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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.