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To establish a genetic susceptibility assessment model of lung cancer risk potentially associated with polycyclic aromatic hydrocarbon (PAH) inhalation exposure among non-smokers in China, a total of 143 patients with lung adenocarcinoma and 143 cancer-free individuals were recruited. Sixty-eight genetic polymorphisms in 10 pathways related to PAH metabolism and tumorigenesis were selected and examined. It was observed that 3 genetic polymorphisms, along with 10 additional genetic polymorphisms via gene-gene interactions, significantly influenced lung cancer risk potentially associated with PAH inhalation exposure. Most polymorphisms were associated with PAH metabolism. According to the established genetic susceptibility score (GSS), lung cancer risk increased with a rise in the GSS level, thereby indicating a positive dose-response relationship.

Thermal gradients from a heating front travelling down a flowline at start-up can cause a flowline to walk much like a worm creeps by repeated contractions and expansions of its body. To stop this for the Malampaya flowline, pipe-clamping mattresses (PCMs) were invented, developed, and deployed within a period of 12 months. The objective of this paper is to share the knowledge and experience from this novel but effective solution to mitigate pipeline walking. PCMs provide a cost-effective alternative to rockdump or conventional mattresses to axially restrain a pipeline at a location chosen so that the required restraint capacity is minimized. They are inspired by conventional mattresses and bear some similarity to them, but they are designed so that the weight of the mattress acts to clamp the pipeline with a high leverage. Thus 100% of the weight of the mattress is effective in generating axial friction with the seabed. This solution can be applied at any point along the line (chosen to minimize the required resistance) without requiring flanges or collars on the pipeline. From the most recent survey results 15 PCMs with a dry weight of around 9 tons per PCM, plus 7 tons for the logmat installed over every PCM appear to be effective to stop the walking of the Malampaya flowline. This performance is as expected from extensive analysis (FE and otherwise) to reproduce the observed walking behavior prior to restraining, to estimate the required restraint capacity, and to estimate the resistance provided by the PCMs. This paper describes the PCM, the clamping forces they generate by leveraging the weight of the PCM and logmats installed over them, and how the friction generated with the soil is estimated from interface shear tests on samples collected from the site, considering cyclic pore pressure generation and dissipation effects. It also briefly covers FE analyses to reproduce the observed walking behavior, and determine the required restraint capacity, the PCM fabrication, installation, and monitoring of the post-installation performance.

RXFP4 is recognised as the cognate G protein-coupled receptor for INSL5 although little is known about its signal transduction pathways and biological roles. This thesis investigates the signalling pathways activated by RXFP4 in a recombinant cell culture system and also identifies tissues and cell lines that endogenously express RXFP4, with subsequent evaluation of its endogenous signalling profile and possible physiological roles.

Background: Accounting for approximately 1.76 million annual deaths worldwide, lung cancer is a significant global health burden. While smoking is the most common cause of lung cancer, up to 25% of all lung cancer patients worldwide are never smokers. Lung cancer is the leading cause of cancer mortality in China, where most women do not smoke, making women in Asia an ideal population to study. Previously conducted genome-wide association studies (GWAS) of lung cancer risk among never-smoking women in Asia identified 10 lung cancer susceptibility loci. Indoor air pollution from coal burned for home cooking and heating is known to contain lung carcinogens and has been found to be causally associated with lung cancer. In the current analysis, we evaluated gene-environment interaction between a polygenic risk score (PRS) and coal use in relation to lung adenocarcinoma. Methods: Three studies (Taiwan, Shanghai, Shenyang) from the Female Lung Cancer Consortium in Asia (FLCCA) were used for the primary analysis (1,419 cases; 1,446 controls). A replication study was conducted using samples from Xuanwei, China (159 cases; 572 controls), where lung cancer rates for never-smokers are among the highest in the world and attributed to widespread coal use. We calculated a PRS as the weighted sum of the risk allele counts across the 10 loci, and modeled PRS as a continuous variable scaled by the standard deviation in controls. Logistic regression was used to estimate the main effects of the PRS and coal use, and a likelihood ratio test was used to evaluate the interaction. Models were adjusted for age ( Results: Coal use was associated with an increased risk of lung adenocarcinoma (OR=1.31, 95% CI: 1.01-1.68). We observed an exposure-response relationship between PRS and lung adenocarcinoma (p-trend= 2x10-16) and found a significant multiplicative interaction between PRS and coal use (p-interaction= 0.005). The association between PRS and lung adenocarcinoma was significantly higher among the never coal users (OR=1.68, 95% CI: 1.52-1.86) compared to ever coal users in the three studies (OR=1.24, 95% CI: 1.03-1.50) (p-interaction=0.005), as well as between never coal users in the three studies and ever coal users in Xuanwei (OR=1.25, 95% CI: 1.04-1.49) (p-interaction=0.004). Conclusion: We observed an antagonistic interaction between PRS and coal use with lung adenocarcinoma, where the genetic effect was attenuated among those exposed to coal combustion in the home. We replicated the finding in Xuanwei. These results suggest that the pathogenesis of lung cancer among never-smoking women in Asia differs by exposure to coal combustion emissions and provides one of the few examples of sub-multiplicative gene-environment interactions in the cancer literature. Citation Format: Batel Blechter, Chao Agnes Hsiung, Zhihua Yin, Xiao-Ou Shu, H. Dean Hosgood, Jason Y.Y Wong, Jianxin Shi, Wei Hu, Bryan Bassig, Wei Jie Seow, Yu -ang Gao, Qiuyin Cai, Yong-Bing Xiang, I-Shou Chang, Baosen Zhou, Wei Zheng, Kyoung-Mu Lee, Stephen Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Qing Lan. Analysis of polygenic risk score interaction with coal use and risk of lung adenocarcinoma among never-smoking women in Asia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2682.

The increasing awareness of climate change has led organizations to demand a standard procedure to measure and communicate greenhouse gas (GHG) emissions linked to their products or services. The publicly available specification PAS 2050 has been developed in response to broad community and industry desire for a consistent method-carbon footprint for assessing the life cycle GHG emissions of goods and services. Specifically, this paper illustrates the implementation of carbon footprint for a baby stroller in accordance with PAS 2050. A fial value of 321 kg per one stroller including package was calculated. Moreover, the study led to identify raw materials production of the stroller as the main source of GHS emissions where efforts need to focus for emission reduction opportunities. This case study is hoped to be a starting point for organizations to benefit from the increasing application of carbon footprint assessment.

Under the background of MEA (More Electric Aircraft), electromechanical actuation system is widely applied in aircraft. A light-weight electromechanical actuation system with fast response and high power density is designed and developed according to the limited space and high level disturbance moment. The following three points are introduced in this paper: (1) the lockable electromechanical actuation system; (2) design and simulation of the electromechanical actuation system; (3) tests of the electromechanical actuation system.

Recent studies have suggested that β-catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of β-catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)-reporter mice (TOPGal mice) and liver-specific β-catenin knockout mice. Liver-specific β-catenin knockout mice showed a delayed onset of DNA synthesis after hepatectomy, whereas recovery of liver mass was not affected. Among putative β-catenin target genes examined, the induction of Ccnd1 expression was reduced, whereas the expression of Myc and Egfr was unaffected. Furthermore, cyclin D1 protein levels were not induced, and the expression of cyclins A, E, and proliferating cell nuclear antigen was delayed. Intriguingly, the analysis of TOPGal mice showed that hepatocytes with active TCF/LEF transcription are confined to the pericentral zone and are not increased in number during regeneration, indicating an uncoupling between β-catenin/TCF signaling activity and hepatocyte proliferation. Conclusion: Our results indicate that β-catenin is critical for the proper regulation of hepatocyte proliferation during liver regeneration; however, the activity of β-catenin/TCF signaling does not correlate with hepatocyte proliferation, suggesting that this regulation might be indirect/secondary. (HEPATOLOGY 2007;45:361–368.)

To explore the effectiveness of absorbable hemostatic fluid gelatin in preventing postoperative cerebrospinal fluid leakage.The clinical data of 17 patients with dura mater tear were retrospectively analyzed from March to September in 2003. There were 16 males and 1 female, aged from 16 to 67 years old with an average of (39.6 ± 15.4) years. The injury site was at cervical vertebrae in 1 case, thoracic vertebrae in 9 cases, thoracolumbar junction in 4 cases, lumbar vertebrae in 3 cases. There were burst fracture in 4 cases and fracture-dislocation in 13 cases. According to ASIA grade, 12 cases were grade A, 2 cases were grade B, 2 cases were grade D, 1 case were grade E. Two cases caused by traffic accident, 10 by high falling, 4 by heavy parts crash, 1 by stairs fell during the earthquake. Absorbable hemostatic fluid gelatins were used to plug the dura mater tear,in order to prevent postoperative cerebrospinal fluid leakage. Postoperative drainage were recorded every day.Of 17 patients, 15 cases did not develop with cerebrospinal fluid leakage. Two cases develop with cerebrospinal fluid leakage after operation and their drainage were removed at 6 to 7 days after operation. In all cases, no complications related with cerebrospinal fluid leakage occurred, such as headache, dizzy, fever,neck resistance, rash, incision disunion, incision infection, hematoma, neurologic symptoms aggravation. No abnormal phenomena was found on incision surrounding at follow-up of 9 months.Using absorbable hemostatic fluid gelatin to plug the dura mater tear during operation is an effective method in preventing postoperative cerebrospinal fluid leakage.

There is accumulating evidence that Wnt/beta-catenin signaling is involved in the regulation of liver development and physiology. The presence of genetic alterations resulting in constitutive beta-catenin stabilization in human and murine liver tumors also implicates this pathway in hepatocyte proliferation. In the present study, we generated hepatocyte-specific beta-catenin knockout mice to explore the role of beta-catenin in liver function. Conditional knockout mice were born at the expected Mendelian ratio and developed normally to adulthood, indicating beta-catenin is dispensable for essential liver function under normal breeding conditions. However, the liver mass of knockout mice was 20% less than those of mice in the control groups. Expression analysis revealed loss of genes required for glutamine synthesis in knockout mice. Loss of the liver glutamine synthesis pathway did not affect the blood ammonia level in mice fed a standard diet, yet, knockout mice showed significantly elevated blood ammonia levels with high-protein dietary feeding. Furthermore, the expression of two cytochrome P450 enzymes, CYP1A2 and CYP2E1, was almost completely abolished in livers from hepatocyte-specific beta-catenin knockout mice. Consequently, these mice were resistant to acetaminophen challenge, confirming the requirement of these cytochrome P450 enzymes for metabolism of xenobiotic substances. In conclusion, in addition to regulating hepatocyte proliferation, beta-catenin may also control multiple aspects of normal liver function.

Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder with a broad clinical heterozygosis, which can be complicated by other connective tissue disorders like Ehlers-Danlos syndrome (EDS). OI/EDS are rarely documented. Most OI/EDS mutations are located in the N-anchor region of type I procollagen and predominated by glycine substitution. We identified a c.3521C>T (p.A1174V) heterozygous mutation in COL1A1 gene in a four-generation pedigree with proposed mild OI/EDS phenotype. The affected individuals had blue sclera and dentinogenesis imperfecta (DI) was uniformly absent. The OI phenotype varied from mild to moderate, with the absence of scoliosis and increased skin extensibility. Easy bruising, joint dislocations and high Beighton score were present in some affected individuals. EDS phenotype is either mild or unremarkable in some individuals. The mutation is poorly conserved and in silico prediction support the relatively mild phenotype. The molecular mechanisms of the mutation that leads to the possible OI/EDS phenotype should be further identified by biochemical analysis of N-propeptide processing and steady state collagen analysis.

Centrifugal compressor is of great importance in industries. High efficiency, high stage pressure ratio, wide operation range, easy to manufacture and easy to maintain make it prevalent in aerospace, automobile and power generation industries. The possibility in improving its efficiency has been pursued all the way along its path of development. Nowadays, energy-saving has been a key competitiveness for any power-consuming product. Dyson V2 centrifugal compressor is powered by a high speed electric motor, and provides suction power to the upstream cyclone separator to separate the dust particles from the air. It is highly desirable that the efficiency can be improved such that less electricity would be consumed. As the first step to improve its efficiency, it is essential to gain some knowledge on the flow phenomena involved, in essence, efficiency is the direct reflection of the quality of the flow field. The flow is viscous, highly unsteady, swirling and transitional inside Dyson V2 centrifugal compressor, strong interaction exists between different flow features, the compound effects of strong curvature, centrifugal force and Coriolis force make it very difficult to obtain an acceptable prediction. Theoretical approach is usually too ideal to take into account different flow features, experimental approach is too costly and generally time-consuming. With the rapid development of CFD techniques and the availability of high performance computers, computational approach is becoming one of the most popular tools during design and development phases.In this work, computational approach has been employed to investigate the performance and the flow behaviour inside the Dyson V2 centrifugal compressor. Validation studies are first conducted to examine the capability of Star CCM+ solver, good agreements are obtained with the experimental data. After that, the flow field inside the Dyson V2 centrifugal compressor is analysed using steady simulation, which is relatively easy to conduct and feasible during the design phase. Different flow phenomena, including tip leakage flow, separation bubble, “jet-wake structure" and corner separation are observed. Vortex roll-up process is identified, it is initialized near the impeller blade leading edge due to tip leakage flow, and grows in the axial part of the impeller, finally, it decays in the radial part of the impeller due to centrifugal force. A loss localization method is employed to identify the sources of significant loss generation, it is found that tip leakage flow is the most significant source of loss, it is initialized near the blade leading edge through vortex roll-up, and very difficult to control. The endwall loss and blade surface loss associated with boundary layer are significant near the impeller outlet and blade suction-side due to the high flow speed, corner separation induced loss in diffuser is also significant. Later, the effects of unsteadiness are investigated through unsteady simulation, it is shown that unsteadiness can help weaken or suppress flow separation and lead to reduced blockage and local loss generation. The impeller-diffuser interaction tends to slow down the high speed flow near the impeller blade suction-side and migrate the high speed flow from suction-side to pressure-side.In literature, riblets have been extensively tested, although the physical mechanisms are not fully understood, it is definitely sure that riblets with proper size can help reduce the turbulent skin friction drag. In this work, riblets have been proposed to reduce the impeller hub endwall loss. However, riblets are of very small size, fully resolved simulation is extremely time-consuming and costly. Curve fitting is applied to correlate the available experimental data on riblets, an expression has been obtained to relate the wall shear stress reduction to non-dimensional spacing and yaw-angle. The riblets are designed and optimized based on the wall shear stress computed from steady simulation, the design value for wall shear stress reduction is around 4%. At the end, the riblets performance is assessed with unsteady simulation, it is confirmed that the riblets design based on steady simulation could perform very well, even under the effects of unsteadiness, a wall shear stress reduction around 4% could be achieved.

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