Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts.

Pancreatic cancer is a complex disease, in need of new therapeutic approaches. In this study, we explored the effect and mechanism of action of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, alone and in combination with current chemotherapeutics on pancreatic cancer cell growth, focusing on glycolysis metabolism. Moreover, we investigated whether EGCG's effect is dependent on its ability to induce reactive oxygen species (ROS). EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner and the growth inhibition effect was further enhanced under glucose deprivation conditions. Mechanistically, EGCG induced ROS levels concentration-dependently. EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase. Cotreatment with catalase abrogated EGCG's effect on phosphofructokinase and pyruvate kinase. Furthermore, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo. EGCG and gemcitabine, given alone, reduced pancreatic tumor xenograft growth by 40% and 52%, respectively, whereas the EGCG/gemcitabine combination reduced tumor growth by 67%. EGCG enhanced gemcitabine's effect on apoptosis, cell proliferation, cell cycle and further suppressed phosphofructokinase and pyruvate kinase levels. In conclusion, EGCG is a strong combination partner of gemcitabine reducing pancreatic cancer cell growth by suppressing glycolysis

Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial-Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine.

Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented "Cadherin switch" and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG's effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial-mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial-mesenchymal transition

Detecting Feature-Interaction Symptoms in Automotive Software Using Lightweight Analysis

Copyright (c) 2019 IEEE Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Modern automotive software systems are large, com- plex, and feature rich; they can contain over 100 million lines of code, comprising hundreds of features distributed across multiple electronic control units (ECUs), all operating in parallel and communicating over a CAN bus. Because they are safety-critical systems, the problem of possible Feature Interactions (FIs) must be addressed seriously; however, traditional detection approaches using dynamic analyses are unlikely to scale to the size of these systems. We are investigating an approach that detects static source-code patterns that are symptomatic of FIs. The tools report Feature-Interaction warnings, which can be investigated further by engineers to determine if they represent true FIs and if those FIs are problematic. In this paper, we present our preliminary toolchain for FI detection. First, we extract a collection of static “facts” from the source code, such as function calls, variable assignments, and messages between features. Next, we perform relational algebra transformations on this factbase to infer additional “facts” that represent more complicated design information about the code, such as potential information flows and data dependencies; then, the full collection of “facts” is matched against a curated set of patterns for FI symptoms. We present a set of five patterns for FIs in automotive software as well a case study in which we applied our tools to the Autonomoose autonomous-driving software, developed at the University of Waterloo. Our approach identified 1,444 possible FIs in this codebase, of which 10% were classified as being probable interactions worthy of further investigation.General Motors Research Project, GAC 2453 Ontario Research Fund, RE05-04

Contemporaneous Imaging Comparisons of the Spotted Giant sigma Geminorum Using Interferometric, Spectroscopic, and Photometric Data

Nearby active stars with relatively rapid rotation and large starspot structures offer the opportunity to compare interferometric, spectroscopic, and photometric imaging techniques. In this paper, we image a spotted star with three different methods for the first time. The giant primary star of the RS Canum Venaticorum binary sigma. Geminorum (sigma Gem) was imaged for two epochs of interferometric, high-resolution spectroscopic, and photometric observations. The light curves from the reconstructions show good agreement with the observed light curves, supported by the longitudinally consistent spot features on the different maps. However, there is strong disagreement in the spot latitudes across the methods.Peer reviewe

Preliminary psychometric properties of the Acceptance and Action Questionnaire – II: A revised measure of psychological flexibility and acceptance.

The present research describes the development and psychometric evaluation of a second version of the Acceptance and Action Questionnaire (AAQ-II), which assesses the construct referred to as, variously, acceptance, experiential avoidance and psychological inflexibility. Results from 2,816 participants across six samples indicate the satisfactory structure, reliability, and validity of this measure. For example, the mean alpha coefficient is .84 (.78 - .88), and the 3- and 12-month test-retest reliability is .81 and .79, respectively. Results indicate that AAQ-II scores concurrently, longitudinally, and incrementally predict a range of outcomes, from mental health to work absence rates,that are consistent with its underlying theory. The AAQ-II also demonstrates appropriate discriminant validity. The AAQ-II appears to measure the same concept as the AAQ-I (r = .97), but with better psychometric consistency

Development and optimization of quantitative PCR for the diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid

Background: The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. Culture and histopathological examination of bronchoalveolar lavage (BAL) fluid are useful but have suboptimal sensitivity and in the case of culture may require several days for fungal growth to be evident. Detection of Aspergillus DNA in BAL fluid by quantitative PCR (qPCR) offers the potential for earlier diagnosis and higher sensitivity. It is important to adopt quality control measures in PCR assays to address false positives and negatives which can hinder accurate evaluation of diagnostic performance. Methods: BAL fluid from 94 episodes of pneumonia in 81 patients was analyzed. Thirteen episodes were categorized as proven or probable IPA using Mycoses Study Group criteria. The pellet and the supernatant fractions of the BAL were separately assayed. A successful extraction was confirmed with a human 18S rRNA gene qPCR. Inhibition in each qPCR was measured using an exogenous DNA based internal amplification control (IAC). The presence of DNA from pathogens in the Aspergillus genus was detected using qPCR targeting fungal 18S rRNA gene. Results: Human 18S rRNA gene qPCR confirmed successful DNA extraction of all samples. IAC detected some degree of initial inhibition in 11 samples. When culture was used to diagnose IPA, the sensitivity and specificity were 84.5% and 100% respectively. Receiver-operating characteristic analysis of qPCR showed that a cutoff of 13 fg of Aspergillus genomic DNA generated a sensitivity, specificity, positive and negative predictive value of 77%, 88%, 50%, 96% respectively. BAL pellet and supernatant analyzed together resulted in sensitivity and specificity similar to BAL pellet alone. Some patients did not meet standard criteria for IPA, but had consistently high levels of Aspergillus DNA in BAL fluid by qPCR. Conclusion: The Aspergillus qPCR assay detected Aspergillus DNA in 76.9% of subjects with proven or probable IPA when the concentrated BAL fluid pellet fraction was used for diagnosis. There was no benefit from analyzing the BAL supernatant fraction. Use of both extraction and amplification controls provided optimal quality control for interpreting qPCR results and therefore may increase our understanding of the true potential of qPCR for the diagnosis of IPA.Supported by NIH grant R01 AI054703 from the National Institute of Allergy and Infectious Diseases

(Re) defining salesperson motivation: current status, main challenges, and research directions

The construct of motivation is one of the central themes in selling and sales management research. Yet, to-date no review article exists that surveys the construct (both from an extrinsic and intrinsic motivation context), critically evaluates its current status, examines various key challenges apparent from the extant research, and suggests new research opportunities based on a thorough review of past work. The authors explore how motivation is defined, major theories underpinning motivation, how motivation has historically been measured, and key methodologies used over time. In addition, attention is given to principal drivers and outcomes of salesperson motivation. A summarizing appendix of key articles in salesperson motivation is provided

Directive versus empowering leadership: A field experiment comparing impacts on task proficiency and proactivity

Using a field experiment in the United Arab Emirates, we compared the impacts of directive and empowering leadership on customer-rated core task proficiency and proactive behaviors. Results of tests for main effects demonstrated that both directive and empowering leadership increased work unit core task proficiency, but only empowering leadership increased proactive behaviors. Examination of boundary conditions revealed that directive leadership enhanced proactive behaviors for work units that were highly satisfied with their leaders, whereas empowering leadership had stronger effects on both core task proficiency and proactive behaviors for work units that were less satisfied with their leaders. We discuss implications for both theory and practice. © Academy of Management Journal

ICAR: endoscopic skull‐base surgery

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