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In this article, we illustrate the flexibility of the algebraic integration formalism introduced in M. Gubinelli (2004), Controlling Rough Paths, J. Funct. Anal. 216, 86-140, by establishing an existence and uniqueness result for delay equations driven by rough paths. We then apply our results to the case where the driving path is a fractional Brownian motion with Hurst parameter H > 1/3.
It has been established since Kanerva’s work that focus conditions phrasing – directly or indirectly – in several other Bantu languages, e.g. Chimwiini (Kisseberth 2007, Downing 2002, Kisseberth & Abasheikh 2004), Xhosa (Jokweni 1995, Zerbian 2004), Chitumbuka (Downing 2006, 2007), Zulu (Cheng & Downing 2006, Downing 2007), Bemba (Kula 2007), etc.
In this paper, I will argue that focus also conditions phrasing in Shingazidja, a Bantu language3 spoken on Grande Comore (or Ngazidja, the largest island of the Comoros).
Many works have been dedicated to the tonology of Shingazidja. The bases of the system were firstly identified by Tucker & Bryan (1970) and reanalyzed by Philippson (1988). Later, Cassimjee & Kisseberth (1989, 1992, 1993, 1998) provide a very convincing analysis of the whole system of the language, and my own research (Patin 2007a) shows a great correspondence with their results. However, little attention has been paid by these authors or others (Jouannet 1989, Rey 1990, Philippson 2005) to the phonology-pragmatics interface, especially on the relation between focus and phrasing. This paper thus proposes to explore this question. It will be claimed that focus, beside syntax, has an influence on phrasing in Shingazidja.
We present the results of an experimental study which targets prosodic correlates of subclausal quotation marks. We found that written sentences containing passages enclosed by quotation marks were read aloud in a manner that significantly differs in prosody from spoken realizations of corresponding disquoted counterparts. However, we also observed that such prosodic marking of subclausal quotation wasn't strong enough to survive subsequent back-translation into written language: there was no correlation between the presence/absence of quotation marks in the original written examples, and the presence/absence of quotation marks in corresponding back-translations from oral renditions. We investigated three different kinds of uses of quotation marks and found no systematic difference between them with respect to prosodic marking.
Rate effects on aerodynamics of intervocalic stops : evidence from real speech data and model data
(2008)
This paper is a first attempt towards a better understanding of the aerodynamic properties during speech production and their potential control. In recent years, studies on intraoral pressure in speech have been rather rare, and more studies concern the air flow development. However, the intraoral pressure is a crucial factor for analysing the production of various sounds.
In this paper, we focus on the intraoral pressure development during the production of intervocalic stops.
Two experimental methodologies are presented and confronted with each other: real speech data recorded for four German native speakers, and model data, obtained by a mechanical replica which allows reproducing the main physical mechanisms occurring during phonation. The two methods are presented and applied to a study on the influence of speech rate on aerodynamic properties.
The unfolding discussion will focus on the internal representation of turbulent sounds in the phonology of German as well as pinpoint the special status of the prime defining the quality of turbulence. It will also be argued that this prime is capable of entering into special types of licensing relations, which results in specific phonetic manifestations of forms. We shall compare the effects of two processes attested in German: consonant degemination and spirantisation with a view to revealing the role of the turbulence-defining element in the two operations. Furthermore, our attention will be focused on the workings of the Obligatory Contour Principle which, as will be shown below, exerts decisive impact on prime interplay and consequently the phonetic realization of sounds and words. We shall see that segmental identity is contingent on the languagespecific interpretation of inter-element bonds.
Aware of the importance of prime autonomy in determining the manifestation of sounds, let us start with a brief outline of the fundamental segment structure principles offered by the theory of Phonological Government.
Much work on the interaction of prosody and focus assumes that, crosslinguistically, there is a necessary correlation between the position of main sentence stress (or accent) and focus, and that an intonational pitch change on the focused element is a primary correlate of focus. In this paper, I discuss primary data from three Bantu languages – Chichewa, Durban Zulu and Chitumbuka – and show that in all three languages phonological re-phrasing, not stress, is the main prosodic correlate of focus and that lengthening, not pitch movement, is the main prosodic correlate of phrasing. This result is of interest for the typology of intonation in illustrating languages where intonation has limited use and where, notably, intonation does not highlight focused information in the way we might expect from European stress languages.
This study is an electropalatographic investigation of clusters composed of /n/ or /l/ followed by the (alveolo)palatal consonants /ʎ, ɲ/ or by dental /t/ in three Catalan dialects, i.e., Majorcan, Valencian and Eastern. Data show that articulatory blending through superposition occurs in the palatalizing environment except when C1 is highly constrained (e.g., dark /l/) or C2 is purely palatal and therefore, produced at a distant articulatory location from C1. Contrary to previous descriptions in the literature, data for /nt, lt/ reveal that blending through superposition rather than assimilation is at work. The implications of these data for theories of speech production are discussed.
The present article illustrates that the specific articulatory and aerodynamic requirements for voiced but not voiceless alveolar or dental stops can cause tongue tip retraction and tongue mid lowering and thus retroflexion of front coronals. This retroflexion is shown to have occurred diachronically in the three typologically unrelated languages Dhao (Malayo-Polynesian), Thulung (Sino-Tibetan), and Afar (East-Cushitic). In addition to the diachronic cases, we provide synchronic data for retroflexion from an articulatory study with four speakers of German, a language usually described as having alveolar stops. With these combined data we supply evidence that voiced retroflex stops (as the only retroflex segments in a language) did not necessarily emerge from implosives, as argued by Haudricourt (1950), Greenberg (1970), Bhat (1973), and Ohala (1983). Instead, we propose that the voiced front coronal plosive /d/ is generally articulated in a way that favours retroflexion, that is, with a smaller and more retracted place of articulation and a lower tongue and jaw position than /t/.
In this paper it is argued that several typologically unrelated languages share the tendency to avoid voiced sibilant affricates. This tendency is explained by appealing to the phonetic properties of the sounds, and in particular to their aerodynamic characteristics. On the basis of experimental evidence it is shown that conflicting air pressure requirements for maintaining voicing and frication are responsible for the avoidance of voiced affricates. In particular, the air pressure released from the stop phase of the affricate is too high to maintain voicing which in consequence leads to a devoicing of the frication part.
Dendrite morphology, a neuron's anatomical fingerprint, is a neuroscientist's asset in unveiling organizational principles in the brain. However, the genetic program encoding the morphological identity of a single dendrite remains a mystery. In order to obtain a formal understanding of dendritic branching, we studied distributions of morphological parameters in a group of four individually identifiable neurons of the fly visual system. We found that parameters relating to the branching topology were similar throughout all cells. Only parameters relating to the area covered by the dendrite were cell type specific. With these areas, artificial dendrites were grown based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy. Although the same branching rule was used for all cells, this yielded dendritic structures virtually indistinguishable from their real counterparts. From these principles we derived a fully-automated model-based neuron reconstruction procedure validating the artificial branching rule. In conclusion, we suggest that the genetic program implementing neuronal branching could be constant in all cells whereas the one responsible for the dendrite spanning field should be cell specific.
Between 1993 and 2005 I investigated the introduced plant species on the Newcastle foreshores at Stockton and Macquaries Pier (lat 32º 56’ S, long 151º 47’ E). At North Stockton in a rehabilitated area, cleared of *Chrysanthemoides monilifera subsp. rotundata, and planted with *Ammophila arenaria interspersed with native shrubs, mainly Acacia longifolia subsp. sophorae and Leptospermum laevigatum, is a rich flora of introduced species of which *Panicum racemosum and *Cyperus conglomeratus have gradually become dominant in the groundcover. Notwithstanding continuing maintenance, *Chrysanthemoides monilifera subsp. rotundata has re-established among the native shrubs, and together with Acacia longifolia subsp. sophorae, is important in sand stabilisation along the seaward edge of the dune terrace. The foredune of Little Park Beach, just inside the Northern Breakwater, is dominated by Spinifex sericeus and backed by Acacia longifolia subsp. sophorae-*Chrysanthemoides monilifera subsp. rotundata shrubbery. In places the shrubbery has given way to introduced species such as *Oenothera drummondii, *Tetragonia decumbens and especially *Heterotheca grandiflora. At Macquaries Pier *Chrysanthemoides monilifera subsp. rotundata forms an almost continuous fringe between the rocks that protect the pier against heavy southerlies. However, its presence on adjacent Nobbys Beach is localised and the general aspect of this beach is no different from any other along the coast as it is dominated by Spinifex sericeus. Many foreign plant species occur around the sandy foreshores at Port Hunter. Since the first coal exports in the 1850s the Newcastle wharves and ballast-ground at Stockton became points of entry for foreign species, either directly, or via stopovers at other Australian ports. Some of these, *Panicum racemosum, *Tetragonia decumbens, *Ursinia speciosa, *Hebenstretia dentata and until recently, *Heterotheca grandiflora, remained restricted to the Newcastle region, while others, e.g. *Chrysanthemum monilifera subsp. rotundata, *Hydrocotyle bonariensis, *Gladiolus gueinzii and *Oenothera drummondii, spread further afield, but only colonised their preferred coastal habitat. Many more species spread far and wide, their port of introduction no longer recognisable. Other species were introduced as garden plants, escaped and became naturalised. However, for most foreign, generally widespread, species their mode of entry can no longer be determined. 99 species were recorded in the six areas regularly visited, about 25% native to Australia, and 75% about evenly divided between species from Africa, Asia and Europe. More detailed information on 15 of the more notable introduced species is provided in an appendix. On the dune terrace vegetation of North Stockton, only about 20% of the 50 species are native to Australia, the only one of any prominence being Acacia longifolia subsp. sophorae. Nevertheless, on first impression this ‘multinational’ assemblage looks quite normal, and when one compares the ecological functioning of the 1930s vegetation with that of the present vegetation, it appears that, due to presence of more graminoids, and the fact that *Panicum racemosum produces a denser sward than Spinifex sericeus, the present vegetation is more effective in sand-catching and dune stabilisation than the vegetation in the 1930s would have been. However in view of the increasing influence of climate change, e.g. a rise in sea level and more extreme weather events, there is no indication that the present terrace, notwithstanding the increased density of the rhizomatous species and a sprawling shrubby vegetation along the crest, will endure such attacks any better than in the 1990s.
The vegetation of montane lagoons of the New England Tablelands Bioregion, New South Wales is examined using flexible UPGMA analysis of frequency scores on all vascular plant taxa, charophytes and one liverworts. Seven communities are described: 1. Hydrocotyle tripartita – Isotoma fluviatilis – Ranunculus inundatus – Lilaeopsis polyantha herbfield; 2. Eleocharis sphacelata – Potamogeton tricarinatus sedgeland; 3. Eleocharis sphacelata – Utricularia australis – Isolepis fluitans, herbfield; 4. Utricularia australis – Nitella sonderi herbfield; 5. Eleocharis sphacelata – Utricularia australis – Ricciocarpus natans sedgeland; 6. Carex gaudichaudiana – Holcus lanatus – Stellaria angustifolia sedgeland; 7. Cyperus sphaeroides – Eleocharis gracilis – Schoenus apogon – Carex gaudichaudiana sedgeland. 58 lagoons were located and identified, only 28% of which are considered to be intact and in good condition. Two threatened species (Aldovandra vesiculosa and Arthaxon hispidus) and three RoTAP-listed taxa were encountered during the survey.
The vegetation of Gibraltar Range National Park and adjoining parts of eastern Washpool National Park, 65 km east of Glen Innes (29° 31’S 152° 18’E) on the eastern escarpment of New South Wales is described. In total 124, 20m x 50m full vascular plant floristic sites were recorded and information from an additional 53 sites was collated. Thirteen vegetation assemblages are defined based on flexible UPGMA analysis of cover-abundance scores of all vascular plant taxa. Many of the vegetation communities are typical of what is found along the north eastern escarpment of NSW. Three communities are considered to be rare and two vulnerable. A total of 878 vascular plant taxa from 138 families were recorded, of which only 21 (2%) were of introduced origin and 81 (9%) were found to be of conservation significance. Pattern diversity, species density, species accumulation and average geographic range size, along with general measures of richness and diversity, were analysed for all communities. Each of the communities described varied considerably in the diversity attributes measured. Communities with a high number of shrubs had greater constancy between sites compared to those that contained a high number of closed forest species. The community from rock outcrops had the largest average geographical range size.
Tropical lowland plant communities in north-eastern Queensland remain under pressure from continuing clearing, fragmentation, exotic species invasion, inappropriate fire regimes, and altered hydrological patterns. Comparatively little scientific research has been conducted on the highly diverse and ecologically significant range of remnant vegetation types. Additionally, most plant communities remain very poorly represented in the existing conservation reserve system. Melaleuca viridiflora Sol. ex Gaertn. open woodlands were selected for investigation based on their relatively simple structure, compared to other lowland communities, and the large extent to which they have been affected by past clearing patterns. A detailed analysis of community structure and composition was conducted at 24 sites throughout the wet-tropics coastal region between Townsville and Cooktown. Surprisingly, a high diversity of structural and floristic types was recorded, with a total of 127 species documented across the 24 sites. Classification analyses of species composition data produced seven or eight main groups of sites (dependent on the statistical technique used), essentially related to a gradient of latitude and rainfall. These floristic groups were not well explained by either species richness, past fire frequencies or soil types. Structural classification analyses based upon DBH data identified six or seven main groups, the singularly most striking of which were sites with annual fire histories. Ordinations based on both the DBH and species composition data produced groupings that supported those detected by the classification techniques. On closer examination of sites with similar fire histories, soil moisture and soil type were both found to have significant effects on community structure and composition. Many of the woodland types recorded are not adequately included (some not at all) in the existing conservation reserve system.
A study was conducted on the Liverpool Plains (30o 43’–31o 44’S; 149o 40’–150o 41’E), North Western Slopes of NSW, to determine the original boundaries of the naturally-treeless grasslands, to determine reasons for the lack of woody vegetation on these areas, and to assess the status of Austrostipa aristiglumis (Plains Grass), a species that is today commonly dominant on the few remaining remnant grassland areas and is commonly assumed to characterise the original grassland community. The original tree line boundaries were reconstructed using NSW Lands Department survey portion plans and other historical records. The lack of woody vegetation was attributed primarily to a combination of fine-textured soil, climate and topography restricting the availability of water below the grass root zone, with waterlogging and deep soil cracking possibly playing minor roles. Published and anecdotal evidence and landholder experience indicate that the Austrostipa aristiglumis dominated remnants are probably a relatively recent anthropogenic feature, a consequence of post-settlement management practices. The pre-settlement grasslands appear to have been composed of a wide range of grasses, possibly dominated by species such as Themeda avenacea (Native Oatgrass) and Eulalia aurea (Silky Browntop), with a range of forbs occupying the interstitial spaces. Management implications are discussed.
Dry rainforests are those communities that have floristic and structural affinities to mesic rainforests and occur in parts of eastern and northern Australia where rainfall is comparatively low and often highly seasonal. The dry rainforests of the western slopes of New South Wales are poorly-understood compared to other dry rainforests in Australia, due to a lack of regional scale studies. This paper attempts to redress this by deriving a broad floristic and structural typology for this vegetation type. Phytogeographical analysis followed full floristic surveys conducted on 400 m2 plots located within dry rainforest across the western slopes of NSW. Cluster analysis and ordination of 208 plots identified six floristic groups. Unlike in some other regional studies of dry rainforest these groups were readily assigned to Webb structural types, based on leaf size classes, leaf retention classes and canopy height. Five community types were described using both floristic and structural data: 1) Ficus rubiginosa–Notelaea microcarpa notophyll vine thicket, 2) Ficus rubiginosa–Alectryon subcinereus–Notelaea microcarpa notophyll vine forest, 3) Elaeodendron australe–Notelaea microcarpa–Geijera parviflora notophyll vine thicket, 4) Notelaea microcarpa– Geijera parviflora–Ehretia membranifolia semi-evergreen vine thicket, and 5) Cadellia pentastylis low microphyll vine forest. Floristic groupings were consistent with those described by previous quantitative studies which examined smaller portions of this study area. There was also general agreement between the present analytical study and a previous intuitive classification of dry rainforest vegetation throughout the study area, but little concurrence with a continental scale floristic classification of rainforest.
Macrozamia johnsonii D. Jones & K. Hill is a locally endemic cycad (family Zamiaceae) with a restricted occurrence in north-eastern New South Wales and currently listed as Endangered. Based on recent field surveys, its mean population size is estimated as approximately 3.5 million mature plants, with the lower bound of the 95% confidence interval at 1.9 million mature plants. Thirty percent of the population occurs in a formal reserve. Macrozamia johnsonii occurs in grassy eucalypt forest, shrubby wet sclerophyll forest and in rainforest. It occurs most frequently on steeply sloping sites with high moisture index. There are no immediate significant threats to the species although timber harvesting is judged to be a potential longer term threat to part of the population. The conservation status of Macrozamia johnsonii is assessed using IUCN criteria and thresholds, using population size and extent data from this study and a plausible range of values based on available circumstantial evidence for parameters for which quantitative estimates are not available. Based on this assessment, we regard the conservation status of Macrozamia johnsonii to be in the category of Least Concern, and that its current listing as an Endangered species under the NSW Threatened Species Conservation Act (1995) needs to be revised.
Rare or threatened vascular plant species of Wollemi National Park, central eastern New South Wales
(2008)
Wollemi National Park (c. 32o 20’– 33o 30’S, 150o– 151oE), approximately 100 km north-west of Sydney, conserves over 500 000 ha of the Triassic sandstone environments of the Central Coast and Tablelands of New South Wales, and occupies approximately 25% of the Sydney Basin biogeographical region. 94 taxa of conservation significance have been recorded and Wollemi is recognised as an important reservoir of rare and uncommon plant taxa, conserving more than 20% of all listed threatened species for the Central Coast, Central Tablelands and Central Western Slopes botanical divisions. For a land area occupying only 0.05% of these divisions, Wollemi is of paramount importance in regional conservation. Surveys within Wollemi National Park over the last decade have recorded several new populations of significant vascular plant species, including some sizeable range extensions. This paper summarises the current status of all rare or threatened taxa, describes habitat and associated species for many of these and proposes IUCN (2001) codes for all, as well as suggesting revisions to current conservation risk codes for some species. For Wollemi National Park 37 species are currently listed as Endangered (15 species) or Vulnerable (22 species) under the New South Wales Threatened Species Conservation Act 1995. An additional 50 species are currently listed as nationally rare under the Briggs and Leigh (1996) classification, or have been suggested as such by various workers. Seven species are awaiting further taxonomic investigation, including Eucalyptus sp. ‘Howes Swamp Creek’ (Doherty 26), known from a single location within the park, and Pultenaea sp. (Olinda) from Dunns Swamp – both these species remain undescribed, but are listed as endangered species. After applying IUCN criteria to the 94 taxa, 2 are considered Critically Endangered; 11 are considered Endangered; 23 are considered Vulnerable; 3 are considered Near Threatened; 19 are considered Data Deficient; and 36 are considered of Least Concern. It is likely that additional highly restricted plant taxa await discovery in remote locations.
This third paper in the NSW Vegetation Classification and Assessment series covers the NSW South-western Slopes Bioregion of 8.192 million hectares being 10% of NSW. A total of 135 plant communities, comprising 97 new communities and 38 previously described communities, are classified. Their protected area and threat status is assessed. A full description of the 135 plant communities is provided in a 400 page report, generated from the NSWVCA database, on the CD accompanying this paper. Eucalyptus-dominated grassy or shrubby woodlands and open forests are the main types of vegetation in the bioregion. The CD also contains a read-only version of Version 2 of the NSWVCA database that includes updated information on the plant communities previously published in Version 1 of the NSWVCA covering the NSW Western Plains. Six new communities are added to the Western Plains. The vegetation classification and assessment is based on published and unpublished vegetation surveys and map unit descriptions that are listed in the NSWVCA Bibliography on the CD, expert advice and extensive field checking. Over 80% of the native vegetation in the NSW South-western Slopes Bioregion has been cleared making it the most cleared and fragmented of the 18 IBRA Bioregions in NSW. Exotic plant species dominate the ground cover outside conservation reserves, state forests, roadsides and travelling stock reserves. As of September 2008 about 1.9% of the Bioregion was in 105 protected areas and 28 of the 135 plant communities were assessed to be adequately protected in reserves. Using NSWVCA Threat Criteria, 18 plant communities were assessed as being Critically Endangered, 33 Endangered, 29 Vulnerable, 25 Near Threatened and 30 Least Concern. Current threats include over-grazing, especially during drought, exotic species dominance of the ground cover, impacts of fragmentation on species persistence and genetic diversity and impacts of lower rainfall due to climate change. To address these threats, linking and enlarging vegetation remnants through revegetation (including regenerating native ground cover) is required. Some progress is being made through re-vegetation schemes driven by the NSW 2003 Natural Resource reforms, however, more incentive funding for landholders would accelerate the re-vegetation program.
The floristic composition and environmental relations of wetland vegetation in the Wallis Lake catchment (32˚ 09’S; 152˚ 20’E), area 1292 km2, on the lower North Coast of NSW are described. The catchment supports wetlands listed as Endangered Ecological Communities (NSW Threatened Species Conservation Act 1995) and plant species of high conservation value. A methodology of air photo interpretation, site-based sampling (114 quadrats) and landscape differentiation was developed. A total of 393 vascular plant taxa were recorded (including 10% exotics). Wetland vegetation formations and subformations including mangrove forest, swamp sclerophyll forest, wet heathland, chenopod shrubland, tussock grassland, sedgeland and rushland are described using numerical classification. 31 plant species of national or regional conservation significance are identified. Four Endangered Ecological Communities are discussed – Coastal Saltmarsh, Swamp Oak Floodplain Forest, Swamp Sclerophyll Forest on Coastal Floodplains, and Freshwater Wetlands on Coastal Floodplains. A key recommendation is the completion of reliable wetland vegetation and soil landscape mapping for all land tenures in the catchment – to assess wetland condition and conservation significance, and representation in formal conservation reserves, thereby directing future priorities for the protection of wetland biodiversity on both public and private lands. The methodology developed can be applied to the survey and conservation of wetland biodiversity in other parts of coastal NSW.
Guidelines and core attributes for site-based vegetation surveying and mapping developed for the Northern Territory, are relevant to botanical research, forestry typing, rangeland monitoring and reporting on the extent and condition of native and non-native vegetated landscapes. These initiatives are consistent with national vegetation guidelines and the National Vegetation Information System (NVIS) framework. This paper provides a synopsis of vegetation site data collection, classification and mapping in the Northern Territory, and discusses the benefits of consistency between the guidelines, core attributes and the NVIS framework; both of which has an emphasis on the NVIS hierarchical classification system for describing structural and floristic attributes of vegetation. The long-term aim of the NVIS framework is that national attributes are adopted at regional levels to enable comparability of vegetation information within survey and jurisdictional boundaries in the Northern Territory and across Australia. The guidelines and core attributes are incorporated in current and future vegetation survey and mapping programs in the Northern Territory.
Fire is an integral component of many ecosystems worldwide. Many plant species require fire-related cues, primarily heat and smoke, to trigger germination. Despite the importance of this process, the responses of many Australian species to these cues are unknown. Without this knowledge fire management strategies may be developed that are inappropriate for individual species and vegetation communities. In this study we examined the responses of a dry sclerophyll forest seed bank to heat and smoke germination cues. Analysis was possible for 48 taxa within the soil seedbank with 34 of these showing a response to one or both of the germination cues. 10 species responded to the heat treatment, 11 species responded to the smoke treatment and 13 species responded to both the heat and smoke treatments. Germination cues acted independently for all species considered. Results in this study were consistent with published reports for most species, although some differences were seen at the species and genus level. The study highlights the importance of fire-related cues in enhancing germination of a large proportion of the species occurring in dry sclerophyll forests.
Introduced perennial grasses are capable of altering the habitat of native species, causing reductions in population size and vigour, and potentially affecting life-history processes such as survival, pollination and seedling recruitment. We examined the utility of herbicide treatment on two exotic grasses, Pennisetum clandestinum (Kikuyu) and Stenotaphrum secundatum (Buffalo grass) to restore the habitat of Calystegia affinis, a critically endangered species endemic to Lord Howe and Norfolk Islands. Using two herbicides, Asset (designed to affect only grasses) and Glyphosate (a general herbicide), we compared effectiveness in reducing grass cover on a population of Calystegia affinis. We protected Calystegia plants from the herbicides by ensuring their leaves were covered by plastic bags during herbicide application. Both herbicides were similarly effective in reducing grass cover after four weeks and had no noticeable adverse affect on Calystegia (suggesting the plastic bag protection was effective). After 26 weeks, Glyphosate was more effective in maintaining a reduced grass cover. Plots treated with either herbicide had a greater relative increase in abundance of Calystegia stems compared to untreated controls. The Glyphosate treatment resulted in the greatest relative increase in stem abundance, but this was not significantly greater than in the Asset treatment. We consider that spraying with Glyphosate treatment, with follow-up monitoring and spot-spraying, will assist the recovery of the Calystegia affinis population. Ultimately, the maintenance of a weed-free zone at the forest edge will provide suitable habitat for additional recruitment of this and other native species.
The Peak Range (22˚ 28’ S; 147˚ 53’ E) is an archipelago of rocky peaks set in grassy basalt rolling-plains, east of Clermont in central Queensland. This report describes the flora and vegetation based on surveys of 26 peaks. The survey recorded all plant species encountered on traverses of distinct habitat zones, which included the ‘matrix’ adjacent to each peak. The method involved effort comparable to a general flora survey but provided sufficient information to also describe floristic association among peaks, broad habitat types, and contrast vegetation on the peaks with the surrounding landscape matrix. The flora of the Peak Range includes at least 507 native vascular plant species, representing 84 plant families. Exotic species are relatively few, with 36 species recorded, but can be quite prominent in some situations. The most abundant exotic plants are the grass Melinis repens and the forb Bidens bipinnata. Plant distribution patterns among peaks suggest three primary groups related to position within the range and geology. The Peak Range makes a substantial contribution to the botanical diversity of its region and harbours several endemic plants among a flora clearly distinct from that of the surrounding terrain. The distinctiveness of the range’s flora is due to two habitat components: dry rainforest patches reliant upon fire protection afforded by cliffs and scree, and; rocky summits and hillsides supporting xeric shrublands. Plants endemic to the Peak Range are mainly associated with the latter of these habitats.
Species area curves from 37 sites spanning the diversity of native vegetation in Queensland were examined. For the majority of sites investigated a 500 m2 plot captured about 80–90% of the vascular plant species present at the time of sampling. Floristic data collected for grassland, heathland, acacia shrublands and most eucalypt woodlands using a 500 m2 plot is appropriate for floristic analysis and adequately represent the vascular plants present at the site at the time. Using a larger plot would only slightly increase the species capture at a site but it would generally be more efficient to increase the number of sites sampled to more adequately capture the diversity across the extent of the vegetation type. However for many Queensland rainforest communities, a much larger sample size is required to capture the full species richness of a site.
Digital document and interpretation : re-thinking "text" and scholarship in electronic settings
(2008)
The contribution starts from outlining the evolution of the scholarly production flow from the print based paradigm to the digital age and in this context it explores the opposition of digital versus analog representation modes. It then develops on the triple paradigm shift caused by genuine digital publishing and its specific consequences for the social sciences and humanities (SSH) which in turn results in re-constituting basic scholarly notions such as 'text' and 'document'. The paper concludes with discussing the specific value that could be added in systematically using digital text resources as a basis for scholarly work and also states some of the necessary conditions for such a 'digital turn' to be successful in the SSH.
The seasonality of transport and mixing of air into the lowermost stratosphere (LMS) is studied using distributions of mean age of air and a~mass balance approach, based on in-situ observations of SF6 and CO2 during the SPURT (Spurenstofftransport in der Tropopausenregion, trace gas transport in the tropopause region) aircraft campaigns. Combining the information of the mean age of air and the water vapour distributions we demonstrate that the tropospheric air transported into the LMS above the extratropical tropopause layer (ExTL) originates predominantly from the tropical tropopause layer (TTL). The concept of our mass balance is based on simultaneous measurements of the two passive tracers and the assumption that transport into the LMS can be described by age spectra which are superposition of two different modes. Based on this concept we conclude that the stratospheric influence on LMS composition is strongest in April with tropospheric fractions (α1) below 20% and that the strongest tropospheric signatures are found in October with (α1 greater than 80%. Beyond the fractions, our mass balance concept allows to calculate the associated transit times for transport of tropospheric air from the tropics into the LMS. The shortest transit times (<0.3 years) are derived for the summer, continuously increasing up to 0.8 years by the end of spring. These findings suggest that strong quasi-horizontal mixing across the weak subtropical jet from summer to mid of autumn and the considerably shorter residual transport time-scales within the lower branch of the Brewer-Dobson circulation in summer than in winter dominates the tropospheric influence in the LMS until the beginning of next year's summer.
his study aims at a detailed characterization of an ultra-fine aerosol particle counting system for operation on board the Russian high altitude research aircraft M-55 "Geophysica" (maximum ceiling of 21 km). The COndensation PArticle counting Systems (COPAS) consists of an aerosol inlet and two dual-channel continuous flow Condensation Particle Counters (CPCs).
The aerosol inlet, adapted for COPAS measurements on board the M-55 "Geophysica", is described concerning aspiration, transmission, and transport losses. The counting efficiencies of the CPCs using the chlorofluorocarbon FC-43 as the working fluid are studied experimentally at two pressure conditions, 300 hPa and 70 hPa. Three COPAS channels are operated with different temperature differences between the saturator and the condenser block yielding smallest detectable particle sizes (dp50 – as 50% detection "cut off" diameters) of 6 nm, 11 nm, and 15 nm, respectively, at ambient pressure of 70 hPa. The fourth COPAS channel is operated with an aerosol heating line (250°C) for a determination of the non-volatile number of particles. The heating line is experimentally proven to volatilize pure H2SO4-H2O particles for a particle diameter (dp) range of 11 nm<dp<200 nm.
Additionally this study includes investigation to exclude auto-nucleation of the working fluid inside the CPCs. An instrumental inter-comparison (cross-correlation) has been performed for several measurement flights and mission flights in the Arctic and the Tropics are discussed. Finally, COPAS measurements are used for an aircraft plume crossing analysis.
The ambient and laboratory molecular and ion clusters were investigated. Here we present data on the ambient concentrations of both charged and uncharged molecular clusters as well as the performance of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC). The ambient molecular cluster concentrations were measured using both instruments, and they were deployed in conjunction with ion spectrometers and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station during 1 March to 30 June 2007. The observed cluster concentrations varied and were from ca. 1000 to 100 000 cm−3. Both instruments showed similar concentrations. The average size of detected clusters was approximately 1.8 nm. As the atmospheric measurements at sub 2-nm particles and molecular clusters are a challenging task, and we were most likely unable to detect the smallest clusters, the reported concentrations are our best estimates for minimum cluster concentrations in boreal forest environment.
Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation.
Interleukin (IL)-18, formerly known as interferon (IFN)-γ-inducing factor, is a crucial mediator of host defence and inflammation. Control of IL-18 bioactivity by its endogenous antagonist IL-18 binding protein (IL-18BP) is a major objective of immunoregulation. IL-18BP is strongly up-regulated by IFN-γ, thereby establishing a negative feedback mechanism detectable in cell culture and in vivo. Here we sought to investigate in D.L. Dexter (DLD) colon carcinoma cells molecular mechanisms of IL-18BP induction under the influence of IFN-γ. Mutational analysis revealed that a proximal γ-activated sequence (GAS) at the IL-18BP promoter is of pivotal importance for expression by IFN-γ-activated cells. Use of siRNA underscored the essential role of the signal transducer and activator of transcription (STAT)-1 in this process. Indeed, electrophoretic mobility shift assay and chromatin immunoprecipitation analysis proved STAT1 binding to this particular GAS site. Maximal expression of IL-18BP was dependent on de novo protein synthesis but unaffected by silencing of interferon regulatory factor-1. Altogether, data presented herein indicate that direct action of STAT1 on the IL-18BP promoter at the proximal GAS element is key to IL-18BP expression by IFN-γ-stimulated DLD-1 colon carcinoma cells.
Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC.
The deposition of the amyloid β-protein (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD). Aβ-deposits show the morphology of senile plaques and cerebral amyloid angiopathy (CAA). Senile plaques and vascular Aβ-deposits occur first in neocorti-cal areas. Then, they expand hierarchically into further brain regions. The distribution of Aβ plaques throughout the entire brain, thereby correlates with the clinical status of the patients. Imaging techniques for Aβ make use of the hierarchical distribution of Aβ to distinguish AD patients from non-AD patients. However, pathology seen in AD patients represents a late stage of a pathological process starting 10–30 years earlier in cognitively normal individuals. In addition to the fibrillar amyloid of senile plaques, oligomeric and monomeric Aβ is found in the brain. Recent studies revealed that oligomeric Aβ is presumably the most toxic Aβ-aggregate, which interacts with glutamatergic synapses. In doing so, dendrites are presumed to be the primary target for Aβ-toxicity. In addition, vascular Aβ-deposits can lead to capillary occlusion and blood flow disturbances presumably contributing to the alteration of neurons in addition to the direct neurotoxic effects of Aβ. All these findings point to an important role of Aβ and its aggregates in the neurodegenerative process of AD. Since there is already significant neuron loss in AD patients, treatment strategies aimed at reducing the amyloid load will presumably not cure the symptoms of dementia but they may stop disease progression. Therefore, it seems to be necessary to protect the brain from Aβ-toxicity already in stages of the disease with minor neuron loss before the onset of cognitive symptoms.
FTY720 is a novel immunosuppressive drug that inhibits the egress of lymphocytes from secondary lymphoid tissues and thymus. In its phosphorylated form FTY720 is a potent S1P receptor agonist. Recently it was also shown that FTY720 can reduce prostaglandin synthesis through the direct inhibition of the cytosolic phospholipase A2 (cPLA2). Since prostaglandins are important mediators of nociception, we studied the effects of FTY720 in different models of nociception. We found that intraperitoneal administration of FTY720 reduced dose-dependently the nociceptive behaviour of rats in the formalin assay. Although the antinociceptive doses of FTY720 were too low to alter the lymphocyte count, prostanoid concentrations in the plasma were dramatically reduced. Surprisingly, intrathecally administered FTY720 reduced the nociceptive behaviour in the formalin assay without altering spinal prostaglandin synthesis, indicating that additional antinociceptive mechanisms beside the inhibition of prostaglandin synthesis are involved. Accordingly, FTY720 reduced also the nociceptive behaviour in the spared nerve injury model for neuropathic pain which does not depend on prostaglandin synthesis. In this model the antinociceptive effect of FTY720 was similar to gabapentin, a commonly used drug to treat neuropathic pain. Taken together we show for the first time that FTY720 possesses antinociceptive properties and that FTY720 reduces nociceptive behaviour during neuropathic pain.
ADAM15 belongs to a family of transmembrane multi-domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up-regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin-mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside-in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co-immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell-adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease.
New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma
(2008)
The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer.
This paper investigates the value of observed river discharge data for global-scale hydrological modeling of a number of flow characteristics that are e.g. required for assessing water resources, flood risk and habitat alteration of aquatic ecosystems. An improved version of the WaterGAP Global Hydrology Model (WGHM) was tuned against measured discharge using either the 724-station dataset (V1) against which former model versions were tuned or an extended dataset (V2) of 1235 stations. WGHM is tuned by adjusting one model parameter (γ) that affects runoff generation from land areas in order to fit simulated and observed long-term average discharge at tuning stations. In basins where γ does not suffice to tune the model, two correction factors are applied successively: the areal correction factor corrects local runoff in a basin and the station correction factor adjusts discharge directly the gauge. Using station correction is unfavorable, as it makes discharge discontinuous at the gauge and inconsistent with runoff in the upstream basin. The study results are as follows. (1) Comparing V2 to V1, the global land area covered by tuning basins increases by 5% and the area where the model can be tuned by only adjusting γ increases by 8%. However, the area where a station correction factor (and not only an areal correction factor) has to be applied more than doubles. (2) The value of additional discharge information for representing the spatial distribution of long-term average discharge (and thus renewable water resources) with WGHM is high, particularly for river basins outside of the V1 tuning area and in regions where the refined dataset provides a significant subdivision of formerly extended tuning basins (average V2 basin size less than half the V1 basin size). If the additional discharge information were not used for tuning, simulated long-term average discharge would differ from the observed one by a factor of, on average, 1.8 in the formerly untuned basins and 1.3 in the subdivided basins. The benefits tend to be higher in semi-arid and snow-dominated regions where the model is less reliable than in humid areas and refined tuning compensates for uncertainties with regard to climate input data and for specific processes of the water cycle that cannot be represented yet by WGHM. Regarding other flow characteristics like low flow, inter-annual variability and seasonality, the deviation between simulated and observed values also decreases significantly, which, however, is mainly due to the better representation of average discharge but not of variability. (3) The choice of the optimal sub-basin size for tuning depends on the modeling purpose. While basins over 60 000 km2 are performing best, improvements in V2 model performance are strongest in small basins between 9000 and 20 000 km2, which is primarily related to a low level of V1 performance. Increasing the density of tuning stations provides a better spatial representation of discharge, but it also decreases model consistency, as almost half of the basins below 20 000 km2 require station correction.
Long-term average groundwater recharge, which is equivalent to renewable groundwater resources, is the major limiting factor for the sustainable use of groundwater. Compared to surface water resources, groundwater resources are more protected from pollution, and their use is less restricted by seasonal and inter-annual flow variations. To support water management in a globalized world, it is necessary to estimate groundwater recharge at the global scale. Here, we present a best estimate of global-scale long-term average diffuse groundwater recharge (i.e. renewable groundwater resources) that has been calculated by the most recent version of the WaterGAP Global Hydrology Model WGHM (spatial resolution of 0.5° by 0.5°, daily time steps). The estimate was obtained using two state-of-the-art global data sets of gridded observed precipitation that we corrected for measurement errors, which also allowed to quantify the uncertainty due to these equally uncertain data sets. The standard WGHM groundwater recharge algorithm was modified for semi-arid and arid regions, based on independent estimates of diffuse groundwater recharge, which lead to an unbiased estimation of groundwater recharge in these regions. WGHM was tuned against observed long-term average river discharge at 1235 gauging stations by adjusting, individually for each basin, the partitioning of precipitation into evapotranspiration and total runoff. We estimate that global groundwater recharge was 12 666 km3/yr for the climate normal 1961–1990, i.e. 32% of total renewable water resources. In semi-arid and arid regions, mountainous regions, permafrost regions and in the Asian Monsoon region, groundwater recharge accounts for a lower fraction of total runoff, which makes these regions particularly vulnerable to seasonal and inter-annual precipitation variability and water pollution. Average per-capita renewable groundwater resources of countries vary between 8 m3/(capita yr) for Egypt to more than 1 million m3/(capita yr) for the Falkland Islands, the global average in the year 2000 being 2091 m3/(capita yr). Regarding the uncertainty of estimated groundwater resources due to the two precipitation data sets, deviation from the mean is 1.1% for the global value, and less than 1% for 50 out of the 165 countries considered, between 1 and 5% for 62, between 5 and 20% for 43 and between 20 and 80% for 10 countries. Deviations at the grid scale can be much larger, ranging between 0 and 186 mm/yr.
We report progress in our exploration of the finite-temperature phase structure of two-flavour lattice
QCD with twisted-mass Wilson fermions and a tree-level Symanzik-improved gauge action
for a temporal lattice size Nt = 8. Extending our investigations to a wider region of parameter
space we gain a global view of the rich phase structure. We identify the finite temperature transition/
crossover for a non-vanishing twisted-mass parameter in the neighbourhood of the zerotemperature
critical line at sufficiently high b . Our findings are consistent with Creutz’s conjecture
of a conical shape of the finite temperature transition surface. Comparing with NLO lattice
cPT we achieve an improved understanding of this shape.
We perform a detailed study of the adjoint static potential in the pseudoparticle approach, which is a model for SU(2) Yang-Mills theory. We find agreement with the Casimir scaling hypothesis and there is clear evidence for string breaking. At the same time the potential in the fundamental representation is linear for large separations. Our results are in qualitative agreement with results from lattice computations.
We present the status of runs performed in the twisted mass formalism with Nf =2+1+1 flavours of dynamical fermions: a degenerate light doublet and a mass split heavy doublet. The procedure for tuning to maximal twist will be described as well as the current status of the runs using both thin and stout links. Preliminary results for a few observables obtained on ensembles at maximal twist will be given. Finally, a reweighting procedure to tune to maximal twist will be described.
We investigate the implications of the r-modes instability on the composition of a compact star rotating at a sub-millisecond period. In particular, the only viable astrophysical scenario for such an object, wich might present inside the Low Mass X-ray Binary associated with the x-ray transient XTE J1739-285, is that it has a strangeness content. Since previous analysis indicate that hyperonic stars or stars containing a kaon condensate are unlikely because of the mass-shedding constraint, the only remaining possibility is that such an object is either a strange quark star or a hybrid quark-hadron star.
The possible role of a first order QCD phase transition at nonvanishing quark chemical potential and temperature for cold neutron stars and for supernovae is delineated. For cold neutron stars, we use the NJL model with nonvanishing color superconducting pairing gaps, which describes the phase transition to the 2SC and the CFL quark matter phases at high baryon densities. We demonstrate that these two phase transitions can both be present in the core of neutron stars and that they lead to the appearance of a third family of solution for compact stars. In particular, a core of CFL quark matter can be present in stable compact star configurations when slightly adjusting the vacuum pressure to the onset of the chiral phase transition from the hadronic model to the NJL model. We show that a strong first order phase transition can have strong impact on the dynamics of core collapse supernovae. If the QCD phase transition sets in shortly after the first bounce, a second outgoing shock wave can be generated which leads to an explosion. The presence of the QCD phase transition can be read off from the neutrino and antineutrino signal of the supernova.
Introduction: Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients.
Methods: Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (< 60 years, between 60 and 64 years, and > 64 years) with primary breast cancer received taxane-based chemotherapy.
Results: Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged < 60 years to 65.5% in patients aged > 64 years (P < 0.001), and neutropenia increased from 46.9% to 57.4% (P < 0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age.
Conclusions: The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo)adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens.
* The Professionalization of General Practice
* 42nd Congress of the DEGAM German Society of General Practice and Family Medicine
* Online Registration for students now possible
* Opera tickets for participants in the PRoMPT study
* MultiCare: Multimorbidity patterns in General Practice
* Berlin Health Prize 2008: Words are not enough
Background: There are several ways to conduct a job task analysis in medical work environments including pencil-paper observations, interviews and questionnaires. However these methods implicate bias problems such as high inter-individual deviations and risks of misjudgement. Computer-based observation helps to reduce these problems. The aim of this paper is to give an overview of the development process of a computer-based job task analysis instrument for real-time observations to quantify the job tasks performed by physicians working in different medical settings. In addition reliability and validity data of this instrument will be demonstrated.
Methods: This instrument was developed in consequential steps. First, lists comprising tasks performed by physicians in different care settings were classified. Afterwards content validity of task lists was proved. After establishing the final task categories, computer software was programmed and implemented in a mobile personal computer. At least inter-observer reliability was evaluated. Two trained observers recorded simultaneously tasks of the same physician.
Results: Content validity of the task lists was confirmed by observations and experienced specialists of each medical area. Development process of the job task analysis instrument was completed successfully. Simultaneous records showed adequate interrater reliability.
Conclusion: Initial results of this analysis supported the validity and reliability of this developed method for assessing physicians' working routines as well as organizational context factors. Based on results using this method, possible improvements for health professionals' work organisation can be identified.
Since 2002, a workshop entitled “Asthma in animal models” has been held once a year in Hannover, Germany. It is organized by the Fraunhofer Institute of Toxicology and Experimental Medicine in collaboration with the collaborative research centre “Sonderforschungsbereich” 587, “Immune reactions of the lung in infection and allergy” (Hannover Medical School). The aim of these meetings is an intense scientific exchange between researchers and clinicians coming from academic or industrial background. Over the years the topics within the extensive field of asthma and COPD have ranged from methodological aspects to the influence of infections and environmental factors up to perspectives in the development of new therapeutic strategies.
Background: Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B) are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity.
Methods: The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique.
Results: Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity.
Conclusion: Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.
Metaphorization and selected translation techniques : the case study of "National Geographic"
(2008)
Judging by appearances : a study of human-oriented metonymic developments in the domain of dress
(2008)
Investigations of the micro- and nanostructures and chemical composition of the sponge skeletons as examples for natural structural biocomposites are of fundamental scientific relevance. Recently, we show that some demosponges (Verongula gigantea, Aplysina sp.) and glass sponges (Farrea occa, Euplectella aspergillum) possess chitin as a component of their skeletons. The main practical approach we used for chitin isolation was based on alkali treatment of corresponding external layers of spicules sponge material with the aim of obtaining alkali-resistant compounds for detailed analysis. Here, we present a detailed study of the structural and physicochemical properties of spicules of the glass sponge Rossella fibulata. The structural similarity of chitin derived from this sponge to invertebrate alpha chitin has been confirmed by us unambiguously using physicochemical and biochemical methods. This is the first report of a silica-chitin composite biomaterial found in Rossella species. Finally, the present work includes a discussion related to strategies for the practical application of silica-chitin-based composites as biomaterials.
P-type ATPases are membrane proteins acting as ion pumps that drive an active transport of cations across the membrane against a concentration gradient. The required energy for the ion transport is provided by binding and hydrolysis of ATP. A reaction mechanism of ion transport and energy transduction is assumed to be common for all P-type ATPases and generally described by the Post-Albers cycle. Transient currents and charge translocation of P-type ATPases were extensively investigated by electrical measurements that apply voltage jumps to initiate the reaction cycle. In this study, we simulate an applied voltage across the membrane by an electric field and perform electrostatic calculations in order to verify the experimentally-driven hypothesis that the energy transduction mechanism is regulated by specific structural elements. Side chain conformational and ionization changes induced by the electric field are evaluated for each transmembrane helix and the selectivity in response is qualitatively analyzed for the Ca2+-ATPase as well as for structural models of the Na+/K+-ATPase. Helix M5 responds with more conformer changes as compared to the other transmembrane helices what is even more emphasized when the stalk region is included. Thus our simulations support experimental results and indicate a crucial role for the highly conserved transmembrane helix M5 in the energy transduction mechanism of P-type ATPases.
Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.
Keywords: apoptosis, cancer, betulinic acid, mitochondria
Keywords: AIF, apoptosis inducing factor; Apaf-1, Apoptotic protease activating factor-1; BA, betulinic acid; DIABLO, direct IAP Binding protein with Low PI; HtrA2, high temperature requirement protein A; IAPs, Inhibitor of Apoptosis Proteins; MOMP, mitochondrial outer membrane permeabilization; ROS, reactive oxygen species; PARP, Poly (ADP-ribose) Polymerase; Smac, second mitochondria-derived activator of caspase; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; zVAD.fmk, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
Science in Wonderland
(2008)
Lewis Carroll's Alice, who first explores Wonderland (1865) and later on the country behind the Looking-Glass (1872), belongs to the most well-known characters in world literature. [...] The scientific reception of Carroll's stories – concerning physics as well as the humanities – has taken place on different levels. On the one hand, […] various Carrollian ideas and episodes obviously correspond to topics, subjects and models that are treated in the contexts of scientific discourses. Therefore, they can be quoted or alluded to in order to represent theories and questions […] – as […] physical models of the world […]or theoretical models of language and communication. […] On a more abstract level of observation, Carroll's stories have been used in order to explain and to discuss the pre-conditions, the procedures, and the limits . of scientific modeling as such. Above all, they make it possible to narrate on the problem of defining and observing an 'object' of research. […] According to Deleuze, the paradox structures of the world that Alice experiences give an idea of all meaning being groundless and all logic being subverted by the illogical. Finally, besides all affinities of Alice's adventures to scientific attempts to explain the world, the absolutely incomprehensible is present in Carroll's books as well. Especially the self proves to be something profoundly incomprehensible […].
Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances
(2008)
Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone.
Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised controlled study in humans.
Methods: The penetration profiles of the hydrophilic dye fluorescein and the lipophilic dye curcumin in separate standard water-in-oil emulsions were determined on the inner forearm of test persons by tape stripping in combination with spectroscopic measurements. Additionally, the penetration was investigated in vivo by laser scanning microscopy. Transepidermal water loss, hydration of the epidermis, and surface temperature were determined. Three different procedures (modes A, B, C) were used in a randomised order on three separate days of investigation in each of 12 test persons. In mode A, the two dyes were applied on different skin areas without water-filtered infrared-A (wIRA) irradiation. In mode B, the skin surface was irradiated with wIRA over 30 min before application of the two dyes (Hydrosun® radiator type 501, 10 mm water cuvette, orange filter OG590, water-filtered spectrum: 590–1400 nm with dominant amount of wIRA). In mode C, the two dyes were applied and immediately afterwards the skin was irradiated with wIRA over 30 min. In all modes, tape stripping started 30 min after application of the formulations. Main variable of interest was the ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum.
Results: The penetration profiles of the hydrophilic fluorescein showed in case of pretreatment or treatment with wIRA (modes B and C) an increased penetration depth compared to the non-irradiated skin (mode A): The ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum showed medians and interquartile ranges for mode A of 0.017 (0.007/0.050), for mode B of 0.084 (0.021/0.106), for mode C of 0.104 (0.069/0.192) (difference between modes: p=0.0112, significant; comparison mode A with mode C: p<0.01, significant). In contrast to fluorescein, the lipophilic curcumin showed no differences in the penetration kinetics, in reference to whether the skin was irradiated with wIRA or not. These effects were confirmed by laser scanning microscopy. Water-filtered infrared-A irradiation increased the hydration of the stratum corneum: transepidermal water loss rose from approximately 8.8 g m-2 h-1 before wIRA irradiation to 14.2 g m-2 h-1 after wIRA irradiation and skin hydration rose from 67 to 87 relative units. Skin surface temperature increased from 32.8°C before wIRA to 36.4°C after wIRA irradiation.
Discussion: The better penetration of the hydrophilic dye fluorescein after or during skin irradiation (modes B and C) can be explained by increased hydration of the stratum corneum by irradiation with wIRA.
Conclusions: As most topically applied substances for the treatment of patients are mainly hydrophilic, wIRA can be used to improve the penetration of substances before or after application of substances – in the first case even of thermolabile substances – with a broad clinical relevance as a contact free alternative to an occlusive dressing.
Background: Water-filtered infrared-A (wIRA) is a special form of heat radiation with a high tissue-penetration and with a low thermal burden to the surface of the skin. wIRA is able to improve essential and energetically meaningful factors of wound healing by thermal and non-thermal effects.
Aim of the study: prospective study (primarily planned randomised, controlled, blinded, de facto with one exception only one cohort possible) using wIRA in the treatment of patients with recalcitrant chronic venous stasis ulcers of the lower legs with thermographic follow-up.
Methods: 10 patients (5 males, 5 females, median age 62 years) with 11 recalcitrant chronic venous stasis ulcers of the lower legs were treated with water-filtered infrared-A and visible light irradiation (wIRA(+VIS), Hydrosun® radiator type 501, 10 mm water cuvette, water-filtered spectrum 550–1400 nm) or visible light irradiation (VIS; only possible in one patient). The uncovered wounds of the patients were irradiated two to five times per week for 30 minutes at a standard distance of 25 cm (approximately 140 mW/cm2 wIRA and approximately 45 mW/cm2 VIS). Treatment continued for a period of up to 2 months (typically until closure or nearly closure of the ulcer). The main variable of interest was “percent change of ulcer size over time” including complete wound closure. Additional variables of interest were thermographic image analysis, patient’s feeling of pain in the wound, amount of pain medication, assessment of the effect of the irradiation (by patient and by clinical investigator), assessment of feeling of the wound area (by patient), assessment of wound healing (by clinical investigator) and assessment of the cosmetic state (by patient and by clinical investigator). For these assessments visual analogue scales (VAS) were used.
Results: The study showed a complete or nearly complete healing of lower leg ulcers in 7 patients and a clear reduction of ulcer size in another 2 of 10 patients, a clear reduction of pain and pain medication consumption (e.g. from 15 to 0 pain tablets per day), and a normalization of the thermographic image (before the beginning of the therapy typically hyperthermic rim of the ulcer with relative hypothermic ulcer base, up to 4.5°C temperature difference). In one patient the therapy of an ulcer of one leg was performed with the fully active radiator (wIRA(+VIS)), while the therapy of an ulcer of the other leg was made with a control group radiator (only VIS without wIRA), showing a clear difference in favour of the wIRA treatment. All mentioned VAS ratings improved remarkably during the period of irradiation treatment, representing an increased quality of life. Failures of complete or nearly complete wound healing were seen only in patients with arterial insufficiency, in smokers or in patients who did not have venous compression garment therapy.
Discussion and conclusions: wIRA can alleviate pain considerably (with an impressive decrease of the consumption of analgesics) and accelerate wound healing or improve a stagnating wound healing process and diminish an elevated wound exudation and inflammation both in acute and in chronic wounds (in this study shown in chronic venous stasis ulcers of the lower legs) and in problem wounds including infected wounds. In chronic recalcitrant wounds complete healing is achieved, which was not reached before. Other studies have shown that even without a disturbance of wound healing an acute wound healing process can be improved (e.g. reduced pain) by wIRA.
wIRA is a contact-free, easily used and pleasantly felt procedure without consumption of material with a good penetration effect, which is similar to solar heat radiation on the surface of the earth in moderate climatic zones. Wound healing and infection defence (e.g. granulocyte function including antibacterial oxygen radical formation of the granulocytes) are critically dependent on a sufficient energy supply (and on sufficient oxygen). The good clinical effect of wIRA on wounds and also on problem wounds and wound infections can be explained by the improvement of both the energy supply and the oxygen supply (e.g. for the granulocyte function). wIRA causes as a thermal effect in the tissue an improvement in three decisive factors: tissue oxygen partial pressure, tissue temperature and tissue blood flow. Besides this non-thermal effects of infrared-A by direct stimulation of cells and cellular structures with reactions of the cells have also been described. It is concluded that wIRA can be used to improve wound healing, to reduce pain, exudation, and inflammation and to increase quality of life.
A wall-sized canvas by Twombly hanging in a purpose-built pavilion by Renzo Piano, commissioned by the Menil Collection in Houston, bears the scrawled inscription »Anatomy of Melancholy.« Untitled (Say Goodbye Catullus, to the Shores of Asia Minor) is the culminating statement of the artist’s maturity: begun in 1972, it was first exhibited in 1994. In this monumental cenotaph, Twombly’s painting displays phrases from Archilochos, Catullus, Keats and Rilke, as well as the title of Burton’s famous tome, worked into the fabric of the composition, integral to the iconic content. It is the aching heart of the select permanent exhibition of his oeuvre at the pavilion, known as the Twombly Gallery (www.menil.org/twombly.html). The austerity of Piano’s architectural setting, as well as the cunningly filtered Texas sunlight, makes this a site of cult, like the chapel containing the dark, final canvases of Mark Rothko, situated around the corner in the same urban grove of old oak. The setting is a modern Dodona, remote seat of the oaken oracle of Zeus, and it makes an evocative home for Twombly’s enigmatic constructions. These disarm conventional vocabularies of aesthetic response, drawing attention to words and snatches of verse as points of association and recognition. Looking at them involves siting a phrase such as »Anatomy of Melancholy« in other dimensions – in lines, patches, figures, colors.
Lichens are the object of investigation within the framework of the BIOTA Southern Africa project, subproject S04 (http://www.biota-africa.org). This interdisciplinary research project, installed in 2000, focuses on the analysis of biodiversity and its changes along climatic and vegetation gradients (transects) in Namibia and in the Republic of South Africa. In the context of this project, studies on the diversity of lichens are carriedout. Special reference is given to the monitoring of lichens growing on soil, which form the so called biological soil crusts.Lichen diversity is assessed and analysed with respect to its spatial and temporal changes. These are related to various abioticand biotic factors such as climate, soil features and land use. The indicator value of certain terricolouslichen taxaand/or lichen groups (communities) is investigated for the study area, and it is intended to use itin a future long-term monitoring programme in the region. In this brochure, we whish to explain what lichens are, how do they live and where do they grow, and why they are so important as bioindicatorsin arid and semi-arid areas of the world. The activities of the S04 subproject along the BIOTA transect are described, as well as the methods used for monitoring environmental changes in Southern Africa using soil-inhabiting lichens.
Die vorliegende Arbeit diskutiert Auffassungen über Authentizität und Nationale Identität in Julian Barnes’ England, England und Brian Moore’s The Great Victorian Collection. Julian Barnes und Brian Moore bearbeiten postmoderne Themen in ihrer Auseinandersetzung mit Realität und Authentizität. Brian Moore diskutiert die Möglichkeit der Ununterscheidbarkeit zwischen Original und Replika, Julian Barnes verdeutlicht die Konsequenzen eines Nationalgefühls, das sich auf die Vorstellung einer verklärten Vergangenheit stützt anstatt sich den Problemen der Gegenwart zu stellen.
Die postmoderne Diskussion hinterfragt Theorien der Moderne. In der Moderne entwickelten sich Nationalstaaten zur grundlegenden politischen Struktur, die eine für den aufkommenden Kapitalismus unabdingbare Einheit und Gleichheit ermöglichte. Die postmoderne Kritik unterstreicht, dass diese Ordnung nicht natürlich ist, sondern auf ein tatsächliches Chaos von Fragmenten aufgezwungen wurde. Theorien der Postmoderne betonen die Uneinigkeit und Künstlichkeit von Nationalstaaten. Es wird aufgezeigt, dass ein Nationalstaat aus vielen verschiedenen und sogar untereinander gegensätzlichen Gruppierungen besteht. Die einheitliche Identifikation der Bürger mit einem Nationalstaat basiert auf der Vorstellung einer andauernden, geteilten Geschichte, und einer Betonung von Gemeinsamkeiten und vermeintlichen Unterschieden gegenüber Anderen. Diese Vorstellung von Einigkeit und Gemeinsamkeit wird in der Postmoderne als Konstrukt enthüllt.
In ähnlicher Weise betonen postmoderne Theorien die Konstruiertheit der Vorstellung eines einheitlichen, wahren Selbst. Das Selbst wird empfunden als eine Ansammlung von zahlreichen, untereinander teilweise widerstreitenden, Teilen.
Die Entwicklung der Industrialisierung im Kapitalismus der Moderne führte zur Auflösung bestehender lokaler Strukturen, und somit zu einer Entwurzelung der Individuen. Am Ende des zwanzigsten Jahrhunderts verlangt der Konsumkapitalismus von den Menschen Mobilität und Wandelbarkeit. In dieser Phase der Globalisierung verlieren Nationalstaaten an Bedeutung. Persönliche Qualitäten wie Charakterstärke und Authentizität geraten in den Hintergrund, während die Fähigkeit zur Verstellung und ein hohes Maß an Flexibilität geachtet werden und Erfolg versprechen.
Diese Entwicklung bringt ein Gefühl des Verlustes mit sich, ein Gefühl von Heimatlosigkeit, Wurzellosigkeit, und Uneinigkeit mit sich selbst.
Die postmoderne nostalgische Sehnsucht nach einer idealisierten Vergangenheit basiert auf diesem Gefühl des Verlustes einer ehemaligen Einigkeit.
Die Besucher von Themenparks und heritage sites sehnen sich nach dem Erlebnis einer glorifizierten Vergangenheit, wobei die Authentizität der dargestellten Geschichte zweitrangig ist.
Julian Barnes und Brian Moore beschreiben die Errichtung und den Erfolg von Themenparks. Ungeachtet der Künstlichkeit der dargebotenen Shows und so mancher Ausstellungsstücke genießen postmoderne Besucher von Themenparks deren Hyperrealität, die ein Gefühl von Ganzheit und Einheit vermittelt.
Das erste Kapitel der Arbeit stellt zunächst die Gedankenwelt der Postmoderne dar. Die postmoderne Welt am Ende des zwanzigsten Jahrhunderts verlangt Mobilität, Anpassung, und Verstellung. Hierin gründet das Gefühl der Nostalgie nach Ganzheit und Zugehörigkeit, welches im zweiten Kapitel untersucht wird. Das dritte Kapitel ist der Struktur des Nationalstaates gewidmet, die in einem komplexen Zusammenspiel von Politik, Geschichte, und den Bedürfnissen der Gegenwart eine Möglichkeit der Identifikation darstellt, welche Ganzheit und Zugehörigkeit verspricht. Das vierte Kapitel zeigt, dass die Identifikation mit einem Nationalstaat auf der Vorstellung einer gemeinsamen Geschichte basiert, wie sie in Museen und heritage sites bewahrt und bestimmt wird, und wie sie durch die Ausübung – oder Einführung – von Traditionen gelebt wird.
Das fünfte Kapitel diskutiert den Zusammenhang zwischen Authentizität und Erschaffung, und zeigt, dass die Grenzen fließend sind, da seit jeher Traditionen und Gepflogenheiten zugunsten der Bedürfnisse der Gegenwart abgewandelt wurden. Julian Barnes und Brian Moore demonstrieren, dass in der Tourismusindustrie Authentizität an Wert verloren hat, da postmoderne Reisende, die an Simulationen gewöhnt sind, sich mit leichter erreichbaren Nachbildungen begnügen. Abschließend lässt sich feststellen, dass die Vorstellung einer ehemaligen Vollkommenheit und Heimat in der Vergangenheit der Auseinandersetzung mit den Bedürfnissen der Gegenwart im Wege steht. Dies äußert sich letztlich politisch, wie das gegenwärtig vorherrschende Misstrauen gegenüber supranationalen Strukturen wie der Europäischen Union zeigt.
The influence of visual tasks on short and long-term memory for visual features was investigated using a change-detection paradigm. Subjects completed 2 tasks: (a) describing objects in natural images, reporting a specific property of each object when a crosshair appeared above it, and (b) viewing a modified version of each scene, and detecting which of the previously described objects had changed. When tested over short delays (seconds), no task effects were found. Over longer delays (minutes) we found the describing task influenced what types of changes were detected in a variety of explicit and incidental memory experiments. Furthermore, we found surprisingly high performance in the incidental memory experiment, suggesting that simple tasks are sufficient to instill long-lasting visual memories. Keywords: visual working memory, natural scenes, natural tasks, change detection
The Göttingen conference Systematics 2008 is the first joint meeting of the Gesellschaft für Biologische Systematik (GfBS) and the German Botanical Society, section Biodiversity and Evolutionary Biology (DBG), being the 10th Annual Meeting of the GfBS and the 18th International Symposium Biodiversity and Evolutionary Biology of the DBG. The conference programme covers biological systematics in the widest sense and provides ample opportunities for oral and poster presentations on new advances in plant, animal and microbial systematics. This volume brings together the abstracts of invited speaches from the plenary sessions on Progress in Deep Phylogeny, Speciation and Phylogeography, and New Trends in Biological Systematics as well as those of submitted talks and poster sessions.The Göttingen conference Systematics 2008 is the first joint meeting of the Gesellschaft für Biologische Systematik (GfBp. and the German Botanical Society, section Biodiversity and Evolutionary Biology (DBG), being the 10th Annual Meeting of the GfBS and the 18th International Symposium Biodiversity and Evolutionary Biology of the DBG. The conference programme covers biological systematics in the widest sense and provides ample opportunities for oral and poster presentations on new advances in plant, animal and microbial systematics. This volume brings together the abstracts of invited speaches from the plenary sessions on Progress in Deep Phylogeny, Speciation and Phylogeography, and New Trends in Biological Systematics as well as those of submitted talks and poster sessions.
Chlamydia are obligate intracellular bacteria that cause variety of human diseases. Host cells infected with Chlamydia are protected against many different apoptotic stimuli. The induction of apoptosis resistance is thought to be an important immune escape mechanism allowing Chlamydia to replicate inside the host cell. Infection with C. trachomatis activates the Raf/MEK/ERK pathway and the PI3K/AKT pathway. Here we show that inhibition of these two pathways by chemical inhibitors sensitized C. trachomatis infected cells to granzyme B-mediated cell death. Infection leads to the Raf/MEK/ERK-mediated up-regulation and PI3K-dependent stabilization of the anti-apoptotic Bcl-2 family member Mcl-1. Consistently, interfering with Mcl-1 up-regulation sensitized infected cells for apoptosis induced via the TNF receptor, DNA damage, granzyme B and stress. Our data suggest that Mcl-1 up-regulation is primarily required to maintain apoptosis resistance in C. trachomatis-infected cells.
Background: The BH3-only protein Bid is an important component of death receptor-mediated caspase activation. Bid is cleaved by caspase-8 or -10 into t-Bid, which translocates to mitochondria and triggers the release of caspase-activating factors. Bid has also been reported to be cleaved by other proteases. Methodology/Principal Findings: To test the hypothesis that Bid is a central mediator of stress-induced apoptosis, we investigated the effects of a small molecule Bid inhibitor on stress-induced apoptosis, and generated HeLa cells deficient for Bid. Stable knockdown of bid lead to a pronounced resistance to Fas/CD95- and TRAIL-induced caspase activation and apoptosis, and significantly increased clonogenic survival. While Bid-deficient cells were equally sensitive to ER stress-induced apoptosis, they showed moderate, but significantly reduced levels of apoptosis, as well as increased clonogenic survival in response to the genotoxic drugs Etoposide, Oxaliplatin, and Doxorubicin. Similar effects were observed using the Bid inhibitor BI6C9. Interestingly, Bid-deficient cells were dramatically protected from apoptosis when subtoxic concentrations of ER stressors, Etoposide or Oxaliplatin were combined with subtoxic TRAIL concentrations. Conclusions/Significance: Our data demonstrate that Bid is central for death receptor-induced cell death and participates in anti-cancer drug-induced apoptosis in human cervical cancer HeLa cells. They also show that the synergistic effects of TRAIL in combination with either ER stressors or genotoxic anti-cancer drugs are nearly exclusively mediated via an increased activation of Bid-induced apoptosis signalling.
Background: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens.
The Kaiserchronik is generically puzzling. In essence it is a spiritual world chronicle, but it lacks the usual historiographical systematisations of its theological content. However it does have three disputations, an unusual feature in a chronicle which has to date not been adequately explained. This essay argues, on the basis of comparisons with works in other literary forms, that these passages function as key expressions of the controlling idea of the entire work, namely the progress of the Gospel from the heathen to the Christian Empire, and that they are strategically located within the chronicle at the turning points in the success of Christian mission.
The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling. Keywords: Acute Myeloid Leukemia (AML), Allogeneic Stem Cell Transplantation (SCT), Indication, Cytogenetics, Polymerase Chain Reaction (PCR)
Communication in the Web 2.0 context mainly works through images. The online video platform YouTube uses this form of visual communication and makes art forms of Western societies visible through their online videos. YouTube, as cultural reservoir and visual archive of moving images, accommodates the whole range of visualising creative processes – from artistic finger exercises to fine arts. A general characteristic of YouTube is the publishing of small everyday gestures of the ‘big ones’ (politicians, stars), like small incidents and their clumsiness in everyday actions, e.g. Beyonce´s fall from the stage or Tom Cruise’s demonic pro-scientology interview. Through their viral distribution on different platforms, these incidents will never be covered up or disappear from the public view. At the same time big gestures and star images are replicated and sometimes reinterpreted by the ‘small people’ who present themselves in the poses and attitudes of the stars. Generally, a coexistence of different perspectives is possible. YouTube allows polysemic and polyvalent views on the everyday and media phenomena. This article relies on YouTube research 2 that started in 2006 at the New Media Department of the Goethe University of Frankfurt. The results of the research have already presented representative forms and basic patterns, that is to say, categories for the clips appearing here. These kinds of clips, recurring in the observation period, have an impact on the basic representation of art or artistic expression within moving images on this platform. Methodologically the focus leads to the investigation (which has to be adequate to the specifics of the medium, or ‘media adequate’) of new visual structures and forms which can create – consciously or unconsciously – an art form. After focusing on the media structures, it will be discussed whether any and, if so, which ‘authentic’ new forms were developed solely on YouTube and whether these forms are innovative and can be characterised as avant-garde. This article first takes a small step in evaluating how to get from a general communication through means of visuality in web 2.0, an often endless chatty cheesy visual noise 3 – to the special quality of a consciously created aesthetic. From where do innovative aesthetic forms emerge, related to their media structures? 4 Are they the products of ‘media amateurs’ 5 or do we have to find new specifications and descriptions for the producers? The definition of a ‘media amateur’ describes technically interested private individuals who acquire and develop technology before commercial use of the technology is even recognisable. Just as artists are developing their own techniques, according to Dieter Daniels, media amateurs are autodidacts who invent techniques, rather than just acquire knowledge about them (see for example the demo scene, the machinima, brickfilm producers as well as many areas of computer gaming in general 6). The media amateur directly intervenes in the production processes of the medium and does not just simply use the medium. What is fascinating is the media amateur’s process of self education – not the result – and the direct impact on the internal structure and the control of the medium. 7 Media amateurs open a previously culturally unformed space of experience. This only partially applies to most of the YouTube clips in the realms of the visual arts; it is here most important to look at the visual content. This article discusses all these concepts and introduces new descriptions for the different forms of production: the technically oriented media master, the do-it-yourselfer, the tinkerer, the amateur handicraftsman and the inventor. It outlines a basic research project on ‘visual media culture’ (a triangulation of research on media structure and iconography) of the presented online video platform. It is a product of the analysis of clips focusing on the media structure, analyzing the creative handling of images and the deviations and differences of pre-set media formats and stereotypes.
The Video Vortex Reader is the first collection of critical texts to deal with the rapidly emerging world of online video – from its explosive rise in 2005 with YouTube, to its future as a significant form of personal media. After years of talk about digital convergence and crossmedia platforms we now witness the merger of the Internet and television at a pace no-one predicted. These contributions from scholars, artists and curators evolved from the first two Video Vortex conferences in Brussels and Amsterdam in 2007 which focused on responses to YouTube, and address key issues around independent production and distribution of online video content. What does this new distribution platform mean for artists and activists? What are the alternatives?
In a charter issued on 5 May 1513, the mayor and city council of the city of Freiburg/Breisgau reported that several citizens wanted to be allowed to establish a bruderschaft der sengerye, a confraternity of singing. “God, the almighty, would be praised thereby, the souls would be consoled, and all men listening to the concerts would be kept from blasphemy, gaming and other secular vices” (“gott der allmechtig [würde] dardurch gelopt, die selen getröst und die menschen zu zyten, so sy dem gesang zuhorten, von gotslesterung, ouch vom spyl vnd anderer weltlicher uppigkeyt gezogen”). Considering not least the “positive effects on the pour souls” (“guettaeten, so den armen selen dardurch nachgeschechen mocht”), the request was allowed. But the petitioners had to establish their bruderschaft in exactly the form that is described in detail in the regulations (ordnung) added to the request and cited “word for word” (“von wort zu wort”) in 17 articles in the foundation charter of the confraternity.
This paper discusses the effect of capital regulation on the risk taking behavior of commercial banks. We first theoretically show that capital regulation works differently in different market structures of banking sectors. In lowly concentrated markets, capital regulation is effective in mitigating risk taking behavior because banks' franchise values are low and banks have incentives to pursue risky strategies in order to increase their franchise values. If franchise values are high, on the other hand, the effect of capital regulation on bank risk taking is ambiguous as banks lack those incentives. We then test the model predictions on a cross-country sample including 421 commercial banks from 61 countries. We find that capital regulation is effective in mitigating risk taking only in markets with a low degree of concentration. The results remain robust after accounting for financial sector development, legal system effciency, and for other country and bank-specific characteristics. Keywords: Banks, market structure, risk shifting, franchise value, capital regulation
TABLE OF CONTENTS (here without authors) Introduction 1. Em Busca dos Sítios do Poder na África Centro Ocidental. Homens e Caminhos, Exércitos e Estradas (1483-1915) 2. The Supply and Deployment of Horses in Angolan Warfare (17th and 18th Centuries) 3. Wagon Technology, Transport and Long-distance Communication in Angola 1885-1908 4. Trade, Slavery, and Migration in the Interior of Benguela: The Case of Caconda, 1830-1870 5. The Economics of the Kwango Rubber Trade, c. 1900 6. As Vias de Comunicação e Meios de Transporte como Factores de Globalização, de Estabilidade Política e de Transformação Económica e Social: Caso do Caminho-de-ferro de Bengela (Benguela) (1889-1950) 7. Nas Malhas da Rede: Aspectos do impacto económicoe social do transporte rodoviário na região do Huambo c. 1920-c. 1960 8. Communications between Angola and East Central Africa Before c. 1700 9. Long-distance Caravans and Communication beyond the Kwango (c. 1850-1890) 10. A Escrita em Angola: Comunicação e Ruído entre as Diferentes Sociedades em Presença 11. Escrever o Poder: Os Autos de Vassalagem e a Vulgarização da Escrita entre as Elites Africanas Ndembu 12. Do Passado ao Presente: Tráfego Comercial e Redes de Comunicação, Factores Privilegiados de “Modernidade” 13. Refugees on Routes. Congo / Zaire and the War in Northern Angola (1961-1974) 14. Crossing the River: Myth and Movement in Central Africa 15. From Group Mobility to Individual Movement: The Colonial Effort to Turn Back History Notes on Contributors
The increasing resistance of almost all pathogenic bacteria to antibiotics (multidrug resistance) causes a severe threat to public health. The mechanisms underlying multidrug resistance include the induced over expression of multidrug transporters which extrude a variety of lipophilic and toxic substrates in an energy dependent fashion through the membrane out of the cell. These proteins are found in all transporter families. The work described in this thesis is dedicated to drug-proton antiporters from the small multidrug resistance (SMR) family. These efflux pumps with just four transmembrane helices per monomer are so far the smallest transporters discovered. Their oligomeric state, topology, three dimensional structure, catalytic cycle and transport mechanism are still rather controversial. Therefore, the aim of this thesis was to directly address these questions for the small multidrug resistance proteins Halobacterium salinarium Hsmr and Escherichia coli (E. coli) EmrE using a number of biophysical methods such as NMR, transport assays, mass spectrometry and analytical ultracentrifugation. Especially the work on Hsmr has been challenging due to the halophilic nature of this protein. In Chapter 1, key questions and the most important biophysical techniques are introduced followed by Material and Methods in Chapter 2. Depending on experimental requirements, cell free or ‘classical’ in vivo expression has been used for this thesis. Cell free expression as an option for the production of small multidrug transporters has been explored in Chapter 3. It has been possible to produce the SMR family members Hsmr, EmrE, TBsmr and YdgF in vitro. The expression of Hsmr was investigated in more detail under different experimental conditions. Hsmr was either refolded from precipitate or maintained in a soluble form during expression in the presence of detergents and liposomes. Furthermore, amino acids for which no auxotrophic strains were available could be labelled successfully. This expression system has been also used for preparing labelled samples of EmrE as described in Chapter 9. In vivo in E. coli expression of Hsmr, as described in Chapter 4, provided large amounts of proteins if fermenter production was used. Uniform labelling and selective unlabelling with stable isotopes (13C, 15N) for NMR spectroscopy was achieved in vivo in a more efficient and cost effective manner than using the cell free approach for this protein. Hsmr could be purified successfully from both in vitro and in vivo expression media. Hsmr is expressed in vivo and in vitro with N-terminal formylation. The Nterminal formylation is unstable and Hsmr in the presence of low salt concentrations was amenable to N-terminal degradation. It was found that Hsmr shows longest stability in Fos-ß-choline® 12 and sodium dodecyl sulphate, but best reconstitution conditions were found, when dodecyl maltoside is used and exchanged with Escherichia coli lipids. A molar protein lipid ratio of 1 to 100, amenable to solid state nuclear magnetic resonance, has been achieved. Sample homogeneity was shown by freeze fracture electron microscopy. The oligomeric state of Hsmr in detergent has been assessed by SDS PAGE, blue native PAGE, size exclusion chromatography, analytical ultracentrifugation and laser induced liquid bead ion desorption mass spectrometry (LILBID) as described in Chapter 5. A concentration and detergent dependent monomer-oligomer equilibrium has been found by all methods. The activity of Hsmr under the sample preparation conditions used here was shown using radioactive and fluorescence binding as well as fluorescence and electrochemical transport assays (Chapter 6). For transport studies, a stable pH gradient was generated by co-reconstitution of Hsmr with bacteriorhodopsin and subsequent sample illumination. Based on the observed long term stability of Hsmr in Fos-ß-choline® 12 and sodium dodecyl sulphate, liquid state NMR experiments were attempted in order to assess the correct folding of Hsmr in detergent micelles (Chapter 7). 1D proton and 2D HSQC spectra of U-15N Hsmr revealed a poor spectral dispersion, low resolution and only a small number of peaks. These are at least partly due to long rotational correlation times of the large protein detergent complex. This problem has been overcome by applying solid-state NMR to Hsmr reconstituted into E. coli lipids (Chapter 8). Uniform 13C labelled samples were prepared and two dimensional proton-driven spin diffusion and double quantum-single quantum correlation spectra were acquired successfully. Unfortunately, the spectral resolution was not yet sufficient for further structural studies. Reasons for the observed linebroadening could be structural heterogeneity or molecular motions which interfere with the NMR timescale. Therefore, the protein mobility has been probed using static 2H solid state NMR on Ala-d3-Hsmr. It could be shown, that parts of Hsmr are remarkably mobile in the membrane and that this mobility can be limited by the addition of the substrate ethidium bromide. Ethidium bromide as well as tetraphenylphosphonium (TPP+) is typical multidrug transporter substrates. The membrane interaction of TPP+ in DMPC membranes has been resolved by 1H MAS NMR. It was found that it penetrates into the interface region of the lipid bilayers and therefore behaves like many other transporter substrates adding to the hypothesis that the membrane could act as a pre-sorting filter. Finally, Chapter 9 is dedicated to the characterisation of the essential and highly conserved residue Glu-14 in EmrE by solid-state NMR. In order to avoid spectral overlap, the single Glu EmrE E25A mutant was chosen instead of the wildtype. The protein has been produced in vitro to take advantage of reduced isotope scrambling in the cell free expression system as verified by analytical NMR spectroscopy. Correct labelling of EmrE was tested by MALDI-TOF and solid-state NMR. The dimeric state of DDM solubilised EmrE has been probed by LILBID. The labelled protein was reconstituted into E. coli lipids to ensure a native membrane environment. Activity was determined by measuring ethidium bromide transport. Freeze fracture EM revealed very homogeneous protein incorporation even after many days of MAS NMR experiments. 2D 13C double quantum filtered experiments were used to obtain chemical shift and lineshape information of Glu-14 in EmrE. Two distinct populations were found with backbone chemical shift differences of 4 - 6 ppm which change upon substrate binding. These findings indicate a structural asymmetry at the assumed dimerisation interface and are discussed in the context of a model for shared substrate/proton binding. These studies represent the first successful use of cell free expression to prepare labelled membrane proteins for solid-state NMR and allow for the first time an NMR insight into the binding pocket of a multidrug efflux pump.