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Role of the urban Transportation Agency in Providing Urban Mobility Services: Cases of London, Dubai, and Singapore
Transportation and mobility in a city are essential for healthy and sustainable growth. A city\u27s mobility concerns can be focused on different elements such as the road system, public transit, shared mobility, and biking. To improve mobility in a city, it is important that all these components are integrated and coherently governed, and/or coordinated by one agency. A public transit agency is a legal entity that is usually owned by the government and integrates the urban transit services of a city under one umbrella. It operates transport services to provide mobility to the people, promote economic development, and support environmental protection and social equality. The agency can be dependent on the government or supported by the private sector for operational support in case if it has insufficient funds. In this research, the structure of several public transit agencies is investigated. The study will include a review of elements typical of public transit agencies as they provide urban transit services by exploring the cases of (TfL) in London, (RTA) in Dubai, and (LTA) in Singapore. In particular, this study is designed to answer the following questions: a) how a centralized and independent public agency is reflected in the level of urban transit services in a city; (b) how do the case study cities measure compared to success variables; and (c) why is it important to integrate transit services under one single entity? This research is also making a deep dive into the structure, financing, and performance data such as population and ridership of the agencies to demonstrate the common success factors amongst them. An assessment of mission, vision, and goals is also provided. After investigating and recognizing the most common success criteria in all three agencies, they will be used to develop and structure a template for the establishment of such an agency. Keywords: Urban Transportation, Public Transit Agency, London, Dubai, and Singapor
Acrolein-Induced Epigenetic Modification of DNA Methylation in Rat Kidney Disease Tissue
Acrolein, an alpha-beta unsaturated aldehyde, and a very reactive and toxic compound is released into the environment from different sources. As a pervasive environmental pollutant, acrolein poses a serious environmental health threat acknowledged by investigators, health, and environmental government agencies. Acrolein is released into the environment through the burning of organic compounds. The main sources of acrolein pertinent to human health and toxicity include cooked foods, combustion of fossil fuels, cigarette smoke, overheating of frying oil, endogenously produced via lipid peroxidation, metabolism of polyamine, and anticancer drug cyclophosphamide. Exposure of humans to acrolein is mainly through inhalation of contaminated air, ingestion of contaminated food, and water and dermal contact. Exposure and buildup of acrolein in the biological system have been linked to different disease conditions such as cancer, cardiovascular diseases, multiple sclerosis, spinal cord injury, and Alzheimer’s diseases. Several mechanisms have been proposed for the toxicity of acrolein including inflammation, protein abduction, oxidative stress, DNA abduction, and membrane disruption. Some studies have linked acrolein-induced toxicity to epigenetic modifications. Epigenetics is the modifications in gene expression that do not alter the DNA sequence of a gene. This alteration could occur naturally or by factors such as age, environmental exposure, individual lifestyle, and disease condition. DNA methylation is an epigenetic process that ensues via the addition of a methyl (CH3) group to DNA and frequently alter the role of the gene and transcription factor and as such influence gene manifestation. DNA methyltransferases ( DNMTs) are a group of enzymes that control the addition of methyl groups at different levels in cells. There are three major types of DNMTs; DNMT1 is the methylation enzyme responsible for the maintenance of established patterns of DNA methylation while DNMT3A and DNMT3B mediate the establishment of new or de novo DNA methylation patterns. On the other hand, Ten Eleven Translocation (TET) enzymes counter the activities of DNA methyltransferases via stepwise biochemical conversion of 5- methylcytosine to 5-carboxyl cytosine, which is then modified by thymine DNA glycosylase (TDG) making it a basic cytosine which allows the regeneration of unmethylated cytosine through base excision repair thereby abolishing DNA methylation. N- Acetylcysteine (NAC) is an antioxidant that is vital for the reduction of oxidative stress and the downstream negative effects that are associated with it. NAC has shown potency in the inhibition of acrolein-induced toxicity based on the recent studies done in our laboratory and other investigators. NAC beneficial effects are through improvement in the production of cellular glutathione, a natural antioxidant enzyme known to defend the body against the invasion of xenobiotics such as acrolein. Our earlier work using Vascular Smooth Muscle Cells (VSMCs) has indicated that acrolein induces cytotoxicity and modifies histones specifically histone H3, through epigenetic modification via methylation and acetylation and NAC blocks the toxicity and inhibits histone modification. Based on current information, we are hypothesizing that acrolein toxicity is through changes in DNA methylation and NAC prevents this toxicity by inhibiting DNA methylation. Specific aims of the study are: Demonstrate that acrolein induces toxicity in rats is through DNA methylation, Evaluate the activities of DNA methylation/demethylation enzymes, Evaluate the effect of N-acetylcysteine (NAC) on the prevention of DNA methylation and subsequent changes. To investigate our hypothesis, male Sprague-Dawley rats were treated with 2mg/kg/day of acrolein for seven days (i.p) in the presence or absence of 600mg/kg/day of NAC (i.p). The dose and duration of exposure were selected based on our previous studies. At the end of the study period, kidney tissue was collected, nuclear protein and DNA samples were extracted for biochemical analysis. Lipid peroxidation was measured using MDA (Malondialdehyde)- based colorimetric assay. 5-mC hydroxylase TET activity, DNMT activity, Thymine DNA glycosylase activity, DNA Demethylase activity, and DNA Damage Quantification (8-OHdG) were measured by ELISA-based colorimetric and fluorometric assay from Epigentek. Global DNA methylation and global DNA hydroxymethylation were measured by ELISA-based colorimetric assay from Abcam and protein expression by western blotting. Our results revealed that acrolein-treated rats showed about a 169% increase in lipid peroxide level when compared to control. The addition of NAC decreases lipid peroxidation level to about 52% compared to the acrolein group. There was about a 67% decrease in 5-mC TET Hydroxylase activity in the acrolein treated group compared to control, the addition of NAC increased 5-mC TET Hydroxylase activity by 28% compared to the acrolein group. Consistently, there was about a 14% decrease in demethylase activity in the acrolein group compared to the control group and the addition of NAC increased demethylase activity to about 20% compared to the acrolein group. Similarly, there was about a 22% decrease in TDG activity in the acrolein treated group compared to the control and the addition of NAC showed an approximately 15% increase in TDG activity compared to the acrolein group. On the contrary, there was about a 30% increase in DNMT activity in the acrolein group compared to the control. The addition of NAC indicated about 32% increase compared to the acrolein group. The reason behind the increase in DNMT activity after the addition of NAC is yet to be understood since NAC is known to repeal acrolein toxicity. There was up to 16% increase in the global 5-mC level in the acrolein treated group compared to the control and the addition of NAC increased it by 16% when compared to the control. The same trend was observed in global 5-HmC where there was a 22% decrease in 5-HmC activity in the acrolein group compared to the control. The addition of NAC increased the level of 5-HmC approximately to 130% compared to the acrolein group. The decrease in global 5-mC and 5-HmC agrees with many investigators’ reports (hypomethylation) as the prognosis of different cancer development. Finally, there was about an 18% decrease in the 8-OHdG level in the acrolein group compared to the control and NAC addition increased the 8-OHdG level by 167% compared to the acrolein group. Based on the present data, we are concluding that epigenetic changes observed in acrolein-treated rats are the results of increased generation of ROS, which contribute to increasing oxidation level, alteration of TET enzymes and their products, and increased DNA methylation and subsequent DNA damage
Can Science and Christianity Coexist in the Medical Profession?
I know my choice of thesis question seems strange for a biology major. Like many of my Honor College brothers and sisters, I could have chosen to stay within the lines of my degree focus. I am admittingly noting that my thesis borders dangerously on a philosophical or moralistic debate. Refreshingly, I hope to defend neither nor endorse a particular sway of opinion. I am simply using this vehicle as a measuring device that challenges and explores an unavoidable dilemma faced by any scientific professional of faith, presumably. I pose this question in terms of Christianity simply because it is relative to my own beliefs. Still, I would assume the same question could be applied to any religion-related to a believing professional regardless of their belief structure, presumably. I hope it stirs an accounting in all that read it regardless of our differences of beliefs or lack thereof. As you will see later, I believe it is our “why” that will be most challenged, and in this area, there are significantly few physical benefits that may be adequate to sustain us in this path, in light of the pandemic effects on our fields. Since we have addressed the elephant in the room, I will continue. I am sure by now you all realize I don’t always follow the crowd. This subject is close to my heart because my ambition is to become an Optometrist and use my skill and influence to help my community and the world. As a strong female and dedicated student, I hope to show you that I can deliver a professional and articulate thesis on this subject in a respectful way. iii The world has changed. It is safe to conclude that our daily lives and status quo changes have been altered irrevocably in many ways. I am sure on this point we can all agree. Our children attend school remotely. We now have to rethink how we meet and socialize. Rethink how we celebrate birthdays and anniversaries. Even our bucket list of travel has been altered or reorganized and, for some, eliminated. Our older parents and younger children need extra protection from the world outside our doors. Many of us have lost someone close or been touched by a villain that we can neither see nor feel, but we all must live with its presence and be aware and purposeful in our avoidance of it. In this time of uncertainty, many aspiring health professionals face the reality of entering fields or career paths that would place us on the vanguard of the battle with this and future pandemics. As someone aspiring to be a medical professional, possibly for the first time in history, we are faced with evident and prevalent negative cons to pursuing such a field. Gone are the days of telling friends and family that you will provide medical professionals and receive enthusiastic cheers. Now we face raised eyebrows and a mix of pity and real fear for our safety and their safety. If we were doing this for the money or because our parents predestined a career in medicine, then this path’s value may fade in its luster. We are leaving you to consider your ‘why\u27. We see the nurses exhausted and discouraged on the news daily. Now more than ever, you must have a calling, a passion, to do this work. The coronavirus pandemic has changed the dynamics of the healthcare system in countless ways. At times like these, many of us have relied on something more profound than the degrees and diplomas we hang on our walls. For some, it comes down to protecting those they love. For others, it is the pursuit of regaining a new normal. For some, it is a faith of some type that inspires them to go on and continue to rise when the world is falling apart. iv My thesis expounds that, within the context of proper application and the regulating core desire to provide beneficial medical services to all people, Christian faith and science are not in conflict and are complementary traits. My goal in this thesis is to conduct a respectful investigation of these two core elements and the effectiveness of their existence as reflected in the performance and professionalism of noted people and organizations who confidently affirm their faith as part of their profession. Using this methodology, I have supported my conclusions
From Etiology to Action: Exploring the Origins, Obstacles, Opportunities and Outcomes of Achieving Social Equity
Addressing Social Inequity: A Case Study of Success
Social equity is relatively easy to define but much harder to accomplish. As a result, achieving social equity continues to be difficult in American society and across the globe. We present a case study of a collaborative effort by two nonprofits to conduct a program for public high schools and local law-enforcement agencies across the United States. The program was designed to acknowledge and address the historic harms that impact police-community relations. Our paper delineates the origins of the problem and our approach, presents data that demonstrate the positive impact the program had on bridging gaps, changing perceptions, and lessening social bias and inequity, and concludes with lessons learned
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Glucuronides hydrolysis by intestinal microbial β-glucuronidases (Gus) is affected by sampling, enzyme preparation, buffer ph, and species
Glucuronides 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
Development And Validation Of A Sensitive, Specific And Reproducible Uplc-ms/ms Method For The Quantification Of Ojt007, A Novel Anti-leishmanial Agent: Application To A Pharmacokinetic Study
OJT007 is a methionine aminopeptidase 1 (MetAP1) inhibitor with potent anti-proliferative effects against Leishmania Major. In order to study its pharmacokinetics as a part of the drug development process, a sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. Voriconazole was used as the internal standard to generate standard curves ranging from 5 to 1000 ng/mL. The separation was achieved using a UPLC system equipped with an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phase under gradient elution at a flow rate of 0.4 mL/min. The mass analysis was performed with a 4000 QTRAP® mass spectrometer using multiple-ion reaction monitoring (MRM) in the positive mode, with the transition of m/z 325 → m/z 205 for OJT007 and m/z 350 → m/z 101 for voriconazole. The intra-and inter-day precision and accuracy were within ±15%. The mean extrac-tion recovery and the matrix effect were 95.1% and 7.96%, respectively, suggesting no significant matrix interfering with the quantification of the drug in rat plasma. This study was successfully used for the pharmacokinetic evaluation of OJT007 using the rat as an animal model
A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver
Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. The Tessari technique was used to create a stable emulsion (20 mg IRI mixed with 2 mL lipiodol) with resultant particle size ranging from 28.9 nm to 56.4 nm. Pharmacokinetic profile established through venous sampling in Buffalo rats demonstrate that the area under the curve (AUC0−∞) of IRI was significantly less after PVCE with IRI-lipiodol as compared to IRI alone (131 vs. 316 µg*min/mL, p-value =.023), suggesting significantly higher amounts of IRI retention in the liver with the IRI-lipiodol nanoemulsion via first-pass extraction. Subseqent biodistribution studies in tumor-bearing WAG/Rjj rats revealed more IRI present in the tumor following TACE versus PVCE (29.19 ± 12.33 µg/g versus 3.42 ± 1.62; p-value =.0033) or IV (29.19 ± 12.33 µg/g versus 1.05 ± 0.47; p-value =.0035). The IRI-lipiodol nanoemulsion demonstrated an acceptable hepatotoxicity profile in all routes of administration. In conclusion, the IRI-lipiodol nanoemulsion via TACE showed promise and warrants further investigation as an option for the treatment of metastatic colorectal cancer
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