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Proton-translocating NADH:ubiquinone oxidoreductase (complex I) transports two electrons from NADH to membranal ubiquinone: in this process protons are translocated across the membrane, producing 40% of the total proton gradient between matrix side and intermembrane space. Mitochondrial complex I contains at least 46 subunits in mammals, and has a molecular weight of around 1000 kDa. Electronic microscopy analysis showed that complex I has an L-form, which consists of two domains: a peripheral “arm” (hydrophilic domain) and a membrane “arm” (hydrophobic domain). The peripheral domain, which protrudes into the matrix, contains one non-covalently bound flavin mononucleotide (FMN) and the iron-sulfur clusters N1a, N1b, N2, N3, N4 and N5 as redox active groups. They transport electrons from NADH to ubiquinone. Cluster N2 is supposed to be the immediate electron donor to ubiquinone by virtue of its highest and pH dependent redox midpoint potential (Em,7 –150 mV). The exact location of the tetra-nuclear cluster N2 is still object of discussion. The TYKY and the PSST subunits contain three binding motifs for tetranuclear clusters which are formed by twelve cysteins. In an effort to investigate the “ubiquinone reduction module” of complex I, in the first part of this work site directed mutagenesis of the TYKY and PSST subunits has been carried out. Mutant strains were characterised in terms of complex I content, catalytic activity and EPR signature of cluster N2. The second part of this work was aimed at developing a substrate inducible version of the internal alternative NADH:ubiquinone oxidoreductase (NDH2i). A substrate inducible NDH2i is expected to offer a “switch” between complex I activity dependent (no NDH2i activity) and independent (NDH2i activity) cell growth, by changing between activating and non-activating substrates. This strategy would allow the screening for two types of complex I mutants, which is a prerequisite for realising a random PCR mutagenesis of single subunits of complex I, that allows the production of a high number of point mutations in relatively short time. Y. lipolytica complex I deficiency mutant strains could be easily identified, by virtue of their inability to survive under complex I dependent growth conditions (no NDH2i activity). By this way, amino acids that have an important role for complex I structure or function could be identified by subsequent sequence analysis. Each of the twelve cysteines that form the above mentioned three binding motifs for iron-sulfur cluster have been mutagenised. In mutant mitochondrial membranes, no assembled complex I could be detected. From these data one may conclude that the mutagenised 6 SUMMARY 92 cysteines play an important role for complex I stability, or that are a prerequisite for complex I assembly in Y. lipolytica, but there is not direct evidence indicating that any of the four mutagenised residues acts as a ligand. Two aspartates in the PSST subunit, Asp-99 and Asp-115, were found to be essential for complex I catalytic activity. EPR spectroscopic analysis indicated that the electron transfer to N2 cluster was not blocked and implied that this was not the reason for the loss of catalytic activity. From these data it can be concluded that D99 and D115 play a vital role for complex I NADH:ubiquinone reductase activity, but are not ligands for cluster N2 and that their position is not close enough to the cluster to influence directly its electromagnetic environment. Three mutations, identified in the PSST and TYKY homologous subunits of patients affected with Leigh syndrome (V119M in PSST, P78L and R101H in TYKY) were reconstructed in the obligate aerobic yeast Y. lipolytica. This approach may help to understand the aetiology of the Leigh syndrome, in terms of the ability of complex I to oxidize NADH and to transport electrons. In fact, all three mutations showed effects on electron transport, reducing the VMax by about 50%. Mutant V119M in the PSST subunit, which had a lethal effect in two patients that were homozygous for this mutation, affects a fully conserved residue. Overall, the results from site directed mutagenesis carried out so far support the theory that the “catalytic core ” (N2 cluster and quinone binding site) of complex I has been evolved from the electron transfer module of the [Ni-Fe] hydrogenases. In fact, mutagenesis of residues that are fully conserved between complex I and [Ni-Fe] hydrogenases, showed dramatic effects on complex I in terms of assembly (cysteine mutants) or catalytic activity (D99-D115). Differently, changing aspartate 174 and glutamic acid 185 (not fully conserved, Fig 4.1A) had little or no effect on the Michaelis-Menten parameters and N2 EPR signal. In recent years Y. lipolytica has been developed as a yeast genetic system to study mitochondrial complex I. The present work introduced the promoter for the isocitrate lyase (pICL1) as a useful tool for the substrate selective expression of the internal version of the alternative NADH:ubiquinone oxidoreductase (pICL1-NDH2i). This allows to rescue complex I deficiencies “in vivo” selectively by growth on acetate (or ethanol) medium. The integration of the pICL1-NDH2i construct into the genome of Y. lipolytica and subsequent deletion of nuclear-coded subunits like PSST, TYKY and 49 kDa, would contribute to further develop this organism as a useful genetic model for studying subunits of mitochondrial complex I by site directed mutagenesis.
Records of 33 species of Odonata from Ankarafantsika National Park are presented. Four additional species have been reported in the literature. Nineteen species are recorded from the site for the first time. The site is the largest remaining block of dry forest in Madagascar’s Western Region. While 80% of Madagascar Odonata species are endemic, only 40% of the species recorded in Ankarafantsika is endemic. Moreover, the endemics recorded are mostly common throughout the island. The dry forests are thus of relatively little importance for Madagascar’s diversity of Odonata.
Recent evidence on the effect of government spending shocks on consumption cannot be easily reconciled with existing optimizing business cycle models. We extend the standard New Keynesian model to allow for the presence of rule-of-thumb (non-Ricardian) consumers. We show how the interaction of the latter with sticky prices and deficit financing can account for the existing evidence on the effects of government spending. JEL Klassifikation: E32, E62.
The study examines the hypotheses that the acquisition of the finite verb is an indispensable and linking constituent of the development of SVO utterances. Four apparently separate or at least separable processes are analysed over 6 months in one Russian and one German child: a) the emergence of verbs in the child’s utterances, b) the occurrence of correctly inflected (finite) verb forms, c) the development of multi-component utterances containing a verb, and c) the emergence of (potential) subjects and objects. Russian and German exhibit rich verb morphology, and in both languages finiteness is strongly correlated with inflectional categories like person, number and tense. With both children we find a correlation in the temporal order of these four processes and – what is more relevant for our study – a dependency of a certain development on the utterance level on the emergence of finite verbs. Further, our investigation shows that language-specific development comes in to play already when children start to acquire verb inflection and becomes more contrastive when we observe the onset of the production of the SVO utterances.
The purpose of this research was to trace the developmental steps in the acquisition of aspectual oppositions in Russian and to examine the validity of the 'aspect before tense' hypothesis for L1-speaking children. Imperfective/perfective verbs and their inflections, as well as aspectual pairs, were analysed in the first five months of verb production (and the respective months in the input) in three children. Additionally, the first four months of verb production were investigated in one boy with less data. Verb forms marked for the past and for the present occur simultaneously in all children. These early forms relate to 'here and now' situations: verbs marked for the past denote 'resultative' events that are perceived by the children as occurring during the speech time or immediately before it, while verbs marked for the present typically denote on-going events. Thus, with early tense oppositions (or tense morphology) children mark aspectual contrasts in the moment of speech: evidence in favour of the 'aspect before tense' hypothesis.
A strong preference in using the perfective aspect for the past and the imperfective aspect for the present events has been found in both adults and children. Further, only very few aspectual pairs were documented within the analysed period (from the onset of verb production to the period when children produce rule-driven inflectional forms). The productive use of the finite forms of perfective and imperfective verbs doesn't concord with the ability of the productive use of the contrastive forms of one lemma. Data suggest that children (start to) learn aspectual forms in an item-based manner. The acquisition of aspectual oppositions (aspectual pairs) is lexically dependent and is guided by the contextual 'thesaurus'. Aspectual pairs are learned in a peace-meal way during much longer, than observed for this article, period of time. Generally, aspect is not learned as a rule, also because there are no (uniform) rules of forming of aspectual pairs, but as the 'satellite' of the inherent lexical meaning of verbs of diverse Aktionsarten.
The issues addressed here are relevant for other Slavic languages, exhibiting the morphological category of aspect.
Results of a production experiment on the placement of sentence accent in German are reported. The hypothesis that German fulfills some of the most widely accepted rules of accent assignment— predicting focus domain integration—was only partly confirmed. Adjacency between argument and verb induces a single accent on the argument, as recognized in the literature, but interruption of this sequence by a modifier often induces remodeling of the accent pattern with a single accent on the modifier. The verb is rarely stressed. All models based on linear alignment or adjacency between elements belonging to a single accent domain fail to account for this result. A cyclic analysis of prosodic domain formation is proposed in an optimality-theoretic framework that can explain the accent pattern.
Background: Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects. Aim of the study: First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA) vs. placebo cream (PLC)" and "irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)". Methods: Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun® radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups. Results: The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA. Conclusions: The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks. © 2004 Fuchs et al; licensee German Medical Science. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL : http://www.egms.de/en/gms/volume2.shtml
Pultenaea glabra Benth. is a recently revised taxon which includes disjunct populations in Victoria, NSW, and Queensland. Victorian populations were previously described as Pultenaea weindorferi Reader, and listed as rare in Victoria. Pultenaea glabra is known from four locations in Victoria; it is locally abundant at the Bunyip and Lerderderg-Wombat localities, is uncommon at Wandin, and is in serious decline at Kinglake. Viable soil-stored seeds were present at all sampled locations, and seed germination was enhanced by heat pre-treatments, though germination of untreated seeds also occurred. Few mature plants remain at Kinglake and the population structure differed markedly from the other sampled populations. It has been suggested that the species requires a specific fire regime for regeneration, but it is likely that the severe decline in the Kinglake population is the result of grazing, rather than an inappropriate fire regime. At this site, germination is occurring but plants have not reached maturity, and the species is represented by only seedlings. Managing the species at Kinglake will require consideration of multiple factors, and reintroducing fire to the site at this stage may jeopardize seedling survival and result in local extinction.
New records are presented based on a collection of Campylopus specimens made by the second author in the Western Cape Province of South Africa. The austral species Campylopus clavatus (R. Brown) Wils. in Hook. and Campylopus vesticaulis Mitt. are reported for the first time for Africa, and Campylopus acuminatus Mitt. var. kirkii (Mitt.) J.-P. Frahm is recorded for the second time for Africa. Campylopus arctocarpus (Hornsch.) Mitt. ssp. madegassus (Besch.) J.-P. Frahm is reported for the first time for the Republic of South Africa, and this is the southernmost record of this species. Campylopus simii Schelpe is not synonymous with C. julaceus Jaeg. ssp. arbogastii (Ren. & Card.) J.-P. Frahm but combined here as new as a variety of C. pilifer Brid.
The Azores are of bryological interest in many respects: They are young volcanic islands with an age between 4 mio and 40.000 years, are situated in an hyperoceanic environment favouring bryophyte growth, the bryophyte flora is composed of European, Neotropical, African and subantarctic elements, there are about as many bryophyte species as flowering plants, the islands have a comparably high rate of endemic species (on single Azorean islands, all Azorean islands or the Macaronesian islands), and the bryophyte flora gives an impression of the bryophyte flora of continental Europe during Tertiary, since many species such as Echinodium spp. or Andoa berthelotiana, known as fossils from the Tertiary of continental Europe, survived here the glaciation periods and got extinct in Europe.
The hadronic final state of central Pb+Pb collisions at 20, 30, 40, 80, and 158 AGeV has been measured by the CERN NA49 collaboration. The mean transverse mass of pions and kaons at midrapidity stays nearly constant in this energy range, whereas at lower energies, at the AGS, a steep increase with beam energy was measured. Compared to p+p collisions as well as to model calculations, anomalies in the energy dependence of pion and kaon production at lower SPS energies are observed. These findings can be explained, assuming that the energy density reached in central A+A collisions at lower SPS energies is sufficient to transform the hot and dense nuclear matter into a deconfined phase.
The hadronic final state of central Pb+Pb collisions at 20, 30, 40, 80, and 158 AGeV has been measured by the CERN NA49 collaboration. The mean transverse mass of pions and kaons at midrapidity stays nearly constant in this energy range, whereas at lower energies, at the AGS, a steep increase with beam energy was measured. Compared to p+p collisions as well as to model calculations, anomalies in the energy dependence of pion and kaon production at lower SPS energies are observed. These findings can be explained, assuming that the energy density reached in central A+A collisions at lower SPS energies is sufficient to force the hot and dense nuclear matter into a deconfined phase.
The Box-Cox quantile regression model using the two stage method introduced by Chamberlain (1994) and Buchinsky (1995) provides an attractive extension of linear quantile regression techniques. However, a major numerical problem exists when implementing this method which has not been addressed so far in the literature. We suggest a simple solution modifying the estimator slightly. This modification is easy to implement. The modified estimator is still [square root] n-consistent and its asymptotic distribution can easily be derived. A simulation study confirms that the modified estimator works well.
This paper analyzes empirically the distribution of unemployment durations in West- Germany before and after the changes during the mid 1980s in the maximum entitlement periods for unemployment benefits for elderly unemployed. The analysis is based on the comprehensive IAB employment subsample containing register panel data for about 500.000 individuals in West Germany. We analyze two proxies for unemployment since the data do not precisely measure unemployment in an economic sense. We provide a theoretical analysis of the link between the durations of nonemployment and of unemployment between jobs. Our empirical analysis finds significant changes in the distributions of nonemployment durations for older unemployed individuals. At the same time, the distribution of unemployment durations between jobs did not change in response to the reforms. Our findings are consistent with an interpretation that many firms and workers used the more bene cial laws as a part of early retirement packages but those workers who were still looking for a job did not reduce their search effort in response to the extension of the maximum entitlement periods. This interpretation is consistent with our theoretical model under plausible assumptions. JEL: C24, J64, J65
0. Introduction 1. Observations concerning the structure of morphosyntactically marked focus constructions 1.1 First observation: SF vs. NSF asymmetry 1.2 Second observation: NSF-NAR parallelism 1.3 Affirmative ex-situ focus constructions (SF, NSF), and narrative clauses (NAR) 2. Grammaticalization 2.1 Cleft hypothesis 2.2 Movement hypothesis 2.3 Narrative hypothesis 2.3.1 Back- or Foregrounding? 2.3.2 Converse directionality of FM and conjunction 3. Language specific analysis 4. Conclusionary remarks References
In dieser Arbeit werden Untersuchungen über die Anwendbarkeit von vier Methoden zur selektiven Einführung von Radikalen in DNA vorgestellt. Hierzu wurde die EPR-Spektroskopie (Elektronen-paramagnetische Resonanz) benutzt. Die selektive Einführung und Erzeugung von Radikalen in DNA ist nötig, um J-Kopplungen in DNA zu untersuchen. Vor dem Fernziel der Bestimmung der Austauschkopplungskonstanten J in biradikalischer DNA und deren Korrelation mit der charge-transfer-Geschwindigkeitskonstanten kCT stellen diese Untersuchungen einen wichtigen Ausgangspunkt dar. Stabile aromatische Nitroxide. Simulationen von Raumtemperatur-CW-X-Band-EPRSpektren fünf verschiedener aromatischer Nitroxide, welche potentielle DNA-Interkalatoren sind, wurden durchgeführt. Die aromatischen Nitroxide zeigen aufgelöste Hyperfeinkopplungen, welche zu dem Schluss führen, dass die Spindichte in hohem Maße delokalisiert ist, was die Verwendung dieser Verbindungen zur Messung von J-Kopplungen in biradikalischer DNA erlaubt. Transiente Guanin-Radikale. Transiente Guanin-Radikale werden in DNA selektiv durch die Flash-Quench-Technik erzeugt, bei der optisch anregbare Ruthenium-Interkalatoren verwendet werden. Transiente Thymyl-Radikale aus UV-bestrahltem 4'-Pivaloyl-Thymidin. Es werden photoinduzierte Prozesse untersucht, welche durch Bestrahlung von Thymin-Nukleosiden, die an der 4’-Position die optisch spaltbare Pivaloyl-Gruppe tragen, erzeugt werden. Dieses Nukleosid wurde speziell dafür entworfen, um Elektronenlöcher in DNA zu injizieren. In dieser Arbeit wird gezeigt, dass diese Verbindung benutzt werden kann, um selektiv eine Thymin-Base zu reduzieren. Transiente Thymyl-Radikale erzeugt durch ein neuartig modifiziertes Thymin nach UV-Bestrahlung. Photoinduzierte Prozesse, welche durch Bestrahlung eines ähnlichen Thymidin-Nukleosids erzeugt wurden, werden hier untersucht. Dieses Thymidin- Nukleosid wurde modifiziert, indem die optisch spaltbare Pivaloyl-Gruppe an eine Seitenkette angehängt wurde, welche an der C6-Position der Thymin-Base sitzt. Die Thymin-Base wurde speziell dafür entworfen, um Elektronen in DNA zu injizieren. In dieser Arbeit wurde bestätigt, dass ein Überschuss-Elektron selektiv auf eine Thymin-Base transferiert werden kann.
We have used the SLIMCAT 3-D off-line chemical transport model (CTM) to quantify the Arctic chemical ozone loss in the year 2002/2003 and compare it with similar calculations for the winters 1999/2000 and 2003/2004. Recent changes to the CTM have improved the model's ability to reproduce polar chemical and dynamical processes. The updated CTM uses σ-θ as a vertical coordinate which allows it to extend down to the surface. The CTM has a detailed stratospheric chemistry scheme and now includes a simple NAT-based denitrification scheme in the stratosphere.
In the model runs presented here the model was forced by ECMWF ERA40 and operational analyses. The model used 24 levels extending from the surface to ~55 km and a horizontal resolution of either 7.5°×7.5° or 2.8°×2.8°. Two different radiation schemes, MIDRAD and the CCM scheme, were used to diagnose the vertical motion in the stratosphere. Based on tracer observations from balloons and aircraft, the more sophisticated CCM scheme gives a better representation of the vertical transport in this model which includes the troposphere. The higher resolution model generally produces larger chemical O3 depletion, which agrees better with observations.
The CTM results show that very early chemical ozone loss occurred in December 2002 due to extremely low temperatures and early chlorine activation in the lower stratosphere. Thus, chemical loss in this winter started earlier than in the other two winters studied here. In 2002/2003 the local polar ozone loss in the lower stratosphere was ~40% before the stratospheric final warming. Larger ozone loss occurred in the cold year 1999/2000 which had a persistently cold and stable vortex during most of the winter. For this winter the current model, at a resolution of 2.8°×2.8°, can reproduce the observed loss of over 70% locally. In the warm and more disturbed winter 2003/2004 the chemical O3 loss was generally much smaller, except above 620 K where large losses occurred due to a period of very low minimum temperatures at these altitudes.
The Basel Committee plans to differentiate risk-adjusted capital requirements between banks regulated under the internal ratings based (IRB) approach and banks under the standard approach. We investigate the consequences for the lending capacity and the failure risk of banks in a model with endogenous interest rates. The optimal regulatory response depends on the banks' inclination to increase their portfolio risk. If IRB-banks are well-capitalized or gain little from taking risks, then they will increase their market share and hold safe portfolios. As risk-taking incentives become more important, the optimal portfolio size of banks adopting intern rating systems will be increasingly constrained, and ultimately they may lose market share relative to banks using the standard approach. The regulator has only limited options to avoid the excessive adoption of internal rating systems. JEL Klassifikation: K13, H41.
In a framework closely related to Diamond and Rajan (2001) we characterize different financial systems and analyze the welfare implications of different LOLR-policies in these financial systems. We show that in a bank-dominated financial system it is less likely that a LOLR-policy that follows the Bagehot rules is preferable. In financial systems with rather illiquid assets a discretionary individual liquidity assistance might be welfare improving, while in market-based financial systems, with rather liquid assets in the banks' balance sheets, emergency liquidity assistance provided freely to the market at a penalty rate is likely to be efficient. Thus, a "one size fits all"-approach that does not take the differences of financial systems into account is misguiding. JEL - Klassifikation: D52 , E44 , G21 , E52 , E58
This paper investigates the nature of the attraction of XPs to clauseinitial position in German (and other languages). It argues that there are two different types of preposing. First, an XP can move when it is attracted by an EPP-like feature of Comp. Comp can, however, also attract elements that bear the formal marker of some semantic or pragmatic (information theoretic) function. This second type of movement is driven by the attraction of a formal property of the moved element. It has often been misanalysed as “operator” movement in the past.
In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SKBR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neuoverexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as anti proliferative agents that display activity against neoplastic cells at very low doses.
We analyze welfare maximizing monetary policy in a dynamic two-country model with price stickiness and imperfect competition. In this context, a typical terms of trade externality affects policy interaction between independent monetary authorities. Unlike the existing literature, we remain consistent to a public finance approach by an explicit consideration of all the distortions that are relevant to the Ramsey planner. This strategy entails two main advantages. First, it allows an accurate characterization of optimal policy in an economy that evolves around a steady-state which is not necessarily efficient. Second, it allows to describe a full range of alternative dynamic equilibria when price setters in both countries are completely forward-looking and households' preferences are not restricted. In this context, we study optimal policy both in the long-run and along a dynamic path, and we compare optimal commitment policy under Nash competition and under cooperation. By deriving a second order accurate solution to the policy functions, we also characterize the welfare gains from international policy cooperation. Klassifikation: E52, F41 . This version: January, 2004. First draft: October 2003 .
This paper considers a theoretical model of n asymmetric firms that reduce their initial unit costs by spending on R&D activities. In accordance with Schumpeterian hypotheses we obtain that more efficient (bigger) firms spend more in R&D and this leads to a more concentrated market structure. We also find a positive relationship between innovation and market concentration. This calls for a corrective tax on R&D activities to curtail strategic incentives to over-invest in R&D trying to achieve a higher market share. Klassifikation: L11, L52, O31 . February, 2004.
The Caruso of Colleen Bawn and Other Short Writings is a collection of short stories and poems from the Zimbabwean author John Eppel. The pieces range from poetry evocative of the sights, sounds and smells of the Zimbabwean bush and suburbia to bitingly satirical prose about present day Zimbabwe. Eppel has proved himself in both fields of writing, being awarded the M-Net Prize for fiction and the Ingrid Jonker Prize for poetry.
We argue that there is a crucial difference between determiner and adverbial quantification. Following Herburger [2000] and von Fintel [1994], we assume that determiner quantifiers quantify over individuals and adverbial quantifiers over eventualities. While it is usually assumed that the semantics of sentences with determiner quantifiers and those with adverbial quantifiers basically come out the same, we will show by way of new data that quantification over events is more restricted than quantification over individuals. This is because eventualities in contrast to individuals have to be located in time which is done using contextual information according to a pragmatic resolution strategy. If the contextual information and the tense information given in the respective sentence contradict each other, the sentence is uninterpretable. We conclude that this is the reason why in these cases adverbial quantification, i.e. quantification over eventualities, is impossible whereas quantification over individuals is fine.
Empirical evidence suggests that even those firms presumably most in need of monitoring-intensive financing (young, small, and innovative firms) have a multitude of bank lenders, where one may be special in the sense of relationship lending. However, theory does not tell us a lot about the economic rationale for relationship lending in the context of multiple bank financing. To fill this gap, we analyze the optimal debt structure in a model that allows for multiple but asymmetric bank financing. The optimal debt structure balances the risk of lender coordination failure from multiple lending and the bargaining power of a pivotal relationship bank. We show that firms with low expected cash-flows or low interim liquidation values of assets prefer asymmetric financing, while firms with high expected cash-flow or high interim liquidation values of assets tend to finance without a relationship bank.
Empirical evidence suggests that even those firms presumably most in need of monitoringintensive financing (young, small, and innovative firms) have a multitude of bank lenders, where one may be special in the sense of relationship lending. However, theory does not tell us a lot about the economic rationale for relationship lending in the context of multiple bank financing. To fill this gap, we analyze the optimal debt structure in a model that allows for multiple but asymmetric bank financing. The optimal debt structure balances the risk of lender coordination failure from multiple lending and the bargaining power of a pivotal relationship bank. We show that firms with low expected cash-flows or low interim liquidation values of assets prefer asymmetric financing, while firms with high expected cash-flow or high interim liquidation values of assets tend to finance without a relationship bank. JEL - Klassifikation: G21 , G78 , G33
This paper suggests a motive for bank mergers that goes beyond alleged and typically unverifiable scale economies: preemtive resolution of banks´ financial distress. Such "distress mergers" can be a significant motivation for mergers because they can foster reorganizations, realize diversification gains, and avoid public attention. However, since none of these potential benefits comes without a cost, the overall assessment of distress mergers is unclear. We conduct an empirical analysis to provide evidence on consequences of distress mergers. The analysis is based on comprehensive data from Germany´s savings and cooperatives banks sectors over the period 1993 to 2001. During this period both sectors faced significant structural problems and superordinate institutions (associations) presumably have engaged in coordinated actions to manage distress mergers. The data comprise 3640 banks and 1484 mergers. Our results suggest that bank mergers as a means of preemtive distress resolution have moderate costs in terms of the economic impact on performance. We do find strong evidence consistent with diversification gains. Thus, distress mergers seem to have benefits without affecting systematic stability adversely.
Two tetrahydroisoquinoline alkaloids were extracted from the alkaloid fraction of a methanol extract of the seeds of Calycotome Villosa Subsp. intermedia. Their structures were established as (R)-1-hydroxymethyl-7-8-dimethoxy-1,2,3,4-tetrahydro- isoquinoline (1) and (S)-7-hydroxymethyl-2-3-dimethoxy-7,8,9,10-tetrahydroisoquinoline chloride (2) by spectroscopic techniques and X-ray diffraction analysis.
This Article concerns the duty of care in American corporate law. To fully understand that duty, it is necessary to distinguish between roles, functions, standards of conduct, and standards of review. A role consists of an organized and socially recognized pattern of activity in which individuals regularly engage. In organizations, roles take the form of positions, such as the position of the director. A function consists of an activity that an actor is expected to engage in by virtue of his role or position. A standard of conduct states the way in which an actor should play a role, act in his position, or conduct his functions. A standard of review states the test that a court should apply when it reviews an actor’s conduct to determine whether to impose liability, grant injunctive relief, or determine the validity of his actions. In many or most areas of law, standards of conduct and standards of review tend to be conflated. For example, the standard of conduct that governs automobile drivers is that they should drive carefully, and the standard of review in a liability claim against a driver is whether he drove carefully. Similarly, the standard of conduct that governs an agent who engages in a transaction with his principal is that the agent must deal fairly, and the standard of review in a claim by the principal against an agent, based on such a transaction, is whether the agent dealt fairly. The conflation of standards of conduct and standards of review is so common that it is easy to overlook the fact that whether the two kinds of standards are or should be identical in any given area is a matter of prudential judgment. In a corporate world in which information was perfect, the risk of liability for assuming a given corporate role was always commensurate with the incentives for assuming the role, and institutional considerations never required deference to a corporate organ, the standards of conduct and review in corporate law might be identical. In the real world, however, these conditions seldom hold, and in American corporate law the standards of review pervasively diverge from the standards of conduct. Traditionally, the two major areas of American corporate law that involved standards of conduct and review have been the duty of care and the duty of loyalty. The duty of loyalty concerns the standards of conduct and review applicable to a director or officer who takes action, or fails to act, in a matter that does involve his own self-interest. The duty of care concerns the standards of conduct and review applicable to a director or officer who takes action, or fails to act, in a matter that does not involve his own self-interest.
Die in Englisch verfasste Dissertation, die unter der Betreuung von Herrn Prof. Dr. H. F. de Groote, Fachbereich Mathematik, entstand, ist der Mathematischen Physik zuzuordnen. Sie behandelt Stonesche Spektren von Neumannscher Algebren, observable Funktionen sowie einige Anwendungen in der Physik. Das abschließende Kapitel liefert eine Verallgemeinerung des Kochen-Specker-Theorems. Stonesche Spektren und observable Funktionen wurden von de Groote eingeführt. Das Stonesche Spektrum einer von Neumann-Algebra ist eine Verallgemeinerung des Gelfand-Spektrums, die observablen Funktionen verallgemeinern die Gelfand-Transformierten. Da de Grootes Ergebnisse zum großen Teil unveröffentlicht sind, folgt nach dem Einleitungskapitel im zweiten Kapitel eine Übersichtsdarstellung dieser Ergebnisse. Das dritte Kapitel behandelt die Stoneschen Spektren endlicher von Neumann-Algebren. Für Algebren vom Typ In wird eine vollständige Charakterisierung des Stoneschen Spektrums entwickelt. Zu Typ-II1-Algebren werden einige Resultate vorgestellt. Das vierte Kapitel liefert. einige einfache Anwendungen des Formalismus auf die Physik. Das fünfte Kapitel gibt erstmals einen funktionalanalytischen Beweis des Kochen-Specker-Theorems und liefert die Verallgemeinerung dieses Satzes, wobei die Situation für alle von Neumann-Algebren geklärt wird.
The Kochen-Specker theorem has been discussed intensely ever since its original proof in 1967. It is one of the central no-go theorems of quantum theory, showing the non-existence of a certain kind of hidden states models. In this paper, we first offer a new, non-combinatorial proof for quantum systems with a type I_n factor as algebra of observables, including I_infinity. Afterwards, we give a proof of the Kochen-Specker theorem for an arbitrary von Neumann algebra R without summands of types I_1 and I_2, using a known result on two-valued measures on the projection lattice P(R). Some connections with presheaf formulations as proposed by Isham and Butterfield are made.
How might retirees consider deploying the retirement assets accumulated in a defined contribution pension plan? One possibility would be to purchase an immediate annuity. Another approach, called the "phased withdrawal" strategy in the literature, would have the retiree invest his funds and then withdraw some portion of the account annually. Using this second tactic, the withdrawal rate might be determined according to a fixed benefit level payable until the retiree dies or the funds run out, or it could be set using a variable formula, where the retiree withdraws funds according to a rule linked to life expectancy. Using a range of data consistent with the German experience, we evaluate several alternative designs for phased withdrawal strategies, allowing for endogenous asset allocation patterns, and also allowing the worker to make decisions both about when to retire and when to switch to an annuity. We show that one particular phased withdrawal rule is appealing since it offers relatively low expected shortfall risk, good expected payouts for the retiree during his life, and some bequest potential for the heirs. We also find that unisex mortality tables if used for annuity pricing can make women's expected shortfalls higher, expected benefits higher, and bequests lower under a phased withdrawal program. Finally, we show that delayed annuitization can be appealing since it provides higher expected benefits with lower expected shortfalls, at the cost of somewhat lower anticipated bequests. Klassifikation: G22, G23, J26, J32, H55 . January 2004.
This paper presents preliminary results of a phonetic and phonological study of the Ntcheu dialect of Chichewa spoken by Al Mtenje (one of the co-authors). This study confirms Kanerva's (1990) work on Nkhotakota Chichewa showing that phonological re-phrasing is the primary cue to information structure in this language. It expands on Kanerva's work in several ways. First, we show that focus phrasing has intonational correlates, namely, the manipulation of downdrift and pause. Further, we show that there is a correlation between pitch prominence and discourse prominence at the left and right periphery which conditions dislocation to these positions. Finally, we show that focus and syntax are not the only factors which condition phonological phrasing in Chichewa.
The goal of this paper is to survey the accent systems of the indigenous languages of Africa. Although roughly one third of the world’s languages are spoken in Africa, this continent has tended to be underrepresented in earlier stress and accent typology surveys, like Hyman (1977). This one aims to fill that gap. Two main contributions to the typology of accent are made by this study of African languages. First, it confirms Hyman's (1977) earlier finding that (stem-)initial and penult are the most common positions, cross-linguistically, to be assigned main stress. Further, it shows that not only stress but also tone and segment distribution can define prominence asymmetries which are best analyzed in terms of accent.
Downey (1998) collated an inventory of mistletoe host species based on herbaria records for every aerial mistletoe species (families Loranthaceae and Viscaceae) in Australia. In this paper the representative nature of those host lists is examined in an extensive field survey of mistletoes and their host species in south-eastern New South Wales (including Australian Capital Territory). Four new host species not in the 1998 inventory, and eight new mistletoe-host combinations (i.e. a previously recorded host but not for that particular mistletoe species) were collected. These new records were distributed throughout the survey area. Interestingly, these new host-mistletoe combinations were for mistletoe species that were well represented in the national inventory (i.e. with many herbarium collections and numerous host species). The initial inventory was incomplete, at least for south-eastern New South Wales, indicating the need for (i) more targeted surveys similar to this one, and/or (ii) regular updates of the host inventory based on voucher specimens. A possible reasons why information on host-mistletoe combinations is incomplete may be that such combinations may be dynamic (i.e. mistletoe species may be expanding their suite of potential hosts, either fortuitously or as result of evolutionary pressures).
The bulk of this paper deals with an analysis of the voice system of Tukang Besi, which, has both a complex verbal agreement system as well as the last fully developed (and obligatory) case marking system among Austronesian languages with an increasingly head-marking trend to the east (case marking of core constituents only becomes functional again in Vanuatu and the Solomons, and is well-developed in Polynesia). For that reason, as well as personal acquaintance with the language, it is a sensible starting point.
The purification and functional reconstitution of a five-component oligopeptide ATP-binding cassette transporter with a remarkably wide substrate specificity are described. High-affinity peptide uptake was dependent on liganded substrate-binding protein OppA, which interacts with the translocator OppBCDF with higher affinity than unliganded OppA. Transport screening with combinatorial peptide libraries revealed that (i) the Opp transporter is not selective with respect to amino acid side chains of the transported peptides; (ii) any peptide that can bind to OppA is transported via Opp, including very long peptides up to 35 residues long; and (iii) the binding specificity of OppA largely determines the overall transport selectivity.
In this paper, we discuss the design and implementation of our first version of the database "ANNIS" (ANNotation of Information Structure). For research based on empirical data, ANNIS provides a uniform environment for storing this data together with its linguistic annotations. A central database promotes standardized annotation, which facilitates interpretation and comparison of the data. ANNIS is used through a standard web browser and offers tier-based visualization of data and annotations, as well as search facilities that allow for cross-level and cross-sentential queries. The paper motivates the design of the system, characterizes its user interface, and provides an initial technical evaluation of ANNIS with respect to data size and query processing.
65 species of Odonata are recorded from Mulanje and its slopes. Only eight species dominate on the high plateau. Among them are two relict species of conservation concern: The endemic Oreocnemis phoenix (monotypic genus) and the restricted-range species Chlorolestes elegans. The absence of mountain marsh specialists on the plateau is noteworthy. Mulanje’s valleys, of which Likabula and Ruo are best known, have a rich dragonfly fauna. The Eastern Arc relict Nepogomphoides stuhlmanni is common here.
Despite powerful advances in yield curve modeling in the last twenty years, comparatively little attention has been paid to the key practical problem of forecasting the yield curve. In this paper we do so. We use neither the no-arbitrage approach, which focuses on accurately fitting the cross section of interest rates at any given time but neglects time-series dynamics, nor the equilibrium approach, which focuses on time-series dynamics (primarily those of the instantaneous rate) but pays comparatively little attention to fitting the entire cross section at any given time and has been shown to forecast poorly. Instead, we use variations on the Nelson-Siegel exponential components framework to model the entire yield curve, period-by-period, as a three-dimensional parameter evolving dynamically. We show that the three time-varying parameters may be interpreted as factors corresponding to level, slope and curvature, and that they may be estimated with high efficiency. We propose and estimate autoregressive models for the factors, and we show that our models are consistent with a variety of stylized facts regarding the yield curve. We use our models to produce term-structure forecasts at both short and long horizons, with encouraging results. In particular, our forecasts appear much more accurate at long horizons than various standard benchmark forecasts. JEL Code: G1, E4, C5
The starting point of Demirovic's text is Adorno's idea that concepts as forms of thinking are constellations of power. Differently from many interpretations of Adorno as resigned, Demirovic shows that this assumption enables Adorno to give his own theory the character of interventions in the ideological consensus of everyday life with regard to emancipation.
Dislocation without movement
(2004)
This paper argues that French Left-Dislocation is a unified phenomenon whether it is resumed by a clitic or a non-clitic element. The syntactic component is shown to play a minimal role in its derivation: all that is required is that the dislocated element be merged by adjunction to a Discourse Projection (generally a finite TP with root properties). No agreement or checking of a topic feature is necessary, hence no syntactic movement of any sort need be postulated. The so-called resumptive element is argued to be a full-fledged pronoun rather than a true syntactic resumptive.
The objective of this paper is the study of the equilibrium behavior of a population on the hierarchical group ΩN consisting of families of individuals undergoing critical branching random walk and in addition these families also develop according to a critical branching process. Strong transience of the random walk guarantees existence of an equilibrium for this two-level branching system. In the limit N→∞ (called the hierarchical mean field limit), the equilibrium aggregated populations in a nested sequence of balls B(N)ℓ of hierarchical radius ℓ converge to a backward Markov chain on R+. This limiting Markov chain can be explicitly represented in terms of a cascade of subordinators which in turn makes possible a description of the genealogy of the population.
In this study, we develop a technique for estimating a firm’s expected cost of equity capital derived from analyst consensus forecasts and stock prices. Building on the work of Gebhardt/Lee/-Swaminathan (2001) and Easton/Taylor/Shroff/Sougiannis (2002), our approach allows daily estimation, using only publicly available information at that date. We then estimate the expected cost of equity capital at the market, industry and individual firm level using historical German data from 1989-2002 and examine firm characteristics which are systematically related to these estimates. Finally, we demonstrate the applicability of the concept in a contemporary case study for DaimlerChrysler and the European automobile industry.
The question whether the adoption of International Financial Reporting Standards (IFRS) will result in measurable economic benefits is of special policy relevance in particular given the European Union’s decision to require the application of IFRS by listed companies from 2005/2007. In this paper, I investigate the common con-jecture that internationally recognized high quality reporting standards (IAS/IFRS or US-GAAP) reduce the cost of capital of adopting firms (e.g. Levitt 1998; IASB 2002). Building on Leuz/Verrecchia (2000), I use a set of German firms which pre-adopted such standards before 2005, but investigate the potential economic benefits by analyzing their expected cost of equity capital utilizing and customizing avail-able implied estimation methods (e.g. Gebhardt/Lee/Swaminathan 2001, Easton/Taylor/Shroff/Sougiannis 2002, Easton 2004). Evidence from a sample of about 13,000 HGB, 4,500 IAS/IFRS and 3,000 US-GAAP firm-month observations in the period 1993-2002 generally fails to document lower expected cost of equity capital and therefore measurable economic benefits for firms applying IAS/IFRS or US-GAAP. Accordingly, I caution to state that reporting under internationally accepted standards, per se, lowers the cost of equity capital of adopting firms.
Maintenance of genomic integrity is essential to avoid cellular transformation, neoplasia, or cell death. DNA synthesis, mitosis, and cytokinesis are important cellular processes required for cell division and the maintenance of cellular homeostasis; they are governed by many extra- and intra-cellular stimuli. Progression of normal cell division depends on cyclin interaction with cyclin-dependent kinases (Cdk) and the degradation of cyclins before chromosomal segregation through ubiquitination. Multiple checkpoints exist and are conserved in the cell cycle in higher eukaryotes to ensure that if one fails, others will take care of genomic integrity and cell survival. Many genes act as either positive or negative regulators of checkpoint function through different kinase cascades, delaying cell cycle progression to repair the DNA lesions and breaks, and assuring equal segregation of chromosomes to daughter cells. Understanding the checkpoint pathways and genes involved in the cellular response to DNA damage and cell division events in normal and cancer cells, provides information about cancer predisposition, and suggests design of small molecules and other strategies for cancer therapy. Key Words: ATM-ATR; ATM/ATR; Aurora kinases; BRCAl; Cdc6; Cdc25; Cdc27-Cdc20/CdhI; Cell cycle; CENP-E; centrosome; checkpoint; Chkl/Chk2; cyc1in-Cdk; cyclindependent kinase inhibitors (CKI); hATRIP; Mad/Bub; MCM; MgcRacGAP; microtubule-associated proteins (MAPs); mitotic exit network (MEN); Mpsl; NIMA kinases; ORC; p53; PCNA; PBK-Akt; Plk; Rad50-Nbsl-Mrell; Ran-GTP; Ras; RB-E2F; SMC; Teml.
Die Ermittlung von Proteinstukturen mittels NMR-Spektroskopie ist ein komplexer Prozess, wobei die Resonanzfrequenzen und die Signalintensitäten den Atomen des Proteins zugeordnet werden. Zur Bestimmung der räumlichen Proteinstruktur sind folgende Schritte erforderlich: die Präparation der Probe und 15N/13C Isotopenanreicherung, Durchführung der NMR Experimente, Prozessierung der Spektren, Bestimmung der Signalresonanzen ('Peak-picking'), Zuordnung der chemischen Verschiebungen, Zuordnung der NOESY-Spektren und das Sammeln von konformationellen Strukturparametern, Strukturrechnung und Strukturverfeinerung. Aktuelle Methoden zur automatischen Strukturrechnung nutzen eine Reihe von Computeralgorithmen, welche Zuordnungen der NOESY-Spektren und die Strukturrechnung durch einen iterativen Prozess verbinden. Obwohl neue Arten von Strukturparametern wie dipolare Kopplungen, Orientierungsinformationen aus kreuzkorrelierten Relaxationsraten oder Strukturinformationen, die sich in Gegenwart paramagnetischer Zentren in Proteinen ergeben, wichtige Neuerungen für die Proteinstrukturrechnung darstellen, sind die Abstandsinformationen aus NOESY-Spektren weiterhin die wichtigste Basis für die NMR-Strukturbestimmung. Der hohe zeitliche Aufwand des 'peak-picking' in NOESY-Spektren ist hauptsächlich bedingt durch spektrale Überlagerung, Rauschsignale und Artefakte in NOESY-Spektren. Daher werden für das effizientere automatische 'Peak-picking' zuverlässige Filter benötigt, um die relevanten Signale auszuwählen. In der vorliegenden Arbeit wird ein neuer Algorithmus für die automatische Proteinstrukturrechnung beschrieben, der automatisches 'Peak-picking' von NOESY-Spektren beinhaltet, die mit Hilfe von Wavelets entrauscht wurden. Der kritische Punkt dieses Algorithmus ist die Erzeugung inkrementeller Peaklisten aus NOESY-Spektren, die mit verschiedenen auf Wavelets basierenden Entrauschungsprozeduren prozessiert wurden. Mit Hilfe entrauschter NOESY-Spektren erhält man Signallisten mit verschiedenen Konfidenzbereichen, die in unterschiedlichen Schritten der kombinierten NOE-Zuordnung/Strukturrechnung eingesetzt werden. Das erste Strukturmodell beruht auf stark entrauschten Spektren, die die konservativste Signalliste mit als weitgehend sicher anzunehmenden Signalen ergeben. In späteren Stadien werden Signallisten aus weniger stark entrauschten Spektren mit einer größeren Anzahl von Signalen verwendet. Die Auswirkung der verschiedenen Entrauschungsprozeduren auf Vollständigkeit und Richtigkeit der NOESY Peaklisten wurde im Detail untersucht. Durch die Kombination von Wavelet-Entrauschung mit einem neuen Algorithmus zur Integration der Signale in Verbindung mit zusätzlichen Filtern, die die Konsistenz der Peakliste prüfen ('Network-anchoring' der Spinsysteme und Symmetrisierung der Peakliste), wird eine schnelle Konvergenz der automatischen Strukturrechnung erreicht. Der neue Algorithmus wurde in ARIA integriert, einem weit verbreiteten Computerprogramm für die automatische NOE-Zuordnung und Strukturrechnung. Der Algorithmus wurde an der Monomereinheit der Polysulfid-Schwefel-Transferase (Sud) aus Wolinella succinogenes verifiziert, deren hochaufgelöste Lösungsstruktur vorher auf konventionelle Weise bestimmt wurde. Neben der Möglichkeit zur Bestimmung von Proteinlösungsstrukturen bietet sich die NMR-Spektroskopie auch als wirkungsvolles Werkzeug zur Untersuchung von Protein-Ligand- und Protein-Protein-Wechselwirkungen an. Sowohl NMR Spektren von isotopenmarkierten Proteinen, als auch die Spektren von Liganden können für das 'Screening' nach Inhibitoren benutzt werden. Im ersten Fall wird die Sensitivität der 1H- und 15N-chemischen Verschiebungen des Proteinrückgrats auf kleine geometrische oder elektrostatische Veränderungen bei der Ligandbindung als Indikator benutzt. Als 'Screening'-Verfahren, bei denen Ligandensignale beobachtet werden, stehen verschiedene Methoden zur Verfügung: Transfer-NOEs, Sättigungstransferdifferenzexperimente (STD, 'saturation transfer difference'), ePHOGSY, diffusionseditierte und NOE-basierende Methoden. Die meisten dieser Techniken können zum rationalen Design von inhibitorischen Verbindungen verwendet werden. Für die Evaluierung von Untersuchungen mit einer großen Anzahl von Inhibitoren werden effiziente Verfahren zur Mustererkennung wie etwa die PCA ('Principal Component Analysis') verwendet. Sie eignet sich zur Visualisierung von Ähnlichkeiten bzw. Unterschieden von Spektren, die mit verschiedenen Inhibitoren aufgenommen wurden. Die experimentellen Daten werden zuvor mit einer Serie von Filtern bearbeitet, die u.a. Artefakte reduzieren, die auf nur kleinen Änderungen der chemischen Verschiebungen beruhen. Der am weitesten verbreitete Filter ist das sogenannte 'bucketing', bei welchem benachbarte Punkte zu einen 'bucket' aufsummiert werden. Um typische Nachteile der 'bucketing'-Prozedur zu vermeiden, wurde in der vorliegenden Arbeit der Effekt der Wavelet-Entrauschung zur Vorbereitung der NMR-Daten für PCA am Beispiel vorhandener Serien von HSQC-Spektren von Proteinen mit verschiedenen Liganden untersucht. Die Kombination von Wavelet-Entrauschung und PCA ist am effizientesten, wenn PCA direkt auf die Wavelet-Koeffizienten angewandt wird. Durch die Abgrenzung ('thresholding') der Wavelet-Koeffizienten in einer Multiskalenanalyse wird eine komprimierte Darstellung der Daten erreicht, welche Rauschartefakte minimiert. Die Kompression ist anders als beim 'bucketing' keine 'blinde' Kompression, sondern an die Eigenschaften der Daten angepasst. Der neue Algorithmus kombiniert die Vorteile einer Datenrepresentation im Wavelet-Raum mit einer Datenvisualisierung durch PCA. In der vorliegenden Arbeit wird gezeigt, dass PCA im Wavelet- Raum ein optimiertes 'clustering' erlaubt und dabei typische Artefakte eliminiert werden. Darüberhinaus beschreibt die vorliegende Arbeit eine de novo Strukturbestimmung der periplasmatischen Polysulfid-Schwefel-Transferase (Sud) aus dem anaeroben gram-negativen Bakterium Wolinella succinogenes. Das Sud-Protein ist ein polysulfidbindendes und transferierendes Enzym, das bei niedriger Polysulfidkonzentration eine schnelle Polysulfid-Schwefel-Reduktion katalysiert. Sud ist ein 30 kDa schweres Homodimer, welches keine prosthetischen Gruppen oder schwere Metallionen enthält. Jedes Monomer enhält ein Cystein, welches kovalent bis zu zehn Polysulfid-Schwefel (Sn 2-) Ionen bindet. Es wird vermutet, dass Sud die Polysulfidkette auf ein katalytischen Molybdän-Ion transferiert, welches sich im aktiven Zentrum des membranständigen Enzyms Polysulfid-Reduktase (Psr) auf dessen dem Periplasma zugewandten Seite befindet. Dabei wird eine reduktive Spaltung der Kette katalysiert. Die Lösungsstruktur des Homodimeres Sud wurde mit Hilfe heteronuklearer, mehrdimensionaler NMR-Techniken bestimmt. Die Struktur beruht auf von NOESY-Spektren abgeleiteten Distanzbeschränkungen, Rückgratwasserstoffbindungen und Torsionswinkeln, sowie auf residuellen dipolaren Kopplungen, die für die Verfeinerung der Struktur und für die relative Orientierung der Monomereinheiten wichtig waren. In den NMR Spektren der Homodimere haben alle symmetrieverwandte Kerne äquivalente magnetische Umgebungen, weshalb ihre chemischen Verschiebungen entartet sind. Die symmetrische Entartung vereinfacht das Problem der Resonanzzuordnung, da nur die Hälfte der Kerne zugeordnet werden müssen. Die NOESY-Zuordnung und die Strukturrechnung werden dadurch erschwert, dass es nicht möglich ist, zwischen den Intra-Monomer-, Inter-Monomer- und Co-Monomer- (gemischten) NOESY-Signalen zu unterscheiden. Um das Problem der Symmetrie-Entartung der NOESY-Daten zu lösen, stehen zwei Möglichkeiten zur Verfügung: (I) asymmetrische Markierungs-Experimente, um die intra- von den intermolekularen NOESY-Signalen zu unterscheiden, (II) spezielle Methoden der Strukturrechnung, die mit mehrdeutigen Distanzbeschränkungen arbeiten können. Die in dieser Arbeit vorgestellte Struktur wurde mit Hilfe der Symmetrie-ADR- ('Ambigous Distance Restraints') Methode in Kombination mit Daten von asymetrisch isotopenmarkierten Dimeren berechnet. Die Koordinaten des Sud-Dimers zusammen mit den NMR-basierten Strukturdaten wur- den in der RCSB-Proteindatenbank unter der PDB-Nummer 1QXN abgelegt. Das Sud-Protein zeigt nur wenig Homologie zur Primärsequenz anderer Proteine mit ähnlicher Funktion und bekannter dreidimensionaler Struktur. Bekannte Proteine sind die Schwefeltransferase oder das Rhodanese-Enzym, welche beide den Transfer von einem Schwefelatom eines passenden Donors auf den nukleophilen Akzeptor (z.B von Thiosulfat auf Cyanid) katalysieren. Die dreidimensionalen Strukturen dieser Proteine zeigen eine typische a=b Topologie und haben eine ähnliche Umgebung im aktiven Zentrum bezüglich der Konformation des Proteinrückgrades. Die Schleife im aktiven Zentrum umgibt das katalytische Cystein, welches in allen Rhodanese-Enzymen vorhanden ist, und scheint im Sud-Protein flexibel zu sein (fehlende Resonanzzuordnung der Aminosäuren 89-94). Das Polysulfidende ragt aus einer positiv geladenen Bindungstasche heraus (Reste: R46, R67, K90, R94), wo Sud wahrscheinlich in Kontakt mit der Polysulfidreduktase tritt. Das strukturelle Ergebnis wurde durch Mutageneseexperimente bestätigt. In diesen Experimenten konnte gezeigt werden, dass alle Aminosäurereste im aktiven Zentrum essentiell für die Schwefeltransferase-Aktivität des Sud-Proteins sind. Die Substratbindung wurde früher durch den Vergleich von [15N,1H]-TROSY-HSQC-Spektren des Sud-Proteins in An- und Abwesenheit des Polysulfidliganden untersucht. Bei der Substratbindung scheint sich die lokale Geometrie der Polysulfidbindungsstelle und der Dimerschnittstelle zu verändern. Die konformationellen Änderungen und die langsame Dynamik, hervorgerufen durch die Ligandbindung können die weitere Polysulfid-Schwefel-Aktivität auslösen. Ein zweites Polysulfid-Schwefeltransferaseprotein (Str, 40 kDa) mit einer fünffach höheren nativen Konzentration im Vergleich zu Sud wurde im Bakterienperiplasma von Wolinella succinogenes entdeckt. Es wird angenommen, dass beide Protein einen Polysulfid-Schwefel-Komplex bilden, wobei Str wässriges Polysulfid sammelt und an Sud abgibt, welches den Schwefeltransfer zum katalytischen Molybdän-Ion auf das aktive Zentrum der dem Periplasma zugewandten Seite der Polysulfidreduktase durchführt. Änderungen chemischer Verschiebungen in [15N,1H]-TROSY-HSQC-Spektren zeigen, dass ein Polysulfid-Schwefeltransfer zwischen Str und Sud stattfindet. Eine mögliche Protein-Protein-Wechselwirkungsfläche konnte bestimmt werden. In der Abwesenheit des Polysulfidsubstrates wurden keine Wechselwirkungen zwischen Sud und Str beobachtet, was die Vermutung bestätigt, dass beide Proteine nur dann miteinander wechselwirken und den Polysulfid-Schwefeltransfer ermöglichen, wenn als treibende Kraft Polysulfid präsent ist.
Twenty-one riparian vascular plant communities are defined, mapped and described using presence/absence data from 460 sites from relatively unmodified stretches of rivers and streams on mainland Tasmania. The process of classification involved selection of groups of floristically distinct sites from a sorted table produced by a polythetic divisive process. The communities have strong geographic patterns. Many communities have a wide range of structural expression and/or dominants. Nearly half of the native vascular flora of Tasmania is present in the sites, including a large number of conservation-significant species, some of which are concentrated in riparian vegetation. In the drier, lowland parts of the State there are large areas with little or no native riparian vegetation remaining. Several of the communities that occur in this environment appear to be totally unreserved, while most of the communities from colder and more humid areas are represented within secure reserves.
We analyze governance with a dataset on investments of venture capitalists in 3848 portfolio firms in 39 countries from North and South America, Europe and Asia spanning 1971-2003. We find that cross-country differences in Legality have a significant impact on the governance structure of investments in the VC industry: better laws facilitate faster deal screening and deal origination, a higher probability of syndication and a lower probability of potentially harmful co-investment, and facilitate board representation of the investor. We also show better laws reduce the probability that the investor requires periodic cash flows prior to exit, which is in conjunction with an increased probability of investment in high-tech companies. Klassifikation: G24, G31, G32.
This dissertation study argues that 'policy advice formation', as a discourse development, is a differentiated hybrid resultant from merger between comparative education and policy studies disciplines. Through discourse analysis based on John Creswell's format, this study identifies revisions, restatements and shifts in emphasis of theories, methodological models and challenge topics of comparative education and policy studies. Findings which display the development of policy advice formation' discourse. In conclusion, this study found differential patterns seemingly formed because of collaborative affects of standardization in education science knowledge expressed within discourse.
In Archaea, bacteria, and eukarya, ATP provides metabolic energy for energy-dependent processes. It is synthesized by enzymes known as A-type or F-type ATP synthase, which are the smallest rotatory engines in nature (Yoshida, M., Muneyuki, E., and Hisabori, T. (2001) Nat. Rev. Mol. Cell. Biol. 2, 669-677; Imamura, H., Nakano, M., Noji, H., Muneyuki, E., Ohkuma, S., Yoshida, M., and Yokoyama, K. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 2312-2315). Here, we report the first projected structure of an intact A(1)A(0) ATP synthase from Methanococcus jannaschii as determined by electron microscopy and single particle analysis at a resolution of 1.8 nm. The enzyme with an overall length of 25.9 nm is organized in an A(1) headpiece (9.4 x 11.5 nm) and a membrane domain, A(0) (6.4 x 10.6 nm), which are linked by a central stalk with a length of approximately 8 nm. A part of the central stalk is surrounded by a horizontal-situated rodlike structure ("collar"), which interacts with a peripheral stalk extending from the A(0) domain up to the top of the A(1) portion, and a second structure connecting the collar structure with A(1). Superposition of the three-dimensional reconstruction and the solution structure of the A(1) complex from Methanosarcina mazei Gö1 have allowed the projections to be interpreted as the A(1) headpiece, a central and the peripheral stalk, and the integral A(0) domain. Finally, the structural organization of the A(1)A(0) complex is discussed in terms of the structural relationship to the related motors, F(1)F(0) ATP synthase and V(1)V(0) ATPases.
Hackethal and Schmidt (2003) criticize a large body of literature on the financing of corporate sectors in different countries that questions some of the distinctions conventionally drawn between financial systems. Their criticism is directed against the use of net flows of finance and they propose alternative measures based on gross flows which they claim re-establish conventional distinctions. This paper argues that their criticism is invalid and that their alternative measures are misleading. There are real issues raised by the use of aggregate data but they are not the ones discussed in Hackethal and Schmidt’s paper. JEL Classification: G30
Fronting a noun phrase changes the focus structure of a sentence. Therefore, it may affect truth conditions, since some operators, in particular quantificational adverbs, are sensitive to focus. However, the position of the quantificational adverb itself, hence its informational status, is usually assumed not to have any semantic effect. In this paper I discuss a reading of some quantificational adverbs, the relative reading, which disappears if the adverb is fronted. I propose that this reading relies not only on focus, but on B-accent (fall-rise intonation) as well. A fronted Q-adverb is usually pronounced with a B-accent; since only one element can be B-accented, this means that the scope of the adverb contains no B-accented material, hence no relative readings. Thus, the effects of fronting range more widely than is usually assumed, and quantificational adverbs are a useful tool with which to investigate these effects.
In this paper, we study the effectiveness of monetary policy in a severe recession and deflation when nominal interest rates are bounded at zero. We compare two alternative proposals for ameliorating the effect of the zero bound: an exchange-rate peg and price-level targeting. We conduct this quantitative comparison in an empirical macroeconometric model of Japan, the United States and the euro area. Furthermore, we use a stylized micro-founded two-country model to check our qualitative findings. We find that both proposals succeed in generating inflationary expectations and work almost equally well under full credibility of monetary policy. However, price-level targeting may be less effective under imperfect credibility, because the announced price-level target path is not directly observable. Klassifikation: E31, E52, E58, E61
An improved approach to predicting preferred habitat and targetting survey effort for threatened plant species is needed to aid discovery and conservation of new populations. This study employs several approaches to aid in the delineation of preferred habitat for the Leafless Tongue Orchid, Cryptostylis hunteriana Nicholls. BIOCLIM, a bioclimatic analysis and prediction system, is used initially to generate a bioclimatic habitat envelope within which the species can be expected to occur, based on all known sites in the Shoalhaven Local Government Area. Within the BIOCLIM envelope it is possible to further investigate the extent to which the species exhibits preferences for other habitat factors such as geology, soil landscapes and forest ecosystems. Multivariate techniques are used to compare floristic data from sites where Cryptostylis hunteriana is present, and sites from forest ecosystems where it has not been recorded historically. These techniques are also used to identify species which are diagnostic of each of these sets of sites. All 25 sites with Cryptostylis hunteriana populations are restricted to six forest ecosystems having a total area of 15% of the Shoalhaven Local Government Area and 47% of the BIOCLIM envelope. Within these forest ecosystems, ten plant species deemed indicative of the possible presence of the Cryptostylis hunteriana are identified.
The MAM (meprin/A5-protein/PTPmu) domain is present in numerous proteins with diverse functions. PTPμ belongs to the MAM-containing subclass of protein-tyrosine phosphatases (PTP) able to promote cell-to-cell adhesion. Here we provide experimental evidence that the MAM domain is a homophilic binding site of PTPμ. We demonstrate that the MAM domain forms oligomers in solution and binds to the PTPμ ectodomain at the cell surface. The presence of two disulfide bridges in the MAM molecule was evidenced and their integrity was found to be essential for MAM homophilic interaction. Our data also indicate that PTPμ ectodomain forms oligomers and mediates the cellular adhesion, even in the absence of MAM domain homophilic binding. Reciprocally, MAM is able to interact homophilically in the absence of ectodomain trans binding. The MAM domain therefore contains independent cis and trans interaction sites and we predict that its main role is to promote lateral dimerization of PTPμ at the cell surface. This finding contributes to the understanding of the signal transduction mechanism in MAM-containing PTPs.
The mode of the antitumoral activity of multimutated oncolytic herpes simplex virus type 1 G207 has not been fully elucidated yet. Because the antitumoral activity of many drugs involves the inhibition of tumor blood vessel formation, we determined if G207 had an influence on angiogenesis. Monolayers of human umbilical vein endothelial cells and human dermal microvascular endothelial cells, but not human dermal fibroblasts, bronchial epithelial cells, and retinal glial cells, were highly sensitive to the replicative and cytotoxic effects of G207. Moreover, G207 infection caused the destruction of endothelial cell tubes in vitro. In the in vivo Matrigel plug assay in mice, G207 suppressed the formation of perfused vessels. Intratumoral treatment of established human rhabdomyosarcoma xenografts with G207 led to the destruction of tumor vessels and tumor regression. Ultrastructural investigations revealed the presence of viral particles in both tumor and endothelial cells of G207-treated xenografts, but not in adjacent normal tissues. These findings show that G207 may suppress tumor growth, in part, due to inhibition of angiogenesis.
We consider three sets of phenomena that feature prominently - and separately - in the financial economics literature: conditional mean dependence (or lack thereof) in asset returns, dependence (and hence forecastability) in asset return signs, and dependence (and hence forecastability) in asset return volatilities. We show that they are very much interrelated, and we explore the relationships in detail. Among other things, we show that: (a) Volatility dependence produces sign dependence, so long as expected returns are nonzero, so that one should expect sign dependence, given the overwhelming evidence of volatility dependence; (b) The standard finding of little or no conditional mean dependence is entirely consistent with a significant degree of sign dependence and volatility dependence; (c) Sign dependence is not likely to be found via analysis of sign autocorrelations, runs tests, or traditional market timing tests, because of the special nonlinear nature of sign dependence; (d) Sign dependence is not likely to be found in very high-frequency (e.g., daily) or very low-frequency (e.g., annual) returns; instead, it is more likely to be found at intermediate return horizons; (e) Sign dependence is very much present in actual U.S. equity returns, and its properties match closely our theoretical predictions; (f) The link between volatility forecastability and sign forecastability remains intact in conditionally non-Gaussian environments, as for example with time-varying conditional skewness and/or kurtosis.
Vowel dispersion in Truku
(2004)
This study investigates the dispersion of vowel space in Truku, an endangered Austronesian language in Taiwan. Adaptive Dispersion (Liljencrants and Lindblom, 1972; Lindblom, 1986, 1990) proposes that the distinctive sounds of a language tend to be positioned in phonetic space in a way that maximizes perceptual contrast. For example, languages with large vowel inventories tend to expand the overall acoustic vowel space. Adaptive Dispersion predicts that the distance between the point vowels will increase with the size of a language's vowel inventory. Thus, the available acoustic vowel space is utilized in a way that maintains maximal auditory contrast.
The current study focuses on the prosodic realization of negators in Saisiyat, an endangered aboriginal language of Taiwan, and compares its prosodic realization of negation with that of English. The results of this study indicate that sentential subjects are the most acoustically prominent items in the Saisiyat negative sentences measured. This contrasts sharply with the English experimental sentences, in which the negator itself was the most acoustically prominent item. These findings suggest that Saisiyat is a pitch-accent language; thus, the presence of negators does not significantly change the prosodic parameters of surrounding words. English, in contrast, is an intonation language, so the presence of negation results in substantial prosodic modification. This suggests that the phenomenon of negation is universally prominent; however, languages with different prosodic systems will adopt different strategies for realizing prominence.
The transporter associated with antigen processing (TAP) is a key component of the cellular immune system. As a member of the ATP-binding cassette (ABC) superfamily, TAP hydrolyzes ATP to energize the transport of peptides from the cytosol into the lumen of the endoplasmic reticulum. TAP is composed of TAP1 and TAP2, each containing a transmembrane domain and a nucleotide-binding domain (NBD). Here we investigated the role of the ABC signature motif (C-loop) on the functional non-equivalence of the NBDs, which contain a canonical C-loop (LSGGQ) for TAP1 and a degenerate C-loop (LAAGQ) for TAP2. Mutation of the leucine or glycine (LSGGQ) in TAP1 fully abolished peptide transport. However, TAP complexes with equivalent mutations in TAP2 still showed residual peptide transport activity. To elucidate the origin of the asymmetry of the NBDs of TAP, we further examined TAP complexes with exchanged C-loops. Strikingly, the chimera with two canonical C-loops showed the highest transport rate whereas the chimera with two degenerate C-loops had the lowest transport rate, demonstrating that the ABC signature motifs control peptide transport efficiency. All single site mutants and chimeras showed similar activities in peptide or ATP binding, implying that these mutations affect the ATPase activity of TAP. In addition, these results prove that the serine of the C-loop is not essential for TAP function but rather coordinates, together with other residues of the C-loop, the ATP hydrolysis in both nucleotide-binding sites.
The transporter associated with antigen processing (TAP) plays a pivotal role in the adaptive immune response against virus-infected or malignantly transformed cells. As member of the ABC transporter family, TAP hydrolyzes ATP to energize the transport of antigenic peptides from the cytosol into the lumen of the endoplasmic reticulum. TAP forms a heterodimeric complex composed of TAP1 and TAP2 (ABCB2/3). Both subunits contain a hydrophobic transmembrane domain and a hydrophilic nucleotide-binding domain. The aim of this work was to study the ATP hydrolysis event of the TAP complex and gain further insights into the mechanism of peptide transport process. To analyze ATP hydrolysis of each subunit I developed a method of trapping 8- azido-nucleotides to TAP in the presence of phosphate transition state analogs followed by photocross-linking, immunoprecipitation, and high-resolution SDS-PAGE. Strikingly, trapping of both TAP subunits by beryllium fluoride is peptide-specific. The peptide concentration required for half-maximal trapping is identical for TAP1 and TAP2 and directly correlates with the peptide-binding affinity. Only background levels of trapping were observed for low affinity peptides or in the presence of the herpes simplex viral protein ICP47, which specifically blocks peptide binding to TAP. Importantly, the peptideinduced trapped state is reached after ATP hydrolysis and not in a backward reaction of ADP binding and trapping. In the trapped state, TAP can neither bind nor exchange nucleotides, whereas peptide binding is not affected. In summary, these data support the model that peptide binding induces a conformation that triggers ATP hydrolysis in both subunits of the TAP complex within the catalytic cycle. The role of the ABC signature motif (C-loop) on the functional non-equivalence of the NBDs was investigated. The C-loops of TAP transporter contain a canonical C-loop (LSGGQ) for TAP1 and a degenerated ABC signature motif (LAAGQ) for TAP2. Mutation of the leucine or glycine (LSGGQ) in TAP1 fully abolished peptide transport. TAP complexes with equivalent mutations in TAP2 showed however still residual peptide transport activity. To elucidate the origin of the asymmetry of the NBDs of TAP, we further examined TAP complexes with exchanged C-loops. Strikingly, the chimera with two canonical C-loops showed the highest transport rate whereas the chimera with two degenerated C-loops had the lowest transport rate, demonstrating that the ABC signature motifs control the peptide transport efficiency. All single-site mutants and chimeras showed similar activities in peptide or ATP binding, implying that these mutations affect the ATPase activity of TAP. In addition, these results prove that the serine of the C-loop is not essential for TAP function, but rather coordinates, together with other residues of the C-loop, the ATP hydrolysis in both nucleotide-binding sites. To study the coupling between the ATP binding/hydrolysis and the peptide binding, the putative catalytic bases of the TAP complex were mutated to generate the so-called EQ mutants. The mutations did not influence the peptide-binding ability. Dimerization of the NBDs of EQ mutants upon ATP binding does not alter the peptide binding property. At 27°C, both ATP and ADP could induce the loss of peptide-binding ability (Bmax) only in the variants bearing a mutated TAP2. Further studies are required to deduce at which stage in the catalytic cycle the peptide-binding site is affected. In addition, mutation of the putative catalytic base of both subunits showed a magnesium-dependent peptide transport activity, demonstrating these mutants did not abolish the ATP hydrolysis. Thus, the function of this acidic residue as the catalytic base is not likely to be universe for all ABC transporters.
This study focuses upon a detailed description and analysis of the phonetic structures of Paiwan, an aboriginal language spoken in Taiwan, with around 53,000 speakers, Paiwan, a member of the Austronesian language family, is not typologically related to the other languages such as Mandarin and Taiwanese spoken in its geographically contiguous districts, Earlier work on phonological features of Paiwan (Chang, 1999; Tseng, 2003) sought an account in terms of segments and isolated facts about reduplication and stress, without accounting for the possible roles of phrase-level and sentence-Ievel prosodic structures, Government Teaching Material (1993) listed 25 consonants and 4 vowels, without any description of phonetic features and phonological rules, Chang's (2000) reference grammar included 22 consonants and 4 vowels, with a very brief description of 5 phonological rules on single words, Regional diversity and 25 consonants have been mentioned in Pulaluyan's (2002) teaching material; however, no description of phonological rules was found in his material.
This paper analyzes banks' choice between lending to firms individually and sharing lending with other banks, when firms and banks are subject to moral hazard and monitoring is essential. Multiple-bank lending is optimal whenever the benefit of greater diversification in terms of higher monitoring dominates the costs of free-riding and duplication of efforts. The model predicts a greater use of multiple-bank lending when banks are small relative to investment projects, firms are less profitable, and poor financial integration, regulation and inefficient judicial systems increase monitoring costs. These results are consistent with empirical observations concerning small business lending and loan syndication. JEL Klassifikation: D82; G21; G32.
We take a simple time-series approach to modeling and forecasting daily average temperature in U.S. cities, and we inquire systematically as to whether it may prove useful from the vantage point of participants in the weather derivatives market. The answer is, perhaps surprisingly, yes. Time-series modeling reveals conditional mean dynamics, and crucially, strong conditional variance dynamics, in daily average temperature, and it reveals sharp differences between the distribution of temperature and the distribution of temperature surprises. As we argue, it also holds promise for producing the long-horizon predictive densities crucial for pricing weather derivatives, so that additional inquiry into time-series weather forecasting methods will likely prove useful in weather derivatives contexts.
The research performed in the DeepThought project aims at demonstrating the potential of deep linguistic processing if combined with shallow methods for robustness. Classical information retrieval is extended by high precision concept indexing and relation detection. On the basis of this approach, the feasibility of three ambitious applications will be demonstrated, namely: precise information extraction for business intelligence; email response management for customer relationship management; creativity support for document production and collective brainstorming. Common to these applications, and the basis for their development is the XML-based, RMRS-enabled core architecture framework that will be described in detail in this paper. The framework is not limited to the applications envisaged in the DeepThought project, but can also be employed e.g. to generate and make use of XML standoff annotation of documents and linguistic corpora, and in general for a wide range of NLP-based applications and research purposes.
In April 2003 I commented on the European Commission’s Action Plan on a More Coherent European Contract Law [COM(2003) 68 final] and the Green Paper on the Modernisation of the 1980 Rome Convention [COM(2002) 654 final].1 While the main argument of that paper, i.e. the common neglect of the inherent interrelation between both the further harmonisation of substantive contract law by directives or through an optional European Civil Code on the one hand and the modernisation of conflict rules for consumer contracts in Art. 5 Rome Convention on the other hand, remain pressing issues, and as the German Law Journal continues its efforts in offering timely and critical analysis on consumer law issues,2 there is a variety of recent developments worth noting.
In the early Nineties the Hague Conference on International Private Law on initiative of the United States started negotiations on a Convention on the Recognition and Enforcement of Foreign Judgments in Civil and Commercial Matters (the "Hague Convention"). In October 1999 the Special Commission on duty presented a preliminary text, which was drafted quite closely to the European Convention on Jurisdiction and Enforcement of Judgments in Civil and Commercial Matters (the "Brussels Convention"). The latter was concluded between the then 6 Member States of the EEC in Brussels in 1968 and amended several times on occasion of the entry of new Member States. In 2000, after the Treaty of Amsterdam altered the legal basis for judicial co-operation in civil matters in Europe, it was transformed into an EC Regulation (the "Brussels I Regulation"). The 1999 draft of the Hague Convention was heavily criticized by the USA and other states for its European approach of a double convention, regulating not only the recognition and enforcement of judgments, but at the same time the extent of and the limits to jurisdiction to adjudicate in international cases. During a diplomatic conference in June 2001 a second draft was presented which contained alternative versions of several articles and thus resembled more the existing dissent than a draft convention would. Difficulties to reach a consensus remained, especially with regard to activity based jurisdiction, intellectual property, consumer rights and employee rights. In addition, the appropriateness of the whole draft was questioned in light of the problems posed by the de-territorialization of relevant conduct through the advent of the Internet. In April 2002 it was decided to continue negotiations on an informal level on the basis of a nucleus approach. The core consensus as identified by a working group, however, was not very broad. The experts involved came to the conclusion that the project should be limited to choice of court agreements. In March 2004 a draft was presented which sets out its aims as follows: "The objective of the Convention is to make exclusive choice of court agreements as effective as possible in the context of international business. The hope is that the Convention will do for choice of court agreements what the New York Convention of 1958 has done for arbitration agreements." In April 2004 the Special Commission of the Hague Conference adopted a Draft "Convention on Exclusive Choice of Court Agreements", which according to its Art. 2 No. 1 a) is not applicable to choice of court agreements, to which a natural person acting primarily for personal, family or household purposes (a consumer) is a party". The broader project of a global judgments convention thus seems to be abandoned, or at least to be postponed for an unlimited time period. There are - of course - several reasons why the Hague Judgments project failed. Samuel Baumgartner has described an important one as the "Justizkonflikt" between the United States and Europe or, more specifically Germany. Within the context of the general topic of this conference, that is (international) jurisdiction for human rights, in the remainder of this presentation I shall elaborate on the socio-cultural aspects of the impartiality of judgments and their enforcement on a global scale.
Semi-permanent quadrats, located in the South and Central Western Slopes botanical regions of New South Wales, were assessed to indicate suitable periods of the year to conduct surveys of botanical diversity. The quadrats were located in woodland communities with a generally herbaceous understorey, and subject to a wide range of domestic stock grazing intensities. In the mid to western South Western Slopes (SWS) the greatest number of species was generally recorded in an October survey. The main exception was in degraded areas (low species diversity, high proportion of annual weed species), where similar results were recorded in September and October. In the cooler and wetter eastern SWS a relatively high proportion of species were recorded in October to early December surveys. However, when compared to species totals compiled from multiple assessments in all seasons, or from August to November, a single optimal survey usually recorded only 60–75% of the plant species at a site. Surveys in mid to late summer, autumn and early winter usually recorded less than 50% of the plant species present. The results reflect the prevailing Mediterranean-type climate, and that the ground layer vegetation (primarily comprised of annuals and herbaceous perennials) dominates the species diversity.
Information literacy is a mosaic of attitudes, understandings, capabilities and knowledge about which there are three myths. The first myth is that it is about the ability to use ICTs to access a wealth of information. The second is that students entering higher education are information literate because student centred, resource based, and ICT focused learning are now pervasive in secondary education. The third myth is that information literacy development can be addressed by library-centric generic approaches. This paper addresses those myths and emphasises the need for information literacy to be recognised as the critical whole of education and societal issue, fundamental to an information-enabled and better world. In formal education, information literacy can only be developed by infusion into curriculum design, pedagogies, and assessment.
We perform a study of the possible existence of hybrid stars with color superconducting quark cores using a specific hadronic model in a combination with an NJL-type quark model. It is shown that the constituent mass of the non-strange quarks in vacuum is a very important parameter that controls the beginning of the hadron–quark phase transition. At relatively small values of the mass, the first quark phase that appears is the two-flavor color superconducting (2SC) phase which, at larger densities, is replaced by the color-flavor locked (CFL) phase. At large values of the mass, on the other hand, the phase transition goes from the hadronic phase directly into the CFL phase avoiding the 2SC phase. It appears, however, that the only stable hybrid stars obtained are those with the 2SC quark cores.
Since the description of sepsis by Schottmüller in 1914, the amount on knowledge available on sepsis and its underlying pathophysiology has substantially increased. Epidemiologic examinations of abdominal septic shock patients show the potential for high risk posed by and the extensive therapy situation in the intensive care unit (ICU) (5). Unfortunately, until now it has not been possible to significantly reduce the mortality rate of septic shock, which is as high as 50-60% worldwide, although PROWESS' results (1) are encouraging. This paper summarizes the main results of the MEDAN project and their medical impacts. Several aspects are already published, see the references. The heterogeneity of patient groups and the variations in therapy strategies is seen as one of the main problems for sepsis trials. In the MEDAN multi-center study of 71 intensive care units in Germany, a group of 382 patients made up exclusively of abdominal septic shock patients who met the consensus criteria for septic shock (3) was analysed. For use within scores or stand-alone experiments variables are often studied as isolated variables, not as a multidimensional whole, e.g. a recent study takes a look at the role thrombocytes play (15). To avoid this limitation, our study compares several established scores (SOFA, APACHE II, SAPS II, MODS) by a multi-dimensional neuronal network analysis. For outcome prediction the data of 382 patients was analysed by using most of the commonly documented vital parameters and doses of medicine (metric variables). Data was collected in German hospitals from 1998 to 2001. The 382 handwritten patient records were transferred to an electronic database giving the amount of 2.5 million data entries. The metric data contained in the database is composed of daily measurements and doses of medicine. We used range and plausibility checks to allow no faulty data in the electronic database. 187 of the 382 patients are deceased (49 %).
In bioinformatics, biochemical signal pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically obtaining the most appropriate model and learning its parameters is extremely interesting. One of the most often used approaches for model selection is to choose the least complex model which “fits the needs”. For noisy measurements, the model which has the smallest mean squared error of the observed data results in a model which fits too accurately to the data – it is overfitting. Such a model will perform good on the training data, but worse on unknown data. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated. Keywords: biochemical pathways, differential equations, septic shock, parameter estimation, overfitting, minimum description length.
Data driven automatic model selection and parameter adaptation – a case study for septic shock
(2004)
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated.
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. In this paper, for the small, important example of inflammation modeling a network is constructed and different learning algorithms are proposed. It turned out that due to the nonlinear dynamics evolutionary approaches are necessary to fit the parameters for sparse, given data. Keywords: model parameter adaption, septic shock. coupled differential equations, genetic algorithm.
We investigate transverse hadron spectra from relativistic nucleus-nucleus collisions which reflect important aspects of the dynamics - such as the generation of pressure - in the hot and dense zone formed in the early phase of the reaction. Our analysis is performed within two independent transport approaches (HSD and UrQMD) that are based on quark, diquark, string and hadronic degrees of freedom. Both transport models show their reliability for elementary pp as well as light-ion (C+C, Si+Si) reactions. However, for central Au+Au (Pb+Pb) collisions at bombarding energies above ~ 5 A.GeV the measured K+- transverse mass spectra have a larger inverse slope parameter than expected from the calculation. Thus the pressure generated by hadronic interactions in the transport models above ~ 5 A.GeV is lower than observed in the experimental data. This finding shows that the additional pressure - as expected from lattice QCD calculations at finite quark chemical potential and temperature - is generated by strong partonic interactions in the early phase of central Au+Au (Pb+Pb) collisions.
We investigate hadron production and transverse hadron spectra in nucleus-nucleus collisions from 2 A·GeV to 21.3 A·TeV within two independent transport approaches (UrQMD and HSD) based on quark, diquark, string and hadronic degrees of freedom. The enhancement of pion production in central Au+Au (Pb+Pb) collisions relative to scaled pp collisions (the ’kink’) is described well by both approaches without involving a phase transition. However, the maximum in the K+ p+ ratio at 20 to 30 A·GeV (the ’horn’) is missed by ~ 40%. Also, at energies above ~5 A·GeV, the measured K± mT-spectra have a larger inverse slope than expected from the models. Thus the pressure generated by hadronic interactions in the transport models at high energies is too low. This finding suggests that the additional pressure - as expected from lattice QCD at finite quark chemical potential and temperature - might be generated by strong interactions in the early pre-hadronic/partonic phase of central heavy-ion collisions. Finally, we discuss the emergence of density perturbations in a first-order phase transition and why they might affect relative hadron multiplicities, collective flow, and hadron mean-free paths at decoupling. A minimum in the collective flow v2 excitation function was discovered experimentally at 40 A·GeV - such a behavior has been predicted long ago as signature for a first order phase transition.
We investigate hadron production as well as transverse hadron spectra in nucleus-nucleus collisions from 2 A.GeV to 21.3 A.TeV within two independent transport approaches (UrQMD and HSD) that are based on quark, diquark, string and hadronic degrees of freedom. The comparison to experimental data demonstrates that both approaches agree quite well with each other and with the experimental data on hadron production. The enhancement of pion production in central Au+Au (Pb+Pb) collisions relative to scaled pp collisions (the 'kink') is well described by both approaches without involving any phase transition. However, the maximum in the K+/Pi+ ratio at 20 to 30 A.GeV (the 'horn') is missed by ~ 40%. A comparison to the transverse mass spectra from pp and C+C (or Si+Si) reactions shows the reliability of the transport models for light systems. For central Au+Au (Pb+Pb) collisions at bombarding energies above ~ 5 A.GeV, however, the measured K +/- m-theta-spectra have a larger inverse slope parameter than expected from the calculations. The approximately constant slope of K+/-spectra at SPS (the 'step') is not reproduced either. Thus the pressure generated by hadronic interactions in the transport models above ~ 5 A.GeV is lower than observed in the experimental data. This finding suggests that the additional pressure - as expected from lattice QCD calculations at finite quark chemical potential and temperature - might be generated by strong interactions in the early pre-hadronic/partonic phase of central Au+Au (Pb+Pb) collisions.
This paper provides an in-depth analysis of the properties of popular tests for the existence and the sign of the market price of volatility risk. These tests are frequently based on the fact that for some option pricing models under continuous hedging the sign of the market price of volatility risk coincides with the sign of the mean hedging error. Empirically, however, these tests suffer from both discretization error and model mis-specification. We show that these two problems may cause the test to be either no longer able to detect additional priced risk factors or to be unable to identify the sign of their market prices of risk correctly. Our analysis is performed for the model of Black and Scholes (1973) (BS) and the stochastic volatility (SV) model of Heston (1993). In the model of BS, the expected hedging error for a discrete hedge is positive, leading to the wrong conclusion that the stock is not the only priced risk factor. In the model of Heston, the expected hedging error for a hedge in discrete time is positive when the true market price of volatility risk is zero, leading to the wrong conclusion that the market price of volatility risk is positive. If we further introduce model mis-specification by using the BS delta in a Heston world we find that the mean hedging error also depends on the slope of the implied volatility curve and on the equity risk premium. Under parameter scenarios which are similar to those reported in many empirical studies the test statistics tend to be biased upwards. The test often does not detect negative volatility risk premia, or it signals a positive risk premium when it is truly zero. The properties of this test furthermore strongly depend on the location of current volatility relative to its long-term mean, and on the degree of moneyness of the option. As a consequence tests reported in the literature may suffer from the problem that in a time-series framework the researcher cannot draw the hedging errors from the same distribution repeatedly. This implies that there is no guarantee that the empirically computed t-statistic has the assumed distribution. JEL: G12, G13 Keywords: Stochastic Volatility, Volatility Risk Premium, Discretization Error, Model Error
Tests for the existence and the sign of the volatility risk premium are often based on expected option hedging errors. When the hedge is performed under the ideal conditions of continuous trading and correct model specification, the sign of the premium is the same as the sign of the mean hedging error for a large class of stochastic volatility option pricing models. We show, however, that the problems of discrete trading and model mis-specification, which are necessarily present in any empirical study, may cause the standard test to yield unreliable results.
When options are traded, one can use their prices and price changes to draw inference about the set of risk factors and their risk premia. We analyze tests for the existence and the sign of the market prices of jump risk that are based on option hedging errors. We derive a closed-form solution for the option hedging error and its expectation in a stochastic jump model under continuous trading and correct model specification. Jump risk is structurally different from, e.g., stochastic volatility: there is one market price of risk for each jump size (and not just \emph{the} market price of jump risk). Thus, the expected hedging error cannot identify the exact structure of the compensation for jump risk. Furthermore, we derive closed form solutions for the expected option hedging error under discrete trading and model mis-specification. Compared to the ideal case, the sign of the expected hedging error can change, so that empirical tests based on simplifying assumptions about trading frequency and the model may lead to incorrect conclusions.
Tractable hedging - an implementation of robust hedging strategies : [This Version: March 30, 2004]
(2004)
This paper provides a theoretical and numerical analysis of robust hedging strategies in diffusion–type models including stochastic volatility models. A robust hedging strategy avoids any losses as long as the realised volatility stays within a given interval. We focus on the effects of restricting the set of admissible strategies to tractable strategies which are defined as the sum over Gaussian strategies. Although a trivial Gaussian hedge is either not robust or prohibitively expensive, this is not the case for the cheapest tractable robust hedge which consists of two Gaussian hedges for one long and one short position in convex claims which have to be chosen optimally.
This paper deals with the superhedging of derivatives and with the corresponding price bounds. A static superhedge results in trivial and fully nonparametric price bounds, which can be tightened if there exists a cheaper superhedge in the class of dynamic trading strategies. We focus on European path-independent claims and show under which conditions such an improvement is possible. For a stochastic volatility model with unbounded volatility, we show that a static superhedge is always optimal, and that, additionally, there may be infinitely many dynamic superhedges with the same initial capital. The trivial price bounds are thus the tightest ones. In a model with stochastic jumps or non-negative stochastic interest rates either a static or a dynamic superhedge is optimal. Finally, in a model with unbounded short rates, only a static superhedge is possible.
We extend the important idea of range-based volatility estimation to the multivariate case. In particular, we propose a range-based covariance estimator that is motivated by financial economic considerations (the absence of arbitrage), in addition to statistical considerations. We show that, unlike other univariate and multivariate volatility estimators, the range-based estimator is highly efficient yet robust to market microstructure noise arising from bid-ask bounce and asynchronous trading. Finally, we provide an empirical example illustrating the value of the high-frequency sample path information contained in the range-based estimates in a multivariate GARCH framework.
Hartmann and his Prague friends, whether German-Gentile or German-Jewish, rallied enthusiastically to the cause of what at first was a reawakening of suppressed Bohemic cultural nationalism and a move towards across-fertilisation of the two main lingual cultures (Czech/German) andthe three main ethnicities (Czech/German/Jewish) of the country. They soon saw themselves as a "Jungböhmische Bewegung" to correspond to Young Germany. The Prague writer Rudolf Glaser founded a literary journal called 'Ost und West' for the express purpose of bringing together German and Slavic literary impulses under the Goethean motto: "Orient und Occident sind nicht mehr zu trennen". With Bohemia as the bridge, 'Ost und West' published German translations from all the Slavic languages including Pushkin and Gogol, contributions by German writers sympathetic to the cause of emerging nations like Heinrich Laube, Ferdinand Freiligrath, Ernst Willkomm, but above all the Prague circle of Young Bohemians like Alfred Meissner, Isidor Heller, Uffo Horn, Gustav Karpeles and Ignatz Kuranda. Also Hartmann made his literary debut in the journal with a love poem entitled "Der Drahtbinder", and featuring a subtitle which was in keeping with the spirit of the times: "nach einem slavischen Lied".
We point out that during the supernova II type explosion the thermodynamical conditions of stellar matter between the protoneutron star and the shock front correspond to the nuclear liquid–gas coexistence region, which can be investigated in nuclear multifragmentation reactions. We have demonstrated, that neutron-rich hot heavy nuclei can be produced in this region. The production of these nuclei may influence dynamics of the explosion and contribute to the synthesis of heavy elements.
Determination of the structure of complex I of Yarrowia lipolytica by single particle analysis
(2004)
Komplex I enthält ein Flavinmononukleotid sowie mindestens acht Eisen- Schwefel Zentren als redoxaktive Cofaktoren. Da ein wesentlicher Teil des mitochondrialen Genoms für Untereinheiten von Komplex I codiert, betrifft eine Vielzahl von mitochondrialen Erkrankungen diesen Enzymkomplex.
Komplex I wurde bisher aus Mitochondrien, Chloroplasten und Bakterien isoliert. Die Minimalform von Komplex I wird in Bakterien gefunden, wo er aus 14 (bzw 13 im Falle einer Genfusion) Untereinheiten besteht und eine Masse von etwa 550 kDa aufweist. Generell werden sieben hydrophile und sieben hydrophobe Untereinheiten mit über 50 vorhergesagten Transmembranhelices gefunden. Im Komplex I aus Eukaryoten wurde eine grössere Anzahl zusätzlicher, akzessorischer Untereinheiten nachgewiesen. Hier werden die sieben hydrophoben Untereinheiten vom mitochondrialen Genom codiert, während alle anderen Untereinheiten kerncodiert sind und in das Mitochondrium importiert werden müssen.
Die obligat aerobe Hefe Yarrowia lipolytica wurde als Modellsystem zur Untersuchung von eukaryotischem Komplex I etabliert. Die bisher am besten untersuchte Hefe Saccharomyces cerevisiae enthält keinen Komplex I. Hier wird die Oxidation von NADH durch eine andere Klasse von sogenannten alternativen NADH Dehydrogenasen durchgeführt. Auch Y. lipolytica enthält ein solches alternatives Enzym, das allerdings mit seiner Substratbindungsstelle zur Aussenseite der inneren Mitochondrienmembran orientiert ist. Durch molekularbiologische Manipulation konnte eine interne Version dieses Enzymes exprimiert werden, wodurch es möglich ist, letale Defekte in Komplex I Deletionsmutanten zu kompensieren. Mittlerweile wurden alle Voraussetzungen geschaffen, um kerncodierte Untereinheiten von Komplex I aus Y. lipolytica gezielt genetisch zu verändern. Die Proteinreinigung wird durch die Verwendung einer auf einem His-tag basierenden Affinitätsreinigung erheblich erleichtert...
The production of strange pentaquark states (e.g., Theta baryons and Ξ−− states) in hadronic interactions within a Gribov–Regge approach is explored. In this approach the Θ+(1540) and the Ξ are produced by disintegration of remnants formed by the exchange of pomerons between the two protons. We predict the rapidity and transverse momentum distributions as well as the 4π multiplicity of the Θ+, Ξ−−, Ξ−, Ξ0 and Ξ+ for s=17 GeV (SPS) and 200 GeV (RHIC). For both energies more than 10−3 Θ+ and more than 10−5 Ξ per pp event should be observed by the present experiments.
Pathologic data indicate that human cytomegalovirus (HCMV) infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB) cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169), were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcriptionpolymerase chain reaction (RT-PCR). The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.
Speakers have a wide range of noncanonical syntactic options that allow them to mark the information status of the various elements within a proposition. The correlation between a construction and constraints on information status, however, is not arbitrary; there are broad, consistent, and predictive generalizations that can be made about the information-packaging functions served by preposing, postposing, and argument-reversing constructions. Specifically, preposed constituents are constrained to represent discourse-old information, postposed constituents are constrained to represent information that is either discourse-new or hearer-new, and argument-reversing constructions require that the information represented by the preposed constituent be at least as familiar as that represented by the postposed constituent (Birner & Ward 1998). The status of inferable information (Clark 1977; Prince 1981), however, is problematic; a study of corpus data shows that such information can be preposed in an inversion or a preposing (hence must be discourse-old), yet can also be postposed in constructions requiring hearer-new information (hence must be hearer-new). This information status – discourse-old yet hearer-new – is assumed by Prince (1992) to be non-occurring on the grounds that what has been evoked in the discourse should be known to the hearer. I resolve this difficulty by arguing for a reinterpretation of the term 'discourse-old' as applying not only to information that has been explicitly evoked in the prior discourse, but rather to any information that provides a salient inferential link to the prior discourse. Extending Prince’s notion in this manner allows us to account for the distribution of noncanonically positioned peripheral constituents in a principled and unified way.
Even though tourism has been recognised as an important field for transnational research today, there are few attempts to place tourism in the context of transnational theories or to think about transnationalism from the perspective of tourists. I argue that in researching tourist practices one can add important aspects to transnational approaches. The prerequisites of mobility and interaction for example are the features chosen by backpackers to describe what their Round-The-World-Trip is about. A form of tourism is adopted, or created, that itself confronts many aspects of globalisation: First of all there is the immense dynamic that is involved. Backpackers try to cover as many places and experiences as possible, travelling at high speed. They adopt all kinds of touristic experiences ranging from beach to adventure to culture tourism. They don't focus on a specific area or country but travel the world. They cross national borders perpetually. Additionally they form a transnational network in which they interact with strangers of similar backgrounds (other backpackers, tourist professionals). This network helps them interacting with people from different backgrounds (the socalled hosts or locals). Considering my research Backpackers forge a certain identity from these transnational practices which I want to name globedentity. Globedentity expresses a type of identity construction that not only refers to the individual (I) but reflects the world (globe) in this identity. This globedentity is not fixed but is perpetually re-created and re-defined. It also embraces the increasing popular awareness of globalisation which backpackers, coming from highly educated middle class backgrounds, in particular have identified with. Due to the constant awareness of the latest global social, cultural and economic developments in these educated milieus they know exactly which tools to use to become successful parts of their societies.
In hindsight, the debate about presupposition following Frege’s discovery that the referential function of names and definite descriptions depended on the fulfillment of an existence and a uniqueness condition was curiously limited for a very long time. On the one hand, it was only in the 1960s that linguists began to take an interest and showed that presupposition was an allpervasive phenomenon far beyond this philosophers’ pet definite descriptions. And on the other hand, and this is our real concern, it is now only too obvious that the uniqueness condition is too restrictive to be applicable to the general case. An utterance of “The cat is on the mat” should not imply that there is only one cat and one mat in the whole world. The obvious move is to limit the uniqueness condition to some notion of utterance context.
Configuration, simulation and visualization of simple biochemical reaction-diffusion systems in 3D
(2004)
Background In biological systems, molecules of different species diffuse within the reaction compartments and interact with each other, ultimately giving rise to such complex structures like living cells. In order to investigate the formation of subcellular structures and patterns (e.g. signal transduction) or spatial effects in metabolic processes, it would be helpful to use simulations of such reaction-diffusion systems. Pattern formation has been extensively studied in two dimensions. However, the extension to three-dimensional reaction-diffusion systems poses some challenges to the visualization of the processes being simulated. Scope of the Thesis The aim of this thesis is the specification and development of algorithms and methods for the three-dimensional configuration, simulation and visualization of biochemical reaction-diffusion systems consisting of a small number of molecules and reactions. After an initial review of existing literature about 2D/3D reaction-diffusion systems, a 3D simulation algorithm (PDE solver), based on an existing 2D-simulation algorithm for reaction-diffusion systems written by Prof. Herbert Sauro, has to be developed. In a succeeding step, this algorithm has to be optimized for high performance. A prototypic 3D configuration tool for the initial state of the system has to be developed. This basic tool should enable the user to define and store the location of molecules, membranes and channels within the reaction space of user-defined size. A suitable data structure has to be defined for the representation of the reaction space. The main focus of this thesis is the specification and prototypic implementation of a suitable reaction space visualization component for the display of the simulation results. In particular, the possibility of 3D visualization during course of the simulation has to be investigated. During the development phase, the quality and usability of the visualizations has to be evaluated in user tests. The simulation, configuration and visualization prototypes should be compliant with the Systems Biology Workbench to ensure compatibility with software from other authors. The thesis is carried out in close cooperation with Prof. Herbert Sauro at the Keck Graduate Institute, Claremont, CA, USA. Due to this international cooperation the thesis will be written in English.