Growing up with one ear : central auditory structure and function in unilateral ear canal atresia

The following thesis aims to give more insight into the functional and structural response of the central auditory system to congenital unilateral ear canal atresia (UCA) and the accompanying asymmetric hearing with conductive hearing loss on the atretic side. There is clear evidence that unilateral hearing loss, including UCA, has a negative impact on sound localization ability and perception of speech in noise. There is a spread in performance within the group, and the reason for this is not well known. In paper I of this thesis we examined sound localization with eye tracking and perception of speech in a cocktail party setting, in participants with congenital unilateral ear canal atresia, who had no hearing aids before age 12 (n=12) and compared to normal hearing references. Results show that the level of hearing loss on the atretic ear was associated with sound localization ability but not to speech perception. In the second study, participants with UCA (n=17) underwent MRI-scanning of the brain with diffusion weighted imaging (DWI). A method is described how to segment the white matter bundle between the medial geniculate body of the thalamus and the primary auditory cortex, the acoustic radiation (AR). Methods to define the AR are previously described in high resolution diffusion weighted imaging (DWI) scans but is very time consuming or has problems with including more structures around the primary auditory cortex (PAC). An algorithm was trained to quickly segment the core of the AR in individual clinical scans. The white matter tract was also assessed with measurements of fractional anisotropy (FA), but no differences were found between UCA and normal hearing (NH) controls. The third study describes the measurements of the grey matter of the primary auditory cortex of the Heschl’s gyrus in the same participants as in paper II. Thickness and volume of the Heschl’s gyrus were compared within the groups of UCA and controls, and between the groups. A difference in thickness was found between the left and right side (right thicker than left, corrected p=0.0012) in UCA, whereas controls had symmetric thickness. Volumes and total thickness were not different compared to controls. Rat brains from 12 months old rats with a surgically constructed left-sided ear canal atresia were examined in study IV. DWI was acquired in a research camera for rodents, 9.4 T magnetic field and a prolonged scanning time. Tractography and FA measurements were obtained both from whole brains and from tracts between auditory regions of interest (ROIs) using two different software. FA was generally higher in UCA rats than in controls. The AR was asymmetric in FA (left<right) in UCA, whereas FA was symmetric in controls. The FA was found to be lower at the left connection (same side as hearing loss) cochlear nucleus -inferior colliculus compared to the right side in UCA, while it was symmetric in controls. This finding (CN-IC) aligns with previous histology findings in ferrets with unilateral conductive hearing loss

Taxation of Multi-National Enterprises - State and corporate responsibility regarding the issue of transfer pricing

Uppsatsen berör frågeställningen hur multinationella företag påverkar skattebasen via internprissättning. När företag överför tillgångar mellan enheter i olika länder krävs det att tillgångarna prissätts så att den beskattningsbara vinsten som uppkommer speglar omsättningen/värdet på enheten i det landet. Prissättningen beräknas med en ’armlängds avstånd’, vilket menas att det interna priset ska vara det samma som om varan handlats med en oberoende part. Marknadsutvecklingen har resulterat i att fler typer av ickemateriella tillgångar överförs mellan bolag. Tillgångarnas originalitet gör det svårt att finna en jämförbar prissättning. Problematiken uppkommer när företagen över- eller under estimerar det interna priset för att kunna överföra vinsten till det land med lägst bolagsskatt. Bristen på jämförbara tillgångar och mängden accepterade metoder som används för att finna ett pris gör att företag lätt manipulerar prissättningen. Problematiken har uppmärksammats på många plan och OECD har utvecklat riktlinjer för hur företag ska agera och stater ska reagera. En konkurrensmässig situation uppstår mellan stater när de vill attrahera företag. Etablering av utländska bolag innebär arbetsmöjligheter och ekonomisk utveckling i regionen. Ett flertal länder erbjuder billig arbetskraft, svag reglering när det kommer till miljöhantering och nu även skattelättnader vilket sammantaget resulterar sämre position för staten och dess invånare. Det finns inget överstatligt organ som ger en övergripande internationell skattereglering, utan det åligger staterna att reglera skatter och företags skyldigheter i landet. Kritiker har ifrågasatt om inte de multinationella företagen borde ta eget ansvar för sina handlingar och inte utnyttja svagheterna i systemet, medan andra menar att företag enda skyldighet är att följa de regler som åligger dem i landet de verkar. Olika organ har uppmärksammat problemet och den främsta rekommendationen för både stater och företag är ökad dokumentation om prissättningar och transparens i systemet. Det är viktigt att alla parter vet vad som förväntas av dem.This thesis concerns the issue of how MNE affects their taxable profit through transfer pricing. When companies transfer assets between subsidiaries in different states they need to price the assets so the taxable profit that arises reflects the value of the subsidiary. The pricing is calculated to comply with ‘arm’s length price’, which means the internal price should be the same as if the asset was purchased from an independent enterprise. The development of the international market has resulted in different non-material assets being transferred between subsidiaries. The uniqueness of the assets makes it hard to find a comparable transfer price. The problem arises when MNE over- or underestimates the transfer price to be able to report the profit in the state with lowest corporate taxation. The lack of comparable assets and the amount of accepted transfer pricing methods makes it easy for MNE to manipulate the pricing. The problem has been given attention on many levels and OECD has developed guidelines on how MNE shall act and how states shall react. A competitive situation arises between states as they try to attract foreign investment to get job opportunities and economic development in the region. Many states offer cheap workforce, poor regulation of environmental control and tax breaks which results in that states and their population ends up in a worse position than before. There is no supranational organisation that offers an international tax regulation. It is within state sovereignty to regulate taxation and impose obligations upon companies. Critics claims MNE should accept responsibility for their acts and not exploit the weaknesses in the system, while others say MNEs’ only obligation is to comply with the regulation within the state. Different organisations have highlighted the issue and recommended increased documentation requirements and transparency in the system. It is imported that each part knows what is expected of them

Photoelectron Spectroscopy for Chemical Analysis

Photoelectron spectroscopy started its modern development in the fifties based on techniques for studies of nuclear decay. Since then, photoelectron spectroscopy has undergone a dramatic expansion of application and is now a prime research tool in basic and applied science. This progress has been largely due to the concomitant development of photon sources, sample handling and electron energy analyzers. The present article describes some of the salient features of modern photoelectron spectroscopy and its applications with particular emphasis on energy relevant issues

On the bond distance in methane

The equilibrium bond distance in methane was optimized using coupled-pair functional and contracted CI wave functions, and a Gaussian basis that includes g-type functions on carbon and d-type functions on hydrogen. The resulting bond distance, when corrected for core-valence correlation effects, agrees with the experimental value of 2.052 a(0) to within the experimental uncertainty of 0.002 a(0). The main source of error in the best previous studies, which showed discrepancies with experiment of 0.007 a(0) is shown to be basis set incompleteness. In particular, it is important that the basis set be close to saturation, at least for the lower angular quantum numbers

Different types of biological proton transfer reactions studied by quantum chemical methods

AbstractDifferent types of proton transfer occurring in biological systems are described with examples mainly from ribonucleotide reductase (RNR) and cytochrome c oxidase (CcO). Focus is put on situations where electron and proton transfer are rather strongly coupled. In the long range radical transfer in RNR, it is shown that the presence of hydrogen atom transfer (HAT) is the most logical explanation for the experimental observations. In another example from RNR, it is shown that a transition state for concerted motion of both proton and electron can be found even if the donors are separated by a quite long distance. In CcO, the essential proton transfer for the OO bond cleavage, and the most recent modelings of proton translocation are described, indicating a few remaining major problems

Energy diagrams and mechanism for proton pumping in cytochrome c oxidase

AbstractThe powerful technique of energy diagrams has been used to analyze the mechanism for proton pumping in cytochrome c oxidase. Energy levels and barriers are derived starting out from recent kinetic experiments for the O to E transition, and are then refined using general criteria and a few additional experimental facts. Both allowed and non-allowed pathways are obtained in this way. A useful requirement is that the forward and backward rate should approach each other for the full membrane gradient. A key finding is that an electron on heme a (or the binuclear center) must have a significant lowering effect on the barrier for proton uptake, in order to prevent backflow from the pump-site to the N-side. While there is no structural gating in the present mechanism, there is thus an electronic gating provided by the electron on heme a. A quantitative analysis of the energy levels in the diagrams, leads to Prop-A of heme a3 as the most likely position for the pump-site, and the Glu278 region as the place for the transition state for proton uptake. Variations of key redox potentials and pKa values during the pumping process are derived for comparison to experiments

The mechanism for proton pumping in cytochrome c oxidase from an electrostatic and quantum chemical perspective

AbstractThe mechanism for proton pumping in cytochrome c oxidase in the respiratory chain, has for decades been one of the main unsolved problems in biochemistry. However, even though several different suggested mechanisms exist, many of the steps in these mechanisms are quite similar and constitute a general consensus framework for discussing proton pumping. When these steps are analyzed, at least three critical gating situations are found, and these points are where the suggested mechanisms in general differ. The requirements for gating are reviewed and analyzed in detail, and a mechanism is suggested, where solutions for all the gating situations are formulated. This mechanism is based on an electrostatic analysis of a kinetic experiment fior the O to E transition. The key component of the mechanism is a positively charged transition state. An electron on heme a opens the gate for proton transfer from the N-side to a pump loading site (PLS). When the negative charge of the electron is compensated by a chemical proton, the positive transition state prevents backflow from the PLS to the N-side at the most critical stage of the pumping process. The mechanism has now been tested by large model DFT calculations, and these calculations give strong support for the suggested mechanism. This article is part of a Special Issue entitled: Respiratory Oxidases

The dissociation energy of N2

The requirements for very accurate ab initio quantum chemical prediction of dissociation energies are examined using a detailed investigation of the nitrogen molecule. Although agreement with experiment to within 1 kcal/mol is not achieved even with the most elaborate multireference CI (configuration interaction) wave functions and largest basis sets currently feasible, it is possible to obtain agreement to within about 2 kcal/mol, or 1 percent of the dissociation energy. At this level it is necessary to account for core-valence correlation effects and to include up to h-type functions in the basis. The effect of i-type functions, the use of different reference configuration spaces, and basis set superposition error were also investigated. After discussing these results, the remaining sources of error in our best calculations are examined

Molecular double core-hole electron spectroscopy for chemical analysis

We explore the potential of double core hole electron spectroscopy for chemical analysis in terms of x-ray two-photon photoelectron spectroscopy (XTPPS). The creation of deep single and double core vacancies induces significant reorganization of valence electrons. The corresponding relaxation energies and the interatomic relaxation energies are evaluated by CASSCF calculations. We propose a method how to experimentally extract these quantities by the measurement of single and double core-hole ionization potentials (IPs and DIPs). The influence of the chemical environment on these DIPs is also discussed for states with two holes at the same atomic site and states with two holes at two different atomic sites. Electron density difference between the ground and double core-hole states clearly shows the relaxations accompanying the double core-hole ionization. The effect is also compared with the sensitivity of single core hole ionization potentials (IPs) arising in single core hole electron spectroscopy. We have demonstrated the method for a representative set of small molecules LiF, BeO, BF, CO, N2, C2H2, C2H4, C2H6, CO2 and N2O. The scalar relativistic effect on IPs and on DIPs are briefly addressed.Comment: 35 pages, 6 figures. To appear in J. Chem. Phys