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IS IT GREENER ON THE OTHER SIDE OF THE STATE LINE? THE ATTRACTIVENESS OF U.S. STATES FOR CANNABIS INDUSTRY EXPANSION
No full textBusiness Administration/Strategic Managemen
A STUDY ON INVESTMENT STRATEGY SELECTION FOR BIG BRANDS OF PHARMACEUTICAL ENTERPRISES
No full textWith the rapid development of national economy, intensified opening up of the pharmaceutical industry, and deepening reform of the medical system, the business environment faced by Chinese pharmaceutical companies is undergoing tremendous changes. As a vital industry to the national economy and people’s livelihood, it is of critical significance for pharmaceutical industry and even the health industry that the pharmaceutical industry can correctly assess its own competitive advantages in the face of increasingly fierce competition at home and abroad, and integrate resources to cultivate and enhance its core competitiveness, thus gaining the upper hand in domestic and international competition.
Product is the lifeblood of corporate survival. The development of big brand with an annual sales exceeding RMB 1 billion has increasingly become a hot spot for pharmaceutical companies. This study analyzes the strategies and approaches for pharmaceutical companies to select competitive big brands from the perspective of core competitive products of the pharmaceutical companies. Firstly, it analyzes the main elements of core competitiveness of big brands, and constructs a big brand evaluation index system through the investigation and screening of specific factors and principal component analysis. The evaluation indicators include: factor 1: influence of the pharmaceutical company and sales of the product, including the market acceptance of the drug, the production and supply capacity of the drug, the sales scope of the drug (the domestic sales scope), the market share of the drug, the market growth potential of the drug, the annual sales of the drug over RMB 1 billion, the production scale of the drug manufacturer, and the reputation of the drug manufacturer (including visibility and recognition); factor 2: scale and influence of drug exports, and influence of the domestic drug list, including the drug list, whether the drug is included in the basic drug list or the basic medical insurance list, the sales scope of drug exports, and the annual sales of drug exports; factor 3: R&D value of the drug, including the unit price of the drug, whether the drug has independent intellectual property rights, and the added value of the drug (such as production technology, and appearance, etc.); factor 4: effect of the drug, including the efficacy of the drug (such as effective rate, and cure rate, etc.), and the incidence and harm of the adverse reaction of the drug; factor 5: special effects of the drug, including whether the drug is for treating difficult diseases, and substitutability of the drug (whether there are similar products with same indications). Levoamlodipine Maleate Tablets (Xuan Ning) produced by CSPC Ouyi Pharmaceutical Co., Ltd., Compound Danshen Dripping Pills produced by Talsly Holding Group, Houttuynia Cordata Injection produced by Shineway Pharmaceutical Group Ltd., and NBP Soft Capsules produced by CSPC Pharmaceutical Limited, which are four big brands certified by the Ministry of Science and Technology, are chosen as the test objects to verify the feasibility and validity of the model.
In view of the increasingly strict safety control over clinical big brands, the incidence of adverse reactions of the big brands has become an important factor in considering and selecting big brands. In this study, a standard game theory model is used to determine the optimized incidence of adverse reaction of big brands, and a game theory equilibrium model of optimized incidence of adverse reactions is constructed.
This study plans to analyze the strategies of pharmaceutical companies for big brand development from four aspects: product, price, distribution and promotion based on the Marketing Theory of 4Ps.Math & Science Educatio
The Interplay Between Stiffness and Hyperglycemia on Diabetic Foot Ulcer Wound Closure
No full textDiabetes impairs fibroblast migration, hindering wound closure and contributing to diabetic foot ulcers. Although diabetic plantar skin exhibits greater stiffness, which should enhance fibroblast mechanotransduction, fibroblasts still fail to migrate effectively. This suggests that impaired wound closure is driven by another factor; hyperglycemia (≥ 11.1 mM glucose), which alters fibroblast mechanotransduction. Mechanotransduction regulates migration parameters such as velocity, directionality, and actin alignment, all of which influence wound healing. A potential mechanism is Rac1 activation at the leading edge of migrating cells, regulating lamellipodia formation and migration direction. We aim to simulate diabetic foot ulcers by developing a 2D circular in vitro wound closure model system to investigate the role of diabetic plantar stiffness and hyperglycemia on fibroblast mechanotransduction. To mimic skin stiffness, polydimethylsiloxane will be used as the cell culture substrate and fabricated at 57±5 kPa for normal plantar skin and 90±6 kPa for diabetic plantar skin. Cell culture media will have altered glycemic concentrations, 5.5 mM glucose represents normal blood glucose, while 11.1 mM represents hyperglycemia. In the model system, I hypothesize that the combination of stiffness and glucose concentration will reveal a new behavioral pattern by fibroblasts in wound healing, specific to DFU. Time-lapse microscopy results reveal a new restrictive effect of higher stiffness on migrating cells under normal glucose, in addition to a biphasic response to hyperglycemia. Cells on normal stiffness have a decreased velocity as predicted, whereas on higher stiffness, high glucose increased cell velocity, overcoming the stiffness's restrictive effect. The relationship between velocity and directionality was reversed at higher stiffness, yet wounds under normal glucose still closed faster than those under diabetic glucose. These findings suggest Rac1 as a key candidate for future investigation, as it directly contributes to migration directionality. Inhibiting Rac1 in the context of higher stiffness could enhance the directed migration of faster-moving fibroblasts in diabetic conditions, aligning their wound closure efficiency with that of normal glucose conditions on the same stiffness. This research establishes a wound closure model that demonstrates significantly slower healing in diabetic plantar skin stiffness and hyperglycemic glucose compared to normal conditions. It also reveals how migration dynamics vary significantly in response to stiffness, emphasizing the importance of considering substrate stiffness in mechanotransduction studies. The fibroblast migration behavior observed in this model suggests that hyperglycemia impairs wound closure in diabetic foot ulcers by disrupting directionality. These findings could inform therapeutic strategies to improve diabetic wound healing, with Rac1 as a promising target.Bioengineerin
Mechanisms of abnormal spinal cord development and biomarkers of open neural tube defects: insights from a fetal rat model
No full textNeural tube defects (NTDs) are major birth defects affecting the central nervous system (CNS). They arise as a result of incomplete closure of the neural tube during early embryonic development, leading to defects in the brain and/or the spinal cord. The pattern of occurrence suggests the multifactorial etiology of NTDs, involving complex interactions between genetic predisposition and environmental factors. However, the precise mechanisms underlying their etiology and pathogenesis remain poorly understood. Myelomeningocele (MMC), the most common and severe form of spina bifida, is an open NTD that affects the developing spinal cord. Afflicted fetuses usually survive birth; however, MMC leaves most individuals with substantial and life-long deficits, including reduced or absent motor and sensory function, bowel and bladder dysfunction and cognitive disabilities. MMC defect, which is typically found in the lumbar region, is characterized by herniation of neural tissue and meninges through a pathological opening in the overlying structures, leading to spinal cord exposure to the surrounding amniotic fluid (AF). The progressive nature of MMC during gestation along with its life-long clinical impact, points to the importance of early prenatal diagnosis. Currently, the measurement of alpha fetoprotein (AFP) levels and/or fetal imaging techniques such as ultrasound are typically used for prenatal diagnosis of open NTDs. However, due to limited sensitivity and specificity, detection of open NTDs through elevated levels of AFP is not definitive, making the early diagnosis of these defects more challenging. Thus, there is a need for the identification of novel biomarkers enabling early and accurate prenatal diagnosis of open NTDs.
The chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, are extracellular matrix (ECM) components of neural origin that are abundant in the developing CNS. With the occurrence of open NTD, these highly soluble forms of ECM proteins could be released from the site of the spinal cord defect into the surrounding AF, resulting in increased levels of neurocan and phosphacan in the AF of affected fetuses. Therefore, using the well-accepted retinoic acid (RA)-induced fetal rat model of MMC, the objective of this part of the project was to determine whether neurocan and/or phosphacan levels are elevated in the AF of affected fetuses compared to age-matched controls at various points of gestation, particularly in early development, and whether the elevated AF levels of neurocan and phosphacan constitute potential biomarkers for open NTDs.
We identified significantly elevated levels of both neurocan and phosphacan in the AF of fetal rats with MMC, when compared to age-matched normal controls. These CSPGs were detected in MMC fetuses starting early in gestation, with their levels increasing with the progression of MMC. We demonstrated that significant differences in the AF levels of neurocan and phosphacan allow for distinction between MMC and normal controls at all examined gestational ages. Therefore, these studies provided two prospective biomarkers with potential applications in early prenatal diagnosis of open NTDs.
In MMC, the failure in neural tube closure results in spinal cord malformation, leading to the disruption in the normal development of the spinal cord at the affected site. The pathological development of MMC spinal cord involves enhanced generation of glial fibrillary acid protein (GFAP)-expressing astrocytes in the spinal cord at the site of MMC defect. However, the mechanisms underlying the abnormal generation of astrocytes in MMC spinal cord are poorly understood. Therefore, investigating the dysregulation in cellular and molecular mechanisms underlying the process of astrogenesis in the MMC spinal cord is essential for better understanding of its impaired development.
The Janus kinase - signal transducer and activator of transcription (JAK-STAT) signaling is the most prominent pathway that regulates GFAP expression and, therefore, the differentiation of neural progenitor cells (NPCs) into astrocytes. However, its effect on GFAP expression is influenced by epigenetic changes, including DNA methylation and histone modifications. In line with the importance of epigenetic changes in the process of astrogenesis, studies of cortical progenitors demonstrated that STAT3 induces GFAP expression and differentiation of NPCs into astrocytes following demethylation of STAT3 binding site in the Gfap promoter. While the relationship between the activation of STAT3 signaling and the epigenetic modifications was investigated in the context of normal astrogenesis using cultures of cortical progenitors, the dysregulation of these mechanisms in the developing MMC spinal cord have not been explored. Therefore, using the fetal rat model of MMC and NPC cultures obtained from MMC spinal cords, the objective of the second part of this project was to determine whether the abnormal activation of STAT3 in NPCs and the epigenetic changes within the Gfap promoter at the STAT3 binding site are involved in the abnormal generation of astrocytes in the MMC spinal cord, and to determine the role of AF exposure in this pathological process.
We found that NPCs in the ventricular zone (VZ) of developing MMC spinal cord, exhibit abnormal STAT3 activation, a feature that is not observed in normal controls. These changes, along with the accelerated epigenetic modifications characterized by reduced DNA methylation at the STAT3 consensus binding site within the Gfap promoter and enrichment of dimethylated histone 3 lysine 4 (H3K4me2), induced early GFAP expression in NPCs, promoting premature astrocyte generation in MMC spinal cords. Moreover, we demonstrated that AF exposure serves as a stimulus for STAT3 activation in NPCs of MMC spinal cord, thereby promoting GFAP expression and driving their differentiation into astrocytes. To validate this mechanism, we showed that exposure of NPCs to MMC AF following CRISPR/Cas9-mediated elimination of STAT3 expression, abolished GFAP expression and inhibited their differentiation into astrocytes. These findings from the fetal rat model of MMC and NPCs isolated from MMC spinal cords reveal the cellular origin and novel mechanistic basis of the abnormal astrocyte development in MMC spinal cords.Biomedical Science
DEVELOPMENT OF MULTI-MODAL NONLINEAR SPECTROSCOPY FOR INTERFACIAL STUDIES
No full textWhile interfaces properties are different from the bulk, probing them is challenging. Iexploit the sensitivity to noncentrosymmetry, intrinsically present at interfaces, of second-order nonlinear optical techniques to investigate oxide interfaces. I have used existing techniques mid-infrared vibrational sum frequency generation (MIR-vSFG) and near-infrared vSFG (NIR-vSFG) and developed new ones NIR second harmonic generation (NIR-vSHG) to study surface phenomena. We revealed the local electric fields of water-acetonitrile mixtures at interfaces with α-Al2O3(0001) and SiO2 by exploiting MIR-vSFG Stark spectroscopy. The nitrile group of acetonitrile probes charged hydroxyl groups (−3.2 MV/cm) at the SiO2 surface at pH 6–11, while at the Al2O3 interface, the local electric field shifts from 4.3 MV/cm at pH 4 to -16 MV/cm at pH 10 due to the influence of multiple charged hydroxyl sites at elevated pH.
We have made progress in understanding electrical permittivity at buried interfaces. We derived an equation for the interfacial dielectric constant ( "!="#"− "# + 6)/2 (2"$ + "#)). Then we validated this expression using MIR-vSFG and Fresnel factor calculations for interfaces of alumina with water (H2O and D2O) and acetonitrile.
We highlighted the impact of NQEs on hydrogen bonding dynamics by comparing the vibrational lifetimes of H2O and D2O at alumina interfaces using ultrafast MIR-pump/MIR-vSFG probe. We propose that the increased anharmonicity of H₂O, driven by its higher zero-point energy compared to pure D₂O, enhances mode coupling, accelerates spectral diffusion, and results in shorter vibrational lifetimes, as confirmed by HOD experiments. We attribute the differences in the vibrational relaxation lifetimes of the OD and the OH to variations in their relaxation pathways, which depend on the charge state of the interfaces. These nuclear quantum effects (NQEs) collectively account for the observed differences in the vibrational relaxation dynamics between water and its isotopomers.
Using NIR-vSHG, a new and user friendly vibrational nonlinear spectroscopy technique, we investigated the overtone of the free OH group on muscovite mica surfaces in air, as well as the CH stretching vibrations in chloroform and acetonitrile at alumina interfaces. We confirmed the vibrational origin of the NIR-vSHG signal by comparing it with the NIR-vSFG response. Additionally, our results provide the determination of the anharmonicity and dissociation energy of these CH and OH bonds at interfaces.
These results offer new insights into hydrogen bonding networks at interfaces, highlighting how they differ from those in the bulk. We expect that our findings will be of interest to diverse audience of experimental and theoretical scientists working in condensed matter and materials, molecular and optical physics, physics of fluids, atmospheric chemistry, and earth and planetary science.Chemistr
GIVE TEACHERS THE MIC: AN INVESTIGATION INTO THE LITERACY GAP AND EDUCATIONAL LEADERSHIP
No full textThis dissertation examines literacy disparities in education, focusing on the roles of leadership, teacher demographics, and professional development in addressing these gaps. Using surveys (n=50) and interviews (n=8), findings highlight the critical influence of transformational, transformative, and distributed leadership in fostering equitable learning environments. Transformative leadership addresses systemic inequities, while transformational leadership inspires innovative practices, and distributed leadership emphasizes collaboration and shared responsibility. Teacher-student demographic alignment emerged as a significant factor in improving engagement and cultural understanding. Professional development and early interventions during transitional academic periods were found to be pivotal in addressing literacy challenges. Recommendations include targeted resource allocation, data-driven interventions, and systemic policy reforms to reduce disparities. This research provides actionable insights for educational leaders and policymakers to create inclusive, effective learning environments that address literacy inequities and improve outcomes for all students.Educational Leadershi
THE DUPE EFFECT: EXPLORING CONSUMER MOTIVATIONS BEHIND DUPE PURCHASES
No full textThis research explores the motivations underlying consumers’ preference for dupe products, alternatives to premium brands that replicate their style or functionality without infringing on intellectual property rights. This research presents two studies. In Study 1, using LIWC and manual coding, we examine the factors influencing dupe purchases and how consumers differentiate them from counterfeits. Findings reveal that consumers perceive dupes as offering greater value, lower risk, and practical benefits while carrying fewer ethical concerns than counterfeits. Building on these insights, Study 2 investigates the role of ethical nudges in shaping dupe purchases. Results demonstrate that while environmental impact messaging effectively reduces purchase likelihood, an appeal for making creative theft salient does not impact consumer’s likelihood to purchase dupes. Importantly, our findings show that the impact of environmental nudge on dupe purchases is mediated by perceived unethicality of purchasing dupes. This research contributes to consumer behavior literature by clarifying the distinct motivations driving dupe purchases and highlighting the impact of different types of ethical messaging nudges on purchase decisions. The findings provide strategic implications for marketers navigating the evolving dupe market and adapting to shifting consumer ethics.Business Administration/Marketin
PARENTAL DECISION-MAKING AND RSV IMMUNIZATION: BIOETHICAL AND QUALITATIVE INSIGHTS FROM NORTH PHILADELPHIA
No full textChildhood immunization remains a critical issue within the evolving landscape of public health. This thesis explores the complexities surrounding immunization acceptance, with a particular focus on the introduction of Respiratory Syncytial Virus (RSV) immunization, Beyfortus. Given the decline in childhood immunization rates across various demographics, the thesis seeks to understand the factors influencing parents' decisions regarding immunization. Through a combination of literature review and qualitative interviews, this research examines how geographic location, culture, politics, socioeconomic status, historical medical mistrust, and misinformation shape immunization hesitancy. Findings from the qualitative interviews reveal that parents' decisions are strongly influenced by personal experiences with illness and immunizations, with RSV illness driving immunization uptake and negative experiences with the COVID-19 vaccine contributing to hesitancy. Social media and political influence played a lesser role in RSV immunization compared to the COVID-19 pandemic. Trust in healthcare providers was higher than expected; however, many parents still relied on inconsistent online sources, highlighting the need for centralized, credible immunization information. Despite trust in healthcare providers, historical medical injustices and unethical practices have fostered lasting mistrust, especially within marginalized communities, which is further exacerbated by misinformation and inconsistent messaging. The thesis also explores bioethical principles in childhood immunization, particularly with respect to requiring Beyfortus for newborn RSV protection. Finally, this thesis suggests several policy implementations to increase immunization rates, including routine RSV immunization in hospitals, prenatal education, and follow-up during pediatric visits. These strategies, combined with enhanced public trust and more accurate messaging, could play a crucial role in improving immunization uptake.Urban Bioethic
DYNAMIC CAUSAL INFERENCE: METHODOLOGICAL FOUNDATIONS AND APPLICATIONS
No full textThis dissertation develops and discusses a potential outcomes causal inference framework for time series data from a foundational perspective. Causal inference, in the potential outcomes setting, is understood to be the effect of an intervention on outcomes. This intervention is what delineates causal inference from inference of association. In classical causal inference, the potential outcomes– bivariate outcomes on whether the unit receives an intervention or not– are atemporal, meaning that each unit has pre-determined outcomes that are instantaneously realized when that unit receives the intervention, or not. Randomized inference, such as randomized control trials, then defines an ideal situation for causal inference in this setting by averaging out biases that may arise from confounding effects. Much of the causal inference literature has been centered around developing methods to overcome problem settings that deviate from this ideal situation, such as propensity score analysis for when the interventions are not randomized, but are within the atemporal framework of potential outcomes. In generalizing the potential outcomes framework to time series data, the temporal nature of the data poses unique problems that have not been sufficiently addressed in the literature. For one, the core assumptions that the potential outcomes are bivariate and atemporal are violated. In a time series setting, even if the instantaneous outcomes are determined, observations continue as time progresses, with the effect itself potentially changing over time. While there have been many methods proposed for specific problems that use time series data, existing methods rely on strong assumptions that reflect the atemporal nature of the classical potential outcomes setting. As these methods are not developed from a solid foundation of temporal potential outcomes, they are often ad hoc, lack clear estimands, and result in poor modeling choices.
We propose a generalization of the potential outcome causal inference framework to estimate treatment effects in a time series context. Using stochastic process theory, we define the causal estimand for time series; the dynamic average treatment effect (DATE). The proposed DATE is defined through randomized inference, where the randomness is not only in the treatment assignment, but the potential temporal paths a unit can take. For observational data, we propose a dynamic inverse probability weighting estimator and show its unbiasedness and consistency. We use the dynamic linear model (DLM) where there are few, or one, treatment series. We show that the dynamic linear model is the best approximation of the dynamic average treatment effect in terms of quadratic loss. The flexibility and the adaptability of this framework provide a firm foundation for handling causal inference with time series data.
Chapter 1 introduces the motivation and related works in the field. In Chapter 2, a preliminary discussion differentiates time series data from i.i.d. data by exploring the complexities of time series data. The causal estimand within the potential outcome framework is the subject of Chapter 3. We use this to create estimators for specific cases and show that, in terms of quadratic loss, the dynamic linear model best approximates the dynamic average treatment effect. Chapter 4 provides the simulations study. We examine unemployment and Covid-19 lockdowns in Chapter 5 by applying economic data to the established framework. Chapter 6 employs the framework to determine the effect of drug policy on Australia’s depression medication. Chapter 7 uses the framework of public health data to assess the effect of lockdown on hospitalizations. In Chapter 8, we extend the framework to financial data to access publication on return anomalies. Finally, Chapter 9 concludes the dissertation with open questions and a discussion of potential future research.Statistic
A NEW FRAMEWORK FOR HOW THE PHYSICAL AND BUILT ENVIRONMENT AFFECTS STROKE CARE AND RECOVERY
No full textThe built environment is a well-described component of the social determinants of health. We understand the built environment to be an intermediate determinant of health when pairing this understanding with the National Institute of Neurologic Disorders and Stroke (NINDS) framework. The built environment, influenced by upstream structural racism, plays a direct mediating role on stroke risk, evident by increased stroke risk in areas heavily historically affected by redlining or slavery. When elements of the built environment are curated to promote social and physical activity, inpatient rehabilitation centers may have a more positive effect on physical and psychological recovery following a stroke. Lastly, the physical environment in a home or community setting has tremendous influence on a stroke survivor’s ability to adapt to their new motor abilities. The foundational principles of bioethics (autonomy, justice, non-maleficence and beneficence) are driven by four themes across the spectrum of stroke risk and recovery affected by the built environment: access, physical safety, health promotion and psychosocial behavior. It is therefore imperative that clinicians and scholars continue to leverage their expertise to advocate for meaningful changes specifically regarding the built environment in order to effectively tackle stroke risk and outcomes.Urban Bioethic