Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study

BackgroundAging is a significant risk factor for many neurodegenerative diseases and neurological tumors. Previous studies indicate that the frailty index, facial aging, telomere length (TL), and epigenetic aging clock acceleration are commonly used biological aging proxy indicators. This study aims to comprehensively explore potential relationships between biological aging and neurodegenerative diseases and neurological tumors by integrating various biological aging proxy indicators, employing Mendelian randomization (MR) analysis.MethodsTwo-sample bidirectional MR analyses were conducted using genome-wide association study (GWAS) data. Summary statistics for various neurodegenerative diseases and neurological tumors, along with biological aging proxy indicators, were obtained from extensive meta-analyses of GWAS. Genetic single-nucleotide polymorphisms (SNPs) associated with the exposures were used as instrumental variables, assessing causal relationships between three neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis), two benign neurological tumors (vestibular schwannoma and meningioma), one malignant neurological tumor (glioma), and four biological aging indicators (frailty index, facial aging, TL, and epigenetic aging clock acceleration). Sensitivity analyses were also performed.ResultsOur analysis revealed that genetically predicted longer TL reduces the risk of Alzheimer’s disease but increases the risk of vestibular schwannoma and glioma (All Glioma, GBM, non-GBM). In addition, there is a suggestive causal relationship between some diseases (PD and GBM) and DNA methylation GrimAge acceleration. Causal relationships between biological aging proxy indicators and other neurodegenerative diseases and neurological tumors were not observed.ConclusionBuilding upon prior investigations into the causal relationships between telomeres and neurodegenerative diseases and neurological tumors, our study validates these findings using larger GWAS data and demonstrates, for the first time, that Parkinson’s disease and GBM may promote epigenetic age acceleration. Our research provides new insights and evidence into the causal relationships between biological aging and the risk of neurodegenerative diseases and neurological tumors

Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study

BackgroundMeningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear.MethodMendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It’s a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome.ResultsThis research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-β, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood.ConclusionThese findings suggest that TNF-β, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Three essays on finance

In Chapter 1, using large lottery jackpots on Saturday as repeated exogenous shocks to investor attention, we find that the Monday effect of market return and the Monday effect of anomalies only exist on Mondays with a large jackpot on the preceding Saturday. For example, the Monday effect of high idiosyncratic volatility stocks is a striking - 64 bps when there was a large Saturday jackpot but is negligible otherwise. This is consistent with the hypothesis that individual investors allocate the weekends to process information and decide on trading strategies. Large jackpots during the weekends distract individual investors’ attention from the stock market, resulting in less buying relative to selling, lower return and larger stock co-movement on the following Monday. The jackpot effect is larger among stocks preferred by individual investors. Interestingly, we do not find similar jackpot effect on weekday drawings. In Chapter 2, we study the real effects of foreign exchange hedging on corporate innovation. Under the information asymmetry hypothesis, corporate hedging reduces firm’s information asymmetry, and alleviates manager’s career concern from undervaluation and helps investors to better monitor the manager, which in turn increases innovation. Under the market pressure hypothesis, hedging imposes more short-term earnings pressure on managers because of mark-to-market hedge accounting, hence leads to lower innovation. Our results support the information asymmetry hypothesis. Hedged firms invest more heavily in innovative projects, generate more patents and have more patent citations. To address endogeneity concerns, we employ both difference-in-differences and instrumental variables regressions, and test for reverse causality explicitly. In Chapter 3, we document a measure of law firm expertise that could predict the outcomes of future lawsuits conducted by the law firm, using securities class action lawsuits from 1996 to 2013. We use prior Dismissed Ratio as law firm expertise measure on a rolling basis, defined as ratio of number of dismissed cases to number of total cases conducted by the law firm in the past 5 years. It is found that law firms with lower prior Dismissed Ratio are more likely to be skilled law firms with less agency problem. Cases conducted by skilled law firms with less agency problem are more likely to be settled, have more negative cumulative abnormal return during the filing date, win larger settlement amount, result in larger probability of CEO turnover and are associated with larger short interest one week prior to the filing event. Skilled law firms contribute to better outcomes by exerting more effort in the litigation process, as evident by the longer Case Length from filing date to status date. In addition, market share of law firms increases after performing as skilled law firms and skilled law firms are less likely to disappear from the market in the future. Overall, predictive power and persistence of law firm expertise suggest law firm fixed effect in securities class action lawsuits. Robustness tests suggest existence of law firm expertise beyond case selection.Doctor of Philosoph

The spatial and temporal evolution characteristics and influencing factors of industrial pollution in North China

Scholars have different observations and undertandings over the relationship between the economic development and environment protection, since the ''Environmental Kuznets Curve'' hypothesis has been raised. The integrated utilization of resources and the collaborative industrial development in North China have improved economic development, and caused nonnegligible environmental pollution simuatenously. Currently, North China is at the critical point to achieve industrial green development. This research analyzes the spatial and temporal distribution patterns and influencing factors of industrial wastewater discharge in North China by using exploratory spatial data analysis (ESDA) and spatial econometric model. The results show that the industrial wastewater discharge shows an inverted ''U'' shape in time, reaching a peak in 2010 and then fluctuating down; spatially, it shows a significant spatial aggregation, while the spatial divergence also appears. Industrial structure is an important factor in promoting wastewater discharge, while economic development has an obvious inhibitory effect on pollution, but the influence of technological progress is not obvious

论萧乾小说中的基督教因素 = Christianity elements in Xiao Qian’s novels

萧乾（1910－1999）自幼接触基督教并熟读《圣经》，他后来的写作风格深受基督教文化与《圣经》叙事手法的影响。尽管因为他的一些小说，他被评论界广泛称为"反基督教作家"，但在了解他的童年经历与所在时代之后，会发现事实并非如此。他曾经表示过自己的立场："我揭露并反对的是二十年代的强迫性信仰，以及宗教和帝国主义的关系，但不反对宗教本身。我尊敬耶稣这位被压迫民族的领袖，也珍视《圣经》以及基督的一生在西方文化史、艺术史上的重要性。我拥护信仰自由，因而没有理由去反对基督教或任何宗教。"[1]正如萧乾所说，他不但承认耶稣的存在，并且大力肯定了耶稣与《圣经》的贡献。通过他的作品而将其定义为"反基督的作家"，是非常片面的。萧乾曾在教会学校度过了苦难的童年。十九世纪二十年代的中国，正承受着帝国主义的侵略与压迫。基督教随着帝国主义的入侵而渗透进中国社会和文化里，同时在这段时期，也出现很多以宗教谋取私利的牧师以及伪教徒。年幼的作者经历并目睹了很多吃教者的行为，因而在之后的作品中塑造这样的形象，对他们进行批判，可以说是时代的投射。在作品深层的叙事视角、对矛盾的制造以及写作手法方面，作者受到基督教及《圣经》的多方面影响。Xiao Qian (1910-1999) was introduced to the Bible at a very young age and was well equipped with Biblical knowledge as he grew up. The heavy influence of the Christianity culture and narrative style of the Bible had later reflected in his own writings. Although he was named the "anti-Christ" writer by the critics due to the contents of some of his writings, one will realize that the criticisms are feasible as one learns about Xiao's childhood and the historical background of that period of time. He had once declared his stand on this matter, "the things that I revealed and criticized about were the obsessive belief in the 20s and the relationship between religion and imperialism, not religion itself. I respect Jesus, the oppressed national leader, and I also treasure the Bible and the importance of Jesus Christ's life in the history of Western art and culture. I respect the freedom of belief and hence there would not be any reasons for me to against Christianity or other religions." Just as what he had said, not only did he acknowledge the existence of Jesus, he even recognized the contribution of Jesus and the Bible. Therefore, we argued that the criticisms based on Xiao's writings were biased. Xiao Qian had spent a tough childhood in the Catholic school. China was suffering from the invasion and oppression from the Western Imperialism in the 1820s. Along with the invasion of imperialism, Christianity had penetrated into the culture and the society of China. At the same time, there were many pastors who abused the power of the religion for personal gain as well as false Christians. Xiao had witnessed and experienced a lot of "rice Christians" in his childhood days, and therefore he created such characters in his writings in order to criticize them. This can be seen as the reflection of that period of time. We believed that the Bible had multiple influences on Xiao's writings, such as the narrative perspective, the use of irony and rhetorical styles.Bachelor of Art

Foreign interest rate shocks and exchange rate regimes of small open economies : experience from Hong Kong and Singapore

Recent decades have witnessed a steady decline in the real interest rates associated with US Treasury securities, especially after 2008 US subprime crisis. Since the spillover effect of developed or large economies on the small open economies is largely through trade and financial linkages, any shocks from other countries could have a significant effect on the domestic economy. This study aims to address the question of whether exchange rate regimes play a role in influencing the macroeconomic performances of comparable small open economies in response to foreign real interest rate shocks. Particularly, experiences from Hong Kong and Singapore are studied from both theoretical and empirical approaches because they are comparable economies with different exchange rate regimes from the period of 1984 to 2010. Theoretical framework was derived based on Mundell-Fleming Model and AD-AS Model, followed by applying Vector Error Correction Model (VECM) to estimate and interpret empirical results in Hong Kong and Singapore. Unit root test and Cointegration test were conducted to select the model before the identification of reduced VECM and structural form. Impulse Response Functions (IRF) were computed and Forecast Error Variance Decompositions (FEVD) were provided as supplementary evidence. This study demonstrates that Hong Kong and Singapore will have different macroeconomic performances under foreign real interest rate shocks, since exchange rate regimes do play a role in the transmission mechanism of foreign real exchange rate shocks. Therefore, our study provides implications for small open economies regarding their policy choices of exchange rate regimes. Moreover, our study could also help explain the increasing popularity of floating exchange rate regimes in the recent decades.Bachelor of Art

Study the Impact of Plateau Pika Activity on the Ecological Dynamics of the Qinghai-Tibet Plateau

The Tibetan Plateau, the world's largest plateau, harbors diverse ecosystems that play vital roles in the global environment. This study aims to investigate the ecological impact of the plateau pika, an endemic species, on the plateau's water resources, carbon storage, biodiversity, and climate. The research advocates for a balanced approach to pika control, emphasizing ecological preservation while addressing the associated challenges. Various statistical tests were employed to quantify the relationship between plateau pika activity and ecological dynamics. Correlation analysis revealed a significant negative correlation between pika burrow density and soil moisture content. T-tests demonstrated a significant difference in soil carbon content between areas with high and low pika burrow densities. A chi-squared test found no significant association between pika population density and the presence of vulnerable species. Ecological protection and sustainable development are crucial, with plant-based pesticides like ricin offering an effective and environmentally friendly means of pika control. However, ecological restoration should be the core of rodent control efforts to maintain a balanced ecosystem. Combining grazing policies with ecological grassland control measures can help mitigate rodent damage while improving grassland productivity

Whom will Granny thank?Thinking about what could have been informs children’s inferences about relative helpfulness

To evaluate others’ actions, we consider action outcomes (e.g.,positive or negative) and the actors’ underlying intentions (e.g.,intentional or accidental). However, we often encounter situ-ations where neither actual outcomes nor intentions provideuseful evidence for evaluation but representations of unreal-ized (counterfactual) outcomes matter. Here we ask whetherpreschool-aged children consider counterfactual outcomes toevaluate whose action was more helpful. When two agentseach caught one of two falling apples (one caught it above atrash can and the other above a fruit basket), children chosethe former as the one who should be thanked (because oth-erwise the apple would’ve fallen into the trash). When theagents caught crushed cans, however, children made the op-posite choice, choosing the agent who caught the can over thefruit basket. Even though preschoolers typically struggle withcounterfactuals, children in our task readily engaged in suchreasoning in the context of social evaluation

Landslide Extraction Using Mask R-CNN with Background-Enhancement Method

The application of deep learning methods has brought improvements to the accuracy and automation of landslide extractions based on remote sensing images because deep learning techniques have independent feature learning and powerful computing ability. However, in application, the quality of training samples often fails the requirement for training deep networks, causing insufficient feature learning. Furthermore, some background objects (e.g., river, bare land, building) share similar shapes, colors, and textures with landslides. They can be confusing to automatic tasks, contributing false and missed extractions. To solve the above problems, a background-enhancement method was proposed to enrich the complexity of samples. Models can learn the differences between landslides and background objects more efficiently through background-enhanced samples, then reduce false extractions on background objects. Considering that the environments of disaster areas play dominant roles in the formation of landslides, landslide-inducing attributes (DEM, slope, distance from river) were used as supplements, providing additional information for landslide extraction models to further improve the accuracy of extraction results. The proposed methods were applied to extract landslides that occurred in Ludian county, Yunnan Province, in August 2014. Comparative experiments were conducted using a mask R-CNN model. The experiment using both background-enhanced samples and landslide-inducing information showed a satisfying result with an F1 score of 89.08%. Compared with the F1 score from the experiment using only satellite images as input data, it was significantly improved by 22.38%, underscoring the applicability and effectiveness of our background-enhancement method