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Identifying Unmeasured Heterogeneity in Microbiome Data via Quantile Thresholding (QuanT)
Get PDFUnmeasured technical and biomedical heterogeneity in microbiome data can arise from differential processing and design. Uncorrected for, they can lead to spurious results. We propose the Quantile Thresholding (QuanT) approach, a comprehensive non-parametric hidden variable inference method that accommodates the complex distributions of microbial read counts. We apply QuanT to synthetic and real data sets and demonstrate its ability to identify unmeasured heterogeneity and improve downstream analysis
INVESTIGATING THE DEPENDENCY OF ANDROGEN RECEPTOR POSITIVE PROSTATE CANCER ON CLASS I MYOSINS
No full textProstate adenocarcinoma is characterized by high expression and activity of the androgen receptor (AR). AR is a nuclear hormone receptor that stimulates anabolic cell metabolism. We hypothesized that the high activity of AR in prostate cancer creates unique dependencies on cellular machinery to support this high rate of anabolism. We observed that androgen treatment of patients with metastatic castration-resistant prostate cancer resulted in increased abundance of MYO1E, a class I myosin that facilitates intracellular vesicular trafficking, in tumor biopsies. Similarly, MYO1E protein increased in AR+ prostate cancer cell lines upon treatment with androgens. Notably, a specific small molecule inhibitor of MYO1E, pentachloropseudilin (PClP), induced cell death of AR-positive prostate cancer cell lines with an IC50 of 2-4uM. Interestingly, AR inhibition did not induce resistance to PClP, which suggests AR may sensitize cells to PClP through a mechanism independent of its canonical regulation of transcription. In AR+ cell lines, PClP seemed to induce RIPK1-dependent apoptosis, as it induced cleavage of PARP and cell death could be rescued by inhibition of caspases or RIPK1. Altogether our studies suggest that class I myosins are essential in AR+ cell lines and may represent a novel drug target for prostate adenocarcinoma
Microbial Biomining of Spent Lithium-Ion Batteries
Get PDFRenewable energy’s rising need for critical metals is exposing shortcomings in the sustainability and efficacy of the existing methods of metal recycling. Common methods of lithium-ion battery recycling, such as pyrometallurgy and hydrometallurgy, are energy- intensive and hazardous to the environment, while microbial biomining, or biohydrometallurgy, can offer a more sustainable and still scalable method of hydrometallurgy. Accordingly, the cultivation of Aspergillus niger, a filamentous fungus which produces organic acids in large quantities, was tested to examine the bioacids’ ability in leaching the cathodes of spent lithium-ion batteries at a concentration of 1% (w/v). Alternative carbon sources for fungal growth (cornstarch, glycerol, molasses, and potato peels) were also explored to find opportunities to lower biomining production costs.
Combined gluconic and oxalic acid were produced at the highest concentration, 2.661 ± 0.617 g/L, in the presence of 1% (w/v) Li-NMC battery powder at inoculation and 20 g/L of glucose in MAG-V medium. The one-step strategy was most efficient at leaching spent lithium-ion batteries, with recoveries greater than 50% for cobalt, lithium, and nickel. When fed with alternative carbon sources, molasses at a concentration of 20 g/L resulted in the highest concentration of citric acid at 0.180 ± 0.026 g/L, with a lithium recovery of 22.05 ± 1.38%. The recovery of lithium was highest when glycerol acted as the substrate at 33.22 ± 3.02%. These findings demonstrate that alternative carbon sources, particularly glycerol, can be successful substrates for A. niger cultures in the bioleaching of spent-lithium batteries
The public–private partnerships in healthcare sector in China：Insights from case studies
No full textDue to constantly rising prices, changing disease patterns and increasing use of sophisticated technology for diagnosis and treatment have made it virtually impossible to imagine any single organization providing services without some type of institutional partnership. Current concerns about government spending and health care costs also make the time ripe for PPPs. The PPP model allows health care officials to share the risk of building new facilities with the private sector. Public-private partnerships help both public and private agencies build on the capabilities of others, leverage collective action, improve performance, and realize cost savings. Public-private partnerships are one of the most promising models for financing successful health care innovations. With the springing of the strongly favorable policy from 2013, PPP has welcomed its own spring in China. The objective of this study is to evaluate the PPP in healthcare sector in China, and to investigate the successful factors and best practice of PPP. Specifically, there are three study aims. First, the study is design to systematically review the evolution and current status of public and private hospitals development in China. Second, to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China. Third, to develop best practice models of PPP among hospitals of China. I will conduct a multiple-case design, the generalizability of constructs and themes across cases can be checked. This could include whether a particular theme observed in one case was also present in other cases. The research literature on PPPs is in its nascent stages and lacks systematic and thorough analyses. Some case studies are provided, but there is little in-depth comparative research or multi-cases studies. Our study is design to bridge the knowledge gap, to evaluate the PPP in healthcare sector in China, and to conclude policy implications on best practice of PPP. I found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure—potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes
Development of a Guidebook for the Onboarding of University Subaward Administrators
Get PDFThe management of subawards within research institutions presents a complex administrative challenge, requiring specialized expertise and attention. This thesis delves into the crucial aspect of onboarding and training for subaward administrators to alleviate the burden on faculty and staff and enhance overall research administration efficiency.
The absence of specialized subaward staff exacerbates administrative burdens, leading to decreased efficiency and heightened frustration among faculty and staff. There is a gap in literature regarding the onboarding and training of subaward administrators, indicating a need for focused research in this area.
Employing an anonymous questionnaire distributed through relevant professional networks, this study gathers insights from 143 respondents involved in subaward administration. The data collected sheds light on key challenges subaward administrators face and informs actionable recommendations for improving training and support mechanisms. Analysis of the questionnaire data reveals recurring themes and issues, providing a comprehensive understanding of the training needs and experiences of subaward administrators. This research identifies areas for improvement in current training practices and offers practical solutions to enhance the effectiveness of subaward administration.
This thesis aims to facilitate the implementation of its findings, ultimately alleviating the administrative burden associated with subaward management and enhancing overall research administration within institutions. Through targeted training and support, research institutions can ensure that they develop skilled subaward administrators capable of efficiently managing the complexities of research awards
Star Formation at the Extreme: The Low-Mass Stellar Initial Mass Function in a Sample of Ultra-Faint Dwarf Galaxies
Get PDFThe stellar initial mass function (IMF) describes the distribution of single stellar masses formed in a given star formation event. The IMF has far-reaching implications for many sub-fields of astrophysics. Despite decades of study, it remains uncertain what physical mechanisms or properties determine the IMF. Thanks to the long main-sequence lifetimes of low-mass stars, essentially all low-mass stars that were ever born are still alive today. Thus, at the low-mass end (below one solar mass), the IMF can be constrained with star-count based techniques. Such analyses in the Milky Way have found that there is a `typical' IMF that describes the stellar populations of the Milky Way, regardless of age, metallicity, et cetera. It is unclear whether star formation in more extreme conditions should also follow the typical Milky Way IMF. In this dissertation, I investigate the IMF in nearby extreme environments: ultra-faint dwarf (UFD) galaxies. These galaxies are low-luminosity, ancient, and metal-poor. I use deep imaging from the Hubble Space Telescope along with forward modeling to constrain the low-mass IMF in a sample of five nearby UFD galaxies: Boötes I, Reticulum II, Ursa Major II, Triangulum II, and Segue 1. The analysis techniques that I adopt depend on the number of low-mass stars in each sample. All five galaxies have a sufficient number of stars to use Kolmogorov-Smirnov (KS) tests to determine whether their observed apparent magnitude distributions reject a given IMF and binary fraction for the underlying population. I find that all five galaxies reject a variety of low-mass IMFs, but those that they cannot reject include IMFs that are identical, or similar, to the typical Milky Way IMF. I also determine the best-fit parameter values for standard functional forms of the IMF for Boötes I, Reticulum II and Ursa Major II. I find that the low-mass IMF in Boötes I and Reticulum II is generally consistent with the typical Milky Way IMF, but that Ursa Major II favors a bottom-heavy IMF. The interpretation of the results for Ursa Major II is complicated by the known presence of background galaxy clusters, which could contribute enhanced contamination
The Effects of Drug-Drug Interactions Between Direct-Acting Oral Anticoagulants and Antiseizure Medications: A Target Trial Emulation
Get PDFAll direct oral anticoagulants (DOAC) and some antiseizure medications (ASM) interact with cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp). Concomitant use of these medications may cause drug-drug interactions that increase the risk for thromboembolism. Existing studies assessing this association are conflicting, limited by small sample size, or are conducted on non-US populations.
This new-user, retrospective cohort study emulates a target trial using Merative MarketScan insurance claims data from 2011 to 2019. We included US adults currently using a DOAC who initiated treatment with an ASM that interacts with CYP3A4 or P-gp or an ASM that does not interact with CYP3A4 or P-gp. We excluded persons who were not continuously insured for a year prior to the start of follow-up or who had history of concomitant DOAC and ASM use. We evaluated time-to-event for thromboembolism as well as the incidence rate in this taking interacting and non-interacting drug combinations. We calculated inverse probability of treatment weights using baseline age, sex, comorbidities, and comedications. We used these in a weighted Cox regression to compute an adjusted hazards ratio.
Among the 33,117 participants included in the study, 5,388 (16%) initiated an interacting drug combination and 27,729 (84%) initiated a non-interacting drug combination. The incidence of thromboembolism per 100 person-years was 2.01 (95% CI: 0.51, 8.01) in the interacting group and 0.88 (95% CI: 0.11, 7.11) in the non-interacting group. After weighting, we found that those taking an interacting combination had 1.46 (95% CI: 0.85, 2.51) times the hazard for a thromboembolic event compared to those taking a non-interacting combination.
Among US adults, concomitantly using a DOAC with an antiseizure medication that interacts with P-gp and CYP3A4 appeared to increase the risk for thromboembolism, but the effect did not achieve statistical significance, possibly due to the limited event count. Additional studies collecting more events are needed to confirm the results of this study
APPLIED PROJECT: AlgebraByExample + PROFESSIONAL DEVELOPMENT ADDRESSING SELF-EFFICACY AND ACHIEVEMENT GAP IN MATHEMATICS
No full textABSTRACT
The achievement gap in mathematics for African American students is a multifaceted and pervasive problem that has persisted for years and continues to be an issue today. Of particular concern is the gap in algebra 1 achievement. This document presents a potential intervention to mitigate the achievement gap in algebra 1 and improve the performance of all algebra 1 students. The intervention is in the form of a specifically designed professional development that instructs teachers on implementing AlgebraByExample in their classrooms. AlgebraByExample leverages cognitive load theory and might improve teachers’ and students’ academic self-efficacy in order to reciprocally impact algebra 1 achievement, instruction, and capacity. All data used in this research was taken from publicly available sources including the Maryland State Department of Education (MSDE) and the Montgomery County Public Schools (MCPS). To address the significant and protracted achievement gap in algebra 1 proficiency for minority students, particularly African American 8th grade students, an extensive needs assessment was conducted. Analysis of extant data was conducted using algebra1 proficiency rates of MCPS middle school students, including racial subgroups, and selected items from the MCPS Climate Survey. It was found that by using worked examples one might reduce cognitive load for both teachers and students. This reduction in cognitive load and increase in Germane resources might mitigate student achievement and improve teacher instruction. AlgebraByExample is a strategy that uses worked examples and reduces cognitive load that can be taught to teachers through effective professional development. An extensive description of this intervention (AlgebraByExample plus professional development) is included in the Appendix.
Advisors: E. Juliana Pare-Blagoev, Chrissy Eith, Cynthia Web
ORAL HEALTHCARE REFORM: ACCESS TO ORAL HEALTHCARE SHOULD BE EQUIVALENT TO THAT OF GENERAL HEALTH CARE
Get PDFOn a frigid February morning, twelve-year-old Maryland schoolboy Deamonte Driver died of a toothache. A routine eighty-dollar extraction could have saved his life; however, by the time his toothache got any attention, the bacterial abscess from the tooth had already traveled to his brain, requiring two invasive brain surgeries. Like many other Americans, Deamonte's family depended on Medicaid insurance for dental healthcare access, but finding dentists who accept Medicaid proved virtually insurmountable1.
This thesis argues for oral health care reform that would elevate it to the same status as overall healthcare. I explore the historical interconnection between general medicine and dentistry as medical practices, delineating their subsequent evolution into separated fields. Then, I accentuate the importance of oral health care through a biopsychosocial approach while also highlighting the consequences related to barriers to oral health access. Furthermore, I propose that an extensive package of preventative dental services be included in healthcare insurance initiatives such as Medicaid for all population ages
Investigations of How Matrix Stiffness Modulates the Cellular Senescence-Associated Phenotypes
No full textCellular senescence is an established driver of aging and a natural cellular mechanism responsible for wound healing and tissue homeostasis. Associated with a wide range of human pathologies such as cancer and tissue fibrosis, senescence phenotype presents a pleiotropic response supporting both tissue function and disease progression. This pleiotropic property of cellular senescence emphasizes the importance of discerning physiological from pathological senescence. Senescence, a hallmark property of aging, is characteristically defined in vitro by the loss of physiological functions such as proliferation, an active secretory profile known as senescence-associated secretory phenotype (SASP), accumulation of senescence-associated-β-galactosidase (SA-β-gal), upregulation of cell cycle-inhibitory proteins, P16INK4A and P21Waf1/Cip1, as well as morphological alterations including enlarged, flattened nucleus and cell bodies. Due to the lack of non-invasive methods for the sensitive and specific identification of senescence, detection of those molecular analogs remains the most used method to identify senescence both in vitro and in vivo. However, the expression of these molecular analogs varies drastically among tissue types. While it is accepted that the mechanical properties of tissue are spatially heterogeneous, the role tissue mechanics have on the development and identification of the senescent phenotype remains underexplored. Here, I utilize two fibroblast cell lines to explore the biophysical role of tissue mechanics on cellular senescence induction and response. Using high-throughput, single-cell imaging platforms, this work reveals the regulatory role of matrix stiffness on both onset and identification of the senescence phenotype