How the Influence of Religion Makes the Foreign Policy of the Bush Administration Revolutionary, and How This Has Affected Our Relations with European Allies

It is widely recognized that the rhetoric and actions of the Bush administration are strongly marked by religious terminology and principles, particularly those o evangelical Christianity. The prominence and new political sophistication of religious groups imply that its current character is a departure from the past. Yet while religious conservatives are seen as a significant force in domestic and electoral politics, their influence in the arena of foreign policy is not generally a topic of serious debate. The omission is significant; not only do domestic politics often influence the direction of foreign policy, but in the case of the religious wing of the Republican Party, there have recently been a considerable number of direct statements and positions taken with regard to international issues. The evidence that there is a political effect from the Christian evangelicals is seen in the fact that their positions have frequently been reflected by US foreign policy under the Bush administration, particularly the policies on terrorism and Iraq. More often the neoconservative wing of the Republican Party tends to be given credit for these policies, but their collaboration with religious conservatives is not often considered. One of the purposes of this thesis will be to demonstrate the alliance between these two factions. My argument that ideology, both religious and political, has been instrumental to the foreign policy of the Bush administration, will be demonstrated trough a comparison of he political dimensions of these ideologies, the examination of key administration figures, and a critical assessment of alternative argument that discounts the importance of ideology. While American scholarship may be relatively unimpressed by arguments regarding the significance of the religious influence on the foreign policy arena, however, policy-makers and intellectuals in several of our traditional European allies are far less skeptical. Statements directly regarding the political influence of religious conservatives as well as the differing attitudes and policies towards religion may shed light on the various responses towards the US invasion of Iraq. Contributing to the differences on religion are the unique foreign policy traditions in Europe as they developed during the 20th century. Reductionism and a US-centric perspective have hindered a strong analysis of the different reactions. The evolution of foreign policy in Britain, France, Germany, Italy and Spain following World War II will be used to discuss for an evaluation of the broader impact that US policy in Iraq, and the political influence of religion in America more generally, may have for future relations

Electrostatic effects in proteins are governed by redistribution of the conformational ensemble

The ability to regulate pH dynamics is one of the hallmarks of all living cells. pH affects biological function predominantly through its effect on proteins, through the binding or release of H+ to ionizable groups. To understand the structural basis of the pH sensitivity of proteins, it is necessary to understand the molecular basis of H+ binding events. The H+-binding affinities of ionizable groups (i.e. pKa values) are known to be sensitive to the properties of their microenvironments. The inability of sophisticated computational methods for structure-based calculations of pKa values to reproduce the experimentally measured pKa values suggest that H+ binding to proteins is a more complex process than currently acknowledged. To examine in detail the molecular determinants of pKa values, I studied variants of staphylococcal nuclease with buried Lys residues. These buried Lys residues were chosen because they have highly anomalous pKa values (depressed, which favors the neutral state) that are difficult to reproduce with structure-based pKa calculations. In dehydrated environments, electrostatic effects such as Coulomb interactions and dehydration energies are stronger relative to those on the well hydrated protein surface and are highly sensitive to the polarity and polarizability of their environments. The studies described in this dissertation examined the hypothesis that the magnitude of electrostatic effects in proteins are not as severely influenced by the properties of the microenvironments of ionizable moieties as they are by the propensity of the conformational ensemble to redistribute in response to changes in pH. In chapter 2, the physical properties of the buried Lys residues were probed using 15N NMR spectroscopy. In most cases, pH-dependent structural reorganization was evident in the pH titrations tracked with the 15Nzeta resonance of the buried Lys residues. In chapter 3, the nature of this reorganization was characterized in 25 variants of SNase with internal Lys residues. These studies used backbone-based NMR spectroscopy experiments. The results of this work demonstrate that the apparent pKa values of the Lys residues measured by linkage thermodynamics report on pH-driven redistribution of the conformational ensemble. The redistribution favors conformational states in which the charged Lys side chains are exposed to solvent. By correlating thermodynamic data (i.e. stability) with detailed structural information about the partially unfolded states that SNase can access, it was possible to map the conformational ensemble of this protein with unprecedented resolution. In chapter 4, the structural and thermodynamic consequences of buried ion pairs in SNase was examined. NMR spectroscopy and X-ray crystallography showed various degrees of structural reorganization that lead to the hydration of at least one of the buried groups. These results demonstrate that not only does structural reorganization govern the properties of individual buried groups, structural reorganization can also determine the properties of buried ion pairs. In chapter 5 I provide irrefutable evidence of strong apparent interactions between buried and surface ionizable groups. NMR spectroscopy and equilibrium thermodynamic experiments demonstrated that the interactions between internal and surface ionizable groups are not Coulomb interactions. Instead, the apparent interactions are mediated by conformational reorganization driven by the ionization of the buried residues. Most of what is known about protein electrostatics reflects insights from decades of structure-based calculations with continuum electrostatic models, and more recently with constant pH molecular dynamics calculations. The data presented in this dissertation demonstrate that conformational reorganization can be the dominant factor that determines the pKa values of ionizable groups in proteins. Structure-based prediction of conformational reorganization remains extremely challenging; my results suggest an explanation for the short-comings of structure-based calculations to reproduce experimental pKa values and other electrostatic properties of proteins.

Identification of the optical counterparts of high-mass X-ray binaries through optical photometry and spectroscopy

We present the results of our search for optical counterparts to high-mass X-ray transient sources discovered by various X-ray missions. We obtained CCD images of the X-ray fields through BVR and Halpha filters in order to identify early-type stars in the R-Halpha versus B-V colour-colour diagram. We also obtained medium-resolution spectroscopy of the candidates in order to confirm the presence of H\alpha emission and perform spectral classification. We report on the discovery of the optical counterparts to two X-ray sources: XTE J1858+034 and IGR J01363+6610, and the follow-up observations of another two, newly identified by our group: SAX J2103.5+4545 and GRO J2058+42. For another source, IGR J00370+6122, we present the first detailed optical spectral analysis. The optical photometry and spectroscopy reveal B-type companions in all five sources; GRO J2058+42, SAX J2103.5+4545 and IGR J01363+6610 are positively identified with Be/X-ray binaries, IGR J00370+6122 with a supergiant X-ray binary, while the nature of XTE J1858+034 is uncertain. We also study the relationship between the optical and X-ray emission during quiescent states.Comment: 10 pages, to be published in A&

RoboPol: AGN polarimetric monitoring data

We present uniformly reprocessed and re-calibrated data from the RoboPol programme of optopolarimetric monitoring of active galactic nuclei (AGN), covering observations between 2013, when the instrument was commissioned, and 2017. In total, the dataset presented in this paper includes 5068 observations of 222 AGN with Dec > -25 deg. We describe the current version of the RoboPol pipeline that was used to process and calibrate the entire dataset, and we make the data publicly available for use by the astronomical community. Average quantities summarising optopolarimetric behaviour (average degree of polarization, polarization variability index) are also provided for each source we have observed and for the time interval we have followed it.Comment: Accepted to MNRA

RoboPol: a four-channel optical imaging polarimeter

We present the design and performance of RoboPol, a four-channel optical polarimeter operating at the Skinakas Observatory in Crete, Greece. RoboPol is capable of measuring both relative linear Stokes parameters q and u (and the total intensity I) in one sky exposure. Though primarily used to measure the polarization of point sources in the R band, the instrument features additional filters (B, V, and I), enabling multiwavelength imaging polarimetry over a large field of view (13.6' x 13.6'). We demonstrate the accuracy and stability of the instrument throughout its 5 yr of operation. Best performance is achieved within the central region of the field of view and in the R band. For such measurements the systematic uncertainty is below 0.1 per cent in fractional linear polarization, p (0.05 per cent maximum likelihood). Throughout all observing seasons the instrumental polarization varies within 0.1 per cent in p and within similar to 1 degrees in polarization angle

RoboPol: AGN polarimetric monitoring data

We present uniformly reprocessed and re-calibrated data from the RoboPol programme of optopolarimetric monitoring of active galactic nuclei (AGN), covering observations between 2013, when the instrument was commissioned, and 2017. In total, the dataset presented in this paper includes 5068 observations of 222 AGN with Dec > −25○. We describe the current version of the RoboPol pipeline that was used to process and calibrate the entire dataset, and we make the data publicly available for use by the astronomical community. Average quantities summarising optopolarimetric behaviour (average degree of polarization, polarization variability index) are also provided for each source we have observed and for the time interval we have followed it.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Electrostatic effects in proteins are governed by redistribution of the conformational ensemble

The ability to regulate pH dynamics is one of the hallmarks of all living cells. pH affects biological function predominantly through its effect on proteins, through the binding or release of H+ to ionizable groups. To understand the structural basis of the pH sensitivity of proteins, it is necessary to understand the molecular basis of H+ binding events. The H+-binding affinities of ionizable groups (i.e. pKa values) are known to be sensitive to the properties of their microenvironments. The inability of sophisticated computational methods for structure-based calculations of pKa values to reproduce the experimentally measured pKa values suggest that H+ binding to proteins is a more complex process than currently acknowledged. To examine in detail the molecular determinants of pKa values, I studied variants of staphylococcal nuclease with buried Lys residues. These buried Lys residues were chosen because they have highly anomalous pKa values (depressed, which favors the neutral state) that are difficult to reproduce with structure-based pKa calculations. In dehydrated environments, electrostatic effects such as Coulomb interactions and dehydration energies are stronger relative to those on the well hydrated protein surface and are highly sensitive to the polarity and polarizability of their environments. The studies described in this dissertation examined the hypothesis that the magnitude of electrostatic effects in proteins are not as severely influenced by the properties of the microenvironments of ionizable moieties as they are by the propensity of the conformational ensemble to redistribute in response to changes in pH. In chapter 2, the physical properties of the buried Lys residues were probed using 15N NMR spectroscopy. In most cases, pH-dependent structural reorganization was evident in the pH titrations tracked with the 15Nzeta resonance of the buried Lys residues. In chapter 3, the nature of this reorganization was characterized in 25 variants of SNase with internal Lys residues. These studies used backbone-based NMR spectroscopy experiments. The results of this work demonstrate that the apparent pKa values of the Lys residues measured by linkage thermodynamics report on pH-driven redistribution of the conformational ensemble. The redistribution favors conformational states in which the charged Lys side chains are exposed to solvent. By correlating thermodynamic data (i.e. stability) with detailed structural information about the partially unfolded states that SNase can access, it was possible to map the conformational ensemble of this protein with unprecedented resolution. In chapter 4, the structural and thermodynamic consequences of buried ion pairs in SNase was examined. NMR spectroscopy and X-ray crystallography showed various degrees of structural reorganization that lead to the hydration of at least one of the buried groups. These results demonstrate that not only does structural reorganization govern the properties of individual buried groups, structural reorganization can also determine the properties of buried ion pairs. In chapter 5 I provide irrefutable evidence of strong apparent interactions between buried and surface ionizable groups. NMR spectroscopy and equilibrium thermodynamic experiments demonstrated that the interactions between internal and surface ionizable groups are not Coulomb interactions. Instead, the apparent interactions are mediated by conformational reorganization driven by the ionization of the buried residues. Most of what is known about protein electrostatics reflects insights from decades of structure-based calculations with continuum electrostatic models, and more recently with constant pH molecular dynamics calculations. The data presented in this dissertation demonstrate that conformational reorganization can be the dominant factor that determines the pKa values of ionizable groups in proteins. Structure-based prediction of conformational reorganization remains extremely challenging; my results suggest an explanation for the short-comings of structure-based calculations to reproduce experimental pKa values and other electrostatic properties of proteins.