Texas Southern University
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Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility
No full textEpithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify bio-features and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10−6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations
Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy
No full textAutophagy is a catabolic process involved in cellular homeostasis. Autophagy is increased above homeostatic levels by chemotherapy, and this can either promote or inhibit tumor growth. We previously demonstrated that aerosol gemcitabine (GCB) has a therapeutic effect against osteosarcoma (OS) lung metastases. However, some tumor cells failed to respond to the treatment and persisted as isolated lung metastasis. Here, we examined the mechanisms underlying the dual role of chemotherapy-induced autophagy in OS and sought to identify biomarkers to predict OS response to treatment. In this study, we demonstrate that treatment of various OS cells with GCB induced autophagy. We also showed that GCB reduces the phosphorylation of AKT, mTOR and p70S6K and that GCB-induced autophagy in OS can lead to either cell survival or cell death. Blocking autophagy enhanced the sensitivity of LM7 OS cells and decreased the sensitivity of CCH-OS-D and K7M3 OS cells to GCB. Using a kinase array, we also demonstrated that differences in the phosphorylated heat shock protein 27 (p-HSP27) expression in the various OS cell lines after treatment with GCB, correlates to whether chemotherapy-induced autophagy will lead to increase or decrease OS cells sensitivity to therapy. Increased p-HSP27 was associated with increased sensitivity to anticancer drug treatment when autophagy is inhibited. The results of this study reveal a dual role of autophagy in OS cells sensitivity to chemotherapy and suggest that p-HSP27 could represent a predictive biomarker of whether combination therapy with autophagy modulators and chemotherapeutic drugs will be beneficial for OS patients
Developing Managerial Expertise: Experiential Learning of Professional Skills
Get PDFWe propose a pedagogical approach that expounds theoretical knowledge through exposure of students to practical experience as effective for developing professional skills. We use decision making as proxy for the relevant critical skills of effective managers. The approach entails reinforcement of abstract constructs with the know-how of managerial decision making among undergraduate business students. To substitute for apprenticeship, we suggest hands-on practice, such as in a simulation, where students apply business concepts so they can experience managerial decision making and the workings of business. Instruction on decision making generally assumes a rational procedure entailing: Defining a goal/problem, generating and evaluating alternative solutions/actions, choosing an optimal action, implementing the chosen action, and evaluating outcome. This approach to learning might lend to a theoretic appreciation of a process of decision making that students might commit to memory. However, for skill development, students need opportunity for involvement and practice. The proposed approach enables students to practice rational decision making in real time so we can monitor incremental skill improvements
Multiobjective optimization model of intersection signal timing considering emissions based on field data: A case study of Beijing
Get PDFThe trade-off between vehicle emissions and traffic efficiencies were investigated based on field data . First, considering the different operating modes of cruising, acceleration, deceleration, and idling, field data of emissions and GPS are collected to estimate emission rates for heavy-duty and light-duty vehicles. Second, multiobjective signal timing optimization model was established based on a genetic algorithm to minimize delay, stops, and emissions. A case study was performed in Beijing. Nine scenarios were designed considering different weights of emission and traffic efficiency. The results compared with those using Highway Capacity Manual 2010 showed that signal timing optimized by the model proposed can decrease vehicles delay and emissions more significantly. The optimization model can be applied in different cities, which provides supports for eco-signal design and development
Keynote Author Presentation
No full textKeynote Author Presentation: Mia K. Wright, author of newly released, Unthinkable... Do the Ordinary to experience the Extraordinary will share excerpts & inspirational tips for pursuing your passion
The Profile of Young Offenders in the City of Maputo, Mozambique
Get PDFThe present study describes the profile of 172 young people who were attending their prison sentences in three Maputo prisons. We examined their Certificates of Judgment and Execution of Sentence based on descriptive statistics and statistical tests. Most participants were male. Young people, especially men, committed a large number of crimes against property. There was higher prevalence of women committing crimes against people’s physical integrity and health. The number of young people charged increased as they progressed in age. The major part of the sample received correctional penalties, were convicted for the first time, had no occupation or worked in the informal sector, and came from the suburban neighborhoods of Maputo City. Our results show the need for focusing on the prevention of criminal acts in young people and in the monitoring of this population during and after incarceration
A simple, sensitive and reliable LC-MS/MS method for the determination of 7-bromo-5-chloroquinolin-8-ol (CLBQ14), a potent and selective inhibitor of methionine aminopeptidases: Application to pharmacokinetic studies
Get PDFCLBQ14 is an 8-hydroxyquinoline analogue that inhibits methionine aminopeptidase (MetAP), an enzyme responsible for the post-translational modification of several proteins and polypeptides. MetAP has been validated as druggable target for some infectious diseases, and its inhibitors have been investigated as potential therapeutic agents. In this study, we developed and validated a liquid chromatography tandem-mass spectrometry (LC-MS/MS) method for the quantification of CLBQ14 in solution, and in rat plasma and urine. This method was applied to the pharmacokinetic evaluation of CLBQ14 in adult male Sprague Dawley (SD) rats. Chromatographic separation was achieved using an ultra-high-performance liquid chromatography (UHPLC) system equipped with Waters XTerra MS C18 column (3.5 μm, 125 Å, 2.1 × 50 mm) using 0.1% formic acid in acetonitrile/water gradient system as mobile phase. Chromatographic analysis was performed with a 4000 QTRAP® mass spectrometer using MRM in positive mode for CLBQ14 transition [M + H]+ m/z 257.919 → m/z 151.005, and IS (clioquinol) transition [M + H]+ m/z 305.783 → m/z 178.917. CLBQ14 was extracted from plasma and urine samples by protein precipitation. The retention times for CLBQ14 and IS were 1.31 and 1.40 min respectively. The standard curves were linear for CLBQ14 concentration ranging from 1 to 1000 ng/mL. The intra-day and inter-day accuracy and precision were found to be within 15% of the nominal concentration. Extraction recoveries were \u3e96.3% and 96.6% from rat plasma and urine respectively, and there was no significant matrix effect from the biological matrices. CLBQ14 is stable in samples subjected to expected storage, preparation, and handling conditions. Pharmacokinetic studies revealed that CLBQ14 has a bi-exponential disposition in SD rats, is extensively distributed with a long plasma half-life and is eliminated primarily by liver metabolism
rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology
No full textThymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3′ gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97-1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03-1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10−28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small
Impact of freeway weaving segment design on light-duty vehicle exhaust emissions
No full textIn the US, 26% of greenhouse gas emissions, e.g., CO, NOx, and HC, is emitted from the transportation sector. Approximately 2.5% and 2.44% of a total exhaust emissions for a petrol and a diesel engine, respectively. These exhaust emissions are typically subject to vehicles’ intermittent operations, including hard acceleration and hard braking. In practice, drivers are inclined to operate intermittently while driving through a weaving segment, due to complex vehicle maneuvering for weaving, resulting to variations in exhaust emissions within a weaving segment from those on a basic segment. To investigate this, the impacts of weaving segment configuration on vehicle emissions and the important predictors for emission estimations were assessed to develop a nonlinear normalized emission factor (NEF) model for weaving segments. An on-board emission test was conducted on 12 subjects on State Highway 288 in Houston, TX. Vehicles’ activity information, road conditions, and real-time exhaust emissions were collected by on-board diagnosis, a smartphone-based roughness app, and a portable emission measurement system, respectively. Five feature selection algorithms were used to identify the important predictors for the response of NEF and the modeling algorithm. The predictive power of four algorithm-based emission models was tested by 10-fold cross-validation. Results showed that emissions were susceptible to the type and length of a weaving segment. Bagged decision tree algorithm was chosen to develop a 50-grown-tree NEF model, which provided a validation error of 0.0051. The estimated NEF were highly correlated with the observed NEF in the training data set as well as in the validation data set. These results propose to involve road configuration, in terms of the type and length of a weaving segment, in constructing an emission nonlinear model, which significantly improves emission estimations at a microscopic level