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This study offers a historical review of the monetary policy reform of October 6, 1979, and discusses the influences behind it and its significance. We lay out the record from the start of 1979 through the spring of 1980, relying almost exclusively upon contemporaneous sources, including the recently released transcripts of Federal Open Market Committee (FOMC) meetings during 1979. We then present and discuss in detail the reasons for the FOMC's adoption of the reform and the communications challenge presented to the Committee during this period. Further, we examine whether the essential characteristics of the reform were consistent with monetarism, new, neo, or old-fashioned Keynesianism, nominal income targeting, and inflation targeting. The record suggests that the reform was adopted when the FOMC became convinced that its earlier gradualist strategy using finely tuned interest rate moves had proved inadequate for fighting inflation and reversing inflation expectations. The new plan had to break dramatically with established practice, allow for the possibility of substantial increases in short-term interest rates, yet be politically acceptable, and convince financial markets participants that it would be effective. The new operating procedures were also adopted for the pragmatic reason that they would likely succeed. JEL Klassifikation: E52, E58, E61, E65.
Lesion of the rat entorhinal cortex denervates the outer molecular layer of the fascia dentata followed by layer-specific axonal sprouting of uninjured fibers in the denervated zone. One of the candidate molecules regulating the laminar-specific sprouting response in the outer molecular layer is the transmembrane chondroitin sulfate proteoglycan NG2. NG2 is found in glial scars and has been suggested to impede axonal regeneration following injury of the spinal cord. The present study adressed the question whether NG2 could also regulate axonal growth in denervated areas of the brain. Therefore, (1) changes in NG2 mRNA and NG2 protein levels, (2) the cellular and the extracellular localisation of the molecule, (3) the identity of NG2 expressing cells, and (4) the generation of NG2-positive cells were studied in the rat fascia dentata before and following entorhinal deafferentation. Laser microdissection was employed to selectively harvest the denervated molecular layer and combined with quantitative reverse transcription-PCR to measure changes in NG2 mRNA amount (6h, 12h, 2d, 4d, 7d post lesion). The study revealed increases of NG2 mRNA at day 2 (2.5-fold) and day 4 (2-fold) post lesion. Immunocytochemistry was used to detect changes in NG2 protein distribution (1d, 4d, 7d, 10d, 14d, 30d, 6 months post lesion). NG2 staining was increased in the denervated outer molecular layer at 1 day post lesion, reached a maximum at 10 days post lesion, and returned to control levels within 6 month. Interestingly, the accumulation of NG2 protein was strongly restricted to the denervated outer molecular layer forming a border to the unaffected inner molecular layer. Using electron microscopy, NG2-immunoprecipitate was localized not only on glial surfaces and in the extracellular matrix but also in the vicinity of neuronal profiles indicating that NG2 is secreted following denervation. Double-labelings of NG2-immunopositive cells with markers for astrocytes, microglia/macrophages, and oligodendrocytes suggested that NG2-cells are a distinct glial subpopulation before and after entorhinal deafferentation. Bromodeoxyuridine-labeling revealed that some of the NG2-positive cells are postlesional generated. Taken together, the data revealed a layer-specific upregulation of NG2 in the denervated outer molecular layer of the fascia dentata that coincides with the sprouting response of uninjured fibers. This suggests that NG2 could regulate lesion-induced axonal growth in denervated areas of the brain.
First paragraph (this article has no abstract) Persistent stimulation of nociceptors results in sensitization of nociceptive sensory neurons, which is associated with hyperalgesia and allodynia. The release of NO and subsequent synthesis of cGMP in the spinal cord are involved in this process. cGMP-dependent protein kinase I (PKG-I) has been suggested to act as a downstream target of cGMP, but its exact role in nociception hadn't been characterized yet. To further evaluate the NO/cGMP/PKG-I pathway in nociception we assessed the effects of PKG-I inhibiton and activaton in the rat formalin assay and analyzed the nociceptive behavior of PKG-I-/- mice. Open access article.
The name Araecerus fasciculatus (DeGeer 1775) is resurrected for the coffee bean weevil, with the following synonyms: Bruchus cacao Fabricius 1775, Bruchus peregrinus Herbst 1797, Bruchus capsinicola Fabricius 1798, Anthribus coffeae Fabricius 1801, Amblycerus japonicus Thunberg 1815 (probably a synonym), Anthribus alternans Germar 1824, Phloeobius griseus of Stephens 1831, not Fabricius 1792, Cratoparis parvirostris Thomson 1858, Araecerus seminarius Chevrolat 1871, and Tropideres (Rhaphitropis) mateui Cobos 1954. Lectotypes are designated for A. fasciculatus, B. capsinicola, and A. alternans. A diagnosis distinguishes Araecerus from all 650 anthribid genera and a diagnosis for the species is as complete as possible with materials studied. Some additional species of Araecerus are discussed: Bruchus crassicornis Fabricius 1798 is distinguished from A. fasciculatus and a lectotype is designated. Araecerus suturalis Boheman 1839 is diagnosed and shown to be dissimilar from the species recently reported as A. suturalis from South Africa. The identity of Araecerus suturalis of Frieser, not Boheman, is not yet clear. Araecerus sambucinus Boisduval 1835 and Trepideres [sic] fragilis Walker 1859 may be synonyms of A. fasciculatus but pertinent data are insufficient. Brachytarsus niveovariegatus Roelofs 1879 (spelled nigrovariegatus by Bovie (1906)), listed as a synonym of A. fasciculatus by Wolfrurn (1929) is removed to Anthribus Forster 1770 with Anthribus lajievorus Chao 1976 as a new synonym.
The semantics of ellipsis
(2005)
There are four phenomena that are particularly troublesome for theories of ellipsis: the existence of sloppy readings when the relevant pronouns cannot possibly be bound; an ellipsis being resolved in such a way that an ellipsis site in the antecedent is not understood in the way it was there; an ellipsis site drawing material from two or more separate antecedents; and ellipsis with no linguistic antecedent. These cases are accounted for by means of a new theory that involves copying syntactically incomplete antecedent material and an analysis of silent VPs and NPs that makes them into higher order definite descriptions that can be bound into.
Let’s not forget that 1492, one of the first landmarks of Modernity, was both the year of the conquest of the Americas and of the fall or of the Reconquista of Granada, both of inner and outer ethnic cleansing of the nation state; that the national state was a colonial state and is now a securitarian state, that colonialism was the very form of Western Modernity, that the French Revolution itself was colonial, that the leader of the first Black revolutionary independence movement, Toussaint Louverture (Haiti), died in a French prison though inspired by the French Revolution. - No-one has access to reason as whole: there is no such thing as the whole of Reason, or Reason as a whole, or the Totality of reason. Reason is patched up of disconnected bits and pieces that reside at different addresses.
Succinctness is a natural measure for comparing the strength of different logics. Intuitively, a logic L_1 is more succinct than another logic L_2 if all properties that can be expressed in L_2 can be expressed in L_1 by formulas of (approximately) the same size, but some properties can be expressed in L_1 by (significantly) smaller formulas.
We study the succinctness of logics on linear orders. Our first theorem is concerned with the finite variable fragments of first-order logic. We prove that:
(i) Up to a polynomial factor, the 2- and the 3-variable fragments of first-order logic on linear orders have the same succinctness. (ii) The 4-variable fragment is exponentially more succinct than the 3-variable fragment. Our second main result compares the succinctness of first-order logic on linear orders with that of monadic second-order logic. We prove that the fragment of monadic second-order logic that has the same expressiveness as first-order logic on linear orders is non-elementarily more succinct than first-order logic.
Labena is a primitive genus known from the Neotropic, Nearctic, Neantarctic, and Australian biogeographic regions. It parasitizes larvae of wood boring beetles in dead twigs and smaller branches of hardwood trees and shrubs. Descriptions are given of 2 new Chilean species: Labena canelensis Porter, from sclerophyll woodland in central Chile, is black with sparse white markings, has a strong tooth at the base of the submetapleural carina, and a short first gastric tergite (2.3-2.6 as long as wide at apex), whereas L. pucon Porter occurs in temperate wet forest of southern Chile and is black with profuse white markings, lacks a submetapleural tooth, and has the first tergite very elongate (4.0-6.2 as long as wide at apex).
In recent methodological work the well known ACD approach, originally introduced by Engle and Russell (1998), has been supplemented by the involvement of an unobservable stochastic process which accompanies the underlying process of durations via a discrete mixture of distributions. The Mixture ACD model, emanating from the specialized proposal of De Luca and Gallo (2004), has proved to be a moderate tool for description of financial duration data. The use of one and the same family of ordinary distributions has been common practice until now. Our contribution incites to use the rich parameterized comprehensive family of distributions which allows for interacting different distributional idiosyncrasies. JEL classification: C41, C22, C25, C51, G14.
This paper addresses remarks made by Flemming (2003) to the effect that his analysis of the interaction between retroflexion and vowel backness is superior to that of Hamann (2003b). While Hamann maintained that retroflex articulations are always back, Flemming adduces phonological as well as phonetic evidence to prove that retroflex consonants can be non-back and even front (i.e. palatalised). The present paper, however, shows that the phonetic evidence fails under closer scrutiny. A closer consideration of the phonological evidence shows, by making a principled distinction between articulatory and perceptual drives, that a reanalysis of Flemming’s data in terms of unviolated retroflex backness is not only possible but also simpler with respect to the number of language-specific stipulations.
Using unobservable conditional variance as measure, latent-variable approaches, such as GARCH and stochastic-volatility models, have traditionally been dominating the empirical finance literature. In recent years, with the availability of high-frequency financial market data modeling realized volatility has become a new and innovative research direction. By constructing "observable" or realized volatility series from intraday transaction data, the use of standard time series models, such as ARFIMA models, have become a promising strategy for modeling and predicting (daily) volatility. In this paper, we show that the residuals of the commonly used time-series models for realized volatility exhibit non-Gaussianity and volatility clustering. We propose extensions to explicitly account for these properties and assess their relevance when modeling and forecasting realized volatility. In an empirical application for S&P500 index futures we show that allowing for time-varying volatility of realized volatility leads to a substantial improvement of the model's fit as well as predictive performance. Furthermore, the distributional assumption for residuals plays a crucial role in density forecasting. Klassifikation: C22, C51, C52, C53
We have used the SLIMCAT 3-D off-line chemical transport model (CTM) to quantify the Arctic chemical ozone loss in the year 2002/2003 and compare it with similar calculations for the winters 1999/2000 and 2003/2004. Recent changes to the CTM have improved the model's ability to reproduce polar chemical and dynamical processes. The updated CTM uses σ-θ as a vertical coordinate which allows it to extend down to the surface. The CTM has a detailed stratospheric chemistry scheme and now includes a simple NAT-based denitrification scheme in the stratosphere.
In the model runs presented here the model was forced by ECMWF ERA40 and operational analyses. The model used 24 levels extending from the surface to ~55km and a horizontal resolution of either 7.5° x 7.5° or 2.8° x 2.8°. Two different radiation schemes, MIDRAD and the CCM scheme, were used to diagnose the vertical motion in the stratosphere. Based on tracer observations from balloons and aircraft, the more sophisticated CCM scheme gives a better representation of the vertical transport in this model which includes the troposphere. The higher resolution model generally produces larger chemical O3 depletion, which agrees better with observations.
The CTM results show that very early chemical ozone loss occurred in December 2002 due to extremely low temperatures and early chlorine activation in the lower stratosphere. Thus, chemical loss in this winter started earlier than in the other two winters studied here. In 2002/2003 the local polar ozone loss in the lower stratosphere was ~40% before the stratospheric final warming. Larger ozone loss occurred in the cold year 1999/2000 which had a persistently cold and stable vortex during most of the winter. For this winter the current model, at a resolution of 2.8° x 2.8°, can reproduce the observed loss of over 70% locally. In the warm and more disturbed winter 2003/2004 the chemical O3 loss was generally much smaller, except above 620K where large losses occurred due to a period of very low minimum temperatures at these altitudes.
The melibiose permease (MelB) of E.coli functions as a secondary-active symporter by using the electrochemical H+, Na+, or Li+ gradient to accumulate, e.g., melibiose [review in Pourcher et al. 1990a]. The global and primary objective of this thesis was to apply pre-steady state methods for the investigation of reaction rates of individual steps in the cycle of MelB. Especially the melibiose binding induced transition was investigated by the solid-supported membrane (SSM) technique [Seifert et al. 1993] in combination with a rapid solution exchange system [Pintchovius and Fendler 1999] and with the Stopped-flow technique [Roughton 1934]. To approach this goal, either wild-type or mutated MelB were purified and reconstituted into liposomes as described [Pourcher et al. 1995]. Although the orientation of the proteins is a critical factor for the activity of MelB, it was, so far, unknown. To determine the orientation of the proteins in the liposomes, single Cys mutants R139C and R141C [Abdel-Dayem et al. 2003] were selectively labeled with 3-(N-maleimidylpropionyl)biocytin (MPB) and analyzed by SDS-PAGE and Western Blot. The assay indicated that most of the proteins are inside-out (ISO) oriented permitting to relate the pre-steady state electrical and fluorescence signals to the reverse transport activity of MelB. The melibiose induced electrical signal was investigated in wild-type MelB with the SSM technique. The transporter was activated by a substrate concentration jump, and transient currents were measured. When the transporter was preincubated with Na+ at saturating concentrations, a charge translocation in the protein upon melibiose binding could still be observed. This result demonstrates that binding of the uncharged substrate melibiose triggers a charge displacement in the protein. Further analysis showed that the charge displacement is neither related to extra Na+ binding to the transporter, nor to the displacement of already bound Na+ within MelB. Electrogenic melibiose binding is explained by a conformational change with concomitant displacement of charged amino acid side chains and/or a reorientation of helix dipoles. A kinetic model is suggested, in which Na+ and melibiose binding are distinct electrogenic processes associated with approximately the same charge displacement. Melibiose binding is fast in the presence of Na+ (k > 50 s-1). Furthermore, two previously identified transport deficient mutants of loop 4-5, R141C and E142C [Abdel-Dayem et al. 2002, Séry 2002], were purified and extensively studied with the SSM. Whereas the electrical signals from control cysteine-less mutant showed a bi-exponential time course of decay, those from R141C or E142C consisted of only a single fast exponential component, and the slow decaying component associated with substrate translocation was missing. The electrical signals evoked by a melibiose concentration jump in the presence of Na+ were much smaller than the corresponding signals in C-less MelB. Furthermore, R141C lost the stimulating effect of melibiose on Na+ binding. Steady-state Trp fluorescence spectroscopy revealed impaired conformational changes after melibiose binding in the mutants and fluorescence resonance energy transfer (FRET) measurements indicated that the mutants still show cooperative modification of their sugar binding sites by Na+. These data suggest that loop 4-5 contributes to the coordinated interactions between the ion- and sugar binding site and participates in conformational changes after melibiose binding that are essential for the subsequent obligatory coupled translocation of substrates. By using the Stopped-flow technique, three different approaches were followed. First, the intrinsic Trp fluorescence of MelB, known to increase upon melibiose binding [Mus-Veteau et al. 1995], revealed a signal with a T 1 of ~15 ms in C-less. This time constant is of the same order of magnitude as that determined with the SSM method suggesting that Trp fluorescence and electrical signal are related processes. Conformation for this assumption came from the fact that the activation energies Ea for both processes are similar (around 45 KJ/mol). Second, by using the fluorescent sugar analog Dns2-S-Gal, which monitors events close to the sugar binding site [Maehrel et al. 1998], a signal with a T 1 of ~18 ms was recorded upon Na+ addition. Finally, the fluorescent dye MIANS was used to selectively label the single Cys mutant E365C of loop 10-11. Stopped-flow measurements revealed a melibiose-induced fluorescent signal with a T 1 of 45 ms. Since electrical measurements with the MIANS-labeled E365C excluded the possibility that the label is responsible for the slower kinetics, the conformational change detected by the MIANS fluorescence was assigned to a slow transition in the cycle of MelB after melibiose binding. Ea was determined to be 96 KJ/mol corroborating, thus, the hypothesis of a different process. In conclusion, it was possible to correlate the electrical and fluorescence signals to partial reactions of the transport cycle and to determine their rate constants. According to this new model, the melibiose-induced signal detected with the Trp and electrical measurements corresponds to a step preceding the carriers’ reorientation (3 <-> 3*, k ~ 65s-1), and the melibiose-induced signal detected with the MIANS fluorescence to the reorientation itself (3* <-> 4, k ~ 20s-1).
This paper describes the processing of MRI and CT images needed for developing a 3D linear articulatory model of velum. The 3D surface that defines each organ constitutive of the vocal and nasal tracts is extracted from MRI and CT images recorded on a subject uttering a corpus of artificially sustained French vowels and consonants. First, the 2D contours of the organs have been manually extracted from the corresponding images, expanded into 3D contours, and aligned in a common 3D coordinate system. Then, for each organ, a generic mesh has been chosen and fitted by elastic deformation to each of the 46 3D shapes of the corpus. This has finally resulted in a set of organ surfaces sampled with the same number of 3D vertices for each articulation, which is appropriate for Principal Component Analysis or linear decomposition. The analysis of these data has uncovered two main uncorrelated articulatory degrees of freedom for the velum's movement. The associated parameters are used to control the model. We have in particular investigated the question of a possible correlation between jaw / tongue and velum's movement and have not find more correlation than the one found in the corpus.
This paper summarizes our research efforts in functional modelling of the relationship between the acoustic properties of vowels and perceived vowel quality. Our model is trained on 164 short steady-state stimuli. We measured F1, F2, and additionally F0 since the effect of F0 on perceptual vowel height is evident. 40 phonetically skilled subjects judged vowel quality using the Cardinal Vowel diagram. The main focus is on refining the model and describing its transformation properties between the F1/F2 formant chart and the Cardinal Vowel diagram. An evaluation of the model based on 48 additional vowels showed the generalizability of the model and confirmed that it predicts perceived vowel quality with sufficient accuracy.
Transverse hadron spectra from proton-proton, proton-nucleus and nucleus-nucleus collisions from 2 AGeV to 21.3 ATeV are investigated within two independent transport approaches (HSD and UrQMD). For central Au+Au (Pb+Pb) collisions at energies above E lab ~ 5 AGeV, the measured K +- transverse mass spectra have a larger inverse slope parameter than expected from the default calculations. The additional pressure - as suggested by lattice QCD calculations at finite quark chemical potential mu q and temperature T - might be generated by strong interactions in the early pre-hadronic/partonic phase of central Au+Au (Pb+Pb) collisions. This is supported by a non-monotonic energy dependence of v2/pT in the present transport model.
Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (| eta | <= 1) and azimuth(full 2 pi ) in bins of transverse momentum (pt) from 0.14 <= pt <= 2.1GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to minijet fragmentation is observed. It evolves with collision centrality and pt in a way not seen before, which suggests strong dissipation of minijet fragmentation in the longitudinally expanding medium.
Trapping black hole remnants
(2005)
Large extra dimensions lower the Planck scale to values soon accessible. The production of TeV mass black holes at the LHC is one of the most exciting predictions. However, the final phases of the black hole's evaporation are still unknown and there are strong indications that a black hole remnant can be left. Since a certain fraction of such objects would be electrically charged, we argue that they can be trapped. In this paper, we examine the occurrence of such charged black hole remnants. These trapped remnants are of high interest, as they could be used to closely investigate the evaporation characteristics. Due to the absence of background from the collision region and the controlled initial state, the signal would be very clear. This would allow to extract information about the late stages of the evaporation process with high precision.
This paper profiles significant differences in syntactic distribution and differences in word class frequencies for two treebanks of spoken and written German: the TüBa-D/S, a treebank of transliterated spontaneous dialogs, and the TüBa-D/Z treebank of newspaper articles published in the German daily newspaper ´die tageszeitung´(taz). The approach can be used more generally as a means of distinguishing and classifying language corpora of different genres.
Trusting the stock market
(2005)
We provide a new explanation to the limited stock market participation puzzle. In deciding whether to buy stocks, investors factor in the risk of being cheated. The perception of this risk is a function not only of the objective characteristics of the stock, but also of the subjective characteristics of the investor. Less trusting individuals are less likely to buy stock and, conditional on buying stock, they will buy less. The calibration of the model shows that this problem is sufficiently severe to account for the lack of participation of some of the richest investors in the United States as well as for differences in the rate of participation across countries. We also find evidence consistent with these propositions in Dutch and Italian micro data, as well as in cross country data. Klassifikation: D1, D8
Fissidens harringtonii from Sierra Leone and F. artsii from Réunion are newly described and illustrated. The taxonomic position of F. harringtonii and F. integerrimus Mitten in Hook.f & Wilson, with which it is compared, is discussed. Fissidens artsii is compared to F. ovatifolius R.Ruthe and F. sublimbatus Grout.
Typology and complexity
(2005)
For the Workshop I was asked to talk about complexity in language from a typological perspective. My way of approaching this topic was to ask myself some questions, and then see where the answers led. The first one was of course, "What sort of system are we looking at complexity in - what kind of system is language?"
Poster presentation: NO-sensitive guanylyl cyclases (GC) are the principal receptors for nitric oxide (NO) and convert GTP into the second messenger cGMP. We showed that GC is prone to tyrosine phosphorylation in COS1 cells overexpressing the human holoenzyme. Similar results were obtained in PC12 cells and in rat aortic tissue slices. The major phosphorylation site was mapped to position 192 in the regulatory domain of the beta1 subunit. Tyrosine phosphorylation of GC was reduced in the presence of the inhibitors PP1 and PP2 indicating that Src-like kinases are critically involved in phosphorylation. Moreover, co-immunoprecipitation experiments revealed an interaction between Src and GC. To further analyse the relevance of this posttranslational modification we generated a phospho-specific antibody raised against pTyr192. This antibody clearly distinguishes between phosphorylated and non-phosphorylated GC and may be a powerful tool to analyse the subcellular localisation of the phosphorylated enzyme.
Seabirds in the UK were generally more productive in 2005 than in 2004, when productivity for many species reached an all-time low. A presumed scarcity of sandeels in 2004, especially in the North Sea, led to widespread starvation of chicks in the Northern Isles and in many places along the east coast of Britain (there is also recent evidence that prey fish were of unusually low energy content in 2004 around SE Scotland). The likely knock-on effect for 2005 was that there were few larger sandeels present (those that hatched in 2004) and it is thought that feeding on these fish allow adults to attain breeding condition in spring. This food scarcity and a cold spring led to what was among the latest breeding seasons on record. However, a late appearance of young sandeels allowed some chicks to fledge, and alternative prey species (such as sprat and small haddock) were taken also. However, it is thought that some chicks starved in this late season, as sandeels become unavailable in late summer, when they settle on the seabed. Unusually, 2005 was a very poor breeding season for many species in NW Scotland, which was spared the food shortages of 2004 and previous years; preferred prey during chick rearing were scarce in this region in 2005.
Abstract: It is commonplace in the debate on Germany's labor market problems to argue that high unemployment and low wage dispersion are related. This paper analyses the relationship between unemployment and residual wage dispersion for individuals with comparable attributes. In the conventional neoclassical point of view, wages are determined by the marginal product of the workers. Accordingly, increases in union minimum wages result in a decline of residual wage dispersion and higher unemployment. A competing view regards wage dispersion as the outcome of search frictions and the associated monopsony power of the firms. Accordingly, an increase in search frictions causes both higher unemployment and higher wage dispersion. The empirical analysis attempts to discriminate between the two hypotheses for West Germany analyzing the relationship between wage dispersion and both the level of unemployment as well as the transition rates between different labor market states. The findings are not completely consistent with either theory. However, as predicted by search theory, one robust result is that unemployment by cells is not negatively correlated with the within cell wage dispersion.
This paper describes the creation and preparation of TUSNELDA, a collection of corpus data built for linguistic research. This collection contains a number of linguistically annotated corpora which differ in various aspects such as language, text sorts / data types, encoded annotation levels, and linguistic theories underlying the annotation. The paper focuses on this variation on the one hand and the way how these heterogeneous data are integrated into one resource on the other hand.
The Dalai Lama, in exile since 1959 in Hindu majority India, has continuously been taking a firm stand on giving importance to an inter-religious dialogue and interaction. He has made it absolutely clear that Buddhism represents just one of the many religious ways open for mankind. Nonetheless, he has always referred to the bond shared between Buddhism and Hinduism as a very special one and has experienced it as a religious tie. Both these religious streams belong to what is known as Bharatiya or Indo-genous Dharma. The Dalai Lama does not restrict his care for nurturing this common bond to a mere academic talk. In fact he has been taking active part in promoting this kind of inter-religious dialogue and has been showing a fiery political commitment as well. He thus took active part in the second World Hindu Congress organized by the Vishwa Hindu Parishad held in Prayag-Allahabad in the year 1979. According to official reports, the organizers in their welcome speech for the Dalai Lama were frank enough to admit that 2500 years ago, the Kashi Pandits (Kashi also known as Varanasi) had stopped Siddharta Gautama Buddha from entering the Vishwanath temple. It was also mentioned that for all these years, there has never been any letup in the conflict between Sanatani Hindus and Bauddhas, despite the fact that later on Shakya Muni was rewarded the status of avatara by Hindus. The fact that these very Kashi Pandits had invite one of the highest religious authorities of Buddhism - the Dalai Lama- to this congress should be seen as "a positive step towards reconciliation." The Dalai Lama was thus pleasantly surprised to see that the highest rung of the religious body of Hindus publicly acknowledged the divine status of Siddharta Gautama Buddha and recognized the presence of the Dalai Lama as a valuable contribution towards the reconciliation between the two religious streams. ...
The thesis entitled „Investigations on the significance of nucleo-cytoplasmic transport for the biological function of cellular proteins" aimed to unreveal molecular mechanisms in order to improve our understanding of the impact of nucleo-cytoplasmic transport on cellular functions. Within the scope of this work, it could be shown that regulated nucleo-cytoplasmic transport of a subfamily of homeobox transcription factors controlled their intra- and intercellular transport, and thereby influencing also their transcriptional activity. This study describes a novel regulatory mechanism, which could in general play an important role for the ordered differentiation of complex organisms. Besides cis-active transport Signals, also post-translational modifications can influence the localization and biological activity of proteins in trans. In addition to the known impact of phosphorylation on the transport and activity of STAT1, experimental evidence was provided demonstrating that acetylation affected the interaction of STAT1 with NF-kB p65, and subsequently modulated the expression of apoptosis-inducing NF-kB target genes. The impact of nucleo-cytoplasmic transport on the regulation of apoptosis was underlined by showing that the evolutionary conservation of a NES within the anti-apoptotic protein survivin plays an essential role for its dual function in the inhibition of apoptosis and ordered cell division. Since survivin is considered a bona fide cancer therapy target, these results strongly encourage future work to identify molecular decoys that specifically inhibit the nuclear export of survivin as novel therapeutics. In order to further dissect the regulation of nuclear transport and to efficiently identify transport inhibitors, cell-based assays are urgently required. Therefore, the cellular assay Systems developed in this work may not only serve to identify synthetic nuclear export and Import inhibitors but may also be applied in systematic RNAi-screening approaches to identify novel components of the transport machinery. In addition, the translocation based protease- and protein-interaction biosensors can be applied in various biological Systems, in particular to identify protein-protein interaction inhibitors of cancer relevant proteins. In summary, this work does not only underline the general significance of nucleo-cytoplasmic transport for cell biology, but also demonstrates its potential for the development of novel therapies against diseases like cancer and viral infections.
Results are presented from a search for the decays D0 -> K min pi plus and D0 bar -> K plus pi min in a sample of 3.8x10^6 central Pb-Pb events collected with a beam energy of 158A GeV by NA49 at the CERN SPS. No signal is observed. An upper limit on D0 production is derived and compared to predictions from several models.
Urwald relict species – Saproxylic beetles indicating structural qualities and habitat tradition
(2005)
On the basis of the list of saproxylic beetles of Germany, the authors present a definition and list of “Urwald relict species”, comprising 115 beetles that are considered to be associated with primeval forest (“Urwald”) structures and features. We use the term “habitat tradition” to describe a continuity in supply of old growth dead wood and forest structures. The selection of species is made on behalf of the following criteria: relict records in Central Europe; attachment to continuity of deadwood resources and habitat tradition; continuity of old growth stand features like tree and deadwood maturity and di-versity; absence from cultivated Central European forest.
The vegetation of Warra National Park (29° 29’S, 151° 56’E; 2041 ha in area) and Wattleridge (29°31’S, 151°54’E; 648 ha in area), located approximately 35 km southeast of Glen Innes and 5 km west of Mount Mitchell, within the Guyra and Severn Shires in the New England Tablelands Bioregion NSW, is described. Nine vegetation communities are defined, based on flexible UPGMA analysis of cover-abundance scores of all vascular plant taxa. These communities have been mapped based on analysis of quadrat data, air photo interpretation, substrate variation and ground-truthing.
Communities described are: (1) Leptospermum novae-angliae (New England Tea-tree) – Bursaria spinosa (Blackthorn) Riparian Scrub & Heath, (2) Eucalyptus pauciflora (Snow Gum) – Eucalyptus nova-anglica (New England Peppermint) Woodland, (3) Haloragis heterophylla (Variable Raspwort) – Carex inversa (Sedge) Herbfield, (4) Baeckea omissa (Baeckea) – Leptospermum gregarium (Swamp Tea-tree) Closed Wet Heath, (5) Eucalyptus cameronii (Die-hard Stringybark) – Eucalyptus campanulata (New England Blackbutt) Shrubby Open Forest, (6) Eucalyptus radiata subsp. sejuncta (Narrow-leaved Peppermint) – Eucalyptus acaciiformis (Wattle-leaved Peppermint) Woodland, (7) Eucalyptus cameronii (Die-hard Stringybark) – Eucalyptus caliginosa (Broad-leaved Stringybark) Grassy Open Forest, (8) Eucalyptus nobilis (Manna Gum) – Eucalyptus obliqua (Messmate) Tall Open Forest, and (9) Eucalyptus obliqua (Messmate) – Eucalyptus nobilis (Manna Gum) Tall Open Forest, (10) Leptospermum novae-angliae – Kunzea obovata – Brachyloma saxicola Shrubby Open Scrub and Closed Heath.
Of 11 communities within the area, four should be considered as threatened, while 18 taxa are considered to be of conservation significance.
The vegetation of Culgoa National Park (22 986 ha in area; 29°15’ S, 147°15’ E) in the central north of New South Wales, approximately 40 km west of Goodooga and adjoining the NSW/Queensland border, is described. Six vegetation communities are delineated based on UPGMA analysis of cover-abundance scores of all vascular plant taxa. These communities are mapped based on ground truthing and air photo interpretation. All communities are simple in structure being primarily woodlands, shrublands and grasslands. Communities described are: 1) Eucalyptus coolabah Woodlands, 2) Muehlenbeckia florulenta Shrubby Thickets, 3) Eucalyptus coolabah – Acacia pendula Woodlands & Grasslands, 4) Eucalyptus largiflorens – Eucalyptus coolabah Woodlands, 5) Eucalyptus largiflorens – Alectryon oleifolius Woodlands, 6) Callitris glaucophylla – Eucalyptus populnea Woodlands and Shrublands. A total of 240 vascular plant taxa were found of which 8% were exotic in origin. Conservation issues are discussed.
Die vorliegende Analyse untersucht die Beschäftigungseffekte von Vermittlungsgutscheinen und Personal-Service-Agenturen mit Hilfe einer makroökonometrischen Evaluation. Neben einer mikroökonometrischen Evaluation, welche die Wirkungen auf individueller Ebene untersucht, kann eine makroökonometrische Analyse Aussagen über die gesamtwirtschaftlichen Effekte der Maßnahmen machen. Die strukturellen Multiplikatorwirkungen im makroökonomischen Kreislaufzusammenhang werden jedoch nicht berücksichtigt. Das ökonometrische Modell zur Analyse der beiden Maßnahmen basiert auf einer Matching-Funktion, die den Suchprozess von Firmen und von Arbeitern nach einem Beschäftigungsverhältnis abbildet. Die empirischen Analysen werden getrennt für Ost- und Westdeutschland sowie für die Strategietypen der Bundesagentur für Arbeit durchgeführt. Sie zeigen, dass die Ausgabe von Vermittlungsgutscheinen nur in „großstädtisch geprägten Bezirken vorwiegend in Westdeutschland mit hoher Arbeitslosigkeit“ (Strategietyp II) einen signifikant positiven Effekt auf den Suchprozess hat. Für die Personal-Service-Agenturen zeigen sich signifikant positive Effekte für Ost- als auch für Westdeutschland. Allerdings fehlt für eine abschließende Bewertung der Ergebnisse für die Personal- Service-Agenturen aufgrund der relativ geringen Teilnehmerzahl noch ein Vergleich mit mikroökonometrischen Analysen.
Virtual screening of potential bioactive substances using the support vector machine approach
(2005)
Die vorliegende Dissertation stellt eine kumulative Arbeit dar, die in insgesamt acht wissenschaftlichen Publikationen (fünf publiziert, zwei eingerichtet und eine in Vorbereitung) dargelegt ist. In diesem Forschungsprojekt wurden Anwendungen von maschinellem Lernen für das virtuelle Screening von Moleküldatenbanken durchgeführt. Das Ziel war primär die Einführung und Überprüfung des Support-Vector-Machine (SVM) Ansatzes für das virtuelle Screening nach potentiellen Wirkstoffkandidaten. In der Einleitung der Arbeit ist die Rolle des virtuellen Screenings im Wirkstoffdesign beschrieben. Methoden des virtuellen Screenings können fast in jedem Bereich der gesamten pharmazeutischen Forschung angewendet werden. Maschinelles Lernen kann einen Einsatz finden von der Auswahl der ersten Moleküle, der Optimierung der Leitstrukturen bis hin zur Vorhersage von ADMET (Absorption, Distribution, Metabolism, Toxicity) Eigenschaften. In Abschnitt 4.2 werden möglichen Verfahren dargestellt, die zur Beschreibung von chemischen Strukturen eingesetzt werden können, um diese Strukturen in ein Format zu bringen (Deskriptoren), das man als Eingabe für maschinelle Lernverfahren wie Neuronale Netze oder SVM nutzen kann. Der Fokus ist dabei auf diejenigen Verfahren gerichtet, die in der vorliegenden Arbeit verwendet wurden. Die meisten Methoden berechnen Deskriptoren, die nur auf der zweidimensionalen (2D) Struktur basieren. Standard-Beispiele hierfür sind physikochemische Eigenschaften, Atom- und Bindungsanzahl etc. (Abschnitt 4.2.1). CATS Deskriptoren, ein topologisches Pharmakophorkonzept, sind ebenfalls 2D-basiert (Abschnitt 4.2.2). Ein anderer Typ von Deskriptoren beschreibt Eigenschaften, die aus einem dreidimensionalen (3D) Molekülmodell abgeleitet werden. Der Erfolg dieser Beschreibung hangt sehr stark davon ab, wie repräsentativ die 3D-Konformation ist, die für die Berechnung des Deskriptors angewendet wurde. Eine weitere Beschreibung, die wir in unserer Arbeit eingesetzt haben, waren Fingerprints. In unserem Fall waren die verwendeten Fingerprints ungeeignet zum Trainieren von Neuronale Netzen, da der Fingerprintvektor zu viele Dimensionen (~ 10 hoch 5) hatte. Im Gegensatz dazu hat das Training von SVM mit Fingerprints funktioniert. SVM hat den Vorteil im Vergleich zu anderen Methoden, dass sie in sehr hochdimensionalen Räumen gut klassifizieren kann. Dieser Zusammenhang zwischen SVM und Fingerprints war eine Neuheit, und wurde von uns erstmalig in die Chemieinformatik eingeführt. In Abschnitt 4.3 fokussiere ich mich auf die SVM-Methode. Für fast alle Klassifikationsaufgaben in dieser Arbeit wurde der SVM-Ansatz verwendet. Ein Schwerpunkt der Dissertation lag auf der SVM-Methode. Wegen Platzbeschränkungen wurde in den beigefügten Veröffentlichungen auf eine detaillierte Beschreibung der SVM verzichtet. Aus diesem Grund wird in Abschnitt 4.3 eine vollständige Einführung in SVM gegeben. Darin enthalten ist eine vollständige Diskussion der SVM Theorie: optimale Hyperfläche, Soft-Margin-Hyperfläche, quadratische Programmierung als Technik, um diese optimale Hyperfläche zu finden. Abschnitt 4.3 enthält auch eine Diskussion von Kernel-Funktionen, welche die genaue Form der optimalen Hyperfläche bestimmen. In Abschnitt 4.4 ist eine Einleitung in verschiede Methoden gegeben, die wir für die Auswahl von Deskriptoren genutzt haben. In diesem Abschnitt wird der Unterschied zwischen einer „Filter“- und der „Wrapper“-basierten Auswahl von Deskriptoren herausgearbeitet. In Veröffentlichung 3 (Abschnitt 7.3) haben wir die Vorteile und Nachteile von Filter- und Wrapper-basierten Methoden im virtuellen Screening vergleichend dargestellt. Abschnitt 7 besteht aus den Publikationen, die unsere Forschungsergebnisse enthalten. Unsere erste Publikation (Veröffentlichung 1) war ein Übersichtsartikel (Abschnitt 7.1). In diesem Artikel haben wir einen Gesamtüberblick der Anwendungen von SVM in der Bio- und Chemieinformatik gegeben. Wir diskutieren Anwendungen von SVM für die Gen-Chip-Analyse, die DNASequenzanalyse und die Vorhersage von Proteinstrukturen und Proteininteraktionen. Wir haben auch Beispiele beschrieben, wo SVM für die Vorhersage der Lokalisation von Proteinen in der Zelle genutzt wurden. Es wird dabei deutlich, dass SVM im Bereich des virtuellen Screenings noch nicht verbreitet war. Um den Einsatz von SVM als Hauptmethode unserer Forschung zu begründen, haben wir in unserer nächsten Publikation (Veröffentlichung 2) (Abschnitt 7.2) einen detaillierten Vergleich zwischen SVM und verschiedenen neuronalen Netzen, die sich als eine Standardmethode im virtuellen Screening etabliert haben, durchgeführt. Verglichen wurde die Trennung von wirstoffartigen und nicht-wirkstoffartigen Molekülen („Druglikeness“-Vorhersage). Die SVM konnte 82% aller Moleküle richtig klassifizieren. Die Klassifizierung war zudem robuster als mit dreilagigen feedforward-ANN bei der Verwendung verschiedener Anzahlen an Hidden-Neuronen. In diesem Projekt haben wir verschiedene Deskriptoren zur Beschreibung der Moleküle berechnet: Ghose-Crippen Fragmentdeskriptoren [86], physikochemische Eigenschaften [9] und topologische Pharmacophore (CATS) [10]. Die Entwicklung von weiteren Verfahren, die auf dem SVM-Konzept aufbauen, haben wir in den Publikationen in den Abschnitten 7.3 und 7.8 beschrieben. Veröffentlichung 3 stellt die Entwicklung einer neuen SVM-basierten Methode zur Auswahl von relevanten Deskriptoren für eine bestimmte Aktivität dar. Eingesetzt wurden die gleichen Deskriptoren wie in dem oben beschriebenen Projekt. Als charakteristische Molekülgruppen haben wir verschiedene Untermengen der COBRA Datenbank ausgewählt: 195 Thrombin Inhibitoren, 226 Kinase Inhibitoren und 227 Faktor Xa Inhibitoren. Es ist uns gelungen, die Anzahl der Deskriptoren von ursprünglich 407 auf ungefähr 50 zu verringern ohne signifikant an Klassifizierungsgenauigkeit zu verlieren. Unsere Methode haben wir mit einer Standardmethode für diese Anwendung verglichen, der Kolmogorov-Smirnov Statistik. Die SVM-basierte Methode erwies sich hierbei in jedem betrachteten Fall als besser als die Vergleichsmethoden hinsichtlich der Vorhersagegenauigkeit bei der gleichen Anzahl an Deskriptoren. Eine ausführliche Beschreibung ist in Abschnitt 4.4 gegeben. Dort sind auch verschiedene „Wrapper“ für die Deskriptoren-Auswahl beschrieben. Veröffentlichung 8 beschreibt die Anwendung von aktivem Lernen mit SVM. Die Idee des aktiven Lernens liegt in der Auswahl von Molekülen für das Lernverfahren aus dem Bereich an der Grenze der verschiedenen zu unterscheidenden Molekülklassen. Auf diese Weise kann die lokale Klassifikation verbessert werden. Die folgenden Gruppen von Moleküle wurden genutzt: ACE (Angiotensin converting enzyme), COX2 (Cyclooxygenase 2), CRF (Corticotropin releasing factor) Antagonisten, DPP (Dipeptidylpeptidase) IV, HIV (Human immunodeficiency virus) protease, Nuclear Receptors, NK (Neurokinin receptors), PPAR (peroxisome proliferator-activated receptor), Thrombin, GPCR und Matrix Metalloproteinasen. Aktives Lernen konnte die Leistungsfähigkeit des virtuellen Screenings verbessern, wie sich in dieser retrospektiven Studie zeigte. Es bleibt abzuwarten, ob sich das Verfahren durchsetzen wird, denn trotzt des Gewinns an Vorhersagegenauigkeit ist es aufgrund des mehrfachen SVMTrainings aufwändig. Die Publikationen aus den Abschnitten 7.5, 7.6 und 7.7 (Veröffentlichungen 5-7) zeigen praktische Anwendungen unserer SVM-Methoden im Wirkstoffdesign in Kombination mit anderen Verfahren, wie der Ähnlichkeitssuche und neuronalen Netzen zur Eigenschaftsvorhersage. In zwei Fällen haben wir mit dem Verfahren neuartige Liganden für COX-2 (cyclooxygenase 2) und dopamine D3/D2 Rezeptoren gefunden. Wir konnten somit klar zeigen, dass SVM-Methoden für das virtuelle Screening von Substanzdatensammlungen sinnvoll eingesetzt werden können. Es wurde im Rahmen der Arbeit auch ein schnelles Verfahren zur Erzeugung großer kombinatorischer Molekülbibliotheken entwickelt, welches auf der SMILES Notation aufbaut. Im frühen Stadium des Wirstoffdesigns ist es wichtig, eine möglichst „diverse“ Gruppe von Molekülen zu testen. Es gibt verschiedene etablierte Methoden, die eine solche Untermenge auswählen können. Wir haben eine neue Methode entwickelt, die genauer als die bekannte MaxMin-Methode sein sollte. Als erster Schritt wurde die „Probability Density Estimation“ (PDE) für die verfügbaren Moleküle berechnet. [78] Dafür haben wir jedes Molekül mit Deskriptoren beschrieben und die PDE im N-dimensionalen Deskriptorraum berechnet. Die Moleküle wurde mit dem Metropolis Algorithmus ausgewählt. [87] Die Idee liegt darin, wenige Moleküle aus den Bereichen mit hoher Dichte auszuwählen und mehr Moleküle aus den Bereichen mit niedriger Dichte. Die erhaltenen Ergebnisse wiesen jedoch auf zwei Nachteile hin. Erstens wurden Moleküle mit unrealistischen Deskriptorwerten ausgewählt und zweitens war unser Algorithmus zu langsam. Dieser Aspekt der Arbeit wurde daher nicht weiter verfolgt. In Veröffentlichung 6 (Abschnitt 7.6) haben wir in Zusammenarbeit mit der Molecular-Modeling Gruppe von Aventis-Pharma Deutschland (Frankfurt) einen SVM-basierten ADME Filter zur Früherkennung von CYP 2C9 Liganden entwickelt. Dieser nichtlineare SVM-Filter erreichte eine signifikant höhere Vorhersagegenauigkeit (q2 = 0.48) als ein auf den gleichen Daten entwickelten PLS-Modell (q2 = 0.34). Es wurden hierbei Dreipunkt-Pharmakophordeskriptoren eingesetzt, die auf einem dreidimensionalen Molekülmodell aufbauen. Eines der wichtigen Probleme im computerbasierten Wirkstoffdesign ist die Auswahl einer geeigneten Konformation für ein Molekül. Wir haben versucht, SVM auf dieses Problem anzuwenden. Der Trainingdatensatz wurde dazu mit jeweils mehreren Konformationen pro Molekül angereichert und ein SVM Modell gerechnet. Es wurden anschließend die Konformationen mit den am schlechtesten vorhergesagten IC50 Wert aussortiert. Die verbliebenen gemäß dem SVM-Modell bevorzugten Konformationen waren jedoch unrealistisch. Dieses Ergebnis zeigt Grenzen des SVM-Ansatzes auf. Wir glauben jedoch, dass weitere Forschung auf diesem Gebiet zu besseren Ergebnissen führen kann.
Dutch has a three-way contrast in labiodental sounds, which causes problems for native speakers of German in their acquisition of Dutch, since German contrasts only two labiodentals. The present study investigates the perception of the Dutch labiodental fricative system by German L2 learners of Dutch and shows that native Germans with no or little knowledge of the Dutch language categorize the Dutch labiodental voiced fricative and approximant as their native voiced fricative. Advanced learners, however, succeed in acquiring a category for the voiced fricative, illustrating that plasticity in the perception of a second language develops with the amount of exposure to the language.
Volatility forecasting
(2005)
Volatility has been one of the most active and successful areas of research in time series econometrics and economic forecasting in recent decades. This chapter provides a selective survey of the most important theoretical developments and empirical insights to emerge from this burgeoning literature, with a distinct focus on forecasting applications. Volatility is inherently latent, and Section 1 begins with a brief intuitive account of various key volatility concepts. Section 2 then discusses a series of different economic situations in which volatility plays a crucial role, ranging from the use of volatility forecasts in portfolio allocation to density forecasting in risk management. Sections 3, 4 and 5 present a variety of alternative procedures for univariate volatility modeling and forecasting based on the GARCH, stochastic volatility and realized volatility paradigms, respectively. Section 6 extends the discussion to the multivariate problem of forecasting conditional covariances and correlations, and Section 7 discusses volatility forecast evaluation methods in both univariate and multivariate cases. Section 8 concludes briefly. JEL Klassifikation: C10, C53, G1.
The contribution of von Kempelen’s “Mechanism of Speech” to the ‘phonetic sciences‘ will be analyzed with respect to his theoretical reasoning on speech and speech production on the one hand and on the other in connection with his practical insights during his struggle in constructing a speaking machine. Whereas in his theoretical considerations von Kempelen’s view is focussed on the natural functioning of the speech organs – cf. his membraneous glottis model – in constructing his speaking machine he clearly orientates himself towards the auditory result – cf. the bag pipe model for the sound generator used for the speaking machine instead. Concerning vowel production his theoretical description remains questionable, but his practical insight that vowels and speech sounds in general are only perceived correctly in connection with their surrounding sounds – i.e. the discovery of coarticulation – is clearly a milestone in the development of the phonetic sciences: He therefore dispenses with the Kratzenstein tubes, although they might have been based on more thorough acoustic modelling. Finally, von Kempelen’s model of speech production will be discussed in relation to the discussion of the acoustic nature of vowels afterwards [Willis and Wheatstone as well as von Helmholtz and Hermann in the 19th century and Stumpf, Chiba & Kajiyama as well as Fant and Ungeheuer in the 20th century].
The contribution of von Kempelen's "Mechanism of Speech" to the 'phonetic sciences' will be analyzed with respect to his theoretical reasoning on speech and speech production on the one hand and on the other in connection with his practical insights during his struggle in constructing a speaking machine. Whereas in his theoretical considerations von Kempelen's view is focussed on the natural functioning of the speech organs – cf. his membraneous glottis model – in constructing his speaking machine he clearly orientates himself towards the auditory result – cf. the bag pipe model for the sound generator used for the speaking machine instead. Concerning vowel production his theoretical description remains questionable, but his practical insight that vowels and speech sounds in general are only perceived correctly in connection with their surrounding sounds – i.e. the discovery of coarticulation – is clearly a milestone in the development of the phonetic sciences: He therefore dispenses with the Kratzenstein tubes, although they might have been based on more thorough acoustic modelling.
Finally, von Kempelen's model of speech production will be discussed in relation to the discussion of the acoustic nature of vowels afterwards [Willis and Wheatstone as well as von Helmholtz and Hermann in the 19th century and Stumpf, Chiba & Kajiyama as well as Fant and Ungeheuer in the 20th century].
Fronting of an infinite VP across a finite main verb - akin to German "VP-topicalization" - can be found also in Czech and Polish. The paper discusses evidence from large corpora for this process and some of its properties, both syntactic and information-structural. Based on this case, criteria for more user-friedly searching and retrieval of corpus data in syntactic research are being developed.