DATA ANALYSIS WORKFLOW FOR GAS CHROMATOGRAPHY MASS SPECTROMETRY-BASED METABOLOMICS STUDIES

Metabolomics has emerged as an integral part of systems biology research that attempts to comprehensively study low molecular weight organic and inorganic metabolites under certain conditions within a biological system. Technological advances in the past decade have made it possible to carry out metabolomics studies in a high- throughput fashion using gas chromatography coupled with mass spectrometry. As a result, large volumes of data are produced from these studies and there is a pressing need for algorithms that can efficiently process and analyze the data in a high-throughput fashion as well. To address this need, we have developed computational algorithms and the associated software tool named an Automated Data Analysis Pipeline (ADAP). ADAP allows data to flow seamlessly through the data processing steps that include de- nosing, peak detection, deconvolution, alignment, compound identification and quantitation. The development of ADAP started in 2009 and the past four years have witnessed continuous improvements in its performance from ADAP-GC 1.0, to ADAP- GC 2.0, and to the current ADAP-GC 3.0. As part of the performance assessment of ADAP-GC, we have compared it with three other software tools. In this dissertation, I will present the computational details about these three versions of ADAP-GC, the capabilities of the software tool, and the results from software comparison

Mortgage Choice, House Price Externalities, and The Default Rate

We study the pathways by which borrowers and lenders influence house prices and default rates via their choices and offerings of fixed-rate and adjustable-rate mortgage products (FRMs and ARMs) in a two-period setting. We extend previous literature on mortgage choice as a tool for borrower risk screening under asymmetric information by incorporating house price externalities. The novelty in our setup is that house prices in the second period are negatively affected by the first-period default rate. We show that when these negative externalities are large, lenders may benefit by offering a lower ARM rate. This outcome, in turn, influences the likelihood of a separating equilibrium in which high-risk (low-risk) borrowers choose ARMs (FRMs) relative to a pooling equilibrium in which both high-risk and low-risk borrowers receive the same contract. When the impact of the negative house price externalities is small, it is more likely that lenders will offer pooling contracts; however, when the impact of the house price externalities is large, it is more likely that lenders will offer separating contracts. We also compare the equilibrium default rates across different contract offerings and find that when the negative house price externalities are large, the pooling FRM contract or the separating contract tends to offer the lowest default rate; however, when the negative house price externalities are small, the pooling ARM contract may result in the lowest default rate

Maternal Pre-Pregnancy BMI, Gestational Weight Gain, And Infant Birth Weight: A Within-Family Analysis In The United States

In the United States, the high prevalence of unhealthy preconception body weight and inappropriate gestational weight gain among pregnant women is an important public health concern. However, the relationship among pre-pregnancy BMI, gestational weight gain, and newborn birth weight has not been well established. This study uses a very large dataset of sibling births and a within-family design to thoroughly address this issue. The baseline analysis controlling for mother fixed effects indicates maternal preconception overweight, preconception obesity, and excessive gestational weight gain significantly increase the risk of having a high birth weight baby, respectively, by 1.3, 3 and 3.9 percentage points, while underweight before pregnancy and inadequate gestational weight gain increase the low birth weight incidence by 1.4 and 2 percentage points. The benchmark results are robust in a variety of sensitivity checks. Since poor birth outcomes especially high birth weight and low birth weight have lasting adverse impacts on one’s health, education, and socio-economic outcomes later in life, the findings of this research suggest promoting healthy weight among women before pregnancy and preventing inappropriate weight gain during pregnancy can generate significant intergenerational benefits

Prenatal Smoking Cessation and Infant Health: Evidence from Sibling Births

This article uses a large data set of sibling births to examine when mothers must quit smoking in pregnancy to deliver healthy babies. It applies sibling fixed effects models to provide robust evidence that smoking cessation in the first trimester has a negligible effect on infant health, but cessation as late as second trimester or smoking throughout pregnancy is associated with substantially lower birth weights and higher risks of delivering low birth weight babies. In particular, about two thirds of the total detrimental smoking impact on birth outcomes occurs in the second trimester. Therefore, reallocating resources on prenatal smoking cessation towards the first trimester can lead to a significant efficiency gain. This study also shows when the timing information of prenatal smoking cessation is improperly used, it will introduce a new nontrivial downward bias in estimating the causality between the conventionally used group measure "prenatal smoker" and infant health

The Effects Of Prenatal Care Utilization On Maternal Health And Health Behaviors

While many economic studies have explored the role of prenatal care in infant health production, the literature is sporadic on the effects of prenatal care on the mother. This research contributes to this understudied but important area using a unique large dataset of sibling newborns delivered by 0.17 million mothers. We apply within-mother estimators to find robust evidence that poor prenatal care utilization due to late onset of care, low frequency of care visits, or combinations of the two significantly increases the risks of maternal insufficient gestational weight gain, prenatal smoking, premature rupture of membranes, precipitous labor, no breastfeeding, postnatal underweight, and postpartum smoking. The magnitude of the estimates relative to the respective sample means of the outcome variables ranges from 3% to 33%. The results highlight the importance of receiving timely and sufficient prenatal care in improving maternal health and health behaviors during pregnancy as well as after childbirth

Time-inconsistent Preference and Reference Dependence

The paper explains time-inconsistent preferences by particularly focusing on the concept of reference dependence. The objective is to propose a short survey on various features of reference dependence and different causes that lead to the change of reference level. The emphasis of the paper is on the interpretation of the concepts and their behavioral implications

Timing Of Prenatal Smoking Cessation Or Reduction And Infant Birth Weight: Evidence From The United Kingdom Millennium Cohort Study

Smoking during pregnancy is a key contributor to poor infant health. Our study presents a dynamic relationship between the timing of prenatal smoking cessation or reduction and infant birth weight. Using a large representative dataset of a birth cohort in the United Kingdom, we apply regression analysis to examine the influences of cessation in smoking or reduction in smoking intensity at different months or trimesters on infant birth weight. For robustness checks, we use a rich set of additional covariates, a series of variable selection procedures, alternative birth outcome measures, and stratified samples. We find robust evidence that mothers who quit smoking by the third month of pregnancy or the end of the first trimester have infants of the same weight as those infants of nonsmokers. However, we find smoking cessation in the fourth month or any time beyond is associated with substantially lower infant birth weights. Two-thirds of the total adverse smoking impact on infant birth weight occurs in the second trimester. Our study also shows mothers who smoke throughout pregnancy but cut smoking intensity by the third month in pregnancy deliver infants of the same weight as those infants born to persistent light smokers. Our research suggests the efficacy of prenatal smoking cessation services can be significantly improved, if health professionals can encourage more pregnant women to quit smoking or reduce smoking intensity timely by the end of the first trimester

Firm Characteristics and Stock Returns during 2008 Financial Crash

The purpose of this paper is to study the characteristics of firms that reported positive price movements during the 2008 crash. In the last decade, the stock market had two crashes; the first one occurred in year 2000 and the second one occurred in year 2008, where the stock market lost more than 50% of its value and shook the global economy. The study highlights the financial characteristics of those firms that reported positive price movements during the 2008 crash period, tests their significance, and attempts to explain their underlying reasons. The study employs both fundamental and market measures. In particular, we study if there is a significant difference between the financial structure of health sector and other sectors, and among the groups of firms within the health sector

VASP Activation via the Gα13/RhoA/PKA Pathway Mediates Cucurbitacin-B-Induced Actin Aggregation and Cofilin-Actin Rod Formation

Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either Gα13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the Gα13/RhoA/PKA/VASP pathway

Necrotizing enterocolitis leads to disruption of tight junctions and increase in gut permeability in a mouse model

Background: Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Neonates weighing <1500 grams are at the highest risk for acquiring NEC, with a prevalence of nearly 7-10%, mortality up to 30%, and several long-term complications among survivors. Despite advancements in neonatal medicine, this disease remains a challenge to treat. The aim of this study is to investigate the effect of NEC on gut epithelial tight junctions and its barrier function using a NEC mouse model. Methods: Three-day old C57BL/6 mouse pups were fed with Esbilac formula every 3 hours and then subjected to hypoxia twice daily followed by cold stress. Dam fed pups from the same litters served as controls. Pups were observed and sacrificed 96 hours after the treatments and intestines were removed for experiments. The successful induction of NEC was confirmed by histopathology. Changes in tight junction proteins in NEC intestines were studied by western blotting and immunofluorescent microscopy using specific protein markers. The gut leakage in NEC was visualized using biotin tracer molecules. Results: Our study results demonstrate that we induced NEC in >50% of experimental pups, pups lost nearly 40% of weight and their intestines showed gross changes and microscopic changes associated with NEC. There were inflammatory changes with loss of tight junction barrier function and disruption of tight junction claudin proteins in the intestines of NEC mouse model. We have demonstrated for the first time that NEC intestines develop increased leakiness as visualized by biotin tracer leakage. Conclusions: NEC leads to breakdown of epithelial barrier due to changes in tight junction proteins with increased leakiness which may explain the transmigration of microbes and microbial products from the gut lumen into the blood stream leading to sepsis like signs clinically witnessed