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IN-SILICO ENGINEERING OF MHETASE-LIKE ENZYME, MLE046
No full textPolyethylene Terephthalate (PET) is a common synthetic polymer from petroleum, used in packaging and clothing. Inadequate plastic waste management has increased plastic pollution, and current recycling methods are not advanced enough to enable effective plastic reuse, rendering recycling efforts insufficient to tackle the problem. The discovery of plastic degradation enzymes enables PET’s biological recycling or upcycling, which shows a promise to achieve a complete cycle of plastic use. For instance, Ideonella sakaiensis (I.S.), which expresses dual enzymes PETase and MHETase, catalyzes PET depolymerization and converts PET into original monomers, terephthalate acid (TPA) and ethylene glycol (EG). However, its conversion efficiency must be improved for promising industrial use. In this regard, engineering existing enzymes or searching for novel enzymes is of timely interest. Mle046 is a promising, yet relatively less studied enzyme from a marine microbial consortium which is a homolog to MHETase with an ability to depolymerize MHET into its building blocks, TPA and EG.We report the results from Molecular Docking and Molecular Dynamics Simulations for the characterization and engineering of Mle046. This study is based on the three-dimensional configuration obtained through homology modeling, as the experimental structure is not yet available. Multiple sequence alignment with its homologs indicates that the active sites of Mle046 remain conserved, displaying a catalytic triad consisting of SER, HIS, and ASP, similar to the known PET hydrolases. In this study, we report on the possibility of improving the enzyme’s stability by adding a disulfide bond. Further, by analyzing the PET binding surface in Mle046, we will show potential mutations that will enhance PET depolymerization activity
MICRO/NANO PARTICLE LABELED ANTIBODY/APTAMER BASED IMMUNOASSAYS FOR THE DETECTION OF OVARIAN CANCER USING LASER BASED SPECTROSCOPIC TECHNIQUES
No full textOvarian cancer is one of the most lethal gynecological conditions among women today. Having around a 50% survival rate, it has been the 5th leading cause for cancer-related deaths for women. Delayed manifestation of symptoms with late stage diagnosis has been a major factor for relatively high mortality. The 5-year survival rate for the early stage is over 90%; therefore, early detection of cancer is essential to improve the survival rate. Even though technology has improved today, early detection has not improved, and still it has been posing challenges. In addition to the clinical practices in diagnosis, scientists are looking for other novel promising methods to detect it at the early stage that would be inexpensive and user-friendly. Currently, cancer antigen 125 (CA125), a type of biomarker that can become elevated in a patient’s blood serum, is recommended mostly for clinical tests in the screening of ovarian cancer. However, because of the lack of sensitivity and specificity associated with CA125, the search for new potential biomarkers is a research priority to diagnose cancer at a localized stage.In this work, I report a nano/micro particle labeled immunoassay method for the detection of ovarian cancer biomarker CA125 in a Phosphate-Buffered Saline (PBS) medium. Here, a sandwich type immunoassay method is presented. For this goal, CA125 biomarkers are immobilized on a solid surface (magnetic beads) using a bioconjugation technique. In order to specifically target CA125, antibody and aptamer molecules are used. Here, the elemental nano/micro particles are used to label the antibody and aptamer. This labeled immunoassay is subjected to surface enhanced Raman spectroscopy (SERS) and laser induced breakdown spectroscopy (LIBS) for the detection of CA125. I establish a calibration curve by acquiring the spectroscopic signal for the known concentration of CA125. In addition to the detection part, other spectroscopic techniques such as attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), UV-Vis spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM) are employed to study the bioconjugation steps. In this regard, chapter 1 gives a general overview about ovarian cancer with necessary statistics. In chapter 2, I have given necessary background information on bioconjugation techniques for immunoassay methods, particularly in the perspective of my experiments. Chapter 3 covers the antibody-based immunoassay using Raman labeled gold nanoparticles. It describes how to build a nano/micro particle based sandwich type immunoassay for CA125 detection and the corresponding results. Chapter 4 describes a similar immunoassay method to chapter 3, using aptamers instead of antibodies for specifically targeting CA125. In both chapters, SERS is employed for detection. In chapter 5, I use LIBS for the detection of an aptamer based assay. Following a similar technique in the previous chapter, I use silica microparticles to label the aptamer instead gold nanoparticles. Chapter 6 focuses on the computational aspect of our experimental work, detailing the molecular docking process and presenting preliminary results regarding the interactions of the antibody and aptamer with the CA125 antigen. Chapter 7 offers a summary of my findings along with the relevant background information
LEVELING UP: THE RISE OF CHINA’S GAMING INDUSTRY IN THE RECONFIGURATION OF TRANSNATIONAL CAPITALISM
No full textThis dissertation examines the development trajectory of China’s gaming industry in the context of the country’s reform and opening-up and its reintegration into transnational capitalism. It explains how the rise of the industry contributes to the reconfiguration of transnational capitalism. Taking a critical political economy perspective, the study focuses on the power dynamics and development logic within the industry. It identifies three pivotal phases in the industry’s evolution: its transformation into a site of capital accumulation, its rise in the mobile gaming sector, and its overseas expansion. The Chinese state, transnational capital, and the Chinese private sector emerge as the primary forces shaping the evolution. Moreover, this research employs a triangulated research approach, with document analysis as the primary method, supplemented by semi-structured interviews and simple observation. This dissertation argues that the Chinese gaming industry has taken a distinctive development path within the transnational capitalist system. Initially, it accumulated experience, technology, and capital at lower tiers of the global industry hierarchy. It then entered the emerging mobile game market and ascended to prominence. On the one hand, this development has reinforced the existing system by providing new momentum and sites for capital accumulation. On the other hand, it has contributed to the reconfiguration of this system by rebalancing the Western-dominated power structures
HYPERVALENT IODINE BASED MACROCYCLES AND THEIR SUPRAMOLECULAR INTERACTIONS WITH GUESTS
Get PDFIn this contribution, we successfully synthesize different variations of hypervalent iodine macrocycles (HIM) including novel phenylalanine base HIM. Next, this study explores the dynamic self-assembly and disassembly of hypervalent iodine-based macrocycles (HIMs) guided by secondary bonding interactions. The reversible disassembly and reassembly of HIMs are facilitated through anion binding via addition of tetrabutylammonium (TBA) salts or removal of the anion by addition of silver nitrate. The association constants for HIM monomers with TBA(Cl) and TBA(Br) are calculated and show a correlation with the strength of the iodine-anion bond. A unique tetracoordinate hypervalent iodine-based compound was identified as the disassembled monomer. In addition, this study also reveals the dynamic bonding nature of these macrocycles in solution, allowing for rearrangement and participation in dynamic bonding chemistry. In second research direction, A series of valine functionalized supramolecular hypervalent iodine macrocycles (HIMs) with enlarged aromatic cores, including naphthalene and anthraquinone, have been synthesized. Single crystal analysis shows the macrocycles consist of a slightly distorted cyclic planner interior with three carbonyl oxygens from the amino acid residues facing towards the center of the cage and all three alkyl groups above one plane. Owing to the enlarged aromatic core, the naphthalene-based HIMs were successfully co-crystallized with Buckminster Fullerene (C60) into a long-range columnar supramolecular structure. The assembled architecture displays a long-range pattern between HIM and C60 in a 2:3 ratio, respectively. Disassembly of the HIMs can be accomplished by adding anions of tetrabutylammonium (TBA) salts that selectively bind with the electron deficient iodine center in HIMs system. A comparative study of the associations constants and the binding energies for different aromatic-based HIMs with TBA(Cl) and TBA(Br) is presented. Lastly, this dissertation describes the solution- and solid-state assembly of phenylalanine based hypervalent iodine macrocycles (HIMs) with lithium and sodium cations. The metal cation binding of HIMs was evaluated by addition of lithium tetrakis(pentafluorophenyl)borate ethyl etherate (Li)BARF and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (Na)BARF. The relatively electron rich, outwardly projected carbonyl oxygens of the HIM co-crystalize with the cations into bent supramolecular architectures. Both crystal structures show a pattern of assembly between HIM and metal cation in 2:1 ratio. While association with sodium leads to a polymer-like network, the lithium crystal structure was limited to dimeric assemblies of HIM. In the lithium coordinating complex, the oxygen-lithium-oxygen bond angle is approximately 98.83°, displaying a closer arrangement of two HIMs. In contrast, the sodium complex exhibits a more open orientation of two HIMs with an oxygen-sodium-oxygen bond angle close to 167.98°. Furthermore, a comparative study of association constants and binding energies for phenylalanine based HIM with (Li)BARF and (Na)BARF are presented
MORALITY AND HEALTHCARE: AN SEM INVESTIGATION OF ADULT ATTITUDES TOWARDS TRANSGENDER ADOLESCENTS\u27 HORMONE REPLACEMENT THERAPY CHOICES
No full textAdolescents largely cannot legally make their own medical decisions, and in some cases, the debate around whether this is right or wrong is an ethical dilemma. Researchers, philosophers, social justice workers, child rights advocates, and healthcare providers have long debated how much say, if any, adolescents should have in making medical decisions about their own health. This decision generally involves two contrasting approaches: (1) a paternalistic approach, where decisions are made for the adolescent, and (2) an autonomous approach, where the adolescent is granted the authority to make their own choices. These decisions are inherently moral in nature, as they involve judgments about what is morally right or wrong (Rozin, 1999). The present research examines how two key moral theories—Theory of Dyadic Morality (TDM) and Moral Foundations Theory (MFT)—apply to the issue of supporting adolescent autonomy in medical decision-making, specifically regarding transgender youth. Dyadic Morality posits that moral decisions are made through a cognitive process involving perceptions of norm violations, negative affect, and perceived harm (Schein & Gray, 2018b), whereas Moral Foundations Theory suggests that moral judgments rely on cognitive heuristics, or foundations, such as harm/care, fairness/cheating, and purity/degradation (Haidt & Joseph, 2004; Graham et al., 2009). Despite extensive research on moral judgments, little work has applied these theories to the context of transgender adolescents’ healthcare decisions.In the present research, 507 participants were recruited via Prolific to complete a survey assessing their moral judgments about transgender adolescents\u27 autonomy in hormone replacement therapy (HRT) decisions. Structural Equation Modeling (SEM) was employed to test several hypotheses and address four research questions regarding the role of both morality theories on support for adolescent autonomy. The results provide mixed support for Moral Foundations Theory (MFT) and challenge the applicability of the Theory of Dyadic Morality (TDM) within the context of transgender healthcare, indicating that these moral frameworks may not fully capture the complexities involved in medical decision-making for transgender adolescents. While both MFT and TDM offer valuable insights into the cognitive processes underlying moral judgments, they may fall short in accounting for the deeper ideological and cultural factors that shape support for or opposition to transgender healthcare. This study did not provide strong theoretical support for morality research, but policy and medical implications are worth noting. To effectively advance transgender rights, particularly adolescent autonomy in medical decisions, it is essential to engage with the broader sociocultural and ideological frameworks that influence public opinion. Both healthcare providers and advocates must address these beliefs in ways that respect the values of individuals and communities while simultaneously promoting inclusive and supportive environments for transgender individuals
CANNABIDIOL VERSUS CHEMO BRAIN: TACKLING DOXORUBICIN-DRIVEN ANXIETY AND DEPRESSION
No full textChemotherapy is one of the widely used treatments for patients with cancer. It has been proven as an effective therapy to lengthen the survival of cancer patients and improve their quality of life. However, more than half of the cancer survivors suffer from cognitive deficits following chemotherapy, which is termed “Chemo brain”. There is ample evidence on the side effects of chemo drugs, the mechanisms of which seem to be ambiguous. Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic reported to induce chemo-brain via DNA damage, disruption of hippocampal neurogenesis, oxidative stress, inflammation, and dysregulation of apoptosis. Cannabinoids have been studied in various neurological disorders. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa that has been identified as a possible therapeutic agent against many neurodegenerative disorders. However, studies regarding the neuroprotection of CBD against chemo-brain remain obscure. The study\u27s long-term goal is to provide mechanistic targets for future therapeutics to treat cognitive deficits arising after chemotherapy treatment. To accomplish the goals above, Female Long Evans Hooded rats received intraperitoneal injections of DOX (6mg/kg) or vehicle (0.9% saline) once a week for four weeks, followed by oral administration of CBD (10mg/kg) three times a week for the same period. Elevated Plus Maze Test, Open Field Test, Marble Burying Test, Novel Object Recognition, and the Sucrose Preference Test were performed to assess anxiety and depression-like behaviors, respectively. Additionally, the String-pulling and Bar-walk tests were performed to assess motor functions. Brain tissues isolated from Dox and CBD-treated rats were processed for gene expression analysis of markers of neuroinflammation and neurogenesis. CBD was significantly protective against Dox-induced anxiety and depression-like behaviors as measured by several behavioral tests. Furthermore, CBD improved DOX-induced alterations of gene expression of biomarkers of neuroinflammation in the hippocampus and prefrontal cortex. This provides insights into future studies on possible mechanisms by which CBD could alleviate Dox-induced cognitive dysfunction
PREDATOR-PREY INTERACTIONS AND SPACE USE STRATEGIES FOR TWO MESOCARNIVORES
Get PDFMesocarnivores, including bobcats (Lynx rufus) and coyotes (Canis latrans), serve an important ecological role, functioning as the top predators throughout much of the eastern United States due to the extirpation of larger-bodied carnivores. Mesocarnivores are often described as generalists due to their flexibility in forage and habitat preferences and their ability to persist in human-dominated landscapes. However, this characterization overlooks the fact that many individuals within these populations act as specialists, with movement, space use, and predation strategies varying between individuals and across environmental contexts. Quantifying variability in mesocarnivore space use and movement from multiple perspectives can provide a better understanding of their ecological function as the current top predators and their potential influence on white-tailed deer (Odocoileus virginianus) populations. To better understand how bobcats and coyotes spatially respond to fawn kill sites, I leveraged two types of habitat selection functions (Resource Selection Functions and Latent Selection Difference Functions) to create a framework describing how bobcats/coyotes and female white-tailed deer respond to fawn kill sites and how these relationships vary with landscape heterogeneity. In certain landscape attributes, does decreased their use of habitats which were associated with an increased risk of fawn predation. Additionally, predators were more efficient at killing fawns in certain areas rather than increasing their selection for areas associated with increased fawn risk. To evaluate how space use strategies varied across individuals and environmental contexts, I also quantified individual- and population-level variation in speed and resource specialization from coyotes located across three disparate environments (forest, agriculture, and urban) in Illinois. After accounting for the influence of various external and internal factors, movement and space use behaviors varied substantially among coyotes within and across populations. Given that the integration of movement ecology and animal personality is relatively new, my work served as a key first step in determining that behavioral patterns for movement and habitat selection at one scale (within a population) do not necessarily hold across broader spatial scales (across populations). Overall, I found that evaluating risk and space use from multiple perspectives can provide a deeper understanding of the predator-prey spatial game and mesocarnivore space use
INSTRUCTORS’ PERCEPTION OF INQUIRY-BASED SCIENCE TEACHING IN SAUDI ARABIA
No full textDr. Edward Pultorak I aimed in this qualitative study to explore the perception of male faculty members of inquiry-based teaching at the Curriculum and Instruction Department at Hail University in Saudi Arabia. I also investigated participants’ perspective on how implementing inquiry-based teaching influences meeting the educational goals of Saudi’s Vision 2030. I asked the following questions:1. How do male faculty members at the Department of Curriculum and Instruction at Hail University in Saudi Arabia perceive inquiry-based teaching? 2. How do you think inquiry-based teaching influences meeting educational goals of Saudi’s Vision 2030? I used a semi-structured interview protocol to collect the data from 18 male faculty members at Curriculum and Instruction Department (C&I). The findings showed that participants have partial knowledge of the role of both teachers and students. Also, only five participants have used an inquiry approach in their teaching. In addition, participants reported five major challenges of implementing inquiry with all participants agreeing that students were the biggest barrier to teaching with inquiry while only two of them mentioned lack of equipment. Finally, although all participants were aware of the scientific role of inquiry model in terms of meeting the educational goals of Saudi’s Vision 2030, majority of them were not able to explain how inquiry model could lead to meet the educational goals of Saudi’s Vision 2030. Moreover, I provided implications and suggestions for future research to enhance teaching in the (C&I) at Hail University through inquiry
To the Dictionary and Beyond! The Personification of Corporations in Burwell v. Hobby Lobby Stores, Inc., 134 S. Ct. 2751 (2014)
Get PDFIn March of 2010, President Obama signed the Patient Protection and Affordable Care Act, which provides that group health plans must provide coverage for certain forms of preventative care and screenings for women. Regulations promulgated pursuant to this provision, commonly known as the contraceptive mandate, required coverage for all FDA-approved contraceptive methods without cost sharing. Two closely held corporations sued the U.S. Department of Health and Human Services under the Religious Freedom Restoration Act (RFRA). The suit was based on the owners’ opposition to abortion, which was rooted in their sincerely held religious beliefs. The plaintiffs sought to enjoin enforcement of the contraceptive mandate to the extent it required them to facilitate access to the four contraceptive methods they found objectionable. In Burwell v. Hobby Lobby Stores, Inc., the United States Supreme Court held that corporations are persons within the meaning of RFRA and the contraceptive mandate burdened the corporations’ exercise of religion.
This Note argues the Court correctly decided Hobby Lobby in holding that corporations are persons under RFRA. It reviews the legal background of the contraceptive mandate, RFRA, and the Dictionary Act, as well as cases where courts have held that corporations are persons within the meaning of a statute, and cases holding that corporations have racial identities and are thus capable of bringing racial discrimination suits. This Note analyzes the Court’s use of the Dictionary Act and compares the decision in Hobby Lobby to case law holding that corporations have racial identities under federal civil rights statutes. Finally, this Note analyzes the Court’s holding that Dictionary Act was applicable and that corporations are persons capable of exercising religion, with a special focus on the similarities between cases holding that corporations are persons within the meaning of RFRA, and cases holding that corporations are persons within the meaning of civil rights legislation
Feeding the Cats: The Corruption Conundrum in the Failed Arab Spring-Egypt
Get PDFThe Egyptian civil society, across generational, religious, gender, and economic lines and without a charismatic leader, has organized itself at the grassroots level, evidencing the people\u27s power in the face of a strong regime. Public order, security, and stability have deteriorated during the past two decades, with increased crime rates and other forms of abuses of power by individuals (e.g., thugs and small criminal bands), which the police have left somewhat unchecked. The people hold the military in high esteem because, in the last forty years, it has never acted against the general public. To prevent manipulation during the investigations and trials, the Egyptian Attorney General ordered the arrest and freezing of assets of several persons under investigation for corruption, bribery, profiteering, and money laundering according to the Egyptian criminal justice system (e.g., Egypt’s Penal Code). Further, after the Attorney General conducted individual investigations to determine how corruption turned into money laundering and how the Egyptian economy is now left holding the bag for what could amount to billions of dollars, some institutional reforms have taken place.
Like its predecessors—the Nasr and Sadat regimes—the Mubarak administration had a military and political establishment. Under former President Mubarak, no one knows precisely how much it grew because its operations, budgets, and profits were secret. This entire sector of the economy was not only beyond civilian control; it was hidden, not taxed, and the military establishment distributed its undisclosed profits as senior leadership saw fit. It fell outside of any type of accountability, was not subject to any operational control, and enjoyed free from import and export duties. The main concerns and goals of the Egyptian people are regime changes, emphasizing the notion that people should govern themselves, democracy, justice (including socio-economic justice), reforming human and civil rights, fighting corruption, and reviving the rule of law. Their slogans were kefaya (enough is enough), alSh‘ab youreed isqaat alnizam (the public wants the regime to fall down), and No more nickel, No more dime, No more money for Mubarak’s crimes. American and Western ideals and values reflected in the U.S. Constitution and—particularly—Islamic norms and principles have influenced Egyptian society. The current administration is entirely understanding that it must meet these particular goals