We definitely believe that the government is behind a cover-up of the subject. Some of these shows I have seen are quite believable. I may be crazy, but I believe there is something out there.
Now for me, I believe in reincarnation. I believe that in the life before this one I was burned to death because as a young child I had horrendous nightmares and saw walls of fire around me. When I was older I did a past life regression and it came up with me dying in a fire and since it was so close to my own birth that I had these visions and dreams we figured it happened in the life just prior to this one. As for what will happen to me after I die, I do believe in heaven.
We had a medium come in after my mother passed away and they described her words and what she said was there to welcome us. Older souls eventually are reincarnated if they choose to be. If you like this post, please share it!
So what is supernatural? Beyond what is natural; unexplainable by natural law. What this definition points out is that magic, in essence, is something that occurs which is unexplainable. Our unique cultural history is full of expressions of pride and also full of disapproval.
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Plus the Catholics. Pride is the first and, therefore, worst deadly sin. Being proud in some religious interpretations meant you were unwilling to surrender—theoretically to a higher power—but logistically to the control of the straight white man standing on the pulpit.
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Certainly, the New World liked the tolerance part of it and established that clear separation in government between church and state, which started to let different attitudes about sinning and behavior—including pride—blossom throughout society. When the writer of the Declaration of Independence becomes a Deist, fire and brimstone speeches naturally become less popular.
The legitimate powers of government extend to such acts only as are injurious to others. But it does me no injury for my neighbour to say there are twenty gods, or no god.
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It neither picks my pocket nor breaks my leg. At the same time, these new Americans in were ecstatic about the nation they were bringing into being. Americans love to revel in their pride of country on July 4th, now replete with parades and festivals. Then struggling again. Lather, rinse, repeat. How they get there is really the story. It was time for a nice little stroll down memory lane. This chapter presents design and molecular docking studies about 8-chloro-quinolone compounds.
The predicted activity has been correlated with the experimental activity who has been determined by agar dilution method [ 15 , 16 ].
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Drugs belonging to the quinolone compound are characterized by a quicker biological activity and a larger antibacterial spectrum. They are active on both gram-positive and gram-negative bacteria, as well as on recently discovered bacteria with intercellular development Legionella, Mycoplasma, etc. The area of use of quinolones has expanded from urinary infections to systemic acute and chronic infections lung and bronchus infections, osteitis, septicemia and endocarditis, chronic infections [chronic bronchitis, purulent osteoarthritis, chronic prostatite, cystitis and chronic sinusitis] [ 15 , 16 ].
Molecular docking studies have been performed with CLC Drug Discovery Workbench Software in order to achieve accurate predictions on optimized conformation for both the quinolone as ligand and their target receptor protein to form a stable complex. Molecular docking studies have been performed on topoisomerase II DNA gyrase with 32 quinolone compounds to understand the binding affinity of all quinolones with DNA gyrase.
The quinolone compounds have been synthesized in our laboratory [ 16 ], and their structures are shown in Figure 1 and Table 1. The polarizability is useful to predict the interactions between nonpolar atoms or groups and other electrically charged species, such as ions and polar molecules having a strong dipole moment. Molecular polar surface area PSA [ 20 ] is a descriptor that has been shown to correlate well with passive molecular transport through membranes and therefore allows the prediction of transport properties of the drugs.
A number of important graphical quantities resulted from quantum chemical calculations were displayed, manipulated and interrogated. Another indicator of electrophilic addition local map is provided by the ionization potential, an overlapping of the energy of electron removal ionization on the electron density.
In addition, the electrostatic potential map , an overlay of the electrostatic potential the attraction or repulsion of a positive charge for a molecule on the electron density, is valuable for describing the overall distribution of molecular charge, as well as to predict the sites of electrophilic addition. Another indicator of the electrophilic addition is supplied by the local ionization potential map , an overlapping of the energy of electron removal ionization on the electron density. In the end, an indicator of nucleophilic addition is offered by the LUMO map , an overlap of the absolute value of the lowest unoccupied molecular orbital LUMO.
The molecular orbital analysis of the Frontier molecular orbitals FMOs plays an essential role in the chemical stability of a molecule and in the interactions between atoms. They provide information that can be used to predict the characteristics of molecules such as optical properties and biological activities. These correspond to positive and negative values of the orbital.
For the HOMO of 7-morpholinylunsubstituted-quinolone, FPQ 25 electron density is localized on morpholine heterocyclic, on aromatic ring and on 4-oxo group. For the HOMO of 7-morpholinylchloro-quinolone, FPQ 28 electron density is localized on morpholine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom.
For the HOMO of 7-pyrrolidinylunsubstituted-quinolone, FPQ 35 electron density is localized on pyrrolidine heterocyclic, on aromatic ring and on 4-oxo group. For the HOMO of 7-pyrrolidinylchloro-quinolone, FPQ 36 electron density is localized on pyrrolidine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom.
For the 6-cloroqinolones, the electron density is located in the same manner as the corresponding fluoroquinolones. The frontier orbital gap helps to characterize chemical reactivity of the molecule Table 2. The MEP is especially important for the identification of the reactive sites of nucleophilic or electrophilic attack in hydrogen-bonding interactions and for the understanding of the process of biological recognition [ 21 , 22 ].
An electrostatic potential map for quinolone compounds shows hydrophilic regions in red negative potential and blue positive potential and hydrophobic regions in green.
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The optimized geometry and electrostatic potential pattern of the surface of a FPQ 28 and b 6ClPQ 28 red—negative, high electron density, blue—positive area, low electron density. The local ionization potential map provides another indicator of electrophilic addition; the local ionization map is an overlay of the energy of electron removal ionization on the electron density Figure 6. LUMO map , map that represents a superposition of the absolute value of the lowest unoccupied molecular orbital the LUMO on the electron density, provides another indicator of the nucleophilic addition Figure 7.
The steps to go through to explore protein-ligand interaction using docking are as follows: set up the binding site in a Molecule Project, import the dock ligands to a Molecule Table and inspect the docking results. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolone compounds Figure 8a — c , e , f , h in the active site of the protein receptor Table 3.
The protein-ligand complex has been realized based on the X-ray structure of S. Molecular docking studies with 2XCT receptor. The list of intermolecular interactions between the ligand molecules docked with 2XCT using CLC drug discovery workbench software. It ensures that the ligand orientations and position obtained from the molecular docking studies are valid and reasonable potential binding modes of ligands; the docking methods and parameters used have been validated by redocking Figure 8d , f.
Number of hydrogen bond donors less than 5 the total number of nitrogen-hydrogen and oxygen-hydrogen bonds ;. Number of hydrogen bond acceptors less than 10 the total number of nitrogen and oxygen atoms ;. The number of violations of the Lipinski rules gives an indication of how drug-likeness for a molecule is. In general, orally active drugs have fewer than two violations. These properties can be useful for identifying potential drug-like molecules, or for removing nondrug-like molecules from a compound library before starting a large virtual screening experiment Table 4.
Molecular docking study has been performed relating to some quinolone compounds known in medical therapeutics: ciprofloxacin, norfloxacin and pefloxacin. For a correct interpretation of the data has been used in the study the corresponding compound of ciprofloxacin, ClCp. ClCp is the compound having a chlorine atom in 6-position of quinolone ring in place of fluorine atom.