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The single most important policy-induced innovation in the international financial system since the collapse of the Bretton-Woods regime is the institution of the European Monetary Union. This paper provides an account of how the process of financial integration has promoted financial development in the euro area. It starts by defining financial integration and how to measure it, analyzes the barriers that can prevent it and the effects of their removal on financial markets, and assesses whether the euro area has actually become more integrated. It then explores to which extent these changes in financial markets have influenced the performance of the euro-area economy, that is, its growth and investment, as well as its ability to adjust to shocks and to allow risk-sharing. The paper concludes analyzing further steps that are required to consolidate financial integration and enhance the future stability of financial markets.
Various concurrency primitives have been added to sequential programming languages, in order to turn them concurrent. Prominent examples are concurrent buffers for Haskell, channels in Concurrent ML, joins in JoCaml, and handled futures in Alice ML. Even though one might conjecture that all these primitives provide the same expressiveness, proving this equivalence is an open challenge in the area of program semantics. In this paper, we establish a first instance of this conjecture. We show that concurrent buffers can be encoded in the lambda calculus with futures underlying Alice ML. Our correctness proof results from a systematic method, based on observational semantics with respect to may and must convergence.
Life-threatening fungal infections are becoming increasingly common for immunocompromised patients such as those with AIDS, or those undergoing organ transplantation or chemotheraphy, as well as for other health-vulnerable patients. Excellent targets for antifungal drugs are chitin synthases, which are essential for survival of the fungus and lacking in humans. To design new antifungal drugs, knowledge of the three-dimensional structure and mechanism of action of chitin synthases are crucial. Chitin synthases are members of an important family of enzymes that synthesize structural polysaccharides, such as cellulose, β(1,3)-glucan, β(1,4)-mannan and hyaluronan. Therefore, chitin synthases could be used as a model system to understand these more complex enzymes, which are also of major medical and commercial importance. Chitin synthase 2 from Saccharomyces cerevisiae (ScChS2), the protein under study, is an integral membrane protein that synthesizes the primary septum between mother and daughter cells in budding yeast. It is essential for proper cell separation and expected to be highly regulated. An important aspect is that ScChS2 shows 55% sequence identity and is functionally analogous to chitin synthase 1 from the human opportunistic pathogen Candida albicans, this enzyme is also essential for cell survival (Munro, Winter et al. 2001). ...
What is the energy function guiding behavior and learningµ Representationbased approaches like maximum entropy, generative models, sparse coding, or slowness principles can account for unsupervised learning of biologically observed structure in sensory systems from raw sensory data. However, they do not relate to behavior. Behavior-based approaches like reinforcement learning explain animal behavior in well-described situations. However, they rely on high-level representations which they cannot extract from raw sensory data. Combinations of multiple goal functions seems the methodology of choice to understand the complexity of the brain. But what is the set of possible goals. ...
A small-world network has been suggested to be an efficient solution for achieving both modular and global processing-a property highly desirable for brain computations. Here, we investigated functional networks of cortical neurons using correlation analysis to identify functional connectivity. To reconstruct the interaction network, we applied the Ising model based on the principle of maximum entropy. This allowed us to assess the interactions by measuring pairwise correlations and to assess the strength of coupling from the degree of synchrony. Visual responses were recorded in visual cortex of anesthetized cats, simultaneously from up to 24 neurons. First, pairwise correlations captured most of the patterns in the population´s activity and, therefore, provided a reliable basis for the reconstruction of the interaction networks. Second, and most importantly, the resulting networks had small-world properties; the average path lengths were as short as in simulated random networks, but the clustering coefficients were larger. Neurons differed considerably with respect to the number and strength of interactions, suggesting the existence of "hubs" in the network. Notably, there was no evidence for scale-free properties. These results suggest that cortical networks are optimized for the coexistence of local and global computations: feature detection and feature integration or binding.
Background One of the central issues in ecology is the question what allows sympatric occurrence of closely related species in the same general area? The non-biting midges Chironomus riparius and C. piger, interbreeding in the laboratory, have been shown to coexist frequently despite of their close relatedness, similar ecology and high morphological similarity. Methodology/Principal Findings In order to investigate factors shaping niche partitioning of these cryptic sister species, we explored the actual degree of reproductive isolation in the field. Congruent results from nuclear microsatellite and mitochondrial haplotype analyses indicated complete absence of interspecific gene-flow. Autocorrelation analysis showed a non-random spatial distribution of the two species. Though not dispersal limited at the scale of the study area, the sister species occurred less often than expected at the same site, indicating past or present competition. Correlation and multiple regression analyses suggested the repartition of the available habitat along water chemistry gradients (nitrite, conductivity, CaCO3), ultimately governed by differences in summer precipitation regime. Conclusions We show that these morphologically cryptic sister species partition their niches due to a certain degree of ecological distinctness and total reproductive isolation in the field. The coexistence of these species provides a suitable model system for the investigation of factors shaping the distribution of closely related, cryptic species.
Introduction : extent, processes and evolutionary impact of interspecific hybridization in animals
(2008)
Since the time of Charles Darwin, studies of interspecific hybridization have been a major focus for evolutionary biologists. Although this phenomenon has often been viewed as problematic in the fields of ecology, taxonomy and systematics, it has become a primary source of data for studies on speciation and adaptation. Effects from genetic/evolutionary processes, such as recombination and natural selection, usually develop over extended periods of time; however, they are accelerated in cases of hybridization. Interspecific hybrids exhibit novel genomes that are exposed to natural selection, thus providing a key to unravel the ultimate causes of adaptation and speciation. Here we provide firstly a historic perspective of hybridization research, secondly a novel attempt to assess the extent of hybridization among animals and thirdly an overview of the reviews and case studies presented in this theme issue.
Using (13)C spin relaxation NMR in combination with molecular dynamic (MD) simulations, we characterized internal motions within double-stranded DNA on the pico- to nano-second time scale. We found that the C-H vectors in all cytosine ribose moieties within the Dickerson-Drew dodecamer (5´-CGCGAATTCGCG-3´) are subject to high amplitude motions, while the other nucleotides are essentially rigid. MD simulations showed that repuckering is a likely motional model for the cytosine ribose moiety. Repuckering occurs with a time constant of around 100 ps. Knowledge of DNA dynamics will contribute to our understanding of the recognition specificity of DNA-binding proteins such as cytosine methyltransferase.
Targeting signals direct proteins to their extra- or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides encompassing at least 40 amino acid residues. We discovered a two-domain organization ("NtraC model") in many long signals from vertebrate precursor proteins. Accordingly, long signal peptides may contain an N-terminal domain (N-domain) and a C-terminal domain (C-domain) with different signal or targeting capabilities, separable by a presumably turn-rich transition area (tra). Individual domain functions were probed by cellular targeting experiments with fusion proteins containing parts of the long signal peptide of human membrane protein shrew-1 and secreted alkaline phosphatase as a reporter protein. As predicted, the N-domain of the fusion protein alone was shown to act as a mitochondrial targeting signal, whereas the C-domain alone functions as an export signal. Selective disruption of the transition area in the signal peptide impairs the export efficiency of the reporter protein. Altogether, the results of cellular targeting studies provide a proof-of-principle for our NtraC model and highlight the particular functional importance of the predicted transition area, which critically affects the rate of protein export. In conclusion, the NtraC approach enables the systematic detection and prediction of cryptic targeting signals present in one coherent sequence, and provides a structurally motivated basis for decoding the functional complexity of long protein targeting signals.
Exported proteases of Helicobacter pylori (H. pylori) are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI). Among these, we found the predicted serine protease HtrA (Hp1019), which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.
A mild synthetic method for N-formyl-Met-Leu-Phe-OH (1) is described. After Fmoc solid phase peptide synthesis, on-bead formylation and HPLC purification, more than 30 mg of the fully 13C/15N-labelled tripeptide 1 could be isolated in a typical batch. This peptide can be easily crystallised and is therefore well suited as a standard sample for setting up solid-state NMR experiments.
Infliximab is a monoclonal antibody directed against TNF-alpha. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role.
Background: Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs) emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results: We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of "chromaffin" granules were significantly increased. Conclusions: BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.
Self-inactivating gammaretroviral vectors for the gene therapy of chronic granulomatous disease
(2008)
Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency characterized by defective intracellular oxidative killing of ingested invading microbes by PMN and monocytes. It is caused by mutations in one of the four genes coding for the essential subunits of the NADPH oxidase (gp91phox, p47phox, p67phox and p22phox). Approximately 75% of the CGD cases are due to mutations in the gp91phox gene. If regular care and conventional therapy fail, the recommended therapy is allogeneic bone marrow transplantation (BMT), but only if a matched donor is available. A therapeutic option for patients lacking suitable donors is the genetic modification of autologous hematopoietic stem cells. The gene therapy offers an interesting alternative to BMT since it implies a less invasive treatment and represents a possibly unique curative option for patients with no suitable donor. Gammaretroviral vectors were already used in some gene therapy trials for CGD and other immunodeficiencies showing relevant clinical benefit. However, these trials uncovered an unexpected mutagenic side effect. If the retrovial integration ocurrs near to, or into proto-oncogenes this might lead to clonal dominance or even malignant transformation (Hacein-Bey-Abina et al., 2003a; Ott et al., 2006). Therefore, there was a need to further improve the safety of these vectors and to this end the self-inactivating gammaretroviral vectors were engineered. Non essential sequences for virus infectivity and integration, which might influence the surrounding gene expression, were deleted in these vectors. In the first set of experiments, a series of SIN gamma retroviral vectors was cloned driving the expression of the wild-type gp91phox cDNA under the control of a viral constitutive SFFV promoter. However initial studies with these vectors failed because the titers of the virus produced by transient transfection protocols were extremely low (<5x105 TU/ml). Therefore, a codon optimization of the gp91phox cDNA was considered as an alternative. The codon optimized synthetic gp91phox gene was used to construct a SIN gammaretroviral vector, again under the control of the SFFV promoter (Schambach et al., 2006c). With this vector an increase in titer was observed compared to the native gp91phox sequence, which was due to the improved transcription in 293T transfected cells. The enhancement of the synthetic gp91phox transcription led to a higher internal transcript production and protein expression. An enhanced superoxide production in transduced myelomonocytic X-CGD PLB-985 populations was also detected. All these data indicate that the synthetic gp91phox might represent an excellent alternative to those former constructs expressing the native gp91phox transgene. Since it was postulated that the SFFV promoter could still cause transactivation of neighboring genes due to its strength (Modlich et al., 2006), three different non-viral promoters were tested, one constitutive (the EFs promoter) and two myeloid-specific promoters (the c-fes and MRP8 promoter). The three SIN gammaretroviral vectors were able to generate high titers after transient transfection of 293T packaging cells, to efficiently transduce the X-CGD PLB-985 cell line and to reconstitute the NADPH oxidase activity to a high degree. In mouse transplantation experiments, the EFs promoter showed a high variable transgene expression in the different lineages analyzed, and the c-fes promoter showed also a ubiquitinous expression. In contrast, the MRP8 promoter showed a high myeloid specificity since gp91phox expression in mSca-1+ cells and lymphoid B cells from transplanted mice was extremly low and even absent. However, the lowest levels of transgene expression were observed in the myeloid populations both in bone marrow and peripheral blood with this vector. When the oxidase reconstitution ability of these promoters was tested, the numbers of superoxide producing cells obtained were similar than those observed in the clinical X-CGD trial conducted by the groups of Dr. M. Grez and Prof. R. A. Seger (over 35% in one patient and ~15% in the second), which led to the eradication of therapy refractory infections (Ott et al., 2006). Between the three constructs, the MRP8 promoter was less effective in restoring the NADPH oxidase activity than the EFs and c-fes promoters. The c-fes promoter reached the highest levels of DHR reactive cells in the highest number of mice. Overall, these data showed that between all constructs tested, the c-fes containing construct in combination with the codon optimized gp91phox sequence showed the best performance within the SIN gammaretroviral backbone. It generated the highest titers in combination with a better NADPH oxidase reconstituting ability. One main goal in the development of SIN gammaretroviral vectors is reducing the genotoxic effect due to random vector integration. An improved gene transfer and expression, and a constant performance are also highly desirable. The present study shows that the c-fes SIN vector in combination with the synthetic gp91phox may be considered as an effective gene therapy strategy for the restoration of the NADPH oxidase activity in CGD. It allows the use of a cellular promoter generating adequate physiological levels of the therapeutic protein and reduces the number of vector copies required for a therapeutic effect.
Conclusion Scale Integration Based on the results of spike-field coherence, the underlying process of shortterm memory seems to involve networks of different sizes within and, most probably, beyond prefrontal cortex. Spikes, which were generated by single neurons, cooperate with local field potentials, which were the slower fluctuations of the environment. Although differences among behavioral conditions appear to be based on rather few instances of phase-locked spikes, the task-related effects on spike-field coherence are highly reliable and cannot be explained by chance, as the comparison of results from experimental and simulated data shows. The differential locking of prefrontal neuron populations with two different frequency bands in their input signals suggests that neuronal activity underlying short-term memory in prefrontal cortex transiently engages cortical circuits on different spatial scales, probably in order to coordinate distributed processes. NeuroXidence method and Synchronizedfiring Based on the results of the calibration datasets, for bi- and multi-variate cases, the extension of NeuroXidence remains its sensitivity and reliability of detecting coordinate firing events for different processes. Based on this extension of NeuroXidence, we demonstrated that in monkey’s prefrontal cortex during short-term memory task, encoding and maintenance of the information rely on the formation of neuronal assemblies characterized by precise and reliable synchronization of spiking activity on a millisecond time scale, which is consistent with the results from spike-spike coherence. The task and performance dependent modulation of synchrony reflects the dynamic formation of group of neurons has large effect on short-term-memory.
Development of chromium(VI)-free defect etching solutions for application on silicon substrates
(2008)
Spectroscopic responses of the potentiometric probe 2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide (DASPMI) were investigated in living cells by means of a time- and space-correlated single photon counting technique. Spatially resolved fluorescence decays from single mitochondria or only a very few organelles of XTH2 cells exhibited three-exponential decay kinetics. Based on DASPMI photophysics in a variety of solvents, these lifetimes were attributed to the fluorescence from the locally excited state, intramolecular charge transfer state, and twisted intramolecular charge transfer state. A considerable variation in lifetimes among mitochondria of different morphologies and within single cells was evident, corresponding to high physiological variations within single cells. Considerable shortening of the short lifetime component ({tau}1) under a high-membrane-potential condition, such as in the presence of ATP and/or substrate, was similar to quenching and a dramatic decrease of lifetime in polar solvents. Under these conditions {tau}2 and {tau}3 increased with decreasing contribution. Inhibiting respiration by cyanide resulted in a notable increase in the mean lifetime and a decrease in mitochondrial fluorescence. Increased DASPMI fluorescence under conditions that elevate the mitochondrial membrane potential has been attributed to uptake according to Nernst distributions, delocalization of {pi}-electrons, quenching processes of the methyl pyridinium moiety, and restricted torsional dynamics at the mitochondrial inner membrane. Accordingly, determination of anisotropy in DASPMI-stained mitochondria in living cells revealed a dependence of anisotropy on the membrane potential. The direct influence of the local electric field on the transition dipole moment of the probe and its torsional dynamics monitor changes in mitochondrial energy status within living cells.
A series of production and perception experiments investigating the prosody and well-formedness of special sentences, called Wide Focus Partial Fronting (WFPF), which consist of only one prosodic phrase and a unique initial accented argument, are reported on here. The results help us to decide between different models of German prosody. The absence of pitch height difference on the accent of the sentence speaks in favor of a relative model of prosody, in which accents are scaled relative to each other, and against models in which pitch accents are scaled in an absolute way. The results also speak for a model in which syntax, but not information structure, influences the prosodic phrasing. Finally, perception experiments show that the prosodic structure of sentences with a marked word order needs to be presented for grammaticality judgments. Presentation of written material only is not enough, and falsifies the results.
Focus asymmetries in Bura
(2008)
This article presents the central aspects of the focus system of Bura (Chadic), which exhibits a number of asymmetries: Grammatical focus marking is obligatory only with focused subjects, where focus is marked by the particle án following the subject. Focused subjects remain in situ and the complement of án is a regular VP. With nonsubject foci, án appears in a cleft-structure between the fronted focus constituent and a relative clause. We present a semantically unified analysis of focus marking in Bura that treats the particle as a focusmarking copula in T that takes a property-denoting expression (the background) and an individual-denoting expression (the focus) as arguments. The article also investigates the realization of predicate and polarity focus, which are almost never marked. The upshot of the discussion is that Bura shares many characteristic traits of focus marking with other Chadic languages, but it crucially differs in exhibiting a structural difference in the marking of focus on subjects and non-subject constituents.
The term cephalic sensory organ (CSO) is used for specialised structures in the head region of adult Opisthobranchia. These sensory organs show a high diversity in form and function, and the gross morphology of these organs differs considerably among taxa. They can be identified as cephalic shields, oral veils, Hancocks organs, lip organs, rhinophores or oral tentacles. Because of this extremely high diversity, the homology and the evolution of these organs have not been clarified yet. My intention was to use neuroanatomical data sets in order to find putative homologous CSOs. In this study, I will show data about immunohistochemical neurotransmitter content and cellular innervation patterns and their applicability as morphological characters for the homologisation of structures. I support earlier investigations that neurotransmitter content is often related to function. In contrast, axonal tracing patterns can be used to homologise nerves. Overall the aim of this study was to reconstruct the evolution of the CSOs of the Opisthobranchia, by projecting our neuroanatomical data sets onto a molecular phylogeny.
Determination of the distribution of halocarbons in the tropical upper troposphere and stratosphere
(2008)
The aim of this thesis was to investigate distributions of 32 volatile chlorinated and/or brominated halocarbons that are currently believed to be present in the tropical upper troposphere and stratosphere and to contribute to stratospheric ozone depletion and also to global warming. For this purpose an analytical system was established, which is capable to measure ultra-low concentrated atmospheric trace gases. A quadrupole Mass Spectrometric (MS) Detector was attached to an existing Gas Chromatograph with pre-concentration system and Electron Capture Detector (ECD). The characterisation of the chromatographic system was significantly enhanced by the subsequent identification of 48 additional volatile organic compounds. Furthermore a Gaussian fit algorithm, which was developed in the workgroup, was applied to the chromatographic signals. This algorithm was proven to reflect peaks quantitatively and to enhance the performance of the integration process – especially the reproducibilities for peaks with a low signal to noise ratio. As it is known that the Electron Capture Detector responds nonlinear the new MS detector was checked for such behaviour and found to respond linear. In logical consistency the complete quantification process including e.g. pre-concentration of trace gases and signal integration can be considered as linear responding within the investigated parameter ranges. Moreover, the long term stability of the targeted halocarbons was proven inside the calibration standard containers over a period of 25 months. Many substances were also found to be stable inside the containers used for storage of air samples but a number of substances showed significant concentration changes. These were mainly CH3Cl (methyl chloride), CH3Br (methyl bromide), CH2Cl2 (dichloromethane), CHCl3 (chloroform), CCl4 (tetrachloromethane), C2Cl4 (tetrachloroethene), CH3CCl3 (methyl chloroform), CH2ClCH2Cl (1,2-dichloroethane) und C2H5Cl (chloroethane). But the number of affected substances and also the corresponding concentration changes varied between the individual containers. A systematic investigation of the influence of possible causes (e.g. air sampling methods, container materials) is recommended. Results from both internal detectors were compared and revealed biases and disadvantages of the ECD caused by its lower selectivity and its nonlinear response behaviour. Consequently the MS detector was chosen for the quantification of atmospheric trace gases. The quantification process was performed relative to externally calibrated air standards. To assess the uncertainties connected with different absolute calibration scales cross-comparisons between calibration standards of three different laboratories were carried out. Most substances’ calibrations agreed within the measurement uncertainties but significant differences were observed for CF2ClBr (H1211), CH3Cl (methyl chloride), CH2Cl2 (dichloromethane), CHCl3 (chloroform), CCl4 (tetrachloromethane) and CH3CCl3 (methyl chloroform). As five of these substances were also observed to show concentration changes inside sample containers it is likely, that such changes are responsible for calibration differences. In addition to the detailed assessment of uncertainties connected with the analytical quantification process a set of air samples was available for measurements. These samples mainly originated from the upper troposphere and lower and middle stratosphere in the tropics and the determined halocarbon quantities were used to investigate their distributions in the respective atmospheric regions. In detail, the altitudinal distributions and interrelations of 17 long-lived halocarbons in the tropical stratosphere were determined and compared with those of other stratospheric regions. Tracer-tracer-correlations of these substances in the tropical stratosphere were found to differ from those in mid- and high-latitudes. Characteristic fit functions relative to CF2Cl2 (F12) which are valid for the tropical stratosphere in 2005 were derived as well as time-independent fit functions of fractional release factors (FRFs) relative to the mean age of air. Both sets of correlations could be used for the parameterisation and evaluation of models and also to reassess the Global Warming Potentials (GWPs) of the corresponding halocarbons which might affect future climate predictions. However, the data set on halocarbons in the tropical stratosphere is still insufficient to investigate the variability of tracer-tracer-correlations and FRFs caused by dynamical and photochemical processes. Therefore it is important for future research to perform additional measurements there and – if possible – to extend the measurements to the upper tropical stratosphere in order to characterise the sink of those halocarbons that are still present in these altitudes. In addition, the amount of chlorine and bromine present in the form of organic compounds inside and above the main stratospheric entrance region (the Tropical Tropopause Layer, TTL) was quantified in the frame of a case study. This was possible because of a cooperation with scientists from the University of East Anglia which carried out measurements of six additional halocarbons leading to a total of 28 quantified target substances. Ten of these substances have short atmospheric lifetimes compared with the mean transport times of tropospheric air to the stratosphere (i.e. lifetimes below 0.5 years) and show non-uniform distributions in the upper troposphere. The contribution of these substances to stratospheric ozone depletion is subject of an ongoing scientific debate. In the performed case study a fraction range of short-lived halocarbons of 6 – 8 % (0.98 – 1.25 ppt) relative to the sum of bromine from organic substances and of 1.1 – 1.4 % (36.6 – 47.1 ppt) for the corresponding sum of chlorine was calculated to enter the stratosphere above Brazil in June 2005. Moreover by combining the data with tropospheric reference data and age of air observations the abundances of inorganic chlorine and bromine (Cly and Bry) were derived. At an altitude of 34 km an amount of 3062 ppt of Cly and 17.5 ppt of Bry from organic source gases was calculated. The latter is significantly lower than Bry mixing ratios inferred from quasisimultaneous BrO measurements at 33 km altitude above Brazil (Dorf, 2005, Dorf et al., 2008). But at the University of East Anglia indications for the presence of unknown brominated organic substances in the TTL were found which might cause this difference. Finally, a major result of this thesis adds to the knowledge of the composition of the troposphere as three Chlorofluorocarbons (CFCs) were first observed. Trifluorochloroethene, 3-chloropentafluoropropene and 4,4-dichlorohexafluoro-1-butene were found in air samples collected at the Taunus Observatory near Frankfurt (Main) and the Jungfraujoch High Altitude Research Station in Switzerland (Laube and Engel, 2008). Identification was possible because of an air plume containing high concentrations of these substances. It is suggested that the abundances found on this occasion originated from a local source. The atmospheric lifetimes of these substances are expected to be rather short as they contain a double bond. A quantitative calibration could only be derived for trifluorochloroethene but not for the other species by now. Thus, a relative sensitivity method was derived to get a first indication of the observed atmospheric abundances. All three CFCs could also be detected in air masses representative of background conditions, though with much lower concentrations. These species and some of their degradation products are toxic and could also be relevant for stratospheric and tropospheric ozone depletion. It is important to find out more about their atmospheric distributions, lifetimes, sinks and sources and their ability to reach the stratosphere to assess their possible influence on the global atmosphere. This will be done in the frame of the project "CLEARFOGG – Checking Layers of the Earths AtmospheRe For halogenated Ozone-depleting and Greenhouse Gases". This research project aims to perform a systematic scan of the atmosphere because there are indications for the presence of a number of halogenated organic compounds which are unknown by now. It was recently decided to be funded by the British National Environmental Research Council and will be carried out at the University of East Anglia mainly by the author of this thesis.
Freeze (1992) argued on the basis of data from several different languages that there is a close relationship between existential sentences (stating the existence of an entity) and locative sentences (stating the location of an entity). Freeze (1992) proposes that they are both derived from the same base structure and that the surface differences are rather due to the distinct information structures.This paper argues against this position with the data from Serbian existentials, which show clear syntactic differences from the locatives. Thus, the close relationship between existential and locative sentences that Freeze (1992) observes is conceptual, but not (necessarily) part of the syntax of the language. In order to account for the data, we propose that existential sentences originate from a different syntactic predication structure than the locative ones. The existential meaning arises, as we will show, from the interaction of this predication structure with the structure and meaning of the noun phrase.
The ACL 2008 Workshop on Parsing German features a shared task on parsing German. The goal of the shared task was to find reasons for the radically different behavior of parsers on the different treebanks and between constituent and dependency representations. In this paper, we describe the task and the data sets. In addition, we provide an overview of the test results and a first analysis.
Prion diseases or transmissible spongiform encephalopathies (TSEs) are rare neurological disorders that may be of genetic or infectious origin, but most frequently occur sporadically in humans. Their outcome is invariably fatal. The infectious agent has been defined as prion (from proteinaceous infectious only) in 1992 by Stanley B. Prusiner and represent mainly, if not solely, an abnormal, protease-resistant isoform (PrPSc) of a cellular protein, the prion protein or PrPC. According to the “protein only” hypothesis, the prion is devoid of informational nucleic acids and consists of an “infectious” protein that is capable of converting the normal host protein PrPC into a likeness of itself. TSEs can be distinguished from other neurodegenerative diseases because of their infectivity and transmission capability. The only organ system in which severe histopathological damage can be demonstrated as a consequence of infection with prions is the nervous system. The communal lesions are neuronal loss, spongiosis and astrogliosis, accompanied by an intra- and extracellular accumulation of PrPSc, occasionally in form of amyloid plaques. Even if a strong activation of microglia and astrocytes occurs, no immunological response is usually detectable as consequence of prion infection. Despite the considerable attention for its involvement in TSEs, the physiological role of the cellular, nonpathogenic isoform of PrPC, has not yet been determined. In the last years, several putative cellular functions have been attributed to PrPC: its localization in “lipid rafts” is consistent with a possible role in cell adhesion, transmembrane signalling or as a recognition molecule. Furthermore, PrPC has been implicated in protection against oxidative stress, copper metabolism, apoptosis, cell proliferation and in the regeneration of blood precursors stem cells in the adult. It has also been shown that PrPC interacts with the neuronal cell adhesion molecule NCAM, promoting neurite outgrowth. However, both the PrPC-mediated effects and the role of PrPC-dependent pathways on neuronal differentiation are still not elucidated. First objective of this Ph.D thesis was the establishment of a novel in vitro cellular model for the study of the role of PrPC in neuronal differentiation and neurite outgrowth. Furthermore, an additional goal of this project was the indentification of the PrPC domains responsible for the induction of neuronal differentiation. A novel PrPC-depleted cell line (PrP0/0 ML) was derived from murine primary PrP-knockout neuronal cells by SV40 large T antigen-mediated immortalization. A temperature sensitive form of this oncogenic protein was used, allowing a temperature-mediated regulation of its expression. This cell line was then characterised for its growth potential, for the expression of specific cellular markers and for its ability to differentiate. It was found that, under culture conditions promoting the expression of the temperature-sensitive SV40 large T antigen, the cells expressed nestin, a specific marker of neuronal precursor cells. Therefore, the PrP0/0 ML cell line was identified as a potential neuronal stem cell line. In fact, under nonpermissive culture conditions when the expression of the temperature-sensitive SV40 large T antigen is downregulated, the PrP0/0 ML cells differentiated into neurons. Noteworthy, maintenance of the cells in conditions that promote cell differentiation induced a progressive reduction in the expression levels of nestin, an event that strongly correlated with the appearance of the specific neuronal markers MAP-2b and NeuN. In order to investigate the role of PrPC in the process of neuronal differentiation, the PrP0/0 ML cells were then reconstituted for the expression of either the full-length PrP or a N-terminal truncated PrPC form (PrPdel32-134). The differentiation potential of both reconstituted cell lines under nonpermissive culture conditions was then compared with that of the parenteral PrP0/0 ML cells. This in vitro study clearly highlights that PrPC expression in the PrP0/0 ML cell line accelerates neuronal differentiation and that the N-terminal domain of the prion protein is not necessary for this PrP-mediated function. Prion diseases like BSE, vCJK, Kuru and the majority of iatrogenic cases of CJK are caused by a peripheral infection. Infectious prions accumulate in the central and peripheral nervous system as well as in extracerebral tissues, such as the secondary lymphoid organs and muscles. The prion pathogenesis is a dynamic process which can be defined temporary and spatially in different phases: i) infection and peripheral replication, ii) neuroinvasion, transport of prions from the periphery to the central nervous system (CNS), and iii) neurodegeneration. In the last years, progresses in the elucidation of the peripheral prion pathogenesis were achieved. The identification of the cell types involved in the lymphoreticular prion replication phase and the recognition of the role of the peripheral nervous system in the process of prion spread from the periphery to the CNS have elucidated some of the cellular mechanisms that are involved in prion uptake, replication and propagation. However, relatively little information is available about the mechanism(s) underlying intercellular prion transfer and tissue-to tissue prion spread. Microvesicles (MVs) are submicron vesicles (0,03-1 microm.) with a single membrane and are shed from most eukaryotic cells undergoing activation or apoptosis. The segregation of specific proteins is followed by blebbing of the membrane surface, leading to the formation of MVs and their release in the extracellular environment. MVs can be also secreted upon fusion of multivesicular endosomes with the plasma membrane (exosomes). The secretion of MVs is the result of a complex cellular process involving changes in the metabolism of lipids and proteins. The functional role of MVs is still largely unknown. However, there is evidence showing that they are important modulators of cell-to-cell communication, participate in a variety of intracellular adhesion processes and are able to induce cellular response(s). The release of PrPC and infectious PrPSc by prion infected epithelial, neuroglial and neuronal cells in association with exosomes has recently been highlighted. Furthermore, it has been shown that exosomes can propagate prion infectivity both in vitro and in vivo, suggesting that PrPSc-bearing exosomes may provide a mechanism for intercellular transmission of infectious prions in addition to cell-to-cell contact. Second objective of this Ph.D thesis was to determine the possible role of plasma membrane-derived microvesicles in the propagation and transmission of prions. The release of MVs was first studied in different murine neuronal cell lines. Here it is shown for the first time that neurons also shed plasma membrane derived MVs, in addition to exosomes. Immunoelectron microscopy and immunoblot analyses clearly demonstrated the presence of PrPC on the membrane of MVs released from PrPC-expressing cells. Characterization of lipid rafts components in MVs highlighted the presence of the ganglioside GM2, the tyrosine kinase p59Fyn, flotillin-2 and the neuronal protein GAP-43. In order to investigate whether MVs are involved in the intercellular transmission of prions, MVs were first isolated from two prion infected murine neuronal cell lines, namely the Neuro-2a PK1 and the N2a58 cells, and then used for in vitro and in vivo infection assays. Immunoblot analyses after proteinase K treatment demonstrated the association of PrPSc with the secreted MVs. The PrPSc-bearing MVs were then used to perform infection experiments on noninfected cells. By the use of cell blot assay, a method that allows the detection of PrPSc-amplification and -accumulation in cultured cells, the kinetic of prion infection in the de novo infected cells was followed. Noteworthy, it was found that PrPSc-bearing MVs were capable to transmit prions in vitro and to stably infect the recipient cells. In order to investigate the role of MVs in the transmission of infectivity in vivo, PrPSc-bearing MVs as well as MVs isolated from noninfected cells (as negative control) were injected intracerebrally in PrPC-overexpressing indicator mice (tga20). The development of clinical disease was followed in a time-dependent manner. Clinical symptoms could be observed only in the group of indicator mice inoculated with the PrPSc-bearing MVs, which then succumbed to desease. These findings clearly demonstrated that MVs are biological carriers of both PrPSc and prion infectivity. MVs could therefore participate in vivo in the processes of intercellular prion transmission and propagation.
Dan Janzen proposed in a paper in 1977 (loc. cit.), that a clone of aphids and for that matter dandelions consists, respectively, of one large ‘super-organism’. In effect a single evolutionary individual able to exploit resources over an expanded geographical range, and sometimes with aphids also, a wider range of resources (different kinds of host plants), much more than if the organism concerned were a single individual. Such a view is of course based on the notion that an asexual lineage (clone) has strict genetic fidelity, that is to say, is genetically identical over its entire genome between clone mates. This seems a highly unlikely scenario and indeed, modern molecular markers have revealed a plethora of mutational events within such so-called clones. Here in this talk I provide evidence from aphids that they are not ‘perfect forms’ but rather show a range of variations, including evidence of hybridization events, and that they can and do adapt to environmental circumstances, sometimes swiftly. Hence that even as asexual lineages, aphids are able to exploit new ecological circumstances and flourish, e.g. host adapted forms, whilst some species, notably the highly polyphagous peach-potato aphid (Myzus persicae), have also evolved resistance to a range of pesticides, and by so doing, have managed to survive in the face of these poisons. However, there are fitness costs associated with such adaptation, more especially in the highly resistant aphids. Because of the variation and adaptation shown by particular aphid species and asexual lineages, they cannot be described as a single evolutionary unit in a ‘Janzenian’ sense. What they show is ecological plasticity and an ability to adapt quickly, in large part enhanced by their incredible rate of reproduction and population expansion. Some migrating winged aphids are constrained in their exploitation of new habitats by environmental factors – geographical, climatic and ecological, especially lack of suitable hosts. In contrast, some other aphid species have seemingly colonized large areas of the world (probably aided by human agency) so that deciding what a population is exactly is a difficult task. It may even be that certain ‘super clones’ detected using molecular markers have indeed spread far and wide, clones which appear to fit the description of being ‘general purpose genotypes’ in that they can feed on a range of plant hosts under a range of different geographical-climatic conditions. As such, they are nearest to Dan Janzen’s views, although here again, strict genetic fidelity is not necessarily proven, only accepted from the application of a limited number of markers, e.g. multilocus genotypes in the case of microsatellite markers.
Before the turn of the millenium the investigation of phylogenetic relationships was revolutionized by two major inputs, the use of molecular sequence data for phylogenetic reconstruction, paralleled by the sophistication of computer aided reconstruction methods. The ever growing number of data however did not only result in clarifications of open questions, but brought forth a number of new conflicting phylogenetic hypotheses. Sometimes they are wrongly referred to as conflicts between morphological and molecular approaches, which sporadically even culminated in the rejection of the usefulness of one of the two approaches (e.g. Scotland et al 2003). These scientists overlook the great advantage of having two a priori largely independent data sets (Wägele 2001) which in a synthetic way enable the greatest progress in phylogenetic research. However, solely putting data together will not suffice to choose among conflicting hypotheses. The increasing number of conflicts necessitates approaches that go beyond mere data congruence, but searching for the possible reasons of conflicts. In the present paper, problems in the reconstruction of the phylogenetic origin of Hexapoda, as well as of the early branchings within the Hexapoda, will exemplify approaches of critical re-evaluation and testing of data used in morphological data matrices for phylogenetic analyses. The early cladogenetic events of hexapods are especially suited for such a discussion for several reasons. The hexapods, as the most species-rich group of organisms, look back at a long and multi-faceted history of taxonomic and phylogenetic studies, culminating in a number of conflicting hypotheses. Triggered by incongruences with morphological analyses the reconstruction of the hexapodan roots likewise became a hot-spot of molecular research activities during^the last two decades. Furthermore the phylogenetic positions of the oldest lineages branching off within the hexapodan clade, the Diplura, Protura and Collembola, are in particular very difficult to reconstruct. While at least the latter two are well defined by morphological autapomorphies their phylogenetic position could not be reconstructed unambiguously, since their morphology seems highly derived with respect to the hexapodan ground pattern.
Hymenopteran endoparasitoids that develop inside their lepidopteran host may exert a multitude of interactions with their host until they are able to emerge successfully from a developmentally arrested host that finally dies. Parasitoid interferences comprise physiological and biochemical modifications in the host endocrine and immune system which in turn affect host growth and development (reviewed in Edwards & Weaver, 2001). We use the gypsy moth, Lymantria dispar (Lep., Lymantriidae) and the endoparasitic, polydnavirus (PDV)-carrying braconid wasp Glyptapanteles liparidis (Hym., Braconidae) as a model system to study the endocrine changes associated with parasitism. Following wasp oviposition into young gypsy moth larvae, the parasitoids develop through two endoparasitic instars, and then emerge as newly molted third instars from a host that dies in the larval stage. In previous studies we have already described the endocrine changes in parasitized gypsy moth larvae which show an increase in juvenile hormone (JH) titers, a shift from JH II to JH III as the dominant homologue, and a prominent decrease in the JH degrading enzymes (Schopf & al., 1996; Schafellner & al., 2004). Here, we investigated the possible mechanisms that account for the JH elevating effects such as (i) stimulated host corpora allata activity, (ii) reduced activity of the JH metabolic enzymes such as JH esterase, and (iii) synthesis and release of JH by the parasitoid larvae.
Aphids annually infest winter wheat, Triticum aestivum L., in late spring and early summer in Central Europe, but densities leading to strong yield losses are reached only occasionally (Basedow et al., 1994). Three aphid species, Sitobion avenae Fabr., Metopolophium dirhodum Walk. and R. padi L., usually occur in cereal crops with increasing densities from late spring onwards (Basedow et al., 1994). Modelling population levels of cereal aphids is a key tool in integrated pest management for winter wheat. Over the last 30 years, considerable efforts have been made to investigate the population dynamics of aphids (DeWit and Rabbinge, 1979; Entwistle and Dixon, 1987). In Central Europe to date, two models have attained greater importance in late spring: LAUS (Friesland, 1986) and GETLAUS01 (Gosselke et al., 2001). The first one estimates the population level of S. avenae in spring in winter wheat fields and has obtained regional significance in practical plant protection. In contrast, the model GETLAUS01 is a scientific model, not designed for practical plant protection. It describes in great detail the population dynamics of S. avenae, R. padi and M. dirhodum. Both models have been improved over time and extended with several factors, e.g. by including the effects of antagonists, fertilisation, crop density, plant protection agents and meteorological parameters on population development. The objective of this study was to analyse the following three factors in terms of their impact on population and migration characteristics: cultivar, proximity between winter and summer hosts and migration (according to meteorological parameters).
Both, G. mellonella and S. exigua, are most important pests in tropical countries. G. mellonella has five to six generations per year (Abid et al. 1997; Ali 1996), there, and feeding in bee combs they find, besides wax, residues of honey, insect skin and pollen (Hachiro & Knox 2000). Li et al. (1987) have shown the efficacy of Bacillus thuringiensis aizawai against G. mellonella. It is registered in the EU as Mellonex for its control, but NeemAzal T/S may also be active, and will have some advantages (Leymann et al. 2000, Melathopoulos et al. 2000). Therefore we conducted new studies here, on the results we shall report. S. exigua is an important polyphagous pest of crops in tropical areas (Brown & Dewhurst 1975). By repeated control with synthetic insecticides, especially by illiterate farmers (Armes et al. 1992; Aggarwal et al. 2006a) resistance to a lot of those insecticides has been built up, making plant protection very difficult. Therefore the need is pronounced for microbial and botanical pesticides (Nagarkatti 1982; Rao et al. 1990), which have different modes of action than synthetic insecticides. Aggarwal et al. (2006b) have started to test such ingredients, but the time of observation was too short (3 days), since the effects of Neem products occur later than those of synthetic insecticides (Basedow et al. 2002). So we conducted new, longer lasting experiments (with 5 to 30 days), on which we give a report here. The experiments were conducted during guest stays of the three co-authors (from Mymensingh, Bangladesh, from Nazreth, Ethiopia, and from Khartoum, Sudan) at the Experimental Station of the Institute of Phytopathology and Applied Zoology at Giessen Univerity.
Reggie-1 (flotillin-2) and reggie-2 (flotillin-1) are membrane microdomain proteins which are associated with the membrane by means of acylation. They influence different cellular signaling processes, such as neuronal, T-cell and insulin signaling. Upon stimulation of the EGF receptor, reggie-1 becomes phosphorylated and undergoes tyrosine 163 dependent translocation from the plasma membrane to endosomal compartments. In addition, reggie-1 was shown to influence actindependent processes. Reggie-2 has been demonstrated to affect caveolin- and clathrin-independent endocytosis. Both proteins form homo- and hetero-oligomers, but the function of these oligomers has remained elusive. Moreover, it has not been clarified if functions of reggie-1 are also influenced by reggie-2 and vice versa. The first aim of the study was to further investigate the interplay and the heterooligomerization of reggie proteins and their functional effects. Both reggie proteins were individually depleted by means of siRNA. In different siRNA systems and various cell lines, reggie-1 depleted cells showed reduced protein amounts of reggie-1 and reggie-2, but reggie-2 knock down cells still expressed reggie-1 protein. The decrease of reggie-2 in reggie-1 depleted cells was only detected at protein but not at mRNA level. Furthermore, reggie-2 expression could be rescued by expression of siRNA resistant wild type reggie-1-EGFP constructs, but not by the soluble myristoylation mutant G2A. This mutant was also not able to associate with endogenous reggie-1 or reggie-2, which demonstrates that membrane association of reggie-1 is necessary for hetero-oligomerization. In addition, fluorescence microscopy studies and membrane fractionations showed that correct localization of overexpressed reggie-2 was dependent on co-overexpressed reggie-1. Thus, hetero-oligomerization is crucial for membrane association of reggie-2 and for its protein stability or protein expression. Moreover, the binding of reggie-2 to reggie-1 required tyrosine 163 of reggie-1 which was previously shown to be important for endosomal translocation of reggie-1. Since reggie-2 was implicated to function in clathrin- and caveolin-independent endocytosis pathways, the effect of reggie-2 depletion on reggie-1 endocytosis was investigated. Indeed, reggie-1 was dependent on reggie-2 for endosomal localization and EGF-induced endocytosis. By FRET-FLIM analysis it could be shown that reggie heterooligomers are dynamic in size or conformation upon EGF stimulation. Thus, it can be concluded that reggie proteins are interdependent in different aspects, such as protein stability or expression, membrane association and subcellular localization. In addition, these results demonstrate that the hetero-oligomers are dynamic and reggie proteins influence each other in terms of function. A further aim was the characterization of reggie-1 and reggie-2 function in actindependent processes, where so far only reggie-1 was known to play a role. Depletion of either of the proteins reduced cell migration, cell spreading and the number of focal adhesions in steady state cells. Thus, also reggie-2 affects actin-dependent processes. Further investigation of the focal adhesions during cell spreading revealed that depletion of reggie-1 displayed different effects as compared to reggie-2 knock down. Reggie-1 depleted cells had elongated cell-matrix-adhesions and showed reduced activation of FAK and ERK2. On the other hand, depletion of reggie-2 resulted in a restricted localization of focal adhesion at the periphery of the cell and decreased ERK2 phosphorylation, but it did not affect FAK autophosphorylation. Hence, reggie proteins influence the regulation of cell-matrix-adhesions differently. A link between reggie proteins and focal adhesions is the actin cross-linking protein -actinin. The interaction of -actinin with reggie-1 could be verified by means of co-immunoprecipitations and FRET-FLIM analysis. Reggie-1 binds -actinin especially in membrane ruffles and in other locations where actin remodeling takes place. Moreover, -actinin showed a different localization pattern during cell spreading in reggie-1 depleted cells, as compared to the control cells. These results provide further insights into the function of both reggie proteins. Their interplay and hetero-oligomerization was shown to be crucial for their role in endocytosis. In addition, both reggie proteins influence actin-dependent processes and differentially affect focal adhesion regulation.
A data set of annual values of area equipped for irrigation for all 236 countries in the world during the time period 1900 - 2003 was generated. The basis for this data product was information available through various online data bases and from other published materials. The complete time series were then constructed around the reported data applying six statistical methods. The methods are discussed in terms of reliability and data uncertainties. The total area equipped for irrigation in the world in 1900 was 53.2 million hectares. Irrigation was mainly practiced in all the arid regions of the globe and in paddy rice areas of South and East Asia. In some temperate countries in Western Europe irrigation was practiced widely on pastures and meadows. The time series suggest a modest rate of increase of irrigated areas in the first half of the 20th century followed by a more dynamic development in the second half. The turn of the century is characterized by an overall consolidating trend resulting at a total of 285.8 million hectares in 2003. The major contributing countries have changed little throughout the century. This data product is regarded as a preliminary result toward an ongoing effort to develop a detailed data set and map of areas equipped for irrigation in the world over the 20th century using sub-national statistics and historical irrigation maps.
The problem of vocalization, or diacritization, is essential to many tasks in Arabic NLP. Arabic is generally written without the short vowels, which leads to one written form having several pronunciations with each pronunciation carrying its own meaning(s). In the experiments reported here, we define vocalization as a classification problem in which we decide for each character in the unvocalized word whether it is followed by a short vowel. We investigate the importance of different types of context. Our results show that the combination of using memory-based learning with only a word internal context leads to a word error rate of 6.64%. If a lexical context is added, the results deteriorate slowly.
How to compare treebanks
(2008)
Recent years have seen an increasing interest in developing standards for linguistic annotation, with a focus on the interoperability of the resources. This effort, however, requires a profound knowledge of the advantages and disadvantages of linguistic annotation schemes in order to avoid importing the flaws and weaknesses of existing encoding schemes into the new standards. This paper addresses the question how to compare syntactically annotated corpora and gain insights into the usefulness of specific design decisions. We present an exhaustive evaluation of two German treebanks with crucially different encoding schemes. We evaluate three different parsers trained on the two treebanks and compare results using EVALB, the Leaf-Ancestor metric, and a dependency-based evaluation. Furthermore, we present TePaCoC, a new testsuite for the evaluation of parsers on complex German grammatical constructions. The testsuite provides a well thought-out error classification, which enables us to compare parser output for parsers trained on treebanks with different encoding schemes and provides interesting insights into the impact of treebank annotation schemes on specific constructions like PP attachment or non-constituent coordination.
We argue for incorporating the financial economics of market microstructure into the financial econometrics of asset return volatility estimation. In particular, we use market microstructure theory to derive the cross-correlation function between latent returns and market microstructure noise, which feature prominently in the recent volatility literature. The cross-correlation at zero displacement is typically negative, and cross-correlations at nonzero displacements are positive and decay geometrically. If market makers are sufficiently risk averse, however, the cross-correlation pattern is inverted. Our results are useful for assessing the validity of the frequently-assumed independence of latent price and microstructure noise, for explaining observed cross-correlation patterns, for predicting as-yet undiscovered patterns, and for making informed conjectures as to improved volatility estimation methods.
The future of securitization
(2008)
Securitization is a financial innovation that experiences a boom-bust cycle, as many other innovations before. This paper analyzes possible reasons for the breakdown of primary and secondary securitization markets, and argues that misaligned incentives along the value chain are the primary cause of the problems. The illiquidity of asset and interbank markets, in this view, is a market failure derived from ill-designed mechanisms of coordinating financial intermediaries and investors. Thus, illiquidity is closely related to the design of the financial chains. Our policy conclusions emphasize crisis prevention rather than crisis management, and the objective is to restore a “comprehensive incentive alignment”. The toe-hold for strengthening regulation is surprisingly small. First, we emphasize the importance of equity piece retention for the long-term quality of the underlying asset pool. As a consequence, equity piece allocation needs to be publicly known, alleviating market pricing. Second, on a micro level, accountability of managers can be improved by compensation packages aiming at long term incentives, and penalizing policies with destabilizing effects on financial markets. Third, on a macro level, increased transparency relating to effective risk transfer, risk-related management compensation, and credible measurement of rating performance stabilizes the valuation of financial assets and, hence, improves the solvency of financial intermediaries. Fourth, financial intermediaries, whose risk is opaque, may be subjected to higher capital requirements.
Proteorhodopsin (PR) originally isolated from uncultivated γ-Proteobacterium as a result of biodiversity screens, is highly abundant ocean wide. PR, a Type I retinal binding protein with 26% sequence identity, is a bacterial homologue of Bacteriorhodopsin (BR). The members within this family share about 78% of sequence identity and display a 40 nm difference in the absorption spectra. This property of the PR family members provides an excellent model system for understanding the mechanism of spectral tuning. Functionally PR is a photoactive proton pump and is suggested to exhibit a pH dependent vectorality of proton transfer. This raises questions about its potential role as pH dependent regulator. The abundance of PR in huge numbers within the cell, its widespread distribution ocean wide at different depths hints towards the involvement of PR in utilization of solar energy, energy metabolism and carbon recycling in the Sea. Contrary to BR, which is known to be a natural 2D crystal, no such information is available for PR til date. Neither its functional mechanism nor its 3D structure has been resolved so far. This PhD project is an attempt to gain a deeper insight so as to understand structural and functional characterization of PR. The approach combines the potentials of 2D crystallography, Atomic Force Microscopy and Solid State NMR techniques for characterization of this protein. Wide range of crystalline conditions was obtained as a result of 2D crystallization screens. This hints towards dominant protein protein interactions. Considering the high number of PR molecules reported per cell, it is likely that driven by such interactions, the protein has a native dense packing in the environment. The projection map represented low resolution of these crystals but suggested a donut shape oligomeric arrangement of protein in a hexagonal lattice with unit cell size of 87Å*87Å. Preliminary FTIR measurements indicated that the crystalline environment does not obstruct the photocycle of PR and K as well as M intermediate states could be identified. Single molecule force spectroscopy and atomic force microscopy on these 2D crystals was used to probe further information about the oligomeric state and nature of unfolding. The data revealed that protein predominantly exists as hexamers in crystalline as well as densely reconstituted regions but a small percentage of pentamers is also observed. The unfolding mechanism was similar to the other relatively well-characterized members of rhodopsin family. A good correlation of the atomic force microscopy and the electron microscopy data was achieved. Solid State NMR of the isotopically labeled 2D crystalline preparations using uniformly and selectively labeling schemes, allowed to obtain high quality SSNMR spectra with typical 15N line width in the range of 0.6-1.2 ppm. The measured 15N chemical shift value of the Schiff base in the 2D crystalline form was observed to be similar to the Schiff base chemical shift values for the functionally active reconstituted samples. This provides an indirect evidence for the active functionality of the protein and hence the folding. The first 15N assignment has been achieved for the Tryptophan with the help of Rotational Echo Double Resonance experiments. The 2D Cross Polarization Lee Goldberg measurements reflect the dynamic state of the protein inspite of restricted mobility in the crystalline state. The behavior of lipids as measured by 31P from the lipid head group showed that the lipids are not tightly bound to the protein but behave more like the lipid bilayer. The 13C-13C homonulear correlation experiments with optimized mixing time based on build up curve analysis, suggest that it is possible to observe individual resonances as seen in case of glutamic acid. The signal to noise was good enough to record a decent spectrum in a feasible period. The selective unlabeling is an efficient method for reduction in the spectral overlap. However, more efficient labeling schemes are required for further characterization. The present spectral resolution is good for individual amino acid investigation but for uniformly labeled samples, further improvement is required.
In this paper, we present an open-source parsing environment (Tübingen Linguistic Parsing Architecture, TuLiPA) which uses Range Concatenation Grammar (RCG) as a pivot formalism, thus opening the way to the parsing of several mildly context-sensitive formalisms. This environment currently supports tree-based grammars (namely Tree-Adjoining Grammars (TAG) and Multi-Component Tree-Adjoining Grammars with Tree Tuples (TT-MCTAG)) and allows computation not only of syntactic structures, but also of the corresponding semantic representations. It is used for the development of a tree-based grammar for German.
This paper investigates the relation between TT-MCTAG, a formalism used in computational linguistics, and RCG. RCGs are known to describe exactly the class PTIME; simple RCG even have been shown to be equivalent to linear context-free rewriting systems, i.e., to be mildly context-sensitive. TT-MCTAG has been proposed to model free word order languages. In general, it is NP-complete. In this paper, we will put an additional limitation on the derivations licensed in TT-MCTAG. We show that TT-MCTAG with this additional limitation can be transformed into equivalent simple RCGs. This result is interesting for theoretical reasons (since it shows that TT-MCTAG in this limited form is mildly context-sensitive) and, furthermore, even for practical reasons: We use the proposed transformation from TT-MCTAG to RCG in an actual parser that we have implemented.
TT-MCTAG lets one abstract away from the relative order of co-complements in the final derived tree, which is more appropriate than classic TAG when dealing with flexible word order in German. In this paper, we present the analyses for sentential complements, i.e., wh-extraction, thatcomplementation and bridging, and we work out the crucial differences between these and respective accounts in XTAG (for English) and V-TAG (for German).
Developing linguistic resources, in particular grammars, is known to be a complex task in itself, because of (amongst others) redundancy and consistency issues. Furthermore some languages can reveal themselves hard to describe because of specific characteristics, e.g. the free word order in German. In this context, we present (i) a framework allowing to describe tree-based grammars, and (ii) an actual fragment of a core multicomponent tree-adjoining grammar with tree tuples (TT-MCTAG) for German developed using this framework. This framework combines a metagrammar compiler and a parser based on range concatenation grammar (RCG) to respectively check the consistency and the correction of the grammar. The German grammar being developed within this framework already deals with a wide range of scrambling and extraction phenomena.
In this paper we present a parsing architecture that allows processing of different mildly context-sensitive formalisms, in particular Tree-Adjoining Grammar (TAG), Multi-Component Tree-Adjoining Grammar with Tree Tuples (TT-MCTAG) and simple Range Concatenation Grammar (RCG). Furthermore, for tree-based grammars, the parser computes not only syntactic analyses but also the corresponding semantic representations.
Women and Halakha Shiur
(2008)
Cellular metabolism can be envisaged by fluorescence lifetime imaging of fluorophores sensitive to specific intracellular factors such as [H+], [Ca2+], [O2], membrane potential, temperature, polarity of the probe environment, and alterations in the conformation and interactions of macromolecules. Lifetime measurements of the probes allow the quantitative determination of the intracellular factors. Fluorescence microscopy taking advantage of time-correlated single photon counting is a novel method that outperforms all other techniques with its single photon sensitivity and picoseconds time resolution. In this work, a time- and space-correlated single photon counting system was established to investigate the behavior of 2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide (DASPMI) in living cells. DASPMI is known to selectively stain mitochondria in living cells. The uptake and fluorescence intensity of DASPMI in mitochondria is a dynamic measure of membrane potential. Hence, an endeavour was made to elucidate the mechanism of DASPMI fluorescence by obtaining spectrally-resolved fluorescence decays in different solvents. A bi-exponential decay model was sufficient to globally describe the wavelength dependent fluorescence in ethanol and chloroform. While in glycerol, a three-exponential decay model was necessary for global analysis. In the polar low-viscous solvent water, a mono-exponential decay model fitted the decay data. The sensitivity of DASPMI fluorescence to solvent viscosity was analysed using various proportions of glycerol/ethanol mixtures. The lifetimes were found to increase with increasing solvent viscosity. The negative amplitudes of the short lifetime component found in chloroform and glycerol at the longer wavelengths validated the formation of new excited state species from the initially excited state. Time-resolved emission spectra in chloroform and glycerol showed a biphasic increase of spectral width and emission maxima. The spectral width had an initial fast increase within 150 ps and a near constant thereafter. A two-state model based on solvation of the initially excited state and further formation of TICT state has been proposed to explain the excited state kinetics and has been substantiated by the de-composition of time-resolved spectra. The knowledge of DASPMI photophysics in a variety of solvents now provides the means of deducing complex physiological parameters of mitochondria from its behavior in living cells. Spatially-resolved fluorescence decays from single mitochondria or only very few organelles of XTH2 cells signified distinctive three-exponential decay kinetics of viscous environment. Based on DASPMI photophysics in a variety of solvents, these lifetimes have been attributed to the fluorescence from locally excited state (LE), intramolecular charge transfer state (ICT) and twisted intramolecular charge transfer (TICT) state. A considerable variation in lifetime among mitochondria of different morphology and within single cell was evident corresponding to the high physiological variations within single cells. Considerable shortening of the short lifetime component (τ1) under high membrane potential condition, such as in the presence of ATP and/or substrate, was similar to quenching and dramatic decrease of lifetime in polar solvents. Under these conditions τ2 and τ3 increased with decreasing contribution. Upon treatment with ionophore nigericin, hyperpolarization of mitochondria resulted in remarkable shortening of τ1 from 159 ps to 38 ps. Inhibiting respiration by cyanide resulted in notable increase of mean lifetime and decrease of mitochondrial fluorescence. Increase of DASPMI fluorescence on conditions elevating mitochondrial membrane potential has been attributed to uptake according Nernst distributions, to de-localisation of π electrons, quenching processes of the methyl pyridinium moiety and restricted torsional dynamics at the mitochondrial inner membrane. Accordingly, determination of anisotropy in DASPMI stained mitochondria in living XTH2 cells, revealed dependence of anisotropy on membrane potential. Such changes in anisotropy attributed to restriction of the torsional dynamics about the flexible single bonds neighboring the olefinic double bond revealed the previously known sub-mitochondrial zones with higher membrane potential along its length. Membrane-potential-dependent changes in anisotropy have further been demonstrated in senescent chick embryo fibroblasts. In conclusion, spectroscopic observations of excited-state kinetics of DASPMI in solvents and its behavior in living cells had revealed for the first time its localisation, mechanism of voltage sensitive fluorescence and its membrane-potential-dependent anisotropy in living cells. The simultaneous dependence of DASPMI photophysics on mitochondrial inner membrane viscosity and transmembrane potential has been highlighted.
Maize and rice constitute some of the most important cereals cultivated in the world, being used as staple food for people especially in Africa. The rice moth, Corcyra cephalonica, and the maize weevil, Sitophilus zeamais, are major pests of stored grains in the tropics. The use of parasitoids in biological pest control is already common in different agricultural and horticultural fields. At present, grain managers tend to look at alternatives to chemicals to control insects in stored grain. Lariophagus distinguendus (Förster) is a synovigenic, solitary larval and pupal ectoparasitoid of several beetle species that infest stored goods. The ability for long-range host finding of this parasitoid mediated by volatiles has been shown (Steidle & Schöller 1997). Habrobracon hebetor (Say) is a gregarious ectoparasitoid of many lepidopterous pests. This wasp occurs naturally in the stored grain ecosystem (Keever & al. 1985) where it attacks several pyralid moths, including the rice moth, Corcyra cephalonica. The present study was conducted to assess the host finding of the two parasitoids H. hebetor and L. distinguendus.
Jüdische Grabsteinepigraphik: R. Yosef Trani (1568-1639), R. Akiva Eger (d. 1837), R. David Hoffmann (d. 1921)
The enigmatic R. David Lida
(2008)
Chemical ozone loss in winter 1991–1992 is recalculated based on observations of the HALOE satellite instrument, Version 19, ER-2 aircraft measurements and balloon data. HALOE satellite observations are shown to be reliable in the lower stratosphere below 400 K, at altitudes where the measurements are most likely disturbed by the enhanced sulfate aerosol loading, as a result of the Mt.~Pinatubo eruption in June 1991. Significant chemical ozone loss (13–17 DU) is observed below 380 K from Kiruna balloon observations and HALOE satellite data between December 1991 and March 1992. For the two winters after the Mt. Pinatubo eruption, HALOE satellite observations show a stronger extent of chemical ozone loss towards lower altitudes compared to other Arctic winters between 1991 and 2003. In spite of already occurring deactivation of chlorine in March 1992, MIPAS-B and LPMA balloon observations indicate that chlorine was still activated at lower altitudes, consistent with observed chemical ozone loss occurring between February and March and April. Large chemical ozone loss of more than 70 DU in the Arctic winter 1991–1992 as calculated in earlier studies is corroborated here.
During the APE-THESEO mission in the Indian Ocean the Myasishchev Design Bureau stratospheric research aircraft M55 Geophysica performed a flight over and within the inner core region of tropical cyclone Davina. Measurements of total water, water vapour, temperature, aerosol backscattering, ozone and tracers were made and are discussed here in comparison with the averages of those quantities acquired during the campaign time frame. Temperature anomalies in the tropical tropopause layer (TTL), warmer than average in the lower part and colder than average in the upper TTL were observed. Ozone was strongly reduced compared to its average value, and thick cirrus decks were present up to the cold point, sometimes topped by a layer of very dry air. Evidence for meridional transport of trace gases in the stratosphere above the cyclone was observed and perturbed water distribution in the TTL was documented. The paper discuss possible processes of dehydration induced by the cirrus forming above the cyclone, and change in the chemical tracer and water distribution in the lower stratosphere 400–430 K due to meridional transport from the mid-latitudes and link with Davina. Moreover it compares the data prior and after the cyclone passage to discuss its actual impact on the atmospheric chemistry and thermodynamics.
Appropriate precautions in the case of flood occurrence often require long lead times (several days) in hydrological forecasting. This in turn implies large uncertainties that are mainly inherited from the meteorological precipitation forecast. Here we present a case study of the extreme flood event of August 2005 in the Swiss part of the Rhine catchment (total area 34 550 km2). This event caused tremendous damage and was associated with precipitation amounts and flood peaks with return periods beyond 10 to 100 years. To deal with the underlying intrinsic predictability limitations, a probabilistic forecasting system is tested, which is based on a hydrological-meteorological ensemble prediction system. The meteorological component of the system is the operational limited-area COSMO-LEPS that downscales the ECMWF ensemble prediction system to a horizontal resolution of 10 km, while the hydrological component is based on the semi-distributed hydrological model PREVAH with a spatial resolution of 500 m. We document the setup of the coupled system and assess its performance for the flood event under consideration. We show that the probabilistic meteorological-hydrological ensemble prediction chain is quite effective and provides additional guidance for extreme event forecasting, in comparison to a purely deterministic forecasting system. For the case studied, it is also shown that most of the benefits of the probabilistic approach may be realized with a comparatively small ensemble size of 10 members.
The main objective of the study presented in this paper was to develop an evaluation scheme which is suitable for spatially explicit groundwater vulnerability assessment according to the Water Framework Directive (WFD). Study area was the Hase river catchment, an area of about 3 000 km2 in north-west Germany which is dominated by livestock farming, in particular pig and poultry production. For the Hase river catchment, the first inventory of the WFD led to the conclusion that 98% of the catchment area is "unclear/unlikely" to reach a good groundwater status due to diffuse nitrogen emissions from agriculture. The groundwater vulnerability assessment was embedded in the PartizipA project ("Participative modelling, Actor and Ecosystem Analysis in Regions with Intensive Agriculture", www.partizipa.net), within which a so-called actors´ platform was established in the study area. The objective of the participatory process was to investigate the effects of the WFD on agriculture as well as to discuss groundwater protection measures which are suitable for an integration in the programme of measures. The study was conducted according to the vulnerability assessment concept of the Intergovernmental Panel on Climate Change, considering sensitivity, exposure and adaptive capacity. Sensitivity was computed using the DRASTIC index of natural groundwater pollution potential. Exposure (for a reference scenario) was computed using the STOFFBILANZ nutrient model. Several regional studies were analysed to evaluate the adaptive capacity. From these studies it was concluded that the adaptive capacity in the Hase river catchment is very low due to the economic importance of the agricultural sector which will be significantly affected by groundwater protection measures. As a consequence, the adaptive capacity was not considered any more in the vulnerability assessment. A groundwater vulnerability evaluation scheme is presented which enjoys the advantage that both exposure and sensitivity can be operationalized in a spatially resolved manner (500×500 m grid) by the two models mentioned above. The evaluation scheme was applied in the Hase river catchment. 21% of the catchment was classified as highly vulnerable, another 73% as medium vulnerable. Only 6% of the Hase river catchment has low vulnerability. Grid cells of the high vulnerability class are considered as priority areas for groundwater protection measures in the programme of measures of the WFD. Measures will be particularly effective in the north-eastern part of the catchment where groundwater vulnerability is mainly due to high nitrogen emissions.
Strong perturbations of the Arctic stratosphere during the winter 2002/2003 by planetary waves led to enhanced stretching and folding of the vortex. On two occasions the vortex in the lower stratosphere split into two secondary vortices that re-merged after some days. As a result of these strong disturbances the role of transport in and out of the vortex was stronger than usual. An advection and mixing simulation with the Chemical Lagrangian Model of the Stratosphere (CLaMS) utilising a suite of inert tracers tagging the original position of the air masses has been carried out. The results show a variety of synoptic and small scale features in the vicinity of the vortex boundary, especially long filaments peeling off the vortex edge and being slowly mixed into the mid latitude environment. The vortex folding events, followed by re-merging of different parts of the vortex led to strong filamentation of the vortex interior. During January, February, and March 2003 flights of the Russian high-altitude aircraft Geophysica were performed in order to probe the vortex, filaments and in one case the merging zone between the secondary vortices. Comparisons between CLaMS results and observations obtained from the Geophysica flights show in general good agreement. Several areas affected by both transport and strong mixing could be identified, allowing explanation of many of the structures observed during the flights. Furthermore, the CLaMS simulations allow for a quantification of the air mass exchange between mid latitudes and the vortex interior. The simulation suggests that after the formation of the vortex was completed, its interior remaind relatively undisturbed. Only during the two re-merging events were substantial amounts of extra-vortex air transported into the polar vortex. When in March the vortex starts weakening additional influence from lower latitudes becomes apparent in the model results. In the lower stratosphere export of vortex air leads only to a fraction of about 5% polar air in mid latitudes by the end of March. An upper limit for the contribution of ozone depleted vortex air on mid-latitude ozone loss is derived, indicating that the maximum final impact of dilution is on the order of 50%.
From July 2002 to March 2004 the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European Space Agency´s Environmental Satellite (Envisat) measured nearly continuously mid infrared limb radiance spectra. These measurements are utilised to retrieve the global distribution of the chlorofluorocarbon CFC-11 by applying a new fast forward model for Envisat MIPAS and an accompanying optimal estimation retrieval processor. A detailed analysis shows that the total retrieval errors of the individual CFC-11 volume mixing ratios are typically below 10% in the altitude range 10 to 25 km and that the systematic components dominate. Contribution of a priori information to the retrieval results are less than 5 to 10% and the vertical resolution of the observations is about 3 to 4 km in the same vertical range. The data are successfully validated by comparison with several other space experiments, an air-borne in-situ instrument, measurements from ground-based networks, and independent Envisat MIPAS analyses. The retrieval results from 425 000 Envisat MIPAS limb scans are compiled to provide a new climatological data set of CFC-11. The climatology shows significantly lower CFC-11 abundances in the lower stratosphere compared with the Reference Atmospheres for MIPAS (RAMstan V3.1) climatology. Depending on the atmospheric conditions the differences between the climatologies are up to 30 to 110 ppt (45 to 150%) at 19 to 27 km altitude. Additionally, time series of CFC-11 mean abundance and variability for five latitudinal bands are presented. The observed CFC-11 distributions can be explained by the residual mean circulation and large-scale eddy-transports in the upper troposphere and lower stratosphere. The new CFC-11 data set is well suited for further scientific studies.
Global distributions of profiles of sulphur hexafluoride (SF6) have been retrieved from limb emission spectra recorded by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on Envisat covering the period September 2002 to March 2004. Individual SF6 profiles have a precision of 0.5 pptv below 25 km altitude and a vertical resolution of 4–6 km up to 35 km altitude. These data have been validated versus in situ observations obtained during balloon flights of a cryogenic whole-air sampler. For the tropical troposphere a trend of 0.230±0.008 pptv/yr has been derived from the MIPAS data, which is in excellent agreement with the trend from ground-based flask and in situ measurements from the National Oceanic and Atmospheric Administration Earth System Research Laboratory, Global Monitoring Division. For the data set currently available, based on at least three days of data per month, monthly 5° latitude mean values have a 1 o standard error of 1%. From the global SF6 distributions, global daily and monthly distributions of the apparent mean age of air are inferred by application of the tropical tropospheric trend derived from MIPAS data. The inferred mean ages are provided for the full globe up to 90° N/S, and have a 1 o standard error of 0.25 yr. They range between 0 (near the tropical tropopause) and 7 years (except for situations of mesospheric intrusions) and agree well with earlier observations. The seasonal variation of the mean age of stratospheric air indicates episodes of severe intrusion of mesospheric air during each Northern and Southern polar winter observed, long-lasting remnants of old, subsided polar winter air over the spring and summer poles, and a rather short period of mixing with midlatitude air and/or upward transport during fall in October/November (NH) and April/May (SH), respectively, with small latitudinal gradients, immediately before the new polar vortex starts to form. The mean age distributions further confirm that SF6 is destroyed in the mesosphere to a considerable degree. Model calculations with the Karlsruhe simulation model of the middle atmosphere (KASIMA) chemical transport model agree well with observed global distributions of the mean age only if the SF6 sink reactions in the mesosphere are included in the model.
This study presents an evaluation of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC) in terms of measuring ambient and laboratory-generated molecular and ion clusters. Ambient molecular cluster concentrations were measured with both instruments as they were deployed in conjunction with an ion spectrometer and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station between 1 March and 30 June 2007. The observed cluster concentrations varied and ranged from some thousands to 100 000 cm -3. Both instruments showed similar (within a factor of ~5) concentrations. An average size of the detected clusters was approximately 1.8 nm. As the atmospheric measurement of sub 2-nm particles and molecular clusters is a challenging task, we conclude that most likely we were unable to detect the smallest clusters. Nevertheless, the reported concentrations are the best estimates to date for minimum cluster concentrations in a boreal forest environment.
We report the first atmospheric observations of the Chlorofluorocarbons (CFCs) trifluorochloroethene, 3-chloropentafluoropropene and 4,4-dichlorohexafluoro-1-butene by means of Gas Chromatography with Electron Capture and Mass Spectrometric detection (GC-ECD-MS) in air samples taken at the Taunus Observatory operated by the University of Frankfurt (Main) and the Jungfraujoch High Altitude Research Station in Switzerland. These substances belong to a class of CFCs containing a double bond and are suspected to originate from the production and thermal degradation of widely used fluoropolymers like polychlorotrifluoroethene (PCTFE). Their atmospheric lifetimes are expected to be rather short. A quantitative calibration could only be derived for trifluorochloroethene but not for the other species by now. Thus, we use a relative sensitivity method to get a first indication of the observed atmospheric abundances. Identification was possible because of an air plume containing high concentrations of these substances. We suggest that the abundances found on this occasion originated from a local source. However, we have also observed the novel CFCs in air masses representative of background conditions, though with much lower concentrations. These species and some of their degradation products are toxic and could also be relevant for stratospheric and tropospheric ozone depletion.
Assessment of ecologically relevant hydrological change in China due to water use and reservoirs
(2008)
As China’s economy booms, increasing water use has significantly affected hydro-geomorphic processes and thus the ecology of surface waters. A large variety of hydrological changes arising from human activities such as reservoir construction and management, water abstraction, water diversion and agricultural land expansion have been sustained throughout China. Using the global scale hydrological and water use model WaterGAP, natural and anthropogenically altered flow conditions are calculated, taking into account flow alterations due to human water consumption and 580 large reservoirs. The impacts resulting from water consumption and reservoirs have been analyzed separately. A modified “Indicators of Hydrologic Alteration” approach is used to describe the human pressures on aquatic ecosystems due to anthropogenic alterations in river flow regimes. The changes in long-term average river discharge, average monthly mean discharge and coefficients of variation of monthly river discharges under natural and impacted conditions are compared and analyzed. The indicators show very significant alterations of natural river flow regimes in a large part of northern China and only minor alterations in most of southern China. The detected large alterations in long-term average river discharge, the seasonality of flows and the inter-annual variability in the northern half of China are very likely to have caused significant ecological impacts.
Transcriptional activation involves the ordered recruitment of coactivators via direct interactions between distinct binding domains and recognition motifs. The p160/SRC/NCoA coactivator family comprises three members (NCoA-1, -2 and -3), which are organized in multiprotein coactivator complexes. We had identified the PAS-B domain of NCoA-1 as an LXXLL motif binding domain. Here we show that NCoA family members are able to interact with other full-length NCoA proteins via their PAS-B domain and they specifically interact with the CBP-interaction domain (CID/AD1) of NCoA-1. Peptide competition, binding experiments and mutagenesis of LXXLL motifs point at distinct binding motif specificities of the NCoA PAS-B domains. NMR studies of different NCoA-1-PAS-B/LXXLL peptide complexes revealed similar although not identical binding sites for the CID/AD1 and STAT6 transactivation domain LXXLL motifs. In mechanistic studies, we found that overexpression of the PAS-B domain is able to disturb the binding of NCoA-1 to CBP in cells and that a CID/AD1 peptide competes with STAT6 for NCoA-1 in vitro. Moreover, the expression of an endogenous androgen receptor target gene is affected by the overexpression of the NCoA-1 or NCoA-3 PAS-B domains. Our study discloses a new, complementary mechanism for the current model of coactivator recruitment to target gene promoters.
In a combined NMR/MD study, the temperature-dependent changes in the conformation of two members of the RNA YNMG-tetraloop motif (cUUCGg and uCACGg) have been investigated at temperatures of 298, 317 and 325 K. The two members have considerable different thermal stability and biological functions. In order to address these differences, the combined NMR/MD study was performed. The large temperature range represents a challenge for both, NMR relaxation analysis (consistent choice of effective bond length and CSA parameter) and all-atom MD simulation with explicit solvent (necessity to rescale the temperature). A convincing agreement of experiment and theory is found. Employing a principle component analysis of the MD trajectories, the conformational distribution of both hairpins at various temperatures is investigated. The ground state conformation and dynamics of the two tetraloops are indeed found to be very similar. Furthermore, both systems are initially destabilized by a loss of the stacking interactions between the first and the third nucleobase in the loop region. While the global fold is still preserved, this initiation of unfolding is already observed at 317 K for the uCACGg hairpin but at a significantly higher temperature for the cUUCGg hairpin.
In Western Europe pedunculate oak (Quercus robur L.) is the forest tree with the highest number of phytophagous insect species (Yela & Lawton 1997). One of these, the green oak leaf roller Tortrix viridana L. is an oligophagous herbivorous moth with a host range limited to the genus Quercus (Hunter 1990, Du Merle 1999). During outbreaks, T. viridana often leads to defoliation of oaks in spring. The abundance of T. viridana is subject to the population size fluctuations typical for herbivorous insects, where periods of small population sizes (latent periods) alternate with periods of high population sizes (outbreak) (e.g. Schütte 1957, Horstmann 1984). Apart from many experimental studies on population dynamics of the moth (e.g. Hunter 1990, Du Merle 1999, Ivashov & al. 2002) so far little attention has been paid to the genetic variation within the species as an important aspect of the genetics of this host-parasite interaction. Simchuk & al. (1999) found changes in the heterozygosity level of different isozyme loci during outbreaks in T. viridana and molecular markers for T. viridana have been developed for analyses of genetic variation within and among populations (Schroeder & Scholz 2005). But, investigations of genetic variation within and among populations of forest pest species are important to predict future pest outbreaks. So far the processes outbreaks based on are not entirely clarified, however it is known that migration plays a major role. Using molecular markers investigations of the genetic variation are possible and offer the opportunity to analyse distribution events. In this paper first results are presented concerning the genetic variation of the green oak leaf roller at three geographic scales: (1) among trees within a population, (2) among populations at a small spatial scale of about 150 km and (3) among populations at a broader geographic scale up to 3000 km. Furthermore results of the genetic variation of oaks at the small spatial scale are represented.
Since the late 1990s, the oak processionary moth, Thaumetopoea processionea (L.), has been occurring at high population densities in eastern Austria. Particularly, infestations in areas of human settlement have created increasing interest in this insect due to health problems caused by the urticating hairs of the larvae. New methods for biological control are desirable. Like essentially all forest Lepidoptera, T. processionea is host for entomopathogenic microsporidia. These obligatory parasitic protists have been evaluated as biocontrol agents against an other oak pest, Lymantria dispar (Weiser & Novotny, 1987; Jeffords & al., 1988). Life history traits of T. processionea make this insect an even more promising target for the use of microsporidia. The larvae are highly gregarious and stay together in nests made of larval silk for resting periods and molting. Microsporidia utilize several pathways for horizontal transmission that would be aided by these features: spores can be released after host death from cadavers as well as from living larvae via silk or feces. Additionally, many microsporidia are vertically transmitted (summarized in Maddox & al., 1998). In this project, T. processionea larvae from various regions in eastern Austria were screened for the natural occurrence of microsporidia. One isolate, Endoreticulatus sp., was further studied and mass produced in a laboratory host, L. dispar, that is easy to rear and does not pose a health hazard for people working with the insects. An inoculative release was attempted on isolated trees infested with T. processionea.
Cantharidin, which is mainly found in blister beetles (Coleoptera: Meloidae), is one of the most intensively studied natural products of insect (Dettner, 1997; McCormick & Carrel, 1987). The involvement of cantharidin in courtship behaviour has been already confirmed for certain canthariphilous insects (Eisner & al. 1996a,b; Frenzel & Dettner 1994; Frenzel & al. 1992; Schütz & Dettner, 1992; Hemp & al. 1999). The function and intrinsinc role of cantharidin in the courtship behaviour of Meloids has been never fully established. McCormick & Carrel (1987) only suggested that cantharidin might be used by female meloids when selecting a mate at close range. Pinto (1974, 1975) was, in fact, the first to consider male cuticular pores as being involved in the courtship behaviour of species from the genus Linsleya and Tegrodera (Meloidae). Based on morphology and chemical analyses of Cyaneolytta sp. (Coleoptera: Meloidae), we have hereby provided some further evidences that cantharidin may act as an infochemical in courtship behaviour of meloid beetles.
Sexual deception of male bees is one of the most remarkable mechanisms of pollination (Ackermann 1986, Proctor & al. 1996). Flowers of the orchid genus Ophrys mimic females of their pollinator species, usually bees and wasps, to attract males, which try to copulate with the flowers. During this so-called “pseudocopulation” the male removes the pollinia and transfers them to another flower to ensure pollination. Apart from visual and tactile cues, floral scent was shown to be most important for eliciting mating behaviour in males (Kullenberg 1961, Schiestl & al. 1999, Ayasse & al. 2003). Pollination in Ophrys is highly specific and usually each Ophrys species attracts only one pollinator species (Paulus & Gack 1990). The high degree of specialization provides the means of reproductive isolation between the intercrossable Ophrys-species (Ehrendorfer 1980). The complex odour-bouquets released by the flowers are species-specific and often consist of more than 100 different chemical compounds (Borg-Karlson & al. 1985, Ayasse 2006). Speciation in Ophrys-orchids may be brought about by changes in the pollinator attracting floral scent. The attraction of a new pollinator may act as a pre-zygotic isolation barrier (Stebbins 1970, Paulus & Gack 1990, Soliva & al. 2001). We investigated three sympatrically occuring Ophrys-species on Sardinia. O. chestermanii and O. normanii are endemic and are both pollinated by males of the bumblebee B. vestalis. O. tenthredinifera is pollinated by Eucera nigrilabris. There are different opinions concerning the taxonomic status of O. normanii. It has been described as an actual hybrid between O. chestermanii and O. tenthredinifera (Wood 1983). Paulus & Gack (1995) suggested that it is an own species, that either has developed from a hybrid between O. chestermanii and O. normanii or that has evolved by radiation from O. tenthredinifera. By conducting behavioural-tests with B. vestalis males, performing gas chromatographic analyses and electrophysiological studies we wanted to identify pollinator attracting scent and to clarify the taxonomic status of O. normanii.
The orchid genus Epipactis is represented by 25 species in Europe (Richards 1982). Epipactis helleborine (L.) Crantz is the most common and widely distributed species of the genus (Wiefelspütz 1970), and is a prime example for wasp-flowers, because it is mainly pollinated by social wasps (Hymenoptera: Vespidae), like Vespula vulgaris and V. germanica (Müller 1873). Darwin (1888) already noticed that E. helleborine is almost exclusively ignored by bees and bumblebees, an observation that was confirmed in recent investigations (Keppert 2001). The flowers of E. helleborine show morphological, physiological and phenological adaptations to the visit and the pollination by Vespidae (Keppert 2001). They possess a reddish-brown or dirty purple coloration of the inflorescence (Keppert 2001), have relatively small, mostly bulbous blossoms with a broad entrance and bulbous widened, nectar-rich juice holders (Müller 1873, 1881; Schremmer 1962). Although there is much reported about wasp-pollinated flowers there is little known about the signals that are responsible for the attraction of wasps. Wiefelspütz (1970) proclaimed the statement that only the visual stimulus is responsible for the wasp attraction. Recently studies, however, assumed that odour is involved in the wasp attraction (Keppert 2001). Hölzler (2003) showed that the main attraction of the wasp-flower Epipactis for pollinators is its olfactory stimulus. It remains an unanswered question why E. helleborine flowers almost exclusively attracts social wasps, as opposed to bees and bumblebees. In this study we analysed the role of floral volatiles which are responsible for the specific attraction of social wasps. We supposed a mimicry-system in E. helleborine for the specific attraction of pollinators for the following reasons. So-called “green leaf volatiles” (GLVs) are emitted by plants while herbivorous insects, for example caterpillars, feed on them. GLVs thereby attract predators or parasitoids of the herbivorous insects (Dicke & Sabelis 1988; Turlings & al. 1990, 1995; Dicke & Vet 1999). Among the GLVs so far identified in former studies there are aldehydes, compounds that were also found in flower extracts of E. helleborine (Hölzler 2003). Therefore, we postulated that E. helleborine flowers produce GLVs in order to attract prey hunting social wasps for pollination. We performed bioassays and analysed flower odour gained to headspace-sampling using gas chromatography (GC), mass spectrometry (GC-MS) and gas chromatography coupled with electrophysiological analysis (GC-EAD) to investigate the hypothesis that E. helleborine flowers mimic “green leaf volatiles” (GLVs) to attract their pollinators.
Solitary bees are important pollinators of flowers. Besides nectar they collect pollen at flowers mainly to provide their larvae with food. Many bee species collect pollen only on a few closely related plant species (oligolecty) (Müller & al. 1997). Little is known about the visual and olfactorial signals they use for host-plant finding (Wcislo & Cane 1996). However, bees can olfactorily distinguish between different pollen species (von Frisch 1923), and a species-specific chemistry of pollen odour is known for some plant species (Bergström & al. 1995, Dobson & al. 1999). Further, it was shown that naïve oligolectic bees recognize their host-plant on the basis pollen volatiles (Dobson & Bergström 2000) and that flower-experienced bees could use pollen odours to assess pollen availability (Dobson & al. 1999). Besides scent, also visual cues are of relevance for host-plant finding, and bees orientate especially spectral contrasts. Biotests with dummy flowers revealed that colour contrast and not intensity and dominant wavelengths are influencing innate behavioural responses (Lunau 1990). Further it was shown that naïve bumblebees were most motivated to land on a flower when visual stimuli from the antheres are combined with olfactorial stimuli from the pollen (1992). We choose Osmia adunca P., which is highly specialized on Echium L., as a model to investigate the importance of floral cues for an oligolectic bee. Because bees learn to associate odours with reward more rapidly than visual cues (Menzel 1985), we hypothesize that scent plays a major role in attraction flower-experienced O. adunca females. We used gas chromatography to compare the scent of three Echium species with the scent of a closely related Anchusa species, and a spectrometer to compare the colour of the three Echium species. Additionally we conducted a biotest to determine the importance of visual and olfactorial signals of Echium for host-plant finding of experienced O. adunca females.
In agroecological research it has been appreciated only fairly recently that plant-insect interactions and other ecological processes depend on scales much larger than a single habitat (Wiens et al. 1997). Crop-pest interactions have mainly been studied on single pest species by focusing either on the impact of field parameters or on landscape structure but only rarely included both factors (Östman et al. 2001). Here we investigated how the abundances of three major insect pest species in oilseed rape (OSR) responded to field parameters and landscape characteristics at various spatial scales. Pest species considered in the current study include (i) ceutorhynchid stem weevils that lay eggs in leaf petioles or midribs of OSR plants while the larvae tunnel in the stems; (ii) pollen beetles that feed on pollen and destroy flower buds and (iii) brassica pod midge that lay eggs into OSR pods where the hatched larvae consume the seeds as well as tissue of the pod walls and cause the pods to split prematurely (Alford et al. 2003). Studying these different groups of pests is especially important because they attack different parts of the crop, use different habitats as overwintering sites and also differ in their mobility; with the exception of pollen beetles these pest species have never been studied in a landscape context. The specific objectives of this study were to determine (i) whether the major OSR pest species differ in their relation to field and landscape characteristics and (ii) at which spatial scales landscape variables are effective.
Agricultural intensification is a major threat to biological diversity worldwide. Land management activities enhancing landscape diversity are therefore regarded as a key strategy to halt species loss in cultural landscapes. Diverse and abundant communities of predatory arthropods, e.g. spiders (Araneae), have a high potential to suppress pest populations (Symondson et al. 2002) and could therefore contribute to allow reductions of pesticide use. Crop fields alone are usually not able to sustain diverse and individual-rich populations of predatory arthropods, because agricultural management results in disturbances and habitat deteriorations (harvest, soil cultivation, pesticide application) that kill or drive away large parts of the populations. Therefore semi-natural and perennial habitats in agricultural landscapes are considered to be of great importance for beneficial arthropods. On the one hand they offer refuge habitats in times when arable fields are hostile, e.g. fields with bare grounds during winter (Schmidt & Tscharntke 2005). On the other hand, viable populations of predatory arthropods in semi-natural habitats can serve as sources for (re-) colonisation of arable fields (Schmidt & Tscharntke 2005). Because of these exchanges between crop and non-crop areas it is important to include the surrounding landscape when investigating field-scale processes. We investigated the relations between spider assemblages in arable fields and the surrounding landscape in 29 fields of winter oilseed rape (OSR) in an agricultural landscape in eastern Austria. The objectives of this study were to estimate (1) how much spider assemblages in oilseed rape fields are influenced by the surrounding landscape, (2) the relative influence of landscape variables compared to field-scale variables and (3) at which spatial scales landscape variables are effective.
The lower wood-feeding Australian termite Mastotermes darwiniensis Froggatt (Fig. 1) is the only living member of the family Mastotermitidae. The complex symbiotic hindgut flora consists of protozoa (formerly named Archaezoa; Cleveland & Grimstone 1964; Brugerolle & al. 1994; Berchtold & König 1995; Fröhlich & König 1999a, b), bacteria (Berchtold & König 1996; Berchtold & al. 1999), archaea (Fröhlich & König 1999a, b) and yeasts (Prillinger & al. 1996; Schäfer & al. 1996). The digestive system of Mastotermes darwiniensis consists of the foregut with the crop and the gizzard, the midgut, and the hindgut (Noirot & Noirot-Timothée 1969; 1995). The hindgut consists of five segments (P1 – P5): the proctodeal segment, the enteric valve, the paunch, the colon and the rectum. The paunch is the main microbial fermentation chamber, but the colon also contains microorganisms. The paunch is subdivided into a dilated thin-walled region (P3a) and a thick walled more tubular region (P3b) (Fig. 1c). In the case of Mastotermes darwiniensis oxygen diffusion gradients could be detected up to 100 μm below the epithelium (Berchtold & al., 1999).
In our present-day landscape in Central Europe major parts of the xylobiontic especially of the saproxylic beetle fauna belong to the group of endangered species assemblages (Speight 1989, Geiser 1994). Oaks, in Central Europe mainly Quercus robur and Q. petraea, are well known for their large number of associated insect species and harbour the highest beetle diversity, especially for dead wood inhabiting species, of all broadleaved tree species in this region (e.g. Palm 1959). A characteristic species associated with oaks in its life-cycle is the endangered Great Capricorn Cerambyx cerdo. C. cerdo is one of the protected species explicitly named in the Habitats Directive of the European Union with the goal of maintaining existing populations and establishing long-term survival (Council of the European Communities 1992). The last remaining colonised areas of this longhorn beetle in Central Europe are well known for the enormous number of very rare xylobiontic beetle species. Thus, we are interested in the following research questions: 1) Are there typical species associated with C. cerdo? 2) If so, what kind of relationship do these associated species have to C. cerdo from a nature conservation point of view?
A high-precision pressure probe is described which allows non-invasive online-monitoring of the water relations of intact leaves. Real-time recording of the leaf water status occurred by data transfer to an Internet server. The leaf patch clamp pressure probe measures the attenuated pressure, Pp, of a leaf patch in response to a constant clamp pressure, Pclamp. Pp is sensed by a miniaturized silicone pressure sensor integrated into the device. The magnitude of Pp is dictated by the transfer function of the leaf, Tf, which is a function of leaf patch volume and ultimately of cell turgor pressure, Pc, as shown theoretically. The power function Tf=f(Pc) theoretically derived was experimentally confirmed by concomitant Pp and Pc measurements on intact leaflets of the liana Tetrastigma voinierianum under greenhouse conditions. Simultaneous Pp recordings on leaflets up to 10 m height above ground demonstrated that changes in Tf induced by Pc changes due to changes of microclimate and/or of the irrigation regime were sensitively reflected in corresponding changes of Pp. Analysis of the data show that transpirational water loss during the morning hours was associated with a transient rise in turgor pressure gradients within the leaflets. Subsequent recovery of turgescence during the afternoon was much faster than the preceding transpiration-induced water loss if the plants were well irrigated. Our data show the enormous potential of the leaf patch clamp pressure probe for leaf water studies including unravelling of the hydraulic communication between neighbouring leaves and over long distances within tall plants (trees).
Chloroplast function depends on the translocation of cytosolically synthesized precursor proteins into the organelle. The recognition and transfer of most precursor proteins across the outer membrane depend on a membrane inserted complex. Two receptor components of this complex, Toc34 and Toc159, are GTPases, which can be phosphorylated by kinases present in the hosting membrane. However, the physiological function of phosphorylation is not yet understood in detail. It is demonstrated that both receptors are phosphorylated within their G-domains. In vitro, the phosphorylation of Toc34 disrupts both homo- and heterodimerization of the G-domains as determined using a phospho-mimicking mutant. In endogenous membranes this mutation or phosphorylation of the wild-type receptor disturbs the association of Toc34, but not of Toc159 with the translocation pore. Therefore, phosphorylation serves as an inhibitor for the association of Toc34 with other components of the complex and phosphorylation can now be discussed as a mechanism to exchange different isoforms of Toc34 within this ensemble.
Gene trapping is used to introduce insertional mutations into genes of mouse embryonic stem cells (ESCs). It is performed with gene trap vectors that simultaneously mutate and report the expression of the endogenous gene at the site of insertion and provide a DNA tag for rapid identification of the disrupted gene. Gene traps have been employed worldwide to assemble libraries of mouse ESC lines harboring mutations in single genes, which can be used to make mutant mice. However, most of the employed gene trap vectors require gene expression for reporting a gene trap event and therefore genes that are poorly expressed may be under-represented in the existing libraries. To address this problem, we have developed a novel class of gene trap vectors that can induce gene expression at insertion sites, thereby bypassing the problem of intrinsic poor expression. We show here that the insertion of the osteopontin enhancer into several conventional gene trap vectors significantly increases the gene trapping efficiency in high-throughput screens and facilitates the recovery of poorly expressed genes.
Comparative studies suggest that at least some bird species have evolved mental skills similar to those found in humans and apes. This is indicated by feats such as tool use, episodic-like memory, and the ability to use one´s own experience in predicting the behavior of conspecifics. It is, however, not yet clear whether these skills are accompanied by an understanding of the self. In apes, self-directed behavior in response to a mirror has been taken as evidence of self-recognition. We investigated mirror-induced behavior in the magpie, a songbird species from the crow family. As in apes, some individuals behaved in front of the mirror as if they were testing behavioral contingencies. When provided with a mark, magpies showed spontaneous mark-directed behavior. Our findings provide the first evidence of mirror self-recognition in a non-mammalian species. They suggest that essential components of human self-recognition have evolved independently in different vertebrate classes with a separate evolutionary history.
Ribosome biogenesis in eukaryotes requires the participation of a large number of ribosome assembly factors. The highly conserved eukaryotic nucleolar protein Nep1 has an essential but unknown function in 18S rRNA processing and ribosome biogenesis. In Saccharomyces cerevisiae the malfunction of a temperature-sensitive Nep1 protein (nep1-1ts) was suppressed by the addition of S-adenosylmethionine (SAM). This suggests the participation of Nep1 in a methyltransferase reaction during ribosome biogenesis. In addition, yeast Nep1 binds to a 6-nt RNA-binding motif also found in 18S rRNA and facilitates the incorporation of ribosomal protein Rps19 during the formation of pre-ribosomes. Here, we present the X-ray structure of the Nep1 homolog from the archaebacterium Methanocaldococcus jannaschii in its free form (2.2 Å resolution) and bound to the S-adenosylmethionine analog S-adenosylhomocysteine (SAH, 2.15 Å resolution) and the antibiotic and general methyltransferase inhibitor sinefungin (2.25 Å resolution). The structure reveals a fold which is very similar to the conserved core fold of the SPOUT-class methyltransferases but contains a novel extension of this common core fold. SAH and sinefungin bind to Nep1 at a preformed binding site that is topologically equivalent to the cofactor-binding site in other SPOUT-class methyltransferases. Therefore, our structures together with previous genetic data suggest that Nep1 is a genuine rRNA methyltransferase.
Bency Eichorn learns in kollel and, on the side, has been researching about various segulos. For his wedding he authored a book, Simchas Zion, discussing the segulah of keeping the afikomom from year-to-year. The post below is a small part of a much larger project on this segulah and has been adapted for the blog.
Market uptake of pegylated interferons for the treatment of hepatitis C in Europe : meeting abstract
(2008)
Introduction and Objectives Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease with life threatening sequelae such as end-stage liver cirrhosis and liver cancer. It is estimated that the infection annually causes about 86,000 deaths, 1.2 million disability adjusted life years (DALYs), and ¼ of the liver transplants in the WHO European region. Presently, only antiviral drugs can prevent the progression to severe liver disease. Pegylated interferons combined with ribavirin are considered as current state-of-the-art treatment. Objective of this investigation was to assess the market uptake of these drugs across Europe in order to find out whether there is unequal access to optimised therapy. Material and Methods We used IMS launch and sales data (April 2000 to December 2005) for peginterferons and ribavirin for 21 countries of the WHO European region. Market uptake was investigated by comparing the development of country-specific sales rates. For market access analysis, we converted sales figures into numbers of treated patients and related those to country-specific hepatitis C prevalence. To convert sales figures into patient figures, the amount of active pharmaceutical ingredients (API) sold was divided by average total patient doses (ATPD), derived by a probability tree-based calculation algorithm accounting for genotype distribution, early stopping rules, body weight, unscheduled treatment stops and dose reductions Ntotal=APIPegIFNalpha-2a/ATPDPegIFNalpha-2a+APIPegIFN&alpha-2b/ATPDPegIFNalpha-2b For more concise result presentation the 21 included countries were aggregated into four categories: 1. EU founding members (1957): Belgium, France, Germany, Italy and Netherlands; 2. Countries joining EU before 2000: Austria (1995), Denmark (1973), Finland (1995), Greece (1981), Republic of Ireland (1973), Spain (1986), Sweden and UK (1973) 3. Countries joining EU after 2000: Czech Republic (2004), Hungary (2004), Poland (2004) and Romania (2007); 4. EU non-member states: Norway, Russia, Switzerland and Turkey. Results Market launch and market uptake of the investigated drugs differed considerably across countries. The earliest, most rapid and highest increases in sales rates were observed in the EU founding member states, followed by countries that joined the EU before 2000, countries that joined the EU after 2000, and EU non-member states. Most new EU member states showed a noticeable increase in sales after joining the EU. Market access analysis yielded that until end of 2005, about 308 000 patients were treated with peginterferon in the 21 countries. Treatment rates differed across Europe. The number of patients ever treated with peginterferon per 100 prevalent cases ranged from 16 in France to less than one in Romania, Poland, Greece and Russia. Discussion Peginterferon market uptake and prevalence adjusted treatment rates were found to vary considerably across 21 countries in the WHO European region suggesting unequal access to optimised therapy. Poor market access was especially common in low-resource countries. Besides budget restrictions, national surveillance and prevention policy should be considered as explanations for market access variation. Although our results allowed for the ranking of countries in order of market access, no final conclusions on over- or undertreatment can be drawn, because the number of patients who really require antiviral treatment is unknown. Further research based on pan-European decision models is recommended to determine the fraction of not yet successfully treated but treatable patients among those ever diagnosed with HCV. ...
Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions.
C2-symmetric bisamidines : chiral Brønsted bases catalysing the Diels-Alder reaction of anthrones
(2008)
C2-symmetric bisamidines 8 have been tested as chiral Brønsted bases in the Diels- Alder reaction of anthrones and N-substituted maleimides. High yields of cycloadducts and significant asymmetric inductions up to 76% ee are accessible. The proposed mechanism involves proton transfer between anthrone and bisamidine, association of the resulting ions and finally a cycloaddition step stereoselectively controlled by the chiral ion pair.
Oscillatory activity in human electro- or magnetoencephalogram has been related to cortical stimulus representations and their modulation by cognitive processes. Whereas previous work has focused on gamma-band activity (GBA) during attention or maintenance of representations, there is little evidence for GBA reflecting individual stimulus representations. The present study aimed at identifying stimulus-specific GBA components during auditory spatial short-term memory. A total of 28 adults were assigned to 1 of 2 groups who were presented with only right- or left-lateralized sounds, respectively. In each group, 2 sample stimuli were used which differed in their lateralization angles (15° or 45°) with respect to the midsagittal plane. Statistical probability mapping served to identify spectral amplitude differences between 15° versus 45° stimuli. Distinct GBA components were found for each sample stimulus in different sensors over parieto-occipital cortex contralateral to the side of stimulation peaking during the middle 200–300 ms of the delay phase. The differentiation between "preferred" and "nonpreferred" stimuli during the final 100 ms of the delay phase correlated with task performance. These findings suggest that the observed GBA components reflect the activity of distinct networks tuned to spatial sound features which contribute to the maintenance of task-relevant information in short-term memory.
Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
The degradation of the poly(A) tail is crucial for posttranscriptional gene regulation and for quality control of mRNA. Poly(A)-specific ribonuclease (PARN) is one of the major mammalian 3’ specific exo-ribonucleases involved in the degradation of the mRNA poly(A) tail, and it is also involved in the regulation of translation in early embryonic development. The interaction between PARN and the m7GpppG cap of mRNA plays a key role in stimulating the rate of deadenylation. Here we report the solution structures of the cap-binding domain of mouse PARN with and without the m7GpppG cap analog. The structure of the cap-binding domain adopts the RNA recognition motif (RRM) with a characteristic a-helical extension at its C-terminus, which covers the b-sheet surface (hereafter referred to as PARN RRM). In the complex structure of PARN RRM with the cap analog, the base of the N7-methyl guanosine (m7G) of the cap analog stacks with the solvent-exposed aromatic side chain of the distinctive tryptophan residue 468, located at the C-terminal end of the second b-strand. These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains.
We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide.
While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion.
Diabrotica virgifera virgifera LeConte, in its original North American habitat also known as western corn rootworm beetle, actively continues its expansion to new territories and uses Homo sapiens as its prime vector. It took only 15 years to spread to and occupy the southeastern and central parts of Europe, so far with the exception of Denmark where it has not been documented as of 2007. Economic thresholds have been reached and surpassed only in Southeast European countries like Slovakia, Hungary, Serbia, Eastern Croatia, Romania and Northern Italy. But both, the area affected and the severity of symptoms are increasing. Model calculations by a number of authors (Baufeld & Enzian, 2005 a and b; Hongmei Li & al. 2006, CLIMEX model) indicate a definitive propensity of D. v. virgifera to expand its currently occupied territory to regions with moderate temperatures and Zea mays cultivation. East Africa and Eastern Asia are included in the list of potential candidates for future inadvertent introduction. In most discussions it is tacitly and erroneously assumed that Z. mays is the only or the only important host of D. v. virgifera. Our recent observations in Eastern Slovenia on the oil pumpkin Cucurbita pepo indicate, however, that this simplifying assumption is notlonger strictly valid. It has to be modified in light of new evidence. Here, we report a few field experiments conducted in August of 2006 clarifying the host status of C. pepo in a European country.
The codling moth, Cydia pomonella (Lep., Tortricidae), is a significant pest of orchard crops such as apple and pear in Southern Germany, and can cause severe economic damage to apple crops. Due to resistance to conventional pesticides and the growing market for organic fruit, Cydia pomonella Granulovirus (CpGV) has been used to control C. pomonella in Germany for over 10 years. Recently, populations exhibiting resistance to CpGV have been reported. In this study, we have used amplified fragment length polymorphism (AFLP) markers to estimate genetic variations between eight different C. pomonella populations, which were obtained from different locations exhibiting varying levels of resistance to CpGV. Three different AFLP primer combinations generated a total of 194 AFLP fragments, ranging from 57.84 to 424.11 bp, with an average of 59.23 amplified fragments per primer combination. The total number of segregating fragments ranged from 181 to 115 and resulted in a high loci polymorphism of 100% in most cases, except for two populations, where it was found to be 88.1% and 93.3%. An analysis of genetic variation based on the obtained AFLP markers resulted in high gene diversity (Hj) values, ranging between 0.2884 to 0.3508. Hj values also indicated a loss in gene diversity within a population over time. The Wright Fixation Index (FST) values indicated a low to moderate genetic differentiation in the populations. The cluster analysis (UPGMA), based on genetic distance values, showed that the majority of C. pomonella populations from different locations were clearly distributed into distinct groups and showed a large genetic variability.
The bee fauna of Taiwan was studied intensively in the first half of last century and was based in large parts on the extensive material collected by Hans Sauter between 1902 and 1914. Subsequent studies on bees of Taiwan have only been sporadic. Within a cooperation between the above mentioned institutions the bee fauna was reinvestigated. It was shown how insufficiently the bee fauna of Taiwan had been investigated so far, in particular, the higher mountain regions. Now about 150 species of bees, belonging to 32 different genera, are known from Taiwan, ten of which have been described or recognized as new for science by the recent cooperation.
Taxonomic, systematic, and biogeography knowledge on the Palaearctic species of Pristaulacus Kieffer 1900 is summarized. Twenty-one valid species are recognized. The most important morphological characters taken into consideration are: shape, cuticular sculpture, and pubescence of head; index length/width of antennomeres; shape, sculpture and cuticular processes of mesosoma, especially of pronotum and mesonotum; number and shape of teeth on claw; shape and sculpture of metasoma; ovipositor length compared with wing and antenna length; and colour pattern (e.g., the dark spots on fore wing, and the colour of hind tarsus). Several characters of the genital capsule of the male were proved to be very useful for species identification, e.g., the shape of the paramere, volsella, cuspis, and digitus. Based on analysis of twenty-five morphological characters, eight species groups are recognized. The critical revision of the chorological data, including many new records, introduced relevant changes of the geographical distribution pattern of most species. Twelve species are restricted to the western part of the Palaearctic Region and eight species are restricted to its eastern part; only one species, P. gibbator, has a wider distribution, including both western and eastern parts of the Palaearctics.
Rising atmospheric CO2 is regarded as the main driver of global warming (Crowley, 2000). While temperature changes directly affect plants and animals (Root et al., 2003; Parmesan, 2006), the effects of CO2 on herbivores are mediated through changes in nutrient quality. Elevated concentrations of atmospheric CO2 are likely to increase photosynthetic activity and thus provide more C-based compounds which may alter plant chemical profiles and plant–herbivore–natural enemy interactions. There are several scenarios how insects will react when confronted with a different food quality. A nutrient poor diet, induced by nitrogen dilution, may result in compensatory feeding with either no adverse effects on insect performance or with negative effects on insect growth due to low digestibility of plant structural compounds (e.g. lignin) or toxic effects of secondary metabolites (e.g. tannins). Here we present data from on-tree feeding trials with larvae of the generalist herbivore Lymantria dispar and one of its natural enemies, the hymenopteran endoparasitoid Glyptapanteles liparidis, studied in 2005. The experiments were conducted at the Swiss free-air CO2 enrichment (FACE) site near Basel, in an approximately 80-100-yr-old, mixed-species forest. The data link changes in foliar chemistry of three tree species (Quercus petraea, Fagus sylvatica, Carpinus betulus) exposed to 540 ppm CO2 with herbivore and parasitoid performance.
The impact of European integration on the German system of pharmaceutical product authorization
(2008)
The European Union has evolved since 1965 into an influential political player in the regulation of pharmaceutical safety standards. The objective of establishing a single European market for pharmaceuticals makes it necessary for member-states to adopt uniform safety standards and marketing authorization procedures. This article investigates the impact of the European integration process on the German marketing authorization system for pharmaceuticals. The analysis shows that the main focal points and objectives of European regulation of pharmaceutical safety have shifted since 1965. The initial phase saw the introduction of uniform European safety standards as a result of which Germany was obliged to undertake “catch-up” modernization. From the mid-1970s, these standards were extended and specified in greater detail. Since the mid-1990s, a process of reorientation has been under way. The formation of the European Agency for the Evaluation of Medicinal Products (EMEA) and the growing importance of the European authorization procedure, combined with intensified global competition on pharmaceutical markets, are exerting indirect pressure for EU member-states to adjust their medicines policies. Consequently, over the past few years Germany has been engaged in a competition-oriented reorganization of its pharmaceutical product authorization system the outcome of which will be to give higher priority to economic interests.
We study the responses of residential property and equity prices, inflation and economic activity to monetary policy shocks in 17 countries, using data spanning 1986-2006, using single-country VARs and panel VARs in which we distinguish between groups of countries depending on their financial systems. The effect of monetary policy on property prices is about three times as large as its impact on GDP. Using monetary policy to guard against financial instability by offsetting asset-price movements thus has sizable effects on economic activity. While the financial structure influences the impact of policy on asset prices, its importance appears limited.
This paper explores the role of trade integration—or openness—for monetary policy transmission in a medium-scale New Keynesian model. Allowing for strategic complementarities in price-setting, we highlight a new dimension of the exchange rate channel by which monetary policy directly impacts domestic inflation. Although the strength of this effect increases with economic openness, it also requires that import prices respond to exchange rate changes. In this case domestic producers find it optimal to adjust their prices to exchange rate changes which alter the domestic currency price of their foreign competitors. We pin down key parameters of the model by matching impulse responses obtained from a vector autoregression on U.S. time series relative to an aggregate of industrialized countries. While we find evidence for strong complementarities, exchange rate pass-through is limited. Openness has therefore little bearing on monetary transmission in the estimated model.
Bayesian learning provides the core concept of processing noisy information. In standard Bayesian frameworks, assessing the price impact of information requires perfect knowledge of news’ precision. In practice, however, precision is rarely dis- closed. Therefore, we extend standard Bayesian learning, suggesting traders infer news’ precision from magnitudes of surprises and from external sources. We show that interactions of the different precision signals may result in highly nonlinear price responses. Empirical tests based on intra-day T-bond futures price reactions to employment releases confirm the model’s predictions and show that the effects are statistically and economically significant.
The popular Nelson-Siegel (1987) yield curve is routinely fit to cross sections of intra-country bond yields, and Diebold and Li (2006) have recently proposed a dynamized version. In this paper we extend Diebold-Li to a global context, modeling a potentially large set of country yield curves in a framework that allows for both global and country-specific factors. In an empirical analysis of term structures of government bond yields for the Germany, Japan, the U.K. and the U.S., we find that global yield factors do indeed exist and are economically important, generally explaining significant fractions of country yield curve dynamics, with interesting differences across countries.
Measuring financial asset return and volatilty spillovers, with application to global equity markets
(2008)
We provide a simple and intuitive measure of interdependence of asset returns and/or volatilities. In particular, we formulate and examine precise and separate measures of return spillovers and volatility spillovers. Our framework facilitates study of both non-crisis and crisis episodes, including trends and bursts in spillovers, and both turn out to be empirically important. In particular, in an analysis of nineteen global equity markets from the early 1990s to the present, we find striking evidence of divergent behavior in the dynamics of return spillovers vs. volatility spillovers: Return spillovers display a gently increasing trend but no bursts, whereas volatility spillovers display no trend but clear bursts.
Research with Keynesian-style models has emphasized the importance of the output gap for policies aimed at controlling inflation while declaring monetary aggregates largely irrelevant. Critics, however, have argued that these models need to be modified to account for observed money growth and inflation trends, and that monetary trends may serve as a useful cross-check for monetary policy. We identify an important source of monetary trends in form of persistent central bank misperceptions regarding potential output. Simulations with historical output gap estimates indicate that such misperceptions may induce persistent errors in monetary policy and sustained trends in money growth and inflation. If interest rate prescriptions derived from Keynesian-style models are augmented with a cross-check against money-based estimates of trend inflation, inflation control is improved substantially.