Influence of Electromagnetic Fields On Biological Signalling: An Experimental and Theoretical Approach

The primary goals of this study were to develop a cell-free in vitro assay for the assessment of nonthermal electromagnetic (EMF) bioeffects and to develop theoretical models in accord with current experimental observations. Based upon the hypothesis that EMF effects operate by modulating Ca2+/CaM binding, an in vitro nitric oxide (NO) synthesis assay was developed to assess the effects of a pulsed radiofrequency (PRF) signal used for treatment of postoperative pain and edema. No effects of PRF on NO synthesis were observed. Effects of PRF on Ca2+/CaM binding were also assessed using a Ca2+-selective electrode, also yielding no EMF Ca2+/CaM binding. However, a PRF effect was observed on the interaction of hemoglobin (Hb) with tetrahydrobiopterin, leading to the development of an in vitro Hb deoxygenation assay, showing a reduction in the rate of Hb deoxygenation for exposures to both PRF and a static magnetic field (SMF). Structural studies using pyranine fluorescence, Gd3+ vibronic sideband luminescence and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were conducted in order to ascertain the mechanism of this EMF effect on Hb. Also, the effect of SMF on Hb oxygen saturation (SO2) was assessed under gas-controlled conditions. These studies showed no definitive changes in protein/solvation structure or SO2 under equilibrium conditions, suggesting the need for real-time instrumentation or other means of observing out-of-equilibrium Hb dynamics. Theoretical models were developed for EMF transduction, effects on ion binding, neuronal spike timing, and dynamics of Hb deoxygenation. The EMF sensitivity and simplicity of the Hb deoxygenation assay suggest a new tool to further establish basic biophysical EMF transduction mechanisms. If an EMF-induced increase in the rate of deoxygenation can be demonstrated in vivo, then enhancement of oxygen delivery may be a new therapeutic method by which clinically relevant EMF-mediated enhancement of growth and repair processes can occur.

Computational Methods in Biophysics and Medicinal Chemistry: Applications and Challenges

In this thesis I described the theory and application of several computational methods in solving medicinal chemistry and biophysical tasks. I pointed out to the valuable information which could be achieved by means of computer simulations and to the possibility to predict the outcome of traditional experiments. Nowadays, computer represents an invaluable tool for chemists. In particular, the main topics of my research consisted in the development of an automated docking protocol for the voltage-gated hERG potassium channel blockers, and the investigation of the catalytic mechanism of the human peptidyl-prolyl cis-trans isomerase Pin1.

Improvement of physical and mental health after transfemoral transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) has emerged as a treatment alternative to surgical aortic valve replacement in elderly high-risk patients with symptomatic severe aortic stenosis. In this patient population, rapid improvement or restoration of quality of life (QoL) is at least as important as improved clinical outcomes. The purpose of the present study was to assess changes in QoL in response to TAVI.

Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors

N,N'-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB(2) inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB(2) inverse agonists with the highest CB(2) binding affinity (CB(2)K(i) of 22-85 nM, EC(50) of 4-28 nM) and best selectivity (CB(1)/CB(2) of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.

[Physical and psychological status of 60-70-year-old citizens of Bern with neurotic symptoms in childhood--a study over more than 50 years (Emmental cohort)]

The present study was undertaken to assess the influence of childhood variables (physical and emotional) to later well-being in a group of rural Swiss (Emmental Cohort). Our study is the first prospective cohort over a time period of more than 50 years. It includes 1537 children who were listed and assessed in 1942 (T1) because they had difficulties in school or were otherwise behaviorally disturbed. In 1995 (T2) more than 60% of the initial population could be reassessed by our study group. We found more subjects at T2 who had been rated as intelligent at T1. More subjects responding to T2 belonged to a higher social class, were more anxious, and had more psychosocial problems at T1. Social income at T2 is correlated to the social class at T1. More subjects have died since who were rated at T1 as being less intelligent, less neurotical, and having higher psychosocial problems. Twice as many men died than women. The emotional situation at T2 is significantly correlated to psychological well-being at T1. The somatic complaints at T2 correlate significantly to neurotic symptoms in childhood (T1). The more intelligent the children were rated at T1, the less emotional and somatic complaints were voiced at T2 and the better the psychic well-being was rated (T2). In addition, the former social milieu (T1) significantly determined somatic and psychological complaints at T2. Our data discern a significant correlation between actual status and former childhood variables more than 50 years later in a rural Swiss cohort (Emmental Cohort).

Assessment of soil erosion vulnerability in rural communities in the vicinity of Motozintla de Mendoza, Chiapas, Mexico : a physical and sociological approach

Soil erosion is a natural geological phenomenon resulting from removal and transportation of soil particles by water, wind, ice and gravity. As soil erosion may be affected from cultural factors as well. The physical and social phenomena of soil erosion are researched in six communities in the upper part of Rio Grijalva Basin in the vicinity of Motozintla de Mendoza, Chiapas, Mexico. For this study, the USDA RUSLE model was applied to estimate soil erosion rates in the six communities based on the available data. The RUSLE model is based on soil properties, topography, and land cover and management factors. These results showed that estimated soil erosion rates ranged from a high of 2,050 metric ton ha-1 yr-1 to a low of 100 metric ton ha-1 yr-1. A survey concerning knowledge, attitudes and practices (KAP) related to soil erosion was also conducted in all 236 households in the six communities. The main findings of the KAP survey were: 69% of respondents did not know what soil erosion was, while over 40% of the population perceived that hurricanes are the biggest factors that cause soil erosion, and about 20 % of the interviewees said that the landslides are the consequences of the soil erosion. People in communities did not perceive cultural factors as important in conservation efforts for reduce vulnerability to erosion; therefore, the results obtained are suggested to be useful for informing efforts to educate stakeholders.

Experimental and theoretical study of microstructure effect on piezoelectric property of one dimensional ZnO nanostructures

Emerging nanogenerators have attracted the attention of the research community, focusing on energy generation using piezoelectric nanomaterials. Nanogenerators can be utilized for powering NEMS/MEMS devices. Understanding the piezoelectric properties of ZnO one-dimensional materials such as ZnO nanobelts (NBs) and Nanowires (NWs) can have a significant impact on the design of new devices. The goal of this dissertation is to study the piezoelectric properties of one-dimensional ZnO nanostructures both experimentally and theoretically. First, the experimental procedure for producing the ZnO nanostructures is discussed. The produced ZnO nanostructures were characterized using an in-situ atomic force microscope and a piezoelectric force microscope. It is shown that the electrical conductivity of ZnO NBs is a function of applied mechanical force and its crystalline structure. This phenomenon was described in the context of formation of an electric field due to the piezoelectric property of ZnO NBs. In the PFM studies, it was shown that the piezoelectric response of the ZnO NBs depends on their production method and presence of defects in the NB. Second, a model was proposed for making nanocomposite electrical generators based on ZnO nanowires. The proposed model has advantages over the original configuration of nanogenerators which uses an AFM tip for bending the ZnO NWs. Higher stability of the electric source, capability for producing larger electric fields, and lower production costs are advantages of this configuration. Finally, piezoelectric properties of ZnO NBs were simulated using the molecular dynamics (MD) technique. The size-scale effect on piezoelectric properties of ZnO NBs was captured, and it is shown that the piezoelectric coefficient of ZnO NBs decreases by increasing their lateral dimensions. This phenomenon is attributed to the surface charge redistribution and compression of unit cells that are placed on the outer shell of ZnO NBs.

Evaluation of physical and mental recovery status after elective liver resection

BACKGROUND AND OBJECTIVE: This prospective, clinical pilot trial compared the Short Form 36 Health Survey (SF-36) and a nine-item quality of recovery [Quality of Recovery 9 (QoR-9)] survey to assess the 1-week outcome after liver resection and prediction of postoperative complications from baseline values before liver resection. METHODS: In 19 patients, the SF-36 was recorded preoperatively (baseline) and on postoperative day (POD) 7. SF-36 z-values (means +/- SD) for the physical component summary (PCS) and mental component summary (MCS) were calculated. QoR-9 (score 0-18) was performed at baseline, POD1, POD3, POD5 and POD7. Descriptive analysis and effect sizes (d) were calculated. RESULTS: From baseline to POD7, PCS decreased from -0.38 +/- 1.30 to -2.10 +/- 0.76 (P = 0.002, d = -1.57) and MCS from -0.71 +/- 1.50 to -1.33 +/- 1.11 (P = 0.061, d = -0.46). QoR-9 was significantly lower at POD1, POD3 and POD5 compared with baseline (P < 0.050, d < -2.0), but not at POD7 (P = 0.060, d = -1.08). Baseline PCS was significantly lower with a high effect size in patients with complications (n = 12) compared with patients without complications (n = 7) (-0.76 +/- 1.46 vs. 0.27 +/- 0.56; P = 0.044, d = -0.84) but not baseline MCS (P = 0.831, d = -0.10) or baseline QoR-9 (P = 0.384, d = -0.44). CONCLUSIONS: The SF-36 indicates that liver resection surgery has a higher impact on physical health than on mental health. QoR-9 determines the feasible time course of recovery with a 1-week return to baseline. Preoperative impaired physical health might predict postoperative complications.