Refine
Year of publication
Document Type
- Article (139)
- Preprint (46)
- Working Paper (6)
Has Fulltext
- yes (191)
Is part of the Bibliography
- no (191)
Keywords
- LHC (8)
- ALICE (3)
- ALICE experiment (3)
- Hadron-Hadron Scattering (3)
- Risikokapital (3)
- pp collisions (3)
- Atmospheric science (2)
- Beauty production (2)
- Biohydrogen (2)
- Climate change (2)
Institute
- Physik (110)
- Informatik (98)
- Frankfurt Institute for Advanced Studies (FIAS) (97)
- Medizin (42)
- Biowissenschaften (17)
- Geowissenschaften (9)
- Institute for Monetary and Financial Stability (IMFS) (6)
- Senckenbergische Naturforschende Gesellschaft (6)
- Biochemie und Chemie (5)
- Biodiversität und Klima Forschungszentrum (BiK-F) (3)
Poster presentation: Here we investigated the role of the amyloid precursor protein (APP) in regulation of Ca2+ store depletion-induced neural cell death. Ca2+ store depletion from the endoplasmic reticulum (ER) was induced by the SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) inhibitor thapsigargin which led to a rapid induction of the unfolded protein response (UPR) and a delayed activation of executioner caspases in the cultures. Overexpression of APP potently enhanced cytosolic Ca2+ levels and cell death after ER Ca2+ store depletion in comparison to vector-transfected controls. GeneChipR and RT-PCR analysis revealed that the expression of classical UPR chaperone genes was not altered by overexpression of APP.Interestingly, the induction of the ER stress-responsive pro-apoptotic transcription factor CHOP was significantly upregulated in APP-overexpressing cells in comparison to vectortransfected controls. Chelation of intracellular Ca2+ with BAPTA-AM revealed that enhanced CHOP expression after store depletion occured in a Ca2+-dependent manner in APPoverexpressing cells. Prevention of CHOP induction by BAPTA-AM and by RNA interference was also able to abrogate the potentiating effect of APP on thapsigargin-induced apoptosis. Application of the store-operated channel (SOC)-inhibitors SK F96365 and 2-APB downmodulated APP-triggered potentiation of cytosolic Ca2+ levels and apoptosis after treatment with thapsigargin. Our data demonstrate that APP-mediated regulation of ER Ca2+ homeostasis significantly modulates Ca2+ store depletion-induced cell death in a SOC- and CHOP-dependent manner, but independent of the UPR.
Chemical ozone loss in winter 1991–1992 is recalculated based on observations of the HALOE satellite instrument, Version 19, ER-2 aircraft measurements and balloon data. HALOE satellite observations are shown to be reliable in the lower stratosphere below 400 K, at altitudes where the measurements are most likely disturbed by the enhanced sulfate aerosol loading, as a result of the Mt.~Pinatubo eruption in June 1991. Significant chemical ozone loss (13–17 DU) is observed below 380 K from Kiruna balloon observations and HALOE satellite data between December 1991 and March 1992. For the two winters after the Mt. Pinatubo eruption, HALOE satellite observations show a stronger extent of chemical ozone loss towards lower altitudes compared to other Arctic winters between 1991 and 2003. In spite of already occurring deactivation of chlorine in March 1992, MIPAS-B and LPMA balloon observations indicate that chlorine was still activated at lower altitudes, consistent with observed chemical ozone loss occurring between February and March and April. Large chemical ozone loss of more than 70 DU in the Arctic winter 1991–1992 as calculated in earlier studies is corroborated here.
Background The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe. Methods In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid. Results Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different. Conclusion Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection. Trial registration : ISRCTN66478538
Background: Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and down-regulation of its major intracellular receptor, the alpha/beta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of sGC's heme and responsiveness to NO.
Results: sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here we show that oxidation-induced down-regulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand, BAY 58-2667, prevented sGC ubiquitination and stabilized both alpha and beta subunits.
Conclusion: Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC.
This article shows that investors financing a portfolio of projects may use the depth of their financial pockets to overcome entrepreneurial incentive problems. Competition for scarce informed capital at the refinancing stage strengthens investors’ bargaining positions. And yet, entrepreneurs’ incentives may be improved, because projects funded by investors with ‘‘shallow pockets’’ must have not only a positive net present value at the refinancing stage, but one that is higher than that of competing portfolio projects. Our article may help understand provisions used in venture capital finance that limit a fund’s initial capital and make it difficult to add more capital once the initial venture capital fund is raised. (JEL G24, G31)
This paper shows that active investors, such as venture capitalists, can affect the speed at which new ventures grow. In the absence of product market competition, new ventures financed by active investors grow faster initially, though in the long run those financed by passive investors are able to catch up. By contrast, in a competitive product market, new ventures financed by active investors may prey on rivals that are financed by passive investors by “strategically overinvesting” early on, resulting in long-run differences in investment, profits, and firm growth. The value of active investors is greater in highly competitive industries as well as in industries with learning curves, economies of scope, and network effects, as is typical for many “new economy” industries. For such industries, our model predicts that start-ups with access to venture capital may dominate their industry peers in the long run. JEL Classifications: G24; G32 Keywords: Venture capital; dynamic investment; product market competition
We study a model of “information-based entrenchment” in which the CEO has private information that the board needs to make an efficient replacement decision. Eliciting the CEO’s private information is costly, as it implies that the board must pay the CEO both higher severance pay and higher on-the-job pay. While higher CEO pay is associated with higher turnover in our model, there is too little turnover in equilibrium. Our model makes novel empirical predictions relating CEO turnover, severance pay, and on-the-job pay to firm-level attributes such as size, corporate governance, and the quality of the firm’s accounting system.
This paper argues that banks must be sufficiently levered to have first-best incentives to make new risky loans. This result, which is at odds with the notion that leverage invariably leads to excessive risk taking, derives from two key premises that focus squarely on the role of banks as informed lenders. First, banks finance projects that they do not own, which implies that they cannot extract all the profits. Second, banks conduct a credit risk analysis before making new loans. Our model may help understand why banks take on additional unsecured debt, such as unsecured deposits and subordinated loans, over and above their existing deposit base. It may also help understand why banks and finance companies have similar leverage ratios, even though the latter are not deposit takers and hence not subject to the same regulatory capital requirements as banks.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.