A caracterização no estado sólido de insumos farmacêuticos constitui uma parte muito importante no entendimento de suas propriedades físicas, químicas e farmacológicas. A partir da análise estrutural por difração de raios X em monocristal, pode-se identificar a conformação no estado sólido do fármaco, assim como sua densidade eletrônica. Estes estudos podem ser complementados com dados provenientes da Modelagem Molecular, que compreende um número de ferramentas e métodos computacionais e teóricos que têm como objetivos compreender e prever o comportamento de sistemas reais. Nesse contexto, visando compreender melhor as propriedades de estado sólido apresentadas pelo fármaco anti-filariose dietilcarbamazina (DEC), foi obtido um novo sal, o maleato de dietilcarbamazina (DEC maleato), cujas propriedades foram comparadas com as das estruturas já reportadas, DEC citrato e DEC pura. A DEC maleato foi caracterizada por difração de raios X em monocristal, espectroscopias Raman e Infravermelho e análise térmica. A DEC maleato cristaliza no grupo espacial triclínico PI com dois confôrmeros da molécula de DEC na unidade assimétrica, ambos exibindo caudas etílicas na conformação syn em relação ao anel piperazina, diferentemente do que ocorre na DEC citrato e na DEC pura, nas quais esses fragmentos moleculares apresentam uma conformação anti. A principal interação intermolecular entre o fármaco e o ácido maleico é do tipo N-H•••O, que caracteriza a formação do sal e, consequentemente, do par iônico (DEC)+(maleato)-. Além disso, uma rede complexa de interações intermoleculares não-clássicas do tipo C-H•••O estão presentes entre as moléculas de DEC, DEC-maleato e maleato-maleato, levando a um empacotamento cristalino na forma de um sanduíche, onde os confôrmeros da DEC acomodam-se em colunas intercaladas por bicamadas de íons maleato. Não foram observadas transições de fase estruturais em função da temperatura entre 100 K e temperatura ambiente. No entanto, devido à variação conformacional observada entre as moléculas de DEC, cálculos quânticos foram realizados na fase gasosa, otimizando as conformações moleculares tanto da molécula de DEC neutra quanto da carregada a fim de determinar as características de sua estrutura eletrônica utilizando o método da Teoria do Funcional de Densidade, com o funcional híbrido B3LYP e o conjunto de função de base 6-31++G. Através dos cálculos teóricos foram obtidas quatro novas conformações, uma para DEC neutra e três da carregada, para as quais analisou-se as energias de conformação, os espectros vibracionais simulados e por fim os mapas de potencial eletrostático e os orbitais de fronteira. / The solid state characterization of active pharmaceutical ingredients (API) constitutes an important part in understanding their physical, chemical and pharmacological properties. From the structural analysis by single crystal X-ray diffraction, the API conformation in the solid form, as well as its electronic density, can be identified. These studies can be supplemented with data from the Molecular Modeling, which includes a number of theoretical and computational tools used to understand and to predict the behavior in real systems. In this context, aiming to better comprehend the solid state properties exhibited by the anti-filarial drug diethylcarbamazine (DEC), a new salt was obtained, the diethylcarbamazine maleate (DEC maleate), and its properties were compared with the ones of the reported structures, DEC citrate and pure DEC. The DEC maleate was characterized by single crystal X-ray diffraction, infrared and Raman spectroscopy and thermal analysis. DEC maleate was found to crystallize in the triclinic space group PI with two very similar conformers of the DEC molecule in the asymmetric unit, both exhibiting the ethylic chains in conformation syn in relation to the piperazine ring, unlike what happens to DEC citrate and pure DEC, where these chains are anti related. The main intermolecular interaction between the API and the maleic acid is of the type NH•••O, characterizing the salt formation, and thus, the ionic pair (DEC)+(maleate)-. Moreover, a complex network of no-classical intermolecular interactions of the type CH•••O occur between DEC-DEC, DEC-maleate, and maleate-maleate molecules, leading to a sandwich like crystal packing, where DEC conformers are accommodated in columns intercalated by maleates bilayers. No phase transitions were observed for the molecule structure in function of temperature between 100 K and room temperature. However, due conformational variations observed among DEC molecules of the three structures, quantum calculations were performed in the gas phase, optimizing the molecular conformations of both, the neutral and the charged DEC molecules to determine the characteristics of the electronic structure using the method of Density Functional Theory with the B3LYP hybrid functional and basis set 6-31++G. new conformations it were found, for which geometrical characteristics, conformation energies, vibrational spectra simulation and finally the electrostatic potential maps and the frontier orbitals, were analyzed.

The development and approval of new drugs is an expensive process. The total cost for the approval of a new compound is on average 1.0 - 1.2 billion dollars and the entire process lasts about 12 - 15 years. The main difficulties are related to poor pharmacokinetics, lack of efficacy and unwanted side effects. These problems have naturally led to the question if new and alternative methodologies can be developed to find reliable and low cost alternatives to existing practices. Nowadays, computer-assisted tools are used to support the decision process along the early stages of the drug discovery path leading from the identification of a suitable biomolecular target to the design/optimization of drug-like molecules. This process includes assessments about target druggability, screening of molecular libraries and the optimization of lead compounds where new drug-like molecules able to bind with sufficiently affinity and specificity to a disease-involved protein are designed. Existing computational methods used by the pharmaceutical industry are usually focused on the screening of library compounds such as docking, chemoinformatics and other ligand-based methods to predict and improve binding affinities, but their reliable application requires improvements in accuracy. New quantitative methods based on molecular simulations of drug binding to a protein could greatly improve prospects for the reliable in-silico design of new potent drug candidates. A common parameter used by medicinal chemists to quantify the affinity between candidate ligands and a target protein is represented by the free energy of binding. However, despite the increased amount of structural information, predicting binding free energy is still a challenge and this technique has found limited use beyond academia. A major reason for limited adoption in the industry is that reliable computer models of drug binding to a protein must reproduce the change in molecular conformations of the drug and protein upon complex formation and this includes the correct modelling of weak non-covalent interactions such as hydrogen bonds, burials of hydrophobic surface areas, Van der Waals interactions, fixations of molecular degrees of freedom solvation/desolvation of polar groups and different entropy contributions related to the solvent and protein interactions. For several classes of proteins these phenomena are not easy to model and often require extremely computationally intensive simulations. The main goal of the thesis was to explore efficient ways of computing binding affinities by using molecular simulations. With this aim, novel software to compute relative binding free energies has been developed. The implementation is based on alchemical transformations and it extended a preexisted piece of software Sire, a molecular modeling framework, by using the OpenMM APIs to run fast molecular dynamics simulations on the latest GPGPU technology. This new piece of software has equipped the scientific community with a flexible and fast tool, not only to predict relative binding affinities, but also a starting point to develop new sampling methods for instance hybrid molecular dynamics and Monte Carlo. The implementation has been validated on the prediction of relative hydration free energy of small molecules, showing good agreement with experimental data. In addition, non-additive effects to binding affinities in series of congeneric Thrombin inhibitors were investigated. Although excellent agreement between predicted and experimental relative binding affinities was achieved, it was not possible to accurately predict the non-additivity levels in most of the examined inhibitors, thus suggesting that improved force fields are required to further advance the state-of-the art of the field.

The main goal of my diploma thesis is to compile a business plan on the level that could be submitted to a potencial investor who would invest his own capital into this business idea. The thesis is separated in theoretical part, in which are main definitions, principles of compilation and main forms of business plan described. The practical part refers to own compilation of business plan. This part is separated according to the units described in theoretical part.

The diploma thesis focuses on theoretical and practical aspects of cost control methodology. The effort is to introduce individual tools and methods for cost management. I introduce various instruments for cost management and outline the connections of company costs, systems of their records and their interaction in the form of cost optimization. At the beginning I explain the importance of cost, the reasons for cost management, cost management concepts and their types according to purpose. Then I focus on methodology of costs calculations and budgets as tools for operating cost control. Last section of theoretical part is focused on strategic cost management as a tool for long term cost control. Second part deals with the application of theoretical aspects in practice. This part starts with description of the methodology of cost management in the selected company and also with application of the recommendations resulting from theoretical findings. The main goal of diploma thesis will be achieved by analysing company's current situation, identifying critical problem areas and proposing steps leading to a solution suited for company's needs. The scope of work presented in the first part of the thesis will be applied on Teplospol a.s.; solutions that suit the company will be proposed.

The purpose of this study is to identify and analyze the relationships that exist between mathematics anxiety and nurse self-efficacy for mathematics, and the medication calculation performance of acute care nurses. This research used a quantitative correlational research design and involved a sample of 84 acute care nurses, LVNs and RNs, from a suburban private hospital. the participants filled out a Mathematics Anxiety Scale, a Nurse Self-Efficacy for Mathematics Scale and also completed a 20-item medication calculation test. Significant practical and statistical relationships were discovered between the variables utilizing multiple linear regression statistics and commonality analysis. As the Nurse’s Mathematics anxiety score increased the scores on the medication test decreased and the scores on nurse self-efficacy for mathematics scale also decreased. the demographic item of “Hours a nurse worked in one week” had the greatest significance. the more hours a nurse worked the lower their score was on the medication calculation test. This study agrees with others that nurses are not good at mathematics. This study also correlated that as the number of hours worked increased so did the medication calculations errors. and many nurses have a measurable level of anxiety about mathematics and dosage calculations and this may influence calculation ability. Suggestions for further research include refinement of instruments used in study, further differentiation of barriers to successful medication calculation performance, and testing of interventions used to teach, train and evaluate accurate medication administration in nurses.

This diploma work deals with Technical and operational comparison of aerotaxi aircraft. I picked out this theme because of SkyService company, which plans to locate upon this form of transportation. In diploma work I attend to basic factors that affect selection of aeronautical technics, also economics and technical calculation

There is a need for reliable rules of thumb for various applications in the area of biochemistry, supramolecular chemistry and material sciences. Simultaneously, the amount of information, which we can gather from X-ray crystal geometries about the nature of recognition processes, is limited. Deeper insight into the noncovalent interactions playing the most important role is needed in order to revise these universal rules governing any recognition process. In this thesis, systematic development and study of the accuracy of the computational chemistry methods followed by their applications in protein DNA and host guest systems, are presented. The non-empirical quantum mechanical tools (DFT-D, MP2.5, CCSD(T) etc. methods) were utilized in several projects. We found and confirmed unique low lying interaction energies distinct from the rest of the distributions in several amino acid−base pairs opening a way toward universal rules governing the selective binding of any DNA sequence. Further, the predictions and examination of changes of Gibbs energies (ΔG) and its subcomponents have been made in several cases and carefully compared with experiments. We determined that the choline (Ch+) guest is bound 2.8 kcal/mol stronger (calculated ΔG) than acetylcholine (ACh+) to self-assembled triple helicate rigid...

<div>This dissertation concerns the development of quantum computing algorithms for solving electronic structure problems. Three projects are contained: comparison of quantum computing methods for the water molecule, the design and implementation of Fully Controlled Variational Quantum Eigensolver(FCVQE) method, and quantum computing for atomic and molecular resonances. </div><div> </div><div>Chapter 1 gives a general introduction to quantum computing and electronic structure calculations. It includes basic concepts in quantum computing, such as quantum bits (qubits), quantum gates, and an important quantum algorithm, Phase Estimation Algorithm(PEA). It also shows the procedure of molecular Hamiltonian derivation for quantum computers.</div><div><br></div><div> </div><div>Chapter 2 discusses several published quantum algorithms and original quantum algorithms to solve molecules' electronic structures, including the Trotter-PEA method, the first- and second-order Direct-PEA methods, Direct Measurement method, and pairwise Variational Quantum Eigensolver(VQE) method. These quantum algorithms are implemented into quantum circuits simulated by classical computers to solve the ground state energy and excited state energies of the water molecule. Detailed analysis is also given for each method's error and complexity. </div><div><br></div><div> </div><div>Chapter 3 proposes an original design for VQE, which is called Fully Controlled Variational Quantum Eigensolver(FCVQE). Based on Givens Rotation matrices, this design constructs ansatz preparation circuits exploring all possible states in the given space. This method is applied to solving the ground state energy curves for different molecules, including NaH, H₂O, and N₂. The results from simulators turn out to be accurate compared with exact solutions. Gate complexity is discussed at the end of the chapter.</div><div><br></div><div> </div><div>Chapter 4 attempts to apply quantum simulation to atomic and molecular resonances. The original design implements the molecule's resonance Hamiltonian into the quantum circuit, and the resonance properties can be obtained from the final measurement results. It is shown that the resonance energy and width of a model system can be calculated by executing the circuit using Qiskit simulators and IBM real quantum computers as well. A proof of concept is also shown for the resonance properties of a real molecule, H₂^-. In the future, when there are more available qubits, longer coherence time, and less noise in quantum computers, this method can be used for larger molecular systems with better accuracy.</div>

The numerical solutions of many types of problems are generally obtained by solving approximating linear algebraic systems. Moreover, in solving a nonlinear problem, one may replace it by a sequence of linear systems providing progressively improved approximations. For the study of these linear systems of equations a geometric terminology with the compact symbolism of vectors and matrices is useful. A resume of the basic principles of higher algebra necessary for the development of the material to follow is therefore included. / "A Paper." / "Submitted to the Graduate Council of Florida State University in partial fulfillment of the requirements for the degree of Master of Science." / Advisor: Paul J. McCarthy, Professor Directing Paper. / "May, 1958." / At head of title: Florida State University. / Typescript. / Includes bibliographical references.

Ab initio and density functional theory calculations confirm Craig's assignment of the fundamental vibrational modes of tetrafluorooxirane with the exception that assignments of the C-F stretching modes v9 (b1) and v13 (b2) should be exchanged. The calculated structural parameters are in good agreement with results of microwave studies except for the C-C bond length for which all the calculated results are slightly too long.