This thesis aims at analyzing the EU policy of AKP (Adalet ve Kalkinma partisi - Justice and Development Party) based on the concepts of Euroscepticism and Europragmatism. Related to that aim initially the Euroscepticism and conjoint concepts are considered. Furthermore, Euroscepticism in Turkey is discussed at public and political party levels. To what extent the EU policy of AKP has undergone a change since it came to power in 2002 is discussed. Moreover the EU policy of MGH (Milli G&ouml / r&uuml / s Hareketi - National Outlook Movement), a political movement from which AKP emanated is discussed. Looking at their EU policy, it is discussed to what extent AKP differs from the National Outlook Movement. Literature review and discourses of the party officials showed that the Political Islam in Turkey has been in a transformation process since 28 February Process and in this process EU has formed an anchor for the Political Islamists. AKP that separated from the Political Islam movement has also been affected by this transformation process. AKP has given support for the EU process if it serves to domestic goals of the party. However since 2005 due to the internal and external factors AKP&rsquo / s commitment to the EU process has declined.

COVID-19 is caused by a novel coronavirus which has a high affinity for ACE-2 receptors in respiratory epithelium. The high affinity for ACE-2 allows the virus to infiltrate cells leading to viral assembly, maturation, and release. COVID-19 presents itself with respiratory and cold-like symptoms which may ultimately develop into ARDS. This study analyzed the demographics of inpatients who tested positive at MGH as well as their eligibility and enrollment status for COVID-19 clinical trials. When looking at the study population, MGH and the state of Massachusetts shared similar distributions of hospitalized men and women. MGH had a slightly higher proportion of Non-Hispanic Black hospitalized patients and a lower proportion of Hispanic hospitalized patients compared to the state of MA. MGH also had a higher percent of hospitalized patients 65 and older compared to the state. This study found statistically significant differences among eligibility status and enrollment status across race/ethnicity and age. There were no statistically significant differences among eligibility status or enrollment status across sex. Differences among eligibility and enrollment status among those 65 and older may be due to the large elderly population that utilizes MGH for care. It may also have to do with the fact that those who were under 65 had shorter hospital stays. The differences between eligibility and enrollment status across race/ethnicity may have to do with the hospital’s program dedicated to clinical trial inclusion of Spanish speaking patients. Findings from this study exemplify MGH’s efforts for equitable clinical trial involvement.

Queratinócitos são um veículo bastante atrativo para a transferência gênica ex vivo e liberação sistêmica uma vez que as proteínas secretadas por estas células podem atingir a circulação via um mecanismo similar ao processo natural. Um eficiente vetor retroviral (LXSN) contendo o gene do hormônio de crescimento de camundongo (mGH) foi utilizado para transduzir queratinócitos humanos primários. Os queratinócitos transduzidos apresentaram um nível de secreção in vitro alto e estável atingindo até 11 g mGH/106 células/dia. Os epitélios formados por estes queratinócitos geneticamente modificados apresentaram, porém, uma queda na taxa de secreção > 80 % quando foram retirados da placa de cultura utilizando um procedimento clássico. A substituição desta metodologia clássica por uma cultura organotípica resolveu completamente este problema. Camundongos anões imunodeficientes (lit/scid) implantados com estes enxertos organotípicos foram acompanhados durante 4 meses, e apresentaram um aumento de peso significativo (P<0,05) nos primeiros 40 dias. Níveis circulatórios de mGH atingiram um pico de 21 ng/mL 1 h após o implante, mas estes níveis rapidamente atingiram níveis basais (~2 ng/mL). Os queratinócitos humanos primários apresentaram portanto altos níveis de expressão in vitro e os maiores níveis circulatórios, porém por um breve período de tempo, reportados até o momento para GH neste tipo de células. Em conjunto com resultados que mostraram uma recuperação considerável da eficiência de secreção de mGH em cultura por enxertos organotípicos retirados dos animais, foram discutidos os fatores que ainda impedem a utilização clínica deste modelo promissor de terapia gênica cutânea. / Keratinocytes are a very attractive vehicle for ex vivo gene transfer and systemic delivery, since proteins secreted by these cells may reach the circulation via a mechanism which mimics the natural process. An efficient retroviral vector (LXSN) encoding the mouse growth hormone gene (mGH) was used to transduce primary human keratinocytes. Organotypic raft cultures were prepared with these genetically modified keratinocytes and were grafted onto immunodeficient dwarf mice (lit/scid). Transduced keratinocytes presented a high and stable in vitro secretion level of up to 11 g mGH/106cells/day. Conventional epidermal sheets made with these genetically modified keratinocytes, however, showed a drop in secretion rates of > 80% simply due to detachment of the epithelium from its substratum. Substitution of conventional grafting methodologies with organotypic raft cultures completely overcame this problem. The stable long-term grafting of such cultures onto immunodeficient dwarf (lit/scid) mice could be followed for more than 4 months, and a significant weight increase (P<0.05) over the control group was observed in the first 40 days. Circulating mGH levels revealed a peak of 21 ng/mL just 1h after grafting, but unfortunately these levels rapidly fell to baseline values (~ 2 ng/mL). mGH-secreting primary human keratinocytes presented the highest in vitro expression and peak circulatory levels reported to date for a form of GH with this type of cells. Together with data showing that excised implants can recover in culture a remarkable fraction of their original in vitro mGH secretion efficiency, the factors that might still hamper the success of this promising model of cutaneous gene therapy are discussed. SUMÁRIO

Queratinócitos são um veículo bastante atrativo para a transferência gênica ex vivo e liberação sistêmica uma vez que as proteínas secretadas por estas células podem atingir a circulação via um mecanismo similar ao processo natural. Um eficiente vetor retroviral (LXSN) contendo o gene do hormônio de crescimento de camundongo (mGH) foi utilizado para transduzir queratinócitos humanos primários. Os queratinócitos transduzidos apresentaram um nível de secreção in vitro alto e estável atingindo até 11 g mGH/106 células/dia. Os epitélios formados por estes queratinócitos geneticamente modificados apresentaram, porém, uma queda na taxa de secreção > 80 % quando foram retirados da placa de cultura utilizando um procedimento clássico. A substituição desta metodologia clássica por uma cultura organotípica resolveu completamente este problema. Camundongos anões imunodeficientes (lit/scid) implantados com estes enxertos organotípicos foram acompanhados durante 4 meses, e apresentaram um aumento de peso significativo (P<0,05) nos primeiros 40 dias. Níveis circulatórios de mGH atingiram um pico de 21 ng/mL 1 h após o implante, mas estes níveis rapidamente atingiram níveis basais (~2 ng/mL). Os queratinócitos humanos primários apresentaram portanto altos níveis de expressão in vitro e os maiores níveis circulatórios, porém por um breve período de tempo, reportados até o momento para GH neste tipo de células. Em conjunto com resultados que mostraram uma recuperação considerável da eficiência de secreção de mGH em cultura por enxertos organotípicos retirados dos animais, foram discutidos os fatores que ainda impedem a utilização clínica deste modelo promissor de terapia gênica cutânea. / Keratinocytes are a very attractive vehicle for ex vivo gene transfer and systemic delivery, since proteins secreted by these cells may reach the circulation via a mechanism which mimics the natural process. An efficient retroviral vector (LXSN) encoding the mouse growth hormone gene (mGH) was used to transduce primary human keratinocytes. Organotypic raft cultures were prepared with these genetically modified keratinocytes and were grafted onto immunodeficient dwarf mice (lit/scid). Transduced keratinocytes presented a high and stable in vitro secretion level of up to 11 g mGH/106cells/day. Conventional epidermal sheets made with these genetically modified keratinocytes, however, showed a drop in secretion rates of > 80% simply due to detachment of the epithelium from its substratum. Substitution of conventional grafting methodologies with organotypic raft cultures completely overcame this problem. The stable long-term grafting of such cultures onto immunodeficient dwarf (lit/scid) mice could be followed for more than 4 months, and a significant weight increase (P<0.05) over the control group was observed in the first 40 days. Circulating mGH levels revealed a peak of 21 ng/mL just 1h after grafting, but unfortunately these levels rapidly fell to baseline values (~ 2 ng/mL). mGH-secreting primary human keratinocytes presented the highest in vitro expression and peak circulatory levels reported to date for a form of GH with this type of cells. Together with data showing that excised implants can recover in culture a remarkable fraction of their original in vitro mGH secretion efficiency, the factors that might still hamper the success of this promising model of cutaneous gene therapy are discussed. SUMÁRIO

Several hydrides of Group 2 and 12 elements were generated in the gas phase using an emission source that combines an electrical discharge with a high temperature furnace, and their high-resolution infrared emission spectra were recorded with a Fourier transform spectrometer. Two classes of molecules were studied: <em>a)</em> diatomic metal hydrides BeH, MgH, CaH, SrH, ZnH and CdH; <em>b)</em> linear triatomic metal hydrides BeH₂, MgH₂, ZnH₂ and HgH₂. <br /><br /> Infrared emission spectra of BeH, MgH, CaH, SrH, ZnH and CdH free radicals contained several vibration-rotation bands in their ²SIGMA⁺ ground electronic state. The new data were combined with all the previous ground state data from diode laser infrared spectra and pure rotation spectra available in the literature. Spectroscopic constants, i. e. , vibrational band origins, rotational, centrifugal distortion, and spin-rotation interaction constants, were determined for each observed vibrational level by least-squares fitting of all the data. In addition, the data from all isotopologues were fitted simultaneously using the empirical Dunham-type energy level expression for ²SIGMA⁺ states, and correction parameters due to the breakdown of the Born-Oppenheimer approximation were determined. The equilibrium internuclear distances (<em>r</em>_e) of ⁹BeH, ²⁴MgH, ⁴⁰CaH, ⁸⁸SrH, ⁶⁴ZnH and ¹¹⁴CdH were determined to be 1. 342424(2), 1. 729721(1), 2. 002360(1), 2. 146057(1), 1. 593478(2) and 1. 760098(3) angstroms, respectively, and the corresponding <em>r</em>^e distances for ⁹BeD, ²⁴MgD, ⁴⁰CaD, ⁸⁸SrD, ⁶⁴ZnD and ¹¹⁴CdD are 1. 341731(2), 1. 729157(1), 2. 001462(1), 2. 145073(1), 1. 593001(2) and 1. 759695(2) angstroms, respectively. <br /><br /> Gaseous BeH², MgH², ZnH² and HgH² molecules were discovered and unambiguously identified by their high-resolution infrared emission spectra. The &nu;₃ antisymmetric stretching fundamental band and several hot bands in the &nu;₃ region were rotationally analyzed, and spectroscopic constants were obtained for almost all naturally-occurring isotopologues. The rotational constants of the 000 ground states were used to determine the <em>r</em>₀ internuclear distances. For BeH₂, ZnH₂, ZnD₂, HgH₂ and HgD₂ molecules, the rotational constants of the 000, 100, 01¹0 and 001 levels were used to determine the equilibrium rotational constants (<em>B</em>_e) and the associated equilibrium internuclear distances <em>r</em>_e. The <em>r</em>_e distances of ZnH₂ and ZnD₂ differed by about 0. 01%, and those of HgH₂ and HgD₂ differed by about 0. 005%. These discrepancies were larger than the statistical uncertainties by one order of magnitude, and were attributed to the breakdown of the Born-Oppenheimer approximation.

The procedures and results of experimental and/or theoretical studies of four transient molecules, GeO, WO, BeH, and MgH are reported in the thesis. Two of them, GeO and WO, are diatomic molecules composed of relatively heavy atoms, and the other two are diatomic molecules with hydrogen as one of their component atoms. The GeO species was generated using a high temperature furnace. The rovibrational spectrum of five isotopomers were detected in emission using a Bruker IFS 120 HR Fourier transform spectrometer. Combined-isotopomer Dunham-type molecular constants have been derived for GeO using the DSParFit computer program. Analysis shows that the Born-Oppenheimer approximation is valid, as expected, for a molecule containing heavy atoms. The WO molecule was generated using a microwave discharge cell, and the spectra of electronic transitions of various systems were detected in emission using both the Bruker IFS 120 HR Fourier transform spectrometer at Waterloo and the McMath Pierce One-Meter Fourier transform spectrometer at the National Solar Observatory in Arizona. The ground electronic state has been confirmed to be X??&#931;^- based on the analysis of seven 0-0 bands. BeH and MgH are typical molecules with hydrogen as one of their component atoms, and the effects of Born-Oppenheimer breakdown were expected. Both of these molecules have rotational perturbations in their excited electronic states. A 'new' method of data processing was used, i. e. , treating the electronic data as if they were from fluorescence series. Thus the harmful influence of the perturbed upper electronic states on the ground electronic state molecular constants is eliminated. By using the DSParFit computer program, accurate sets of combined-isotopomer Dunham-type molecular constants have been derived for the ground electronic states of the two molecules, and Born-Oppenheimer breakdown correction terms have been obtained.

Several hydrides of Group 2 and 12 elements were generated in the gas phase using an emission source that combines an electrical discharge with a high temperature furnace, and their high-resolution infrared emission spectra were recorded with a Fourier transform spectrometer. Two classes of molecules were studied: <em>a)</em> diatomic metal hydrides BeH, MgH, CaH, SrH, ZnH and CdH; <em>b)</em> linear triatomic metal hydrides BeH₂, MgH₂, ZnH₂ and HgH₂. <br /><br /> Infrared emission spectra of BeH, MgH, CaH, SrH, ZnH and CdH free radicals contained several vibration-rotation bands in their ²SIGMA⁺ ground electronic state. The new data were combined with all the previous ground state data from diode laser infrared spectra and pure rotation spectra available in the literature. Spectroscopic constants, i. e. , vibrational band origins, rotational, centrifugal distortion, and spin-rotation interaction constants, were determined for each observed vibrational level by least-squares fitting of all the data. In addition, the data from all isotopologues were fitted simultaneously using the empirical Dunham-type energy level expression for ²SIGMA⁺ states, and correction parameters due to the breakdown of the Born-Oppenheimer approximation were determined. The equilibrium internuclear distances (<em>r</em>_e) of ⁹BeH, ²⁴MgH, ⁴⁰CaH, ⁸⁸SrH, ⁶⁴ZnH and ¹¹⁴CdH were determined to be 1. 342424(2), 1. 729721(1), 2. 002360(1), 2. 146057(1), 1. 593478(2) and 1. 760098(3) angstroms, respectively, and the corresponding <em>r</em>^e distances for ⁹BeD, ²⁴MgD, ⁴⁰CaD, ⁸⁸SrD, ⁶⁴ZnD and ¹¹⁴CdD are 1. 341731(2), 1. 729157(1), 2. 001462(1), 2. 145073(1), 1. 593001(2) and 1. 759695(2) angstroms, respectively. <br /><br /> Gaseous BeH², MgH², ZnH² and HgH² molecules were discovered and unambiguously identified by their high-resolution infrared emission spectra. The &nu;₃ antisymmetric stretching fundamental band and several hot bands in the &nu;₃ region were rotationally analyzed, and spectroscopic constants were obtained for almost all naturally-occurring isotopologues. The rotational constants of the 000 ground states were used to determine the <em>r</em>₀ internuclear distances. For BeH₂, ZnH₂, ZnD₂, HgH₂ and HgD₂ molecules, the rotational constants of the 000, 100, 01¹0 and 001 levels were used to determine the equilibrium rotational constants (<em>B</em>_e) and the associated equilibrium internuclear distances <em>r</em>_e. The <em>r</em>_e distances of ZnH₂ and ZnD₂ differed by about 0. 01%, and those of HgH₂ and HgD₂ differed by about 0. 005%. These discrepancies were larger than the statistical uncertainties by one order of magnitude, and were attributed to the breakdown of the Born-Oppenheimer approximation.

The procedures and results of experimental and/or theoretical studies of four transient molecules, GeO, WO, BeH, and MgH are reported in the thesis. Two of them, GeO and WO, are diatomic molecules composed of relatively heavy atoms, and the other two are diatomic molecules with hydrogen as one of their component atoms. The GeO species was generated using a high temperature furnace. The rovibrational spectrum of five isotopomers were detected in emission using a Bruker IFS 120 HR Fourier transform spectrometer. Combined-isotopomer Dunham-type molecular constants have been derived for GeO using the DSParFit computer program. Analysis shows that the Born-Oppenheimer approximation is valid, as expected, for a molecule containing heavy atoms. The WO molecule was generated using a microwave discharge cell, and the spectra of electronic transitions of various systems were detected in emission using both the Bruker IFS 120 HR Fourier transform spectrometer at Waterloo and the McMath Pierce One-Meter Fourier transform spectrometer at the National Solar Observatory in Arizona. The ground electronic state has been confirmed to be X³&#931;^- based on the analysis of seven 0-0 bands. BeH and MgH are typical molecules with hydrogen as one of their component atoms, and the effects of Born-Oppenheimer breakdown were expected. Both of these molecules have rotational perturbations in their excited electronic states. A 'new' method of data processing was used, i. e. , treating the electronic data as if they were from fluorescence series. Thus the harmful influence of the perturbed upper electronic states on the ground electronic state molecular constants is eliminated. By using the DSParFit computer program, accurate sets of combined-isotopomer Dunham-type molecular constants have been derived for the ground electronic states of the two molecules, and Born-Oppenheimer breakdown correction terms have been obtained.