Master of Arts

thesisRecent scholarship has explored the expansion of the Ming and Qing States into the southwest borderlands which became Guizhou and Yunnan Provinces. While many scholars have focused on the effect this expansion had on both the area's non-Chinese inhabitants and the imperial officials and military officers trying to administer them, little attention has been paid to the millions of Chinese who immigrated to the region during the eighteenth and nineteenth centuries. This paper examines the formation of Han Chinese identity among these immigrants by analyzing local gazetteers (difangzhi) produced during the Qing era. The purpose of the paper is to examine the aims of gazetteer production; particularly during times of social unrest and violent conflict. The primary sources utilized are two gazetteers from Qianxi Department in Guizhou Province: one published in 1835 and one published in 1884. By comparing the format and content of the Qianxi gazetteers produced before and after the "Miao rebellion" of the 1850s, this paper seeks to explore these documents not only as references but as actual tools of empire. Employing this approach, the research demonstrates that the production of these gazetteers was a conscious act requiring the cooperation of local elites who utilized the process to demonstrate their loyalty to the state while simultaneously imagining themselves as part of a larger Han Chinese identity group

The genetic basis of thyroid function: Novel findings and new approaches

Context: Genetic factors are major determinants of thyroid function. Over the last two decades,multiple genetic variants have been associated with variations in normal range thyroid functiontests. Most recently, a large-scale genome-wide association study (GWAS) doubled the number ofknown variants associated with normal range thyrotropin (TSH) and free thyroxine (FT4) levels.Evidence Acquisition: This review summarizes the results of genetic association studies onnormal range thyroid function and explores how these genetic variants can be used in futurestudies to improve our understanding of thyroid hormone regulation and disease.Evidence Synthesis: Serum TSH and FT4 levels are determined by multiple genetic variantson virtually all levels of the hypothalamus-pituitary-thyroid (HPT) axis. Functional followup studies on top of GWAS hits has the potential to discover new key players in thyroidhormone regulation, as exemplified by the identification of the thyroid hormone transporterSLC17A4 and the metabolizing enzyme AADAT. Translational studies may use these geneticvariants to investigate causal associations between thyroid function and various outcomes inMendelian Randomization (MR) studies, to identify individuals with an increased risk of thyroiddysfunction, and to predict the individual HPT axis setpoint.Conclusions: Recent genetic studies have greatl

Mendelian randomization indicates causal effects of estradiol levels on kidney function in males

ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.DesignWe performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (n = 206,927) and women (n = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, n = 567,460), urine albumin-to-creatinine ratio (UACR, n = 547,361), and CKD (n = 41,395 cases and n = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (n = 11,798 men and n = 6,835 women) to identify novel genetic associations with levels of estradiol, and then used these variants as instruments in a one-sample MR.ResultsThe two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; p = 5.2E-05). We identified a single locus at chromosome 14 associated with estradiol levels in men being significant in the one-sample MR on eGFR (beta = 0.199; p = 0.017). We revealed significant results with eGFR in postmenopausal women and with UACR in premenopausal women, which did not reach statistical significance in the sensitivity MR analyses. No causal effect of eGFR or UACR on estradiol levels was found.ConclusionsWe conclude that serum estradiol levels may have a causal effect on kidney function. Our MR results provide starting points for studies to develop therapeutic strategies to reduce kidney disease

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed > 50 loci at which common variants with minor allele frequency > 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 x 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria

Feasibility Study for a Chemical Process Particle Size Characterization System for Explosive Environments Using Low Laser Power

The industrial particle sensor market lacks simple, easy to use, low cost yet robust, safe and fast response solutions. Towards development of such a sensor, for in-line use in micro channels under continuous flow conditions, this work introduces static light scattering (SLS) determination of particle diameter using a laser with an emission power of less than 5 µW together with sensitive detectors with detection times of 1 ms. The measurements for the feasibility studies are made in an angular range between 20° and 160° in 2° increments. We focus on the range between 300 and 1000 nm, for applications in the production of paints, colors, pigments and crystallites. Due to the fast response time, reaction characteristics in microchannel designs for precipitation and crystallization processes can be studied. A novel method for particle diameter characterization is developed using the positions of maxima and minima and slope distribution. The novel algorithm to classify particle diameter is especially developed to be independent of dispersed phase concentration or concentration fluctuations like product flares or signal instability. Measurement signals are post processed and particle diameters are validated against Mie light scattering simulations. The design of a low cost instrument for industrial use is proposed

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/thy.2020.0393

A bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure

Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM