Time-Dependent Effects of Anesthetic Isoflurane on Reactive Oxygen Species Levels in HEK-293 Cells

The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. The time course of these effects, however, remains to be determined. Therefore, we performed a pilot study to determine the effects of treatment with isoflurane for various times on ROS levels in HEK-293 cells. The cells were treated with 2% isoflurane plus 21% O2 and 5% CO2 for 15, 30, 60, or 90 min. We then used fluorescence imaging and microplate fluorometer to detect ROS levels. We show that 2% isoflurane for 60 or 90 min, but not 15 or 30 min, induced ROS accumulation in the cells. These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity

Do uncertainties affect clean energy markets? Comparisons from a multi-frequency and multi-quantile framework

Clean energy market has great potential to promote the balance between economic development and environmental protection, and has gradually become one of the vital energy markets. This paper investigates the real effects of external uncertainties from oil price shocks (supply, demand, and risk shocks) and political factors on the clean energy market based on a multi-frequency and multi-quantile framework. The empirical results show that both oil price shocks significantly impact the clean energy market, especially the oil demand shock. Two political factors, economic policy uncertainty and geopolitical risk, also have a one-way influence on the clean energy market. Additionally, the impact of most external uncertainties on the clean energy market is more prominent in the long term than in the short and medium term. Finally, the clean energy market with different market conditions also has different abilities to resist external uncertainties. Our research analyses all the joint distributions between each external uncertainty and the clean energy index in identical time frames. It is helpful for investors to construct more rational investment strategies and for policymakers to make appropriate policy arrangements

Three essays in real option models of real estate development

Real estate developments make great applications for real option theory. However, current real option models for real estate development do not pick up the important features of real estate development such as the land-use right as an on-going lease agreement or the entitlement processes in every development project. We build and solve mathematically parsimoneous yet plausible stochastic-control models to capture these features and the models yield rich implications. We then test these implications empirically using manually-collected data. In chapter one, we model the real estate development process as a compound real option in a parsimonious continuous-time feedback control framework. The acquisition of a land-use right is the first option, and the decision to begin construction is the second option. We model the cost of maintaining the land-use right as a running cost during the waiting period before construction. This feature allows the running cost to be stochastic and interacts with both the decision to obtain the right and the decision to start construction. We obtain a closed-form solution for the value of the compound option and demonstrate rich implications using numerical examples. A higher running cost squeezes the two decisions together while a lower running cost encourages the acquisition of the land-use right and delays construction simultaneously. In chapter two, we recognize that entitlement process is highly risky and out of control of the investors in reality. Moreover, the real estate market in the U.S. has shown a trend towards more stringent entitlement regulation. Therefore, we model entitlement process as a separate stage in development process in which the investor has little control. In particular, we model the entitlement stage as a European style real option with a stochastic entitlement cost. We solve the model analytically. Our main result implies that, to the contrary of tradition real option theory, higher entitlement risk urges the investors to start entitlement process earlier in order to counter the lack of control. In chapter three, we test the empirical implications of entitlement in the previous chapter using hand-collected Charlotte local data of rezoning petitions. In particular, we collect waiting time, number of revisions, size of lot, decision outcome as well as other characteristics for rezoning petition from 2001 to 2012, published on Charlotte-Mecklenburg City Planning website. The results of negative binomial regressions confirm our earlier theoretical prediction that the investors start earlier when facing more difficult and riskier entitlement process. Moreover, house price is overall negatively correlated with the entitlement riskiness, which aggravates the hastening effect of entitlement risk. In conclusion, our real option models of land-use right and entitlement in real estate development prove to be mathematically novel, economically insightful, and show potential for wide applications

Mild Hypothermia Attenuates the Anesthetic Isoflurane-Induced Cytotoxicity

The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C). We assessed the cell viability by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assay. We determined DNA damage by measuring levels of phosphorylation of the histone protein H2A variant X at Ser139 (γH2A.X), the marker of DNA damage. We also measured ATP levels in the cells. Here we showed that the treatment with 2% isoflurane for 6 h induced cytotoxicity and DNA damage in the cells. Moreover, the treatment with 2% isoflurane for 3 h decreased ATP levels without inducing cytotoxicity. Mild hypothermia attenuated the isoflurane-induced cytotoxicity, DNA damage, and ATP reduction in the cells. Taken together, these data suggest that the isoflurane-induced reduction in ATP levels occurred before the isoflurane-induced cytotoxicity. Isoflurane may induce DNA damage and cause cytotoxicity through reducing ATP levels. Mild hypothermia would ameliorate isoflurane-induced DNA damage and cytotoxicity by attenuating the isoflurane-induced reduction in ATP levels. These pilot studies have established a system and will promote the future investigations of anesthesia neurotoxicity

Genome-Wide Differential Expression Profiling of Pulmonary circRNAs Associated With Immune Reaction to Pasteurella multocida in Goats

Pasteurella multocida is a highly versatile pathogen that infects a wide range of animals, including goats, causing pneumonia and hemorrhagic septicemia. Circular RNA (circRNA) is a type of non-coding RNA that plays an important role in regulating cellular metabolism. However, whether and how circRNA is involved in regulating immune responses in the goat lung has not been reported. Thus, this study was designed to examine the function of circRNA in goats infected with Pasteurella multocida. Goats were assigned into one of two groups: an uninfected control group (CK) and an infected group challenged with P. multocida. Compared with the CK group, which remained healthy, the infected goats showed clinical signs of infection, including depression, cough, nasal discharge, and dyspnea, along with elevated body temperature and lesions in the lung. Whole-transcriptome sequencing and small RNA sequencing were then performed using lung samples from goats from each group. A total of 138 circRNA, 56 microRNAs (miRNA), and 2,673 messenger RNA (mRNA) molecules were significantly differentially expressed in the P. multocida-infected group compared with the CK group. Randomly selected differentially expressed circRNA, miRNA, and mRNA molecules (n = 5 per group) were then validated by quantitative reverse-transcriptase polymerase chain reaction analysis. Gene ontology (GO) analysis of the source genes indicated that six immune-related terms were enriched among the differentially expressed cirRNA molecules, including inflammatory response, immune effector process, cell activation involved in immune response, cytokine-mediated signaling pathway, response to endogenous stimulus, and immune response. The corresponding circRNA molecules were then selected for construction of a competitive endogenous RNA network to identify networks that may be involved in the immune response to P. multocida infection. The results indicated that P. multocida HN01 may cause pneumonia and stimulate an immune response in goats via regulation of circRNA expression. This study presents the first comprehensive circRNA profile in response to P. multocida infection in goats, thus, providing a basis for understanding the function of circRNA in the host immune response to P. multocida infection

Protocol for a Single-Center Randomized Controlled Trial of Percutaneous Coronary Intervention Via Distal Transradial Access Versus Transradial Access

Background: Although transradial access (TRA) has become the main vascular access for coronary intervention, its high radial artery occlusion rate limits its application in some patients. Studies have shown that compared with TRA, distal transradial access (dTRA) with the snuffbox area or the Hegu acupoint area as the puncture point significantly decreases the incidence of radial artery occlusion. However, no randomized controlled study has confirmed the safety and efficacy of coronary artery intervention via dTRA in China. Methods and analyses: This single-center, prospective, randomized controlled, superiority open-label study will enroll 428 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention as the study population. After preoperative evaluation, the participants will be randomly divided into a study group (dTRA) and control group (TRA) in a 1:1 ratio. The primary endpoint (radial artery occlusion at 24 hours after operation) and secondary endpoint events will be evaluated and recorded. Study registration: This study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300073902)

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented