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This paper evaluates trills [r] and their palatalized counterparts [rj] from the point of view of markedness. It is argued that [r]s are unmarked sounds in comparison to [rj]s which follows from the examination of the following parameters: (a) frequency of occurrence, (b) articulatory and aerodynamic characteristics, (c) perceptual features, (d) emergence in the process of language acquisition, (e) stability from a diachronic point of view, (f) phonotactic distribution, and (g) implications. Several markedness aspects of [r]s and [rj] are analyzed on the basis of Slavic languages which offer excellent material for the evaluation of trills. Their phonetic characteristics incorporated into phonetically grounded constraints are employed for a phonological OT-analysis of r-palatalization in two selected languages: Polish and Czech.
This paper evaluates trills [r] and their palatalized counterparts [rj] from the point of view of markedness. It is argued that [r]s are unmarked sounds in comparison to [r ]s which follows from the examination of the following parameters: (a) frequency of occurrence, (b) articulatory and aerodynamic characteristics, (c) perceptual features, (d) emergence in the process of language acquisition, (e) stability from a diachronic point of view, (f) phonotactic distribution, and (g) implications.
Several markedness aspects of [r]s and [rj] are analyzed on the basis of Slavic languages which offer excellent material for the evaluation of trills. Their phonetic characteristics incorporated into phonetically grounded constraints are employed for a phonological OT-analysis of r-palatalization in two selected languages: Polish and Czech.
We discuss gapless colour superconductivity for neutral quark matter in β equilibrium at zero as well as at nonzero temperature. Basic properties of gapless superconductors are reviewed. The current progress and the remaining problems in the understanding of the phase diagram of strange quark matter are discussed.
We study the phase diagram of a generalized chiral SU(3)-flavor model in mean-field approxi- mation. In particular, the influence of the baryon resonances, and their couplings to the scalar and vector fields, on the characteristics of the chiral phase transition as a function of temperature and baryon-chemical potential is investigated. Present and future finite-density lattice calculations might constrain the couplings of the fields to the baryons. The results are compared to recent lattice QCD calculations and it is shown that it is non-trivial to obtain, simultaneously, stable cold nuclear matter.
This article analyses the German discourse particle wohl 'I suppose', 'presumably' as a syntactic and semantic modifier of the sentence types declarative and interrogative. It is shown that wohl does not contribute to the propositional, i.e. descriptive content of an utterance. Nor does it trigger an implicature. The proposed analysis captures the semantic behaviour of wohl by assuming that it moves to SpecForceP at LF, from where it can modify the sentence type operators in Force0 in compositional fashion. Semantically, a modification with wohl results in a weaker commitment to the proposition expressed in declaratives and in a request for a weaker commitment concerning the questioned proposition in interrogatives. Cross-linguistic evidence for a left-peripheral position of wohl (at LF) comes from languages in which the counterpart of wohl occurs in the clausal periphery overtly. Overall, the analysis sheds more light on the semantic properties of the left periphery, in particular of the functional projection ForceP.
Structural and functional characterization of the dimerization region of soluble guanylyl cyclase
(2004)
Soluble guanylyl cyclase (sGC) is a ubiquitous enzyme that functions as a receptor for nitric oxide. Despite the obligate heterodimeric nature of sGC, the sequence segments mediating subunit association have remained elusive. Our initial screening for relevant interaction site(s) in the most common sGC isoenzyme, α1 β1, identified two regions in each subunit, i.e. the regulatory domains and the central regions, contributing to heterodimer formation. To map the relevant segments in the β1 subunit precisely, we constructed multiple N- and C-terminal deletion variants and cotransfected them with full-length α1 in COS cells. Immunoprecipitation revealed that a sequence segment spanning positions 204–408 mediates binding of β1 to α1 The same region of β1[204–408] was found to promote β /β1 homodimerization. Fusion of [204 β1–408] to enhanced green fluorescent protein conferred binding activity to the recipient protein. Coexpression of β1[204–408] with α1 or β1 targeted the sGC subunits for proteasomal degradation, suggesting that β1[204–408] forms structurally deficient complexes with α1 and β1. Analysis of deletion constructs lacking portions of the β1 dimerization region identified two distinct segments contributing to α1 binding, i.e. an N-terminal site covering positions 204–244 and a C-terminal site at 379–408. Both sites are crucial for sGC function because deletion of either site rendered sGC dimerization-deficient and thus functionally inactive. We conclude that the dimerization region of β1 extends over 205 residues of its regulatory and central domains and that two discontinuous sites of 41 and 30 residues, respectively, facilitate binding of β1 to the α1 subunit of sGC.
In the present study the cryo-immunogold technique was used and optimized for investigating the ultrastructure and immunolabeling of synaptic proteins. It is evidently a suitable method for the localization of membrane proteins since the antigens are not treated with any chemical denaturation before immunolabeling except for the fixation and since the antigens are directly exposed to the surface of the cryo-ultrasections. The v-SNARE VAMP II and the vesicle-associated proteins SV2 and Rab3A were detected extensively at small vesicles in the mossy fiber terminals. The t-SNARE SNAP-25, and N-type and P/Q type Ca2+ channels were allocated to the plasma membrane both at the active zone and outside the active zone. SNAP-25 and N-type Ca2+ channels appeared also at synaptic vesicles. A significantly increased immunolabeling of VAMP II, SV2, Rab3A, SNAP-25 and N-type Ca2+ channels was found at the active zones of fast synapses, indicating a concentration of these proteins at sites of exocytosis. The widespread distribution of the t-SNARE SNAP-25 at the axonal plasma membrane reveals that membrane-targeting specificity cannot be determined solely by v/t-SNARE interactions. Additional control components are required to assure the docking and exocytosis of the synaptic vesicles at active zones. The novel protein Bassoon was only found at active zones of central synapses and showed the highest specific labeling among all proteins investigated. Its labeling pattern implies an association of Bassoon with the presynaptic dense projections, the structural guide for vesicle exocytosis. The involvement of Bassoon in the organization of the neurotransmitter release site suggests that Bassoon may play an important role in determining the specificity of vesicle docking and fusion. In the neurosecretory endings of neurohypophysis the synaptic proteins VAMP II, SNAP- 25, SV2, Rab3A, and the N-type Ca2+ channels showed a preferential labeling over microvesicles. Moreover, the immunolabeling intensity of these proteins over microvesicles corresponded closely to that over synaptic vesicles. This suggests that these synaptic proteins share an identical association with synaptic vesicle and microvesicles. A significant labeling of SNAP-25, the N-type Ca2+ channels and VAMP II was also detected at the plasma membrane near the clustered microvesicles, indicating the competence of microvesicles for docking and exocytosis along the plasma membrane in the absence of active zones. No significant labeling of VAMP II, SNAP-25, SV2 and N-type Ca2+ channel was observed at the membrane of neurosecretory granules. This is in agreement with the notion that synaptic vesicles and microvesicles possess regulatory mechanisms for exocytosis different from those of granules. In contrast, a/ß-SNAP and NSF were found on the granules, and Rab3A and the P/Q-type Ca2+ channels on granules in a subset of terminals. Rab3A is associated specifically with the oxytocin-containing granule population. Interestingly, some plasma membrane proteins, such as SNAP-25 and even N-type Ca2+ channels and P/Q-type Ca2+ channels, were observed not only at the plasma membrane but also at the vesicular organelles. This suggests that these vesicular organelles may be involved in transporting newly synthesized proteins from the soma to the plasma membrane of the terminal. Furthermore, the vesicular pool of the Ca2+ channels may serve in the stimulationinduced translocation into the plasma membrane when required. Using the conventional preembedding method with Epon and the post-embedding method with LR Gold, VAMP II was localized at vesicular organelles of varying size and on horseradish peroxidase filled endocytic organelles in cultured astrocytes, with and without stimulation in the presence of the horseradish peroxidase. This indicates that VAMP II is involved in the cycle of vesicular exocytosis and endocytosis in astrocytes. U373 cells are capable of expressing all three members of the synaptic SNARE complex (v-SNARE VAMP II, t-SNARE syntaxin I and SNAP25). This indicates the competence of U373 to carry out regulated exocytosis by means of the classical SNARE mechanism. In addition, the ubiquitous v-SNARE cellubrevin and the endosome-associated small GTPbinding protein Rab5 could be expressed in U373 cells. All recombinant synaptic proteins investigated in U373 cells revealed a punctuate cellular distribution under the fluorescence microscope, suggesting that they are mainly associated with intracellular compartments. The cryo-electron microscopy provided direct evidence for the association of all expressed proteins with electron-lucent vesicular organelles. It further supports the potential of U373 MG cells to release low molecular weight messengers by a regulated exocytosis mechanism. In addition, myc-VAMP II was found on dispersed granules. Probably, VAMP II also participates in the exocytosis event of granules in U373 cells. Gold labeling for the two presumptive t-SNAREs syntaxin I and SNAP-25 in U373 cells was confined to the vesicular organelles. At the ultrastructural level no significant labeling was identified at the plasma membrane. The high level of colocalization of the two SNARE proteins VAMP II and syntaxin I in the cell body and in cell processes suggests that the two proteins are mostly sorted into identical vesicular organelles. A partial colocalization of VAMP II and cellubrevin as well as of VAMP II and Rab5 was observed under the fluorescence microscope. At the ultrastructural level, a colocalization of VAMP II and cellubrevin as well as of VAMP II and Rab5 was found on some clustered vesicles. The partial colocalization of VAMP II and cellubrevin implies that they similarly function as v-SNAREs. The partial colocalization of Rab5 with VAMP II in U373 cells suggests that the endosomal protein Rab5 is associated with VAMP II-containing organelles during some stages of their life cycle.
This paper investigates how syntax and focus interact in deriving the phonological phrasing of utterances in Xhosa, a Bantu language spoken in South Africa. Although the influence of syntax on phrasing is uncontroversial, a purely syntactic analysis cannot account for all the data reported for Xhosa by Jokweni (1995). Focus influences the phrasing in that it inserts a phonological phrase-boundary after the focused constituent. This generalization can account for the variation found in the phrasing of adverbials.
The findings are dealt with in an OT-based framework following Truckenbrodt's work on Chichewa (1995, 1999) which is extended to the phrasing of adjuncts.
Left dislocation in Zulu
(2004)
This paper examines left dislocation constructions in Zulu, a Southern Bantu language belonging to the Nguni group (Zone S 40). In Zulu left dislocation configurations, a topic phrase in the beginning of the sentence is linked to a resumptive element within the associated clause. Typically, the resumptive element is an incorporated pronoun (cf. Bresnan & Mchombo 1987), as illustrated by the examples in (1) and (2). In these examples, the object pronoun (in italics) is part of the verbal morphology and agrees with the noun class (gender) of the dislocate. This situation is schematically illustrated in (3), where co-indexation represents agreement: ...
Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair.
As for the relation between Islam and pluralism, it seems a little bit complicated. There are some verses in The Koran for pluralism and at the same time we have some verses against. Among the sayings of Prophet Muhammad like the some Koranic verses, we came across with something good and bad for non-Muslims in special contexts. By another saying, we find both positive and negative statements for Jews and Christians in different circumstances. Muslim scholars the complexity still exists. We find both positive and negative stances. So it is difficult to see a standard or official view on this issue. However, we should point out that Islam recognizes all the sacred (Semitic) books and their messages. It accepts all prophets of that traditions. It defines itself as the last and perfect religion of Semitic tradition and states that no other religion will be accepted from anybody else other then itself. It criticizes both the Jews and Christians especially about their failure to uphold the Oneness of God, tawhid, and to preserve the authenticity of their scripture from interventions. This exclusivist aspect of Islam as many conservative scholars formed with putting together some evidences from the Koran is generally accepted by Muslims.
The principal aim of this paper is to present a comprehensive theory of coordination of unlikes, i.e., a theory that is capable of dealing with every phenomenon resulting from coordination of unlikes. The proposed theory accounts not just for standard cases of coordination of unlike arguments and coordination of unlike functors but also for cases involving single-conjunct agreement and what will be called each-conjunct agreement. In the course of the argumentation, it is also shown that, even in a language like English, predicate-argument agreement needs to be described in terms of a relational constraint that is not simply an identity requirement.
With this study, the fauna of Hispaniolan Phyllophaga is now composed of 48 species, all of which are endemic (precinctive), including 22 new species described herein (4 attributed to Woodruff and Sanderson: approxima, bonfils, jimenezi, rex; 18 to Woodruff: aceitillar, alcoa, androw, baoruco, carnegie, davidsoni, eladio, haitiensis, jaragua, larimar, marcano, nunezi, ortizi, pedernales, rawlinsi, rustica, santachloe, toni). Additionally, allotypes are described for 7 species with previously unknown males (aliada, canoa) or females (esquinada, fossoria, imprima, kenscoffi, panicula), and 6 new country records (Dominican Republic) are provided (aliada, leptospica, minutissima, panicula, permagna, recorta). Of the 48, only 1 male remains unknown (barrosa), and 9 females are missing (aceitillar, carnegie, costura, davidsoni, espina, garrota, probaporra, rustica, toni); 32 are recorded only from the Dominican Republic, and 5 are known only from Haiti. The 727 Figures include 50 habitus illustrations for all species, as well as SEM photos of male and female genitalia, and other salient morphological characters. The discovery of “sister species”, on opposite sides of the Enriquillo basin, provides significant data to support the 2 island concept; 15 species are known only from the paleo “south island”, and 23 are restricted to the “north island”.
The cloud forest amphibians and reptiles constitute the most important herpetofaunal segment in Honduras, due to the prevalence of endemic and Nuclear Middle American-restricted species. This segment, however, is subject to severe environmental threats due to the actions of humans. Of the 334 species of amphibians and reptiles currently known from Honduras, 122 are known to be distributed in cloud forest habitats. Cloud forest habitats are found throughout the mountainous interior of Honduras. They are subject to a Highland Wet climate, which features annual precipitation of >1500 mm and a mean annual temperature of <18°C. Cloud forest vegetation falls into two Holdridge formations, the Lower Montane Wet Forest and Lower Montane Moist Forest. The Lower Montane Wet Forest formation generally occurs at elevations in excess of 1500 m, although it may occur as low as 1300+ m at some localities. The Lower Montane Moist Forest formation generally occurs at 1700+ m elevation. Of the 122 cloud forest species, 18 are salamanders, 38 are anurans, 27 are lizards, and 39 are snakes. Ninety-eight of these 122 species are distributed in the Lower Montane Wet Forest formation and 45 in the Lower Montane Moist Forest formation. Twenty species are distributed in both formations. The cloud forest species are distributed among restricted, widespread, and peripheral distributional categories. The restricted species range as a group in elevation from 1340 to 2700 m, the species that are widespread in at least one of the two cloud forest formations range as a group from sea level to 2744 m, and the peripheral species range as a group from sea level to 1980 m. The 122 cloud forest species exemplify ten broad distributional patterns ranging from species whose northern and southern range termini are in the United States (or Canada) and South America, respectively, to those species that are endemic to Honduras. The largest segment of the herpetofauna falls into the endemic category, with the next largest segment being restricted in distribution to Nuclear Middle America, but not endemic to Honduras. Cloud forest species are distributed among eight ecophysiographic areas, with the largest number being found in the Northwestern Highlands, followed by the North-Central Highlands and the Southwestern Highlands. The greatest significance of the Honduran herpetofauna lies in its 125 species that are either Honduran endemics or otherwise Nuclear Middle American-restricted species, of which 83 are distributed in the country’s cloud forests. This segment of the herpetofauna is seriously endangered as a consequence of exponentially increasing habitat destruction resulting from deforestation, even given the existence of several biotic reserves established in cloud forest. Other, less clearly evident environmental factors also appear to be implicated. As a consequence, slightly over half of these 83 species (50.6%) have populations that are in decline or that have disappeared from Honduran cloud forests. These species possess biological, conservational, and economic significance, all of which appear in danger of being lost.
The conservation status of the members of the Honduran herpetofauna is discussed. Based on current and projected future human population growth, it is posited that the entire herpetofauna is endangered. The known herpetofauna of Honduras currently consists of 334 species, including 117 amphibians and 217 reptiles (including six marine reptiles, which are not discussed in this paper). The greatest number of species occur at low and moderate elevations in lowland and/or mesic forest formations, in the Northern and Southern Cordilleras of the Serranía, and the ecophysiographic areas of the Caribbean coastal plain and foothills. Slightly more than one-third of the herpetofauna consists of endemic species or those otherwise restricted to Nuclear Middle America. Honduras is an area severely affected by amphibian population decline, with close to one-half of the amphibian fauna threatened, endangered, or extinct. The principal threats to the survival of members of the herpetofauna are uncontrolled human population growth and its corollaries, habitat alteration and destruction, pollution, pest and predator control, overhunting, and overexploitation. No Honduran amphibians or reptiles are entirely free of human impact. A gauge is used to estimate environmental vulnerability of amphibian species, using measures of extent of geographic range, extent of ecological distribution, and degree of specialization of reproductive mode. A similar gauge is developed for reptiles, using the first two measures for amphibian vulnerability, and a third scale for the degree of human persecution. Based on these gauges, amphibians and reptiles show an actual range of Environmental Vulnerability Scores (EVS) almost as broad as the theoretical range. Based on the actual EVS, both amphibian and reptilian species are divided into three categories of low, medium, and high vulnerability. There are 24 low vulnerability amphibians and 47 reptiles, 43 medium vulnerability amphibians and 111 reptiles, and 50 high vulnerability amphibians and 53 reptiles. Theoretical EVS values are assessed against available information on current population status of endemic and Nuclear Middle American taxa. Almost half (48.8%) of the endemic species of Honduran amphibians are already extinct or have populations that are in decline. Populations of 40.0% of the Nuclear Middle American amphibian species are extirpated or in decline. A little less than a third (27.0%) of the endemic reptiles are thought to have declining populations. Almost six of every ten (54.5%) of the Nuclear Middle American reptilian species are thought to have declining populations. EVS values provide a useful indicator of potential for endangerment, illustrating that the species whose populations are currently in decline or are extinct or extirpated have relatively high EVS. All high EVS species need to be monitored closely for changes in population status. A set of recommendations are offered, assuming that biotic reserves in Honduras can be safeguarded, that it is hoped will lead to a system of robust, healthy, and economically self-sustaining protected areas for the country’s herpetofauna. These recommendations will have to be enacted swiftly, however, due to unremitting pressure from human population growth and the resulting deforestation.
In morphological systems of the agglutinative type we sometimes encounter a nearly perfect one-to-one relation between form and function. Turkish inflectional morphology is, of course, the standard textbook example. Things seem to be quite different in systems of the flexive type. Declension in Contemporary Standard Russian (henceforth Russian, for short) may be cited as a typical example: We find, among other things, cumulative markers, “synonymous” endings (e.g., dative singular noun forms in -i, -e, or -u), and “homonymous” endings (e.g., -i, genitive, dative, and prepositional singular). True, some endings are more of an agglutinative nature, being bound to a specific case-number combination and applying across declensions, e.g., -am (dative plural, all nouns); and some cross the boundaries of word classes, e.g., -o, which serves as the nominative/accusative singular ending of neuter forms of pronouns (and adjectives) and as the nominative/accusative singular ending of (most) neuter nouns as well. Still, many observers have been struck by the impression that what we face here are rather uneconomic or even, so to speak, unnatural structures. But perhaps flexive systems are not as complicated as they seem. What seems to be uneconomic complexity may be, at least partially, an artifact of uneconomic descriptions.
The receptor tyrosine kinase ErbB2 (HER2) is overexpressed in multiple human tumors of epithelial origin. High ErbB2 expression is functionally involved in tumorigenesis and correlates with poor clinical prognosis. For immunotherapy of ErbB2 expressing tumors, we developed a strategy to supply the tumor cells with costimulatory activity. A bispecific fusion protein was constructed (BIg5), containing the IgV-like domain of huCD86, the CH2/CH3 domain of huIgG1 and the ErbB2-specific single chain antibody fragment scFv(FRP5). A similar fusion protein lacking the CD86 domain (Ig5) was used as a control. Upon binding of BIg5 to ErbB2 on tumor cells, these cells display CD86 on their surface and thus can deliver costimulatory signals for T-cell activation. In addition, NK cells could be activated by CD86 binding to CD28. BIg5 is secreted by eukaryotic cells as a homodimer with increased stability compared to monomers and possibly enhanced costimulatory activity due to crosslinking of CD28 on effector cells. By FACS analysis, specific binding of the scFv(FRP5) domain to ErbB2 as well as CD86 IgV binding to CTLA-4 could be demonstrated. Together with anti-CD3 antibody, BIg5 stimulates proliferation of human CD2-purified lymphocytes in vitro. After binding to ErbB2 on murine Renca-lacZ/ErbB2 tumor cells, about 50% of initially bound BIg5 is still present on the cell surface after 4 hours. For delivery of chimeric fusion proteins in vivo, we used syngeneic, stably transfected HC11 mammary epithelial cells continuously secreting the proteins. Inoculation of these bystander cells close to subcutaneously growing Renca-lacZ/ErbB2 tumors should provide a long-lasting source to achieve high local concentrations of BIg5 at the tumor site. In vivo HC11-BIg5 cells proved to be non-tumorigenic and secreted BIg5 for several weeks, causing a strong anti-BIg5 antibody response. Treatment of established Renca-lacZ/ErbB2 or ErbB2-negative Renca-lacZ tumors by peritumoral inoculation of either HC11-BIg5 or HC11-Ig5 cells led to rejection of all Renca-lacZ/ErbB2, but none of the Renca-lacZ tumors. HC11neo control cells had no effect on tumor growth. Rejection of ErbB2+ tumors led to long-term protection also against subsequent challenge with intravenously injected ErbB2- tumor cells. Intraperitoneal injection of bystander cells secreting the fusion proteins did not lead to tumor regression suggesting that high local concentrations at the tumor site are necessary to target ErbB2 on tumor cells and to overcome elimination of BIg5 or Ig5 by neutralizing antibodies. The CD86 IgV domain of BIg5 did not play a major role in the observed antitumoral immune response suggesting NK-cell mediated ADCC as the initial effector mechanism followed by activation of tumor specific T cells. Targeting of ErbB2 on tumor cells with antibody fusion proteins that interact specifically with the host immune system could be an efficient and specific approach for therapy of solid ErbB2+ tumors.
A version of this paper was originally written for a plenary session about "The Futures of Ethnography" at the 1998 EASA conference in Frankfurt/Main. In the preparation of the paper, I sent out some questions to my former fellow researchers by e-mail. I thank Douglas Anthony, Jan-Patrick Heiß, Alaine Hutson, Matthias Krings, and Brian Larkin for their answers.
The cytochrome bc1 complex or ubiquinol:cytochrome c oxidoreductase (QCR) catalyses electron transfer from ubiquinol to cytochrome c in respiration and photosynthesis coupled to a vectorial proton transport across the membrane, in which the enzyme resides. In both bacteria and eukaryotic organisms, QCR participates in supramolecular assembly of membrane proteins that comprise the respiratory or photosynthetic chain. In the present work, proton transfer pathways, substrate binding and the supramolecular assembly of the respiratory chain in yeast were probed by structure-based site-directed mutagenesis and characterization of the variants. Both active sites centre P, the place of quinol oxidation, and centre N, where quinone reduction takes place, lack direct access to the bulk solvent necessary for proton release and uptake. Based on the X-ray structure, proton transfer pathways were postulated. Analysis at centre P showed, that E272 and Y132 of cytochrome b are important for QCR catalysis as indicated by increased superoxide production and lowered Cyc1p reductase activity in these variants. Pre-steady state heme reduction kinetics in combination with stigmatellin resistance indicated that charge and length of the side chain at position 272 are crucial for efficient docking of the ISP to form the enzyme substrate complex and for electron bifurcation at centre P. Variants of Y312 and F129, both residues of cytochrome b, showed an increased Km indicating participation of these residues in coordination of ubiquinol or the possible intermediate semiquinone anion radical. F129 proved to be crucial for a functional Q-cycle as indicated by respiratory negative growth phenotype and a lowered H+/e- stoichiometry of F129 variants. At centre N, the postulated CL/K and E/R proton transfer pathways are located at opposite sites of the bound ubiquinone. Variants in the surface residues R218 (cytochrome b) and E52 (Qcr7) of the E/R pathway and E82 (Qcr7) of the CL/K pathway showed instability upon purification indicating an important role of these residues for QCR integrity. The slowed down centre N reduction kinetics in H85 (CL/K), R218 and N208 (both E/R) variant was attributed to a destabilised semiquinone anion consistent with the observed decreased sensitivity towards the site-specific inhibitor antimycin and an increased Km. Variants of residues of both pathway, E82Q and R218M, exhibited a decreased H+/e- stoichiometry indicating a crucial role of both residue for maintaining a working Q-cycle and supporting the proposed protonation of the substrate via the Cl/K and the E/R pathway. Long-range interaction between centre N and centre P were observed by altered reduction kinetics of the high potential chain and increased superoxide production in the centre N variants. The role of the cation-pi-interaction between F230 of Cyt1p and R19 of cytochrome c in binding of the redox carrier to QCR was analysed. In F230L hydrophobic interaction were partially lost as was deduced from the ionic strength dependence of Cyc1p reductase activity and Cycp1 binding, as detected by ionic strength sensitive Kd and Km for Cyc1p. The decreased enzymatic rate of F230W could be explained by a disturbed binding of Cyc1p to the variant enzyme. F230 may influence the heme mid point potential and thereby the electron transfer rate to Cyc1p. Reduction of Cobp via both centre P and centre N was disturbed suggesting an interaction between high and low potential chain. Supramolecular association between QCR and cytochrome c oxidase (COX) in yeast mitochondria was probed by affinity chromatography of a his-tagged QCR in the presence of the mild detergent digitonin. In comparison to purification with laurylmaltoside, the presence of both QCR and COX subunits was detected in the elution fractions by SDS-PAGE, Cyc1p reductase and TMPD oxidase activity assays and immunoblot analysis. The CL-dependent formation of the supercomplex between QCR and COX was analysed by replacement variants in the CL-binding site of QCR in CL containing and CL free environment. With an increasing number of replacements of the three lysines the CL-binding pocket supercomplex formation was not abolished, when CL is present as shown by BN-PAGE analysis. This was supported by the synergetic decrease in enzyme activity for both enzymes upon increased number of replacements. In the CL-free environment, no supracomplex formation was observed for a wildtype CL binding site. By replacements of two lysines in the CL-binding pocket, supercomplex formation could be recovered as revealed by BN-PAGE. This indicates, that CL may serve as a charge neutralizer for the lysines near the presumed interaction domain between complex III and complex IV. The obtained results for centre P provide new information of residues critical for stabilisation of ubiquinol and controlling electron short circuit reactions. The observations for centre N variants clearly support the proposed two proton transfer pathways and the role of the bound phospholipids in centre N kinetics. Variants in the Cyc1p binding site suggest a role for F230 both in Cyc1p binding and electron transfer. Clear interaction between the high and low potential chain in both Cyt1p and centre N variants strongly support long-range interactions in the complex. Studies on the supramolecular association of complex III and complex IV indicate a new role of Cl in stabilising a supracomplex.
During the past decade, processes associated with what is popularly though perhaps misleadingly known as globalization have come within the purview of anthropology. Migration and mobility ‐ and the footloose or even rootless social groups that they produce ‐ as well as the worldwide diffusion of commodities, media images, political ideas and practices, technologies and scientific knowledge today are on anthropology's research agenda. As a consequence, received notions about the ways in which culture relates to territory have been abandoned. The term transnationalisation captures cultural processes that stream across the borders of nation states. Anthropologists have been forced to revise the notion that transnationalisation would inevitably bring about a culturally homogenized world. Instead, we are witnessing a surge of greatly increasing cultural diversity. New cultural forms grow out of historically situated articulations of the local and the global. Rather than left-over relics from traditional orders, these are decidedly modern, yet far from uniform. The essay engages the idea of the pluralization of modernities, explores its potential for interdisciplinary research agendas, and also inquires into problematic assumptions underlying this new theoretical concept.
A small electrostatic storage ring is the central machine of the Frankfurt Ion Storage Experiments (FIRE) which will be built at the new Stern-Gerlach Center of Frankfurt University. As a true multiuser, multipurpose facility with ion energies up to 50 keV, it will allow new methods to analyze complex many-particle systems from atoms to very large biomolecules. With envisaged storage times of some seconds and beam emittances in the order of a few mm mrad, measurements with up to 6 orders of magnitude better resolutions as compared to single-pass experiments become possible. In comparison to earlier designs, the ring lattice was modified in many details: Problems in earlier designs were related to, e.g., the detection of light particles and highly charged ions with different charge states. Therefore, the deflectors were redesigned completely, allowing a more flexible positioning of the diagnostics. Here, after an introduction to the concept of electrostatic machines, an overview of the planned FIRE is given and the ring lattice and elements are described in detail.
The genetic variability of hepatitis B virus (HBV) represents a challenge for the sensitivity of immunodiagnosis, especially for the detection of surface antigen (HBsAg). There are two types of variants of HBV. Naturally occurring variants are the results of random changes selected over years of population pressure. These variants include HBV genotypes and unusual sequences, which may be poorly detected by immunoassays. The selected variants are mutants that arise in individuals under medically (vaccine, hepatitis B immune globulin and antiviral therapy) or naturally (chronic hepatitis B) induced immune pressure. HBV S-gene mutants have been identified in successfully immunized people worldwide. Based on the assumption that current vaccines containing S protein do not cross-protect against S gene mutants, a mathematical model predicts the disappearance of wild-type HBV in areas with HBsAg endemicity and the emergence of S gene mutants in approximately 100 years as a consequence of universal HBV vaccination. Mutant viruses may escape detection by commercial HBsAg kits. There are several reports on HBsAg negative carriers (HBVDNA positive) of S gene mutants with immunosilent infection or ‘‘unusual’’ serologic constellations. Although S gene mutants have been found to be associated with a more severe clinical course of HBV infection and hepatocellular carcinoma, the clinical significance of the genetic variability of HBV genotypes and HBsAg mutants needs to be further investigated. Detection of HBsAg needs to be improved by the introduction of new HBsAg assays able to recognize S gene mutants described so far and with a lower detection threshold than current immunoassays in order to detect smallest amounts of HBsAg in low-level carriers. There is also a need for more complete epidemiological data on the prevalence of HBsAg mutants in Western Europe and assays for the (differential) screening of mutants need to be developed and evaluated.
We study the returns the venture capital and private equity investment from 221 venture capital and private equity funds that are part of 72 venture capital and private equity firms, 5040 entrepreneurial firms (3826 venture capital and 1214 private equity), and spanning 32 years (1971 - 2003) and 39 countries from North and South America, Europe and Asia. We make use of four main categories of variables to proxy for value-added activities and risks that explain venture capital and private equity returns: market and legal environment, VC characteristics, entrepreneurial firm characteristics, and the characteristics and structure of the investment. We show Heckman sample selection issues in regards to both unrealized and partially realized investments are important to consider for analysing the determinants of realized returns. We further compare the actual unrealized returns, as reported to investment managers, to the predicted unrealized returns based on the estimates of realized returns from the sample selection models. We show there exists significant systematic biases in the reporting of unrealized investments to institutional investors depending on the level of the earnings aggressiveness and disclosure indices in a country, as well as proxies for the degree of information asymmetry between investment managers and venture capital and private equity fund managers. Klassifikation: G24, G28, G31, G32, G35
The fires of January 2003 burnt much of the treeless high mountain country of Victoria, New South Wales and the Australian Capital Territory, and were the first extensive conflagration of this area since 1939. For this reason there are remarkably few studies of the response of alpine plants and vegetation to fire. A flora survey of treeless subalpine vegetation in the Kosciuszko area in late 2002 sampled 215 sites. Of the 119 sites that were burnt, 60 were relocated and re-sampled in late 2003 to assess the mode and extent of regeneration in a range of treeless plant communities. Twenty-four species (including 3 exotics) were recorded only in the pre-fire sampling. Fifty species (including 18 exotics) were recorded only in the post-fire sampling. One species, Chenopodium erosum, had not previously been recorded in Kosciuszko National Park, and is believed to be the first native chenopod recorded in alpine vegetation in Australia. There was no significant difference in mean number of species per quadrat between pre-fire and post-fire quadrats. The average number of weeds per quadrat was, however, significantly greater post-fire. Most of this difference was attributable to the significantly greater number of weeds per quadrat in bog vegetation after the fire. Of the 290 species recorded, 111 species regenerated from seed, 197 species regenerated from resprouting organs (roots, tubers and/or basal stems) and 49 species regenerated from both seed and resprouts. Based on the regeneration observed, most plant communities will return naturally to their pre-fire species composition and cover over a period between a few years and a few decades. Major exceptions will be those communities where the ‘keystone’ species appear to have been lost at least at a local scale. Principal amongst these are bog communities that incorporated significant biomass of Sphagnum cristatum pre-fire, Podocarpus lawrencei shrublands and Celmisia costiniana closed herbfields. Consideration might be given to augmenting their recovery. It will be important to exclude fire from these communities until their recovery is complete.
Respiratory chain complex I contains 8-9 iron-sulfur clusters. In several cases, the assignment of these clusters to subunits and binding motifs is still ambiguous. To test the proposed ligation of the tetranuclear iron-sulfur cluster N5 of respiratory chain complex I, we replaced the conserved histidine 129 in the 75-kDa subunit from Yarrowia lipolytica with alanine. In the mutant strain, reduced amounts of fully assembled but destabilized complex I could be detected. Deamino-NADH: ubiquinone oxidoreductase activity was abolished completely by the mutation. However, EPR spectroscopic analysis of mutant complex I exhibited an unchanged cluster N5 signal, excluding histidine 129 as a cluster N5 ligand.
This paper reports the results of a corpus investigation on case conflicts in German argument free relative constructions. We investigate how corpus frequencies reflect the relative markedness of free relative and correlative constructions, the relative markedness of different case conflict configurations, and the relative markedness of different conflict resolution strategies. Section 1 introduces the conception of markedness as used in Optimality Theory. Section 2 introduces the facts about German free relative clauses, and section 3 presents the results of the corpus study. By and large, markedness and frequency go hand in hand. However, configurations at the highest end of the markedness scale rarely show up in corpus data, and for the configuration at the lowest end we found an unexpected outcome: the more marked structure is preferred.
Weak function word shift
(2004)
The fact that object shift only affects weak pronouns in mainland Scandinavian is seen as an instance of a more general observation that can be made in all Germanic languages: weak function words tend to avoid the edges of larger prosodic domains. This generalisation has been formulated within Optimality Theory in terms of alignment constraints on prosodic structure by Selkirk (1996) in explaining thedistribution of prosodically strong and weak forms of English functionwords, especially modal verbs, prepositions and pronouns. But a purely phonological account fails to integrate the syntactic licensing conditions for object shift in an appropriate way. The standard semantico-syntactic accounts of object shift, onthe other hand, fail to explain why it is only weak pronouns that undergo object shift. This paper develops an Optimality theoretic model of the syntax-phonology interface which is based on the interaction of syntactic and prosodic factors. The account can successfully be applied to further related phenomena in English and German.
German dialects vary in which of the possible orders of the verbs in a 3-verb cluster they allow. In a still ongoing empirical investigation that I am undertaking together with Tanja Schmid, University of Stuttgart (Schmid and Vogel (2004)) we already found that each of the six logically possible permutations of the 3-verb cluster in (1) can be found in German dialects.
The aim of this paper is the exploration of an optimality theoretic architecture for syntax that is guided by the concept of "correspondence": syntax is understood as the mechanism of "translating" underlying representations into a surface form. In minimalism, this surface form is called "Phonological Form" (PF). Both semantic and abstract syntactic information are reflected by the surface form. The empirical domain where this architecture is tested are minimal link effects, especially in the case of "wh"-movement. The OT constraints require the surface form to reflect the underlying semantic and syntactic representations as maximally as possible. The means by which underlying relations and properties are encoded are precedence, adjacency, surface morphology and prosodic structure. Information that is not encoded in one of these ways remains unexpressed, and gets lost unless it is recoverable via the context. Different kinds of information are often expressed by the same means. The resulting conflicts are resolved by the relative ranking of the relevant correspondence constraints.
The argument that I tried to elaborate on in this paper is that the conceptual problem behind the traditional competence/performance distinction does not go away, even if we abandon its original Chomskyan formulation. It returns as the question about the relation between the model of the grammar and the results of empirical investigations – the question of empirical verification The theoretical concept of markedness is argued to be an ideal correlate of gradience. Optimality Theory, being based on markedness, is a promising framework for the task of bridging the gap between model and empirical world. However, this task not only requires a model of grammar, but also a theory of the methods that are chosen in empirical investigations and how their results are interpreted, and a theory of how to derive predictions for these particular empirical investigations from the model. Stochastic Optimality Theory is one possible formulation of a proposal that derives empirical predictions from an OT model. However, I hope to have shown that it is not enough to take frequency distributions and relative acceptabilities at face value, and simply construe some Stochastic OT model that fits the facts. These facts first of all need to be interpreted, and those factors that the grammar has to account for must be sorted out from those about which grammar should have nothing to say. This task, to my mind, is more complicated than the picture that a simplistic application of (not only) Stochastic OT might draw.
To model the pied piping in interrogative and exclamative clauses Ginzburg & Sag (2000) proposes a nonlocal head-driven treatment, thus emphasizing the resemblances with extraction. This treatment has a number of drawbacks: it relies on poorly motivated lexical rules and nonbranching phrase structure rules, it makes false predictions about pied piping in PPs, and it presupposes an implausible structure for NPs with predeterminers. To solve these problems I propose an alternative in which pied piping is treated as a local functor-driven dependency. Technically, the WH feature is integrated in the CATEGORY objects, and the propagation of its values is modeled by constraints which are independently needed for the treatment of other phenomena.
Hybrid robust deep and shallow semantic processing for creativity support in document production
(2004)
The research performed in the DeepThought project (http://www.project-deepthought.net) aims at demonstrating the potential of deep linguistic processing if added to existing shallow methods that ensure robustness. Classical information retrieval is extended by high precision concept indexing and relation detection. We use this approach to demonstrate the feasibility of three ambitious applications, one of which is a tool for creativity support in document production and collective brainstorming. This application is described in detail in this paper. Common to all three applications, and the basis for their development is a platform for integrated linguistic processing. This platform is based on a generic software architecture that combines multiple NLP components and on robust minimal recursive semantics (RMRS) as a uniform representation language.
Transforming constituent-based annotation into dependency-based annotation has been shown to work for different treebanks and annotation schemes (e.g. Lin (1995) has transformed the Penn treebank, and Kübler and Telljohann (2002) the Tübinger Baumbank des Deutschen (TüBa-D/Z)). These ventures are usually triggered by the conflict between theory-neutral annotation, that targets most needs of a wider audience, and theory-specific annotation, that provides more fine-grained information for a smaller audience. As a compromise, it has been pointed out that treebanks can be designed to support more than one theory from the start (Nivre, 2003). We argue that information can also be added to an existing annotation scheme so that it supports additional theory-specific annotations. We also argue that such a transformation is useful for improving and extending the original annotation scheme with respect to both ambiguous annotation and annotation errors. We show this by analysing problems that arise when generating dependency information from the constituent-based TüBa-D/Z.
The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated genetically modified NK-92 cells expressing chimeric antigen receptors specific either for the tumor-associated ErbB2 (HER2/neu) antigen or the human Epithelial Cell Adhesion Molecule (Ep-CAM). Both antigens are overexpressed by many tumors of epithelial origin. The chimeric antigen receptors consist of either the ErbB2 specific scFv(FRP5) antibody fragment or the Ep-CAM specific scFv(MOC31), a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta or NK-92-scFv(MOC31)-zeta cells express high levels of the fusion proteins on the cell surface as determined by FACS analysis. In europium release assays no difference in cytotoxic activity of NK-92 and transduced NK-92 cells towards ErbB2 or Ep-CAM negative targets was found. However, even at low effector to target ratios transduced NK-92 cells specifically and efficiently lysed established ErbB2 or Ep-CAM expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. Similarly, ErbB2-positive primary breast cancer cells isolated from pleural effusions of patients with recurrent disease were selectively killed by NK-92-scFv(FRP5)-zeta. In an in vivo model in immunodeficient mice treatment with retargeted NK-92-scFv(FRP5)-zeta, but not parental NK-92 cells resulted in markedly delayed growth of ErbB2 transformed cancer cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved, and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2 and Ep-CAM expressing malignancies. This therapeutic approach might be applicable for a large variety of different cancers where suitable cell surface antigens have been identified.
Religious Anthropology studies the origins, evolution and functions of religions. The discipline researching religious beliefs and rituals comparatively with cross-cultural perspectives tries to enlighten the belief world of the mankind. Religion, as a term, can be defined as "believing as well as worshipping to the supernatural powers and/or beings by the individual who are emotionally or consciously devoted to them" (Örnek 1988: 127). There have been a number of theories so far which try to bring an explanation to the origins and the evolution of religion. In these theories, Fetishism, cults of nature, animism, Totemism, dynamism, Manism, magic, polytheism, monotheism as well as certain physiological phenomena have been particularized as evolutionary stages and forms of belief (Evans-Pritchard 1998: 124). All of these theories have the perspective of so called "progressive" and / or "unilinear" that maintain a religion which has reached ongoing stages and that communities which have developed from primitiveness to civilization. They argue that there has only been one single line of progress, and all of the communities are bound to go through the same evolutionary stages.
Much has been written on the success of the Indian software industry, enumerating systemic factors like first-class higher education and research institutions, both public and private; low labour costs, stimulating (state) policies etc. However, although most studies analyzing the 'Indian' software industry cover essentially the South (and West) Indian clusters, this issue has not been tackled explicitly. This paper supplements the economic geography explanations mentioned above with the additional factor social capital, which is not only important within the region, but also in transnational (ethnic) networks linking Indian software clusters with the Silicon Valley. In other words, spatial proximity is complemented with cultural proximity, thereby, extending the system of innovation. The main hypothesis is that some Indian regions are more apt to economic development and innovation due to their higher affinity to education and learning, as well as, their more general openness, which has been a main finding of my interviews. In addition, the transnational networks of Silicon Valley Indians seem to be dominated by South Indians, thus, corroborating the regional clustering of the Indian software industry. JEL Classifications: O30, R12, Z13, L86
This paper aims to analyze the impact of different types of venture capitalists on the performance of their portfolio firms around and after the IPO. We thereby investigate the hypothesis that different governance structures, objectives and track record of different types of VCs have a significant impact on their respective IPOs. We explore this hypothesis by using a data set embracing all IPOs which occurred on Germany's Neuer Markt. Our main finding is that significant differences among the different VCs exist. Firms backed by independent VCs perform significantly better two years after the IPO compared to all other IPOs and their share prices fluctuate less than those of their counterparts in this period of time. Obviously, independent VCs, which concentrated mainly on growth stocks (low book-to-market ratio) and large firms (high market value), were able to add value by leading to less post-IPO idiosyncratic risk and more return (after controlling for all other effects). On the contrary, firms backed by public VCs (being small and having a high book-to-market ratio) showed relative underperformance. Klassifikation: G10, G14, G24 . 29th January 2004 .
This paper sets out to analyze the influence of different types of venture capitalists on the performance of their portfolio firms around and after IPO. We investigate the hypothesis that different governance structures, objectives, and track records of different types of VCs have a significant impact on their respective IPOs. We explore this hypothesis using a data set embracing all IPOs that have occurred on Germany's Neuer Markt. Our main finding is that significant differences among the different VCs exist. Firms backed by independent VCs perform significantly better two years after IPO as compared to all other IPOs, and their share prices fluctuate less than those of their counterparts in this period of time. On the contrary, firms backed by public VCs show relative underperformance. The fact that this could occur implies that market participants did not correctly assess the role played by different types of VCs.
As the exilic experience, initiated in 587 B.C.E., continued over millennia, no one has been able to settle the question of what it means to be a diaspora Jew. Are those who actively participate in non-Jewish life still in a position to claim the heritage of Israel? And what about Jews who actively seek assimilation and renounce their roots altogether: are they still Jews in spite of themselves? Authors, from Joseph Roth to Sholom Aleichem to Chaim Potok, have tried to deal with this issue in light of different diaspora circumstances. One of the most recent perspectives on Jewish identity comes to us through "Sunshine", a powerful film by the Hungarian director Istvan Szabó (1999). Szabó, who wrote the screenplay with Israel Horowitz, tells the story of several generations in one Hungarian Jewish family: the Sonnenscheins. Living at the turn of the twentieth century, the patriarch of the Sonnenschein clan is Emmanuel, a successful distiller who seems to have found a balance between the two exilic extremes: neither complete assimilation, nor a retreat from gentile society.
This paper focuses on aspects of the licensing of adverbial noun phrases (AdvNPs) in the HPSG grammar framework. In the first part, empirical issues will be discussed. A number of AdvNPs will be examined with respect to various linguistic phenomena in order to find out to what extent AdvNPs share syntactic and semantic properties with non-adverbial NPs.Based on empirical generalizations, a lexical constraint for licensing both AdvNPs and non-adverbial NPs will be provided. Further on, problems of structural licensing of phrases containing AdvNPs that arise within the standard HPSG framework of Pollard and Sag (1994) will be pointed out, and a possible solution will be proposed. The objective is to provide a constraint-based treatment of NPs which describes non-redundantly both their adverbial and non-adverbial usages. The analysis proposed in this paper applies lexical and phrasal implicational constraints and does not require any radical modifications or extensions of the standard HPSG geometry of Pollard and Sag (1994).
Im Rahmen dieser Dissertation wurde die Photophysik und die elektronische Struktur einer Klasse neuartiger Donator-Akzeptor-Ladungstransfer-Komplexe untersucht. Im Wesentlichen bestehen diese Verbindungen aus einem Ferrocen-Donator (Fc) und organischen Akzeptoren, die über B-N-Bindungen verbrückt sind, welche sich bei dieser Art von makromolekularen Systemen spontan bilden. Zentraler Gegenstand dieser Arbeit war die spektroskopische Untersuchung des Metall-zu-Ligand-Ladungstransfers (engl. Abkürzung: MLCT) im elektronischen Anregungszustand dieser kationischen Komplexverbindungen, die im Weiteren als „Fc-B-bpy“-Verbindungen bezeichnet werden. Die vorliegende Arbeit analysiert eine Vielzahl miteinander verwandter Fc-B-bpy-Derivate. Die Arbeit ist gegliedert in 1.) die Analyse der Absorptionsspektren vom UV- bis zum nahen Infrarot-Spektralbereich (250-1000 nm) von Lösungen, dotierten Polymer-Dünnfilmen und Einkristallen, 2.) die zeitaufgelöste optische Spektroskopie des angeregten Zustands auf der Pikosekunden-Zeitskala, 3.) die Analyse elektrochemischer Messungen an Lösungen, und 4.) die Auswertung quantenchemischer Berechnungen. Für die zeitaufgelösten Messungen wurde ein komplexes optisches Spektroskopie-System mit breitbandigen Femtosekunden-Pulsen sowie den entsprechenden zeitaufgelösten Detektionsmethoden (spektral gefilterte Weißlicht-Detektion) aufgebaut. Die Ergebnisse dieser Arbeit beweisen die Existenz eines MLCT-Übergangs mit fast vollständigem Übergang eines Fc-Donator-Elektrons zum B-bpy-Akzeptor bei optischer Anregung. Die vergleichenden Untersuchungen der spektroskopischen Eigenschaften verschiedener Derivate liefern wichtige Information für die Entwicklung neuartiger Derivate, einschließlich verwandter Polymere, mit verbesserten spektroskopischen Eigenschaften. Es wurden transiente Absorptionsmessungen bestimmter Fc-B-bpy-Derivate in Lösung nach gepulster Anregung der MLCT-Bande (bei 500 nm) über einen Zeitbereich von 0,1-1000 ps und einen Wellenlängenbereich von 460-760 nm vorgenommen. Aus den Messergebnissen geht hervor, dass die Relaxation aus dem angeregten MLCT-Zustand in den Grundzustand auf verschiedenen Zeitskalen geschehen kann, welche im Bereich zwischen ~18 und 900 ps liegen. Ein Vergleich verschiedener Derivate mit unterschiedlicher Flexibilität in der Konformation zeigt, dass die Starrheit der Bindungen zwischen Donatoren und Akzeptoren ein wesentlicher Faktor für die Lebensdauer des angeregten Zustands ist. Wenn die Akzeptorgruppen relativ frei rotieren können, ist es der Verbindung möglich, eine Geometrie einzunehmen, von der aus ein effizienter, strahlungsfreier Übergang in den Grundzustand erfolgen kann. Dieser Befund zeigt einen Weg auf, wie neuartige, verwandte Verbindungen mit größerer Lebensdauer das angeregten Zustands synthetisiert werden können, indem darauf geachtet wird, daß eine starre molekulare Architektur zwischen Donator und Akzeptor verwirklicht wird.
In the wake of Kayne's Antisymmetry Hypothesis and Linear Correspondence Axiom (LCA), there has been much fruitful research attempting to adjust syntactic analyses to those permitted by Kayne's restrictive system. In doing so, analyses which at first seem counter-intuitive may tum out to provide solutions to old problems. Two cases in point are the analysis of Malagasy involving extensive Remnant Movement [henceforth RM1 described in Rackowski & Travis (2000), Pearson (2001), and elsewhere; on the one hand, and the analysis of Hungarian and Dutch verbal clusters in Koopman & Szabolcsi (2000) [henceforth R&T, Pearson, and K&Sz].
The original motivation (in part) for examining L&Sz and subsequently R&T was that it is the extensive use of iterated RM which increases the computational complexity of languages generatable in Stabler's "Strict Minimalist Grammar" formalism over that of context-free grammars. It has also been noted that allowing extraction from complex specifiers created by Merge (as opposed to Move) increases the level of complexity even further (lens Michaelis, p.e.). Both R&T and K&Sz make extensive use of RM; R&T allow extraction from complex specifiers, while K&Sz do not. Although the specifiers in both cases are created by Move, not Merge, we nevertheless feel that there is enough intrinsic linguistic interest in trying to limit extraction possibilities to pursue the comparison of these two systems with regard to this point.
The purpose of this paper is to describe the TüBa-D/Z treebank of written German and to compare it to the independently developed TIGER treebank (Brants et al., 2002). Both treebanks, TIGER and TüBa-D/Z, use an annotation framework that is based on phrase structure grammar and that is enhanced by a level of predicate-argument structure. The comparison between the annotation schemes of the two treebanks focuses on the different treatments of free word order and discontinuous constituents in German as well as on differences in phrase-internal annotation.
Relative clauses (RCs) in Persian are head-modifying constituents, all typically introduced by the invariant complementizer ke. Persian RCs are Unbounded Dependency Constructions (UDCs), containing either a gap or a resumptive pronoun (RP). In some positions only gaps are allowed, and in other positions only RPs. There are also some positions where both gaps and RPs are alternatively allowed. Illustrating the striking similarities between Persian gaps and RPs, I will provide an HPSG unified approach to take care of the dependency between the licensing structure and the gap/RP with a single mechanism, using only the SLASH feature. Similar to Pollard and Sag s (1994) approach to the bottom of the dependency, I will assume a special sign at the bottom. However, my sign may have a nonempty PHON value. I will introduce a feature called GAPTYPE which is a NONLOCAL feature whose value can be either trace or rp. I will introduce two constraints to capture the pattern of distribution of RPs and traces. At the top of the dependency, I will bind the nonempty SLASH at the complementizer point. I will propose a lexical entry for the complementizer ke that will account for the binding of SLASH by the feature BIND, which has a nonempty set as value.
A compound matrix
(2004)
This paper presents a suplement to the Grammar Matrix, namely what I call a Compound Matrix ; in reality, it is not a matrix, since the type file includes a fully specified cross-linguistic inventory of compound types. The idea is that the grammar writer can comment out the ungrammatical types for his or her own language. The theory behind the typology is presented here in a bottom-up fashion, from the basic assumptions to the actual linguistic types.
Negation and negative indefinites raise problems for the principle of compositionality of meaning, because we find both double and single negation readings in natural languages. De Swart and Sag (2002) solve the compositionality problem in a polyadic quantifier framework. The syntax-semantics interface exploits an extension of the Cooper storage mechanism that HPSG uses to account for scope ambiguities. In de Swart and Sag (2002), all negative quantifiers are collected into an N-store, and are interpreted by means of iteration (double negation) or resumption (negative concord) upon retrieval. This puts the ambiguity between single and double negation readings in the grammar, rather than in the lexical items. This paper extends the earlier analysis with a typology of negation and negative indefinites using bi-directional optimality theory (OT). The constraints defined are universal, but their ranking varies from one language to the next. In negative concord languages, the functional motivation for the marking of 'negative variables' wins out, so we use n-words. Double negation languages value first-order iteration, so we use plain indefinites or negative polarity items within the scope of negation. The bi-directional set-up is essential, for syntactic and semantic variation go hand in hand.
Stability, unfolding and refolding of the outer membrane protein porin from Paracoccus denitrificans was investigated using genetic and spectroscopic methods. Structural and functional activity studies on wild type and mutant porins: The site-directed mutants were constructed based on conserved residues and evidences on the role of certain amino acids from previous studies with OmpF. Secondary structure analysis of wild type and mutants E81Q, W74C, E81Q/D148N, E81Q/D148N/W74C by FTIR and CD spectroscopy are in line with the fact that porins are predominantly ß-sheet structure. The functional activity studies by black lipid bilayer techniques showed that the wild type and mutants W74C, E81Q/D148N, E81Q/D148N/W74C have a conductance of 3.25 nS. For mutant E81Q conductance of 1.25nS was more predominant over 3.25 nS. The activity of the mutants was observed to be far less than the wild type. This indicates that structural similarities does not implies similar functional activity. Thermal stability analysis of porin in detergent micelles and reconstituted into liposomes: Thermal stability analysis of wild type and mutants in detergent micelles showed changes in secondary and quaternary structure. It was found that wild type porin unfolds into aggregated structure with a high transition temperature of 86.2 °C. For mutants E81Q, W74C, E81Q/D148N the transition temperature was found to be 84.2 °C, 80.3 °C and 80.2 °C respectively. Functional activity assays at high temperatures revealed that the protein tends to loose its activity on heating up to 50 °C. This shows that structural stability does not imply functionality in the case of porins. Thermal stability analysis of porin reconstituted into liposomes showed that there was no change in the secondary and quaternary structure of the protein up to 100 °C, revealing that the protein becomes more thermostable when it is reconstituted into liposomes. Refolding of aggregated porin: This study shows that disaggregation of ß-sheet membrane protein porin is possible by changing its chemical and thermodynamic parameters. An increase of the solution pH to 12 or above results in opening up of the aggregated protein into unordered structure, as observed by FTIR and CD spectroscopy. This unordered structure could be refolded into native-like structure forming trimers. The secondary structure of the refolded protein deviated slightly from the native one. The thermal stability analysis of the native-like refolded proteins showed that the unfolding pattern is entirely different when compared to the native porins. pH dependent unfolding of porin: Thermal stability of porin at different pH values showed that the protein is stable in a pH range of 1-11. At pH 12 and above the protein unfolds into unordered structure instead of aggregating. The high pH unfolding of porin is a reversible process. The secondary structure of the refolded protein varied slightly from the native-one. Whereas thermal stability was entirely different. This shows that even though the unfolding of porin at high pH is reversible, it results in changes in local interaction between the amino acids resulting in a difference in stability. Unfolding in presence of urea and guanidinium hydrochloride (GuHCl): Denaturation of porin in the presence of chemical denaturants like urea and GuHCl showed that porin unfold into unordered structure. The unfolding is a reversible process. Unfolded protein was refolded into detergent micelles and liposomes. Refolding into detergent micelles was faster compared to refolding into liposomes, as seen by kinetic gel shift assays. The refolding into liposomes showed the presence of intermediates similar to those reported for OmpF. This study shows the difference in thermal stability of the outer membrane protein porin from Paracoccus denitrificans in detergent micelles and native-like liposomes. It suggests various unfolding pathways, which can be further investigated for unfolding and refolding kinetics. This report also suggests that it is possible to refold a heat-aggregated protein.
To be published in J. Phys. G - Proceedings of SQM 2004 : We review the results from the various hydrodynamical and transport models on the collective flow observables from AGS to RHIC energies. A critical discussion of the present status of the CERN experiments on hadron collective flow is given. We emphasize the importance of the flow excitation function from 1 to 50 A.GeV: here the hydrodynamic model has predicted the collapse of the v2-flow ~ 10 A.GeV; at 40 A.GeV it has been recently observed by the NA49 collaboration. Since hadronic rescattering models predict much larger flow than observed at this energy we interpret this observation as evidence for a first order phase transition at high baryon density r b. Moreover, the connection of the elliptic flow v2 to jet suppression is examined. It is proven experimentally that the collective flow is not faked by minijet fragmentation. Additionally, detailed transport studies show that the away-side jet suppression can only partially (< 50%) be due to hadronic rescattering. Furthermore, the change in sign of v1, v2 closer to beam rapidity is related to the occurence of a high density first order phase transition in the RHIC data at 62.5, 130 and 200 A.GeV.
A critical discussion of the present status of the CERN experiments on charm dynamics and hadron collective flow is given. We emphasize the importance of the flow excitation function from 1 to 50 A·GeV: here the hydrodynamic model has predicted the collapse of the v1-flow and of the v2-flow at 10 A·GeV; at 40 A·GeV it has been recently observed by the NA49 collaboration. Since hadronic rescattering models predict much larger flow than observed at this energy we interpret this observation as potential evidence for a first order phase transition at high baryon density B. A detailed discussion of the collective flow as a barometer for the equation of state (EoS) of hot dense matter at RHIC follows. Here, hadronic rescattering models can explain < 30% of the observed elliptic flow, v2, for pT > 2 GeV/c. This is interpreted as evidence for the production of superdense matter at RHIC with initial pressure far above hadronic pressure, p > 1 GeV/fm3. We suggest that the fluctuations in the flow, v1 and v2, should be measured in future since ideal hydrodynamics predicts that they are larger than 50 % due to initial state fluctuations. Furthermore, the QGP coe cient of viscosity may be determined experimentally from the fluctuations observed. The connection of v2 to jet suppression is examined. It is proven experimentally that the collective flow is not faked by minijet fragmentation. Additionally, detailed transport studies show that the awayside jet suppression can only partially (< 50%) be due to hadronic rescattering. We, finally, propose upgrades and second generation experiments at RHIC which inspect the first order phase transition in the fragmentation region, i.e. at µB 400 MeV (y 4 5), where the collapse of the proton flow should be seen in analogy to the 40 A·GeV data. The study of Jet-Wake-riding potentials and Bow shocks caused by jets in the QGP formed at RHIC can give further information on the equation of state (EoS) and transport coe cients of the Quark Gluon Plasma (QGP).
Assessing enhanced knowledge discovery systems (eKDSs) constitutes an intricate issue that is understood merely to a certain extent by now. Based upon an analysis of why it is difficult to formally evaluate eKDSs, it is argued for a change of perspective: eKDSs should be understood as intelligent tools for qualitative analysis that support, rather than substitute, the user in the exploration of the data; a qualitative gap will be identified as the main reason why the evaluation of enhanced knowledge discovery systems is difficult. In order to deal with this problem, the construction of a best practice model for eKDSs is advocated. Based on a brief recapitulation of similar work on spoken language dialogue systems, first steps towards achieving this goal are performed, and directions of future research are outlined.
In the last decade, much effort went into the design of robust third-person pronominal anaphor resolution algorithms. Typical approaches are reported to achieve an accuracy of 60-85%. Recent research addresses the question of how to deal with the remaining difficult-toresolve anaphors. Lappin (2004) proposes a sequenced model of anaphor resolution according to which a cascade of processing modules employing knowledge and inferencing techniques of increasing complexity should be applied. The individual modules should only deal with and, hence, recognize the subset of anaphors for which they are competent. It will be shown that the problem of focusing on the competence cases is equivalent to the problem of giving precision precedence over recall. Three systems for high precision robust knowledge-poor anaphor resolution will be designed and compared: a ruleset-based approach, a salience threshold approach, and a machine-learning-based approach. According to corpus-based evaluation, there is no unique best approach. Which approach scores highest depends upon type of pronominal anaphor as well as upon text genre.
Stable supercomplexes of bacterial respiratory chain complexes III (ubiquinol:cytochrome c oxidoreductase) and IV (cytochrome c oxidase) have been isolated as early as 1985 (Berry, E. A., and Trumpower, B. L. (1985) J. Biol. Chem. 260, 2458-2467). However, these assemblies did not comprise complex I (NADH:ubiquinone oxidoreductase). Using the mild detergent digitonin for solubilization of Paracoccus denitrificans membranes we could isolate NADH oxidase, assembled from complexes I, III, and IV in a 1:4:4 stoichiometry. This is the first chromatographic isolation of a complete “respirasome.” Inactivation of the gene for tightly bound cytochrome c552 did not prevent formation of this supercomplex, indicating that this electron carrier protein is not essential for structurally linking complexes III and IV. Complex I activity was also found in the membranes of mutant strains lacking complexes III or IV. However, no assembled complex I but only dissociated subunits were observed following the same protocols used for electrophoretic separation or chromatographic isolation of the supercomplex from the wild-type strain. This indicates that the P. denitrificans complex I is stabilized by assembly into the NADH oxidase supercomplex. In addition to substrate channeling, structural stabilization of a membrane protein complex thus appears as one of the major functions of respiratory chain supercomplexes.
The paper explains the absence of resultative secondary predication in Russian as arising from a conflict of inferential interpretations. It formalises the framework necessary to express this proposal in terms of abductive reasoning with Poole systems in Gricean contexts. The conflict is shown to arise for default rules regulating alternative realisation of verb-internally specified consequent states. The paper thus indicates that typological variation may be due not only to different parameter values but to general inferential properties of the syntax-semantics mapping. The proposed theory also contradicts some widespread proposals that the absence of resultative secondary predication is due to the absence of some particular language feature.
Transmembrane proteins play crucial roles in biological systems as active or passive channels and receptors. Experimentally only few structures could be determined so far. Gaining structural insights enables besides a general understanding of biological mechanisms also further processing such as in drug design. Due to the lack of experimental data, reliable theoretical predictions would be of high value. However, for the same reason, missing data, the knowledge-based class of prediction methods that is well established for soluble proteins can not be applied. The goal of predicting transmembrane protein structures with ab initio methods demands locating the free energy minimum. Main difficulties here are, first, the computational costs of explicitly calculating all involved interactions and, second, providing an algorithm that is capable of finding the minimum within an extremely complex and rugged energy landscape. We have developed promising energy functions that describe the interactions of amino acids on a residue level, reducing computational costs while still containing most information on the atomistic level. We have also found a way to describe the interaction of the residues with its surrounding in a realistic manner by distinguishing residues exposed to the environment from those buried within helices using a sphere algorithm. The sphere algorithm can also be applied for a different purpose: one can measure how densely sidechains are packed for certain helical conformations, and thereby get an estimate of the sidechain entropy. In addition, overcrowding effects can be identified which are not well-described by the energy functions due to the pairwise calculation. To determine the absolute free energy minimum, we assume the helices to be located on an equidistance grid with slightly larger distances than to be expected. Optimizing the helices on the grid provides a starting point that should enable common minimizing algorithms, gradient-based or not, to find the absolute minimum beyond the grid. To simulate the dynamics of the helices on large time scales, we split them into rigid body dynamics and internal dynamics in terms of the dihedrals. The former one is well-known with its inherent problem of numerical drift and plenty of approaches to it, among which we have chosen the quaternions to represent the rotation of the rigid bodies. The latter one requires a detailed analysis of the torque size exerted on the dihedrals caused by the forces acting on the residues.
A revised and updated literature-based checklist of Hawaiian mosses is presented. Geographic coverage includes the eight main Hawaiian Islands; the Northwestern Hawaiian Islands are excluded. The checklist is alphabetically ordered by scientific names; the family is noted for each genus. Synonyms and misapplied names are cross-referenced to the accepted names. A bibliography of supporting references is included.
The major light-harvesting complex (LHC-II) of higher plants plays a crucial role in capturing light energy for photosynthesis and in regulating the flow of energy within the photosynthetic apparatus. Native LHC-II isolated from plant tissue consists of three isoforms, Lhcb1, Lhcb2, and Lhcb3, which form homo- and heterotrimers. All three isoforms are highly conserved among different species, suggesting distinct functional roles. We produced the three LHC-II isoforms by heterologous expression of the polypeptide in Escherichia coli and in vitro refolding with purified pigments. Although Lhcb1 and Lhcb2 are very similar in polypeptide sequence and pigment content, Lhcb3 is clearly different because it lacks an N-terminal phosphorylation site and has a higher chlorophyll a/b ratio, suggesting the absence of one chlorophyll b. Low temperature absorption and fluorescence emission spectra of the pure isoforms revealed small but significant differences in pigment organization. The oligomeric state of the pure isoforms and of their permutations was investigated by native gel electrophoresis, sucrose density gradient centrifugation, and SDS-PAGE. Lhcb1 and Lhcb2 formed trimeric complexes by themselves and with one another, but Lhcb3 was able to do so only in combination with one or both of the other isoforms. We conclude that the main role of Lhcb1 and Lhcb2 is in the adaptation of photosynthesis to different light regimes. The most likely role of Lhcb3 is as an intermediary in light energy transfer from the main Lhcb1/Lhcb2 antenna to the photosystem II core.
The filling of the 'Vorfeld' in German sentences is basically obligatory; which constituent, however, actually moves to the Vorfeld is underdetermined by syntax and thus governed presumably by discourse factors. Coming from English, there are certain competing expectations one could have: either the topic — more specifically, the backward-looking center — of a sentence is moved to the Vorfeld, or an element in a poset relationship to a set mentioned in the previous discourse, or elements with other functions, such as the exposition of brand-new information or the setting of a scene. A study of a corpus of texts of different stylistic levels showed that indeed all elements expected to appear in the Vorfeld are eligible for Vorfeld-movement, but that there is a strict ranking. Preferred Vorfeld-fillers are phrases containing brand-new information as well as scene-setting elements; only if no such elements are present can elements in a poset relationship with some previously mentioned set be moved to the Vorfeld. Finally, if such elements are not present either, backward-looking centers can move to the Vorfeld. Backward-looking centers have, for this reason, a relatively poor quota among Vorfeld-fillers, namely around 50%.
Tortula flavinervis Dixon var. parviretis Sainsbury is Barbula crinita Schultz. The type of Phasconia balansae Müll. Hal. was not located, only a plate of the type material was seen. Phasconia balansae Müll. Hal. and Astomum platystegium Dixon are considered as identical. The occurrence of Weissia brachycarpa (Nees & Hornsch.) Jur. in Australia is doubtful. Comments on several nomina nuda are given. No material was located for Hymenostomum pertortile Müll. Hal. nom. nud. Weissia latiuscula Müll. Hal. is reported new for Australia.
We investigate the effects of strong color fields and of the associated enhanced intrinsic transverse momenta on the phi-meson production in ultrarelativistic heavy ion collisions at RHIC. The observed consequences include a change of the spectral slopes, varying particle ratios, and also modified mean transverse momenta. In particular, the composition of the production processes of phi-mesons, that is, direct production vs. coalescence-like production, depends strongly on the strength of the color fields and intrinsic transverse momenta and thus represents a sensitive probe for their measurement.
We investigate hadron production as well as transverse hadron spectra from proton-proton, proton-nucleus and nucleus-nucleus collisions from 2 A·GeV to 21.3 A·TeV within two independent transport approaches (HSD and UrQMD) that are based on quark, diquark, string and hadronic degrees of freedom. The comparison to experimental data on transverse mass spectra from pp, pA 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, furthermore, the measured K± transverse mass spectra have a larger inverse slope parameter than expected from the default calculations. We investigate various scenarios to explore their potential effects on the K± spectra. In particular the initial state Cronin effect is found to play a substantial role at top SPS and RHIC energies. However, the maximum in the K+/..+ ratio at 20 to 30 A·GeV is missed by 40% and the approximately constant slope of the K± spectra at SPS energies is not reproduced either. Our systematic analysis suggests that the additional pressure - as expected from lattice QCD calculations at finite quark chemical potential µq and temperature T- should be generated by strong interactions in the early pre-hadronic/partonic phase of central Au+Au (Pb+Pb) collisions.
In this contribution we propose a new module for handling idioms and distributional idiosyncrasies. Based on the concept by Richter/Sailer (1999) the new feature COLL (context of lexical licensing) plays the central role in our approach. We provide a way to handle decomposable and nondecomposable idioms and idioms containing bound words. Our module guarantees the co-occurrence of all idiom parts and of bound word and licensing context, respectively. A prerequisite for our analysis is a means to select for particular elements in the lexicon. We introduce another feature, LISTEME, which gives each lexical item its unique identifier andmakes it possible to select for a particular lexical word or phrase. Finally, we compare our proposal with alternative approaches and give some ideas regarding further applications beyond idiomaticity.
This work examines English echo questions (EQs) against the background of Rizzi's (1997) analysis of split CP. It argues that EQs do not behave as the split CP analysis predicts that they should, and that their behavior can instead be straightforwardly explained within the classic CP analysis. Further, what are termed here 'echo negations' of negative inversion constructions are shown not to parallel EQs, a surprising result if negative inversion architecture parallels question architecture, as claimed by split CP proponents. In general, classic CP architecture is more appropriate for analysing this range of phenomena.
Quantitative analysis of the cardiac fibroblast transcriptome implications for NO/cGMP signaling
(2004)
Cardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signaling pathways. The NO/cGMP signaling pathway was represented by the mRNAs for α1 and β1 subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I), and, interestingly, the G-kinase-anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP analog inhibited the proliferation of serum-stimulated cardiac fibroblasts, which express cGK I, but not higher passage fibroblasts, which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth. Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.
Safety concerns associated with the use of viral vectors in gene therapy applications have attracted considerable attention towards the development of nonviral vectors as alternatives for DNA delivery. While nonviral vectors are commonly not associated with safety problems, they are still very inefficient compared to viral vectors, and require significant improvements to approach the efficiency of their viral counterparts. Meanwhile ligands or single-chain antibody fragments that bind to cell surface receptors for increased and/or specific cellular uptake, endosome escape activities, and nuclear localization sequences (NLSs) to enhance transport of plasmid DNA into the nucleus, have become available that can be incorporated into nonviral vectors to improve their efficacy. However, as gene delivery is a multistep process, the challenge is to incorporate multiple of these functional elements into a single nonviral vector system, while retaining their specific activities. A promising method to attach such entities to plasmid DNA is the use of multifunctional fusion proteins that bind to DNA through a DNA-binding domain. In principle, two types of DNA-binding domains/proteins can be used to anchor additional functional domains or peptides to a plasmid, namely sequence-specific DNA-binding domains, described in the first part of this thesis, or those that bind DNA independent of its sequence, exemplified in the second part of this work by a derivative of the human HMGB2 protein. The first fusion protein constructed and analyzed contained the E. coli LexA repressor as a sequence-specific DNA-binding domain. In addition, this DNA-carrier protein, termed TEL, included a bacterial translocation domain as an integrated endosome escape activity, and human TGF-a for specific targeting to the EGF-receptor (EGFR). TEL was expressed in E. coli and purified under both native and denaturing conditions. Purified, denatured TEL was refolded and subsequently shown to bind specifically to EGFR-expressing cells. However, inclusion of TEL in complexes of plasmid DNA and poly-L-lysine (pL) did not lead to increased gene delivery into EGFR-expressing COS-1 cells. Most likely this was due to the absence of DNA-binding activity of the LexA moiety in TEL. In contrast, native TEL was able to interact specifically with DNA. Nevertheless, since this interaction was rather weak, and refolding of denatured TEL had not resulted in functional activity of all of its protein domains, it seemed unlikely that fusion proteins containing LexA would exhibit gene transfer capabilities superior to those of similar DNA-carrier proteins previously constructed in our group. Further work therefore focused on the use of the E2C-Sp1C protein as an alternative sequencespecific DNA-binding domain. This artificial zinc-finger protein was fused to the single-chain antibody fragment scFv(FRP5), directed against the human ErbB2 growth factor receptor. The resulting 5-E2C fusion protein was expressed in E. coli and purified under native and denaturing conditions. Refolded and native 5-E2C were found to bind specifically to ErbB2-expressing cells, indicating that scFv(FRP5) in 5-E2C was functional in both preparations. In contrast, whereas refolded 5-E2C bound DNA only weakly, significant DNA binding was observed for native 5-E2C. In addition, it could not only be shown that the interaction of native 5-E2C with DNA containing its recognition sequence was specific, but also that this protein was able to bind DNA and recombinant ErbB2 simultaneously, demonstrating the functionality of both domains in native 5-E2C. Despite these encouraging results, the inclusion of native 5-E2C in pL- or polyethyleneimine (PEI)-DNA complexes did not lead to an (5-E2C-specific) enhancement of gene transfer efficiency, irrespective of the presence of the endosome-disruptive reagent chloroquine during transfection. In the second part of this thesis an alternative approach for the development of DNA-carrier proteins for nonviral gene delivery is described, based on human HMGB2, a DNA-binding protein without sequence specificity. HMGB2 contains an acidic C-terminus that has been found to decrease the affinity of the protein for DNA. Therefore, this C-terminal tail was deleted, resulting in an HMGB2-variant consisting of amino acids 1-186. HMGB2186, purified under native conditions from E. coli lysates, was able to interact with DNA and bound to the surface of different cell lines. Importantly, after binding to plasmid DNA HMGB2186 mediated gene delivery into COS-7 cells with higher efficiency than pL. In addition, HMGB2186-mediated gene transfer was strongly enhanced in the presence of chloroquine, indicating that the endocytic pathway was involved in cellular uptake. To improve internalization and intracellular routing of HMGB2186 as a DNA-carrier, a derivative containing the TAT47-57 cell-penetrating peptide (CPP), reported to facilitate cell entry independent of endocytosis, was constructed. Since this peptide also contains an NLS, in addition an HGMB2186-variant containing the SV40-NLS was constructed to investigate the effect of a peptide that has only nuclear localizing properties. Interestingly, the resulting TAT-HMGB2186 and SV40-HMGB2186 fusion proteins displayed DNA-binding activities similar to HMGB2186, but mediated gene delivery into different cell lines clearly more efficiently than the parental molecule. Furthermore, the efficacy of both fusion proteins was enhanced markedly in the presence of chloroquine, an indication that endocytosis was involved in the transfection process mediated by these proteins. This suggests that the increased transfection efficiency observed for TAT-HMGB2186 was more likely due to the NLS function present in the TAT47-57 peptide, rather than to its ‘cell penetrating properties’. Finally, the incorporation of functional peptides derived from human proteins into HMGB2186 was investigated. An uncharged CPP originating from Kaposi-FGF, reported to facilitate efficient cellular uptake of fused protein domains in an endocytosis-independent manner, was fused to HMGB2186 together with the SV40-NLS. Interestingly, the resulting KSV40-HMGB2186 fusion protein bound DNA similarly as previously tested DNA-carrier proteins, but did not mediate enhanced transfection compared to HMGB2186. In addition, the importin-b-binding (IBB) domain derived from human importin-a2 was investigated as a component of a DNA-carrier protein. Since the IBB domain can function as an NLS, it was fused to HMGB2186 resulting in the DNA-carrier protein IBBHMGB2186. Although IBB-HMGB2186 bound DNA in a similar manner as the other HMGB2186-derivatives, gene delivery mediated by IBB-HMGB2186 was only as effective as HMGB2186 mediated transfection, suggesting no significant role of the IBB domain. However, addition of chloroquine resulted in a remarkable enhancement of IBB-HMGB2186-mediated gene transfer, which was now more efficient than with any other HMGB2186-variant tested, and not much lower than gene transfer mediated by PEI, one of the most efficient transfection reagents available to date. To enhance nonviral gene delivery even further, the HMGB2186-based DNA-carrier proteins described in this thesis might now serve as building blocks for novel fusion proteins that include additional complementing activities. In this respect it seems particularly promising that, under conditions of effective end some escape, IBB-HMGB2186, which consists entirely of protein domains of human origin, was the most efficient of all proteins tested in this work.
Background: Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV) has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results: We inserted the coding sequences for green fluorescent protein (GFP) into the proline-rich region (PRR) of the ecotropic envelope protein (Env) and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP) and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions: Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.
Western cultures have witnessed a tremendous cultural and social transformation of sexuality in the years since the sexual revolution. Apart from a few public debates and scandals, the process has moved along gradually and quietly. Yet its real and symbolic effects are probably much more consequential than those generated by the sexual revolution of the sixties. Sigusch refers to the broad-based recoding and reassessment of the sexual sphere during the eighties and nineties as the "neosexual revolution". The neosexual revolution is dismantling the old patterns of sexuality and reassembling them anew. In the process, dimensions, intimate relationships, preferences and sexual fragments emerge, many of which had submerged, were unnamed or simply did not exist before. In general, sexuality has lost much of its symbolic meaning as a cultural phenomenon. Sexuality is no longer the great metaphor for pleasure and happiness, nor is it so greatly overestimated as it was during the sexual revolution. It is now widely taken for granted, much like egotism or motility. Whereas sex was once mystified in a positive sense - as ecstasy and transgression, it has now taken on a negative mystification characterized by abuse, violence and deadly infection. While the old sexuality was based primarily upon sexual instinct, orgasm and the heterosexual couple, neosexualities revolve predominantly around gender difference, thrills, self-gratification and prosthetic substitution. From the vast number of interrelated processes from which neosexualities emerge, three empirically observable phenomena have been selected for discussion here: the dissociation of the sexual sphere, the dispersion of sexual fragments and the diversification of intimate relationships. The outcome of the neosexual revolution may be described as "lean sexuality" and "self-sex".
Japanese is often taken to be strictly head-final in its syntax. In our work on a broad-coverage, precision implemented HPSG for Japanese, we have found that while this is generally true, there are nonetheless a few minor exceptions to the broad trend. In this paper, we describe the grammar engineering project, present the exceptions we have found, and conclude that this kind of phenomenon motivates on the one hand the HPSG type hierarchical approach which allows for the statement of both broad generalizations and exceptions to those generalizations and on the other hand the usefulness of grammar engineering as a means of testing linguistic hypotheses.
Japanese is often taken to be strictly head-final in its syntax. In our work on a broad-coverage, precision implemented HPSG for Japanese, we have found that while this is generally true, there are nonetheless a few minor exceptions to the broad trend. In this paper, we describe the grammar engineering project, present the exceptions we have found, and conclude that this kind of phenomenon motivates on the one hand the HPSG type hierarchical approach which allows for the statement of both broad generalizations and exceptions to those generalizations and on the other hand the usefulness of grammar engineering as a means of testing linguistic hypotheses.
Research on dialectal varieties was for a long time concentrated on phonetic aspects of language. While there was a lot of work done on segmental aspects, suprasegmentals remained unexploited until the last few years, despite the fact that prosody was remarked as a salient aspect of dialectal variants by linguists and by naive speakers. Actual research on dialectal prosody in the German speaking area often deals with discourse analytic methods, correlating intonations curves with communicative functions (P. Auer et al. 2000, P. Gilles & R. Schrambke 2000, R. Kehrein & S. Rabanus 2001). The project I present here has another focus. It looks at general prosodic aspects, abstracted from actual situations. These global structures are modelled and integrated in a speech synthesis system. Today, mostly intonation is being investigated. However, rhythm, the temporal organisation of speech, is not a core of actual research on prosody. But there is evidence that temporal organisation is one of the main structuring elements of speech (B. Zellner 1998, B. Zellner Keller 2002). Following this approach developed for speech synthesis, I will present the modelling of the timing of two Swiss German dialects (Bernese and Zurich dialect) that are considered quite different on the prosodic level. These models are part of the project on the "development of basic knowledge for research on Swiss German prosody by means of speech synthesis modelling" founded by the Swiss National Science Foundation.
Band II von II
Band I von II
In this paper, we investigate two pairs of structures in German and English: German Weak Pronoun Left Dislocation and English Topicalization, on the one hand, and German and English Hanging Topic Left Dislocation, on the other. We review the prosodic, lexical, syntactic, and discourse evidence that places the former two structures into one class and the latter two into another, taking this evidence to show that dislocates in the former class are syntactically integrated into their 'host' sentences while those in the latter class are not. From there, we show that the most straightforward way to account for this difference in 'integration' is to take the dislocates in the latter structures to be 'orphans', phrases that are syntactically independent of the phrases with which they are associated, providing additional empirical and theoretical support for this analysis — which, we point out, has a number of antecedents in the literature.
Die 5 Lipoxygenase (5 LO) ist das Schlüsselenzym in der Synthese von Leukotrienen. Sie wird auf transkriptioneller und posttranskriptioneller Ebene reguliert. Die Differenzierung myeloider Zelllinien mit 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) und transformierendem Wachstumsfaktor beta (TGFbeta) führt zu einer Erhöhung der 5 LO mRNA-, Protein-Bildung und der zellulären Enzymaktivität. Hier wurde gezeigt, dass dabei reife, nicht jedoch prä-mRNA der 5 LO im Zytosol und im Zellkern stark angereichert wird und dass beide Agentien in die mRNA-Prozessierung eigreifen. Obwohl die Bindung von VDR-Retinoid-X-Rezeptor (RXR)-Heterodimeren an Bindungsstellen im 5 LO-Promotor mittels DNAseI-Footprinting und EMSAs nachgewiesen wurde, konnten Reportergene unter der Kontrolle des 5 LO-Promotors in transienten und stabilen Transfektionen durch 1,25(OH)2D3/TGFbeta nicht stimuliert werden. Offensichtlich wird die Induktion der Expression der 5 LO durch 1,25(OH)2D3/TGFbeta durch Elemente außerhalb des Promotors vermittelt. In transienten Transfektionen führte der Einbau der kodierenden Sequenz der 5 LO in Luziferase-Plasmide bei Cotransfektion von VDR/RXR zu einer 5 fachen Induktion der Reportergen-Aktivität durch 1,25(OH)2D3/TGFbeta, was durch zusätzlichen Einbau der letzten vier Introns auf eine 13-fache Erhöhung gesteigert wurde. Der VDR zeigte einen Ligand-unabhängigen Effekt. Diese Reportergen-Effekte waren promotorunabhängig und von der kodierenden Sequenz gesteuert. RT-PCR-Analyse wies auf eine Deletion von Teilen der kodierenden Sequenz im Laufe der mRNA-Prozessierung hin, was durch 1,25(OH)2D3/TGFbeta verhindert wird. Auch Cotransfektion der TGFbeta-Effektoren Smads 3/4 führte in Abhängigkeit von der kodierenden Sequenz und in geringerem Maße von der 3'-UTR und den Introns J M, aber unabhängig vom Promotor, zu einer starken Erhöhung der Reportergenaktivität. Die 5 LO-Expression wird in den untersuchten Zellen vermutlich durch posttranskriptionelle Prozesse (Splicing, mRNA-Reifung) herunterreguliert, während 1,25(OH)2D3/TGFbeta die Expression der 5 LO durch eine Gegenregulation zu erhöhen, an der Komplexe beteiligt sind, die vermutlich Smads, VDR-RXR-Dimere, andere Transkriptionsfaktoren, Coaktivatoren, RNA-Polymerase II und Splicing-Faktoren enthalten. Hyperacetylierung des 5 LO-Promoters durch Inkubation mit mit dem Histondeacetylase-Inhibitor TsA führte zu einer transkriptionellen Aktivierung. Die kodierende Sequenz (und die Introns) wirkt diesem Effekt vermutlich durch die Rekrutierung von HDACs an VDR oder Smads, die direkt oder indirekt an die kodierende Region binden, entgegen.
RcsB is a central transcriptional regulator in enteric bacteria involved in exopolysaccharide (EPS) biosynthesis, in cell division, in the expression of osmoregulated genes, and regulates at least 20 other genes and operons. It is a member of a phosphorelay system and signal transfer is mediated by phosphorylation through the RcsC/YojN phosphorelay. RcsB proteins modified with the phosphorylation mimic BeF3- as shown by its conformational changes and DNA binding properties and resulted phosphorylated RcsB derivatives with sufficient stability. Both, the wild type RcsB protein and the mutant RcsBD11A could be modified with BeF3-. Non-phosphorylated RcsB has been shown to bind as a heterodimer with the coinducer RcsA at the conserved RcsAB box in Rcs regulated promoters. In this study, it has been shown that the modification of RcsB by BeF3 - (I) has a negative effect on its homodimerization, (II) abolishes the complex formation of RcsAB with the RcsAB box as shown by the EMSA and SPR technique. All the effects were found to be reversible by increasing the NaF concentration in the assays presumably leading to the formation of the inactive BeF4 2- salt. This hypothesis of RcsB being modified by BeF3- was also supported by other phosphodonors like ATP and acetyl phosphate, both of them showed the same negative effect on DNA binding by RcsAB heterodimer giving evidence that BeF3- could be used as a phosphorylation mimic. In addition, the phosphorylation mimic BeF3- was found to be a better phosphorylating agent than ATP and acetyl phosphate. This is the first evidence that phosphorylation of RcsB might have a negative effect on the activation of RcsAB regulated operons. Autophosphorylation of RcsB proves that it has the ability to take up phosphoryl groups and the mutant protein also become autophosphorylated with less efficiency or stability than the wild type protein. RcsB probably takes up phosphoryl groups through RcsC -> YojN -> RcsB phosphorelay pathway. To study the interaction among the proteins in this pathway, fluorescence spectroscopy, NMR spectroscopy, and an in vivo ß galactosidase assay were performed by using two domains of RcsC (T-RcsC and R-RcsC), HPt domain of the protein YojN, and RcsB. The interactions between R-RcsC/YojN-HPt and YojN-HPt/RcsB supports the proposed pathway of phosphorylating RcsB. RcsB might also be phosphorylated by YojN-HPt that is phosphorylated by other sensor kinase other than RcsC in a cross-talk mechanism. The phosphorylation of RcsB by YojN-HPt probably has the same negative effect on cps induction as obtained with BeF3 - effect on DNA binding by RcsAB heterodimer.
The transcriptional regulator RcsB controls the expression of a minimum of 20 different genes having diverse functionalities and biosynthetic operons in the family of Enterobacteriaceae. While in the heterodimeric complex with the co activator RcsA, the RcsAB box consensus is recognized, DNA binding sites for RcsB without RcsA have also been identified. The conformation of RcsB might therefore be modulated upon interaction with various co activators, resulting in recognition of different DNA targets. In this study the interaction of RcsB with some of these DNA targets have been analysed by a diverse array of techniques including gel shift assay and SPR. The solution structure of the C-terminal DNA-binding domain of RcsB from Erwinia amylovora spanning amino acid residues 129-215 has been solved in this study by heteronuclear NMR spectroscopy. The C-terminal domain is composed of four α-helices where the two central helices of the H-T-H motif are similar to the structures of the regulatory proteins GerE, NarL and TraR. The DNA-binding activity of the C-terminal domain alone is established for the first time in this study and was specified by fluorescence spectroscopy, SPR and NMR titration experiments. The molecular interaction between the individual RcsB domains was analysed by cross-linking experiments and heteronuclear NMR spectroscopy and the amino acid residues of the C-terminal domain involved in this interaction were identified precisely. Another important part of this project was the cell-free production of different Trp analogue labelled RcsB protein. RcsB protein was produced in quite a good yield with different Trp analogue having spectrally enhanced properties. The isolated RcsB alloproteins proved to be ideal for protein interaction studies by fluorescence spectroscopy and the very first evidence of an oligomerization of RcsB due to molecular association has been put forth from these studies. The phosphorylated state of the RcsB protein was mimicked by a beryllofluoride complex in order to study its role in transcriptional regulation. It was found that RcsB alone could bind to DNA targets upon this modification by the beryllofluoride complex. Thus the phosphorylation of the protein that involves the Asp 56 residue induces a structural change of the protein followed probably by a domain movement also, so that the C-terminal domain having the H-T-H DNA binding motif that was previously eclipsed by the N-terminal domain is relieved of this constraint.
In 1875, the Liebig Extract of Meat Company began to distribute a series of pictures printed on small (11 x 7 cm), colorful, collectible cardboard cards along with its main product, Fleischextrakt. While not the first to adopt this advertising technique, Liebig quickly became the best-known purveyor of Sammelbilder. ...
The development of image-guided neurosurgery represents a substantial improvement in the microsurgical treatment of tumors, vascular malformations and other intracranial lesions. Despite the wide applicability and many fascinating aspects of image-guided navigation systems, a major drawback of this technology is they use images, mainly MRI pictures, acquired preoperatively, on which the planning of the operative procedure as well as its intraoperative performance is based. As dynamic changes of the intracranial contents regularly occur during the surgical procedure, the surgeon is faced with a continuously changing intraoperative field. Only intraoperatively acquired images will provide the neurosurgeon with the information he needs to perform real intraoperative image-guided surgery. A number of tools have been developed in recent years, like intraoperative ultrasound and dedicated moveable intraoperative CT units. Because of its excellent imaging qualities, combined with the avoidance of ionizing radiation, MRI currently is and definitely will be in the future for the superior imaging method for intraoperative image guidance. In this short overview, the development as well as some of the current and possible future applications of MRI-guided neurosurgery is outlined.
The hypothesis that oxidative stress plays a role in the pathogenesis of Alzheimer’s disease (AD) was tested by studying oxidative damage, acitvities of antioxidant enzymes and levels of reactive oxygen species (ROS) in several models. To this end, mouse models transgenic for mutant presenilin (PS1M146L) as well as mutant amyloid precursor protein (APP) and human post mortem brain tissue from sporadic AD patients and age-matched controls were studied. Aging leads to an upregulation of antioxidant enzyme activities of Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in brains from C57BL/6J mice. Simultaneously, levels of lipid peroxidation products malondialdehyde MDA and 4-hydroxynonenal HNE were reduced. Additionally, pronounced gender effects were observed, as female mice display better protection against oxidative damage due to higher activity of GPx. Hence, antioxidant enzymes provide an important contribution to the protection against oxidative damage. In PS1M146L transgenic mice oxidative damage was only detectable in 19-22 months old mice, arguing for an additive effect of aging and the PS1 mutation. Both HNE levels in brain tissue as well as mitochondrial and cytosolic levels of ROS in splenic lymphocytes were increased in PS1M146L mice. Antioxidant defences were unaltered. In PDGF-APP and PDGF-APP/PS1 trangenic mice no changes in any of the parameters studied were observed in any age group. In contrast, Thy1-APP transgenic mice display oxidative damage as assessed by increased HNE levels. Reduced activity of Cu/Zn-SOD may explain this observation. Additionally, gender modified this effect, as female APP transgenic mice display higher b-secretase cleavage of APP and simultaneously increased HNE levels and reduced Cu/Zn-SOD activity earlier than male mice, i.e. from an age of 3 months and before the formation of Ab plaques. Reduced Cu/Zn-SOD activity was also found in another APP transgenic mouse model, in APP23 mice. In post mortem brain tissue from sporadic AD patients activities of Cu/Zn-SOD and GPx were however increased, and changes were most pronounced in temporal cortex. Simultaneously, levels of HNE but not MDA were elevated. Additionally, in vitro stimulation of lipid peroxidation led to increased MDA formation in samples from AD patients, indicating that increased activity of Cu/Zn-SOD and GPx are insufficient to protect against oxidative damage. Furthermore, the observed changes were subject to a gender effect, as samples from female AD patients showed increased activities of Cu/Zn-SOD and GPx as well as increased HNE levels, indicating that brain tissue from females is more sensitive towards oxidative damage. Levels of soluble Ab1-40 were positively correlated with with MDA levels and activities of Cu/Zn-SOD and GPx. Additionally, levels of lipid peroxidation products MDA and HNE are gene-dose-dependently modulated by the Apolipoprotein E4 allele, the most important genetic risk factor for AD known so far. While MDA levels were negatively correlated with MMSE scores, a measure for cognitive function, HNE levels were highest in AD patients with moderate cognitive impairment. Hence, increased HNE levels may play an important role in neurodegenerative events at an early disease stage. In summary, oxidative damage, as assessed by increased HNE levels, could be detected in sporadic AD patients and in different transgenic mouse models. The results of this thesis therefore support the further research of pharmacological targets aiming at augmentation of antioxidant defences for therapy or prophylaxis of Alzheimer’s disease.
Financial theory creates a puzzle. Some authors argue that high-risk entrepreneurs choose debt contracts instead of equity contracts since risky but high returns are of relatively more value for a loan-financed firm. On the contrary, authors who focus explicitly on start-up finance predict that entrepreneurs are the more likely to seek equity-like venture capital contracts, the more risky their projects are. Our paper makes a first step to resolve this puzzle empirically. We present microeconometric evidence on the determinants of debt and equity financing in young and innovative SMEs. We pay special attention to the role of risk for the choice of the financing method. Since risk is not directly observable we use different indicators for financial and project risk. It turns out that our data generally confirms the hypothesis that the probability that a young high-tech firm receives equity financing is an increasing function of the financial risk. With regard to the intrinsic project risk, our results are less conclusive, as some of our indicators of a risky project are found to have a negative effect on the likelihood to be financed by private equity.
Course management software : supporting the university’s teaching with technology initiatives
(2004)
An increasingly important element of the teaching with technology activities at Northwestern University is the course management system, a web-based class communication and administration environment. The usage growth of the system is substantial and amplifies the need for integration with other web services and resources. Integration is particularly material in area of library services. This presentation contains a case study of Northwestern University's implementation of its course management system software and highlights examples of how the system is being used to enhance the teaching and learning. A description of the integration efforts with library resources is provided. The goal of the presentation is to equip librarians with the basic knowledge required to engage with their colleagues in conversations surrounding the nature of integration of these systems within the teaching and learning landscapes of their home institutions.
We modify the concept of LLL-reduction of lattice bases in the sense of Lenstra, Lenstra, Lovasz [LLL82] towards a faster reduction algorithm. We organize LLL-reduction in segments of the basis. Our SLLL-bases approximate the successive minima of the lattice in nearly the same way as LLL-bases. For integer lattices of dimension n given by a basis of length 2exp(O(n)), SLLL-reduction runs in O(n.exp(5+epsilon)) bit operations for every epsilon > 0, compared to O(exp(n7+epsilon)) for the original LLL and to O(exp(n6+epsilon)) for the LLL-algorithms of Schnorr (1988) and Storjohann (1996). We present an even faster algorithm for SLLL-reduction via iterated subsegments running in O(n*exp(3)*log n) arithmetic steps.
Hinreichend kalte und dichte Quarkmaterie ist ein Farbsupraleiter. Ähnlich wie Elektronen in einem gewöhnlichen Supraleiter bilden Quarks Cooper-Paare. Während bei Elektronen der Austausch von Phononen zu einer Anziehung führt, ist im Falle von Quarks der Antitriplett-Kanal der starken Wechselwirkung attraktiv. Arbeiten in den letzten Jahren haben verschiedene Phasen von farbsupraleitender Quarkmaterie untersucht und sich dabei vor allem auf Phasen konzentriert, m denen der Gesamtspin eines Cooper-Paares verschwindet. In der vorliegenden Dissertation habe ich hauptsächlich Farbsupraleiter diskutiert, deren Cooper-Paare im Spin-Triplett-Kanal kondensieren, d.h. die Cooper-Paare haben den Gesamtspin 1. Diese Art von Supraleiter ist möglicherweise relevant für Systeme in der Natur, wie z.B. das Innere von Neutronensternen. Denn bei der Spin-0-Farbsupraleitung wird vorausgesetzt, dass die Fermi-Impulse zweier Quark-Flavor gleich ist oder zumindest hinreichend klein, was für realistische Systeme, also für nicht zu große Dichten, fragwürdig ist. Diese Einschränkung gibt es im Falle von Spin-1-Farbsupraleitern nicht, da hier Quarks des gleichen Flavors Cooper-Paare bilden. Ich habe in meiner Dissertation die verschiedenen möglichen Phasen eines Spin-1-Farbsupraleiters systematisch klassifiziert. Dies wurde mit Hilfe von gruppen-theoretischen Methoden durchgeführt, basierend auf der Tatsache, dass die Farbsupraleitung durch das theoretische Konzept der spontanen Symmetriebrechung beschrieben werden kann. Ähnlich wie bei supraflüssigem Helium-3 gibt es eine Vielzahl theoretisch möglicher Phasen. Ich habe die physikalischen Eigenschaften von vier dieser Phasen untersucht, nämlich der polaren und planaren Phasen sowie der A- und CSL-(color-spin-locked)Phasen. Mit Hilfe der QCD-Lückengleichung wurde die Energielücke sowie die kritische Temperatur bestimmt. Es stellt sich heraus, dass die Energielücke eines Spin-1-Farbsupraleiters um 2-3 Größenordnungen kleiner ist als die eines Spin-0-Farbsupraleiters, d.h. sie liegt im Bereich von 10 - 100 keV. Zwei besondere Eigenschaften der Energielücke werden diskutiert, nämlich eine 2-Lücken-Struktur, die in zwei der untersuchten Fälle auftritt, sowie mögliche Anisotropien, insbesondere Nullstellen der Lückenfunktion. Die Berechnung der kritischen Temperatur zeigt, dass es durchaus farbsupraleitende Materie in einer Spin-1-Phase im Innern von Neutronensternen geben kann, da die Temperatur von alten Neutronensternen im Bereich von einigen keV oder sogar darunter liegt. Darüber hinaus wurde die Frage untersucht, ob ein Farbsupraleiter auch ein gewöhnlicher Supraleiter ist. In diesem Zusammenhang ist die Frage von Interesse, ob ein Spin-1-Farbsupraleiter gewöhnliche Magnetfelder aus seinem Innern verdrängt, was sicherlich Auswirkungen auf die Observablen eines Neutronensterns hätte. Tatsächlich stellt sich heraus, dass ein Spin-1-Farbsupraleiter, im Gegensatz zu einem Spin-0-Farbsupraleiter, einen elektronmagnetischen Meissner-Effekt aufweist. Dieses Ergebnis wurde mit Hilfe von gruppentheoretischen Überlegungen vorausgesagt und mit Hilfe einer detaillierten Berechnung der Photon-Meissner-Massen bestätigt.
This paper proves correctness of Nocker s method of strictness analysis, implemented for Clean, which is an e ective way for strictness analysis in lazy functional languages based on their operational semantics. We improve upon the work of Clark, Hankin and Hunt, which addresses correctness of the abstract reduction rules. Our method also addresses the cycle detection rules, which are the main strength of Nocker s strictness analysis. We reformulate Nocker s strictness analysis algorithm in a higherorder lambda-calculus with case, constructors, letrec, and a nondeterministic choice operator used as a union operator. Furthermore, the calculus is expressive enough to represent abstract constants like Top or Inf. The operational semantics is a small-step semantics and equality of expressions is defined by a contextual semantics that observes termination of expressions. The correctness of several reductions is proved using a context lemma and complete sets of forking and commuting diagrams. The proof is based mainly on an exact analysis of the lengths of normal order reductions. However, there remains a small gap: Currently, the proof for correctness of strictness analysis requires the conjecture that our behavioral preorder is contained in the contextual preorder. The proof is valid without referring to the conjecture, if no abstract constants are used in the analysis.
The paper is a follow-up to an article published in Technique Financière et Developpement in 2000 (see the appendix to the hardcopy version), which portrayed the first results of a new strategy in the field of development finance implemented in South-East Europe. This strategy consists in creating microfinance banks as greenfield investments, that is, of building up new banks which specialise in providing credit and other financial services to micro and small enterprises, instead of transforming existing credit-granting NGOs into formal banks, which had been the dominant approach in the 1990s. The present paper shows that this strategy has, in the course of the last five years, led to the emergence of a network of microfinance banks operating in several parts of the world. After discussing why financial sector development is a crucial determinant of general social and economic development and contrasting the new strategy to former approaches in the area of development finance, the paper provides information about the shareholder composition and the investment portfolio of what is at present the world's largest and most successful network of microfinance banks. This network is a good example of a well-functioning "private public partnership". The paper then provides performance figures and discusses why the creation of such a network seems to be a particularly promising approach to the creation of financially self-sustaining financial institutions with a clear developmental objective.
We investigate the connection between corporate governance system configurations and the role of intermediaries in the respective systems from a informational perspective. Building on the economics of information we show that it is meaningful to distinguish between internalisation and externalisation as two fundamentally different ways of dealing with information in corporate governance systems. This lays the groundwork for a description of two types of corporate governance systems, i.e. insider control system and outsider control system, in which we focus on the distinctive role of intermediaries in the production and use of information. It will be argued that internalisation is the prevailing mode of information processing in insider control system while externalisation dominates in outsider control system. We also discuss shortly the interrelations between the prevailing corporate governance system and types of activities or industry structures supported.
Alix/AIP1 is an adaptor protein involved in regulating the function of receptor and cytoskeleton-associated tyrosine kinases. Here, we investigated its interaction with and regulation by Src. Tyr319 of Alix bound the isolated Src homology-2 (SH2) domain and was necessary for interaction with intact Src. A proline-rich region in the C terminus of Alix bound the Src SH3 domain, but this interaction was dependent on the release of the Src SH2 domain from its Src internal ligand either by interaction with Alix Tyr319 or by mutation of Src Tyr527. Src phosphorylated Alix at a C-terminal region rich in tyrosines, an activity that was stimulated by the presence of the Alix binding partner SETA/CIN85. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2. As a consequence of this, Src antagonized the negative regulation of receptor tyrosine kinase internalization and cell adhesion by Alix. We propose a model whereby Src antagonizes the effects of Alix by phosphorylation of its C terminus, leading to the disruption of interactions with target proteins.
The paper explores factors that influence the design of financing contracts between venture capital investors and European venture capital funds. 122 Private Placement Memoranda and 46 Partnership Agreements are investigated in respect to the use of covenant restrictions and compensation schemes. The analysis focuses on the impact of two key factors: the reputation of VC-funds and changes in the overall demand for venture capital services. We find that established funds are more severely restricted by contractual covenants. This contradicts the conventional wisdom which assumes that established market participants care more about their reputation, have less incentive to behave opportunistically and therefore need less covenant restrictions. We also find that managers of established funds are more often obliged to invest own capital alongside with investors money. We interpret this as evidence that established funds have actually less reason to care about their reputation as compared to young funds. One reason for this surprising result could be that managers of established VC funds are older and closer to retirement and therefore put less weight on the effects of their actions on future business opportunities. We also explore the effects of venture capital supply on contract design. Gompers and Lerner (1996) show that VC-funds in the US are able to reduce the number of restrictive covenants in years with high supply of venture capital and interpret this as a result of increased bargaining power by VC-funds. We do not find similar evidence for Europe. Instead, we find that VC-funds receive less base compensation and higher performance related compensation in years with strong capital inflows into the VC industry. This may be interpreted as a signal of overconfidence: Strong investor demand seems to coincide with overoptimistic expectations by fund managers which make them willing to accept higher powered incentive schemes. JEL: G32 Keywords: Venture Capital, Contracting, Limited Partnership, Funds, Principal Agent, Compensation, Covenants, Reputation, Bargaining Power
In this article, we investigate risk return characteristics and diversification benefits when private equity is used as a portfolio component. We use a unique dataset describing 642 US-American portfolio companies with 3620 private equity investments. Information about precisely dated cash flows at the company level enables for the first time a cash flow equivalent and simultaneous investment simulation in stocks, as well as the construction of stock portfolios for benchmarking purposes. With respect to the methodology involved, we construct private equity, stock-benchmark and mixed-asset portfolios using bootstrap simulations. For the late 1990s we find a dramatic increase in the extent to which private equity outperforms stock investment. In earlier years private equity was underperforming its stock benchmarks. Within the overall class of private equity, returns on earlier private equity investment categories, like venture capital, show on average higher variations and even higher rates of failure. It is in this category in particular that high average portfolio returns are generated solely by the ability to select a few extremely well performing companies, thus compensating for lost investments. There is a high marginal diversifiable risk reduction of about 80% when the portfolio size is increased to include 15 investments. When the portfolio size is increased from 15 to 200 there are few marginal risk diversification effects on the one hand, but a large increase in managing expenditure on the other, so that an actual average portfolio size between 20 and 28 investments seems to be well balanced. We provide empirical evidence that the non-diversifiable risk that a constrained investor, who is exclusively investing in private equity, has to hold exceeds that of constrained stock investors and also the market risk. From the viewpoint of unconstrained investors with complete investment freedom, risk can be optimally reduced by constructing mixed asset portfolios. According to the various private equity subcategories analyzed, there are big differences in optimal allocations to this asset class for minimizing mixed-asset portfolio variance or maximizing performance ratios. We observe optimal portfolio weightings to be between 3% and 65%.
We present an overview of the mathematics underlying the quantum Zeno effect. Classical, functional analytic results are put into perspective and compared with more recent ones. This yields some new insights into mathematical preconditions entailing the Zeno paradox, in particular a simplified proof of Misra's and Sudarshan's theorem. We empahsise the complex-analytic structures associated to the issue of existence of the Zeno dynamics. On grounds of the assembled material, we reason about possible future mathematical developments pertaining to the Zeno paradox and its counterpart, the anti-Zeno paradox, both of which seem to be close to complete characterisations. PACS-Klassifikation: 03.65.Xp, 03.65Db, 05.30.-d, 02.30.T . See the corresponding presentation: Schmidt, Andreas U.: "Zeno Dynamics of von Neumann Algebras" and "Zeno Dynamics in Quantum Statistical Mechanics"
We study the quantum Zeno effect in quantum statistical mechanics within the operator algebraic framework. We formulate a condition for the appearance of the effect in W*-dynamical systems, in terms of the short-time behaviour of the dynamics. Examples of quantum spin systems show that this condition can be effectively applied to quantum statistical mechanical models. Furthermore, we derive an explicit form of the Zeno generator, and use it to construct Gibbs equilibrium states for the Zeno dynamics. As a concrete example, we consider the X-Y model, for which we show that a frequent measurement at a microscopic level, e.g. a single lattice site, can produce a macroscopic effect in changing the global equilibrium. PACS - Klassifikation: 03.65.Xp, 05.30.-d, 02.30. See the corresponding papers: Schmidt, Andreas U.: "Zeno Dynamics of von Neumann Algebras" and "Mathematics of the Quantum Zeno Effect" and the talk "Zeno Dynamics in Quantum Statistical Mechanics" - http://publikationen.ub.uni-frankfurt.de/volltexte/2005/1167/
Dialectal variation in german 3-verb clusters : a surface-oriented optimality theoretic account
(2004)
We present data from an empirical investigation on the dialectal variation in the syntax of German 3-verb clusters, consisting of a temporal auxiliary, a modal verb, and a predicative verb. The ordering possibilities vary greatly among the dialects. Some of the orders that we found occur only under particular stress assignments. We assume that these orders fulfil an information structural purpose and that the reordering processes are changes only in the linear order of the elements which is represented exclusively at the surface syntactic level, PF (Phonetic Form). Our Optimality theoretic account offers a multifactorial perspective on the phenomenon.