Evaluating and Prioritizing Duke’s Natural Landscapes

Duke University prides itself as being a “university in a forest”. But, Duke must also continue to advance its academic mission, provide space for the world-renowned hospital system, and a myr-iad of other things. In order to inform built environment planning and natural resource manage-ment decisions, our work provides a framework with which to evaluate natural spaces on Duke’s campus and offers a relative value (high, medium, low) of these spaces based on five key crite-ria: ecological, programmatic, cultural, pedagogical, and aesthetic values. The study was carried out at the request of, and with feedback from, the University’s Campus Sustainability Committee and its Natural Resources Subcommittee. We then tested the validity of the framework on a test site on campus. We believe the framework can be used to further the conversation about Duke’s natural areas, and that it will be a useful tool in campus development decisions

Modulation of immunity by tryptophan microbial metabolites

Tryptophan (Trp) is an essential amino acid that can be metabolized via endogenous and exogenous pathways, including the Kynurenine Pathway, the 5-Hydroxyindole Pathway (also the Serotonin pathway), and the Microbial pathway. Of these, the Microbial Trp metabolic pathways in the gut have recently been extensively studied for their production of bioactive molecules. The gut microbiota plays an important role in host metabolism and immunity, and microbial Trp metabolites can influence the development and progression of various diseases, including inflammatory, cardiovascular diseases, neurological diseases, metabolic diseases, and cancer, by mediating the body’s immunity. This review briefly outlines the crosstalk between gut microorganisms and Trp metabolism in the body, starting from the three metabolic pathways of Trp. The mechanisms by which microbial Trp metabolites act on organism immunity are summarized, and the potential implications for disease prevention and treatment are highlighted

Explain the US Stock Market’s Evolution during the COVID-19 Pandemic: Using SVIX Index

I exploit Martin’s (2016) proxy of the equity premium to examine the reasons behind the US stock market evolution during the COVID-19 pandemic. Based on Knox and Vissing-Jorgensen’s (2021) decomposition of unexpected stock returns, I present that changes in the short-term equity premium can explain 58%–65% of the stock market evolution. I further construct an index (CARS) to reveal households’ concerns about coronavirus using Google search as in Da et al. (2014). Results show that a standard deviation increase in CARS coincides with an increase of 7.05 basis points of contemporary change in the 1-month equity premium. My findings indicate that policymakers and investors should pay attention to aggregate market fears about the pandemic or other crisis events in the future. Additionally, the equity premium from 1996 to 2020 illustrates that the US stock market has different regimes during crisis and non-crisis periods, and the term structure of equity premium is procyclical

The Combined Effects of Arsenite and Ethanol on Brain Endothelial Cells and Microglial Cells

Arsenic (As) is a natural compound widely distributed in air, water, and soil. Drinking ground water is the major source of As exposure. As exposure causes many health issues, including nausea, vomiting, pain, diarrhea, cancer and neurotoxicity [1]. Alcohol drinks may also contain As because grapes and rice which are used in making wine and beer, take up As from soil, water, and fungicides containing As. Emerged evidence showed that ethanol (EtOH) also impairs neurological functions [2]. However, the combined toxic effects of As and EtOH on the brain is still unclear. Our long-term goal is to understand the effects of As combined with EtOH on the blood brain barrier (BBB). The BBB controls molecule exchange between peripheral and cerebral compartments [3]. Alterations of the BBB are a critical risk factor of pathology and progression of different neurological diseases [4]. Many studies have shown that As as well as EtOH induced BBB abnormalities [5, 6]. Since brain endothelial cells play a crucial role in the BBB, we used Rat Brain Endothelia (RBE4) cells to investigate the combined toxic effects of As and EtOH on the BBB. Overproduction of reactive oxygen species (ROS) results in destruction of cellular structures, lipid, and proteins [7]. Previously, our lab showed that As increased endothelial cell permeability through a ROS-vascular endothelial growth factor pathway in mouse brain vascular endothelial cells (bEnd 3 cells) [8]. Others have shown that EtOH also impairs the barrier function and junctional organization of human brain microvascular endothelial cell monolayer [9]. In neurons, EtOH-induced ROS mainly come from damaged mitochondria [10]. Since mitochondria are major source of ROS generation, we proposed that As-EtOH-combined treatment impairs the BBB through ROS released by damaged mitochondria. Mitochondrial oxidative stress affected microglia-associated neurodegenerative diseases through their role as pro-inflammatory molecules and modulators of pro-inflammatory processes [11]. BBB disruption is mediated by neuroinflammation which is associated with increase in pro-inflammatory cytokines [12]. Research showed that inflammatory mediators control BBB permeability through regulating the structural components [13]. As induced cytotoxicity in brains via regulation of oxidative stress and TNF-a associated inflammatory pathways [14]. Alcohol consumption enhanced oxidative and inflammatory stress, resulting in cognitive deficit [15]. Since microglial cells are the main effectors in the inflammatory process of the central nervous system [16], we used microglial cells (BV2) to investigate the combined effects of As and EtOH on microglia. Our results showed that As and EtOH increased RBE4 cell monolayer permeability. As-EtOH combined treatment increased the permeability more than As or EtOH treatment alone. RBE4 cells and BV2 cells showed an increase in ROS by the combined treatment. Mitochondrial ROS generation was increased by the combined treatment of As and EtOH but reduced by antioxidant Tempol in RBE4 cells and microglia BV2 cells. The combined treatment of As and EtOH decreased mitochondrial bioenergetics (mtBE) in RBE4 cells but increased by antioxidant Tempol. BV2 cells viability decreased as As or EtOH concentration increased and further decreased by the combined treatment. In conclusion, our results suggest that the combined treatment of As and EtOH induced toxicity on both endothelial cells and microglial cells via increased oxidative stress induced by mitochondrial dysfunction

METHODS IN RANDOMIZATION BASED ANCOVA FOR NOVEL CROSSOVER DESIGNS AND SENSITIVITY ANALYSIS FOR MISSING DATA

In clinical trials, statistical inference is preferably conducted with less stringent assumptions. This dissertation proposes a non-parametric method for dichotomous and ordinal missing data, and it proposes a structure for the hypothesis testing and estimation for innovative crossover designs. When data missing not at random (MNAR) arise from randomized multi-visit, multi-center clinical trials, sensitivity analyses to address possibly informative missing are needed. We propose a closed form point and variance matrix estimation for dichotomized missing data by probabilistically redistributing missing counts, adjusting for a stratification factor and/or baseline covariables. The parameter estimates are computed via weighted least squares asymptotic regression through randomization based methods. We further extend the methods to sensitivity analyses for ordinal endpoints. A novel crossover design, the sequential parallel comparison design (SPCD), where information from placebo responders in the second period are excluded, serves as a design for studies with high placebo response. Estimators for sources of comparison in the traditional SPCD design, as well as other sources of information that are available, are constructed with methods based on the randomization distribution of the observed population using the nonparametric mean and variance estimates under the null hypothesis, which control Type I error well in hypothesis testing. Baseline imbalance is adjusted by randomization-based ANCOVA. Simulations are performed to study the statistical properties of the proposed methods, which are compared to those of a repeated measures model proposed by Doros et al. (2013). Point and confidence interval estimation is also addressed by assuming the study population comes from a simple random sample of an almost infinite population. A consistent covariance matrix estimator is constructed and properties of the proposed estimators are studied with simulations, particularly for coverage of confidence intervals. The nominal coverage level is achieved with a t distribution for the approximation to the asymptotic distribution when the sample size is not sufficiently large. The methodologies are extended to the two-way enrichment design (TED) introduced by Ivanova and Tamura (2011), and to a related bilateral design that applies the four sequence group design to two sides of the same subject instead of two periods.Doctor of Philosoph

Acetylshikonin Sensitizes Hepatocellular Carcinoma Cells to Apoptosis through ROS-Mediated Caspase Activation

This work is licensed under a Creative Commons Attribution 4.0 International License.The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown strong and explicit cancer cell-selectivity, which results in little toxicity toward normal tissues, and has been recognized as a potential, relatively safe anticancer agent. However, several cancers are resistant to the apoptosis induced by TRAIL. A recent study found that shikonin b (alkannin, 5,8-dihydroxy-2-[(1S)-1-hydroxy-4-methylpent-3-en-1-yl]naphthalene-1,4-dione) might induce apoptosis in TRAIL-resistant cholangiocarcinoma cells through reactive oxygen species (ROS)-mediated caspases activation. However, the strong cytotoxic activity has limited its potential as an anticancer drug. Thus, the current study intends to discover novel shikonin derivatives which can sensitize the liver cancer cell to TRAIL-induced apoptosis while exhibiting little toxicity toward the normal hepatic cell. The trypan blue exclusion assay, western blot assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay as well as the ‘comet’ assay, were used to study the underlying mechanisms of cell death and to search for any mechanisms of an enhancement of TRAIL-mediated apoptosis in the presence of ASH. Herein, we demonstrated that non-cytotoxic doses of acetylshikonin (ASH), one of the shikonin derivatives, in combination with TRAIL, could promote apoptosis in HepG2 cells. Further studies showed that application of ASH in a non-cytotoxic dose (2.5 μM) could increase intracellular ROS production and induce DNA damage, which might trigger a cell intrinsic apoptosis pathway in the TRAIL-resistant HepG2 cell. Combination treatment with a non-cytotoxic dose of ASH and TRAIL activated caspase and increased the cleavage of PARP-1 in the HepG2 cell. However, when intracellular ROS production was suppressed by N-acetyl-l-cysteine (NAC), the synergistic effects of ASH and TRAIL on hepatocellular carcinoma (HCC) cell apoptosis was abolished. Furthermore, NAC could alleviate p53 and the p53 upregulated modulator of apoptosis (PUMA) expression induced by TRAIL and ASH. Small (or short) interfering RNA (siRNA) targeting PUMA or p53 significantly reversed ASH-mediated sensitization to TRAIL-induced apoptosis. In addition, Bax gene deficiency also abolished ASH-induced TRAIL sensitization. An orthotopical HCC implantation mice model further confirmed that co-treated ASH overcomes TRAIL resistance in HCC cells without exhibiting potent toxicity in vivo. In conclusion, the above data suggested that ROS could induce DNA damage and activating p53/PUMA/Bax signaling, and thus, this resulted in the permeabilization of mitochondrial outer membrane and activating caspases as well as sensitizing the HCC cell to apoptosis induced by TRAIL and ASH treatment

Analysis of OAM Mode Purity in Phased Array Antenna

In this paper, the orbital angular momentum of different modes in electric field is decomposed, and the definition of purity of OAM mode in OAM antenna are proposed. Based on the purity theory, the purity of circular array is derived. And the effects of different parameters on the purity are analyzed. An intuitive and quantifiable dimension for comparing the OAM performance in phased array antenna is provided in this paper

Subsonic steady-states for bipolar hydrodynamic model for semiconductors

In this paper, we study the well-posedness, ill-posedness and uniqueness of the stationary 3-D radial solution to the bipolar isothermal hydrodynamic model for semiconductors. The density of electron is imposed with sonic boundary and interiorly subsonic case and the density of hole is fully subsonic case

Single-shot quantitative differential phase contrast imaging combined with programmable polarization multiplexing illumination

We propose a single-shot quantitative differential phase contrast (DPC) method with polarization multiplexing illumination. In the illumination module of our system, the programmable LED array is divided into four quadrants and covered with polarizing films of four different polarization angles. We use a polarization camera with polarizers before the pixels in the imaging module. By matching the polarization angle between the polarizing films over the custom LED array and the polarizers in the camera, two sets of asymmetric illumination acquisition images can be calculated from a single-shot acquisition image. Combined with the phase transfer function, we can calculate the quantitative phase of the sample. We present the design, implementation, and experimental image data demonstrating the ability of our method to obtain quantitative phase images of the phase resolution target, as well as Hela cells.Comment: 5 pages,4figure