Universitätspublikationen
Refine
Year of publication
- 2004 (84) (remove)
Document Type
- Article (84) (remove)
Language
- English (61)
- German (20)
- Portuguese (2)
- Multiple languages (1)
Has Fulltext
- yes (84)
Is part of the Bibliography
- no (84) (remove)
Keywords
- septic shock (2)
- Abort (1)
- Adorno (1)
- Angiogenesis (1)
- Aspirin (1)
- COPD (1)
- Calycotome villosa (Poiret) Link Subsp. Intermedia (1)
- Cardiac fibroblast (1)
- Chronic obstructive pulmonary disease (1)
- Critical Theory (1)
Institute
- Medizin (19)
- Physik (16)
- Rechtswissenschaft (9)
- E-Finance Lab e.V. (8)
- Biochemie und Chemie (6)
- Philosophie (6)
- Biowissenschaften (4)
- Informatik (4)
- Exzellenzcluster Die Herausbildung normativer Ordnungen (3)
- Gesellschaftswissenschaften (3)
We report results on rho (770)0--> pi + pi - production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[sNN]=200 GeV. This is the first direct measurement of rho (770)0--> pi + pi - in heavy-ion collisions. The measured rho 0 peak in the invariant mass distribution is shifted by ~40 MeV/c2 in minimum bias p+p interactions and ~70 MeV/c2 in peripheral Au+Au collisions. The rho 0 mass shift is dependent on transverse momentum and multiplicity. The modification of the rho 0 meson mass, width, and shape due to phase space and dynamical effects are discussed.
We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account.
his Erratum replaces incorrect plots shown in Fig. 7 with the corrected ones. In the publication, the NA57 [1] ratios of Ξ− and Ξ¯¯¯¯+ to the number of wounded nucleons at ⟨NW⟩=349 by mistake were plotted at the wrong values. The ratios were calculated and plotted by mistake using ⟨NW⟩=249.
The correct normalization does not change the conclusions of the paper. The correctly normalized results are presented in Fig. 7.
The transverse mass mt distributions for deuterons and protons are measured in Pb+Pb reactions near midrapidity and in the range 0<mt–m<1.0 (1.5) GeV/c2 for minimum bias collisions at 158A GeV and for central collisions at 40 and 80 A GeV beam energies. The rapidity density dn/dy, inverse slope parameter T and mean transverse mass <mt> derived from mt distributions as well as the coalescence parameter B2 are studied as a function of the incident energy and the collision centrality. The deuteron mt spectra are significantly harder than those of protons, especially in central collisions. The coalescence factor B2 shows three systematic trends. First, it decreases strongly with increasing centrality reflecting an enlargement of the deuteron coalescence volume in central Pb+Pb collisions. Second, it increases with mt. Finally, B2 shows an increase with decreasing incident beam energy even within the SPS energy range. The results are discussed and compared to the predictions of models that include the collective expansion of the source created in Pb+Pb collisions.
Sommer 1789: Frankreich revoltiert, Preußen evaluiert. Staatsminister Johann Christoph von Wöllner, Chef des geistlichen Departements, entsendet einen bewährten Berliner Schulmann ins deutsche Reich, mit dem Auftrag, die außerpreußischen Lehranstalten zu begutachten, "teils überhaupt die Verfassung der fremden Universitäten kennen zu lernen, teils von dem Vortrag solcher Professoren, auf die einmal bei irgend einer preußischen Universität reflektiert werden könnte, zuverlässig Nachricht und Kenntnis einzuziehen". Es ist Friedrich Gedike, der durch ministeriale Order zum Headhunter für das Königreich ernannt wird. Seine Beobachtungen legt er in einem Bericht an den König nieder, der, 1905 ediert, 61 Blätter umfasst. ...
P-O bond destabilization accelerates phosphoenzyme hydrolysis of sarcoplasmic reticulum Ca2+-ATPase
(2004)
The phosphate group of the ADP-insensitive phosphoenzyme (E2-P) of sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) was studied with infrared spectroscopy to understand the high hydrolysis rate of E2-P. By monitoring an autocatalyzed isotope exchange reaction, three stretching vibrations of the transiently bound phosphate group were selectively observed against a background of 50,000 protein vibrations. They were found at 1194, 1137, and 1115 cm–1. This information was evaluated using the bond valence model and empirical correlations. Compared with the model compound acetyl phosphate, structure and charge distribution of the E2-P aspartyl phosphate resemble somewhat the transition state in a dissociative phosphate transfer reaction; the aspartyl phosphate of E2-P has 0.02 Å shorter terminal P–O bonds and a 0.09 Å longer bridging P–O bond that is ∼20% weaker, the angle between the terminal P–O bonds is wider, and –0.2 formal charges are shifted from the phosphate group to the aspartyl moiety. The weaker bridging P–O bond of E2-P accounts for a 1011–1015-fold hydrolysis rate enhancement, implying that P–O bond destabilization facilitates phosphoenzyme hydrolysis. P–O bond destabilization is caused by a shift of noncovalent interactions from the phosphate oxygens to the aspartyl oxygens. We suggest that the relative positioning of Mg2+ and Lys684 between phosphate and aspartyl oxygens controls the hydrolysis rate of the ATPase phosphoenzymes and related phosphoproteins.
Solidarität!
(2004)
Rechtshistorikern ist das Thema der Solidarität – und das damit verbundene Antithema eines ausufernden Individualismus – alt vertraut. Die Frage des sozialen Defizits jener Privatrechtskodifikation, die uns das 19. Jahrhundert hinterlassen hat, gehört zu den Königsthemen der Disziplin, seit Menger und Gierke mit den rechtstheoretischen Protagonisten des BGB die Klingen kreuzten. Und vor allem die Diskurse des Arbeits-, Sozial- und Verfassungsrechts, aber beileibe nicht nur sie, haben sich seit jenen Tagen in eindringlicher Weise mit den Konsequenzen beschäftigt, die sich aus der Integration kollektiver und solidaristischer Elemente in die Rechtsstruktur für das Recht selbst und für seine innergesellschaftliche Umwelt ergeben haben. ...
Regieren durch Solidarität?
(2004)
In Thomas Bernhards "Am Ziel" blickt der Dramatische Schriftsteller auf die Familienkämpfe seiner Jugend zurück: "Sie zogen mir eine Jacke an und sagten – so das ist die lebenslängliche Jacke für dich – und ich zog die Jacke wieder aus. Sie zogen Sie mir an – und ich zog sie wieder aus – immer so fort sie zogen sie mir an – ich zog sie wieder aus." "Ich ging weg ich machte mich selbständig." Dann gleichsam bilanzierend: "Ich fühlte mich mit mir selbst solidarisch – mit keinem Andern – Ich rettete mich aus den Andern heraus." Und die Kommunikationspartnerin echot unwidersprochen: "Sie retteten sich auf Kosten der Ihrigen." ...
Das erstmals Ende 2002 im Süden Chinas aufgetretene schwere akute respiratorische Syndrom (SARS) führte bis zum August 2003 zu insgesamt über 8000 Erkrankungen und über 700 Todesfällen. Eine von der Weltgesundheitsorganisation (WHO) ins Leben gerufene Kooperation verschiedener Laboratorien weltweit ermöglichte innerhalb von nur vier Wochen die Identifizierung des kausalen Agens, eines bislang unbekannten Coronavirus (vorläufig bezeichnet als SARS-assoziiertes Coronavirus oder SARS-CoV), welches die Koch’schen Postulate erfüllt. Der Erreger lässt sich (unter Hochsicherheitsbedingungen) gut in Zellkulturen vermehren, was weitere Studien zur Stabilität sowie die Entwicklung von antiviral wirksamen Substanzen und Impfstoffen erleichtert.
Obwohl schon rasch diagnostische Labortests, insbesondere zum Nachweis der viralen Nukleinsäure und virusspezifischer Antikörper, zur Verfügung standen, basiert die Falldefinition von SARS weiterhin auf klinisch-epidemiologischen Kriterien. In Hinblick auf die Gefahr eines (saisonalen) Wiederauftretens der Infektion müssen die verfügbaren Labormethoden dringend überprüft und weiter verbessert werden.
SARS ist ein gutes Beispiel dafür, wie schnell sich eine Infektionskrankheit über den internationalen Reiseverkehr ausbreiten kann, aber auch dafür, wie wichtig in einem solchen Falle eine gut koordinierte internationale Kooperation ist; durch Einsatz neuester, aber auch bewährter konventioneller Labormethoden und ständigen Austausch aktueller (Zwischen-)Ergebnisse sowie von Patientenproben und Reagenzien führte eine bisher einmalige Zusammenarbeit schnell zu einem Durchbruch. Dies lässt auf ähnliche Fortschritte beim Kampf gegen weitere neuartige Infektionserreger hoffen.
Pathologic data indicate that human cytomegalovirus (HCMV) infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB) cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169), were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcriptionpolymerase chain reaction (RT-PCR). The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.
The production of strange pentaquark states (e.g., Theta baryons and Ξ−− states) in hadronic interactions within a Gribov–Regge approach is explored. In this approach the Θ+(1540) and the Ξ are produced by disintegration of remnants formed by the exchange of pomerons between the two protons. We predict the rapidity and transverse momentum distributions as well as the 4π multiplicity of the Θ+, Ξ−−, Ξ−, Ξ0 and Ξ+ for s=17 GeV (SPS) and 200 GeV (RHIC). For both energies more than 10−3 Θ+ and more than 10−5 Ξ per pp event should be observed by the present experiments.
We point out that during the supernova II type explosion the thermodynamical conditions of stellar matter between the protoneutron star and the shock front correspond to the nuclear liquid–gas coexistence region, which can be investigated in nuclear multifragmentation reactions. We have demonstrated, that neutron-rich hot heavy nuclei can be produced in this region. The production of these nuclei may influence dynamics of the explosion and contribute to the synthesis of heavy elements.
In bioinformatics, biochemical signal pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically obtaining the most appropriate model and learning its parameters is extremely interesting. One of the most often used approaches for model selection is to choose the least complex model which “fits the needs”. For noisy measurements, the model which has the smallest mean squared error of the observed data results in a model which fits too accurately to the data – it is overfitting. Such a model will perform good on the training data, but worse on unknown data. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated. Keywords: biochemical pathways, differential equations, septic shock, parameter estimation, overfitting, minimum description length.
Data driven automatic model selection and parameter adaptation – a case study for septic shock
(2004)
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated.
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. In this paper, for the small, important example of inflammation modeling a network is constructed and different learning algorithms are proposed. It turned out that due to the nonlinear dynamics evolutionary approaches are necessary to fit the parameters for sparse, given data. Keywords: model parameter adaption, septic shock. coupled differential equations, genetic algorithm.
Since the description of sepsis by Schottmüller in 1914, the amount on knowledge available on sepsis and its underlying pathophysiology has substantially increased. Epidemiologic examinations of abdominal septic shock patients show the potential for high risk posed by and the extensive therapy situation in the intensive care unit (ICU) (5). Unfortunately, until now it has not been possible to significantly reduce the mortality rate of septic shock, which is as high as 50-60% worldwide, although PROWESS' results (1) are encouraging. This paper summarizes the main results of the MEDAN project and their medical impacts. Several aspects are already published, see the references. The heterogeneity of patient groups and the variations in therapy strategies is seen as one of the main problems for sepsis trials. In the MEDAN multi-center study of 71 intensive care units in Germany, a group of 382 patients made up exclusively of abdominal septic shock patients who met the consensus criteria for septic shock (3) was analysed. For use within scores or stand-alone experiments variables are often studied as isolated variables, not as a multidimensional whole, e.g. a recent study takes a look at the role thrombocytes play (15). To avoid this limitation, our study compares several established scores (SOFA, APACHE II, SAPS II, MODS) by a multi-dimensional neuronal network analysis. For outcome prediction the data of 382 patients was analysed by using most of the commonly documented vital parameters and doses of medicine (metric variables). Data was collected in German hospitals from 1998 to 2001. The 382 handwritten patient records were transferred to an electronic database giving the amount of 2.5 million data entries. The metric data contained in the database is composed of daily measurements and doses of medicine. We used range and plausibility checks to allow no faulty data in the electronic database. 187 of the 382 patients are deceased (49 %).
We perform a study of the possible existence of hybrid stars with color superconducting quark cores using a specific hadronic model in a combination with an NJL-type quark model. It is shown that the constituent mass of the non-strange quarks in vacuum is a very important parameter that controls the beginning of the hadron–quark phase transition. At relatively small values of the mass, the first quark phase that appears is the two-flavor color superconducting (2SC) phase which, at larger densities, is replaced by the color-flavor locked (CFL) phase. At large values of the mass, on the other hand, the phase transition goes from the hadronic phase directly into the CFL phase avoiding the 2SC phase. It appears, however, that the only stable hybrid stars obtained are those with the 2SC quark cores.
The transporter associated with antigen processing (TAP) is a key component of the cellular immune system. As a member of the ATP-binding cassette (ABC) superfamily, TAP hydrolyzes ATP to energize the transport of peptides from the cytosol into the lumen of the endoplasmic reticulum. TAP is composed of TAP1 and TAP2, each containing a transmembrane domain and a nucleotide-binding domain (NBD). Here we investigated the role of the ABC signature motif (C-loop) on the functional non-equivalence of the NBDs, which contain a canonical C-loop (LSGGQ) for TAP1 and a degenerate C-loop (LAAGQ) for TAP2. Mutation of the leucine or glycine (LSGGQ) in TAP1 fully abolished peptide transport. However, TAP complexes with equivalent mutations in TAP2 still showed residual peptide transport activity. To elucidate the origin of the asymmetry of the NBDs of TAP, we further examined TAP complexes with exchanged C-loops. Strikingly, the chimera with two canonical C-loops showed the highest transport rate whereas the chimera with two degenerate C-loops had the lowest transport rate, demonstrating that the ABC signature motifs control peptide transport efficiency. All single site mutants and chimeras showed similar activities in peptide or ATP binding, implying that these mutations affect the ATPase activity of TAP. In addition, these results prove that the serine of the C-loop is not essential for TAP function but rather coordinates, together with other residues of the C-loop, the ATP hydrolysis in both nucleotide-binding sites.
The mode of the antitumoral activity of multimutated oncolytic herpes simplex virus type 1 G207 has not been fully elucidated yet. Because the antitumoral activity of many drugs involves the inhibition of tumor blood vessel formation, we determined if G207 had an influence on angiogenesis. Monolayers of human umbilical vein endothelial cells and human dermal microvascular endothelial cells, but not human dermal fibroblasts, bronchial epithelial cells, and retinal glial cells, were highly sensitive to the replicative and cytotoxic effects of G207. Moreover, G207 infection caused the destruction of endothelial cell tubes in vitro. In the in vivo Matrigel plug assay in mice, G207 suppressed the formation of perfused vessels. Intratumoral treatment of established human rhabdomyosarcoma xenografts with G207 led to the destruction of tumor vessels and tumor regression. Ultrastructural investigations revealed the presence of viral particles in both tumor and endothelial cells of G207-treated xenografts, but not in adjacent normal tissues. These findings show that G207 may suppress tumor growth, in part, due to inhibition of angiogenesis.
The MAM (meprin/A5-protein/PTPmu) domain is present in numerous proteins with diverse functions. PTPμ belongs to the MAM-containing subclass of protein-tyrosine phosphatases (PTP) able to promote cell-to-cell adhesion. Here we provide experimental evidence that the MAM domain is a homophilic binding site of PTPμ. We demonstrate that the MAM domain forms oligomers in solution and binds to the PTPμ ectodomain at the cell surface. The presence of two disulfide bridges in the MAM molecule was evidenced and their integrity was found to be essential for MAM homophilic interaction. Our data also indicate that PTPμ ectodomain forms oligomers and mediates the cellular adhesion, even in the absence of MAM domain homophilic binding. Reciprocally, MAM is able to interact homophilically in the absence of ectodomain trans binding. The MAM domain therefore contains independent cis and trans interaction sites and we predict that its main role is to promote lateral dimerization of PTPμ at the cell surface. This finding contributes to the understanding of the signal transduction mechanism in MAM-containing PTPs.
In Archaea, bacteria, and eukarya, ATP provides metabolic energy for energy-dependent processes. It is synthesized by enzymes known as A-type or F-type ATP synthase, which are the smallest rotatory engines in nature (Yoshida, M., Muneyuki, E., and Hisabori, T. (2001) Nat. Rev. Mol. Cell. Biol. 2, 669-677; Imamura, H., Nakano, M., Noji, H., Muneyuki, E., Ohkuma, S., Yoshida, M., and Yokoyama, K. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 2312-2315). Here, we report the first projected structure of an intact A(1)A(0) ATP synthase from Methanococcus jannaschii as determined by electron microscopy and single particle analysis at a resolution of 1.8 nm. The enzyme with an overall length of 25.9 nm is organized in an A(1) headpiece (9.4 x 11.5 nm) and a membrane domain, A(0) (6.4 x 10.6 nm), which are linked by a central stalk with a length of approximately 8 nm. A part of the central stalk is surrounded by a horizontal-situated rodlike structure ("collar"), which interacts with a peripheral stalk extending from the A(0) domain up to the top of the A(1) portion, and a second structure connecting the collar structure with A(1). Superposition of the three-dimensional reconstruction and the solution structure of the A(1) complex from Methanosarcina mazei Gö1 have allowed the projections to be interpreted as the A(1) headpiece, a central and the peripheral stalk, and the integral A(0) domain. Finally, the structural organization of the A(1)A(0) complex is discussed in terms of the structural relationship to the related motors, F(1)F(0) ATP synthase and V(1)V(0) ATPases.
The objective of this paper is the study of the equilibrium behavior of a population on the hierarchical group ΩN consisting of families of individuals undergoing critical branching random walk and in addition these families also develop according to a critical branching process. Strong transience of the random walk guarantees existence of an equilibrium for this two-level branching system. In the limit N→∞ (called the hierarchical mean field limit), the equilibrium aggregated populations in a nested sequence of balls B(N)ℓ of hierarchical radius ℓ converge to a backward Markov chain on R+. This limiting Markov chain can be explicitly represented in terms of a cascade of subordinators which in turn makes possible a description of the genealogy of the population.
Wohl kaum wird der amerikanische "Imperator" den gefangenen "Barbaren von Bagdad" im Triumphwagen durch die Straßen von Washington ziehen lassen, auch wenn sich die publizistische Rhetorik seit den Kriegen gegen Afghanistan und den Irak mit Vergleichen zwischen dem antiken Rom und dem neuen Amerika förmlich überschlägt. "Sind die Amerikaner die Römer unserer Zeit?", fragt sich als einer unter vielen der Publizist und Althistoriker Peter Bender. Expansionen der alten wie der neuen Imperatoren werden miteinander verglichen, Parallelen und Unterschiede in der geographischen Lage, in den Interessen und Willen der Akteure ausgemacht. So habe bei den Amerikanern der Sendungsglaube als universale Macht schon am Anfang des Imperiums und nicht erst an dessen Ende wie bei den Römern gestanden. Roms Ostkriege und der kalteOst-West-Krieg hingegen zeitigten dasselbe historische Ergebnis: "Davor waren Rom und Amerika die ersten Weltmächte ihrer Zeit, danach waren sie die einzigen." Von "Aufstiegen" ist die Rede, nicht aber von "Untergängen", wie es die zyklischen Zivilisationsgeschichten der Kulturmorphologen verkünden. Das hat seinen Grund. Hinter der Analyse kommt Normatives zum Vorschein, wenn es um den Schutz der "Zivilisation des Abendlandes" in "einer künftigen Welt" geht, "in der andere Kulturen sich gegen den 'Westen' behaupten, stärken und vordringen …" Bender lässt das imperium romanum nicht untergehen, weil er das amerikanische Imperium als Bollwerk westlicher Kultur braucht. ...
The starting point of Demirovic's text is Adorno's idea that concepts as forms of thinking are constellations of power. Differently from many interpretations of Adorno as resigned, Demirovic shows that this assumption enables Adorno to give his own theory the character of interventions in the ideological consensus of everyday life with regard to emancipation.
The purification and functional reconstitution of a five-component oligopeptide ATP-binding cassette transporter with a remarkably wide substrate specificity are described. High-affinity peptide uptake was dependent on liganded substrate-binding protein OppA, which interacts with the translocator OppBCDF with higher affinity than unliganded OppA. Transport screening with combinatorial peptide libraries revealed that (i) the Opp transporter is not selective with respect to amino acid side chains of the transported peptides; (ii) any peptide that can bind to OppA is transported via Opp, including very long peptides up to 35 residues long; and (iii) the binding specificity of OppA largely determines the overall transport selectivity.
Zeichen der Herrschaftsausübung, der Gerichtsbarkeit und der Marktfreiheit, öffentlich angebrachte Maße und Gewichte zur Kontrolle des Wirtschaftslebens, mittelalterliche und frühneuzeitliche Gerichtsstätten, Orte und Gegenstände des Strafvollzugs, die der Rechtshistoriker Karl Frölich in den dreißiger bis fünfziger Jahren des 20. Jahrhunderts auf große Glasplatten gebannt hat, berichten anschaulich von der Rechtsausübung vergangener Epochen, indem sie "Sachzeugen des Rechtslebens" abbilden. Die Platten dieser umfangreichen Fotosammlung werden derzeit durch die Bibliothek des Max- Planck-Instituts für europäische Rechtsgeschichte eingescannt, um die Bilder der Forschung zu erhalten und zur Verfügung zu stellen. Ein Teil der "Sammlung Frölich" befindet sich heute in der Obhut von Prof. Dr. Gerhard Dilcher, Frankfurt am Main. Ein weiterer, größerer Teil, ist nach München ins Leopold-Wenger-Institut gelangt (Prof. Dr. Hermann Nehlsen); auch diese Bilder werden nun durch Scannen mit der "Frankfurter Partie" virtuell zusammengeführt. ...
Two tetrahydroisoquinoline alkaloids were extracted from the alkaloid fraction of a methanol extract of the seeds of Calycotome Villosa Subsp. intermedia. Their structures were established as (R)-1-hydroxymethyl-7-8-dimethoxy-1,2,3,4-tetrahydro- isoquinoline (1) and (S)-7-hydroxymethyl-2-3-dimethoxy-7,8,9,10-tetrahydroisoquinoline chloride (2) by spectroscopic techniques and X-ray diffraction analysis.
In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SKBR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neuoverexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as anti proliferative agents that display activity against neoplastic cells at very low doses.
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 ~55 km and a horizontal resolution of either 7.5°×7.5° or 2.8°×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°×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 620 K where large losses occurred due to a period of very low minimum temperatures at these altitudes.
Nach Hause…
(2004)
Read only memory. Eine CD ROM ist ein Festwertspeicher. Die Daten kann man lesen, aber nicht verändern, ergänzen oder löschen. Man kann die Scheibe zertrümmern oder die Platte zerstören, aber die Daten manipulieren kann man nicht. Eine CD ROM schützt sich selbst vor Variation. Die Erfindung dieser Technik hat eine neue, kleine Gewissheit in der chronisch unsicheren Welt geschaffen. Was auf der CD ROM steht, steht fest. Und da viel auf ihr stehen kann – ganze Bibliotheken der Vergangenheit –, steht viel fest. Das macht Historiker glücklich. Drohen ihnen schon die Fakten abhanden zu kommen, verfügen sie immerhin noch über Festwerte, die aus einer zuverlässigen "Quelle" (Oexle, S. 165) fließen. ...
The main results obtained within the energy scan program at the CERN SPS are presented. The anomalies in energy dependence of hadron production indicate that the onset of deconfinement phase transition is located at about 30 A GeV. For the first time we seem to have clear evidence for the existence of a deconfined state of matter in nature. PACS numbers: 24.85.+p
We propose a method to experimentally study the equation of state of strongly interacting matter created at the early stage of nucleus–nucleus collisions. The method exploits the relation between relative entropy and energy fluctuations and equation of state. As a measurable quantity, the ratio of properly filtered multiplicity to energy fluctuations is proposed. Within a statistical approach to the early stage of nucleus–nucleus collisions, the fluctuation ratio manifests a non-monotonic collision energy dependence with a maximum in the domain where the onset of deconfinement occurs.
The signal transducer and activator of transcription (Stat) gene family comprises seven members with similarities in their domain structure and a common mode of activation. Members of this gene family mediate interferon induction of gene transcription and the response to a large number of growth factors and hormones. Extracellular ligand binding to transmembrane receptors causes the intracellular activation of associated tyrosine kinases, phosphorylation of Stat molecules, dimerization, and translocation to the nucleus. Prolactin-induced phosphorylation of Stat5 is a key event in the development and differentiation of mammary epithelial cells. In addition to the crucial phosphorylation at tyrosine 694, we have identified an O-linked N-acetylglucosamine (O-GlcNAc) as another secondary modification essential for the transcriptional induction by Stat5. This modification was only found on nuclear Stat5 after cytokine activation. Similar observations were made with Stat1, Stat3, and Stat6. Glycosylation of Stat5, however, does not seem to be a prerequisite for nuclear translocation. Mass spectrometric analysis revealed a glycosylated peptide in the N-terminal region of Stat5. Replacement of threonine 92 by an alanine residue (Stat5a-T92A) strongly reduced the prolactin induction of Stat5a glycosylation and abolished transactivation of a target gene promoter. Only the glycosylated form of Stat5 was able to bind the coactivator of transcription CBP, an essential interaction for Stat5-mediated gene transcription.
We suggest that the fluctuations of strange hadron multiplicity could be sensitive to the equation of state and microscopic structure of strongly interacting matter created at the early stage of high energy nucleus–nucleus collisions. They may serve as an important tool in the study of the deconfinement phase transition. We predict, within the statistical model of the early stage, that the ratio of properly filtered fluctuations of strange to non-strange hadron multiplicities should have a non-monotonic energy dependence with a minimum in the mixed phase region.
We have studied the ubiquinone-reducing catalytic core of NADH:ubiquinone oxidoreductase (complex I) from Yarrowia lipolytica by a series of point mutations replacing conserved histidines and arginines in the 49-kDa subunit. Our results show that histidine 226 and arginine 141 probably do not ligate iron-sulfur cluster N2 but that exchanging these residues specifically influences the properties of this redox center. Histidines 91 and 95 were found to be essential for ubiquinone reductase activity of complex I. Mutations at the C-terminal arginine 466 affected ubiquinone affinity and inhibitor sensitivity but also destabilized complex I. These results provide further support for a high degree of structural conservation between the 49-kDa subunit of complex I and its ancestor, the large subunit of water-soluble [NiFe] hydrogenases. In several mutations of histidine 226, arginine 141, and arginine 466 the characteristic EPR signatures of iron-sulfur cluster N2 became undetectable, but specific, inhibitor-sensitive ubiquinone reductase activity was only moderately reduced. As we could not find spectroscopic indications for a modified cluster N2, we concluded that these complex I mutants were lacking most of this redox center but were still capable of catalyzing inhibitor-resistant ubiquinone reduction at near normal rates. We discuss that this at first surprising scenario may be explained by electron transfer theory; after removal of a single redox center in a chain, electron transfer rates are predicted to be still much faster than steady-state turnover of complex I. Our results question some of the central mechanistic functions that have been put forward for iron-sulfur cluster N2.
Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations.
The majority of bacterial membrane-bound NiFe-hydrogenases and formate dehydrogenases have homologous membrane-integral cytochrome b subunits. The prototypic NiFe-hydrogenase of Wolinella succinogenes (HydABC complex) catalyzes H2 oxidation by menaquinone during anaerobic respiration and contains a membrane-integral cytochrome b subunit (HydC) that carries the menaquinone reduction site. Using the crystal structure of the homologous FdnI subunit of Escherichia coli formate dehydrogenase-N as a model, the HydC protein was modified to examine residues thought to be involved in menaquinone binding. Variant HydABC complexes were produced in W. succinogenes, and several conserved HydC residues were identified that are essential for growth with H2 as electron donor and for quinone reduction by H2. Modification of HydC with a C-terminal Strep-tag II enabled one-step purification of the HydABC complex by Strep-Tactin affinity chromatography. The tagged HydC, separated from HydAB by isoelectric focusing, was shown to contain 1.9 mol of heme b/mol of HydC demonstrating that HydC ligates both heme b groups. The four histidine residues predicted as axial heme b ligands were individually replaced by alanine in Strep-tagged HydC. Replacement of either histidine ligand of the heme b group proximal to HydAB led to HydABC preparations that contained only one heme b group. This remaining heme b could be completely reduced by quinone supporting the view that the menaquinone reduction site is located near the distal heme b group. The results indicate that both heme b groups are involved in electron transport and that the architecture of the menaquinone reduction site near the cytoplasmic side of the membrane is similar to that proposed for E. coli FdnI.
Vom Terror : [Szene aus einer Montage-Fassung des Dramenfragments "Moloch" von Friedrich Hebbel]
(2004)
Szene aus einer Montage-Fassung des Dramenfragments "Moloch" von Friedrich Hebbel. Die Szene steht als Einschub zwischen dem Ersten und Zweiten Akt der Tragödie, als eine Art Interludium. Im Laufe des Stückes wechselt die Perspektive mehrmals zwischen den Schauplätzen Germanischer Wald und Rom, dem Zentrum des Imperiums. Geplant ist eine Aufführung der Gesamtbearbeitung an der Volksbühne Berlin, voraussichtlich Ende 2004.
We study issues of duality in 3D field theory models over a canonical noncommutative spacetime and obtain the noncommutative extension of the self-dual model induced by the Seiberg–Witten map. We apply the dual projection technique to uncover some properties of the noncommutative Maxwell–Chern–Simons theory up to first-order in the noncommutative parameter. A duality between this theory and a model similar to the ordinary self-dual model is established. The correspondence of the basic fields is obtained and the equivalence of algebras and equations of motion are directly verified. We also comment on previous results in this subject.
Eine in Verfassungslehre und Europarechtswissenschaft weit verbreitete Annahme lautet: "Europa muss, um eine Zukunft haben zu können, sich zu einer Geschichtsgemeinschaft entwickeln." Was man dabei übersieht: So wenig sich nationale Geschichtsgemeinschaften identifizieren lassen, so wenig wird sich eine europäische Geschichtsgemeinschaft konstituieren.
Modifications of the gyromagnetic moment of electrons and muons due to a minimal length scale combined with a modified fundamental scale Mf are explored. First-order deviations from the theoretical SM value for g−2 due to these string theory-motivated effects are derived. Constraints for the fundamental scale Mf are given.
Case numbers of endemic Ca-deficiency rickets (CDR) have been reported to be alarmingly rising among children of subsistence farms in developing countries within the last 30 years. Fluoride toxicities in the environment are known to not be related to the disease. To investigate if, instead, CDR is caused by a nutrient deficiency in the environment, subsistence farms in an endemic CDR area near Kaduna, northern Nigeria, were investigated for bedrock, slope forms, soil types, and soil characteristics. The natural environment was investigated according to the World Reference Base, soil texture was analysed by pipette and sieving, and plant-available macronutrients were determined using barium-chloride or Ca-acetate-lactate extraction. The analyses showed that granite and slope deposits were the dominant parent materials. The typical slope forms and soil types were Lixisols and Acrisols on pediments, Fluvisols in river valleys, and Plinthosols and Acrisols on plains. Compared with West African background values, all of the soils had normal soil textures but were low in macronutrients. Comparisons to critical limits, however, showed that only the P concentrations were critically low, which are typical for savanna soils. A link between nutrient deficiency in soils and CDR in the Kaduna area was therefore considered unlikely.
The adaptive response of Sorghum bicolor landraces from Egypt to drought stress and following recovery was analyzed using two-dimensional difference gel electrophoresis, 2D-DIGE. Physiological measurements and proteome alterations of accession number 11434, drought tolerant, and accession number 11431, drought sensitive, were compared to their relative control values after drought stress and following recovery. Differentially expressed proteins were analysed by Matrix assisted laser desorption ionisation time-of-flight mass spectrometry, MALDI-TOF-MS. Alterations in protein contents related to the energy balance, metabolism (sensu Mewes et al. 1997), and chaperons were the most apparent features to elucidate the differences between the drought tolerant and sensitive accessions. Further alterations in the levels of proteins related to transcription and protein synthesis are discussed.
Nitric oxide (NO) represents a short lived mediator that pivotally drives keratinocyte movements during cutaneous wound healing. In this study, we have identified p68 DEAD box RNA helicase (p68) from an NO-induced differential keratinocyte cDNA library. Subsequently, we have analyzed regulation of p68 by wound-associated mediators in human and murine keratinocytes. NO, serum, growth factors, and pro-inflammatory cytokines were potent inducers of p68 expression in the cells. p68 was constitutively expressed in the epithelial compartment of murine skin. Upon injury, we found a transient down-regulation of overall p68 protein in wound tissue. However, p68 did not completely disappear during early wound repair, as we found an expression of p68 protein in isolated wound margin tissue 24 h after wounding. Moreover, immunohistochemistry and cell fractionation analysis revealed a restricted localization of p68 in keratinocyte nuclei of the developing epithelium. Accordingly, cultured keratinocytes also showed a nuclear localization of the helicase. Moreover, confocal microscopy revealed a strong localization of p68 protein within the nucleoli of the cells. Functional analyses demonstrated that p68 strongly participated in keratinocyte proliferation and gene expression. Keratinocytes that constitutively overexpressed p68 protein were characterized by a marked increase in serum-induced proliferation and vascular endothelial growth factor expression, whereas down-regulation of endogenous p68 using small interfering RNA markedly attenuated serum-induced proliferation and vascular endothelial growth factor expression. Altogether, our results suggest a tightly controlled expression and nucleolar localization of p68 in keratinocytes in vitro and during skin repair in vivo that functionally contributes to keratinocyte proliferation and gene expression.
"Eines der schwierigsten geschichtlichen Probleme stellt sich mit der Frage, wie der Aufstieg Roms zu erklären ist und wie sein Untergang. Das Verständnis für diese weltgeschichtlichen Vorgänge wird erleichtert, wenn man sich vergegenwärtigt, dass sie nicht eine, sondern viele Ursachen hatten. Der Untergang des Römischen Weltreiches war kein Ereignis, sondern ein Prozess, der sich über 300 Jahre erstreckte. Es gibt Nationen, die nicht so lange existiert haben, wie Rom allein brauchte, um unterzugehen." So die bedeutungsvollen Worte aus dem Off über dem Vorspann des fast dreistündigen Hollywood-Filmes "Der Untergang des Römischen Reiches" (1963) von Anthony Mann – in den Hauptrollen Alec Guinness als Marc Aurel und Sophia Loren als dessen Tochter Lucilla. ...