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V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) Knockdown and its Role in a Triple Negative Breast Cancer
Get PDFTriple Negative Breast Cancer (TNBC) is defined as negative for three genes, estrogen receptor (ESR), progesterone receptor (PR) and Human epidermal growth factor receptor (HER2-neu) genes. Previous data show the V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) gene is over-expressed in Triple negative breast cancer cell line (MDA-MB231). MYBL1 belongs to the MYB family of genes which are transcription factors and proto-oncogenes which are associated with cell cycle regulation, apoptosis, and differentiation, all of which are key events associated with cancers. It could be that MYBL1 contributes to these same processes in TNBC. Instead of studying MYBL1’s contribution to several of these processes, we were mainly concerned with identifying genes that were either directly or indirectly affected by down-regulation of MYBL1 gene. Utilizing a gene silencing approach helps to identify genes that cooperate with MYBL1 in the signaling processes in cancer. Although the focus of our laboratory is TNBC, there are two parts to this current study, one that examines MYBL1 in luminal cancers cell line (MCF7) and one that examines MYBL1 in TNBC, designated Part 1 and Part 2, respectively. For Part 1, we performed analyses of MCF7 (Luminal breast cancer cell line) receptor positive cells where estrogen receptor gene was silenced; and another MCF7 preparation where cMYB gene was silenced. Both datasets were obtained from Gene Expression Omnibus (GEO). These datasets were chosen because even though they were neither TNBC or directly involved MYBL1 as the primary target, comparative analyses of both datasets showed MYBL1 knock-down (KD). We reasoned that even under these conditions, genes either directly or indirectly associated with MYBL1 might be identified. For Part 2 of this study, short hairpin RNA (shRNA) lentiviral transduction was used to down-regulate MYBL1 in MDA MB231 TNBC cells. A substantial number of reliable differentially expressed genes were identified here. Overall, genes recognized as associated with MYBL1 in the MCF7 luminal preparations (Part 1) were drastically different from genes identified as associated with MYBL1 in the TNBC KD study (Part 2). In both datasets, we identify novel genes that appear to be coordinately expressed with MYBL1 in breast cancers. This study led to identification of candidate genes that might be important towards the study of characterizing MYBL1 expression in TNBC. Two of these genes, transcription factor 19 (TCF19) and Kinesin-like protein (kinesin family member 18B) (KIF18B) have been experimentally validated. MYBL1 is a strong candidate gene to study for its contribution to the development of TNBC. Continued analyses of these genes and their relationship to MYBL1 should lead to a better understanding of signaling processes in breast cancers
The Political and Criminological Conspiracy of Terrosism: A Case Study of Nigeria
Get PDFNigeria has recently witnessed the repeated prevalence of a fog of terror that has threatened the stability, peace, and sovereignty of the nation. While the world\u27s attention focuses on Afghanistan, Iraq, and bombings in embassies around the Western world, shocking terrorist activities with immeasurably devastating impacts are regularly ignored by the Nigerian government and the international community. Since 1970, Nigeria has continued to experience repeated domestic attacks entrenched in different forms of tensions and motivations. The Global Terrorism Index (2019) ranked Nigeria as the third most terrorized country in the world, behind only Iraq and Afghanistan with 1,634 attacks, 16,108 dead, 7,575 injured, and 2,828 held in captivity from 2013 to 2017. The Nigerian state has become an unfortunate theater of insecurity, bloodshed, and a genocidal arena caused by the bloodshed by Boko Haram and Fulani herdsmen. The objective of this dissertation is to illustrate and underscore the apparent method in the designation of a violent group as a terrorist group, and explain how some groups are labeled as terrorists, while some organizations that deserved to be designated as terrorist groups are not. This researcher analyzed mainly data from the Global terrorism Database and other scholarly literature, using qualitative approaches with descriptive analysis. This dissertation should help inform policymakers about terrorism and counterterrorism policies, initiate policies that will curb terrorists’ activities in Nigeria, and provide knowledge for future research. Criminological theories such as labeling, anomie/strain, deterrence were applied to examine the menacing activities of terrorism in Nigeria
Impact of Chronic Exposure of Selected Azo Dyes on the Model Organism Caenorhabditis Elegans
Get PDFAzo dyes are dyes used to color textiles, paper, leather, plastics, foods, cosmetics, pharmaceuticals, brewed beverages, tattoo inks, printing inks, and more. They account for over 50% of all commercially used dyes produced annually and identified by aromatic rings connected by nitrogen-nitrogen double bonds (N=N). Azo dyes yield colorless aromatic amines and become potentially carcinogenic after biotransformation. Lipid-soluble azo dyes are the most toxic and some are banned for food usage, yet still detected at low concentrations in palm oils, chili powders, eggs, and other food products.
The nematode Caenorhabditis elegans (C. elegans) has been used in many environmental studies to determine the effects of toxicants. C. elegans are used as an effective model system for predicting human physiological response. The C. elegans genome is fully sequenced and is 60% homologous to humans. This study investigated the effects of lipid-soluble azo dyes on C. elegans. Three reproductive endpoints (brood size, egg-laying, and egg hatching), two behavioral endpoints (body bend frequency and pharyngeal pumping rate), and one enzymatic endpoint (reactive oxygen species [ROS]) were selected for the assessment of azo dye (Sudan I, Sudan II, Chrysoidine G, and Disperse Orange 3) toxicity.
Chrysoidine G and Disperse Orange 3 caused severe lifespan defects. Chrysoidine G, Sudan I, and Disperse Orange 3 exposure resulted in reproductive defects that significantly reduced brood size. Locomotion (body bends and tracks) and pharyngeal pumping were significantly impaired by Chrysoidine G, Sudan I, and Disperse Orange 3. The stress responses to azo dye exposure suggested severe toxicity. With endpoints of locomotion, pharyngeal pumping, reproduction, and ROS production, the toxicity of the examined azo dyes was: Chrysoidine G \u3e Disperse Orange 3 \u3e Sudan I \u3e Sudan II. This study found that C. elegans exposed to sublethal concentrations of three (Chrysoidine G, Sudan I, and Disperse Orange 3) of the four azo dyes selected for this study resulted in deleterious and negative effects of multiple biological defects by affecting the life span, development, reproduction, locomotion and pharyngeal pumping behaviors
Hidden Markov models for pipeline damage detection using piezoelectric transducers
No full textOil and gas pipeline leakages lead to not only enormous economic loss but also environmental disasters. How to detect the pipeline damages including leakages and cracks has attracted much research attention. One of the promising leakage detection method is to use lead zirconate titanate (PZT) transducers to detect the negative pressure wave when leakage occurs. PZT transducers can generate and detect guided waves for crack detection also. However, the negative pressure waves or guided stress waves may not be easily detected with environmental interference, e.g., the oil and gas pipelines in an offshore environment. In this paper, a Gaussian mixture model-hidden Markov model (GMM-HMM) method is proposed to process PZT transducers’ outputs for detecting the pipeline leakage and crack depth in changing environment and time-varying operational conditions. Leakages in different sections or crack depths are considered as different states in hidden Markov models (HMMs). One time-domain damage index and one frequency domain damage index are extracted from signals collected from PZT transducers, then extracted indices are formed as observation emissions in the HMM. The observation probability distribution matrix in HMM is initialized by a Gaussian mixture model (GMM) to address signal uncertainties. After the HMM parameter initialization, an iterative training process through the Baum–Welch algorithm is applied to get the optimized parameters of the GMM-HMM. Leakage location or crack depth is decided by the maximum posterior probability from the trained model. Two different experimental settings and results show that the GMM-HMM method can recognize the crack depth and leakage of pipeline such as whether there is a leakage, where the leakage is
Single Variable-Constrained NDT Matching in Traffic Data Collection Using a Laser-Based Detector
No full textAs indispensable components of intelligent transportation systems, traffic detection and surveillance technologies deliver speed monitoring, traffic counting, and vehicle identification and classification. This paper proposes a normal distribution transform (NDT) algorithm to improve the speed accuracy and robustness of a laser-based detector. This method can deliver more accurate estimation of vehicle speed, enabling computation of the parameters of length and height. The results of simulation with different detector update rates suggest that the average estimation errors of vehicle parameters can be reduced using the NDT matching method, especially for the low detector update rate. The study also implemented a series of field experiments using the proposed detector prototype to verify the detector\u27s measurements of vehicle parameters. The proposed method is a promising way in which to improve the laser-based traffic detector. In simulation test, initial experiments show that the accuracy of speed estimation can reach 95%, given the update rate of 1000 Hz for detector, the average length error can be reduced by approximately 60%. Even for speeding vehicles traveling at 150 km/h, the estimated speed error is limited to 10 km/h. In field test, for a vehicle at the speed of 80km/h, the estimation errors are within the threshold of the maximum errors of simulation, that is, 32 cm for length error and 5.71 km/h for speed error results
The Impact of Pedestrian and Nonmotorized Vehicle Violations on Vehicle Emissions at Signalized Intersections in the Real World: A Case Study in Beijing
No full textEmission around intersections has become an issue in the urban traffic network. This paper aims to investigate the impact of pedestrian and nonmotorized vehicle violations on emissions at mixed-traffic flow intersection based on the volumes of vehicles, nonmotor vehicles, and pedestrians. Also, it focuses on the arterial and collector intersections with high vehicle volume and limited space. Running red light and crossing intersection diagonally are two critical violations, accounting for 91.75% of effective violations (interference with vehicles\u27 operation). In this context, a violation blocking model is developed to estimate the blocking probability for each vehicle based on the volumes of pedestrians and nonmotor vehicles. The model includes two scenarios. (1) Through phase: the violation blocking model of running red light is developed based on the survival curve (the relationship between waiting time and running red light probability). (2) Left-turn phase: the violation blocking model at this phase includes two parts: (i) crossing the intersection diagonally model is developed for the first vehicle and (ii) running red light model is developed for subsequent vehicles. The existing emission model can estimate the emissions based on the blocking positions. In the case study, emissions increase with the vehicle volume approaching the saturated flow rate and the volumes of nonmotor vehicles and pedestrians increasing. Results show that the maximum emission increase of CO (carbon monoxide) for through phase and left-turn phase can reach 16.7% and 36.4%
Investigating Officer Involved Shootings: Don’t Ignore the Evidence
Get PDFThis presentation sheds light on a part of officer involved shootings not always discussed at a legal symposium: the potential bias that emerges at a crime scene during an investigation. The speaker explores the evidentiary challenges associated with an officer involved shooting, and describes the reconstruction project that he led as a consultant during the investigation and trial of off-duty police officer Amber Guyger, who was convicted of the murder of Botham Jean
Ramipril blunts glycerol-induced acute renal failure in rats through its antiapoptosis, anti-inflammatory, antioxidant, and renin-inhibiting properties
Get PDFAcute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn\u27t been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats. Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out. Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group. The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties
Glucuronides hydrolysis by intestinal microbial β-glucuronidases (Gus) is affected by sampling, enzyme preparation, buffer ph, and species
Get PDFGlucuronides hydrolysis by intestinal microbial β-Glucuronidases (GUS) is an important procedure for many endogenous and exogenous compounds. The purpose of this study is to deter-mine the impact of experimental conditions on glucuronide hydrolysis by intestinal microbial GUS. Standard probe 4-Nitrophenyl β-D-glucopyranoside (pNPG) and a natural glucuronide wogonoside were used as the model compounds. Feces collection time, buffer conditions, interindividual, and species variations were evaluated by incubating the substrates with enzymes. The relative reaction activity of pNPG, reaction rates, and reaction kinetics for wogonoside were calculated. Fresh feces showed the highest hydrolysis activities. Sonication increased total protein yield during enzyme preparation. The pH of the reaction system increased the activity in 0.69–1.32-fold, 2.9–12.9-fold, and 0.28–1.56-fold for mouse, rat, and human at three different concentrations of wogonoside, respectively. The Vmax for wogonoside hydrolysis was 2.37 ± 0.06, 4.48 ± 0.11, and 5.17 ± 0.16 µmol/min/mg and Km was 6.51 ± 0.71, 3.04 ± 0.34, and 0.34 ± 0.047 µM for mouse, rat, and human, respectively. The inter-individual difference was significant (4–6-fold) using inbred rats as the model animal. Fresh feces should be used to avoid activity loss and sonication should be utilized in enzyme preparation to increase hydrolysis activity. The buffer pH should be appropriate according to the species. Inter-individual and species variations were significant
Cytotoxicity analysis of pre- and post-hurricane harvey soil samples collected from greater houston bayous
Get PDFRapid urbanization, anthropogenic pollution and frequent flooding events are affecting the soil and water quality along the streams and bayous of Houston. Soil acts as sink and reservoir of heavy metals and nutrients affecting human and animal health. The objectives of the study are 1) to analyze the effects of the metal and nutrient concentration of bayou flood plain surface soil samples on the gut cell cytotoxicity and 2) to evaluate the spatial and temporal difference in soil contamination on cell viability of colon cancer (HT-29) and normal colon epithelial (CCD 841 CoN) cell lines. To evaluate soil contamination between pre- and post-hurricane (Summer and Fall) conditions in six Bayous (Brays, Buffalo, Halls, Hunting, Greens and White Oak Bayous) of Harris County, Texas, in vitro bioassay analysis was applied to soil extracts. The MTT assay determined that, with increase in concentration of Bayou soil from 12.5% to 100%, the viability of CCD 841 CoN and HT-29 cells decreased significantly, across all sampling locations during both summer and fall seasons. Among all the bayous, the viability of CCD 841 CoN cells in summer and fall followed the pattern of White Oak \u3e Greens \u3e Halls \u3e Brays Bayou, where the viability of cells exposed to White Oak soils was 3–4 times higher than cells exposed to Brays Bayou soil at 100% soil concentration. The viability of HT-29 cells in both seasons followed the pattern of Greens \u3e White Oak \u3e Halls \u3e Brays Bayou, where the viability of cells exposed to Greens Bayou soil was more than 3–4 times higher than the cells exposed to Brays Bayou soil at 100% concentration. The higher concentration of metals and nutrients such as P, Zn, Cd, and Cu might have contributed to the significant cell lethality in Brays Bayou samples compared to other locations