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A Third Pandemic is on the Horizon
Get PDFThe emergence of the novel SARS-CoV-2 virus and the resultant COVID-19 pandemic has brought the world to a standstill. In the United States, the morbidity and mortality associated with COVID-19 infection has disproportionately impacted Black, Indigenous and People of Color (BIPOC) communities, highlighting an underlying “second pandemic” perpetuated by the deeply-rooted health care inequities and social determinants of health. In this manuscript, we warn about a “Third Pandemic” on the horizon which could be driven by federal policies that fail to ensure equitable access to COVID-specific therapeutics for BIPOC communities, and the potential inequitable implementation of such policies that could further perpetuate disparities in health outcomes
Police Militarization And Overuse of Force: An Analysis of the Efficacy of Paramilitary Units And Society
Get PDFThe role of the police is to maintain social order and safety through the enforcement of law. They investigate, prevent, and detect criminal activity. However, the problem with police protection today is overuse of force which often comes through the term militarism regarding agency tenets and dogma. Also, social media has focused on police overuse of force, exacerbating race riots and retaliatory police killings. Because of this, police reform has become a significant concern, not only in the United States but also abroad. The methodological approach for this dissertation is a quantitative analysis, data used is secondary, statistical procedure is chi square (cross tabulation) and multiple linear regression. This dissertation’s expected findings are to answer whether there is a statistically significant difference in police overuse of force by race and geographic areas; is there a relationship between DHS 1033 Program and violent crimes and property crimes; how accurately can a DHS 1033 Program index be predicted from a linear combination of crime rates
Design and Synthesis of Curcumin Analogs for Anticancer Activity and Discovery of Novel Hit Molecules Targeting CXCR4.
Get PDFCurcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, we have synthesized 9 pyrazole and 4 triazole curcumin analogs and studied their anticancer activity against CAL 27 and UM-SCC-74A as head & neck cancer cell lines, MDA-MB-231 as breast cancer cell line, HPAF as pancreatic cancer cell line, and MG118 as glioblastoma cancer cell lines. We have studied the effect of these analogs on head & neck cancer cell lines by using cell proliferation assay and western blotting analysis. Compound 49 was shown the best anticancer activity on these cancer cell lines. Western blotting analysis revealed that compounds 49, 81, and 77, showed anticancer activity. We did MTS assay study on MDA-MB 231 as a human cancer cell line and the study revealed that compounds 6 and 81 had good anticancer activity against these cancer cell lines, while triazole analogs showed weak anticancer activity. We also used MTS assay study to investigate the effect of curcumin analogs. Compounds 6 and 86 showed good anticancer activity against HPAF cell line. Cell Titer Glo-2 assay study on MG118 cell line revealed that compounds 49, 51, and 80 had good anticancer activity against glioblastoma cancer cell lines. The expression of the CXCR4 gene leads to making a CXCR4 protein which is a GPCR protein. Research showed that this protein is involved in different cancer types. Overexpression of CXCR4 leads to cancer metastasis. The objective of this study as the second part of my Ph.D. project is the discovery of novel hit molecules targeting CXCR4. We did the virtual screening of 229358 natural product compounds. Based on the crystallography structure, we generated the receptor file. FRED docking led to the identification of 500 hit compounds out of 229358 compounds. 500 hit compounds were filtered based on several parameters which led to the identification of 4 hit molecules. Root Mean Square Deviation study has shown that two of these hit molecules stabilized the protein Structure. Moreover, based on the Radius of the gyration study, three of these molecules maintain the compactness of protein. The hydrogen bond study of these complexes showed that two complexes made hydrogen bonds with targets. So, molecular dynamic analysis by Gromacs led to the identification of 2 hit molecules for CXCR4 antagonist activity. Keywords: Curcumin, Cancers, In-vitro study
Discovery of OJT010 as a Novel Inhibitor of Severe Acute Respiratory Syndrome Coronavirus 2
Get PDFThe current pandemic of coronavirus disease (COVID-19) caused by the highly infectious pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global public health challenge. The emergence of deadly SARS-CoV-2 variants with mutations on the viral genes has made it more imperative to discover therapeutics that target the host receptors for COVID-19 treatment. Therefore, our research has targeted the critical host entry receptors: Angiotensin-converting enzyme-2 (ACE2) for SARS-CoV-2 entry into the human cells. SARS-CoV-2 is an enveloped RNA beta coronavirus that infects human cells via interaction with the ACE2 receptor, followed by viral replication and virus dissemination. Spike protein of SARS-CoV-2 has a receptor-binding domain (RBD), which binds to the host ACE2 receptor. ACE2 is an essential component of the Renin-Angiotensin system that converts Angiotensin II (Ang II) to Angiotensin 1-7, a potent vasopressor. Even though ACE2 facilitates viral entry, it provides defense against acute lung injury, indicating that the ACE2/Ang 1-7 pathway must be carefully manipulated to reduce SARS-CoV-2 induced lung injuries. Herein, we discovered that OJT010 targets the interaction between RBD and rhACE2 without inactivating the exopeptidase activity of rhACE2. Our findings reveal that OJT010 binding to rhACE2 may preserve its physiological function and prevention exacerbation of the disease. Furthermore, it will potentially prevent non-target cardiac toxicities observed in other ACE2 modulating drugs. Moreover, we discover that OJT010 inhibits the cellular entry and further replication of the SARS-CoV-2 and B.1.617.2 Delta Variant in three individual assays; Infection Induced Cytopathic Effect (CPE), Nanoluciferase reporter assay (NLRV), and Pseudotyped Lentiviral assay. In addition, we have also assessed the molecular interactions of the compounds with the host and viral receptor using molecular dynamic simulation of the best-fit docking complex to elucidate the binding sites of OJT010. Next, we have determined the pharmacokinetics (PK) parameters of OJT010 in healthy rats. We have further advanced into a hamster of model SARS-CoV-2 infection to evaluate the efficacy of OJT010 against SARS-COV-2 infection in vivo. Based on our findings, OJT010 represents a promising drug class that could be further evaluated as a lead series in developing chemotherapeutics for COVID-19 treatment
An Assessment of Drinking Water from Zip Codes in the Greater Houston Area for Potential Heavy Metal Contamination Using ICPMS
Get PDFThe objective of this experiment is to identify and determine the concentration of heavy metals in drinking water for different resident zip codes in the greater Houston area. Heavy metals such as arsenic, antimony, cadmium, chromium, copper, lead, selenium, and others can be leaked into drinking water through household plumbing and service lines, mining operations, petroleum refineries, electronics manufacturers, chemical spills, municipal waste disposals, cement plants, and natural mineral deposits. Modern society is characterized by an increasing number of activities that can contaminate drinking water. When chemicals, animal waste, and human waste are disposed of improperly, it is more likely that they will contaminate groundwater and drinking water. A poorly treated or disinfected water supply may also cause acute and chronic toxicity in liver damage, kidney damage, intestinal damage, anemia, and cancer if the distribution system is not properly maintained. There is an increase in the demand for water suppliers to meet and comply with drinking water quality standards, they should be set by EPA, WHO, and SDWA. Consequently, the quality of drinking water varies from place to place based on the source and treatment, as contaminants can enter water supplies due to human or animal activities, threats to the drinking water may exist in the neighborhood or many miles away. Additionally, prolonged exposure to high levels of pollutants in drinking water might have negative health impacts. Therefore, the experimental protocols were as follows: the standard solutions were maintained in polypropylene or other inert containers since metals might leach from glass containers, and all 30 collected samples from 10 distinct resident zip codes (each zip code had three samples) were used. Because this procedure was suited for the quantification and qualification of heavy metals, the standards and all samples were prepared by producing the required dilutions of intermediate standard solutions with (v/v) 2% HNO3 and measured by 8800 QQQ-ICP-MS in ppb or ppm levels. And to reduce the risk of contamination, all locations and objects that used in sample preparation and analysis were maintained as dustfree as feasible. The peaks and concentrations of the samples were identified by using standard calibrations. Individual elemental graphic schemes were used to depict the data from the analyte sample findings. A literature study was used to investigate these data in further detail. The 30 drinking water samples were tested by ICP-MS multi-element analysis and determined to be compliant with government regulations; even though, the analytes for each zip code sample had different trace metal detection levels
Student and Faculty Preferences Regarding Instructional Modalities at an HBCU Business School as a Result of Covid-19 – A Change Management Approach and Mindset
Get PDFThe COVID-19 pandemic has had a major impact on the higher education community, especially the Historically Black Colleges and Universities (HBCUs). At a micro-level, the HBCU business schools have felt the effects as well, particularly in critical areas such as instructional modalities and the overall classroom experience. Since COVID-19 has changed the educational game, what do key stakeholder groups now prefer regarding instructional modalities in the HBCU business school? This study will answer this question and more while incorporating a change management approach and mindset for leadership and decision-making
How To Create Cash Flows That Give A Priori IRRs?
Get PDFWe illustrate algebraically the way to numerically derive the cash flows of an investment project yielding a set of desired IRRs. This is significant given the dearth of practice questions with the appropriate cash flow numbers, and their corresponding sign, in widely adopted Finance textbooks that will allow students to find multiple IRRs as learning exercises. The note serves to fill that void by allowing the readers to change the IRR inputs in an Excel spreadsheet and have the corresponding cash flows output ready for an assignment. Instructors can use the Excel codes to create different cash flows that yield multiple IRRs with ease so that students in the same class or those in different semesters need not be given the same set of cash flows where plagiarism could compromise the learning process
Impact of Stand Your Ground, Background Checks and Conceal and Carry Laws on Homicide Rates in the U.S
Get PDFIn recent years, the number of gun related killings appear to be on the rise. In fact, data show that gun related murders rose 32% between 2014 and 2017 (Gramlich 2019). While the second amendment to the U.S. Constitution allows citizens to bear weapons, many states have passed additional laws regulating the industry. These include restrictive and prohibitive laws. The goal of this paper is to assess the impact of changes in hand gun related legislation on firearm homicide rates in the United States for the period 1999-2015. More specifically, we focus on the impact of stand your ground, right to carry and background checks laws and how they impact changes in homicide rates. Using a unique data set, we created a change point model and used regression models to show that changes to handgun laws do in fact impact homicide rates in many state
COVID-19 and African Americans: A Problem Decades in the Making
Get PDFCOVID-19 has exposed health care disparities long known and discussed in medical and public policy literature. While there have been many discussions regarding our “offense” – how to attack a global pandemic (vaccines, treatment algorithms, etc), there has also been a renewed interest regarding our “defense” (limiting exposure, strengthening the host) – i.e., how to protect our most vulnerable populations. In June 2020, The U.S. Health and Human Services Department announced a $40 million, three-year partnership with the Morehouse School of Medicine to focus on this topic. As described by Danie Dawes (director of Morehouse’s Satcher Health Leadership Institute), this national COVID-19 resiliency network (NCRN) will focus on at-risk communities and social determinants of health. With a few policy changes this “perfect storm” (deadly virus + high exposure + overly susceptible hosts) might not have occurred, so it is imperative that we learn from mistakes of the past and act quickly so that lives may be saved. While we work on vaccines, better testing options and social distancing – our defense for the next pandemic can begin now by creating a healthier society for us all. Health equity is needed now more than ever
A Seat at the Table: Minority Representation and County Governing Boards
Get PDFThis study focuses on minority representation on county governing boards to determine the extent of minority representation, and then to provide explanation for the exiting patterns in its representation. The dependent variable used in this paper is a count variable employing a Zero-Inflated Negative Binomial model. The results indicate that minority populations, counties located in the South, partisan elections, the size of county governing boards and urban counties have positive effects on increased minority representation, while at-large voting districts have a negative effect. Furthermore, it advances the need for greater research on county governing boards, county governments in general and a new agenda for the future study of minority representation on local governing bodies