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Enzymatic and antisense effects of a specific anti-Ki-ras ribozyme in vitro and in cell culture
(1999)
Due to their mode of action, ribozymes show antisense effects in addition to their specific cleavage activity. In the present study we investigated whether a hammerhead ribozyme is capable of cleaving mutated Ki-ras mRNA in a pancreatic carcinoma cell line and whether antisense effects contribute to the activity of the ribozyme. A 2[prime]-O-allyl modified hammerhead ribozyme was designed to cleave specifically the mutated form of the Ki-ras mRNA (GUU motif in codon 12). The activity was monitored by RT-PCR on Ki-ras RNA expression by determination of the relative amount of wild type to mutant Ki-ras mRNA, by 5-bromo-2[prime]-deoxy-uridine incorporation on cell proliferation and by colony formation in soft agar on malignancy in the human pancreatic adenocarcinoma cell line CFPAC-1, which is heterozygous for the Ki-ras mutation. A catalytically inactive ribozyme was used as control to differentiate between antisense and cleavage activity and a ribozyme with random guide sequences as negative control. The catalytically active anti-Ki-ras ribozyme was at least 2-fold more potent in decreasing cellular Ki-ras mRNA levels, inhibiting cell proliferation and colony formation in soft agar than the catalytically inactive ribozyme. The catalytically active anti-Ki-ras ribozyme, but not the catalytically inactive or random ribozyme, increased the ratio of wild type to mutated Ki-ras mRNA in CFPAC-1 cells. In conclusion, both cleavage activity and antisense effects contribute to the activity of the catalytically active anti-Ki-ras hammerhead ribozyme. Specific ribozymes might be useful in the treatment of pancreatic carcinomas containing an oncogenic GTT mutation in codon 12 of the Ki-ras gene.
Customer channel migration
(2006)
Customer Channel Migration deals with the active management of a customer's channel usage behavior with the aim to increase her profitability and lifetime. Hence, the dissertation answers two distict questions: on one hand, it investigates the impact of channel use on a customer's profitability and lifetime. On the other hand, it is researched how a customer's channel usage behavior can be influenced and managed. The cumulative dissertation consists of five articles: the first article describes the matching method and its application to marketing problems. The matching method is necessary to estimate the unbiased impact of channel use on a customer's profitability and lifetime. The second article describes the application of the matching method in order to determine the monetary implications of using the internet in the financial services industry. The third article investigates the impact of the internet use on a customer's lifetime. The forth and the fifth article of the dissertation both investigate the management of a customer's channel usage behavior. The forth article designs a scale to measure a customer's perceived channel value. The fifth article builds upon these findings and develops a model which explains a customer's channel usage behavior. Based on these insights this article derives some managerial implications on how to manage customers between different channels.
Nuclear matter, that takes the form of protons and neutrons under normal conditions, is subject to a phase transition at high temperatures and densities, liberating the quarks and gluons that are usually confined in nucleons and creating a medium of free partons: the Quark-Gluon-Plasma. It is generally believed that this state of matter can be created in relativistic collisions of heavy nuclei. The study of the medium created in these collisions is the subject of heavy-ion physics. One topic within this field are particles with high transverse momentum, that are created in initial hard collisions between partons of the incoming nuclei. The energetic partons lose energy due to interactions with the medium before they fragment into a jet of hadrons. Due to momentum conservation, these jets are usually created as back-to-back pairs, or less commonly as three-jet or photon-jet events, where a single jet is balanced by a hard photon. The energy loss can be measured using correlations between particles with high transverse momenta. A trigger particle is selected with very high transversemomentum and the distribution of the azimuthal angle of associated particles in the same event is studied, relative to the azimuth of the trigger particle.These azimuthal correlations show a peak for opening angles around 0 from particles selected from the same jet, and a second peak at opening angles around 180 degrees from back-to-back di-jets. Random combinations with the underlying event generate a flat background, extending over the full range of opening angles. The STAR experiment observed a modification of these correlations in central Au+Au collisions, where trigger particles with 4GeV < pT(trigger) < 6GeV and associated particles with 2GeV < pT(trigger) < 4GeV were selected. A strong suppression has been observed for away-side correlations in central Au+Au collisions, relative to p+p, d+Au and peripheral Au+Au data. This can be explained by assuming two partons going in opposite directions, where at least one has to travel a large distance through the medium, causing energy loss and effectively removing the event from the analysis. For near-side correlations, no significant modification has been observed, which can be explained by surface emission, assuming that the observed jets have travelled only a short distance in themedium, not leaving enough time for interactions with the medium. Both trigger- and associated particles in a correlation analysis with charged hadrons are subject to modifications due to the medium. This can be avoided by using photon-jet events instead of di-jets, because the photon does not interact with the medium and therefore provides the best available measure of the properties of the opposite jet in the presence of the underlying event. This thesis studies azimuthal correlations between regions of high energy deposition in the electro-magnetic calorimeter as trigger- and charged tracks as associated particles. The data sample had been enriched by online event selection, allowing for the selection of trigger particles with a transverse energy of more than 10GeV and associated particles with more than 2,3 or 4 GeV. The away-side yield per trigger particle is strongly suppressed like in correlations between charged particles. The near-side yield is also reduced by about a factor two, clearly different from charged correlations. The trigger particles are a mixture of photon pairs from the decays of neutral pions and single photons, mainly from photon-jet events, with small contributions from other hadron decays and fragmentation photons. Pythia simulations predict a ratio of neutral pions to prompt photons of 3.5:1 in p+p collisions with the same cuts as in the presented analysis. Single particle suppression further reduces this ratio in central Au_Au collisions, down to about 0.8:1, indicating that the majority of trigger particles in central Au+Au collisions are prompt photons. The increasing fraction of prompt photon triggers without an accompanying jet and therefore zero associated yield reduces the average yield per trigger particle. The magnitude of the observed effect agrees well with the expectation from Pythia simulations and the assumption of a single particle suppression by a factor 4-5. An analysis of away-side correlations is more difficult, because both photon-jet and di-jet events contribute. The aim is the separation of these two contributions. As a clear separation is not possible with the available dataset, a comparison with two different scenarios is given, where a surprisingly small suppression by only a factor of about 5 is favoured for both dijet- and photon-jet-correlations. A separate measurement of both contributions will be possible by a shower-shape analysis with the EM calorimeter or a comparison with charged correlations in the same kinematic region.
Revers, L. F ; Cardone, Jacqueline Moraes ; Bonatto, Diego ; Saffi, Jenifer ; Grey, Martin ; Feldmann, H. ; Brendel, Martin ; Henriques, Joao A. P.
The conditionally-lethal pso4-1 mutant allele of the spliceosomal-associated PRP19 gene allowed us to study this gene’s influence on pre-mRNA processing, DNA repair and sporulation. Phenotypes related to intron-containing genes were correlated to temperature. Splicing reporter systems and RT–PCR showed splicing efficiency in pso4-1 to be inversely correlated to growth temperature. A single amino acid substitution, replacing leucine with serine, was identified within the N-terminal region of the pso4-1 allele and was shown to affect the interacting properties of Pso4-1p. Amongst 24 interacting clones isolated in a two-hybrid screening, seven could be identified as parts of the RAD2, RLF2 and DBR1 genes. RAD2 encodes an endonuclease indispensable for nucleotide excision repair (NER), RLF2 encodes the major subunit of the chromatin assembly factor I, whose deletion results in sensitivity to UVC radiation, while DBR1 encodes the lariat RNA splicing debranching enzyme, which degrades intron lariat structures during splicing. Characterization of mutagen-sensitive phenotypes of rad2{Delta}, rlf2{Delta} and pso4-1 single and double mutant strains showed enhanced sensitivity for the rad2{Delta} pso4-1 and rlf2{Delta} pso4-1 double mutants, suggesting a functional interference of these proteins in DNA repair processes in Saccharomyces cerevisiae.
Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair.
The radiation-sensitive mutant pso4-1 of Saccharomyces cerevisiae shows a pleiotropic phenotype, including sensitivity to DNA cross-linking agents, nearly blocked sporulation and reduced mutability. We have cloned the putative yeast DNA repair gene PSO4 from a genomic library by complementation of the blocked UV-induced mutagenesis and of sporulation in diploids homozygous for pso4-1. Sequence analysis revealed that gene PSO4 consists of 1512 bp located upstream of UBI4 on chromosome XII and encodes a putative protein of 56.7 kDa. PSO4 is allelic to PRP19, a gene encoding a spliceosome-associated protein, but shares no significant homology with other yeast genes. Gene disruption with a destroyed reading frame of our PSO4 clone resulted in death of haploid cells, confirming the finding that PSO4/PRP19 is an essential gene. Thus, PSO4 is the third essential DNA repair gene found in the yeast S.cerevisiae.
Mismatch repair is a highly conserved system that ensures replication fidelity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSα (hMSH2‐hMSH6) and hMutLα (hMLH1‐hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSα recruits hMutLα, which then is thought to transduce the repair signal to the excision machinery. We have expressed an ATPase mutant of hMutLα as well as its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by examination of their interaction properties with hMutSα using a novel interaction assay. We show that, although the interaction requires ATP, hMutLα does not need to hydrolyse this nucleotide to join hMutSα on DNA, suggesting that ATP hydrolysis by hMutLα happens downstream of complex formation. The analysis of the individual subunits of hMutLα demonstrated that the hMutSα–hMutLα interaction is predominantly conferred by hMLH1. Further experiments revealed that only the N‐terminus of hMLH1 confers this interaction. In contrast, only the C‐terminus stabilised and co‐immunoprecipitated hPMS2 when both proteins were co‐expressed in 293T cells, indicating that dimerisation and stabilisation are mediated by the C‐terminal part of hMLH1. We also examined another human homologue of bacterial MutL, hMutLβ (hMLH1–hPMS1). We show that hMutLβ interacts as efficiently with hMutSα as hMutLα, and that it predominantly binds to hMutSα via hMLH1 as well.
Aim of the study: Investigation, whether water-filtered infrared-A (wIRA) irradiation during moderate bicycle ergometer endurance exercise has effects especially on local fat reduction and on weight reduction beyond the effects of ergometer exercise alone.
Methods: Randomised controlled study with 40 obese females (BMI 30-40 (median: 34.5), body weight 76-125 (median: 94.9) kg, age 20-40 (median: 35.5) years, isocaloric nutrition), 20 in the wIRA group and 20 in the control group. In both groups each participant performed 3 times per week over 4 weeks for 45 minutes bicycle ergometer endurance exercise with a constant load according to a lactate level of 2 mmol/l (aerobic endurance load, as determined before the intervention period). In the wIRA group in addition large parts of the body (including waist, hip, and thighs) were irradiated during all ergometries of the intervention period with visible light and a predominant part of water-filtered infrared-A (wIRA), using the irradiation unit “Hydrosun® 6000” with 10 wIRA radiators (Hydrosun® Medizintechnik, Müllheim, Germany, radiator type 500, 4 mm water cuvette, yellow filter, water-filtered spectrum 500-1400 nm) around a speed independent bicycle ergometer.
Main variable of interest: change of “the sum of circumferences of waist, hip, and both thighs of each patient” over the intervention period (4 weeks). Additional variables of interest: body weight, body mass index BMI, body fat percentage, fat mass, fat-free mass, water mass (analysis of body composition by tetrapolar bioimpedance analysis), assessment of an arteriosclerotic risk profile by blood investigation of variables of lipid metabolism (cholesterol, triglycerides, high density lipoproteins HDL, low density lipoproteins LDL, apolipoprotein A1, apolipoprotein B), clinical chemistry (fasting glucose, alanin-aminotransferase ALT (= glutamyl pyruvic transaminase GPT), gamma-glutamyl-transferase GGT, creatinine, albumin), endocrinology (leptin, adiponectin (= adipo Q), homocysteine, insulin). All variables were at least measured before and after the intervention period. Ergometry (ECG, blood pressure behaviour, lactate curve with power at 2, 3 and 4 mmol/l) before the intervention period. In addition: nutrition training ahead of and during the intervention period with a nutrition protocol over one week for assessment of the daily energy intake; calculation of basic metabolic rate and total energy requirement. Assessment of undesired effects.
Only methods of non-parametric statistics were used, both descriptive (median, percentiles of 25 and 75 (= interquartile range), minimum, maximum) and confirmatory (two-sided Mann-Whitney U test for unpaired samples for the only one main variable of interest). Total error probability: .05 (5%). An intention to treat analysis ITT with last observed carry forward method was used preferably (presented results) and in addition an on treatment analysis OT. Only 2 (treatment group) and 4 (control group) drop-outs occurred (mostly due to lack of time).
Results: The “sum of circumferences of waist, hip, and both thighs of each patient” decreased during the 4 weeks significantly more (p<.001) in the wIRA group than in the control group: medians and interquartile ranges: -8.0 cm (-10.5 cm/-4.1 cm) vs. -1.8 cm (-4.4 cm/0.0 cm).
As well “body weight of each patient” decreased during the 4 weeks markedly more in the wIRA group than in the control group: medians and interquartile ranges: -1.9 kg (-4.0 kg/0.0 kg) vs. 0.0 kg (-1.5 kg/+0.4 kg); median of body weight changed from 99.3 kg to 95.6 kg (wIRA) vs. 89.9 kg to 89.6 kg (control). A similar effect showed the body mass index BMI.
Blood variables of interest remained unchanged or showed some slight improvements during the treatment period, concerning most variables with no obvious differences between the two groups; insulin showed a slight trend to decrease in the wIRA group and to increase in the control group.
Undesired effects of the treatment were not seen.
Discussion: The results of the study suggest, that wIRA – during moderate bicycle ergometer endurance exercise as lipolytic stimulus – increases local lipolysis with a local fat reduction (thighs) in the otherwise bradytrophic fatty tissue. The presumably underlying mechanisms of wIRA have already been proven: wIRA acts both by thermal effects and by non-thermal effects. Thermal effects of wIRA are the generation of a therapeutic field of warmth with the increase of tissue temperature, tissue oxygen partial pressure, and tissue blood flow, and by this regional metabolism. As fatty tissue normally has a slow metabolism (bradytrophic and hypothermic tissue) with a low rate of lipolysis, wIRA can increase lipolysis in fatty tissue and the mobilized fats are burned in musculature during the ergometer exercise.
Conclusion: The results of the study indicate, that wIRA irradiation during moderate ergometer endurance exercise can be used – in combination with an appropriate nutrition – to improve body composition, especially local fat distribution, and the reduction of fat and body weight in obese persons.
RNA interference (RNAi) has emerged as a powerful tool to induce loss-of-function phenotypes by post-transcriptional silencing of gene expression. In this study we wondered whether inducible RNAi-cassettes integrated into cellular DNA possess the power to trigger neoplastic growth. For this purpose inducible RNAi vectors containing tetracycline (Tet)-responsive derivatives of the H1 promoter for the conditional expression of short hairpin RNA (shRNA) were used to target human polo-like kinase 1 (Plk1), which is overexpressed in a broad spectrum of human tumors. In the absence of doxycycline (Dox) HeLa clones expressing TetR, that carry the RNAi-cassette stably integrated, exhibited no significant alteration in Plk1 expression levels. In contrast, exposure to Dox led to marked downregulation of Plk1 mRNA to 3% and Plk1 protein to 14% in cell culture compared to mismatch shRNA/Plk1-expressing cells. As a result of Plk1 depletion cell proliferation decreased to 17%. Furthermore, for harnessing RNAi for silencing disease-related genes in vivo we transplanted inducible RNAi-HeLa cells onto nude mice. After administration of Dox knockdown of Plk1 expression was observed correlating to a significant inhibition of tumor growth. Taken together, our data revealed that genomically integrated RNAi-elements are suitable to hamper tumor growth by conditional expression of shRNA.
Natural objects provide partially redundant information to the brain through different sensory modalities. For example, voices and faces both give information about the speech content, age, and gender of a person. Thanks to this redundancy, multimodal recognition is fast, robust, and automatic. In unimodal perception, however, only part of the information about an object is available. Here, we addressed whether, even under conditions of unimodal sensory input, crossmodal neural circuits that have been shaped by previous associative learning become activated and underpin a performance benefit. We measured brain activity with functional magnetic resonance imaging before, while, and after participants learned to associate either sensory redundant stimuli, i.e. voices and faces, or arbitrary multimodal combinations, i.e. voices and written names, ring tones, and cell phones or brand names of these cell phones. After learning, participants were better at recognizing unimodal auditory voices that had been paired with faces than those paired with written names, and association of voices with faces resulted in an increased functional coupling between voice and face areas. No such effects were observed for ring tones that had been paired with cell phones or names. These findings demonstrate that brief exposure to ecologically valid and sensory redundant stimulus pairs, such as voices and faces, induces specific multisensory associations. Consistent with predictive coding theories, associative representations become thereafter available for unimodal perception and facilitate object recognition. These data suggest that for natural objects effective predictive signals can be generated across sensory systems and proceed by optimization of functional connectivity between specialized cortical sensory modules.
Background The proto-oncogene pituitary tumor-transforming gene (PTTG) has been shown to be abundantly overexpressed in a large variety of neoplasms likely promoting neo-vascularization and tumor invasiveness. In this study, we investigated a potential role for PTTG mRNA expression as a marker to evaluate the future clinical outcome of patients diagnosed with primary cancer of the head and neck. Methods Tumor samples derived from primary tumors of 89 patients suffering from a squamous cell carcinoma were analyzed for PTTG mRNA-expression and compared to corresponding unaffected tissue. Expression levels were correlated to standard clinico-pathological parameters based on a five year observation period. Results In almost all 89 tumor samples PTTG was found to be overexpressed (median fold increase: 2.1) when compared to the unaffected tissue specimens derived from the same patient. The nodal stage correlated with PTTG transcript levels with significant differences between pN0 (median expression: 1.32) and pN+ (median expression: 2.12; P = 0.016). In patients who developed a tumor recurrence we detected a significantly higher PTTG expression in primary tumors (median expression: 2.63) when compared to patients who did not develop a tumor recurrence (median expression: 1.29; P = 0.009). Since the median expression of PTTG in patients with tumor stage T1/2N0M0 that received surgery alone without tumor recurrence was 0.94 versus 3.82 in patients suffering from a tumor recurrence (P = 0.006), PTTG expression might provide a feasible mean of predicting tumor recurrence. Conclusion Elevated PTTG transcript levels might be used as a prognostic biomarker for future clinical outcome (i.e. recurrence) in primary squamous cell carcinomas of the head and neck, especially in early stages of tumor development.
The paper will provide a brief background to the history of the organization and cooperative efforts of African studies librarians in the United States including their efforts at international cooperation. Particular emphasis will be placed on the current opportunities for improved cooperation as digitization activities increase. Examples will include the DISA and Aluka initiatives and well as the Timbuktu manuscript digitization project at the Center for Research Libraries. Particular emphasis will placed on the possibilities for German-North American cooperation in the area of digital projects of historical photographs given the extensive collections held at Northwestern and Frankfurt.
... This year's Scientific Symposium of the University Library is already number six in the row. It was again prepared and organised like some of the previous conferences together with our North American partners. This means that a continuous specialists’ discussion and a professional partnership have been already installed. All librarians and information managers are invited to learn more about the results of this cooperation every year when it's time for the next Symposium during Frankfurt Book Fair. ...
Large American research libraries have been acquiring - by purchase and by lease - huge multi-disciplinary electronic collections of primary and secondary source materials. For example, the Digital Evans and Canadian Poetry easily make available to scholars primary materials that once were scattered in libraries across North America and Europe. The American State Papers, 1789 – 1838 collection allows easier searching of fragile rare materials. Collections made by libraries digitizing their own holdings, such the Archive of Early American Images from the John Carter Brown Library at Brown University, make research materials more discoverable and usable. Yet recent scholarship in American Studies by American and European scholars makes relatively little use of these new materials. Both disparities and congruities in what scholars use and what research libraries collect are apparent. Some simple reasons explain the dissonance. Furthermore, conversations with scholars suggest that materials and collections alone will not suffice to support research. Librarians’ skills and actions will increase the value of the new research materials.
Betz, Barbara ; Bleicher, Marcus ; Harbach, Ulrich ; Humanic, Thomas J. ; Koch, Benjamin ; Stöcker, Horst
We examine experimental signatures of TeV-mass black hole formation in heavy ion collisions at the LHC. We find that the black hole production results in a complete disappearance of all very high p_T (> 500 GeV) back-to-back correlated di-jets of total mass M > M_f ~ 1 TeV. We show that the subsequent Hawking-decay produces multiple hard mono-jets and discuss their detection. We study the possibility of cold black hole remnant (BHR) formation of mass ~ M_f and the experimental distinguishability of scenarios with BHRs and those with complete black hole decay. Finally we point out that a Heckler-Kapusta-Hawking plasma may form from the emitted mono-jets. In this context we present new simulation data of Mach shocks and of the evolution of initial conditions until the freeze-out.
Schweda, Kai ; Zhu, Xianglei ; Bleicher, Marcus ; Huang, Shengli ; Stöcker, Horst ; Xu, Nu ; Zhuang, Pengfei
We propose to measure azimuthal correlations of heavy-flavor hadrons to address the status of thermalization at the partonic stage of light quarks and gluons in high-energy nuclear collisions. In particular, we show that hadronic interactions at the late stage cannot significantly disturb the initial back-to-back azimuthal correlations of DDbar pairs. Thus, a decrease or the complete absence of these initial correlations does indicate frequent interactions of heavy-flavor quarks and also light partons in the partonic stage, which are essential for the early thermalization of light partons.
The experimental signatures of TeV-mass black hole (BH) formation in heavy ion collisions at the LHC is examined. We find that the black hole production results in a complete disappearance of all very high p_T (> 500 GeV) back-to-back correlated di-jets of total mass M > M_f ~ 1 TeV. We show that the subsequent Hawking-decay produces multiple hard mono-jets and discuss their detection. We study the possibility of cold black hole remnant (BHR) formation of mass ~ M_f and the experimental distinguishability of scenarios with BHRs and those with complete black hole decay. Due to the rather moderate luminosity in the first year of LHC running the least chance for the observation of BHs or BHRs at this early stage will be by ionizing tracks in the ALICE TPC. Finally we point out that stable BHRs would be interesting candidates for energy production by conversion of mass to Hawking radiation.
The concept of Large Extra Dimensions (LED) provides a way of solving the Hierarchy Problem which concerns the weakness of gravity compared with the strong and electro-weak forces. A consequence of LED is that miniature Black Holes (mini-BHs) may be produced at the Large Hadron Collider in p+p collisions. The present work uses the CHARYBDIS mini-BH generator code to simulate the hadronic signal which might be expected in a mid-rapidity particle tracking detector from the decay of these exotic objects if indeed they are produced. An estimate is also given for Pb+Pb collisions.
We develop a 1+1 dimensional hydrodynamical model for central heavy-ion collisions at ultrarelativistic energies. Deviations from Bjorken's scaling are taken into account by implementing finite-size profiles for the initial energy density. The calculated rapidity distributions of pions, kaons and antiprotons in central Au+Au collisions at the c.m. energy 200 AGeV are compared with experimental data of the BRAHMS Collaboration. The sensitivity of the results to the choice of the equation of state, the parameters of initial state and the freeze-out conditions is investigated. The best fit of experimental data is obtained for a soft equation of state and Gaussian-like initial profiles of the energy density.
Reasoning about the correctness of program transformations requires a notion of program equivalence. We present an observational semantics for the concurrent lambda calculus with futures Lambda(fut), which formalizes the operational semantics of the programming language Alice ML. We show that natural program optimizations, as well as partial evaluation with respect to deterministic rules, are correct for Lambda(fut). This relies on a number of fundamental properties that we establish for our observational semantics.
The paper presents an overview about some of the international relevant projects of digital resources in Germany. Online presentations of primary sources, e.g. photographic material, and bibliographic tools supporting research, such as cross searching, will be presented as potential partners of resource sharing with North America. Not only the possibility of cooperation will be sketched, but also necessary preliminary work and some obstacles will be outlined. This report is accompanied by a short characterization of African studies in Germany and the status quo of Open Access-initiatives.
This work gives a detailed introduction into a fully new experimental method to investigate the quantum crystal behavior of solid Helium-4. It has been found that a fascinating new effect occurs in the expansion of solid Helium-4 into a vacuum through pinhole orifices with diameters between 1 and 5 µm. It is observed that the beam flux intensity shows a periodic behavior for source conditions corresponding to the solid phase of Helium-4. The period is in the range of seconds up to minutes. It shows a strong dependence on temperature and source pressure. The oscillating part of the beam flux intensity amounts several percent of the total flux. This new phenomenon has been studied for temperatures between 2.1 K and 1.3 K and pressures up to 30 bar above the melting pressure. The beam flux intensity has been recorded by the vacuum pressure in a pitot vacuum chamber. The jet velocity in the range of 200 m/sec indicates that surprisingly the beam is a liquid jet, whereas the conditions in the source correspond to the solid state. In this work mainly the behavior of the flux modulation has been studied as a function of pressure and temperature and the influence of the isotope Helium-3. Furthermore geometrical aspects such as the influence of the nozzle diameter d0 have been investigated. In order to explain this novel phenomenon a kinetic model based on the injection of excess vacancies into the solid is proposed. According to this model the vacancies are generated at a solid/liquid interface. Forced by drift and diffusion they accumulate at some distance from the orifice, leading to the collapse of the solid. With the subsequent re-injection of vacancies the effect repeats and turns out to be periodical. The reproducibility of the time dependent beam flux intensity is demonstrated for a wide range of temperatures and pressures and gives direct access to values such as the temperature and pressure dependence of the vacancy diffusion coefficient Dv in the range of 10 high -5 cm high 2/sec, the recombination time of vacancies with interstitials T r near 1-20 sec and the vacancy activation energy f near 20 K. The good agreement with former experimental results by Zuev et al. [131] confirms the applicability of the theoretical model. As a result from the kinetic model the vacancy concentration is increased above the equilibrium vacancy concentration, caused by the injection of excess vacancies. Therefore, the most important discovery is the possibility of generating a non-equilibrium quantum solid. The investigation of this non-equilibrium solid leads to the discovery of a fluid-like regime in the solid phase of Helium-4 at temperatures below T = 1.58 K. The result gives a strong indication for the supersolid state, especially because the fluid-like behavior of the solid can be eliminated with smallest concentrations of Helium-3.
The development of resistance to multiple drugs is a major problem in treatment of number of infectious diseases and cancer. The phenomenon of multidrug resistance (MDR) is based on the synergetic interplay of a number of mechanisms such as target inactivation, target alteration, prevention of drug influx as well as active extrusion of drugs from the cell. The latter is mediated by over-expression of multidrug efflux pumps. The first discovered and the best characterized until now the human MDR transporter is P-glycoprotein. It is a member of the ATP binding cassette (ABC) superfamily and acts as an active transporter for a variety of anticancer agents using the energy released by ATP hydrolysis. The closest structure and functional homologue of P-glycoprotein found in bacteria is LmrA from Lactococcus lactis. The major goals of this work are to establish the selective isotope labelling of LmrA in Lactococcus lactis, to optimize LmrA sample preparation for solid-state NMR, and finally to perform first solidstate NMR investigations on LmrA shedding light on its catalytic cycle and substrate binding. For a long time the solid-state NMR applications to biological science has been limited to investigation of small molecules mostly. Recently, the solid-state NMR methods have shown potential for structuraland non-perturbing, site directed functional studies of large membrane proteins as well as ligands bound to them. However, to our knowledge neither selective isotope amino acid labelling of any ABC transporter, nor NMR investigations on full-length ABC transporter have been reported to date. Solidstate NMR experiments on a membrane protein require reconstitution of purified proteins into a membrane environment at a high density and either isotopic enrichment of the protein or bound drugs or inhibitors. Therefore, the large quantities of LmrA reconstituted at a high density in lipid membranes, sufficient for advanced NMR studies have been produced and its functional state in reconstituted form has been assessed. In the next step, a procedure for cost effective selective amino acids isotope labelling of LmrA in Lactococcus lactis has been established. Using this protocol deuterium alanine labelled LmrA reconstituted into E. coli liposomes has been prepared. Deuterium NMR has been used extensively to assess the proteins dynamics in past. However, it has never been applied to ABC transporter. Here, we report 2H NMR on selective alanine isotope labelled LmrA which has been used to shed light on the dynamics changes in the protein occurred under AMP-PNP, non-hydrolysable ATP analogue, binding and in ATP/ADP-Vanadate trapped state. It has been found that the major conformation changes affecting the protein motional characteristics occur in the ATP binding domains but not in the transmembrane domains. Additionally, the binding of several substrates to LmrA has been studied by fluorescence spectroscopy as well as by 19F and 31P solid-state NMR. The binding constants for several LmrA substrates have been obtained by fitting the concentration dependant tryptophan intrinsic fluorescence quenching curves. Based on the fluorescence studies and solid-state NMR data, the conformation changes in LmrA under substrate binding have been discussed. In addition, the preferable location of nine LmrA and P-glycoprotein substrates within the model membrane has been studied via 1H-MAS-NOESY-NMR. The results have been interpreted with respect to LmrA and P-glycoprotein binding site accessibility from the membrane interface region.
We develop a proof method to show that in a (deterministic) lambda calculus with letrec and equipped with contextual equivalence the call-by-name and the call-by-need evaluation are equivalent, and also that the unrestricted copy-operation is correct. Given a let-binding x = t, the copy-operation replaces an occurrence of the variable x by the expression t, regardless of the form of t. This gives an answer to unresolved problems in several papers, it adds a strong method to the tool set for reasoning about contextual equivalence in higher-order calculi with letrec, and it enables a class of transformations that can be used as optimizations. The method can be used in different kind of lambda calculi with cyclic sharing. Probably it can also be used in non-deterministic lambda calculi if the variable x is "deterministic", i.e., has no interference with non-deterministic executions. The main technical idea is to use a restricted variant of the infinitary lambda-calculus, whose objects are the expressions that are unrolled w.r.t. let, to define the infinite developments as a reduction calculus on the infinite trees and showing a standardization theorem.
The Na+/proline transporter of E. Coli (PutP) is responsible for the uptake of proline which is subsequently used not only as a carbon and nitrogen source and a constituent of proteins but also as a particularly effective osmoprotectant. However, for a long time there was little known about the single steps in the reaction cycle of this transporter and only few details about its structure-function relationship are available. Aim of the present work was to achieve a deeper understanding about the kinetic properties of the Na+/proline transporter and to get insights into the structure-function relationship of the substrate binding. To answer these questions different techniques were used. By using the novel SSM technique combining the preparation of PutP proteoliposomes it was possible to demonstrate for the first time the electrogenic substrate binding to PutP transporter. Due to rapid solution exchange measurements on the SSM it was additionally possible to obtain time resolved information about the kinetic details of the cytoplasmic substrate binding sites which were not available by previous steady state and equilibrium binding measurements. Pre-steady-state charge translocation was observed after rapid addition of one or both of the cosubstrates Na+ and/or proline to the PutP-WT proteoliposomes adsorbed on the SSM. Thereby it was possible to link the observed electrical signals with the binding activity of PutP. The observed Na+ and/or proline induced charge displacement were assigned to an electrogenic Na+ and/or proline binding process at the cytoplasmic face of the enzyme with a rate constant of k > 50 s-1 proceeding the rate limiting step of the reaction cycle. Furthermore, based on the kinetic analysis of the electrical signals obtained from the measurements of PutP on SSM, the following characteristics of the substrates binding in PutP were deduced: (1) both Na+ and proline can bind individually to the transporter. Under physiological conditions, an ordered binding mechanism prevails; while at sufficiently high concentrations, each substrate can bind in the absence of the other; (2) substrate binding is electrogenic not only for Na+, but also for the uncharged cosubstrate proline. The charge displacement associated with Na+ binding and proline binding is of comparable size and independent of the presence of the respective cosubstrate. In addition, it was concluded that Na+ accesses its binding site through a high-field access channel resulting in a charge translocation, whereas the binding of the electroneutral proline induces a conformation alteration involving the displacement of charged amino acid residue(s) of the protein; (3) Na+ and proline binding sites interact cooperatively with each other by increasing the affinity and/or the speed of binding of the respective cosubstrate; (4) proline binding proceeds in a two step process: low affinity (~ 0.9 mM) electroneutral substrate binding followed by a nearly irreversible electrogenic conformational transition; (5) membrane impermeable PCMBS inhibits both Na+ and proline binding to the inside-out orientated PutP transporter, indicating that rather than selectively blocking a specific binding site, PCMBS probably locks the enzyme in an inactive state. The possible targets for this SH-reagent are cysteines 281 and 344 located close to the cytoplasmic surface of the protein. Beyond it, transient electrical currents of PutP were also observed on the BLM after rapid addition of proline in the presence of Na+. This was possible by combining the conventional BLM technique with high-speed flash-photolysis of caged-proline. Indeed the signals on the BLM indicate the detection of a different underlying reaction process in comparison to the data achieved by the SSM technique. This has paved the way for supplemental information about the reaction cycle since it was possible to assign the flash-photolysis BLM signals to the proline binding step followed by the internalization of Na+ and proline into the liposome. Thereby it was found, that the presence of Na+ is indispensable and the time constant for the process is ~ 63 ms. Moreover, structure-function information about the Na+ and proline binding sites of PutP was obtained by investigating the functionally important amino acid residues Asp55, Gly63 and Asp187 with site-directed mutagenesis and the combined SSM technique. One finding is that the mutated proteins PutP-D55C and PutP-G63C showed no activity on the SSM. Therefore, it can be assumed that either both Asp55 and Gly63 are crucial for the structure of PutP protein, or they are located at or close to the Na+ and proline binding sites. Furthermore, the results obtained from PutP-D187N and PutP-D187C mutants on SSM suggest that Asp187 of PutP is likely to be involved in the Na+ binding at the cytoplasmic side of the backward running carrier. Taken together the results of the present work have substantially broadened the known picture of the Na+/proline transporter PutP thereby several steps of the reaction cycle were elucidated, and moreover, valuable insights into the structure-function relationship of the transporter have become available.
The technique of site-specific fluorescence labelling with Tetramethylrhodaminemaleimide (TMRM) in combination with two electrode voltage-clamp technique (TEVC), an approach that has been named voltage clamp fluorometry (VCF), has been used in this work to study the Na,K-ATPase. The TMRM dye has the ability to attach covalently to cysteine residues and it responds to changes in the hydrophobicity of its local environment. We exploited this property using a construct of the Na-pump in which the native, extracellularly accessible cysteines were removed and cysteine residues were introduced by site-directed mutagenesis in specific positions of the Na-pump. In this way it was possible to detect site-specific conformational rearrangements of the Na-pump in a time-resolved fashion within a native membrane environment. In particular this technique allows to resolve reactions with low electrogenicity that cannot be satisfactorily analyzed with purely electrophysiological techniques and to identify the conformations of the enzyme under specific ionic composition of the measuring buffers. We used VCF to study the influence that several cations like Na+, K+, NMG+, TEA+ and BTEA+ exert on the distribution of the Na,K-ATPase between several enzymatic intermediates and on some of the reactions related to cation transport. To this end we utilized the mutants N790C in the loop M5-M6 and the mutant E307C, T309C, L311C and E312C in the loop M3-M4. From the correspondence of the fluorescence changes with the activation and inhibition of pumping current, by K+ and ouabain respectively, and from the fact that in Na+/Na+ exchange conditions the voltage distribution of charge movement and fluorescence changes evoked by voltage jumps are in reasonable agreement we conclude that through the fluorescence signals measured from these mutants, we can indeed monitor conformational changes linked to transport activity of the enzyme. For the mutants N790 and L311, it was found that the Na+ dependence of the amplitude and kinetics of the fluorescence signal associated with the E1P-E2P transition is in agreement with the prediction of an access channel model describing the regulation of the access of extracellular Na+ to its binding site. In particular for the mutants E307 and T309 it was found that in Na+/Na+ exchange conditions, the conformational change tracked by the fluorescence was much slower than the charge relaxation at hyperpolarized potentials while the kinetics was very similar at depolarized potentials. This implies that at hyperpolarized potentials the conformational change connected to the E1P-E2P transition does not give a large contribution to the electrogenicity of the process which is also consistent with the access channel model. On the mutant N790C it was found that the external pH does not seem to have any effect on the E1P-E2P equilibrium even if it seems to modulate the fluorescence quantum yield of the dye. Fluorescence quenching experiments with iodide and D2O indicate that at hyperpolarized potentials the local environment of the mutant N790C, experiences a small change in the accessibility to water without major changes in the local electrostatic field ...
Sodium proton antiporters are ubiquitous membrane proteins found in the cytoplasmic and organelle membranes of cells of many different origins, including plants, animals and microorganisms. They are involved in cell energetics, and play primary roles in the homeostasis of intracellular pH, cellular Na+ content and cell volume. Adaptation to high salinity and/or extreme pH in plants and bacteria or in human heart muscles requires the action of such Na+/H+ antiporters. NhaA is the essential Na+/H+ antiporter for pH and Na+ homeostasis (at alkaline pH) in Escherichia coli and many other enterobacteria. NhaA is an electrogenic Na+/H+ antiporter that exchanges 2H+ for 1Na+ (or Li+). NhaA shares with many other prokaryotic and eukaryotic antiporters a very strong dependence on pH. In order to achieve three-dimensional structure of NhaA, the previously described NhaA protein preparation was modified: (i) the wild type bacterial strain (TA16) used for homologous over-expression of NhaA was replaced with a delta nhaA strain (RK20). As a result, the purity and homogeneity of the sample was significantly improved; (ii) the previously two-step purification procedure was shortened to a single step affinity chromatography purification; (iii) a wide-range screening of crystallisation conditions, more than 20,000, was performed; (iv) a Seleno-L-methionine (SeMet) NhaA derivative was produced in order to solve the phases during structure determination. In parallel, attempts of production and crystallisation of co-complexes composed of NhaA and antibody fragments have been made. Four different monoclonal antibodies were available against NhaA. Selected antibody fragments were produced and the stability of the complex analysed. Here, the crystal structure of the pH down-regulated secondary transporter NhaA of Escherichia coli is presented at 3.45 Å resolution. A negatively charged ion funnel opens to the cytoplasm and ends in the middle of the membrane at the putative ion-binding site. There, a unique assembly of two pairs of short helices connected by crossed, extended chains creates a balanced electrostatic environment. A possible mechanism is proposed: the binding of charged substrates causes electric imbalance inducing movements, which allow for a rapid alternating access mechanism. This ion exchange machinery is regulated by a conformational change elicited by a pH signal perceived at the cytoplasmic funnel entry. The structure represents a novel fold that provides two major insights: it reveals the structural basis for the mechanism of Na+/H+ exchange and its unique regulation by pH in NhaA and in many other similar antiporters. Furthermore, it is also important for the understanding of the architecture of membrane proteins in general. However, although many aspects of the ion-translocation mechanism and pH regulation are clarified by the NhaA structure, higher resolution structures with Li+ or Na+ bound are required for understanding the ligand binding and the translocation mechanism at the atomic level. The alkaline pH-induced conformation is essential to further understand the pH-control and proton access to the binding site.
In this thesis, we opened the door towards a novel estimation theory for homogeneous vectors and have taken several steps into this new and uncharted territory. Present state of the art for homogeneous estimation problems treats such vectors p 2 Pn as unit vectors embedded in Rn+1 and approximates the unit hypersphere by a tangent plane (which is a n-dimensional real space, thus having the same number of degrees of freedom as Pn). This approach allows to use known and established methods from real space (e.g. the variational approach which leads to the FNS algorithm), but it only works well for small errors and has several drawbacks: • The unit sphere is a two-sheeted covering space of the projective space. Embedding approaches cannot model this fact and therefore can cause a degradation of estimation quality. • Linearization breaks down if distributions are not highly concentrated (e.g. if data configurations approach degenerate situations). • While estimation in tangential planes is possible with little error, the characterization of uncertainties with covariance matrices is much more problematic. Covariance matrices are not suited for modelling axial uncertainties if distributions are not concentrated. Therefore, we linked approaches from directional statistics and estimation theory together. (Homogeneous) TLS estimation could be identified as central model for homogeneous estimation and links to axial statistics were established. In the first chapters, a unified estimation theory for the point data and axial data was developed. In contrast to present approaches, we identified axial data as a specific data model (and not just as directional data with symmetric probability density function); this led to the development of novel terms like axial mean vectors, axial variances and axial expectation values. Like a tunnel which is constructed from both ends simultaneously, we also drilled from the parameter estimation side towards directional/axial statistics in the second part. The presentation of parameter estimation given in this thesis deviates strongly from all known textbooks by presenting homogeneous estimation problems as a distinguished class of problems which calls for different estimation tools. Using the results from the first part, the TLS solution can be interpreted as the weighted anti-mean vector of an axial sample. This link allows to use our results from axial statistics; for instance, the certainty of the anti-mode (i.e. of the TLS solution!) can be described with a weighted Bingham distribution (see (3.91)). While present approaches are only interested in the eigenvector of the some matrix, we can now exploit the whole mean scatter matrix to describe TLS solution and its certainty. Algorithms like FNS, HEIV or renormalization were presented in a common context and linked to each other. One central result is that all iterative homogeneous estimation algorithms essentially minimize a series of evolving Rayleigh coefficients which corresponds to a series of (converging?) cost functions. Statistical optimization is only possible if we clearly identify every step as what it exactly is. For instance, the vague statement “solving Xp ... 0” means nothing but setting ˆp := arg minp pTXp pT p . We identified the most complex scenario for which closed form optimal solutions are possible (in terms of axial statistics: the type-I matrix weighted model). The IETLS approach which is developed in this thesis then solves general type-II matrix weighted problems with an iterative solution of a series of type-I matrix weighted problems. This approach also allows to built converging schemes including robust and/or constrained estimation – in contrast to other approaches which can have severe convergence problems even without such extensions if error levels are not low. Chapter 6 then is another big step forward. We presented the theoretical background of homogeneous estimation by introducing novel concepts like singular vector unbiasedness of random matrices and solved the problem of optimal estimation for correlated data. For instance, these results could be used for better estimation of local image orientation / optical flow (see section 7.2). At the end of this thesis, simulations and experiments for a few computer vision applications were presented; besides orientation estimation, especially the results for robust and constrained estimation for fundamental matrices is impressive. The novel algorithms are applicable for a lot of other applications not presented here, for instance camera calibration, factorization algorithm formulti-view structure from motion, or conic fitting. The fact that this work paved the way for a lot of further research is certainly a good sign.
The N-terminal domain (matrix protein or MA) of a retroviral Gag polyprotein precursor plays a critical role in several stages of the retrovirus life cycle. MA is involved in the effective membrane targeting, assembly and release of the immature viral particles from the infected cell. In order to understand the structural basis of these functions, the full length MA from Moloney Murine Leukemia Virus (MoMuLV) was purified and the solution structure of the MA MoMuLV was determined by means of heteronuclear high-resolution NMR spectroscopy and compared with that of the X-ray diffraction analysis as well as with the structures of several MA proteins from geterologous viruses. Structural features were also obtained from CD spectroscopy, dynamic light scattering, sedimentation velocity, differential scanning calorimetry and other methods. It was found that the MA MoMuLV globular core (residues 8-98) is comprised of 7 well-defined helices (five alpha-helices and two 310 helices), with the general fold typical for MA proteins from other retroviral species. The N-terminus (residues Met1-Leu7) and the C-terminal proline-rich part (residues Pro103-Tyr131) are not structured in solution. Although MA MoMuLV has a low sequence identity compared with other matrix proteins for which the three-dimensional structure is known, it was shown that its overall topology and pattern of secondary structural units is similar to other retroviral matrix proteins. The monomeric state is observed for the correctly folded MA MoMuLV in a variety of external conditions and protein concentrations, indicating that virion assembly starts with the plasma membrane targeting of the nascent Gag precursor. The denaturation of MA MoMuLV is irreversible and is connected with protein aggregation. For Moloney Murine Leukemia Virus (MoMuLV) a proteolytic processing of the R-peptide (last 16 amino acids from the C-terminus of the Envelope protein (Env)) has been described as a second mode of fusion and activation preceding the receptor contact between the viral particle and the cellular membrane. An interaction between the R-peptide and MA MoMuLV has been proposed, since the R-peptide and MA are localized at the inner part of the membrane. Therefore the interaction between 15N labelled purified MA MoMuLV and synthesized R-peptide has been investigated using high-resolution NMR. It was found that in water solution MA MoMuLV and R-peptide do not form a tight complex, but in a mature virion in the presence of membranes or other protein factors it might be possible. In the case of HIV-1 the cytoplasmic part (EnvC) of the Env protein is much longer than in other retroviruses and again as for MoMuLV little is known about the interaction between EnvC and HIV MA. Hence, the full length HIV MA, and the last 150 amino acids from HIV Env have been subcloned with suitable expression vectors, purified and analysed by native gel electrophoresis, a pull down assay and by high resolution NMR for the purpose to detect the complex formation of EnvC and HIV MA. Finally, after all those experiments, it was found that a stable complex is not formed, but a weak interaction between the two proteins can not be excluded.
Reynders, Veerle ; Loitsch, Stefan Marcel ; Steinhauer, Constanze ; Wagner, Thomas ; Steinhilber, Dieter ; Bargon, Joachim
Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response.
Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay.
Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit.
Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF.
Studies and measurements of linear coupling and nonlinearities in hadron circular accelerators
(2006)
In this thesis a beam-based method has been developed to measure the strength and the polarity of corrector magnets (skew quadrupoles and sextupoles) in circular accelerators. The algorithm is based on the harmonic analysis (via FFT) of beam position monitor (BPM) data taken turn by turn from an accelerator in operation. It has been shown that, from the differences of the spectral line amplitudes between two consecutive BPMs, both the strength and the polarity of non-linear elements placed in between can be measured. The method has been successfully tested using existing BPM data from the SPS of CERN, since presently the SIS-18 is not equipped with the necessary hardware. The magnet strength of seven SPS extraction sextupoles was measured with a precision of about 10%. The polarities have been unambiguously measured. This method can be used to detect polarity errors and wrong power supply connections during machine commissioning, as well as for a continuous monitoring of the "nonlinearity budget" in superconducting machines. A second beam-based method has been studied for a fast measurement and correction of betatron coupling driven by skew quadrupole field errors and tilted focusing quadrupoles. Traditional methods usually require a time-consuming scan of the corrector magnets in order to minimize the coupling stop band |C|. In this thesis it has been shown how the same correction can be performed in a single machine cycle from the harmonic analysis of multi-BPM data. The method has been successfully applied to RHIC. It has been shown that the stop band |C| (also known in the American literature as Delta-Qmin) measured in a single machine cycle with the new algorithm is compatible with the value obtained by traditional methods. The measurement of the resonance phase Theta defines automatically the best corrector setting, which was found in agreement with the one obtained with a traditional scan. A third theoretical achievement is a new description of the betatron motion close to the difference resonance in presence of linear coupling. Compared to the matrix formalism the motion is parametrized as a function of the resonance driving term f1001 only (which is proven to be an observable), whereas making use of the matrix approach four parameters need to be measured. Formulae describing the exchange of RMS emittances when approaching the resonances have been already derived in the 70s in the smooth approximation. New formulae have been derived here making use of Lie algebra providing a better description of the emittance behavior. The emittance exchange curves are predicted by new formulae with excellent agreement with multi-particle simulations and the counter-intuitive emittance variation along the ring of the emittance is proven to be related to the variation of f1001. A new way to decouple the equations of motion and explicit expressions for the individual single particle invariants have been found. For the first time emittance exchange studies have been carried out in the SIS-18 of GSI. Transverse RMS emittances have been measured during 2005 from rest gas monitor (RGM) data. Crossing the linear coupling resonance, the transverse emittances exchange completely. It has been observed that this effect is reversible. Applications of this manipulation are: emittance equilibration under consideration for future operations of the SIS-18 as booster for the SIS-100; emittance transfer during multi-turn injection to improve the eficiency and to protect the injection septum in high intensity operations, by shifting part of the horizontal emittance into the vertical plane. The emittance exchange curves obtained experimentally have been compared with analytic formulae providing a fast measurement (in few machine cycles only) of the linear coupling stop band |C|. Technical problems prevented the use of the eight skew quadrupoles installed in the SIS-18 to compensate the linear coupling resonance. It has been observed that the emittance exchange curve is highly sensitive to the beam intensity. Multi-particle simulations with 2D PIC space-charge solver have been run to infer heuristic scaling laws able to quantify the observable stop band, to be used for the resonance compensation. The analysis of BPM and RGM data has been performed making use of new software applications developed for this purpose. The bpm2rdt code for the harmonic analysis of BPM data has been written and tested with real data. The software reads the BPM turn-by-turn data and the Twiss parameters. Then it performs the FFT of these data, finds the peaks of the Fourier spectra and infers the RDT fjklm, the strengths ^hjklm and the local terms lambda-jklm. All these observables are printed out together with the corresponding values of the model, computed from the nominal values of strengths and the Twiss parameters. From the FFT of dual-plane BPM data the linear optics (beta functions and phase advances Delta phi) at the corresponding location is also inferred. From the measurement of f1000, the linear coupling coeffcient C (amplitude and phase) is also computed. The code has been tested by using existing SPS data and new RHIC data. For the on-line analysis of RGM data the rgm2emitt code has been written. The application reads in input the raw data files from the RGM and the beam loss monitor (BLM) respectively, the latter created by the RGM on-line software itself. From the RGM data the transverse beam sizes and emittances are inferred and used together with the BLM data to compute the tune shift during the machine cycle.
Alzheimer’s Disease (AD) is the most common neurodegenerative disorder marked by progressive loss of memory and cognitive ability. The pathology of AD is characterised by the presence of amyloid plaques, intracellular neurofibrillary tangles and pronounced cell death. The aim of this thesis was to investigate pathways involved in the Aß cascade of neurodegeneration. Since novel findings indicate that already this Aß species exerts neurotoxic effects long before hyperphosphorylated tau, neurofibrillary tangles and extracellular Aß plaques appear, the investigations were accomplished with specific regard to the effects of intracellular Aß. The Swedish double mutation in the APP gene results in six- to eightfold increased Aß production of both Aß1-40 and Aß1-42 compared to human wildtype APP cells (APPwt). Data obtained from PC12 cells indicate that it is possible to specifically increase the Aß load without enhancing APP expression levels. On the basis of these findings, it seemed possible to investigate dose-dependent effects of Aß in multiple experimental designs. These assay designs were created in order to mimick different in-vivo situations that are discussed to occur in AD patients: APPsw PC12 cells exhibit low physiological concentrations of Aß within picomolar range in contrast to APPsw HEK cells, expressing Aß levels within the nanomolar range. Of note, the APPsw HEK cells showed a specific and highly significant increase in the intracellular accumulation of insoluble Aß1-42. Moreover, an intracellular accumulation of Aß and APP was found in the mitochondria of the HEK APPsw cells suggesting a direct impact on mitochondrial function on these cells. This effect might finally lead to disturbances in the energy metabolism of the cell or to increased cell death. Furthermore, baseline g- and ß-secretase activity was assessed since these enzymes represent promising therapeutic targets to slow or halt the disease process. As expected, ß-secretase activity was significantly elevated in all APPsw cell lines. This might be due to the proximity of the Swedish double mutation next to the N-terminus of the Aß sequence. Interestingly, g-secretase activity was similarly increased in PC12 APPsw cells. In addition, the toxicity of different Aß species was investigated in SY5Y and PC12 cells with regard to their effect on cellular viability mirrored by mitochondrial activity using MTT assay. Here, it turned out that not monomers, but already dimers are neurotoxic correlates. Fibrillar Aß species showed the highest toxicity. In the next step, SY5Y cells forming endogenous, dimeric APP and Aß were investigated. In accordance with previous findings, these cells showed a decreased MTT reduction potential in comparison to APPwt and control SY5Y cells reflecting a decrease of cellular viability. The impaired energy metabolism of the cells was even more drastically mirrored by reduced baseline ATP levels. In the second part of this thesis, the expression and intracellular distribution of Bcl-2 family proteins and pro-apoptotic mitochondrial factors under baseline conditions and during oxidative stress were analyzed in the APPwt and APPsw bearing cells. The most prominent finding was the reduction of expression levels of the anti-apoptotic factor Bcl-xL in the cytosolic fractions of APPwt and APPsw PC12 cells. This might indicate that a lack of anti-apoptotic factors or their altered intracellular distribution, rather than an increase in caspase-dependent pro-apoptotic factors, could be responsible for the increased vulnerability of APPwt- and APPsw-transfected PC12 cells against oxidative stress. Since total Bcl-xL expression was unaffected in PC12 cells, in contrast to APPwt and APPsw-expressing SY5Y and HEK cells revealing significantly decreased Bcl-xL expression levels. Thus, alterations in Bcl-xL distribution seem to be an early event in the disease process. Increasing Bcl-xL expression might potentially be one promising strategy for AD modification. PC12 and HEK cells bearing APPsw or APPwt were treated with the potent g-secretase inhibitor DAPT. Of note, DAPT did not only efficiently block Aß production, but additionally led to an elevation of the MTT reduction potential, reflecting an increase in cellular viability. As another disease-modifying strategy, several efforts are undertaken to ameliorate AD-relevant symptoms by the treatment with nerve growth factor (NGF). Generally, it is known that substituted pyrimidines have modest growth-promoting effects. Here, KP544, a novel substituted pyrimidine, was characterised. This drug increased MTT reduction potential in terminally differentiated and undifferentiated PC12 cells. Furthermore, treatment with KP544 led to a reduction in Aß1-40 secretion. Thus, one may conclude that the target of KP544, GSK-3ß, represents a connecting link between the two main pathological hallmarks of AD and might thus be a very promising therapeutic target for AD.
I derive a general effective theory for hot and/or dense quark matter. After introducing general projection operators for hard and soft quark and gluon degrees of freedom, I explicitly compute the functional integral for the hard quark and gluon modes in the QCD partition function. Upon appropriate choices for the projection operators one recovers various well-known effective theories such as the Hard Thermal Loop/ Hard Dense Loop Effective Theories as well as the High Density Effective Theory by Hong and Schaefer. I then apply the effective theory to cold and dense quark matter and show how it can be utilized to simplify the weak-coupling solution of the color-superconducting gap equation. In general, one considers as relevant quark degrees of freedom those within a thin layer of width 2 Lambda_q around the Fermi surface and as relevant gluon degrees of freedom those with 3-momenta less than Lambda_gl. It turns out that it is necessary to choose Lambda_q << Lambda_gl, i.e., scattering of quarks along the Fermi surface is the dominant process. Moreover, this special choice of the two cutoff parameters Lambda_q and Lambda_gl facilitates the power-counting of the numerous contributions in the gap-equation. In addition, it is demonstrated that both the energy and the momentum dependence of the gap function has to be treated self-consistently in order to determine the imaginary part of the gap function. For quarks close to the Fermi surface the imaginary part is calculated explicitly and shown to be of sub-subleading order in the gap equation.
Background: The flavin in its FMN and FAD forms is a versatile cofactor that is involved in catalysis of most disparate types of biological reactions. These include redox reactions such as dehydrogenations, activation of dioxygen, electron transfer, bioluminescence, blue light reception, photobiochemistry (as in photolyases), redox signaling etc. Recently, hitherto unrecognized types of biological reactions have been uncovered that do not involve redox shuffles, and might involve the reduced form of the flavin as a catalyst. The present work addresses properties of reduced flavin relevant in this context. Results: N(5)-H exchange reactions of the flavin reduced form and its pH dependence were studied using the 15N-NMR-signals of 15N-enriched, reduced flavin in the pH range from 5 to 12. The chemical shifts of the N(3) and N(5) resonances are not affected to a relevant extent in this pH range. This contrasts with the multiplicity of the N(5)-resonance, which strongly depends on pH. It is a doublet between pH 8.45 and 10.25 that coalesces into a singlet at lower and higher pH values. From the line width of the 15N(5) signal the pH-dependent rate of hydrogen exchange was deduced. The multiplicity of the 15N(5) signal and the proton exchange rates are little dependent on the buffer system used. Conclusion: The exchange rates allow an estimation of the pKa value of N(5)-H deprotonation in reduced flavin to be ≥ 20. This value imposes specific constraints for mechanisms of flavoprotein catalysis based on this process. On the other hand the pK ≈ 4 for N(5)-H protonation (to form N(5)+-H2) would be consistent with a role of N(5)-H as a base.
Burjanivova, Tatiana ; Madzo, Jozef ; Muzikova, Katerina ; Meyer, Claus ; Schneider, Bjoern ; Votava, Felix ; Marschalek, Rolf ; Stary, Jan ; Trka, Jan ; Zuna, Jan
Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases.
Meulen, Jan ter ; Brink, Edward van den ; Leo L. M., Poon ; Marissen, Wilfred E. ; Leung, Cynthia S. W. ; Cox, Freek ; Cheung, Chung Y. ; Bakker, Arjen Q. ; Bogaards, Johannes A. ; Deventer, Els van ; Preiser, Wolfgang ; Doerr, Hans Wilhelm ; Chow, Tak-Kwong Vincent ; Kruif, John de ; Peiris, Joseph Sriyal Malik ; Goudsmit, Jaap
Background: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. Methods and Findings: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. Conclusions: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.
CFSnewsletter is a documentation of past, present and future CFS activities in the fields of research, executive development and events. Printed versions of all issues published since 1997 can be ordered free of charge. To download the latest issues, you need ADOBE Acrobat Reader. Contact: Lut De Moor Phone: +49-(0)69-798-30060 Fax: +49-(0)69-798-30077 media_contact (AT) ifk-cfs.de
We review arguments for and against reserve requirements and conclude that the main question is whether a distinction between money creation and intermediation can be made. We argue that such a distinction can be made in a money-in-advance economy and show that if the money-in-advance constraint is universally binding then reserve requirements on checkable accounts have no effect on intermediation. We then proceed to show that in a model in which trade is uncertain and sequential, a fractional reserve banking system gives rise to endogenous monetary shocks. These endogenous monetary shocks lead to fluctuations in capacity utilisation and waste. When the money-in-advance constraint is universally binding, a 100% reserve requirement on checkable accounts can eliminate this waste.
This paper employs a multi-country large scale Overlapping Generations model with uninsurable labor productivity and mortality risk to quantify the impact of the demographic transition towards an older population in industrialized countries on world-wide rates of return, international capital flows and the distribution of wealth and welfare in the OECD. We find that for the U.S. as an open economy, rates of return are predicted to decline by 86 basis points between 2005 and 2080 and wages increase by about 4.1%. If the U.S. were a closed economy, rates of return would decline and wages increase by less. This is due to the fact that other regions in the OECD will age even more rapidly; therefore the U.S. is “importing” the more severe demographic transition from the rest of the OECD in the form of larger factor price changes. In terms of welfare, our model suggests that young agents with little assets and currently low labor productivity gain, up to 1% in consumption, from higher wages associated with population aging. Older, asset-rich households tend to lose, because of the predicted decline in real returns to capital. Klassifizierung: E17, E25, D33, C68
When liquidity plays an important role as in times of financial crisis, asset prices in some markets may reflect the amount of liquidity available in the market rather than the future earning power of the asset. Mark-to-market accounting is not a desirable way to assess the solvency of a financial institution in such circumstances. We show that a shock in the insurance sector can cause the current value of banks’ assets to be less than the current value of their liabilities so the banks are insolvent. In contrast, if historic cost accounting is used, banks are allowed to continue and can meet all their future liabilities. Mark-to-market accounting can thus lead to contagion where none would occur with historic cost accounting. Klassifizierung: G21, G22, M41
The focus of this thesis is on quantum Heisenberg magnets in low dimensions. We modify the method of spin-wave theory in order to address two distinct issues. In the first part we develop a variant of spin-wave theory for low-dimensional systems, where thermodynamic observables are calculated from the Gibbs free energy for fixed order parameter. We are able to go beyond linear spin-wave theory and systematically calculate two-loop correction to the free energy. We use our method to determine the low-temperature physics of Heisenberg ferromagnets in one, two and three spatial dimensions. In the second part of the thesis, we treat a two-dimensional Heisenberg antiferromagnet in the presence of a uniform external magnetic field. We determine the low-temperature behavior of the magnetization curve within spin-wave theory by taking the absence of the spontaneous staggered magnetization into account. Additionally, we perform quantum Monte Carlo simulations and subsequently show that numerical findings are qualitatively comparable to spin-wave results. Finally, we apply our method to an experimentally motivated case of the distorted honeycomb lattice in order to determine the strength of the exchange interactions.
The botanical exploration of Eastern Asia by European travellers and botanists has for a long time attracted the author's attention, and the greater part of the materials for the present work were brought together, many years ago, from various sources of information, frequently unprinted, some of which were only obtainable in China. ...
The formation of vegetable mould : through the action of worms with observations on their habits
(1881)
Illustrations of the British flora : a series of wood engravings with dissections of British plants
(1924)
The illustrations contained in this volume were drawn, with the few exceptions presently referred to, by W. H. Fitch, F.L.S., for the original illustrated edition of Bentham's "Handbook of the British Flora." Since that edition was exhausted they have been issued separately, forming a companion volume to the "Handbook" and to other general, county and local Floras. Additional drawings by W. G. Smith, F.L.S., and others, have been incorporated from time to time illustrating additions to the Flora. The arrangement in the present edition follows that of the latest edition of Bentham's "Handbook."
IAD annual report
(2003)
The Institute for Aboriginal Development Incorporated (IAD) was established by the Uniting Church in 1969 to assist community development for Aboriginal people and provide cross-cultural education between Aboriginal and non-Aboriginal society. It is now an independent Aboriginal community-controlled language resource centre and adult education centre serving the Aboriginal community of Central Australia. General IAD activities include: * education programs which range from literacy and numeracy to vocational and higher education level courses; * an Aboriginal language and culture centre specialising in language cross-culture and cultural maintenance programs, as well as providing interpreter services and language research * a publishing arm, IAD Press, which produces material on the Aboriginal people, language and culture of Central Australia.
One of the central research topics in the field of biophysical chemistry is the structure and function of membrane proteins involved in energy transduction. Both, the aerobic and the anaerobic respiration include electron transfer and proton translocation across the mitochondrial and bacterial membranes. These electron transfer processes lead to changes in oxidation states of cofactors some of which are paramagnetic. Therefore, EPR spectroscopy is the method of choice to obtain electronic and structural information directly related to the function of the respiratory chain proteins. In this work, multifrequency continuous wave (CW) and pulsed EPR spectroscopy has been used to characterize the molybdenum active site of polysulfide reductase (Psr) from the anaerobic bacterium Wolinella succinogenes and the protein-protein complex between cytochrome c oxidase (CcO) and cytochrome c from the aerobic bacterium Paracoccus denitrificans. Molybdenum in Psr-Psr is an enzyme essential for the sulfur respiration of Wolinella succinogenes. Biochemical studies suggested that the active site of this enzyme contains a mononuclear Mo center, which catalyzes the reduction of the substrate polysulfide to sulfide. Until now there is no crystal structure available for Psr. Consequently, current characterizations of this enzyme have to rely on biochemical and spectroscopic investigations. Within the present work, CW and modern pulsed EPR techniques were applied to investigate its catalytically active site. In the first part of this thesis, different redox agents have been used to generate paramagnetic states of Psr. Multifrequency CW-EPR spectroscopy was applied to identify the Mo(V) states. Using simulations of the experimental spectra, three spectroscopically distinct states have been identified based on the Mo hyperfine- and g-tensor values. Comparison of their EPR parameters with those of related enzymes indicated five or six sulfur ligands at the Mo center depending on the state. The state generated by addition of polysulfide is suggested to be the catalytically active form, in which the Mo is coordinated by a sulfur of the polysulfide chain as the sixth ligand. 33S (I = 3/2) labeled polysulfide was prepared to probe the proximity of the polysulfide to the molybdenum center via its hyperfine coupling. 1D-ESEEM and 2D122 HYSCORE spectroscopy was used to detect these hyperfine and quadrupole interactions, which are too small to be observed in conventional CW EPR spectra. To date there has been only one pulsed-EPR study involving a 33S nucleus [Finazzo et.al. 2003]. The reasons are that this nucleus has a high nuclear spin of I = 3/2 and a large nuclear quadrupole moment in addition to the low Larmor frequency. All these make the detection of sulfur and the extraction of structural information demanding. However, analysis of the 2D-data led to a Mo(V) 33S distance in a range of about 2 to 2.5 Å. Mo-S distances found in molybdenum enzymes of the same family are in a range of 1.8 to 2.8 Å suggesting that the 33S is indeed the sixth ligand of the Mo(V) center and demonstrating that polysulfide is the actual substrate for this enzyme. Thus HYSCORE experiments have been proved to be a powerful technique to gain further insight into the active site structures of molybdenum enzymes and the trafficking of substrate atoms during catalysis. Density functional theory (DFT) calculations together with quantitative numerical simulations of the 2D-data will help to obtain more structural details about the molybdenum binding site in Psr. CcO:cytochrome c complex Protein-protein complex formation is an important step in energy conversion biological processes such as respiration and photosynthesis. These protein-protein complexes are involved in long range electron transfer reactions and are known to be of transient nature. Within the bacterial and mitochondrial respiratory electron transport chains such a complex is formed between CcO and cytochrome c. Upon complex formation cytochrome c donates the electrons required for the CcO catalyzed reduction of dioxygen to water. Here, the protein-protein complex formation between CcO and cytochrome c from Paracoccus denitrificans was investigated by pulsed EPR spectroscopy. The idea was to use the relaxation enhancement due to the distance and orientation dependent magnetic dipole-dipole interaction between the paramagnetic centers in the different CcO constructs and cytochromes. Two-pulse electron spin echo experiments were carried out on mixtures of the CuA containing soluble subunit II or the full size CcO with the physiological partner cytochrome c552 or horse heart cytochrome c. Significantly enhanced relaxation of CuA due to specific protein-protein complex formation has been observed in all four cases. In contrast the non-binding cytochrome c1 showed only a very weak relaxation enhancement due to unspecific protein-protein interactions. The echo decays of the slowly relaxing observer spin (CuA of CcO) measured in the absence and presence of the fast relaxing spin (Fe(III) of cytochrome c) permitted the extraction of the pure dipolar relaxation contributions for the different complexes. Measurements at different temperatures proved the dipolar nature of the relaxation enhancement. Furthermore, it was demonstrated experimentally that this approach also works for the full-size CcO, which contains four paramagnetic metal centers, in complex with cytochrome c. Quantitative simulations of the data suggest a broad distribution in distances (2 - 4 nm) and orientations between the CuA and Fe(III) in the complex between CcO and cytochrome c. High-field EPR spectroscopy will be useful to further analyze and prove these complex structures. Within the present work, it has been shown that pulsed relaxation enhancement experiments can be used to investigate the distance and relative orientation between paramagnetic metal centers. Furthermore, it has been demonstrated on a qualitative level, that this method can be used complimentary to other biophysical approaches to study transient electron transfer protein-protein complexes. Finally, within this work it has been proven that this method can be applied also to biological systems where more than two paramagnetic centers are present. This is particularly interesting for supercomplexes between membrane proteins.
Saint Clare of Assisi was born in 1194 to a family of notable social standing. Against her family’s wishes, she left home at the age of eighteen to join the Order of Saint Francis. She soon established the convent of the Poor Ladies in Assisi, which later became officially recognized as the Second Franciscan Order, and went on to govern it for 40 years. Like Saint Francis, who died in 1226 and was officially declared a saint in 1228, her canonization also took place only two years after her death in 1253, thereby demonstrating the tremendous impact she had on her contemporaries. ...
Die Autorin behandelt am Beispiel Brasilien das universelle Thema der Gewalt gegen Frauen in einem international vergleichenden und interkulturell kommunikativen Zusammenhang. Wichtiges Anliegen ihrer Fallstudie zur Gewalt gegen Frauen ist deutlich zu machen, dass die kontextbedingt aktive Bewegung der Frauen wider Gewalt in Brasilien sich nicht nur von Aktionen und Diskursen aus dem internationalen Bereich inspiriert hat, sondern einen beachtenswerten eigenen Beitrag leistet, von dem auch andere Frauenbewegungen lernen könnten. Voraussetzung hierzu ist allerdings, dass in allen diesen Gesellschaften, denen innerhalb der stratifizierten globalen Zusammenhänge unterschiedlicher Status zugewiesen wird, ein interkulturell kommunikativer Lernprozess stattfindet. In der Einleitung zu dieser Studie wird auf die spezifische Problematik des Themas hingewiesen, die Untersuchungsmethode und die eigene Argumentationsweise vorgestellt, die eng mit der Motivation zur Behandlung des Themas verwoben ist. Im ersten Kapitel wird die Gewalt gegen Frauen als zugleich universales wie auch partikulares Problem diskutiert, und dementsprechend die divergierenden Definitionen der Gewalt gegen Frauen, die vielfältigen Ansätze zum Verständnis von Frauen aus verschiedenen Gesellschaften und schließlich die Vielfalt der Erfahrungen von Frauen gegenüber Gewalt im Licht der interkulturellen Kommunikation vorgestellt und kritisch analysiert. Im zweiten Kapitel werden die diskursiv analytischen Interpretationen der Gewalt gegen Frauen im Licht der interkulturellen Kommunikation behandelt. Die Autorin knüpft an das diskursive Modell der Bedürfnisinterpretation von Nancy Fraser an und wendet es als methodischer Ansatz zur Interpretation der Gewalt gegen Frauen an. Sie weist auf die gesellschaftspolitischen und kulturellen Grenzen dieses Modells (auf die nördliche Hemisphäre beschränkt) hin und versucht es im Lichte des Ansatzes von Patrick Dias zu interkulturellem Lernen im Kontext der international ungleichen Machtstrukturen kritisch weiterzuentwickeln. Das dritte Kapitel analysiert die relevanten gesellschaftlichen Bedingungen mit ihren diskursiven Konstruktionen zum Verständnis von Frauen und deren Stellung im spezifischen Kontext Brasiliens. Das vierte Kapitel stellt die brasilianische Frauenbewegung wider Gewalt gegen Frauen in ihren historischen Zusammenhängen dar: von ihren Anfängen über deren Strategien in den Achtzigern bis im ausgehenden zwanzigsten Jahrhundert hinein; und es schließt mit den Diskussionen im 21. Jahrhundert ab, die verstärkt unter der Metapher der Cidadania (Aufbau der Zivilgesellschaft) steht. Kapitel fünf fasst die Ergebnisse der Untersuchung zusammen und führt den in der Studie angewandten diskursiv analytischen Ansatz im Rahmen der interkulturell immer noch bestehenden herrschaftlichen Kommunikationsstruktur mit einem Plädoyer für ein interkulturelles Lernen, das die globalen Ungleichheiten nicht verkennt, weiter.
The Way of the Beer analyses how Mafa re-enact their history in the ritual transfer of sorghum beer from junior to senior members of their society. Beer is the ‘Eucharist’ of Mafa religion, standing for the linkage between God, the ancestors, the fertility of the living and the agricultural land. The ritual sequences in which beer is exchanged and offered at family and community shrines are an encoding of settlement history. The CD-ROM version of the "Way of the Beer" not only contains everything found in the printed version of this work, but also a digital map (figure 8) whichis too large to be printed. The key to the digital map (figure 9) is electronically linked to the map. Please note that figure 9 is displayed when the option "key", found under each ward name (in the bookmark section of figure 8), is activated. If this is done for the first time, figure 8 needs to be brought up again in order to be tiled next to figure 9. However, the best option for exploring the map is to print out the key. Please refer to "The Way of the Beer"(pages 142-144) for further information on how the large digital map needs to be read. The text, maps and images can be viewed in Word (please install the linguistic fonts before using the Word version) or Acrobat Reader (version 4.0 has beencopied on to the CD-ROM). The CD-ROM also contains version 1.03 of the Northern Mandaras Homepage which must be viewed with Microsoft Explorer. The CD-ROM is organised in five main folders which are labelled "Text", "Figures", "Tables", "Plates" and "Homepage". Each folder contains a Word 97 as well as an Adobe Acrobat version of "The Way of the Beer". It is only the large digital map which does not exist as a Word but only as an Adobe Acrobat version. The page numbering apart from figure 8) continues through the sections, beginning with the text and ending with the plates.
An alternative theoretical description of axial electron channeling in the multi-GeV region has been developed. We solve a kinetic equation to evaluate an electron distribution function in axially oriented single crystals. Based on the single-string model, the required matrix elements for radiation and scattering by lattice vibrations are calculated employing solutions of the Dirac equation in cylindrical coordinates. Results obtained for 150-GeV electrons propagating along the <110> axis of germanium are in good agreement with experimental observations.
The experimental cold-fission yields for the system 233U(nth, f) are analyzed as function of the effective total excitation energy (TXE). The nuclear level density effect is taken into account at higher TXE, in order to benefit by the lower experimental data uncertainty as well as to avoid the quantitative account of the level densities close to fragment ground states. In this way the odd-even staggering which appears in the yields extrapolated at zero excitation energy by using the level densities, vanishes. We conclude that the cold nuclear fragmentation theory including the dynamical model describes well the experimental data.
The components of the nuclear inertia tensor, functions of the separation distance R and of the radius of the light fragment R2, BRR(R,R2), BRR2(R,R2), and BR2R2(R,R2) are calculated within the Werner-Wheeler approximation, by using the parametrization of two intersected symmetric or asymmetric spheres. Analytical relationships are derived. When projected to a path R2=R2(R), the reduced mass is obtained at the touching point. The two one-dimensional parametrizations with R2=const, and the volume V2=const previously studied, are found to be particular cases of the present more general approach. Illustrations for the cold fission, cluster radioactivity, and α decay of 252Cf are given.
We have investigated the channeling process of charged particles in a bent crystal. Invoking simple assumptions we derive a criterion, which determines whether channeling occurs or not. We obtain the same criterion using the Dirac equation. It is shown that the centrifugal force acting on the particle in the bent crystal significantly alters the effective transverse potential. The cases of axial and planar channeling are considered. The channeling probability and the dechanneling probability due to tunneling of the particle under the barrier in the effective transverse potential are estimated. These probabilities depend on the specific scaling parameter characterizing the process. Using the quasiclassical theory of synchrotron radiation we have calculated the contribution to the radiation spectrum, which arises due to the curvature of the channel. This contribution becomes significant to TeV electrons or positrons. Some practical consequences of our results are briefly discussed.
A coplanar three body cluster model (two deformed fragments and an alpha particle) similar to the model used for the description of cold binary fission was employed for the description of cold (neutronless) alpha accompanied fission of 252Cf. No preformation factors were considered. The three body potential was computed with the help of a double folding potential generated by the M3Y-NN effective interaction and realistic fragment ground state deformations. From the minimum action principle, the alpha particle trajectory equations, the corresponding ternary barriers, and an approximate WKB expression for the barrier penetrability are obtained. The relative cold ternary yields were calculated as the ratio of the penetrability of a given ternary fragmentation and the sum of the penetrabilities of all possible cold ternary fragmentations. Different scenarios were considered depending on the trajectories of the fragments. It was shown that two regions of cold fragmentation exist, a deformed one corresponding to large fragment deformations and a spherical one around 132Sn, similarly to the case of the cold binary fission of 252Cf. We have shown that for the scenario corresponding to the Lagrange point, where all forces acting on the alpha particle are in equilibrium, the cold alpha ternary yields of 252Cf are strongly correlated with the cold binary yields of the daughter nucleus 248Cm into the same heavy fragments. For all other scenarios only the spherical splittings are favored. We concluded that due to the present available experimental data on cold alpha ternary yields only the Lagrange scenario could describe the cold alpha ternary fission of 252Cf.
For cold (neutronless) fission we consider an analytical model of quantum tunneling with dissipation through a barrier U(q) evaluated with a M3Y nucleon-nucleon force. We calculate the tunneling spectrum, i.e., the fission rate as a function of the total kinetic energy of the fragments. The theoretical results are compared with the experimental data obtained for the fine structure of two cold fission modes of 252Cf: 148Ba+104Mo and 146Ba+106Mo. Taking into account the dissipative coupling of the potential function U(q) and of the momentum p with all the other neglected coordinates, we obtain a remarkable agreement with the experimental data. We conclude that the cold fission process is a spontaneous decay with a spectrum determined by the shape of the barrier and an amplitude depending on the strength of the dissipative coupling.
We discuss the prospects for parity-nonconservation experiments with highly charged heavy ions. Energy levels and parity mixing for heavy ions with 2–5 electrons are calculated. We investigate two-photon transitions and the possibility of observing interference effects between weak-matrix elements and Stark matrix elements for periodic electric field configurations.
A first testing ground for QED in the combined presence of a strong Coulomb field and a strong magnetic field is provided by the precise measurement of the hyperfine structure splitting of hydrogenlike 209Bi. We present a complete calculation of the one-loop self-energy correction to the first-order hyperfine interaction for various nuclear charges. In the low-Z regime we almost perfectly agree with the Z alpha expansion, but for medium and high Z there is a substantial deviation.
We compute the vacuum polarization correction to the binding energy of nuclear matter in the Walecka model using a nonperturbative approach. We first study such a contribution as arising from a ground-state structure with baryon-antibaryon condensates. This yields the same results as obtained through the relativistic Hartree approximation of summing tadpole diagrams for the baryon propagator. Such a vacuum is then generalized to include quantum effects from meson fields through scalar-meson condensates which amounts to summing over a class of multiloop diagrams. The method is applied to study properties of nuclear matter and leads to a softer equation of state giving a lower value of the incompressibility than would be reached without quantum effects. The density-dependent effective sigma mass is also calculated including such vacuum polarization effects.
An investigation of the transition to delta matter is performed based on a relativistic mean field formulation of the nonlinear sigma and omega model. We demonstrate that in addition to the Delta-meson coupling, the occurrence of the baryon resonance isomer also depends on the nucleon-meson coupling. Our results show that for the favored phenomenological value of m* and K, the Delta isomer exists at baryon density ~ 2–3 p0 if beta=1.31 is adopted. For universal coupling of the nucleon and Delta, the Delta density at baryon density ~ 2–3 p0 and temperature ~ 0.4–0.5 fm-1 is about normal nuclear matter density, which is in accord with a recent experimental finding.
We study here hot nuclear matter in the quark meson coupling model which incorporates explicitly quark degrees of freedom, with quarks coupled to scalar and vector mesons. The equation of state of nuclear matter including the composite nature of the nucleons is calculated at finite temperatures. The calculations are done taking into account the medium-dependent bag constant. Nucleon properties at finite temperatures as calculated here are found to be appreciably different from the value at T=0.
We study the binary cold fission of 252Cf in the frame of a cluster model where the fragments are born to their respective ground states and interact via a double-folded potential with deformation effects taken into account up to multipolarity lambda=4. The preformation factors were neglected. In the case when the fragments are assumed to be spherical or with ground-state quadrupole deformation, the Q-value principle dictates the occurrence of a narrow region around the double magic 132Sn, like in the case of cluster radioactivity. When the hexadecupole deformation is turned on, an entire mass region of cold fission in the range 138–156 for the heavy fragment arise, in agreement with the experimental observations. This fact suggests that in the above-mentioned mass region, contrary to the usual cluster radioactivity where the daughter nucleus is always a neutron/proton (or both) closed shell or nearly closed shell spherical nucleus, the clusterization mechanism seems to be strongly influenced by the hexadecupole deformations rather than the Q value.
We investigate the structure of the potential energy surfaces of the superheavy nuclei 158258Fm100, 156264Hs108, 166278112, 184298114, and 172292120 within the framework of self-consistent nuclear models, i.e., the Skyrme-Hartree-Fock approach and the relativistic mean-field model. We compare results obtained with one representative parametrization of each model which is successful in describing superheavy nuclei. We find systematic changes as compared to the potential energy surfaces of heavy nuclei in the uranium region: there is no sufficiently stable fission isomer any more, the importance of triaxial configurations to lower the first barrier fades away, and asymmetric fission paths compete down to rather small deformation. Comparing the two models, it turns out that the relativistic mean-field model gives generally smaller fission barriers.
We calculate the asymptotic high-energy amplitude for electrons scattering at one ion, as well as at two colliding ions, by means of perturbation theory. We show that the interaction with one ion eikonalizes and that the interaction with two ions causally decouples. We are able to put previous results on perturbative grounds and propose further applications for the obtained rules for interactions on the light cone. We discuss the implications of the eikonal amplitude on the pair production probability in ultrarelativistic peripheral heavy-ion collisions. In this context the Weizsäcker-Williams method is shown to be exact in the ultrarelativistic limit, irrespective of the produced particles’ mass. A new equivalent single-photon distribution is derived, which correctly accounts for Coulomb distortions. The impact on single-photon induced processes is discussed.
We study the extrapolation of nuclear shell structure to the region of superheavy nuclei in self-consistent mean-field models—the Skyrme-Hartree-Fock approach and the relativistic mean-field model—using a large number of parametrizations which give similar results for stable nuclei but differ in detail. Results obtained with the folded-Yukawa potential which is widely used in macroscopic-macroscopic models are shown for comparison. We focus on differences in the isospin dependence of the spin-orbit interaction and the effective mass between the models and their influence on single-particle spectra. The predictive power of the mean-field models concerning single-particle spectra is discussed for the examples of 208Pb and the spin-orbit splittings of selected neutron and proton levels in 16O, 132Sn, and 208Pb. While all relativistic models give a reasonable description of spin-orbit splittings, all Skyrme interactions show a wrong trend with mass number. The spin-orbit splitting of heavy nuclei might be overestimated by 40%–80%, which exposes a fundamental deficiency of the current nonrelativistic models. In most cases the occurrence of spherical shell closures is found to be nucleon-number dependent. Spherical doubly magic superheavy nuclei are found at 184298114, 172292120, or 184310126 depending on the parametrization. The Z=114 proton shell closure, which is related to a large spin-orbit splitting of proton 2f states, is predicted only by forces which by far overestimate the proton spin-orbit splitting in 208Pb. The Z=120 and N=172 shell closures predicted by the relativistic models and some Skyrme interactions are found to be related to a central depression of the nuclear density distribution. This effect cannot appear in macroscopic-microscopic models or semiclassical approaches like the extended Thomas-Fermi-Strutinski integral approach which have a limited freedom for the density distribution only. In summary, our findings give a strong argument for 172292120 to be the next spherical doubly magic superheavy nucleus.
G protein-coupled receptors (GPCRs) play regulatory roles in many different physiological processes and they represent one of the most important class of drug targets. However, due to the lack of three-dimensional structures, structure based drug design has not been possible. The major bottleneck in getting three-dimensional crystal structure of GPCRs is to obtain milligram quantities of pure, homogenous and stable protein. Therefore, during my Ph.D. thesis, I focused on expression, characterization and isolation of three GPCRs namely human bradykinin receptor subtype 2 (B2R), human angiotensin II receptor subtype 1 (AT1aR), and human neuromedin U receptor subtype 2 (NmU2R). These receptors were heterologously produced in three different expression systems (i.e. Pichia pastoris, insect cells and mammalian cells), biochemically characterized and subsequently solubilized and purified for structural studies The human bradykinin receptor subtype 2 (B2R) is constitutively expressed in a variety of cells, including endothelial cells, vascular smooth muscle cells and cardiomyocytes. Activation of B2R is important in pathogenesis of inflammation, pain, tissue injury and cardioprotective mechanisms. During this study, recombinant B2R was produced in methylotrophic yeast Pichia pastoris (3.5 pmol/mg), insect cells (10 pmol/mg) and mammalian cells (60 pmol/mg). The recombinant receptor was characterized in terms of [3H] bradykinin binding, G protein coupling, localization, and glycosylation. Subsequently, it was solubilized and purified using affinity chromatography. Homogeneity and stability of purified B2R was monitored by gel filtration analysis. Milligram amounts of pure and stable receptor were obtained from BHK cells and Sf9 cells, which were used for three-dimensional crystallization attempts. The second receptor, which I worked on, is human angiotensin II receptor subtype 1 (AT1aR). AT1aR is distributed in smooth muscle cells, liver, kidney, heart, lung and testis. Activation of AT1aR is implicated in the regulation of blood pressure, hypertension and cardiovascular diseases. Recombinant AT1aR was produced at high levels in Pichia pastoris (167 pmol/mg), while at moderate levels in insect cells (29 pmol/mg) and mammalian cells (32 pmol/mg). The recombinant receptor was characterized in terms of [3H] angiotensin II binding, localization, and glycosylation. Subsequently, the receptor was solubilized and purified using affinity chromatography. Homogeneity and stability of purified AT1aR was monitored by gel filtration analysis. Milligram amounts of pure and stable receptor were obtained from Pichia pastoris, which were used for threedimensional crystallization attempts. In addition to B2R and AT1aR, I also attempted to produce and isolate the human neuromedin U receptor subtype 2 (NmU2R), which was deorphanized recently. It is found in highest abundance in the central nervous system, particularly the medulla oblongata, spinal cord and thalamus. The distribution of this receptor suggests its regulatory role in sensory transmission and modulation. During this study, recombinant NmU2R was produced in Pichia pastoris (6 pmol/mg) and BHK cells (9 pmol/mg). Recombinant receptor was characterized with regard to [125I] NmU binding, localization and glycosylation. Subsequently, the receptor was solubilized and purified using affinity chromatography. Due to its low expression level, further expression optimization is required in order to obtain milligram amounts for structural studies. The long-term goal of this study was to obtain three-dimensional crystal structure of recombinant GPCRs. However, 3-dimensional crystallization of human recombinant membrane proteins still remains a difficult task. On the other hand, recent advances in the solid-state NMR spectroscopy offer ample opportunities to study receptor-ligand systems, provided milligram quantities of purified receptor are available. Therefore, in parallel to 3-dimensional crystallization trials, purified B2R was also used for solid-state NMR analysis in order to investigate the receptor bound conformation of bradykinin. Preliminary results are promising and indicate significant structural changes in bradykinin upon binding to B2R. Further experiments are ongoing and will hopefully result in the structure of receptor bound bradykinin. One of the challenges in GPCR crystallization is the small hydrophilic surface area that is available to make crystal contacts. One possibility to overcome this problem can be the reconstitution of a GPCR complex with an interacting protein for cocrystallization. For this purpose, I coexpressed B2R and AT1aR, which form a stable heterodimer complex, in BHK cells. I could successfully isolate the heterodimer complex by using two-step affinity purification. Unfortunately, this complex was not stable over time and disassociates within three days of purification. However, during coexpression of B2R and AT1aR in BHK cells, I observed that B2R was localized in the plasma membrane in coexpressing cells while it was retained intracellularly when expressed alone. This coexpression of AT1aR with B2R resulted in a four-fold increase in [3H] bradykinin binding sites on the cell surface. In addition, these two receptors were cointernalized in response to their individual specific ligands. Interestingly, colocalization of B2R and AT1aR was also found in human foreskin fibroblasts (which endogenously express both receptors), in line with the possibility that heterodimerization may be required for surface localization of B2R in native tissues as well. This is the first report where surface localization of a peptide GPCR is triggered by a distantly related peptide GPCR. These data support the hypothesis that heterodimerization may be a prerequisite for cell surface localization of some GPCRs. A second approach that I followed to stabilize the purified B2R was to reconstitute the B2R-β-arrestin complex. β-arrestin is a cytosolic protein that participates in agonist mediated desensitization of GPCRs and therefore dampens the cellular responses initiated by the activation of GPCRs. I tried to reconstitute B2R-β-arrestin complex in vitro by mixing purified B2R and purified β-arrestin. But, no interaction of these two proteins was observed in the pull-down assays. However, a C-terminal mutant of B2R (where a part of the C-terminus of the B2R is exchanged with that of the vasopressin receptor) was found to interact with β-arrestin in vitro as revealed by pull-down assays. In conclusion, this work establishes the production, characterization and isolation of three recombinant human GPCRs. Recombinant receptors were produced in milligram amounts and therefore, pave the way for structural analysis. The heterodimer complex of B2R-AT1aR and B2R-β-arrestin complex can be of great help during crystallization. In addition, it was also found for the first time that the surface localization of a peptide GPCR can be triggered by heterodimerization with a distantly related peptide GPCR.
Multiple lenders and corporate distress: evidence on debt restructuring : [Version Juni 2006]
(2006)
In the recent theoretical literature on lending risk, the coordination problem in multi-creditor relationships have been analyzed extensively. We address this topic empirically, relying on a unique panel data set that includes detailed credit-file information on distressed lending relationships in Germany. In particular, it includes information on creditor pools, a legal institution aiming at coordinating lender interests in borrower distress. We report three major findings. First, the existence of creditor pools increases the probability of workout success. Second, the results are consistent with coordination costs being positively related to pool size. Third, major determinants of pool formation are found to be the number of banks, the distribution of lending shares, and the severity of the distress shock.
A calculation of the vacuum-polarization contribution to the hyperfine splitting for hydrogenlike atoms is presented. The extended nuclear charge distribution is taken into account. For the experimentally interesting case 209Bi82+ we predict a delta-lambda- -1.6 nm shift for the transition wavelength of the ground-state hyperfine splitting.
The electron-positron pairs observed in heavy-ion collisions at Gesellschaft für Schwerionen-forschung Darmstadt mbH have been interpreted as the decay products of yet unknown particles with masses around 1.8 MeV. The negative results of resonant Bhabha scattering experiments, however, do not support such an interpretation. Therefore we focus on a more complex decay scenario, where the e+e- lines result from a two-collision process. We discuss the induced decay of a metastable 1++ state into e+e- pairs. For most realizations of a 1++ state such a decay in leading order can only take place in the Coulomb field of a target atom. This fact has the attractive consequence that for such a state the Bhabha bounds are no longer valid. However, the absolute value of the e+e- production cross section turns out to be unacceptably small.
We investigate the possibility that high-energy photons are channeled, when passing through an oriented single crystal, due to Delbrück scattering. For this purpose the exact electron propagator for the single-string model is constructed. Starting from a separation of variables, we solve the Dirac equation for a cylindrical electrostatic potential. The propagator for such external fields is constructed from solutions of the radial Dirac equation. This propagator is applied to a calculation of the S matrix for Delbrück scattering. We specify the conditions under which photon channeling takes place. Unfortunately these conditions are only matched for a very small fraction of those photons being produced by channeled electrons.
We investigate the influence of nuclear masses, radii, and interaction potentials on 12C radioactivity of 114the best representative of a new island of cluster emitters leading to daughter nuclei around the doubly magic 100Sn. Three different models are considered: one derived by Blendowske, Fliessbach, and Walliser (BFW) from the many-body theory of alpha decay, as well as our analytical (ASAF) and numerical (NuSAF) superasymmetric fission models. A Q value larger by 1 MeV or an ASAF potential barrier reduced by 3% are producing a half-life shorter by 2 orders of magnitude. A similar effect can be obtained within BFW and NuSAF by a decrease of the action integral with less than 10% and 5%, respectively. By increasing the radius constant within ASAF or BFW models by 10%, the half-life becomes shorter by 3 orders of magnitude.
The properties of nuclear matter are studied in the framework of quantum hadrodynamics. Assuming an ω-meson field, periodic in space, a self-consistent set of equations is derived in the mean-field approximation for the description of nucleons interacting via σ-meson and ω-meson fields. Solutions of these self-consistent equations have been found: The baryon density is constant in space, however, the baryon current density is periodic. This high density phase of nuclear matter can be produced by anisotropic external pressure, occurring, e.g., in relativistic heavy ion reactions. The self-consistent fields developing beyond the instability limit have a special screw symmetry. In the presence of such an ω field, the energy spectrum of the relativistic nucleons exhibits allowed and forbidden bands, similar to the energy spectrum of the electrons in solids.
We investigate the production of heavy quarks in continuum and bound states in nuclear collisions. Creation rates for free bb and tt quark pairs and for bottomonium and toponium in the ground state are computed at energies of the BNL Relativistic Heavy Ion Collider, CERN Large Hadron Collider (LHC), and Superconducting Super Collider. Central and peripheral heavy-ion collisions are discussed. For top-quark creation we assumed a mass range of 90≤mt≤250 GeV. The creation rate for top quarks in peripheral collisions is estimated to be by a factor 40 to 130 smaller compared with corresponding central collisions. For mt=130 GeV we calculated a creation rate of about 4760 top-quark pairs per day at the LHC (3.5 TeV/nucleon) for Pb-Pb collisions.
We discuss the multiplicity distribution of electron-positron pairs created in the strong electromagnetic fields of ultrarelativistic heavy-ion transits. Based on nonperturbative expressions for the N-pair creation amplitudes, the Poisson distribution is derived by neglecting interference terms. The source of unitarity violation is identified in the vacuum-to-vacuum amplitude, and a perturbative expression for the mean number of pairs is given.
The Gottfried sum-rule violation reported by the New Muon Collaboration was interpreted as an indication for a flavor asymmetry of the sea quark in the nucleon. We investigate the alternative possibility that isospin symmetry between the proton and the neutron is breaking. We examine systematically the consequences of this possibility for several processes, namely, neutrino deep inelastic scattering, the charged pion Drell-Yan process, the proton Drell-Yan process, and semi-inclusive deep inelastic scattering, and conclude that a decision between the two alternative explanations is possible.
A new region of proton-rich parent nuclei decaying by spontaneous cluster emission with a measurable branching ratio relative to alpha decay is predicted within the analytical superasymmetric fission model. After a brief presentation of the model and of the seven mass tables used to calculate the released energy, the obtained results are discussed. Measurable half-lives and branching ratios are estimated for 12C, 16O, 28Si, and other cluster radioactivities of some nuclides having proton and neutron numbers in the range Z=56–64 and N=58–72. Such nuclei far from stability could be produced in reactions induced by radioactive beams.
Ionization, pair creation, and electron excitations in relativistic heavy-ion collisions are investigated in the framework of the coupled-channel formalism. Collisions between heavy projectiles and Pb82+ are considered for various bombarding energies in the region E=500 up to 2000 MeV/u. Useful symmetry relations for the matrix elements are derived and the influence of gauge transformations onto the coupled-channel equations is explored.
Using relativistic Green’s-function techniques we examined single-electron excitations from the occupied Dirac sea in the presence of strong external fields. The energies of these excited states are determined taking into account the electron-electron interaction. We also evaluate relativistic transition strengths incorporating retardation, which represents a direct measure of correlation effects. The shifts in excitation energies are computed to be lower than 0.5%, while the correlated transition strengths never deviate by more than 10% from their bare values. A major conclusion is that we found no evidence for collectivity in the electron-positron field around heavy and superheavy nuclei.
A method is presented to define unique continuum states for the two-center Dirac Hamiltonian. In the spherical limit these states become the familiar angular-momentum eigenstates of the radial Coulomb potential. The different states for a fixed total energy ‖E‖>m may be distinguished by considering the asymptotic spin-angular distribution of states with unique scattering phases. The first numerical solutions of the two-center Dirac equation for continuum states are presented.
We present calculations for the impact-parameter dependence of K-shell ionization rates in p¯-Cu and in p¯-Ag collisions at various projectile energies. We show that the effect of the attractive Coulomb potential on the Rutherford trajectory and the antibinding effect caused by the negative charge of the antiproton result in a considerable increase of the ionization probability. Total ionization cross sections for proton and antiproton projectiles are compared with each other and with experimental ionization cross sections for protons.
Positron creation in crossed-beam collisions of high-energy, fully stripped heavy ions is investigated within the coupled-channel formalism. In comparison with fixed-target collisions of highly stripped heavy-ion projectiles positron production probabilities are enhanced by more than one order of magnitude. The increase results from the possibility to excite electrons from the negative energy continuum into all bound states. The positron spectrum is shifted towards higher energies because of the absence of electron screening. Rutherford scattering as well as nuclear collisions with time delay are investigated. We also discuss the filling of empty bound states by electrons from pair-production processes.
We study a relativistic model of the nucleus consisting of nucleons coupled to mesonic degrees of freedom via an effective Lagrangian whose parameters are determined by a fit to selected nuclear ground-state data. We find that the model allows a very good description of nuclear ground-state properties. Because of the relativistic nature of the model, the spin properties are uniquely fixed. We discuss variations of the parametrization and of the data which suggest that the present fit has exhausted the limits of the mean-field approximation, and discuss extensions which go beyond the mean field.
The properties of symmetric nuclear matter are investigated in the nonlinear relativistic mean field theory of nuclear matter. We consider the constraints imposed by four nuclear ground state properties on the coupling constants and on the equation of state at zero and at finite temperature. We find that the compression constant K(ρ0) as well as the temperature is irrelevant for the stiffness of the equation of state for m*(ρ0)≤0.7. The main point is that the relativistic mean field theory exhibits acausal and unphysical behavior for compressibilities below K(ρ0)=200 MeV. Every set of coupling constants with a negative quartic coupling constant c is unstable against small quantum fluctuations.
We investigate the influence of additional nonlinear terms in the Dirac Lagrangian on strongly bound electron states in heavy and superheavy atoms. Upper bounds for the coupling constants are deduced by comparison with precision spectroscopy data in QED. We demonstrate that nonlinear interactions may cause significant modifications of electron binding energies in superheavy quasiatomic systems which would not be visible in ordinary atomic-physics measurements.