, which were not beneficial to improve the industry safety though strict liability has been accepted in our country. Therefore, product liability system should be improved, and the method of design defect determination should be established. At the same time, carrying out the risk evaluation of the products, increasing the amount and scope of compensation are also important to realize the product safety and industrial inherent safety

Hematopoietic Pyk2 regulates migration of differentiated HL-60 cells

<p>Abstract</p> <p>Background</p> <p>Pyk2 is a non-receptor cytoplasmic tyrosine kinase that belongs to the focal adhesion kinase family and has been implicated in neutrophil spreading and respiratory burst activity caused by TNF-α. However, the role of Pyk2 in neutrophil migration is incompletely defined. In this study, we tested the hypothesis that Pyk2 regulates the migration of neutrophil-like differentiated HL-60 cells subsequent to β2-integrin mediated cell adhesion.</p> <p>Methods</p> <p>HL-60 cells were induced to differentiate into neutrophil-like cells (dHL60) by incubation in medium containing 1.25% DMSO for up to 4 days. Pyk2 expression and tyrosine phosphorylation was measured by Western blot analysis. Adhesion of dHL60 cells to plated fibrinogen was measured by residual myeloperoxidase activity. dHL60 cell migration was evaluated using a 96-well chemoTx chamber.</p> <p>Results</p> <p>Western blot analysis demonstrated that hematopoietic Pyk2 was predominantly expressed after HL60 cell differentiation. Pyk2 was tyrosine phosphorylated upon adhesion of dHL60 cells to plated fibrinogen in the presence of fMLP. By contrast, tyrosine phosphorylation of Pyk2 was insignificant in dHL60 cells treated in suspension with fMLP. Antibodies against CD18 blocked both phosphorylation of Pyk2 and adhesion of dHL60 cells to fibrinogen, demonstrating that phosphorylation of Pyk2 was β₂-integrin dependent. TAT-Pyk2-CT, a dominant negative fusion protein in which the TAT protein transduction domain was fused to the c-terminal Pyk2, attenuated fMLP-stimulated spreading, migration and phosphorylation of endogenous Pyk2 without blocking adhesion of dHL-60 cells to fibrinogen. Similarly, silencing of Pyk2 expression by siRNA in dHL60 cells also attenuated dHL60 cell migration caused by fMLP. Phospho-Pyk2 was evenly distributed around cell membrane circumferentially in unstimulated dHL-60 cells adherent to plated fibrinogen. In dHL60 cells treated with fMLP to cause cell spreading and polarization, Pyk2 was concentrated at the leading edge of pseudopods or at the trailing edge of uropods during migration of neutrophilic dHL-60 cells.</p> <p>Conclusions</p> <p>We conclude that Pyk2 is activated by β2-integrin adhesion. The activated concentration of Pyk2 and colocalization with F-actin in pseudopodia suggests that Pyk2 may regulate cell spreading and migration in dHL60 cells.</p

Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

<p>Abstract</p> <p>Background</p> <p>Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo.</p> <p>Methods</p> <p>C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically.</p> <p>Results</p> <p>Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment.</p> <p>Conclusions</p> <p>These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and that pharmacological inhibition of Pyk2 might provide a potential therapeutic strategy in the pretreatment for patients at imminent risk of developing acute lung injury.</p

Paeoniflorin and Albiflorin Attenuate Neuropathic Pain via MAPK Pathway in Chronic Constriction Injury Rats

Neuropathic pain remains as the most frequent cause of suffering and disability around the world. The isomers paeoniflorin (PF) and albiflorin (AF) are major constituents extracted from the roots of Paeonia (P.) lactiflora Pall. Neuroprotective effect of PF has been demonstrated in animal models of neuropathologies. However, only a few studies are related to the biological activities of AF and no report has been published on analgesic properties of AF about neuropathic pain to date. The aim of this study was to compare the effects of AF and PF against CCI-induced neuropathic pain in rat and explore the underlying mechanism. We had found that both PF and AF could inhibit the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway in spinal microglia and subsequent upregulated proinflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). AF further displayed remarkable effects on inhibiting the activation of astrocytes, suppressing the overelevated expression of phosphorylation of c-Jun N-terminal kinases (p-JNK) in astrocytes, and decreasing the content of chemokine CXCL1 in the spinal cord. These results suggest that both PF and AF are potential therapeutic agents for neuropathic pain, which merit further investigation

A Multi-Robot Cooperation Framework for Sewing Personalized Stent Grafts

This paper presents a multi-robot system for manufacturing personalized medical stent grafts. The proposed system adopts a modular design, which includes: a (personalized) mandrel module, a bimanual sewing module, and a vision module. The mandrel module incorporates the personalized geometry of patients, while the bimanual sewing module adopts a learning-by-demonstration approach to transfer human hand-sewing skills to the robots. The human demonstrations were firstly observed by the vision module and then encoded using a statistical model to generate the reference motion trajectories. During autonomous robot sewing, the vision module plays the role of coordinating multi-robot collaboration. Experiment results show that the robots can adapt to generalized stent designs. The proposed system can also be used for other manipulation tasks, especially for flexible production of customized products and where bimanual or multi-robot cooperation is required.Comment: 10 pages, 12 figures, accepted by IEEE Transactions on Industrial Informatics, Key words: modularity, medical device customization, multi-robot system, robot learning, visual servoing, robot sewin

Experimental study on sinomenine derivative modulating chemokine receptor in multiple myeloma cells

Background and purpose: The interaction of CXC motif chemokine receptor (CXCR) on the cell surface of multiple myeloma (MM) with chemokines in the bone marrow microenvironment is involved in proliferation, survival and extramedullary invasion of MM cells. Sinomenine derivative YL064 exerts its biological effects by targeting intracellular signaling regulators in MM cells. This study aimed to explore possible modulating and biological effects of sinomenine derivative YL064 on CXCR3 in MM cells. Methods: The MM cell lines H929 and MM1.S were used as in vitro models. H929-OE and MM1.S-OE cells with stable overexpression of CXCR3 were constructed with lentivirus vector. The effects of CXCR3 on clonal formation and migration of MM cells were detected by clone spot formation and transwell migration assay. Meanwhile, flow cytometry was used to analyze apoptotic rates of H929, H929-OE, MM1.S and MM1.S-OE cells treated with different concentrations of YL064. Furthermore, real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot assay were applied to detect expression levels of CXCR3 and its downstream signal regulators extracellular regulated protein kinase (ERK) and p-protein kinase B (p-AKT) in H929 and MM1.S cells before and after the treatment with YL064. Results: The clonal formation rates of H929-OE and MM1.S-OE cells with CXCR3 overexpression reached to 81.33%±5.79% and 73.00%±4.90%, which were significantly higher compared with H929 (58.33%±3.30%) and MM1.S cells (41.00%±3.14%). The migration proportion of H929-OE and MM1.S-OE cells were 7.90%±0.81% and 23.00%±1.63%, which were significantly higher compared with H929 (4.63%±0.37%) and MM1.S cells (14.63%±1.04%). After treatment with YL064, the apoptotic rates of H929-OE and MM1.S-OE cells were 29.80%±0.30% and 14.20%±0.26%, which were lower than those of H929 (33.40%±0.25%) and MM1.S cells (21.60%±0.21%). It was also shown that YL064 could reduce clonal formation and migration, inhibit CXCR3 gene transcription and downregulate expressions of CXCR3, ERK and AKT in H929 and MM1.S cells. Conclusions: CXCR3 might promote proliferation and invasion of MM cells. Sinomenine derivative YL064 could downregulate expressions of CXCR3 and its downstream signal regulators in MM cells, reduce abilities of clonal formation and migration, and induce apoptosis

Survival outcomes of low-risk papillary thyroid carcinoma at different risk levels: a corollary for active surveillance

BackgroundThis study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice.MethodsThe study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS).ResultsA total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal.ConclusionThe treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small