Characterizing Rhodopsin-Arrestin Interactions with the Fragment Molecular Orbital (FMO) Method

Arrestin binding to G protein-coupled receptors (GPCRs) plays a vital role in receptor signaling. Recently, the crystal structure of rhodopsin bound to activated visual arrestin was resolved using XFEL (X-ray free electron laser). However, even with the crystal structure in hand, our ability to understand GPCR-arrestin binding is limited by the availability of accurate tools to explore receptor-arrestin interactions. We applied fragment molecular orbital (FMO) method to explore the interactions formed between the residues of rhodopsin and arrestin. FMO enables ab initio approaches to be applied to systems that conventional quantum mechanical (QM) methods would be too compute-expensive. The FMO calculations detected 35 significant interactions involved in rhodopsin-arrestin binding formed by 25 residues of rhodopsin and 28 residues of arrestin. Two major regions of interaction were identified: at the C-terminal tail of rhodopsin (D330-S343) and where the "finger loop" (G69-T79) of arrestin directly inserts into rhodopsin active core. Out of these 35 interactions, 23 were mainly electrostatic and 12 hydrophobic in nature

Geology and Geochronology of the Younger Cenozoic of Oga Peninsula

The present study is undertaken to clarify the age of deposition and extent of geographic distribution of the younger Cenozoic strata (Fig. 2) developed in the Oga Peninsula, Akita Prefecture (Fig. 1). Detailed tephrochronological investigation of the sedimentary rocks was done to trace the geographic distribution of the strata. A total of thirty key beds were traced over the Oga Peninsula area and a few of them were traced further to the Akita oil fields lying southeast of the Oga Peninsula (Fig. 9). Lithologic descriptions and type localities of the key tuff beds are given in Table 1. Magnetostratigraphy, microbiostratigraphy and radiometric dating assumed as the principal means to establish the geochronology of the strata. However, these methods were not accompanied by each other in most of previous works. Accordingly, an attempt was made to apply these methods to the same sections simultaneously and to synthesize their results for comparison. Two routes, the Oga Peninsula main route and the Sarukawa route, were selected in the Oga Peninsula for study. Along these routes, collected were 149 samples for paleomagnetic measurement, 30 samples for microfossil study and 4 samples for radiometric dating. The sampling localities and stratigraphic position in columnar sections are shown in Figs. 4 and 5. Magnetostratigraphy : -In the laboratory, samples were demagnetized in the alternation field of 150 Oersted to remove the unstable secondary components and then the samples were demagnetized in 200℃ thermal field. These samples were measured at every 45° around three axes of the sample with the automatic parastatic-type magnetometer. All numerical values obtained from the measurement were processed by an electric computer, NEAC 2200, Model 500, at the Computer Center of the Tohoku University. The result of measurements are shown in Fig. 6-a, b. The paleomagnetic studies indicate that the lowermost Kitaura, upper half of the middle Kitaura and upper Kitaura to Shibikawa formations are normaly magnetized and the uppermost Funakawa and lower to lower half of the middle Kitaura are reversely magnetized. The rest of the Funakawa Formation is interpreted as being remagnetized and unreliable for magnetostratigraphy. In order to magnetostratigraphic classification, these magnetic reversal patterns are named as AKOG-A, AKOG-B, AKOG-C, AKOG-D, AKOG-E at the Oga Peninsula main route, while AKSK-B, AKSK-C, AKSK-D, AKSK-E, AKSK-F at the Sarukawa route in descending order. Microbiostratigraphy : -Samples for microfossil study were used for planktonic foraminifera and Radiolaria. A part of samples used for paleomagnetic measurement were examined in calcareous nannoplankton and diatom. The results are shown in Figs. 7-a, b. The faunal and floral assemblages are generally monotonous in composition, as same as the present-day biota living in the North Pacific. Among them, species were found to be significant for biostratigraphical correlation, though they occurred sporadically both in the northern and southern sections : they are, planktonic foraminifera : -Globoquadrina asanoi, Globoquadrina kagaensis, Globoquadrina himiensis ; calcareous nannoplankton : -Gephyrocapsa spp. ; Radiolaria : - Eucyrtidium matuyamai, Ommatartus antepenultimus, Ommatartus penultimus, Ommatartus tetratharamus ; diatom : -Actinocyclus oculatus, Pseudoeunotia doliolus and Rhizosolenia praebergonii. Correlation : -Correlation of the magneto-zones with the Cenozoic magnetic time scale of marine sediments (Opdyke, 1972) were accomplished by correlating the associated micro-biostratigraphic events to those recognized already in the paleomagnetic polarity sequence of deep-sea cores (Fig. 8). From the interval of AKSK-F, occurence of Actinocyclus oculatus and Globoquadrina asanoi were recorded. Because of the first appearance of Actinocyclus oculatus and the last appearance of Globoquadrina asanoi, AKSK-F is correlated to the Matuyama reversed Epoch below the "Olduvai" event. Globoquadrina asanoi, Globoquadrina kagaensis, Globoquadrina himiensis, Actinocyclus oculatus and Rhizosolenia praebergonii were found in the intervals of AKOG-E, AKSK-F. The first appearance of Actinocyclus oculatus and Globoquadrina himiensis and the last appearance of Globoquadrina asanoi, Globoquadrina kagaensis, GloBoquadrina himiensis and Rhizosolenia praebergonii indicate that AKOG-E and AKSK-E are correlated to the "Olduvai" event. Within the interval of AKOG-D, AKSK-D, Gephyrocapsa spp., Eucyrtidium matuyamai, Pseudoeunotia doliolus and Actinocyclus oculatus were recognized. The first appearance of Gephyrocapsa spp., Eucyrtidium matuyamai and Pseudoeunotia doliolus and the last appearance of Actinocyclus oculatus and Eucyrtidium matuyamai assure that AKOG-D, AKSK-D can be correlated to the Matuyama reversed Epoch between "Olduvai" event and Jaramillo event. Correlation of the rest of magneto-zones are reserved because of poor occurrence in microfossils. Radiometric dating : -Dating was carried out by K-Ar method at the laboratory of Prof. Y. Uyeda of the Tohoku University. Measured minerals were biotite. The results of measurement are shown in Table 2. A distinct discrepancy is noticed between the radiometric age obtained and the results of magnetostratigraphic and microbiostratigraphic correlation

Vista y plano de Toledo

In View and plan of Toledo, a faithful representation of the city and homage to it, the vision of the Virgin as well as the nude on the left, allegory of the river Tagus, sustenance of the life of the region represented by the youth clothed in olive-green, all are casual images presented in the sky, on the earth and in the thicket. El Greco’s imagination operates with almost mathematical rigour. A genealogical link can be traced between Jesus’ tunic in the Modena-Triptych, the tunic of the kneeled angel of the Baptism of the Prado and the chasuble carried by the Virgin in Vista y plano. The composition of the picture is related to the Adoration of the first period, repeating the youth with the map the same role of Saint Jerome with the Vulgata.En Vista y plano de Toledo, que es fiel retrato y homenaje a la ciudad, tanto la visión de la Virgen como el desnudo de la izquierda, alegoría del río Tajo, sustento básico para la vida de la región representada por el joven de la derecha, son imágenes casuales aparecidas en el cielo, en la tierra y en los matorrales. La fantasía grequiana opera con un rigor casi matemático. Se observa una genealogía establecida entre la túnica de Jesús del Tríptico de Módena, la del ángel arrodillado del Bautismo del Prado y la casulla portada por la Virgen en Vista y plano. La composición de Vista y plano está relacionada con la Adoración de la primera época toledana, estableciendo un vínculo entre el joven con el plano y san Jerónimo con la Vulgata

Transfer Pricing in European Union VAT Law

The aim of the thesis is to analyse the transfer pricing rules in the VAT system, namely Articles 72 and 80 of the Recast VAT directive. The thesis specifically aims to investigate the application of the open market value to improperly valued transactions between related parties, what the open market value in the VAT system is and how it is determined. The second chapter of the thesis presents an analysis of transfer pricing in European Union law and international tax law. In line with the aim of the thesis, the chapters main focus is on the transfer pricing provision of Article 80. It presents an analysis of the provision and puts it into the context of the common system of VAT, specifically by looking at how it relates to the general principles of the taxable amount being based on a subjective valuation based on the actual consideration paid for a transaction, and especially how it relates to the general principle of fiscal neutrality inherent in the VAT system. The chapter then briefly looks at transfer pricing rules in, on the one hand European Union customs law, and on the other hand international corporate income tax law. The third chapter presents an analysis of the concept of open market value as it is provided in Article 72 of the Recast VAT Directive. The concept is compared to the rules on re-valuation of the customs value in transactions between related parties in customs law. The concept of open market value is then compared to that of the arm‘s length principle used in international corporate income tax law. Lastly, the chapter asks the question whether customs valuation methods would be accepted as a basis for calculating the open market value in VAT before the European Court of Justice, and attempts to answer it. Finally, in the fourth chapter, the main conclusions of the thesis are summed up. The main findings of the thesis are that the transfer pricing provisions may be too far reaching, and possibly go against the principle of proportionality, harming the neutrality of the VAT system unnecessarily when a re-valuation to the cost or purchase price would similarly prevent tax evasion and avoidance. The provisions the thesis set out to examine are both lacking in clarity due to definitions of key concepts being to general. The corresponding concepts in the Community Customs Code don‘t suffer from this lack of clarity and it could be worthwhile looking in that direction for clarification of the VAT transfer pricing rules

Micro-Fresnel Zone Plate Optical Devices Using Densely Accumulated Ray Points

An embodiment generally relates to an optical device suitable for use with an optical medium for the storage and retrieval of data. The optical device includes an illumination means for providing a beam of optical radiation of wavelength .lamda. and an optical path that the beam of optical radiation follows. The optical device also includes a diffractive optical element defined by a plurality of annular sections. The plurality of annular sections having a first material alternately disposed with a plurality of annular sections comprising a second material. The diffractive optical element generates a plurality of focal points and densely accumulated ray points with phase contrast phenomena and the optical medium is positioned at a selected focal point or ray point of the diffractive optical element

Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m(2 )AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF

Quantum Chemical Investigation of the Dihydrogen Bonding and Its Implications in the Metal-free Hydrogen Activation

二氢键（DHB）是氢键的一种，其作用可以表示为X-H+•••-H-M（其中M一般为过渡金属或硼原子，X-H是通常的质子给体）。这种氢键的特别之处在于质子受体也包含一个氢原子，一般把它归为非常规氢键。和常规氢键一样，二氢键可以影响物质在液相和固相中的结构、反应活性和选择性；在催化、晶体工程和材料科学中二氢键也有着重要的作用。这种H+•••-H作用主要存在于过渡金属化合物中，自从20世纪90年代中期被发现之后理论和实验都对这种非常规氢键表示了极大的关注。分子氢（H...Dihydrogen bonding (DHB) is a kind of hydrogen bond and the interactions within DHBs can be generally represented as a quartet X-H+•••-H-M (typical element M can be a transition metal or boron and X-H is usual proton donor). The unique feature for this type of hydrogen bond, which is usually classified as nonconventional hydrogen bond, is that a hydrogen atom is i...学位：理学博士院系专业：化学化工学院化学系_物理化学(含化学物理)学号：2052006015323