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Ethics of Artificial Intelligence in Society 人工智能在社会中的伦理学
Pub Date : 2023-03-31 DOI: 10.33697/ajur.2023.070
Emma Johnson, Eloy Parrilla, Austin Burg
ABSTRACT: Every day, artificial intelligence (AI) is becoming more prevalent as new technologies are presented to the public with the intent of integrating them into society. However, these systems are not perfect and are known to cause failures that impact a multitude of people. The purpose of this study is to explore how ethical guidelines are followed by AI when it is being designed and implemented in society. Three ethics theories, along with nine ethical principles of AI, and the Agent, Deed, Consequence (ADC) model were investigated to analyze failures involving AI. When a system fails to follow the models listed, a set of refined ethical principles are created. By analyzing the failures, an understanding of how similar incidents may be prevented was gained. Additionally, the importance of ethics being a part of AI programming was demonstrated, followed by recommendations for the future incorporation of ethics into AI. The term “failure” is specifically used throughout the paper because of the nature in which the events involving AI occur. The events are not necessarily “accidents” since the AI was intended to act in certain ways, but the events are also not “malfunctions” because the AI examples were not internally compromised. For these reasons, the much broader term “failure” is used. KEYWORDS: Ethics; Artificial Intelligence; Agent-Deed-Consequence (ADC) Model; Principles of Artificial Intelligence; Virtue Ethics; Deontology; Consequentialism; AI Systems
摘要:人工智能(AI)正变得越来越流行,新技术呈现在公众面前,目的是使其融入社会。然而,这些系统并不完美,并且已知会导致影响许多人的故障。本研究的目的是探讨人工智能在设计和在社会中实施时如何遵循道德准则。研究了人工智能的三种伦理理论、九种伦理原则以及Agent, Deed, Consequence (ADC)模型,以分析涉及人工智能的失败。当一个系统不能遵循所列出的模式时,就会创建一套精炼的道德原则。通过分析故障,可以了解如何防止类似事件的发生。此外,还展示了伦理作为人工智能编程一部分的重要性,随后提出了将伦理纳入人工智能的建议。“失败”一词在整篇文章中被特别使用,因为涉及AI的事件发生的性质。这些事件并不一定是“意外”,因为AI是以某种方式行动的,但这些事件也不是“故障”,因为AI的例子并没有受到内部损害。由于这些原因,使用了更广泛的术语“失败”。关键词:伦理;人工智能;代理-行为-后果模型;人工智能原理;美德伦理;义务论;结果论;人工智能系统
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引用次数: 0
Student Perceptions of Instructor-Student Rapport and Motivation In Hybrid Courses During COVID-19 COVID-19期间学生对混合课程中师生关系和动机的看法
Pub Date : 2023-03-31 DOI: 10.33697/ajur.2023.072
Bianca Candelaria, M. Clements
The relationship between instructors and their students is essential for developing a classroom climate where students feel motivated to learn. The current study surveyed 658 undergraduate students to examine the relationship between instructor-student rapport and motivation in online and face-to-face classes during the COVID-19 pandemic. Results indicated (1) students experienced more rapport with their instructors during face-to-face classes compared to their online classes, (2) students perceived their motivation was greater during face-to-face classes than in online classes, and (3) there was a significant positive relationship between instructor-student rapport and student motivation in both online and face-to-face classes. This study’s findings lend further support to research that emphasizes the importance of creating a sense of community in online classes, where students feel connected to their instructors and, consequently, motivated to learn. KEYWORDS: Instructor-Student Rapport; Motivation; Hybrid Courses; COVID-19; Online Learning
教师和学生之间的关系对于培养学生感到有动力学习的课堂气氛至关重要。目前的研究调查了658名本科生,以研究2019冠状病毒病大流行期间在线和面对面课程中师生关系与动机之间的关系。结果表明:(1)面对面课堂比在线课堂与教师的关系更融洽;(2)面对面课堂与在线课堂相比,学生对教师动机的感知更强;(3)在线和面对面课堂的师生关系与学生动机之间存在显著的正相关关系。这项研究的发现进一步支持了一项研究,该研究强调在在线课程中创造一种社区意识的重要性,在这种意识中,学生们与老师有联系,从而有动力学习。关键词:师生关系;动机;混合课程;COVID-19;在线学习
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引用次数: 0
“The Strong, Silent Type”: Analyzing the Portrayal of the Cost of Masculine Gender Performances in The Sopranos “坚强、沉默型”:《黑道家族》男性化性别表演成本的刻画分析
Pub Date : 2023-03-31 DOI: 10.33697/ajur.2023.073
H. Taylor, Annaleigh E. Curtis
Media portrayals of the “strong, silent type” reinforce the expectation that men should not demonstrate or even acknowledge their emotions. This trope, however, reflects more significant societal norms around masculine practices that can have profoundly negative impacts on individual men as well as those around them. Emotional compression (or modern stoicism) is fundamentally different from emotional repression. Emotional compression practices can allow men to process their feelings privately and then communicate their feelings clearly without the distortion of uncontrolled bursts of emotion. The treatment of mental health and masculinity in Season 5 of The Sopranos “holds up a mirror” to the costs of emotional repression for men as part of masculine gender performances. The show highlights, sometimes quite brutally, the costs of emotional repression to men and the people around them. In doing so, the content of the show implies that therapy could help men learn to face their feelings and alleviate their suffering as well as that of their families, though only if men are willing to face the feelings of vulnerability that come with having emotions. KEYWORDS: Stoicism; Alexithymia; Hegemonic masculinity; Emotional repression; Mental health; Gender performances
媒体对“坚强、沉默型”的描述强化了人们的期望,即男性不应该展示甚至承认自己的情绪。然而,这个比喻反映了围绕男性行为的更重要的社会规范,这些规范可能会对男性个体及其周围的人产生深远的负面影响。情感压缩(或现代坚忍)与情感压抑有着根本的不同。情感压缩练习可以让男性私下处理自己的感受,然后在没有失控情绪爆发的情况下清晰地传达自己的感受。《黑道家族》第五季对心理健康和男性气质的处理“为男性性别表演中男性情感压抑的代价提供了一面镜子”。该节目强调了男性及其周围人情感压抑的代价,有时甚至相当残酷。通过这样做,该节目的内容暗示,治疗可以帮助男性学会面对自己的感受,减轻他们和家人的痛苦,尽管前提是男性愿意面对情绪带来的脆弱感。关键词:斯多葛主义;述情障碍;霸权男子气概;情绪压抑;心理健康;性别表现
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引用次数: 0
The By-Product of Ozone from Electrostatic Air Cleaners 静电空气净化器臭氧的副产物
Pub Date : 2023-03-31 DOI: 10.33697/ajur.2023.071
Giovanni Cerrato, N. Fumo
Indoor Air Quality (IAQ) contributes to the health and comfort of people living and working indoors. Poor IAQ can be linked to indoor and outdoor sources of contaminants. One recent solution for improving IAQ is the use of Electrostatic (ES) Air Cleaning technology. An ES air cleaner can be installed in an heating, ventilation, and air conditioning system where it pre-filters large dust particles and shocks smaller particles into a collection tray. However, ES air cleaners have been known to give off ozone as a by-product, which is, itself, an air contaminant. Ozone is found outdoors as product of sunlight combining nitrogen oxides and volatile organic compounds generated from man-made pollution. Indoor ozone concentration will depend on the introduction of outdoor ozone indoors through natural ventilation, mechanical ventilation, and infiltration through the building’s envelope (in order of importance). Two different ES air cleaners, A and B, were installed in the air conditioning system of research House #2 of the TRANE Residential Heating and Cooling Research Lab at the University of Texas at Tyler. A series of ozone experiments were conducted, which included measuring the baseline ozone levels at the research houses with different levels of insulation, observing the increase in ozone due to the powering on of mechanical ventilation, and observing the increase in ozone due to the powering on of the installed ES air cleaners. The baseline ozone levels observed in research house #2, whose envelope is more tightly insulated, was found to be lower than in research house #1 whose envelope is less tightly insulated. With regards to mechanical ventilation, an increase in ozone levels were seen in addition to an even higher increase in ozone levels when the ES air cleaners were powered on in tandem. In terms of the single contribution of the ES air cleaners in raising indoor ozone levels, the data shows that although the ES air cleaners increased the ozone concentration in the house, the levels are not of concern as they were less than the FDA limit on indoor ozone generation. KEYWORDS: Indoor Air Quality; Ozone; Electrostatic Air Cleaner; Infiltration; Mechanical Ventilation; HVAC; Pollutant; Indoor Contaminant
室内空气质量(IAQ)有助于人们在室内生活和工作的健康和舒适。室内空气质量差可能与室内外污染物来源有关。改善室内空气质量的一个最新解决方案是使用静电(ES)空气净化技术。ES空气净化器可以安装在供暖、通风和空调系统中,预过滤较大的灰尘颗粒,并将较小的颗粒冲击到收集托盘中。然而,众所周知,ES空气净化器会释放出臭氧作为副产品,而臭氧本身就是一种空气污染物。臭氧是在户外发现的,是阳光将氮氧化物和人为污染产生的挥发性有机化合物结合在一起的产物。室内臭氧浓度将取决于室外臭氧通过自然通风、机械通风和通过建筑物围护结构渗透(按重要性排序)引入室内。德克萨斯大学泰勒分校TRANE住宅供暖和制冷研究实验室2号研究室的空调系统中安装了两种不同的ES空气净化器A和B。进行了一系列臭氧实验,包括测量具有不同绝缘水平的研究室的基线臭氧水平,观察机械通风通电后臭氧的增加,以及观察已安装的ES空气净化器通电后的臭氧增加。在2号研究室观察到的基线臭氧水平比1号研究室低,2号研究屋的外壳隔热更紧密。关于机械通风,当ES空气净化器同时通电时,臭氧水平增加,臭氧水平甚至更高。就ES空气净化器在提高室内臭氧水平方面的单一贡献而言,数据显示,尽管ES空气净化器提高了室内臭氧浓度,但这些水平并不令人担忧,因为它们低于美国食品药品监督管理局对室内臭氧产生的限值。关键词:室内空气质量;臭氧静电空气净化器;渗透;机械通风;暖通空调;污染物室内污染物
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引用次数: 0
Novel Interactors of the SH2 Domain of the Signaling Adaptors CRK and CRKL Identified in Neuro2A Cells 在Neuro2A细胞中鉴定的CRK和CRKL信号适配器SH2结构域的新相互作用体
Pub Date : 2022-12-31 DOI: 10.33697/ajur.2022.068
Caroline M. Dumas, Anna M. Schmoker, Shannon N. Bennett, Amara Chittenden, Chelsea Darwin, Helena Gaffney, H. Lewis, Eliana Moskovitz, Jonah Rehak, Anna Renzi, Claire Rothfelder, Adam Slamin, Megan Tammaro, L. Sweet, B. Ballif
CT10 regulator of kinase (CRK) and CRK-like (CRKL) form a family of signaling adaptor proteins that serve important roles in the regulation of fundamental cellular processes, including cell motility and proliferation, in a variety of cell types. The Src Homology 2 (SH2) domain of CRK and CRKL interacts with proteins containing phosphorylated tyrosine-X-X-proline (pYXXP) motifs, facilitating complex formation during signaling events. A handful of CRK/CRKL-SH2-specific interactors have been identified to date, although in silico analyses suggest that many additional interactors remain to be found. To identify CRK/CRKL-SH2 interactors with potential involvement in neuronal development, we conducted a mass spectrometry-based proteomics screen using a neuronal cell line (Neuro2A, or N2A). This resulted in the identification of 132 (6 known and 126 novel) YXXP-containing CRK/CRKL-SH2 interactors, of which 77 were stimulated to bind to the CRK/CRKL-SH2 domain following tyrosine phosphatase inhibition. Approximately half of the proteins identified were common interactors of both the CRK- and CRKL-SH2 domains. However, both CRK family member SH2 domains exhibited unique binding partners across experimental replicates. These findings reveal an abundance of novel neuronal CRK/CRKL-SH2 domain binding partners and suggest that CRK family SH2 domains possess undescribed docking preferences beyond the canonical pYXXP motif. KEYWORDS: CRK; CRKL; SH2; LC-MS/MS; Proteomics; Neurodevelopment; Signal Transduction
CT10激酶调控因子(CRK)和CRK样蛋白(CRKL)构成了一个信号转导蛋白家族,在多种细胞类型的基本细胞过程调控中发挥重要作用,包括细胞运动和增殖。CRK和CRKL的Src Homology 2 (SH2)结构域与含有磷酸化酪氨酸- x - x -脯氨酸(pYXXP)基序的蛋白相互作用,促进信号事件中复合物的形成。到目前为止,已经确定了少数CRK/ crkl - sh2特异性相互作用因子,尽管计算机分析表明仍有许多其他相互作用因子有待发现。为了鉴定可能参与神经元发育的CRK/CRKL-SH2相互作用物,我们使用神经细胞系(Neuro2A或N2A)进行了基于质谱的蛋白质组学筛选。结果鉴定出132个(已知6个,新发现126个)含有yxxp的CRK/CRKL-SH2相互作用物,其中77个在酪氨酸磷酸酶抑制后被刺激结合到CRK/CRKL-SH2结构域。大约一半的鉴定蛋白是CRK-和CRKL-SH2结构域的共同相互作用物。然而,两个CRK家族成员SH2结构域在实验重复中表现出独特的结合伙伴。这些发现揭示了大量新的神经元CRK/CRKL-SH2结构域结合伙伴,并表明CRK家族SH2结构域除了典型的pYXXP基元外,还具有未描述的对接偏好。关键词:CRK;CRKL;SH2;质/女士;蛋白质组学;神经发育;信号转导
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引用次数: 0
Comparison of Genotypic and Phenotypic Predictions for Heavy Metal Resistance in Salmonella enterica and Escherichia coli 肠炎沙门氏菌和大肠杆菌重金属抗性基因型和表型预测的比较
Pub Date : 2022-12-31 DOI: 10.33697/ajur.2022.064
Jeevan Rivera-Díaz, H. Phillippi, Nyduta Mbogo, Erin M. Nawrocki, E. Dudley
Salmonella enterica and Escherichia coli are two pathogenic bacteria of worldwide importance that can infect the gastrointestinal tract. Contamination in the food supply chain is an area of concern. Animal feed may be supplemented with essential trace elements, which function as nutritional additives to promote growth & health and optimize production. Bacteria have acquired many metal resistance genes to adapt to the exposure of metals. In this study, our objectives were to evaluate in S. enterica and E. coli, the correlation between the resistance genotype and phenotype to certain heavy metals, and the ability of conjugative plasmids to transfer antimicrobial resistance genes (AMRGs) and heavy metal resistance genes (HMRGs). A total of 10 strains, five S. enterica and five E. coli, were used for this study. Minimal inhibitory concentrations (MICs) were determined for heavy metals: copper, silver, arsenic, and tellurite. The tested isolates showed resistance to copper (5/10; 50%), arsenic (7/10; 70%), and silver (9/10; 90%). Cohen’s Kappa statistics were used to analyze genotype to phenotype agreements. Among the 10 strains sampled, the accordance between geno- and phenotypic heavy metal resistance was fair for copper (kappa = 0.4), none to slight for arsenic (kappa = 0.19) and tellurite (kappa = 0), and no agreement for silver (kappa = -0.19). The transfer of HMRGs was determined in a conjugation experiment performed for all five Salmonella strains as donors using mixed broth cultures. Transconjugants were obtained only from the genotypically tellurite-resistant strain PSU-3260, which yielded a transfer frequency of 10⁻³ transconjugants per donor. In such strain, the tellurite-resistant genes reside on an IncHI2-type plasmid that shares high DNA sequence identity with known HMRG-disseminating Salmonella plasmids. Our results indicated no considerable correlation between the geno- and phenotypic resistance towards heavy metals in the sampled S. enterica and E. coli. The necessity of research in this area is supported by the lack of standardized protocols and MIC clinical breakpoints for heavy metals. KEYWORDS: Heavy metal; resistance; Salmonella; E. coli; agriculture; genotype; phenotype; MIC
肠道沙门氏菌和大肠杆菌是两种在世界范围内具有重要意义的致病菌,可感染胃肠道。食品供应链中的污染是一个令人关注的领域。动物饲料中可添加必需的微量元素,这些元素可作为营养添加剂,促进生长和健康,优化生产。细菌已经获得了许多金属抗性基因来适应金属的暴露。在这项研究中,我们的目的是评估肠道杆菌和大肠杆菌对某些重金属的抗性基因型和表型之间的相关性,以及偶联质粒转移抗微生物抗性基因(AMRGs)和重金属抗性基因(HMRGs)的能力。本研究共使用了10株菌株,其中5株为肠炎沙门氏菌,5株为大肠杆菌。测定了重金属的最低抑制浓度(MIC):铜、银、砷和碲。测试的分离物显示出对铜(5/10;50%)、砷(7/10;70%)和银(9/10;90%)的抗性。Cohen的Kappa统计用于分析基因型与表型的一致性。在取样的10个菌株中,遗传和表型重金属抗性之间的一致性对铜(kappa=0.4)是公平的,对砷(kappa=0.19)和碲化物(kappa=0)从零到轻微,对银(kappa=-0.19)没有一致性。在使用混合肉汤培养物对作为供体的所有5个沙门氏菌菌株进行的缀合实验中确定了HMRGs的转移。转移偶联物仅从基因型碲化物抗性菌株PSU-3260获得,其产生的转移频率为10⁻³每个供体的转运偶联物。在这种菌株中,碲化物抗性基因位于IncHI2型质粒上,该质粒与已知的HMRG传播沙门氏菌质粒具有高DNA序列同一性。我们的结果表明,在采样的肠炎沙门氏菌和大肠杆菌中,对重金属的基因和表型抗性之间没有显著的相关性。缺乏重金属的标准化方案和MIC临床断点支持了该领域研究的必要性。关键词:重金属;反对沙门氏菌大肠杆菌农业基因型;表型;麦克风
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引用次数: 0
Preventing the Activation of a Stress Gene Response in Escherichia coli Using Acetate, Butyrate, and Propionate 乙酸盐、丁酸盐和丙酸盐预防大肠杆菌应激基因反应的激活
Pub Date : 2022-12-31 DOI: 10.33697/ajur.2022.065
Kaylee Weigel, Kathleen Ruff-Schmidt, B. Prüß, D. Condry
Regulation of microbial symbiosis in the human intestinal tract is imperative to maintain overall human health and prevent dysbiosis-related diseases, such as inflammatory bowel disease and obesity. Short-chain fatty acids (SCFA) in the intestine are produced by bacterial fermentation and aid in inflammation reduction, dietary fiber digestion, and metabolizing nutrients for the colon. SCFA, notably acetate, butyrate, and propionate, are starting to be used in clinical interventions for GI diseases. While acetate has been shown to mitigate a stress response in the proteome of Escherichia coli cells, little is known about the effects of butyrate and propionate on the same cells. This study aims to evaluate the effects that butyrate and propionate have on the activation of stress promoters in E. coli when induced with a known stressor. Three different strains of E. coli containing the pUCD615 plasmid were used, each with a different promoter fused to the structural genes of the lac operon on the plasmid. Each promoter detected a unique stress response: grpE’::lux fusion (heat shock), recA’::lux fusion (SOS response), and katG’::lux fusion (oxidative damage). Activation of these stress promoters by treatment groups resulted in the emission of bioluminescence which was quantified and compared across treatment groups. All three SCFAs at 25 mM added to cultures prior to stressing the bacteria caused significantly lower bioluminescence levels when compared to the stressed culture without prior addition of SCFA. This indicates that these SCFAs may reduce the stress response in E. coli. KEYWORDS: Short-chain fatty acids; acetate; butyrate; propionate; Escherichia coli; stress response; Vibrio fischeri luxCDABE; grpE; katG; recA
调节肠道内的微生物共生对于维持人体整体健康和预防与生态失调有关的疾病,如炎症性肠病和肥胖,是必不可少的。肠道中的短链脂肪酸(SCFA)由细菌发酵产生,有助于减少炎症,消化膳食纤维,并为结肠代谢营养物质。SCFA,特别是醋酸酯、丁酸酯和丙酸酯,开始用于胃肠道疾病的临床干预。虽然醋酸盐已被证明可以减轻大肠杆菌细胞蛋白质组的应激反应,但丁酸盐和丙酸盐对同一细胞的影响却知之甚少。本研究旨在评估丁酸盐和丙酸盐在已知应激源诱导下对大肠杆菌应激促进子激活的影响。使用了三种不同的含有pUCD615质粒的大肠杆菌菌株,每种菌株都有不同的启动子与质粒上lac操纵子的结构基因融合。每个启动子检测到独特的应激反应:grpE '::lux融合(热休克),recA '::lux融合(SOS反应)和katG '::lux融合(氧化损伤)。处理组激活这些应激启动子导致生物发光的发射,并在处理组之间进行量化和比较。与没有事先添加SCFA的培养物相比,在胁迫细菌之前添加25 mM的三种SCFA的培养物显著降低了生物发光水平。这表明这些SCFAs可能会降低大肠杆菌的应激反应。关键词:短链脂肪酸;乙酸;丁酸;丙酸;大肠杆菌;应激反应;费氏弧菌;grpE;katG;recA
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引用次数: 0
Quantification of Microfibers from Marine Sediments from Three Locations in Southern California: An Exposed Beach (Ventura County), a Watershed (Los Angeles County), and an Enclosed Harbor (Orange County) 南加州三个地点海洋沉积物中微纤维的量化:暴露的海滩(文图拉县)、分水岭(洛杉矶县)和封闭的港口(奥兰治县)
Pub Date : 2022-12-31 DOI: 10.33697/ajur.2022.066
Adrianna Ebrahim, Mia LeClerc
Microfibers are small (<5 mm) fibers made of synthetic materials that are ubiquitous in the environment. The purpose of this observational study was to quantify the number of microfibers in marine sediments and determine which locations have the highest risk for this type of pollution. Sediment samples were taken from three locations in Southern California (Sycamore Watershed, Ventura State Beach Jetty, and Newport Beach Harbor) to determine which had the highest number of microfibers. It was hypothesized that microfibers would be found at each sample site and that the most microfibers would be found at Sycamore Watershed due to its proximity to a wastewater discharge point. The microfibers were separated from the sediment through a process of stratification and filtration and analyzed by a one-way ANOVA and Tukey’s test. Per sample, there was an average of 111.5 (土99.3, n=14) microfibers found per sample at Sycamore Watershed, 59 (土17.4, n=18) at Newport Beach Harbor, and 53 (土14.4, n=18) at Ventura State Beach Jetty. A total of 3,590 microfibers were found from all three sample sites. Analysis revealed that Sycamore Watershed had significantly more microfibers than any other site (p<.05). It is likely that Sycamore Watershed had the most microfibers because of its proximity to a sewage-sludge disposal site that contains the polluted water from our washing machines. In conclusion, microfibers are polluting the sediments in harbors, open coastlines, and watersheds in California, negatively affecting the ecosystems in these areas. KEYWORDS: Microfiber; Microplastic; Macroplastic; Marine Pollution; Synthetic Materials; Wastewater Treatment Plants; Sediments; Watershed; Harbor; Jetty
微纤维是由合成材料制成的小纤维(<5毫米),在环境中随处可见。这项观察性研究的目的是量化海洋沉积物中微纤维的数量,并确定哪些地方受到这种污染的风险最高。从南加州的三个地点(Sycamore Watershed、Ventura State Beach Jetty和Newport Beach Harbor)采集沉积物样本,以确定哪些地方的微纤维数量最多。据推测,在每个采样点都会发现微纤维,而Sycamore分水岭由于靠近废水排放点,因此会发现最多的微纤维。通过分层和过滤过程将微纤维从沉积物中分离出来,并通过单因素方差分析和Tukey检验进行分析。每个样本的平均值为111.5(土99.3,n=14)在Sycamore Watershed的每个样本中发现的微纤维,59(土17.4,n=18),以及53(土14.4,n=18)。在所有三个采样点共发现3590根微纤维。分析显示,Sycamore Watershed的微纤维比任何其他地点都多(p<0.05)。Sycamore分水岭可能是微纤维最多的地方,因为它靠近一个污水污泥处理场,里面有我们洗衣机的污水。总之,微纤维正在污染加利福尼亚州港口、开放海岸线和流域的沉积物,对这些地区的生态系统产生负面影响。关键词:超细纤维;微塑料;宏观塑性;海洋污染;合成材料;废水处理厂;沉积物;转折点港口码头
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引用次数: 0
Stabilization of Cisplatin via Coordination of Ethylenediamine 乙二胺配位稳定顺铂
Pub Date : 2022-12-30 DOI: 10.33697/ajur.2022.067
Samantha Rea, Alex H. Smith, Brooke Hornberger, Grace Fillmore, Jeremy Burkett, Timothy Dwyer
While the chemotherapeutic cisplatin is used to treat a variety of cancers, metal toxicity and cisplatin resistance via genetic and epigenetic changes limits its use and calls for alternative therapies. To combat the observed toxicities and create a more stable compound, which avoids isomerization into a trans configuration, three cisplatin analogues including cispalladium, dichloro-(ethylenediamine)-platinum(II), and dichloro-(ethylenediamine)-palladium(II) were synthesized as potential cisplatin alternatives. Each compound was evaluated for cytotoxicity on SK-OV-3 cells against cisplatin. Synthesis of dichloro-(ethylenediamine)-platinum(II) yielded 20.5% of the theoretical yield, while dichloro-(ethylenediamine)-palladium(II) yielded 49.1%. Results from the cytotoxicity trial revealed that cispalladium was not effective against SK-OV-3 cells, and dichloro-(ethylenediamine)-palladium had minimal effects. The dichloro-(ethylenediamine)-platinum(II) was the most efficacious with an IC50 value of 0.77 µg/ml compared to the IC50 of 0.61 µg/ml for cisplatin. With a similar IC50 to cisplatin, these results suggest that dichloro-(ethylenediamine)-platinum(II) has the potential to serve as a cisplatin alternative for cancer patients who develop resistance following their clinical course of cisplatin. Future studies on the cytotoxicity of dichloro-(ethylenediamine)-platinum(II) to induce cell death on cisplatin-resistance cell lines are necessary to determine the ability of the compound to be utilized as a cisplatin alternative. KEYWORDS: Cisplatin; Ovarian Cancer; SK-OV-3; Drug Resistance; Stability; Palladium; Ethylenediamine; Cispalladium; Dichloro-(ethylenediamine)-platinum(II); Dichloro-(ethylenediamine)-palladium(II)
虽然化疗药物顺铂用于治疗多种癌症,但金属毒性和通过遗传和表观遗传学变化产生的顺铂耐药性限制了其使用,并需要替代疗法。为了对抗观察到的毒性并产生一种更稳定的化合物,避免异构化为反式构型,合成了三种顺铂类似物,包括顺钯、二氯-(乙二胺)-铂(II)和二氯-。评估每种化合物对SK-OV-3细胞对顺铂的细胞毒性。二氯-(乙二胺)-铂(II)的合成产率为理论产率的20.5%,而二氯--(乙二胺)-钯(II)产率为49.1%。细胞毒性试验结果表明,顺式钯对SK-OV-3细胞无效,二氯-。二氯-(乙二胺)-铂(II)是最有效的,IC50值为0.77µg/ml,而顺铂的IC50为0.61µg/ml。与顺铂具有相似的IC50,这些结果表明,二氯-(乙二胺)-铂(II)有潜力作为癌症患者的顺铂替代品,这些患者在顺铂临床疗程后出现耐药性。未来有必要对二氯-(乙二胺)-铂(II)在顺铂耐药细胞系上诱导细胞死亡的细胞毒性进行研究,以确定该化合物用作顺铂替代品的能力。关键词:顺铂;癌症;SK-OV-3;耐药性;稳定性钯;乙二胺;顺钯;二氯-(乙二胺)-铂(II);二氯-(乙二胺)-钯(II)
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引用次数: 0
Differential Expression of Hub Genes and Activation of p53 by Anti-cancer Compound Curaxin CBL0137 抗癌化合物Curaxin CBL0137对中枢基因的差异表达和p53的激活
Pub Date : 2022-10-06 DOI: 10.33697/ajur.2022.061
Tanvi M. Patel, Rochelle Ratner, N. Nath
Cancer is a global concern and there is a need for effective drugs. CBL0137 is a small water-soluble molecule and a new second-generation compound in the family of curaxins with potential anti-cancer activity. Curaxins in general, including CBL0137 intercalate into DNA, and act by targeting the histone chaperone ‘facilitates chromatin transcription’ (FACT) complex and have the potential to treat tumors by reducing the growth of cancer cells which is shown in a variety of cell lines and animal models. CBL0137 is found to activate the tumor suppressor gene p53. However, the mechanism of p53 activation is poorly understood. Utilizing bioinformatics analysis on available datasets of CBL0137 treated cancer cells of glioma, cervical and multiple myeloma, differentially expressed genes (DEGs) that may lead to the activation of p53 were examined. Three GEO datasets of cells treated with various concentrations of CBL0137 were analyzed, namely HSJD-DIPG007 (GSE153441), MM1.S (GSE117611) and HeLa S3 (GSE117611). The DEGs were identified based on p-values less than 0.05, logFC values greater than 1 and less than -1 and analyzed using GEO2R, Enrichr, and STRING, and data visualization was performed on Tableau. Compared to the controls, a total of 229, 1425, and 1005 genes were upregulated while 368, 2322, and 1673 genes were downregulated for HSJD-DIPG007, MM1.S and HeLa S3 datasets, respectively. Further collective analysis revealed a total of 38 common DEGs among the three datasets. Using Enrichr and STRING on these 38 DEGs, seven hub genes were obtained, SKP2, RGS16, CSRP2, CENPA, HJURP, DTL, and HEXIM1 with these possible mechanisms: inhibition of AKT phosphorylation by upregulated genes RGS16 and CSRP2, p300-mediated acetylation of p53 via SKP2, inhibition of MDM2 by DTL downregulation and HEXIM1 upregulation, and inhibition of AURKB via CENPA and HJURP downregulation. This study analyzed the three datasets and highlighted how these identified hub genes may play a role in leading to p53 activation by CBL0137. KEYWORDS: Curaxin; CBL0137; Differentially Expressed Genes; Cancer; p53; Glioblastoma; Cervical; Myeloma
癌症是全球关注的问题,需要有效的药物。CBL0137是一种水溶性小分子,是curaxins家族中新的第二代化合物,具有潜在的抗癌活性。Curaxins,包括CBL0137,通常插入DNA,通过靶向组蛋白伴侣“促进染色质转录”(FACT)复合物发挥作用,并具有通过减少癌症细胞生长来治疗肿瘤的潜力,这在各种细胞系和动物模型中都有显示。发现CBL0137激活肿瘤抑制基因p53。然而,p53激活的机制尚不清楚。利用CBL0137处理的神经胶质瘤、子宫颈和多发性骨髓瘤癌症细胞的可用数据集的生物信息学分析,检测了可能导致p53激活的差异表达基因(DEGs)。分析了用不同浓度的CBL0137处理的细胞的三个GEO数据集,即HSJD-DIPG007(GSE153441)、MM1.S(GSE117611)和HeLa S3(GSE1176 11)。DEG基于小于0.05的p值、大于1且小于-1的logFC值进行识别,并使用GEO2R、Enrichr和STRING进行分析,并在Tableau上进行数据可视化。与对照组相比,HSJD-DIPG007、MM1.S和HeLa S3数据集共有2291425和1005个基因上调,3682322和1673个基因下调。进一步的集体分析显示,三个数据集中共有38个常见的DEG。在这38个DEG上使用Enrichr和STRING,获得了7个枢纽基因,即SKP2、RGS16、CSRP2、CENPA、HJURP、DTL和HEXIM1,其可能机制为:上调基因RGS16和CSRP2抑制AKT磷酸化,p300介导的通过SKP2的p53乙酰化,DTL下调和HEXIM2上调抑制MDM2,以及通过CENPA和HJURP下调抑制AURKB。这项研究分析了三个数据集,并强调了这些已鉴定的枢纽基因如何在导致CBL0137激活p53中发挥作用。关键词:Curaxin;CBL0137;差异表达基因;癌症p53;胶质母细胞瘤;宫颈;骨髓瘤
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American journal of undergraduate research
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