Refine
Year of publication
Document Type
- Article (16008)
- Part of Periodical (2730)
- Working Paper (2355)
- Preprint (2196)
- Doctoral Thesis (2069)
- Book (1736)
- Part of a Book (1071)
- Conference Proceeding (1055)
- Report (471)
- Review (165)
Language
- English (30021) (remove)
Has Fulltext
- yes (30021) (remove)
Keywords
- taxonomy (746)
- new species (448)
- morphology (175)
- Deutschland (142)
- Syntax (126)
- Englisch (120)
- distribution (117)
- biodiversity (103)
- inflammation (100)
- Deutsch (98)
Institute
- Medizin (5400)
- Physik (4003)
- Wirtschaftswissenschaften (1919)
- Frankfurt Institute for Advanced Studies (FIAS) (1811)
- Biowissenschaften (1566)
- Center for Financial Studies (CFS) (1495)
- Informatik (1451)
- Biochemie und Chemie (1090)
- Sustainable Architecture for Finance in Europe (SAFE) (1073)
- House of Finance (HoF) (709)
Background: Murine leukemia virus (MLV) vector particles can be pseudotyped with a truncated variant of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) and selectively target gene transfer to human cells expressing both CD4 and an appropriate co-receptor. Vector transduction mimics the HIV-1 entry process and is therefore a safe tool to study HIV-1 entry. Results: Using FLY cells, which express the MLV gag and pol genes, we generated stable producer cell lines that express the HIV-1 envelope gene and a retroviral vector genome encoding the green fluorescent protein (GFP). The BH10 or 89.6 P HIV-1 Env was expressed from a bicistronic vector which allowed the rapid selection of stable cell lines. A codon-usage-optimized synthetic env gene permitted high, Rev-independent Env expression. Vectors generated by these producer cells displayed different sensitivity to entry inhibitors. Conclusion: These data illustrate that MLV/HIV-1 vectors are a valuable screening system for entry inhibitors or neutralizing antisera generated by vaccines.
One of the dangers of harmonisation and unification processes taking place within the framework of the EU is that they may result in the codification of the lowest common denominator. This is precisely what is threatening to happen in respect of assignment. Referring the transfer of receivables by way of assignment to the law of the assignor’s residence, as article 13 of the Proposal does, would be opting for the most conservative solution and would for many Member States be a step backward rather than forward. A conflict rule referring assignment to the law of the assignor's residence is too rigid to do justice to the dynamic nature of assignments in cross-border transactions and it is unjustly one-sided. It offers no real advantages when compared to other conflict rules; it even has serious disadvantages which make the conflict rule unsuitable for efficient assignment-based cross-border transactions. It is not unconceivable that this conflict rule would even be contrary to the fundamental freedoms of the ECTreaty. The Community legislators in particular should be careful not to needlessly adopt rules which create insurmountable obstacles for cross-border business where choice-of-law by the parties would perfectly do. Community legislation has a special responsibility to create a smooth legal environment for single market transactions.
This Paper will look at the changing nature of asset management, and will examine the nature of the European framework for collective investment undertakings, enshrined in the UCITS Directive2 in that light. This question whether the UCITS Directive in its current form remains an appropriate European response to the changing investment management landscape is an issue with which the European Commission is actively engaging through its Green Paper on the Enhancement of the EU Framework for Investment Funds, published in July 2005.3 But before considering these important questions, it is necessary to begin with an idea of what a collective investment, more specifically a UCITS actually is and how it fits conceptually in the broader world of pooled investments.....
We analyze the degree of contract completeness with respect to staging of venture capital investments using a hand-collected German data set of contract data from 464 rounds into 290 entrepreneurial firms. We distinguish three forms of staging (pure milestone financing, pure round financing and mixes). Thereby, contract completeness reduces when going from pure milestone financing via mixes to pure round financing. We show that the decision for a specific form of staging is determined by the expected distribution of bargaining power between the contracting parties when new funding becomes necessary and the predictability of the development process. To be more precise, parties choose the more complete contracts the lower the entrepreneur's expected bargaining power - the maximum level depending on the predictability of the development process. JEL Classification: G24, G32, D86, D80, G34
This paper investigates whether the stock market reacts to unsolicited ratings for a sample of S&P rated firms from January 1996 to December 2005. We first analyze the stock market reaction associated with the assignment of an initial unsolicited rating. We find evidence that this reaction is negative and particularly accentuated for Japanese firms. A comparison between S&P’s initial unsolicited ratings with previously published ratings of two Japanese rating agencies for a Japanese subsample shows that ratings assigned by S&P are systematically worse. Further, we find that the stock market does not react to the transition from an unsolicited to a solicited rating. Comparison of the upgrades in the sample with a matched-sample of upgrades of solicited ratings reveals that the price reactions are no different. In addition, abnormal returns are worse for firms whose rating remained unchanged after the solicitation compared to those for upgraded firms. Finally, we find that Japanese firms are less likely to receive an upgrade. Our findings suggest that unsolicited ratings are biased downwards, that the capital market therefore expects upgrades of formerly unsolicited ratings and punishes firms whose ratings remain unchanged. All these effects seem to be more pronounced for Japanese firms.
In this paper, we propose a model of credit rating agencies using the global games framework to incorporate information and coordination problems. We introduce a refined utility function of a credit rating agency that, additional to reputation maximization, also embeds aspects of competition and feedback effects of the rating on the rated firms. Apart from hinting at explanations for several hypotheses with regard to agencies' optimal rating assessments, our model suggests that the existence of rating agencies may decrease the incidence of multiple equilibria. If investors have discretionary power over the precision of their private information, we can prove that public rating announcements and private information collection are complements rather than substitutes in order to secure uniqueness of equilibrium. In this respect, rating agencies may spark off a virtuous circle that increases the efficiency of the market outcome.
Background: Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV) has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results: We inserted the coding sequences for green fluorescent protein (GFP) into the proline-rich region (PRR) of the ecotropic envelope protein (Env) and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP) and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions: Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.
Using data of US domestic mergers and acquisitions transactions, this paper shows that acquirers have a preference for geographically proximate target companies. We measure the ‘home bias’ against benchmark portfolios of hypothetical deals where the potential targets consist of firms of similar size in the same four-digit SIC code that have been targets in other transactions at about the same time or firms that have been listed at a stock exchange at that time. There is a strong and consistent home bias for M&A transactions in the US, which is significantly declining during the observation period, i.e. between 1990 and 2004. At the same time, the average distances between target and acquirer increase articulately. The home bias is stronger for small and relatively opaque target companies suggesting that local information is the decisive factor in explaining the results. Acquirers that diversify into new business lines also display a stronger preference for more proximate targets. With an event study we show that investors react relatively better to proximate acquisitions than to distant ones. That reaction is more important and becomes significant in times when the average distance between target and acquirer becomes larger, but never becomes economically significant. We interpret this as evidence for the familiarity hypothesis brought forward by Huberman (2001): Acquirers know about the existence of proximate targets and are more likely to merge with them without necessarily being better informed. However, when comparing the best and the worst deals, we are able to show a dramatic difference in distances and home bias: The most successful deals display on average a much stronger home bias and distinctively smaller distance between acquirer and target than the least successful deals. Proximity in M&A transactions therefore is a necessary but not sufficient condition for success. The paper contributes to the growing literature on the role of distance in financial decisions.
The 5'-terminal cloverleaf (CL)-like RNA structures are essential for the initiation of positive- and negative-strand RNA synthesis of entero- and rhinoviruses. SLD is the cognate RNA ligand of the viral proteinase 3C (3Cpro), which is an indispensable component of the viral replication initiation complex. The structure of an 18mer RNA representing the apical stem and the cGUUAg D-loop of SLD from the first 5'-CL of BEV1 was determined in solution to a root-mean-square deviation (r.m.s.d.) (all heavy atoms) of 0.59 A (PDB 1Z30). The first (antiG) and last (synA) nucleotide of the D-loop forms a novel ‘pseudo base pair’ without direct hydrogen bonds. The backbone conformation and the base-stacking pattern of the cGUUAg-loop, however, are highly similar to that of the coxsackieviral uCACGg D-loop (PDB 1RFR) and of the stable cUUCGg tetraloop (PDB 1F7Y) but surprisingly dissimilar to the structure of a cGUAAg stable tetraloop (PDB 1MSY), even though the cGUUAg BEV D-loop and the cGUAAg tetraloop differ by 1 nt only. Together with the presented binding data, these findings provide independent experimental evidence for our model [O. Ohlenschläger, J. Wöhnert, E. Bucci, S. Seitz, S. Häfner, R. Ramachandran, R. Zell and M. Görlach (2004) Structure, 12, 237–248] that the proteinase 3Cpro recognizes structure rather than sequence.
We have isolated the human protein SNEV as downregulated in replicatively senescent cells. Sequence homology to the yeast splicing factor Prp19 suggested that SNEV might be the orthologue of Prp19 and therefore might also be involved in pre-mRNA splicing. We have used various approaches including gene complementation studies in yeast using a temperature sensitive mutant with a pleiotropic phenotype and SNEV immunodepletion from human HeLa nuclear extracts to determine its function. A human–yeast chimera was indeed capable of restoring the wild-type phenotype of the yeast mutant strain. In addition, immunodepletion of SNEV from human nuclear extracts resulted in a decrease of in vitro pre-mRNA splicing efficiency. Furthermore, as part of our analysis of protein–protein interactions within the CDC5L complex, we found that SNEV interacts with itself. The self-interaction domain was mapped to amino acids 56–74 in the protein's sequence and synthetic peptides derived from this region inhibit in vitro splicing by surprisingly interfering with spliceosome formation and stability. These results indicate that SNEV is the human orthologue of yeast PRP19, functions in splicing and that homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly and that it might also be important for spliceosome stability.
We estimate the effect of pension reforms on households' expectations of retirement outcomes and private wealth accumulation decisions exploiting a decade of intense Italian pension reforms as a source of exogenous variation in expected pension wealth. The Survey of Household Income and Wealth, a large random sample of the Italian population, elicits expectations of the age at which workers expect to retire and of the ratio of pension benefits to pre-retirement income between 1989 and 2002. We find that workers have revised expectations in the direction suggested by the reform and that there is substantial offset between private wealth and perceived pension wealth, particularly by workers that are better informed about their pension wealth. Klassifikation: E21, H55
We present a multivariate generalization of the mixed normal GARCH model proposed in Haas, Mittnik, and Paolella (2004a). Issues of parametrization and estimation are discussed. We derive conditions for covariance stationarity and the existence of the fourth moment, and provide expressions for the dynamic correlation structure of the process. These results are also applicable to the single-component multivariate GARCH(p, q) model and simplify the results existing in the literature. In an application to stock returns, we show that the disaggregation of the conditional (co)variance process generated by our model provides substantial intuition, and we highlight a number of findings with potential significance for portfolio selection and further financial applications, such as regime-dependent correlation structures and leverage effects. Klassifikation: C32, C51, G10, G11
We model the impact of bank mergers on loan competition, reserve holdings and aggregate liquidity. A merger changes the distribution of liquidity shocks and creates an internal money market, leading to financial cost efficiencies and more precise estimates of liquidity needs. The merged banks may increase their reserve holdings through an internalization effect or decrease them because of a diversification effect. The merger also affects loan market competition, which in turn modifies the distribution of bank sizes and aggregate liquidity needs. Mergers among large banks tend to increase aggregate liquidity needs and thus the public provision of liquidity through monetary operations of the central bank. Klassifikation: D43, G21, G28, L13
When a spot market monopolist has a position in a corresponding futures market, he has an incentive to deviate from the spot market optimum to make this position more profitable. Rational futures market makers take this into account when setting prices. We show that the monopolist, by randomizing his futures market position, can strategically exploit his market power at the expense of other futures market participants. Furthermore, traders without market power can manipulate futures prices by hiding their orders behind the monopolist's strategic trades. The moral hazard problem stemming from spot market power thus provides a venue for strategic trading and manipulation that parallels the adverse selection problem stemming from inside information. Klassifikation: D82, G13
We study a set of German open-end mutual funds for a time period during which this industry emerged from its infancy. In those years, the distribution channel for mutual funds was dominated by the brick-and-mortar retail networks of the large universal banks. Using monthly observations from 12/1986 through 12/1998, we investigate if cross-sectional return differences across mutual funds affect their market shares. Although such a causal relation has been established in highly competitive markets, such as the United States, the rigid distribution system in place in Germany at the time may have caused retail performance and investment performance to uncouple. In fact, although we observe stark differences in investment performance across mutual funds (and over time), we find no evidence that cross-sectional performance differences affect the market shares of these funds. Klassifikation: G 23
Large banks often sell part of their loan portfolio in the form of collateralized debt obligations (CDO) to investors. In this paper we raise the question whether credit asset securitization affects the cyclicality (or commonality) of bank equity values. The commonality of bank equity values reflects a major component of systemic risks in the banking market, caused by correlated defaults of loans in the banks' loan books. Our simulations take into account the major stylized fact of CDO transactions, the non-proportional nature of risk sharing that goes along with tranching. We provide a theoretical framework for the risk transfer through securitization that builds on a macro risk factor and an idiosyncratic risk factor, allowing an identification of the types of risk that the individual tranche holders bear. This allows conclusions about the risk positions of issuing banks after risk transfer. Building on the strict subordination of tranches, we first evaluate the correlation properties both within and across risk classes. We then determine the effect of securitization on the systematic risk of all tranches, and derive its effect on the issuing bank's equity beta. The simulation results show that under plausible assumptions concerning bank reinvestment behaviour and capital structure choice, the issuing intermediary's systematic risk tends to rise. We discuss the implications of our findings for financial stability supervision. Klassifikation: G28
In this paper, we consider expected value, variance and worst-case optimization of nonlinear models. We present algorithms for computing optimal expected values, and variance, based on iterative Taylor expansions. We establish convergence and consider the relative merits of policies beaded on expected value optimization and worst-case robustness. The latter is a minimax strategy and ensures optimal cover in view of the worst-case scenario(s) while the former is optimal expected performance in a stochastic setting. Both approaches are used with a macroeconomic policy model to illustrate relative performances, robustness and trade-offs between the strategies. Klassifikation: C61, E43
In order to further understand how DNA polymerases discriminate against incorrect dNTPs, we synthesized two sets of dNTP analogues and tested them as substrates for DNA polymerase a (pol alpha) and Klenow fragment (exo-) of DNA polymerase I (Escherichia coli ). One set of analogues was designed to test the importance of the electronic nature of the base. The bases consisted of a benzimidazole ring with one or two exocyclic substituent(s) that are either electron-donating (methyl and methoxy) or electronwithdrawing (trifluoromethyl and dinitro). Both pol a and Klenow fragment exhibit a remarkable inability to discriminate against these analogues as compared to their ability to discriminate against incorrect natural dNTPs. Neither polymerase shows any distinct electronic or steric preferences for analogue incorporation. The other set of analogues, designed to examine the importance of hydrophobicity in dNTP incorporation, consists of a set of four regioisomers of trifluoromethyl benzimidazole. Whereas pol a and Klenow fragment exhibited minimal discrimination against the 5- and 6-regioisomers, they discriminated much more effectively against the 4- and 7-regioisomers. Since all four of these analogues will have similar hydrophobicity and stacking ability, these data indicate that hydrophobicity and stacking ability alone cannot account for the inability of pol a and Klenow fragment to discriminate against unnatural bases. After incorporation, however, both sets of analogues were not efficiently elongated. These results suggest that factors other than hydrophobicity, sterics and electronics govern the incorporation of dNTPs into DNA by pol {alpha} and Klenow fragment.
Background: Costly structures need to represent an adaptive advantage in order to be maintained over evolutionary times. Contrary to many other conspicuous shell ornamentations of gastropods, the haired shells of several Stylommatophoran land snails still lack a convincing adaptive explanation. In the present study, we analysed the correlation between the presence/absence of hairs and habitat conditions in the genus Trochulus in a Bayesian framework of character evolution. Results: Haired shells appeared to be the ancestral character state, a feature most probably lost three times independently. These losses were correlated with a shift from humid to dry habitats, indicating an adaptive function of hairs in moist environments. It had been previously hypothesised that these costly protein structures of the outer shell layer facilitate the locomotion in moist habitats. Our experiments, on the contrary, showed an increased adherence of haired shells to wet surfaces. Conclusion: We propose the hypothesis that the possession of hairs facilitates the adherence of the snails to their herbaceous food plants during foraging when humidity levels are high. The absence of hairs in some Trochulus species could thus be explained as a loss of the potential adaptive function linked to habitat shifts.
Market efficiency today
(2006)
This CFS Working Paper has been presented at the CFSsymposium "Market Efficiency Today" held in Frankfurt/Main on October 6, 2005. In 2004 the Center for Financial Studies (CFS) in cooperation with the Johann Wolfgang Goethe University, Frankfurt/Main established an international academic prize, which is to be known as The Deutsche Bank Prize in Financial Economics. The prize will honor an internationally renowned researcher who has excelled through influential contributions to research in the fields of finance and money and macroeconomics, and whose work has lead to practice and policy-relevant results. The Deutsche Bank Prize in Financial Economics has been awarded for the first time in October 2005. The prize, sponsored by the Stiftungsfonds Deutsche Bank im Stifterverband für die Deutsche Wissenschaft, carries a cash award of € 50,000. The prize will be awarded every two years and the prize holder will be appointed a "Distinguished Fellow" of the CFS. The role of media partner for the Deutsche Bank Prize in Financial Economics is to be filled by the internationally renowned publication, The Economist and the Handelsblatt, the leading German-language financial and business newspaper.
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
Stem cells capable of self-renewal and differentiation into multiple tissues are important in medicine to reconstitute the hematopoietic system after myelo-ablative chemo- or radiotherapy. In the present situation, adult stem cells such as Mesenchymal stem cells (MSC) and Hematopoietic stem cells (HSC) are used for therapeutic purposes. For tissue regeneration and tissue constitution, engraftment of transplanted stem cells is a necessary feature. However, in many instances, the transplanted stem cells reach the tissues with low efficiency. Considering the three-step model of leukocyte extravasation by Springer et al, the rolling, adhesion and transmigration form the three major steps for the transplanted stem cells to enter the desired tissues. One of the molecular switches reported to be involved in these mechanisms are the Rho family GTPases. The present study investigates the role of Rho GTPases in adhesion and migration of stem and progenitor cells. Chemotactic and chemokinetic migration assays, transendothelial migration assays, migration of cells under shear stress, microinjection, retroviral and lentiviral gene transfer methods, oligonucleotide microarray analysis and pull down assays were employed in this study for the elucidation of Rho GTPase involvement in migration and adhesion of stem and progenitor cells. The transmigration assay used for the migration determination of the adherent cell type, MSC, was optimized for the efficient and effective assessment of the migrating cells. The involvement of Rho was found to be critical for stem and progenitor cell migration where inactivation of Rho by C2I-C3 transferase toxin and/or overexpression of C3 transferase cDNA increased the migration rate of Hematopoietic progenitor cells (HPC) and MSC. Moreover, modulation of Rho caused predictable cytoskeletal and morphological changes in MSC. Assessment of Rho GTPase involvement in the interacting partner, the endothelial cells during stem cell migration, revealed that active Rho expression induced E-selectin expression. The increased levels of E-selectin were functionally confirmed by the increased adhesion of progenitor cells (HPC) to the Human umbilical vein endothelial cell (HUVEC) layer. Moreover, inhibition of Rac in the migrating endothelial progenitor cells (eEPC) increased their adhesion to HUVEC correlating with the increased percentage expression of cell surface receptor, CD44 in Rac inactivated eEPC. In conclusion, this study shows that Rho GTPases control the adhesion and migration of stem and progenitor cells, HPC and MSC. Rho inhibition drives the cells to migrate in the blood vessels. The substantial increase in the level of active Rho in endothelial layer, manifested by the E-selectin surface expression assists the better adhesion of stem and progenitor cells to the endothelial layer. Serum factors and growth factors in the physiological system influence the Rho GTPase expression in both migrating stem cells and the barrier endothelial cells. Thus, specific modulation of Rho GTPases in the transplanted stem and progenitor cells could be an interesting tool to improve the migration and homing processes of stem cells for cellular therapy in future.
This work is dedicated to the investigation of nuclear matter at non-zero temperatures within an effective hadronic model based on the Walecka model. It includes fermions as well as a vector omega meson and a scalar sigma meson where for the latter a quartic self-interaction has been considered. The coupling constants have been adapted to the saturation properties of infinite nuclear matter. A set of self-consistent Schwinger-Dyson equations has been set up for all included particles within the Cornwall-Jackiw-Tomboulis formalism. This has been expanded to non-zero temperatures via the imaginary time formalism. Beside tree-level two different stages of approximations have been considered: the Hartree approximation which takes into account the double-bubble diagram for the scalar meson, and an improved approximation where in addition two-particle irreducible sunset diagrams for all fields were included. In the Hartree-approximation the Schwinger-Dyson equations can be solved by quasi-particle ansaetze, while in the improved approximation spectral functions with non-zero widths have to be introduced. The Schwinger-Dyson equations are solved by the fully dressed propagators. Comparing the two levels of approximation shows the influence of finite widths on the temperature dependence of the particle properties. The consideration of finite widths in fact has a significant influence on the transition from a phase of heavy nucleons to a transition of light nucleons, observed in the Walecka-model. The temperature dependence is weakend when finte widths are taken into account.
The present work was devised to address the systematic analysis of samples from a range of Roman non-ferrous metal artefacts from different archaeological contexts and sites in the Roman provinces of Germania Superior. One of the focal points of this study is the provenancing of different lead objects from five important Roman settlements between 15 BC and the beginning of fourth century AD. For this purpose, measurements were made on lead and copper ore samples from the Siegerland, Eifel, Hunsrück and Lahn-Dill area in Germany and supplemented with data from the literature to create a data bank of lead isotope ratios of European deposits. Compositional analysis of lead objects by Electron Microprobe analysis showed that Romans were able to purify lead from ore up to 99%. Multi-Collector Inductively Coupled Plasma Mass-Spectrometry was used to determine the source of lead, which played an important role in nearly all aspects of Roman life. Lead isotope ratios were measured for ore samples from German deposits from the eastern side of the Rhine (Siegerland, Lahn-Dill, Ems) and the western side of the Rhine (Eifel, Hunsrück), which contained enough ore reserves to answer the increasing local demand and are believed to have been mined during the Roman period. This data together with those from Mediterranean ore deposits from the literature was used to establish a data bank. The Mediterranean ore deposits range from Cambrian (high 207Pb/206Pb) to tertiary (lower 207Pb/206Pb) values. In particular, the Cypriot deposits are younger, while the Spanish deposits fall either with the younger Sardic ores or close to the older Cypriot ores. The lead isotope ratios of most German ore deposits fall in between the 208Pb/206Pb vs. 207Pb/206Pb ratios of Sardinia and Cyprus, where the lead isotope signature of ore deposits from France and Britain are also found. Over 240 lead objects were measured from Wallendorf (second century BC to first century AD) Dangstetten (15-8 BC), Waldgirmes (AD 1-10), Mainz (AD 1-300), Martberg (first to fourth centuries AD) & Trier (third to fourth centuries AD). Comparing the lead isotope ratios of lead objects and those from German ores shows that the source of over 85 percent of objects are Eifel ore deposits, but the Roman’s had also imported lead from the Southern Massif Central and from Great Britain. A further topic of this work was the systematic study of the variation of copper isotope ratios in different copper minerals and the mechanisms, which controls copper isotope fractionation in ores deposits. For this purpose, copper isotope analyses were made by Multi-Collector Inductively Coupled Plasma Mass-Spectrometry from a series of hydrothermal copper sulphides and their alteration products. Copper and lead isotope ratios were measured in coexisting phases of chalcopyrite and malachite and also coexisting malachite and azurite. No significant fractionation was observed in malachite-azurite phases, but in chalcopyrite-malachite coexisting phases, malachite always shows a positive fractionation to heavier isotope values. Zhu et al. and Larson et al. showed that isotopic variations in copper principally reflect mass fractionation in response to low temperature processes rather than source heterogeneity. The low temperature ore formation processes are mostly represented by weathering of primary sulphide ores to produce secondary carbonate phases and therefore are usually observed on the surface of ore deposits, which were probably removed during the early Bronze Age. Using this concept, copper isotope ratios were measured in some Early Bronze Age copper alloys and Roman copper alloys. However, no large copper isotope fractionation has been observed. Lead and copper isotope ratios were measured on samples from the Kupferschiefer. Two profiles were investigated; 1) Sangerhausen, which was not directly influenced by the oxidizing brines of Rote Fäule and 2) Oberkatz, where both Rote Fäule-controlled and structure-controlled mineralization were observed. Results from maturation studies of organic matter suggest the maximum temperature affecting the Kupferschiefer did not exceed 130°C. delta-65-Cu ranges between -0.78-+0.58‰, shows a positive correlation with copper concentration. Maximum temperature in the Kupferschiefer profile from Oberkatz is supposed to be around 150°C. delta-65Cu in this profile ranges between -0.71-+0.68‰. The pattern of copper isotope fractionation and copper concentration is same as the for profile of Sangerhausen. Origina lead isotope ratios are strongly overprinted by high concentrations of uranium in bottom of both profiles causing more radiogenic lead.
We present a higher-order call-by-need lambda calculus enriched with constructors, case-expressions, recursive letrec-expressions, a seq-operator for sequential evaluation and a non-deterministic operator amb, which is locally bottom-avoiding. We use a small-step operational semantics in form of a normal order reduction. As equational theory we use contextual equivalence, i.e. terms are equal if plugged into an arbitrary program context their termination behaviour is the same. We use a combination of may- as well as must-convergence, which is appropriate for non-deterministic computations. We evolve different proof tools for proving correctness of program transformations. We provide a context lemma for may- as well as must- convergence which restricts the number of contexts that need to be examined for proving contextual equivalence. In combination with so-called complete sets of commuting and forking diagrams we show that all the deterministic reduction rules and also some additional transformations keep contextual equivalence. In contrast to other approaches our syntax as well as semantics does not make use of a heap for sharing expressions. Instead we represent these expressions explicitely via letrec-bindings.
Static analysis of different non-strict functional programming languages makes use of set constants like Top, Inf, and Bot denoting all expressions, all lists without a last Nil as tail, and all non-terminating programs, respectively. We use a set language that permits union, constructors and recursive definition of set constants with a greatest fixpoint semantics. This paper proves decidability, in particular EXPTIMEcompleteness, of subset relationship of co-inductively defined sets by using algorithms and results from tree automata. This shows decidability of the test for set inclusion, which is required by certain strictness analysis algorithms in lazy functional programming languages.
Extending the method of Howe, we establish a large class of untyped higher-order calculi, in particular such with call-by-need evaluation, where similarity, also called applicative simulation, can be used as a proof tool for showing contextual preorder. The paper also demonstrates that Mann’s approach using an intermediate “approximation” calculus scales up well from a basic call-by-need non-deterministic lambdacalculus to more expressive lambda calculi. I.e., it is demonstrated, that after transferring the contextual preorder of a non-deterministic call-byneed lambda calculus to its corresponding approximation calculus, it is possible to apply Howe’s method to show that similarity is a precongruence. The transfer is not treated in this paper. The paper also proposes an optimization of the similarity-test by cutting off redundant computations. Our results also applies to deterministic or non-deterministic call-by-value lambda-calculi, and improves upon previous work insofar as it is proved that only closed values are required as arguments for similaritytesting instead of all closed expressions.
The paper examines challenges in effectively implementing the lender-of-last-resort function in the EU single financial market. Briefly highlighted are features of the EU financial landscape that could increase EU systemic financial risk. Briefly described are the complexities of the EU’s financial-stability architecture for preventing and resolving financial problems, including lender-of-last-resort operations. The paper examines how the lender-of-last-resort function might materialize during a systemic financial disturbance affecting more than one EU Member State. The paper identifies challenges and possible ways of enhancing the effectiveness of the existing architecture.
In order to investigate the role of neuronal synchronization in perceptual grouping, a new method was developed to record selectively from multiple cortical sites of known functional specificity as determined by optical imaging of intrinsic signals. To this end, a matrix of closely spaced guide tubes was developed in cooperation with a company providing the essential manufacturing technique RMPD® (Rapid Micro Product Development). The matrix was embedded into a framework of hard and software that allowed for the mapping of each guide tube onto the cortical site an electrode would be led to if inserted into that guide tube. With these developments, it was possible to determine the functional layout of the cortex by optical imaging and subsequently perform targeted recordings with multiple electrodes in parallel. The method was tested for its accuracy and found to target the electrodes with a precision of 100 µm to the desired cortical locations. Using the developed technique, neuronal activity was recorded from area 18 of anesthetized cats. For stimulation, Gabor-patches in different geometrical configurations were placed over the recorded receptive fields merging into visual objects appropriate for testing the hypothesis of feature binding by synchrony. Synchronization strength was measured by the height of the cross-correlation centre peaks. All pairwise synchronizations were summarized in a correlation index which determined the mean difference of the correlation strengths between conditions in which recording sites should or should not fire in synchrony according to the binding hypothesis. The correlation index deviated significantly from zero for several of these configurations, further supporting the hypothesis that synchronization plays an important role in the process of perceptual grouping. Furthermore, direct evidence was found for the independence of the synchronization strength from the neuronal firing rate and for neurons that change dynamically the ensemble they participate in. In parallel to the experimental approach, mechanisms of oscillatory long range synchronization were studied by network simulations. To this end, a biologically plausible model was implemented using pyramidal and basket cells with Hodgkin-Huxley like conductances. Several columns were built from these cells and intra- and inter-columnar connections were mimicked from physiological data. When activated by independent Poisson spike trains, the columns showed oscillatory activity in the gamma frequency range. Correlation analysis revealed the tendency to locally synchronize the oscillations among the columns, but a rapid phase transition occurred with increasing cortical distance. This finding suggests that the present view of the inter-columnar connectivity does not fully explain oscillatory long range synchronization and predicts that other processes such as top-down influences are necessary for long range synchronization phenomena.
Systematisch verabreichte Chemotherapeutika sind oft uneffektiv bei der Behandlung von Krankheiten des zentralen Nervensystems (ZNS). Eine der Ursachen hierfür ist der unzureichende Arzneistoff-Transport ins Gehirn aufgrund der Blut-Hirn-Schranke. Eine der Strategien für den nicht-invasiven Wirkstoff-Transport ins Gehirn ist die Verwendung von Nanopartikeln. Polybutylcyanoacrylat-Nanopartikel, die mit Polysorbat 80 (Tween® 80) überzogen wurden, können die Blut-Hirn-Schranke passieren und somit Wirkstoffe ins Gehirn transportieren. Wird die Blut-Hirn-Schranke durch einen Hirntumor partiell beschädigt und hierdurch ihre Permeabilität am Ort des Tumors erhöht, können Nanopartikel den Tumor zusätzlich durch den sogenannten EPR-Effekt erreichen. Im ersten Teil der vorliegenden Arbeit wurde die Beladung der Nanopartikel durch Variation der Formulierungparameter mit dem Ziel optimiert, eine Formulierung mit höherer Wirksamkeit für die Therapie von Glioblastom-tragenden Ratten zu entwickeln. Außerdem wurde das Potential von Doxorubicin, das an mit „Stealth Agents“ überzogenen Polybutylcyanoacrylat-Nanopartikel gebunden war, für die Chemotherapie von Hirntumoren untersucht. Im zweiten Teil dieser Studie wurden die Gehirn- und Körperverteilung in gesunden und in Glioblastom-101/8-tragenden Ratten nach i.v.-Gabe von Poly(butyl-2-cyano[3- 14C]acrylat)-Nanopartikeln, die mit Polysorbat 80 beschichtet wurden, und solchen, die noch zusätzlich mit Doxorubicin geladen waren (DOX-14C-PBCA + PS), untersucht. Die Standardformulierung von Doxubicin-Polybutylcyanoacrylat-Nanopartikeln (DOX-NP) wurde durch anionische Polymerisierung von Butylcyanoacrylat in Anwesenheit von DOX hergestellt. Zusätzlich wurden unterschiedliche DOX-NP Formulierungen durch Veränderung der Herstellung produziert. Das therapeutische Potential der Formulierungen wurde in Ratten mit ins Gehirn transplantieren Glioblastom 101/8 untersucht. Neben Polysorbat 80 wurden Poloxamer 188 und Poloxamin 908 als Überzugsmaterial verwendet. Die Resultate ergaben, dass die mit Polysorbat 80 überzogene Standardformulierung am effektivsten war. Die höhere Wirksamkeit von DOX-NP+PS 80 könnte durch die Fähigkeit dieser Träger erklärt werden, den Wirkstoff während eines frühen Stadiums der Tumorentwicklung durch einen Rezeptor-vermittelten Mechanismus, der durch den PS 80-Überzug aktiviert wurde über die intakte Blut-Hirn-Schranke, zu transportieren. Unsere Ergebnisse zeigen auch, dass Poloxamer 188 und Poloxamin 908 den antitumoralen Effekt von DOX-PBCA beträchtlich verbessern. Der anti-tumorale Effekt dieser Formulierungen könnte möglicherweise dem EPR-Effekt zugeschrieben werden. Es ist bekannt, dass die tumorale Arzneistoff-Aufnahme durch den EPR-Effektes für lang-zirkulierende Wirkstoffträger ausgeprägter ist und so mehr Wirkstoff durch die Tumor-geschädigte Blut-Hirn-Schranke gelangt. Unbeschichtete Nanopartikel, Polysorbat 80-beschichtete Nanopartikel oder mit Doxorubicin beladene und mit Polysorbat 80 beschichtete Nanopartikel wurden in gesunden und Tumor-tragenden Ratten injiziert. Diese Nanopartikel-Präparationen zeigten einer unterschiedliche Korpenverteilung in den Ratten. Unbeschichtete Nanopartikel sammelten sich in den RES-Organen an. Mit PS 80 beschichtete NP reduzierten die Aufnahme der NP in Leber und Milz, während sich die Konzentration der NP in der Lunge erhöhte. Diese Beobachtungen deuten darauf hin, dass die Änderung der Oberflächeneigenschaften der NP durch das Tensid, zu einer Interaktion mit unterschiedlichen Opsoninen führt, welches die Aufnahme der NP von verschiedenen phagozitierenden Zellen erleichtert. Hingegen war die Aufnahme der mit DOX beladenen, PS 80-beschichteten Nanopartikel den unbeschichteten Partikel ähnlich. Im Vergleich mit gesunden Ratten und mit Tumor-tragenden Ratten hingegen war die Konzentration der NP im Gehirn von Tumor tragenden Ratten 10 Tage nach der Tumor-implantation signifikant höher. In Anwesenheit des Glioblastoms ist der Transport von NP in das Gehirn das Resultat verschiedener Faktoren: zusätzlich zur Fähigkeit von PS 80-Nanopartikeln, die Blut-Hirn-Schranke zu passieren, extravasieren diese Träger wegen des EPR Effekts über das durch den Tumor undichte Endothelium. Die Konzentration von PS 80 [14C]-PBCA NP war im Glioblastom signifikant höher als mit DOX [14C]-PBCA NP. Dieses Phänomen kann durch die unterschiedliche Mikroumgebung von zerebralem intra-tumoralen und intaktem Gehirngewebe erklärt werde. Insbesondere können sich die positive Ladung der tumoralen Regionen und die positive Ladung der DOX [14C]-PBCA NP negativ beeinflussen. Dennoch waren die Doxorubicin-Konzentration in Glioblastom ausreichend, einen therapeutischen Effekt zu ermöglichen.
Group III presynaptic metabotropic glutamate receptors (mGluRs) play a central role in regulating presynaptic activity through G-protein effects on ion channels and signal transducing enzymes. Like all Class C G-protein coupled receptors, mGluR8 has an extended intracellular C-terminal domain (CTD) presumed to allow for modulation of downstream signaling. To elucidate the function and modulation of mGluR8, yeast two-hybrid screens of an adult rat brain cDNA library were performed with the CTDs of mGluR8a and 8b (mGluR8-C) as baits. Different components of the sumoylation cascade (ube2a, sumo-1, Pias1, Pias gamma and Pias xbeta) and some other proteins were identified as mGluR8 interacting proteins. Binding assays using recombinant GST-fusion proteins confirmed that Pias1 interacts not only with mGluR8-C, but all group III mGluR CTDs. Pias1 binding to mGluR8-C required a region N-terminally to a consensus sumoylation motif and was not affected by arginine substitution of the conserved lysine K882 within this motif. Co-transfection of fluorescently tagged mGluR8a-C, sumo-1 and enzymes of the sumoylation cascade into HEK 293 cells showed that mGluR8a-C can be sumoylated in cells. Arginine substitution of lysine K882 within the consensus sumoylation motif, but not of other conserved lysines within the CTD, abolished in vivo sumoylation. The results are consistent with post-translational sumoylation providing a novel mechanism of group III mGluR regulation.
We introduce a smooth mapping of some discrete space-time symmetries into quasi-continuous ones. Such transformations are related with q-deformations of the dilations of the Euclidean space and with the non-commutative space. We work out two examples of Hamiltonian invariance under such symmetries. The Schrodinger equation for a free particle is investigated in such a non-commutative plane and a connection with anyonic statistics is found. PACS: 03.65.Fd, 11.30.Er
Chemokines play a key role in the cellular infiltration of inflamed tissue. They are released by a wide variety of cell types during the initial phase of host response to injury, allergens, antigens, or invading microorganisms, and selectively attract leukocytes to inflammatory foci, inducing both migration and activation. Monocyte chemoattractant protein-1 (MCP-1), a member of the CC chemokine superfamily, functions in attracting monocytes, T lymphocytes, and basophils to sites of inflammation. MCP-1 is produced by monocytes, fibroblasts, vascular endothelial cells and smooth muscle cells in response to various stimuli such as tumour necrosis factor-a (TNF-a), interferon-g (IFN-g), and interleukin-1b (IL-1b). It also plays an important role in the pathogenesis of chronic inflammation, and overexpression of MCP-1 has been implicated in diseases including glomerulonephritis and rheumatoid arthritis. Oligonucleotide-directed triple helix formation offers a means to target specific sequences in DNA and interfere with gene expression at the transcriptional level. Triple helix-forming oligonucleotides (TFOs) bind to homopurine/homopyrimidine sequences, forming a stable, sequence-specific complex with the duplex DNA. Purine-rich sequences are frequent in gene regulatory regions and TFOs directed to promoter sequences have been shown to prevent binding of transcription factors and inhibit transcription initiation and elongation. Exogenous TFOs that bind homopurine/ homopyrimidine DNA sequences and form triple-helices can be rationally designed, while the intracellular delivery of single-stranded RNA TFOs has not been studied in detail before. In this study, expression vectors were constructed which directed transcription of either a 19 nt triplex-forming pyrimidine CU-TFO sequence targeting the human MCP-1 or two different 19 nt GU- or CA-control sequences, respectively, together with the vector encoded hygromycin resistance mRNA as one fusion transcript. HEK 293 cells were stable transfected with these vectors and several TFO and control cell lines were generated. Functional relevant triplex formation of a TFO with a corresponding 19 bp GC-rich AP-1/SP-1 site of the human MCP-1 promoter was shown. Binding of synthetic 19 nt CUTFO to the MCP-1 promoter duplex was verified by triplex blotting at pH 6.7. Underlining binding specificity, control sequences, including the GU- and CA-sequence, a TFO containing one single mismatch and a MCP-1 promoter duplex containing two mismatches, did not participate in triplex formation. Establishing a magnetic capture technique with streptavidin microbeads it was verified that at pH 7.0 the 19 nt TFO embedded in a 1.1 kb fusion transcript binds to a plasmid encoded MCP-1 promoter target duplex three times stronger than the controls. Finally, cell culture experiments revealed 76 ± 10.2% inhibition of MCP-1 protein secretion in TNF-a stimulated CU-TFO harboring cell lines and up to 88% after TNF-a and IFN-g costimulation in comparison to controls. Expression of interleukin-8 (IL-8) as one TNF-a inducible control gene was not affected by CU-TFO, demonstrating both highly specific and effective chemokine gene repression. Furthermore, another chemokine target, regulated upon activation normal T cell expressed and secreted (RANTES), which plays an essential role in inflammation by recruiting T lymphocytes, macrophages and eosinophils to inflammatory sites, was analysed using the triplex approach. A 28 nt TFO was designed targeting the murine RANTES gene promoter, and gel mobility shift assays demonstrated that the phosphodiester TFO formed a sequencespecific triplex with the double-stranded target DNA with a Kd of 2.5 x 10-7 M. It was analysed whether RANTES expression could be inhibited at the transcriptional level testing the TFO in two different cell lines, T helper-1 lymphocytes and brain microvascular endothelial cells (bend3 cells). Although there was a sequence-specific binding of the TFO detectable in the gel shift assays, there was no inhibitory effect of the exogenously added and phosphorothioate stabilised TFO on endogenous RANTES gene expression visible. Additionally, the small interfering RNA (siRNA) approach was tested as another strategy to inhibit expression of the pro-inflammatory chemokines MCP-1 and RANTES. Two different methods were pursuit, describing transient transfection with vector derived and synthetic siRNA. The vector pSUPER containing the siRNA coding sequence was used to suppress endogenous MCP-1 in HEK 293 cells. An empty vector without RNA sequence served as a control. Inhibition due to the siRNA was measured in stimulated and unstimulated cells. In TNF-a stimulated cells MCP-1 protein synthesis was decreased by 35 ± 11% after siRNA transfection. Using a synthetic double-stranded siRNA, the TNF-a induced MCP-1 protein secretion could be successfully inhibited about 62.3 ± 10.3% in HEK 293 cells, indicating that the siRNA is functional in these cells to suppress chemokine expression. The siRNA approach targeting murine RANTES in Th1 cells and b-end3 cells revealed no inhibition of endogenous gene expression. Gene therapy approaches rely on efficient transfer of genes to the desired target cells. A wide variety of viral and nonviral vectors have been developed and evaluated for their efficiency of transduction, sustained expression of the transgene, and safety. Among them, lentiviruses have been widely used for gene therapy applications. In order to improve the delivery of TFOs or siRNAs into the target cells, cloning of the lentiviral transfer vector SEW, the production of lentiviral particles by transient transfection were performed with the aim to generate lentiviral vector-derived TFOs in further experiments. Here, Th1 cells were transduced with infectious lentiviral particles and transduction efficacy was measured. Transduction efficacy higher than 82% could be achieved using the lentiviral vector SEW, opening optimal possibilities for the TFO or siRNA approach.
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.
Results from various theoretical approaches and ideas presented at this exciting meeting (summary talk at the 5th International Conference on Physics and Astrophysics of Quark Gluon Plasma (ICPAQGP - 2005)) are reviewed. I also point towards future directions, in particular hydrodynamic behaviour induced by jets traveling through the quark-gluon plasma, which might be worth looking at in more detail.
In this dissertation a non-deterministic lambda-calculus with call-by-need evaluation is treated. Call-by-need means that subexpressions are evaluated at most once and only if their value must be known to compute the overall result. Also called "sharing", this technique is inevitable for an efficient implementation. In the lambda-ND calculus of chapter 3 sharing is represented explicitely by a let-construct. Above, the calculus has function application, lambda abstractions, sequential evaluation and pick for non-deterministic choice. Non-deterministic lambda calculi play a major role as a theoretical foundation for concurrent processes or side-effected input/output. In this work, non-determinism additionally makes visible when sharing is broken. Based on the bisimulation method this work develops a notion of equality which respects sharing. Using bisimulation to establish contextual equivalence requires substitutivity within contexts, i.e., the ability to "replace equals by equals" within every program or term. This property is called congruence or precongruence if it applies to a preorder. The open similarity of chapter 4 represents a new concept, insofar that the usual definition of a bisimulation is impossible in the lambda-ND calculus. So in section 3.2 a further calculus lambda-Approx has to be defined. Section 3.3 contains the proof of the so-called Approximation Theorem which states that the evaluation in lambda-ND and lambda-Approx agrees. The foundation for the non-trivial precongruence proof is set out in chapter 2 where the trailblazing method of Howe is extended to be capable with sharing. By the use of this (extended) method, the Precongruence Theorem proves open similarity to be a precongruence, involving the so-called precongruence candidate relation. Joining with the Approximation Theorem we obtain the Main Theorem which says that open similarity of the lambda-Approx calculus is contained within the contextual preorder of the lambda-ND calculus. However, this inclusion is strict, a property whose non-trivial proof involves the notion of syntactic continuity. Finally, chapter 6 discusses possible extensions of the base calculus such as recursive bindings or case and constructors. As a fundamental study the calculus lambda-ND provides neither of these concepts, since it was intentionally designed to keep the proofs as simple as possible. Section 6.1 illustrates that the addition case and constructors could be accomplished without big hurdles. However, recursive bindings cannot be represented simply by a fixed point combinator like Y, thus further investigations are necessary.
A new approach to optimize multilevel logic circuits is introduced. Given a multilevel circuit, the synthesis method optimizes its area while simultaneously enhancing its random pattern testability. The method is based on structural transformations at the gate level. New transformations involving EX-OR gates as well as Reed–Muller expansions have been introduced in the synthesis of multilevel circuits. This method is augmented with transformations that specifically enhance random-pattern testability while reducing the area. Testability enhancement is an integral part of our synthesis methodology. Experimental results show that the proposed methodology not only can achieve lower area than other similar tools, but that it achieves better testability compared to available testability enhancement tools such as tstfx. Specifically for ISCAS-85 benchmark circuits, it was observed that EX-OR gate-based transformations successfully contributed toward generating smaller circuits compared to other state-of-the-art logic optimization tools.
Retiming is a widely investigated technique for performance optimization. It performs powerful modifications on a circuit netlist. However, often it is not clear, whether the predicted performance improvement will still be valid after placement has been performed. This paper presents a new retiming algorithm using a highly accurate timing model taking into account the effect of retiming on capacitive loads of single wires as well as fanout systems. We propose the integration of retiming into a timing-driven standard cell placement environment based on simulated annealing. Retiming is used as an optimization technique throughout the whole placement process. The experimental results show the benefit of the proposed approach. In comparison with the conventional design flow based on standard FEAS our approach achieved an improvement in cycle time of up to 34% and 17% on the average.
Retiming is a widely investigated technique for performance optimization. In general, it performs extensive modifications on a circuit netlist, leaving it unclear, whether the achieved performance improvement will still be valid after placement has been performed. This paper presents an approach for integrating retiming into a timing-driven placement environment. The experimental results show the benefit of the proposed approach on circuit performance in comparison with design flows using retiming only as a pre- or postplacement optimization method.
Channel routing is an NP-complete problem. Therefore, it is likely that there is no efficient algorithm solving this problem exactly.In this paper, we show that channel routing is a fixed-parameter tractable problem and that we can find a solution in linear time for a fixed channel width.We implemented our approach for the restricted layer model. The algorithm finds an optimal route for channels with up to 13 tracks within minutes or up to 11 tracks within seconds.Such narrow channels occur for example as a leaf problem of hierarchical routers or within standard cell generators.
We present a theoretical analysis of structural FSM traversal, which is the basis for the sequential equivalence checking algorithm Record & Play presented earlier. We compare the convergence behaviour of exact and approximative structural FSM traversal with that of standard BDD-based FSM traversal. We show that for most circuits encountered in practice exact structural FSM traversal reaches the fixed point as fast as symbolic FSM traversal, while approximation can significantly reduce in the number of iterations needed. Our experiments confirm these results.
We present the FPGA implementation of an algorithm [4] that computes implications between signal values in a boolean network. The research was performed as a masterrsquos thesis [5] at the University of Frankfurt. The recursive algorithm is rather complex for a hardware realization and therefore the FPGA implementation is an interesting example for the potential of reconfigurable computing beyond systolic algorithms. A circuit generator was written that transforms a boolean network into a network of small processing elements and a global control logic which together implement the algorithm. The resulting circuit performs the computation two orders of magnitudes faster than a software implementation run by a conventional workstation.
This paper presents a new timing driven approach for cell replication tailored to the practical needs of standard cell layout design. Cell replication methods have been studied extensively in the context of generic partitioning problems. However, until now it has remained unclear what practical benefit can be obtained from this concept in a realistic environment for timing driven layout synthesis. Therefore, this paper presents a timing driven cell replication procedure, demonstrates its incorporation into a standard cell placement and routing tool and examines its benefit on the final circuit performance in comparison with conventional gate or transistor sizing techniques. Furthermore, we demonstrate that cell replication can deteriorate the stuck-at fault testability of circuits and show that stuck-at redundancy elimination must be integrated into the placement procedure. Experimental results demonstrate the usefulness of the proposed methodology and suggest that cell replication should be an integral part of the physical design flow complementing traditional gate sizing techniques.
One of the most severe short-comings of currently available equivalence checkers is their inability to verify integer multipliers. In this paper, we present a bit level reverse-engineering technique that can be integrated into standard equivalence checking flows. We propose a Boolean mapping algorithm that extracts a network of half adders from the gate netlist of an addition circuit. Once the arithmetic bit level representation of the circuit is obtained, equivalence checking can be performed using simple arithmetic operations. Experimental results show the promise of our approach.