Pharmacophore derivation using discotech and comparison of semi-emperical, AB initio and density functional CoMFA studies for sigma 1 and sigma 2 receptor-ligands

This study describes the development of pharmacophore and CoMFA models for sigma receptor ligands. CoMFA studies were performed for 48 bioactive sigma 1 receptorligands using [H3 ](+) pentazocine as the radioligand, for 30 PCP derivatives for sigma 1 receptor-ligands using [3H](+)SK-F 10047 as the radioligand and for 24 bioactive sigma 2 receptor-ligands using the radioligand [H3](+)DTG in the presence of pentazocine. Distance Comparisons (DISCOtech) was used as the starting point for CoMFA studies. The conformers, derived by DISCOtech were optimized using AMi, or HF/3-21G* in Gaussian 98. The optimized geometries were aligned with the pharmacophore, derived using DISCOtech. Atomic charges were calculated using AMl, HF/3-21G*, B3LYP/3-21G*, MP2/3-21G* methods in Gaussian 98. The CoMFA Maps that were developed using Sybyl 6.9 were compared on steric and electrostatic field differences. With leaveone-out cross validation the numbers of optimal components were decided. Using these numbers of optimal components no cross validation was performed in a training set. After a test set, it was known that CoMFA models derived from HF/3-21G* optimized geometries were more reliable in predicting bioactivities than CoMFA models derived from AMi optimized geometries

Thermochemical properties of methyl and chloro-methyl hyplochlorites and ethers and reaction of methyl radical with CLO

Hypochlorites are formed from reactions of chlorine monoxide (ClO) addition to unsaturates and association with radicals. ClO is a prevalent and an important species in chemistry of the atmosphere and in combustion systems where chlorine is present. Thermochemical property data on these oxy-chlorocarbon species are important to understanding the reaction pathways and kinetics in these environments. Enthalpy, ΔHf°298, entropy, S°298, and heat capacities, Cp(T) from 300 to 1500 K are determined for methyl hypochlorite and three chloro-methyl hypochlorites and formaldehyde-C1 atomcomplex radicals (CH2O--Cl, CHClO--CI, CCI2O--Cl) by density functional, and ab initio calculation methods. Molecular structures and vibration frequencies are determined at the B3LYP /6-3 1 G(d,p) density functional calculation level, with single point calculations energy at the B3LYP/G(d,p), B3LYP/6-311+G(3df,2p), QCISD(T)/6-31G(d,p), and CBS-Q levels of calculation. Enthalpies of formation are determined at each calculation level using the ΔH°rxn, and known enthalpies of other reactants in each of several working reactions (up to seven). Barriers for intramolecule rotation are calculated and contributions to entropy and heat capacity from internal rotation in the chloro-methyl hypochlorite, chloro-dimethyl ether, chloro-methoxy and formaldehyde-Cl atom coupling radicals are determined. Evaluation of enthalpy data from reaction (up to seven) schemes and the statistical distribution of rotation conformers, result in ΔHf°298for CH3OCI of - 15,4 ± 1.5, CH2 ClOCL of -22.1 ± 2, CHCl2OCl of -26.1 ± 4 and CCl3OCI of -26.7 ± 5 kcal/mol in CBS-Q//B3LYP/6-31 G(d,p) method. Evaluation of data from all 7 reaction schemes, and the statistical distribution analysis of rotation conformers, result in ΔHf°298 values for CH2ClOCH3 of -55.4 ± 1, CHCl2OCH3 of -61.8 ± 2, and CCl3OCH3 62.8 ± 3 kcal/mol at the CBS-Q//B** level. Enthalpies of formation are determined at each calculation level using the ΔHf°rxn298 and known enthalpies of other reactants in each of 6 different working reactions. The statistical distribution analysis of rotation conformers is also considered; ΔHf°rxn298 values for CH2ClO · of -4.5 ± 0.3, CHCl2O · of -5.6 ± 0.3, CCl3O· of - 7.5 ± 0.3, CH2O--Cl of - 2.1 ± 0.3, CHClO--Cl of - 17.5 ± 0.3, and CCl2O-Cl of -24.7 ± 0.3 kcal/mol at the CBS-Q//B3**. The reaction system (CH3Cl + ClO \u3c--\u3e CH3OCl \u3c--\u3e Products) is very important to understanding the depletion effect of chlorine chemistry on stratospheric ozone layer. Monochlorine monoxide radical (ClO) is known the cause of ozone depletion and alkyl and alkyl halides are most abundant atmosphere. The kinetics for the reactions of monochlorine monoxide radical (ClO) methyl radical are analyzed by using quantum Rice- Ramsperger- Kassel (QRRK) theory for k, (E).and a modified strong collision approach for falloff

The Effect of Health Service Quality on Health Facility Choice and Health Outcomes in Malawi

We study the impact of health care service quality on health facility choice and health outcomes in Malawi. We use Malawi Demographic and Health Survey (MDHS) 2015 and Malawi Service Provision Assessment (MSPA) 2013-2014 to examine the effect. MSPA provides many useful health care service quality information that has not been examined much in the previous studies. We create health care service quality measures to represent infrastructure quality, medical supplies quality and health facility management quality. We examine the impact of these quality measures on the demand for health services and health outcomes. We find that people who live closer to quality health facilities are more likely to utilize health services such as facility delivery. However, we do not find strong and significant evidences that healthcare quality is associated with positive health outcomes due to the insufficient data and the weak identification strategies

The Effect of Health Facility Births on Newborn Mortality in Malawi

We examine the effect of health facility births on newborn mortality in Malawi using data from a unique survey of mothers in the Chimutu district, Malawi and data from the Malawi Demographic and Health Survey 2015. The study exploits two instrumental variables to overcome endogeneity of health facility births—labor contraction time and interaction of distance to health facilities and rainfall at birth. The results show that health facility births significantly reduce 7-day and 28-day mortality rates. We find suggestive evidence that readily available medical resources are the potential mechanisms through which health facility births reduce newborn mortality

Optimal Synthesis of Horizontally Aligned Single-Walled Carbon Nanotubes and Their Biofunctionalization for Biosensing Applications

As an influential candidate for highly sensitive biomolecule sensor, which can capture disease related biomolecules, carbon nanotube is useful material due to its unique properties. To adopt as a sensing platform, it is strongly needed to find optimal refined synthetic condition. In order to find the optimal synthetic conditions of horizontally aligned CNT, we performed quantity control of themixed gases of H-2 and CH4 injected. We successfully find that the formation of amorphous-like carbon was critically affected by some gas condition such as the flow rate of injected gases and ratios of gas mixture. Moreover, it should be noted that our horizontally aligned carbon nanotube array platform developed would offer another potential in developing nanoscale light source, where light emission results from electron-hole carrier recombinationope

Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site

Benzo[a]pyrene (BaP) is a known genotoxicant that affects both mitochondrial and nuclear DNA (mtDNA, nDNA). Here, we examined mtDNA and nDNA damage in the Atlantic killifish (Fundulus heteroclitus) from a highly contaminated Superfund site (Elizabeth River, VA, USA) and from a reference site (King’s Creek, VA, USA) that were dosed with 10 mg/kg BaP. Using the long amplicon quantitative PCR technique, we observed similar increases in mitochondrial and nuclear DNA damage in King’s Creek fish treated with BaP. Killifish from the Elizabeth River showed high levels of basal nDNA and mtDNA damage compared to fish from the reference site, but the level of damage induced due to BaP treatment was much lower in Elizabeth River killifish compared to King’s Creek fish. Laboratory-reared offspring from both populations showed increased BaP-induced damage in mtDNA, relative to nDNA. Similar to the adult experiment, the Elizabeth River larvae had higher levels of basal DNA damage than those from the reference site, but were less impacted by BaP exposure. Measurements of oxidative DNA damage (8-oxo-deoxyguanine by LC-MS/MS) showed no differences among treatment groups, suggesting that the majority of DNA damage is from covalent binding of BaP metabolites to DNA. This study shows for the first time that mitochondria can be an important target of BaP toxicity in fish, indicating that BaP exposures could have important energetic consequences. Results also suggest that multi-generational exposures in the wild may lead to adaptations that dampen DNA damage arising from BaP exposure

Social distancing policy and mental health during COVID-19 pandemic: an 18-month longitudinal cohort study in South Korea

BackgroundDespite the effectiveness of social distancing policies in preventing the spread of Coronavirus Disease 2019 (COVID-19), their impact on mental health remains a concern. Longitudinal studies investigating the psychological effects of social distancing are limited.MethodsLongitudinal data on psychological variables were collected eight times between May 2020 and November 2021 through online surveys in South Korea.ResultsThe participants in the study reported a worsening of depressive and anxiety symptoms, suicide risk, and psychological distress with increasing levels of social distancing. Specifically, during the third wave, when social distancing levels peaked, the highest levels of depression, anxiety, and psychological distress were observed, and the second-lowest levels of vitality were reported. Furthermore, psychological risk factors, such as depressive symptoms, anxiety symptoms, and suicidal risk, were closely associated with vitality levels in daily life.DiscussionsDuring the pandemic, although social distancing helped prevent the spread of COVID-19, it also led to increased depression, anxiety, suicide risk, psychological distress, and decreased vitality. Engagement at a personal level in fundamental daily activities is important to cope with psychological distress. Our results indicate that commitment to fundamental daily activities and following routines is an important protective factor against psychological distress, notwithstanding COVID-19