Contribution of laser microdissection-based technology to proteomic analysis in hepatocellular carcinoma developing on cirrhosis

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.     

A comparative proteomic study to characterize the vinblastine resistance in human ovarian cancer cells

Drug resistance is a major impediment to the successful treatment of human cancers, including ovarian cancer. Vinblastine (VLB), an antimicrotubule agent, is one of the chemotherapeutic drugs that exhibit resistance in ovarian cancer patients. To determine the protein factors that are involved in vinblastine resistance in human ovarian cancer cells, a combination of sample pre-fractionation and high-resolution 2-DE proteomic analysis was performed. Approximately 1200 proteins were detected and quantitatively compared in both nuclear/membrane and cytosolic fractions. Sixty-nine proteins from the nuclear/membrane fraction showed altered expression levels, whereas 59 were altered in the cytosolic fraction between SKOV3 (vinblastine-sensitive) and SKVLB (vinblastine-resistant) cell lines. These proteins include membrane-associated, chromatin remodeling, cytoskeletal, and microtubule-associated proteins as well as others that regulate signal transduction. This study not only demonstrates a novel understanding of the mechanism of drug resistance but also provides a valuable resource for future studies on drug resistance to vinblastine. In addition, it also represents a good example of how to increase the protein dynamic range and reduce sample complexity using currently available tools.     

Predicting user response to sponsored advertising on social media via the technology acceptance model

Sponsored advertising has generated strong advertising revenues for Facebook in recent years. As sponsored ads are built on an interactive platform that could be seen as invasive to user privacy, the growth of this advertising platform has important implications for consumers, and advertisers alike. As little research is available on consumer response to sponsored advertising as an interactive technology innovation, the current study assesses the effects of user perceptions of privacy risk, intrusiveness concerns and utilities of sponsored advertising on consumer attitudes and purchase intent. Testing a model derived form the technology acceptance model (TAM), the study found that privacy and intrusiveness concerns are both valid antecedent variables to perceived usefulness but not perceived ease of use of sponsored advertising. While both antecedent variables also influence consumer attitudes toward sponsored advertising, only privacy concerns have an impact product purchase intentions. The hypothesized relations between perceived usefulness, ease of use, attitudes and purchase intentions were also validated.     

Using an adapted,task-level technology acceptance model to explain why instructors in higher education intend to use some learning management system tools more than others

Instructors in higher education perform some instructional tasks much more often using a learning management system (LMS) tool than other tasks. In studies that aim to explain these differences, the Technology Acceptance Model (TAM) perspective is missing. In this study, an adapted, task-level TAM questionnaire was used to measure task importance, task performance, LMS usefulness, LMS ease of use, and intention to use an LMS for 18 different instructional tasks among 180 instructors at a Dutch research university. The results show that low intention to use an LMS can be explained by (1) low task importance or performance, and/or (2) low LMS usefulness, and/or (3) low LMS ease of use level. The LMS tools and tasks within each of the three groups were not related substantively. This raises a question regarding whether an instructor's LMS intention level can best be explained by the combination of a specific tool, a specific instructional task, and a specific user interface.     

Effects of customer response to fashion product stockout on holding costs,order sizes,and profitability in omnichannel retailing

In retailing practice, customers may actively respond in one of the following ways after experiencing stockout of a preferred brand: switch to a substitutable brand, switch to another store (where the preferred brand could be available), or delay purchase (backlogging). This paper presents a model of active customer responses to stockout of fashion products. In the single‐period model, a retailer maximizes profit by selling two substitutable brands through two different stores. Analytical results and numerical experiments suggest that active response to stockout increase the retailer's profitability due to (a) additional revenue from backlogging and brand and store switching and (b) decrease in optimal order size resulting in lower holding costs. Omnichannel fulfillment offers additional opportunities for retailers to benefit from active responses to stockout.     

A route and speed optimization model to find conflict-free routes for automated guided vehicles in large warehouses based on quick response code technology

This paper focuses on exploring conflict-free routes for automated guided vehicles (AGVs) based on quick response (QR) code technology. Intelligent warehousing has become an industrial development trend, with an increasing number of enterprises deploying AGVs based on QR code technology for transportation tasks, especially in large warehouses. Unlike the early single lane path following navigation systems, AGVs using QR code technology can freely switch tracks at any position. And two AGVs can be accommodated side by side. The conditions of conflict-free routes are analyzed firstly when AGVs use QR code navigation system. After that, a route and speed optimization model (RSOM) that aims at minimizing energy consumption and taking conflict-free routes with time windows as the constraint condition is established. Then a branch-and-bound (B&B) algorithm scheme is proposed by altering AGV routes or speed to arrive at schemes with conflict-free routes to complete transportation tasks. Lastly, the effectiveness and validity of our proposed model and algorithm are verified by numerical examples and a case study. The results show that resolving conflicts during route planning for AGVs guided through QR code have advantages over avoiding collision in the running phase by technology and path following techniques in both aspects of solution time and energy. In addition, the established B&B algorithm has better performance than the rapid-exploring random tree (RRT) algorithm in numerical examples. The gaps between them widen as the size of AGVs increases. The research work has potential for application to meet the requirements of AGV development.     

A simple,physically motivated model of sea-level contributions from the Greenland ice sheet in response to temperature changes

Sea level could rise by several meters over the next centuries. The Greenland ice sheet could be an important contributor to future sea-level rise, because of its large volume and its high sensitivity to surface air temperature increases. Frameworks for the integrated climate risk management often require fast, simplified treatments of sea-level rise, in particular for estimating the risks associated with low probabilities but potentially high impacts. State-of-the-art ice sheet models provide important insights, but are often computationally too demanding to evaluate tail-area risks. Here we present SIMPLE, a physically motivated model of the Greenland ice sheet in response to temperature changes. SIMPLE can skillfully reproduce the results from a three-dimensional ice sheet model and outperforms existing simple models, after similar calibration. We anticipate that SIMPLE will be calibrated to other ice sheet models and can provide a fast approximation (emulator) for such models in studies that require many model evaluations.     

Predicting satellite-derived patterns of large-scale disturbances in forests of the Pacific Northwest Region in response to recent climatic variation

Across the Pacific Northwest, the climate between 1950 and 1975 was exceptionally cool and wet compared with more recent conditions (1995-2005). We reasoned that the changes in climate could result in expanded outbreaks of insects, diseases, and fire. To test this premise, we first modeled monthly variation in photosynthesis and growth of the most widely distributed species, Douglas-fir (Pseudotsuga menziesii), using a process-based model (3-PG) for the two periods. To compare with remotely sensed variables, we converted modeled growth potential into maximum leaf area index (LAImax), which was predicted to range from 1 to 9 across the region. On most sites, varying soil moisture storage capacity (θcap) from 200 to 300 mm while holding soil fertility constant, made slight but insignificant difference in simulated LAImax patterns. Both values of θcap correlated well with LAI estimates acquired from NASA's MODIS satellites in June, 2005 (r² = 0.7). To evaluate where 15 coniferous tree species might be prone to wide-scale disturbance, we used climatically-driven decision-tree models, calibrated in the 1950-1975 period, to identify vulnerable areas in 1995-2005. We stratified predictions within 34 recognized ecoregions and compared these results with large-scale disturbances recorded on MODIS imagery acquired between 2005 and 2009. The correlation between the percent of species judged as vulnerable within each ecoregion and the percent of forested areas recorded as disturbed with a MODIS-derived Global Disturbance Index was linear and accounted for 65 to 73% of the observed variation, depending on whether or not disturbance by fire was excluded from the analysis. Based on climate projections through the rest of the rest of the 21st century, we expect continued high levels of disturbance in ecoregions located beyond the climatically buffering influence of the Pacific Ocean.