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Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
Description
This study investigates the relation between credit supply competition among banks and their clients’ conditional accounting conservatism (i.e., asymmetric timely loss recognition). The Interstate Banking and Branching Efficiency Act (IBBEA) of 1994 permits banks and bank holding companies to expand their business across state lines, introducing a positive shock to credit supply competition in the banking industry. The increase in credit supply competition weakens banks’ bargaining power in the negotiation process, which in turn may weaken their ability to demand conservative financial reporting from borrowers. Consistent with this prediction, results show that firms report less conservatively after the IBBEA is passed in their headquartered states. The effect of the IBBEA on conditional conservatism is particularly stronger for firms in states with a greater increase in competition among banks, firms whose operations are more concentrated in their headquarter states, firms with greater financial constraints, and firms subject to less external monitoring. Robustness tests confirm that the observed decline in conditional conservatism is causally related to the passage of IBBEA. Overall, this study highlights the impact of credit supply competition on financial reporting practices.
ContributorsHuang, Wei (Author) / Li, Yinghua (Thesis advisor) / Huang, Xiaochuan (Committee member) / Kaplan, Steve (Committee member) / Arizona State University (Publisher)
Created2018
Description摘要
在复杂多变的商业环境中，企业传统的人力资源管理已经难以应对日益频发的员工职业倦怠、人际间矛盾冲突、频繁跳槽等局面与问题。企业员工工作的价值与意义早已不再是传统的雇佣模式下，通过出卖劳动力或智力从而获得工资以实现“养家糊口”的目的那么单纯与简单，员工也希望通过辛勤的工作，以获得个体的幸福感、荣誉感与认同感等。对于现代企业的管理者而言，员工追求事业的提升、个人价值的实现，不仅体现在薪酬、福利待遇的提升，更重要的是员工个人的成长以及潜能和竞争力的提升。
随着组织行为学和心理学的不断发展与演变，与员工幸福感相关的研究备受关注。对现代企业而言，管理者借助制度设计对员工幸福积极管理，可以最大限度地发挥员工的积极性、主动性与创造性，实现员工与企业之间的利益相趋同，从而更为高效地实现组织的目标。基于此，本文以民营企业员工工作幸福感作为研究的切入点，借助理论分析、问卷调查和实证分析相结合的研究方法，系统深入地研究我国民营企业员工工作幸福感的构成、可控前因和绩效后果等问题。
本文研究发现：
第一，员工薪酬的提高有助于员工工作幸福感的提升，薪资对基层员工幸福感的影响显著高于其对高层员工幸福感的影响；
第二，完善的晋升机制对于中层员工而言更能提升其幸福感，完善的晋升机制更有利于中层员工；
第三，公平性的提高有助于提高员工工作幸福感，而且这种正效应更多体现在基层员工群体之中；
第四，高层员工更注重自我价值的实现，高层员工的工作挑战性越高，其自我实现需求获得的满足感则约高，但是对于基层员工和中层员工而言，其效果则恰恰相反，基础员工和高层员工更多地将工作挑战性和压力看作是一种负面的因素；
第五，员工幸福感的确会给企业带来正向的绩效。
本文的研究框架和实证结论不仅可以丰富学术界有关员工工作幸福感的研究，而且为企业管理者进行绩效管理以及员工工作质量的提升提供理论和实证借鉴。
在复杂多变的商业环境中，企业传统的人力资源管理已经难以应对日益频发的员工职业倦怠、人际间矛盾冲突、频繁跳槽等局面与问题。企业员工工作的价值与意义早已不再是传统的雇佣模式下，通过出卖劳动力或智力从而获得工资以实现“养家糊口”的目的那么单纯与简单，员工也希望通过辛勤的工作，以获得个体的幸福感、荣誉感与认同感等。对于现代企业的管理者而言，员工追求事业的提升、个人价值的实现，不仅体现在薪酬、福利待遇的提升，更重要的是员工个人的成长以及潜能和竞争力的提升。
随着组织行为学和心理学的不断发展与演变，与员工幸福感相关的研究备受关注。对现代企业而言，管理者借助制度设计对员工幸福积极管理，可以最大限度地发挥员工的积极性、主动性与创造性，实现员工与企业之间的利益相趋同，从而更为高效地实现组织的目标。基于此，本文以民营企业员工工作幸福感作为研究的切入点，借助理论分析、问卷调查和实证分析相结合的研究方法，系统深入地研究我国民营企业员工工作幸福感的构成、可控前因和绩效后果等问题。
本文研究发现：
第一，员工薪酬的提高有助于员工工作幸福感的提升，薪资对基层员工幸福感的影响显著高于其对高层员工幸福感的影响；
第二，完善的晋升机制对于中层员工而言更能提升其幸福感，完善的晋升机制更有利于中层员工；
第三，公平性的提高有助于提高员工工作幸福感，而且这种正效应更多体现在基层员工群体之中；
第四，高层员工更注重自我价值的实现，高层员工的工作挑战性越高，其自我实现需求获得的满足感则约高，但是对于基层员工和中层员工而言，其效果则恰恰相反，基础员工和高层员工更多地将工作挑战性和压力看作是一种负面的因素；
第五，员工幸福感的确会给企业带来正向的绩效。
本文的研究框架和实证结论不仅可以丰富学术界有关员工工作幸福感的研究，而且为企业管理者进行绩效管理以及员工工作质量的提升提供理论和实证借鉴。
ContributorsShu, Man (Author) / Shen, Wei (Thesis advisor) / Wu, Fei (Thesis advisor) / Chen, Xin (Committee member) / Arizona State University (Publisher)
Created2019
Description当前，上市公司的盈余管理问题已是我国资本市场中普遍存在的突出问题。一般来说，一些企业为了满足资本市场对于上市、增发等条件的要求,以及为有效推动企业的并购、重组等行为的顺利实现,甚至为了谋求公司管理层的个别利益,往往运用盈余管理等举措实施公司财报及关键指标的粉饰修正，让不知情的股民蒙受一定的损失。普遍分析显示，我国股市中民营企业比其他企业遭遇的问题和压力更多、更大、更突出,因此民营企业从客观上来说拥有更强的盈余管理动机。而从当前我国资本市场的实际情况来看，我国相关专家学者对盈余管理的系统性深入研究，一般都瞄准了上市企业群体或持续亏损企业，对盈余管理的研究不系统、不全面、不深入，这将对我国进一步提升盈余管理监管水平构成一定不利影响。当前，由于我国民企在自身管理及发展动力方面的特殊性,我国民企的管理、盈余管理特点和国外上市公司还存在着很大的不同,进一步深入研究我国民企上市公司自身管理方面的突出特点，以及其对企业盈余管理等方面的深层次影响,有助于监管层对症下药，更有针对性地研究出台全新的监管措施,进一步提升管理水平。这还可以为公司发展的决策层及相关会计信息使用人员提供一定的决策参考, 因此其拥有十分重要的意义。
本文首先认真总结分析了有关上市企业治理结构和盈余管理等方面的历史文献资料，依托当前资本市场上普遍运用的委托代理、内部人控制和契约等理论，系统研究了我国民企上市公司在自身治理结构方面的突出特征以及其对盈余管理方面所构成影响的深层次原理。在此基础上，本文通过2015-2017年我国上市企业数据，基于截面Jones模型对民营企业和非民营企业盈余管理程度进行测算和比较分析，发现民营企业盈余管理程度更高；从四个层面系统研究民企公司自身的治理结构突出特点,设立回归模型论证了民营企业独特的公司治理结构特征对盈余管理程度确实会产生影响；最后,本文进一步利用修正的费尔萨姆一奥尔森估价模型对民营上市公司盈余管理有公司价值的关系进行了验证，发现两者具有显著相关性。
本文首先认真总结分析了有关上市企业治理结构和盈余管理等方面的历史文献资料，依托当前资本市场上普遍运用的委托代理、内部人控制和契约等理论，系统研究了我国民企上市公司在自身治理结构方面的突出特征以及其对盈余管理方面所构成影响的深层次原理。在此基础上，本文通过2015-2017年我国上市企业数据，基于截面Jones模型对民营企业和非民营企业盈余管理程度进行测算和比较分析，发现民营企业盈余管理程度更高；从四个层面系统研究民企公司自身的治理结构突出特点,设立回归模型论证了民营企业独特的公司治理结构特征对盈余管理程度确实会产生影响；最后,本文进一步利用修正的费尔萨姆一奥尔森估价模型对民营上市公司盈余管理有公司价值的关系进行了验证，发现两者具有显著相关性。
ContributorsChen, Hui (Author) / Shen, Wei (Thesis advisor) / Chang, Chun (Thesis advisor) / Huang, Xiaochuan (Committee member) / Arizona State University (Publisher)
Created2019
Description中国律师制度自“文化大革命”结束后恢复至今，已有近四十年。中国律师行业伴随着中国改革开放的进程，得到了飞速的发展，当然，同时也面临着诸多的问题。重要的问题之一便是，中国律师事务所采用“加盟制合伙人”模式和采用“权益制合伙人”模式之争。本文试图从回顾企业边界的三大理论出发，提出“加盟制合伙人”模式和 “权益制合伙人”模式与合伙人律师的业务专业化程度、业务复杂化程度以及大客户和律师事务所规模关系的四个假设，通过实证分析的方式，试图以企业边界三大理论解释前述四个假设中的关系，并以此期望对律师行业的发展有所启发。
ContributorsChu, Xiaoqing (Author) / Pei, Ker-Wei (Thesis advisor) / Cheng, Shijun (Thesis advisor) / Shen, Wei (Committee member) / Arizona State University (Publisher)
Created2019
Description近些年来，我国城市化进程不断加快，到2020年我国常住人口城镇化率将达到60%左右，户籍人口城镇化率将会达到45%左右。伴随着我国城市化进程的高速推进以及经济水平的不断提高，公共物品及服务的需求程度加大，政府单独出资建设公共项目会导致资金不足、经营管理效率低下等问题。与此同时，我国当前不同层级地方政府的政府性债务都达到了一个非常高的水平，截至2017年末，中国地方政府债务16.47万亿元，债务率（债务余额/综合财力）为76.5%，其中地方负有偿还责任的债务约12.9万亿，地方政府性债务的控制和转化成为经济新常态下重要特征之一。在地方债务压力较大的情况下，PPP将替代土地财政和地方政府融资，为我国新型城镇化建设提供可持续的资金支持，PPP模式成为当前城市建设领域融资的重要选项。
据此，本文基于实证研究方法探讨在债务约束的背景下，在地方政府债务约束下，PPP模式的引入，对城市规划中建设用地面积、人口规划规模与容量、建设用地属性等的城市规划变量的影响；与此同时，考虑到地方政府的政策很大程度上受到是由地方官员，特别是受到作为地方政府党政“一把手”的市委书记和市长的晋升压力和激励的影响，讨论市委书记/市长的晋升压力和激励对PPP模式引入效果的影响。研究发现，在地方政府债务约束下，PPP模式的引入，显著增加城市规划中建设用地面积、人口规划规模与容量、建设用地属性等的城市规划变量；同时，地方政府官员存在利用PPP放大城市建设和规划规模的行为，反映了PPP项目在引入和使用的过程中很大程度上受政府官员的激励的影响。
据此，本文基于实证研究方法探讨在债务约束的背景下，在地方政府债务约束下，PPP模式的引入，对城市规划中建设用地面积、人口规划规模与容量、建设用地属性等的城市规划变量的影响；与此同时，考虑到地方政府的政策很大程度上受到是由地方官员，特别是受到作为地方政府党政“一把手”的市委书记和市长的晋升压力和激励的影响，讨论市委书记/市长的晋升压力和激励对PPP模式引入效果的影响。研究发现，在地方政府债务约束下，PPP模式的引入，显著增加城市规划中建设用地面积、人口规划规模与容量、建设用地属性等的城市规划变量；同时，地方政府官员存在利用PPP放大城市建设和规划规模的行为，反映了PPP项目在引入和使用的过程中很大程度上受政府官员的激励的影响。
ContributorsXu, Ke (Author) / Chen, Pei-Yu (Thesis advisor) / Zhu, Qigui (Thesis advisor) / Chen, Xin (Committee member) / Arizona State University (Publisher)
Created2019
Description
Environmental changes are occurring at an unprecedented rate, and these changes will undoubtedly lead to alterations in resource availability for many organisms. To effectively predict the implications of such changes, it is critical to better understand how organisms have adapted to coping with seasonally limited resources. The vast majority of previous work has focused on energy balance as the driver of changes in organismal physiology. While energy is clearly a vital currency, other resources can also be limited and impact physiological functions. Water is essential for life as it is the main constituent of cells, tissues, and organs. Yet, water has received little consideration for its role as a currency that impacts physiological functions. Given the importance of water to most major physiological systems, I investigated how water limitations interact with immune function, metabolism, and reproductive investment, an almost entirely unexplored area. Using multiple species and life stages, I demonstrated that dehydrated animals typically have enhanced innate immunity, regardless of whether the dehydration is a result of seasonal water constraints, water deprivation in the lab, or high physiological demand for water. My work contributed greatly to the understanding of immune function dynamics and lays a foundation for the study of hydration immunology as a component of the burgeoning field of ecoimmunology. While a large portion of my dissertation focused on the interaction between water balance and immune function, there are many other physiological processes that may be impacted by water restrictions. Accordingly, I recently expanded the understanding of how reproductive females can alter metabolic substrates to reallocate internal water during times of water scarcity, an important development in our knowledge of reproductive investments. Overall, by thoroughly evaluating implications and responses to water limitations, my dissertation, when combined previous acquired knowledge on food limitation, will enable scientists to better predict the impacts of future climate change, where, in many regions, rainfall events are forecasted to be less reliable, resulting in more frequent drought.
ContributorsBrusch, George, IV (Author) / DeNardo, Dale F (Thesis advisor) / Blattman, Joseph (Committee member) / French, Susannah (Committee member) / Sabo, John (Committee member) / Taylor, Emily (Committee member) / Arizona State University (Publisher)
Created2019
Description
The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and Drug Administration (FDA) published several guidance documents encouraging researchers to exclude women from early clinical drug research. The motivation to publish those documents and the subsequent guidance documents in which the FDA and other regulatory offices established their standpoints on women in drug research may have been connected to current events at the time. The problem of whether women should be involved in drug research is a question of who can assume risk and who is responsible for disseminating what specific kinds of information. The problem tends to be framed as one that juxtaposes the health of women and fetuses and sets their health as in opposition. That opposition, coupled with the inherent uncertainty in testing drugs, provides for a complex set of issues surrounding consent and access to information.
ContributorsMeek, Caroline Jane (Author) / Maienschein, Jane (Thesis director) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Social-emotional learning (SEL) methods are beginning to receive global attention in primary school education, yet the dominant emphasis on implementing these curricula is in high-income, urbanized areas. Consequently, the unique features of developing and integrating such methods in middle- or low-income rural areas are unclear. Past studies suggest that students exposed to SEL programs show an increase in academic performance, improved ability to cope with stress, and better attitudes about themselves, others, and school, but these curricula are designed with an urban focus. The purpose of this study was to conduct a needs-based analysis to investigate components specific to a SEL curriculum contextualized to rural primary schools. A promising organization committed to rural educational development is Barefoot College, located in Tilonia, Rajasthan, India. In partnership with Barefoot, we designed an ethnographic study to identify and describe what teachers and school leaders consider the highest needs related to their students' social and emotional education. To do so, we interviewed 14 teachers and school leaders individually or in a focus group to explore their present understanding of “social-emotional learning” and the perception of their students’ social and emotional intelligence. Analysis of this data uncovered common themes among classroom behaviors and prevalent opportunities to address social and emotional well-being among students. These themes translated into the three overarching topics and eight sub-topics explored throughout the curriculum, and these opportunities guided the creation of the 21 modules within it. Through a design-based research methodology, we developed a 40-hour curriculum by implementing its various modules within seven Barefoot classrooms alongside continuous reiteration based on teacher feedback and participant observation. Through this process, we found that student engagement increased during contextualized SEL lessons as opposed to traditional methods. In addition, we found that teachers and students preferred and performed better with an activities-based approach. These findings suggest that rural educators must employ particular teaching strategies when addressing SEL, including localized content and an experiential-learning approach. Teachers reported that as their approach to SEL shifted, they began to unlock the potential to build self-aware, globally-minded students. This study concludes that social and emotional education cannot be treated in a generalized manner, as curriculum development is central to the teaching-learning process.
ContributorsBucker, Delaney Sue (Author) / Carrese, Susan (Thesis director) / Barab, Sasha (Committee member) / School of Life Sciences (Contributor, Contributor) / School of Civic & Economic Thought and Leadership (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05