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Inhibitor of apoptosis (IAPs) proteins are characterized by the presence of evolutionarily conserved baculoviral inhibitor of apoptosis repeat (BIR) domains, predominantly known for their role in inhibiting caspases and, thereby, apoptosis. We have shown previously that multi-BIR domain-containing IAPs, cellular IAPs, and X-linked IAP can control tumor cell migration by directly regulating the protein stability of C-RAF kinase. Here, we extend our observations to a single BIR domain containing IAP family member melanoma-IAP (ML-IAP). We show that ML-IAP can directly bind to C-RAF and that ML-IAP depletion leads to an increase in C-RAF protein levels, MAPK activation, and cell migration in melanoma cells. Thus, our results unveil a thus far unknown role for ML-IAP in controlling C-RAF stability and cell migration.
ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions
(2012)
ADAM15, a disintegrin and metalloproteinase, is capable of counteracting genotoxic stress-induced apoptosis by the suppression of caspase-3 activation. A cell line expressing the membrane-bound ADAM15 without its cytoplasmic tail, however, lost this anti-apoptotic property, suggesting a crucial role of the intracellular domain as a scaffold for recruitment of survival signal-transducing kinases. Accordingly, an enhanced phosphorylation of FAK at Tyr-397, Tyr-576, and Tyr-861 was detected upon genotoxic stress by camptothecin in ADAM15-transfected T/C28a4 cells, but not in transfectants expressing an ADAM15 mutant without the cytoplasmic tail. Accordingly, a specific binding of the cytoplasmic ADAM15 domain to the C terminus of FAK could be shown by mammalian two-hybrid, pulldown, and far Western studies. In cells expressing full-length ADAM15, a concomitant activation of Src at Tyr-416 was detected upon camptothecin exposure. Cells transfected with a chimeric construct consisting of the extracellular IL-2 receptor α-chain and the cytoplasmic ADAM15 domain were IL-2-stimulated to prove that the ADAM15 tail can transduce a percepted extracellular signal to enhance FAK and Src phosphorylation. Our studies further demonstrate Src binding to FAK but not a direct Src interaction with ADAM15, suggesting FAK as a critical intracellular adaptor for ADAM15-dependent enhancement of FAK/Src activation. Moreover, the apoptosis induction elicited by specific inhibitors (PP2, FAK 14 inhibitor) of FAK/Src signaling was significantly reduced by ADAM15 expression. The newly uncovered counter-regulatory response to genotoxic stress in a chondrocytic survival pathway is potentially also relevant to apoptosis resistance in neoplastic growth.
The social amoeba Dictyostelium discoideum is a widely used model organism for studying basic functions of protozoan and metazoan cells, such as osmoregulation and cell motility. There is evidence from other species that cellular water channels, aquaporins (AQP), are central to both processes. Yet, data on D. discoideum AQPs is almost absent. Despite cloning of two putative D. discoideum AQPs, WacA, and AqpA, water permeability has not been shown. Further, WacA and AqpA are expressed at the late multicellular stage and in spores but not in amoebae. We cloned a novel AQP, AqpB, from amoeboidal D. discoideum cells. Wild-type AqpB was impermeable to water, glycerol, and urea when expressed in Xenopus laevis oocytes. Neither stepwise truncation of the N terminus nor selected point mutations activated the water channel. However, mutational truncation by 12 amino acids of an extraordinary long intracellular loop induced water permeability of AqpB, hinting at a novel gating mechanism. This AqpB mutant was inhibited by mercuric chloride, confirming the presence of a cysteine residue in the selectivity filter as predicted by our structure model. We detected AqpB by Western blot analysis in a glycosylated and a non-glycosylated form throughout all developmental stages. When expressed in D. discoideum amoebae, AqpB-GFP fusion constructs localized to vacuolar structures, to the plasma membrane, and to lamellipodia-like membrane protrusions. We conclude that the localization pattern in conjunction with channel gating may be indicative of AqpB functions in osmoregulation as well as cell motility of D. discoideum.
Mitochondria and chloroplasts are of endosymbiotic origin. Their integration into cells entailed the development of protein translocons, partially by recycling bacterial proteins. We demonstrate the evolutionary conservation of the translocon component Tic22 between cyanobacteria and chloroplasts. Tic22 in Anabaena sp. PCC 7120 is essential. The protein is localized in the thylakoids and in the periplasm and can be functionally replaced by a plant orthologue. Tic22 physically interacts with the outer envelope biogenesis factor Omp85 in vitro and in vivo, the latter exemplified by immunoprecipitation after chemical cross-linking. The physical interaction together with the phenotype of a tic22 mutant comparable with the one of the omp85 mutant indicates a concerted function of both proteins. The three-dimensional structure allows the definition of conserved hydrophobic pockets comparable with those of ClpS or BamB. The results presented suggest a function of Tic22 in outer membrane biogenesis.
Background: Although Tic22 is involved in protein import into chloroplasts, the function in cyanobacteria is unknown.
Results: Cyanobacterial Tic22 is required for OM biogenesis, shares structural features with chaperones, and can be substituted by plant Tic22.
Conclusion: Tic22, involved in outer membrane biogenesis, is functionally conserved in cyanobacteria and plants.
Significance: The findings are important for the understanding of periplasmic protein transport.
Background: Radiofrequency ablation is a minimal invasive therapy in the treatment of bone metastases. In this study we present a new ablation system enabling an ablation in multiple directions and with an adaptable size and shape.
Material and methods: VX-2 tumor was used for the induction of experimental bone metastases in the femur of six New Zealand white rabbits. X-ray imaging as well as CT and MRI scans before and after treatment was carried out. After detecting bone tumor, radiofrequency ablation was performed. The ablation instrument contained a 10 g bipolar, articulated extendable electrode and a proprietary generator with an impedance controlled algorithm. All bones and the soft tissue were examined histologically.
Results: All animals developed local bone tumor. Mean duration until first osteolytic lesions on CT-scans was 48±14 days. The mean lesion area was 26 mm(2). No systemic tumor spread was seen. 6 radiofrequency procedures were carried out with a mean application time of 6 min±2:30 and an average temperature in the region of effect of 55 °C±4. MRI imaging demonstrated an ablation zone of 23±6 mm around the electrode. Histopathology showed an extensive heat necrosis with no remaining tumor cells in the ablation area.
Conclusion: Radiofrequency ablation is a quickly developing treatment option on the field of minimal invasive bone tumor therapy. The electrode enables an ablation adapted to size and shape of the metastases. Further clinical studies are necessary to test and enhance this radiofrequency system.
Lantibiotics are peptide-derived antibiotics that inhibit the growth of Gram-positive bacteria via interactions with lipid II and lipid II-dependent pore formation in the bacterial membrane. Due to their general mode of action the Gram-positive producer strains need to express immunity proteins (LanI proteins) for protection against their own lantibiotics. Little is known about the immunity mechanism protecting the producer strain against its own lantibiotic on the molecular level. So far, no structures have been reported for any LanI protein. We solved the structure of SpaI, a LanI protein from the subtilin producing strain Bacillus subtilis ATCC 6633. SpaI is a 16.8-kDa lipoprotein that is attached to the outside of the cytoplasmic membrane via a covalent diacylglycerol anchor. SpaI together with the ABC transporter SpaFEG protects the B. subtilis membrane from subtilin insertion. The solution-NMR structure of a 15-kDa biologically active C-terminal fragment reveals a novel fold. We also demonstrate that the first 20 N-terminal amino acids not present in this C-terminal fragment are unstructured in solution and are required for interactions with lipid membranes. Additionally, growth tests reveal that these 20 N-terminal residues are important for the immunity mediated by SpaI but most likely are not part of a possible subtilin binding site. Our findings are the first step on the way of understanding the immunity mechanism of B. subtilis in particular and of other lantibiotic producing strains in general.
Escherichia coli nitrate reductase A (NarGHI) is a membrane-bound enzyme that couples quinol oxidation at a periplasmically oriented Q-site (Q(D)) to proton release into the periplasm during anaerobic respiration. To elucidate the molecular mechanism underlying such a coupling, endogenous menasemiquinone-8 intermediates stabilized at the Q(D) site (MSQ(D)) of NarGHI have been studied by high-resolution pulsed EPR methods in combination with (1)H2O/2H2O exchange experiments. One of the two non-exchangeable proton hyperfine couplings resolved in hyperfine sublevel correlation (HYSCORE) spectra of the radical displays characteristics typical from quinone methyl protons. However, its unusually small isotropic value reflects a singularly low spin density on the quinone carbon α carrying the methyl group, which is ascribed to a strong asymmetry of the MSQ(D) binding mode and consistent with single-sided hydrogen bonding to the quinone oxygen O1. Furthermore, a single exchangeable proton hyperfine coupling is resolved, both by comparing the HYSCORE spectra of the radical in 1H2O and 2H2O samples and by selective detection of the exchanged deuterons using Q-band 2H Mims electron nuclear double resonance (ENDOR) spectroscopy. Spectral analysis reveals its peculiar characteristics, i.e. a large anisotropic hyperfine coupling together with an almost zero isotropic contribution. It is assigned to a proton involved in a short ∼1.6 Å in-plane hydrogen bond between the quinone O1 oxygen and the Nδ of the His-66 residue, an axial ligand of the distal heme b(D). Structural and mechanistic implications of these results for the electron-coupled proton translocation mechanism at the Q(D) site are discussed, in light of the unusually high thermodynamic stability of MSQ(D).
We proposed previously that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane after ethanol exposure leads to suppression of mitochondrial metabolite exchange. Because ureagenesis requires extensive mitochondrial metabolite exchange, we characterized the effect of ethanol and its metabolite, acetaldehyde (AcAld), on total and ureagenic respiration in cultured rat hepatocytes. Ureagenic substrates increased cellular respiration from 15.8 ± 0.9 nmol O(2)/min/10(6) cells (base line) to 29.4 ± 1.7 nmol O(2)/min/10(6) cells in about 30 min. Ethanol (0-200 mM) suppressed extra respiration after ureagenic substrates (ureagenic respiration) by up to 51% but not base line respiration. Urea formation also declined proportionately. Inhibition of alcohol dehydrogenase, cytochrome P450 2E1, and catalase with 4-methylpyrazole, trans-1,2-dichloroethylene, and 3-amino-1,2,3-triazole restored ethanol-suppressed ureagenic respiration by 46, 37, and 66%, respectively. By contrast, inhibition of aldehyde dehydrogenase with phenethyl isothiocyanate increased the inhibitory effect of ethanol on ureagenic respiration by an additional 60%. AcAld, an intermediate product of ethanol oxidation, suppressed ureagenic respiration with an apparent IC(50) of 125 μM. AcAld also inhibited entry of 3-kDa rhodamine-conjugated dextran in the mitochondrial intermembrane space of digitonin-permeabilized hepatocytes, indicative of VDAC closure. In conclusion, AcAld, derived from ethanol metabolism, suppresses ureagenesis in hepatocytes mediated by closure of VDAC.
DNA translocators of natural transformation systems are complex systems critical for the uptake of free DNA and provide a powerful mechanism for adaptation to changing environmental conditions. In natural transformation machineries, outer membrane secretins are suggested to form a multimeric pore for the uptake of external DNA. Recently, we reported on a novel structure of the DNA translocator secretin complex, PilQ, in Thermus thermophilus HB27 comprising a stable cone and cup structure and six ring structures with a large central channel. Here, we report on structural and functional analyses of a set of N-terminal PilQ deletion derivatives in T. thermophilus HB27. We identified 136 N-terminal residues exhibiting an unusual ααβαββα fold as a ring-building domain. Deletion of this domain had a dramatic effect on twitching motility, adhesion, and piliation but did not abolish natural transformation. These findings provide clear evidence that the pilus structures of T. thermophilus are not essential for natural transformation. The truncated complex was not affected in inner and outer membrane association, indicating that the 136 N-terminal residues are not essential for membrane targeting. Analyses of complex formation of the truncated PilQ monomers revealed that the region downstream of residue 136 is required for multimerization, and the region downstream of residue 207 is essential for monomer stability. Possible implications of our findings for the mechanism of DNA uptake are discussed.
Searching for new strategies to trigger apoptosis in rhabdomyosarcoma (RMS), we investigated the effect of two novel classes of apoptosis-targeting agents, i.e. monoclonal antibodies against TNF-related apoptosis-inducing ligand (TRAIL) receptor 1 (mapatumumab) and TRAIL receptor 2 (lexatumumab) and small-molecule inhibitors of inhibitor of apoptosis (IAP) proteins. Here, we report that IAP inhibitors synergized with lexatumumab, but not with mapatumumab, to reduce cell viability and to induce apoptosis in several RMS cell lines in a highly synergistic manner (combination index <0.1). Cotreatment-induced apoptosis was accompanied by enhanced activation of caspase-8, -9, and -3; loss of mitochondrial membrane potential; and caspase-dependent apoptosis. In addition, IAP inhibitor and lexatumumab cooperated to stimulate the assembly of a cytosolic complex containing RIP1, FADD, and caspase-8. Importantly, knockdown of RIP1 by RNA interference prevented the formation of the RIP1·FADD·caspase-8 complex and inhibited subsequent activation of caspase-8, -9, and -3; loss of mitochondrial membrane potential; and apoptosis upon treatment with IAP inhibitor and lexatumumab. In addition, RIP1 silencing rescued clonogenic survival of cells treated with the combination of lexatumumab and IAP inhibitor, thus underscoring the critical role of RIP1 in cotreatment-induced apoptosis. By comparison, the TNFα-blocking antibody Enbrel had no effect on IAP inhibitor/lexatumumab-induced apoptosis, indicating that an autocrine TNFα loop is dispensable. By demonstrating that IAP inhibitors and lexatumumab synergistically trigger apoptosis in a RIP1-dependent but TNFα-independent manner in RMS cells, our findings substantially advance our understanding of IAP inhibitor-mediated regulation of TRAIL-induced cell death.
A simple and fast method of lipid analysis of isolated intact mitochondria by means of MALDI-TOF mass spectrometry is described. Mitochondria isolated from bovine heart and yeast have been employed to set up and validate the new method of lipid analysis. The mitochondrial suspension is directly applied over the target and, after drying, covered by a thin layer of the 9-aminoacridine matrix solution. The lipid profiles acquired with this procedure contain all peaks previously obtained by analyzing the lipid extracts of isolated mitochondria by TLC and/or mass spectrometry. The novel procedure allows the quick, simple, precise, and accurate analysis of membrane lipids, utilizing only a tiny amount of isolated organelle; it has also been tested with intact membranes of the bacterium Paracoccus denitrificans for its evolutionary link to present-day mitochondria. The method is of general validity for the lipid analysis of other cell fractions and isolated organelles.
Membrane-embedded β-barrel proteins are found in the outer membranes (OM) of Gram-negative bacteria, mitochondria and chloroplasts. In eukaryotic cells, precursors of these proteins are synthesized in the cytosol and have to be sorted to their corresponding organelle. Currently, the signal that ensures their specific targeting to either mitochondria or chloroplasts is ill-defined. To address this issue, we studied targeting of the chloroplast β-barrel proteins Oep37 and Oep24. We found that both proteins can be integrated in vitro into isolated plant mitochondria. Furthermore, upon their expression in yeast cells Oep37 and Oep24 were exclusively located in the mitochondrial OM. Oep37 partially complemented the growth phenotype of yeast cells lacking Porin, the general metabolite transporter of this membrane. Similarly to mitochondrial β-barrel proteins, Oep37 and Oep24 expressed in yeast cells were assembled into the mitochondrial OM in a pathway dependent on the TOM and TOB complexes. Taken together, this study demonstrates that the central mitochondrial components that mediate the import of yeast β-barrel proteins can deal with precursors of chloroplast β-barrel proteins. This implies that the mitochondrial import machinery does not recognize signals that are unique to mitochondrial β-barrel proteins. Our results further suggest that dedicated targeting factors had to evolve in plant cells to prevent mis-sorting of chloroplast β-barrel proteins to mitochondria.
The role of TolC has largely been explored in proteobacteria, where it functions as a metabolite and protein exporter. In contrast, little research has been carried out on the function of cyanobacterial homologues, and as a consequence, not much is known about the mechanism of cyanobacterial antibiotic uptake and metabolite secretion in general. It has been suggested that the TolC-like homologue of the filamentous, heterocyst-forming cyanobacterium Anabaena sp. PCC 7120, termed heterocyst glycolipid deposition protein D (HgdD), is involved in both protein and lipid secretion. To describe its function in secondary metabolite secretion, we established a system to measure the uptake of antibiotics based on the fluorescent molecule ethidium bromide. We analyzed the rate of porin-dependent metabolite uptake and confirmed the functional relation between detoxification and the action of HgdD. Moreover, we identified two major facilitator superfamily proteins that are involved in this process. It appears that anaOmp85 (Alr2269) is not required for insertion or assembly of HgdD, because an alr2269 mutant does not exhibit a phenotype similar to the hgdD mutant. Thus, we could assign components of the metabolite efflux system and describe parameters of detoxification by Anabaena sp. PCC 7120.
Protein-tyrosine phosphatases (PTPs) and protein-tyrosine kinases co-regulate cellular processes. In pathogenic bacteria, they are frequently exploited to act as key virulence factors for human diseases. Mycobacterium tuberculosis, the causative organism of tuberculosis, secretes a low molecular weight PTP (LMW-PTP), MptpA, which is required for its survival upon infection of host macrophages. Although there is otherwise no sequence similarity of LMW-PTPs to other classes of PTPs, the phosphate binding loop (P-loop) CX5R and the loop containing a critical aspartic acid residue (D-loop), required for the catalytic activity, are well conserved. In most high molecular weight PTPs, ligand binding to the P-loop triggers a large conformational reorientation of the D-loop, in which it moves ∼10 Å, from an “open” to a “closed” conformation. Until now, there have been no ligand-free structures of LMW-PTPs described, and hence the dynamics of the D-loop have remained largely unknown for these PTPs. Here, we present a high resolution solution NMR structure of the free form of the MptpA LMW-PTP. In the absence of ligand and phosphate ions, the D-loop adopts an open conformation. Furthermore, we characterized the binding site of phosphate, a competitive inhibitor of LMW-PTPs, on MptpA and elucidated the involvement of both the P- and D-loop in phosphate binding. Notably, in LMW-PTPs, the phosphorylation status of two well conserved tyrosine residues, typically located in the D-loop, regulates the enzyme activity. PtkA, the kinase complementary to MptpA, phosphorylates these two tyrosine residues in MptpA. We characterized the MptpA-PtkA interaction by NMR spectroscopy to show that both the P- and D-loop form part of the binding interface.
Infrared spectroscopy in combination with a specially developed attenuated total reflection (ATR) flow cell and multivariate analysis was used for the quantitative analysis of beer and other beverages. IR spectra of samples were obtained in the range from below 1000 cm-1 to 4000 cm-1 and subjected to a multivariate analysis based on calibration sets with laboratory reference standards. In the case of beer, this calibration set included 240 beer samples spanning the entire range of ethanol content, extract and CO2. Based on this calibration, an infrared and UV/Vis spectroscopy-based sensor for the quick and quantitative quality control of beer was developed and subjected to extensive tests in breweries. This sensor meets and exceeds all requirements from brewers for the routine control in the production and bottling. Its use for other beverages, for example wine, juices or apple wine, requires only another set of calibration data for the specific beverage.
Transmetallation and oxidative substitution were utilized to prepare examples of group 14, group 6 and group 10 complexes from lithiated or chlorinated 4,4-dimethyl-2-(2-thienyl) oxazoline or its N-alkylated analogs. Two of the product types (2and 5) can be classified as a-thio or remote carbene complexes, depending on the position (3- or 5-) of attachment to the substituted thiophene ring. Spectroscopic measurements as well as crystal and molecular structure determinations clarified the bonding within the new compounds.
The bis(trimethyl)silylamido complex Na(THF){Fe[N(SiMe3)2]3} and the disilane tBu3SiSitBu3 were obtained from the reaction of Fe[N(SiMe3)2]3 with the sodium silanide Na(THF)2[SitBu3] in a mixture of benzene and THF. Single crystals of Na(THF){Fe[N(SiMe3)2]3} suitable for X-ray diffraction were grown from the reaction solution at ambient temperature (orthorhombic, C2221, Z = 4). The solid-state structure features a contact-ion pair with two short N-Na contacts. The THF adducts {M(THF)2[N(SiMe3)2]2} reacted with 2,2´-bipyridine to give the corresponding complexes {M(2,2´bipy)[N(SiMe3)2]2} (M= Mn; Fe). Their structures (M= Fe: orthorhombic, Pca21, Z = 8; M = Mn: orthorhombic, Pbca, Z = 8) feature monomeric units. The cyclic voltammogram of Fe[N(SiMe3)2]3 revealed a reversible redox transition with the potential of -0;523 V (E½), which was assigned to the Fe(III)[N(SiMe3)2]3 → Fe(II)[N(SiMe3)2]-3 redox transition, whereas the compounds {Fe(THF)2[N(SiMe3)2]2} (Eox = -0;379 V) and {Fe(2,2´bipy)[N(SiMe3)2]2} (Eox = -0;436 V) featured irreversible oxidation waves. The related manganese bis(trimethylsilyl)amido complexes {Mn(THF)2[N(SiMe3)2]2} (Eox = -0;458 V) and {Mn(2,2´bipy)[N(SiMe3)2]2} (Eox = -0513 V) also underwent irreversibile electron transfer processes.
The enantioselective synthesis of 2-aryl-substituted 2,3-dihydroquinolin-4-ones, a class of heterocyclic compounds with interesting biological activities, has been achieved through a Brønsted acidcatalyzed enantioselective intramolecular Michael addition. The products are available in moderate to high yields and with good enantioselectivities.
Dodecins, a group of flavin-binding proteins with a dodecameric quaternary structure, are able to incorporate two flavins within each of their six identical binding pockets building an aromatic tetrade with two tryptophan residues. Dodecin from the archaeal Halobacterium salinarum is a riboflavin storage device. We demonstrate that unwanted side reactions induced by reactive riboflavin species and degradation of riboflavin are avoided by ultrafast depopulation of the reactive excited state of riboflavin. Intriguingly, in this process, the staggered riboflavin dimers do not interact in ground and photoexcited states. Rather, within the tetrade assembly, each riboflavin is kept under the control of the respective adjacent tryptophan, which suggests that the stacked arrangement is a matter of optimizing the flavin load. We further identify an electron transfer in combination with a proton transfer as a central element of the effective excited state depopulation mechanism. Structural and functional comparisons of the archaeal dodecin with bacterial homologs reveal diverging evolution. Bacterial dodecins bind the flavin FMN instead of riboflavin and exhibit a clearly different binding pocket design with inverse incorporations of flavin dimers. The different adoption of flavin changes photochemical properties, making bacterial dodecin a comparably less efficient quencher of flavins. This supports a functional role different for bacterial and archaeal dodecins.
The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface.
The Wood-Ljungdahl pathway of anaerobic CO(2) fixation with hydrogen as reductant is considered a candidate for the first life-sustaining pathway on earth because it combines carbon dioxide fixation with the synthesis of ATP via a chemiosmotic mechanism. The acetogenic bacterium Acetobacterium woodii uses an ancient version of the pathway that has only one site to generate the electrochemical ion potential used to drive ATP synthesis, the ferredoxin-fueled, sodium-motive Rnf complex. However, hydrogen-based ferredoxin reduction is endergonic, and how the steep energy barrier is overcome has been an enigma for a long time. We have purified a multimeric [FeFe]-hydrogenase from A. woodii containing four subunits (HydABCD) which is predicted to have one [H]-cluster, three [2Fe2S]-, and six [4Fe4S]-clusters consistent with the experimental determination of 32 mol of Fe and 30 mol of acid-labile sulfur. The enzyme indeed catalyzed hydrogen-based ferredoxin reduction, but required NAD(+) for this reaction. NAD(+) was also reduced but only in the presence of ferredoxin. NAD(+) and ferredoxin reduction both required flavin. Spectroscopic analyses revealed that NAD(+) and ferredoxin reduction are strictly coupled and that they are reduced in a 1:1 stoichiometry. Apparently, the multimeric hydrogenase of A. woodii is a soluble energy-converting hydrogenase that uses electron bifurcation to drive the endergonic ferredoxin reduction by coupling it to the exergonic NAD(+) reduction.
Cytochrome c oxidase (COX), the last enzyme of the respiratory chain of aerobic organisms, catalyzes the reduction of molecular oxygen to water. It is a redox-linked proton pump, whose mechanism of proton pumping has been controversially discussed, and the coupling of proton and electron transfer is still not understood. Here, we investigated the kinetics of proton transfer reactions following the injection of a single electron into the fully oxidized enzyme and its transfer to the hemes using time-resolved absorption spectroscopy and pH indicator dyes. By comparison of proton uptake and release kinetics observed for solubilized COX and COX-containing liposomes, we conclude that the 1-μs electron injection into CuA, close to the positive membrane side (P-side) of the enzyme, already results in proton uptake from both the P-side and the N (negative)-side (1.5 H+/COX and 1 H+/COX, respectively). The subsequent 10-μs transfer of the electron to heme a is accompanied by the release of 1 proton from the P-side to the aqueous bulk phase, leaving ∼0.5 H+/COX at this side to electrostatically compensate the charge of the electron. With ∼200 μs, all but 0.4 H+ at the N-side are released to the bulk phase, and the remaining proton is transferred toward the hemes to a so-called “pump site.” Thus, this proton may already be taken up by the enzyme as early as during the first electron transfer to CuA. These results support the idea of a proton-collecting antenna, switched on by electron injection.
Verb production in stroke induced aphasia and semantic dementia: similarities and dissociations
(2012)
Altered metabolism in tumor cells is increasingly recognized as a core component of the neoplastic phenotype. Because p53 has emerged as a master metabolic regulator, we hypothesized that the presence of wild-type p53 in glioblastoma cells could confer a selective advantage to these cells under the adverse conditions of the glioma microenvironment. Here, we report on the effects of the p53-dependent effector Tp53-induced glycolysis and apoptosis regulator (TIGAR) on hypoxia-induced cell death. We demonstrate that TIGAR is overexpressed in glioblastomas and that ectopic expression of TIGAR reduces cell death induced by glucose and oxygen restriction. Metabolic analyses revealed that TIGAR inhibits glycolysis and promotes respiration. Further, generation of reactive oxygen species (ROS) levels was reduced whereas levels of reduced glutathione were elevated in TIGAR-expressing cells. Finally, inhibiting the transketolase isoenzyme transketolase-like 1 (TKTL1) by siRNA reversed theses effects of TIGAR. These findings suggest that glioma cells benefit from TIGAR expression by (i) improving energy yield from glucose via increased respiration and (ii) enhancing defense mechanisms against ROS. Targeting metabolic regulators such as TIGAR may therefore be a valuable strategy to enhance glioma cell sensitivity toward spontaneously occurring or therapy-induced starvation conditions or ROS-inducing therapeutic approaches.
Introduction. Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.
Material and methods. Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa2a (40KD) 180 or 90 Mg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.
Results. The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.
Conclusion. Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
Introduction: We report on successful endovascular treatment of a hydrofluoric acid burn to the hand.
Report: A worker complained of severe pain in the fingers D II to D V after injury with 60% hydrofluoric acid. A digital subtraction angiography showed vasospasm of the common palmar digital artery. We selectively applied 20% calcium gluconate intra-arterially.
After treatment all arteries were perfused. Alprostadil, acetylsalicylic acid and clopidogrel were administered in conjunction. Pain symptoms improved and sensory and motor functions were restored.
Discussion: Immediate angiography and intra-arterial application of calcium gluconate are recommended to treat hydrofluoric acid burn to a limb.
Background: The transcription factor T-bet is pivotal for initiation of Th1-related immunoactivation. Identification of novel genes directly regulated by T-bet is crucial.
Results: Genome-wide analysis and subsequent experiments revealed that T-bet up-regulates IL-36γ/IL-1F9 in myeloid cells.
Conclusion: IL-1-related IL-36γ is a direct T-bet target in myeloid cells.
Significance: Observations suggest that IL-36γ , besides IFNγ, contributes to T-bet functions in immunopathology
By concerted action in dendritic (DC) and T cells, T-box expressed in T cells (T-bet, Tbx21) is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet-regulated genes is crucial for further understanding the biology of this transcription factor. By combining siRNA technology with genome-wide mRNA expression analysis, we sought to identify new T-bet-regulated genes in predendritic KG1 cells activated by IL-18. One gene robustly dependent on T-bet was IL-36γ, a recently described novel IL-1 family member. Promoter analysis revealed a T-bet binding site that, along with a κB site, enables efficient IL-36γ induction. Using knock-out animals, IL-36γ reliance on T-bet was extended to murine DC. IL-36γ expression by human myeloid cells was confirmed using monocyte-derived DC and M1 macrophages. The latter model was employed to substantiate dependence of IL-36γ on endogenous T-bet in human primary cells. Ectopic expression of T-bet likewise mediated IL-36γ production in HaCaT keratinocytes that otherwise lack this transcription factor. Additional experiments furthermore revealed that mature IL-36γ has the capability to establish an inflammatory gene expression profile in human primary keratinocytes that displays enhanced mRNA levels for TNFα, CCL20, S100A7, inducible NOS, and IL-36γ itself. Data presented herein shed further light on involvement of T-bet in innate immunity and suggest that IL-36γ, besides IFNγ, may contribute to functions of this transcription factor in immunopathology.
Ubiquitin-binding modules are constituents of cellular proteins that mediate the effects of ubiquitylation by making transient, non-covalent interactions with ubiquitin molecules. While some ubiquitin-binding modules bind single ubiquitin moieties, others are selective for specific ubiquitin chains of different linkage types and lengths. In recent years, functions of ubiquitin chains that are polymerized through their Lys or N-terminal Met (i.e. linear chains) residues have been linked to a variety of cellular processes. Selectivity of ubiquitin-binding modules for different ubiquitin chain types appears as a key to the distinct regulatory consequences during protein quality control pathways, receptor endocytosis, gene transcription, signaling via the NF-κB pathway, and autophagy.
Recent data have clearly shown that a sustained virologic response can be achieved in different HCV infected patient populations with various interferon-free treatment regimens. Despite the successful implementation of telaprevir- and boceprevir-based triple therapies, all-oral regimens will certainly become a first choice for a number of HCV-infected patients in the very near future, as triple therapy approaches are burdened with significant side-effects and limited success in patients with advanced liver fibrosis and prior null-response to pegylated interferon-α (pegIFN-α)/ribavirin therapy. However, available data from phase I and II clinical trials evaluating interferon-free regimens have not yet revealed a clearly outstanding all-oral combination, and numerous challenges remain to be addressed by intensive ongoing and future research. In particular, thus far evaluated all-oral regimens did not cure a satisfactory percentage of patients with unfavorable baseline characteristics, namely patients infected with HCV genotype 1a, previous null-response to pegIFN-α/ribavirin, or liver cirrhosis. In this review, we summarize available data of interferon-free regimens for the treatment of chronic hepatitis C and assess implications for perspectives and challenges in the further development of all-oral therapies.
We investigate the ratios βη≡η/τπ and βζ≡ζ/τΠ, i.e., the ratios of shear, η, and bulk, ζ, viscosities to the relaxation times τπ, τΠ of the shear stress tensor and bulk viscous pressure, respectively, in the framework of causal relativistic dissipative fluid dynamics. These viscous transport coefficients are computed both in a field-theoretical and a kinetic approach based on the Boltzmann equation. Our results differ from those of the traditional Boltzmann calculation by Israel and Stewart. The new expressions for the viscous transport coefficients agree with the results obtained in the field-theoretical approach when the contributions from pair annihilation and creation (PAC) are neglected. The latter induce non-negligible corrections to the viscous transport coefficients.
Using a microscopic transport model we investigate the evolution of conical structures originating from the supersonic projectile moving through the hot matter of ultrarelativistic particles. Using different scenarios for the interaction between projectile and matter, and different transport properties of the matter, we study the formation and structure of Mach cones. Especially, a dependence of the Mach cone angle on the details and rate of the energy deposition from projectile to the matter is investigated. Furthermore, the two-particle correlations extracted from the numerical calculations are compared to an analytical approximation. We find that the propagation of a high energetic particle through the matter does not lead to the appearance of a double peak structure as observed in the ultrarelativistic heavy-ion collision experiments. The reason is the strongly forward-peaked energy and momentum deposition in the head shock region. In addition, by adjusting the cross section we investigate the influence of the viscosity to the structure of Mach cones. A clear and unavoidable smearing of the profile depending on a finite ratio of shear viscosity to entropy density is clearly visible.
Driven by the loss of energy, isolated rotating neutron stars (pulsars) are gradually slowing down to lower frequencies, which increases the tremendous compression of the matter inside of them. This increase in compression changes both the global properties of rotating neutron stars as well as their hadronic core compositions. Both effects may register themselves observationally in the thermal evolution of such stars, as demonstrated in this Letter. The rotation-driven particle process which we consider here is the direct Urca (DU) process, which is known to become operative in neutron stars if the number of protons in the stellar core exceeds a critical limit of around 11% to 15%. We find that neutron stars spinning down from moderately high rotation rates of a few hundred Hertz may be creating just the right conditions where the DU process becomes operative, leading to an observable effect (enhanced cooling) in the temperature evolution of such neutron stars. As it turns out, the rotation-driven DU process could explain the unusual temperature evolution observed for the neutron star in Cas A, provided the mass of this neutron star lies in the range of 1.5 to 1.9M⊙ and its rotational frequency at birth was between 40 (400 Hz) and 70% (800 Hz) of the Kepler (mass shedding) frequency, respectively.
The spatial configuration of initial partons in high multiplicity proton–proton scatterings at 14 TeV is assumed as three randomly positioned “hot spots”. The parton momentum distribution in the hot spots is calculated by HIJING2.0 with some modifications. This initial condition causes not only large eccentricity ϵ2 but also triangularity ϵ3 and the correlation of ϵ2−ϵ3 event-plane angles. The final elliptic flow v2, triangular flow v3, and the correlation of v2−v3 event-plane angles are calculated by using the parton cascade model BAMPS to simulate the space–time parton evolution. Our results show that the v2−v3 correlation is different from that of ϵ2−ϵ3. This finding indicates that translations of different Fourier components of the initial spatial asymmetry to the final flow components are not independent. A dynamical correlation between the elliptic and triangular flow appears during the collective expansion.
The ALICE Collaboration has measured inclusive J/ψ production in pp collisions at a center-of-mass energy √s=2.76 TeV at the LHC. The results presented in this Letter refer to the rapidity ranges |y|<0.9 and 2.5<y<4 and have been obtained by measuring the electron and muon pair decay channels, respectively. The integrated luminosities for the two channels are Linte=1.1 nb−1 and Lintμ=19.9 nb−1, and the corresponding signal statistics are NJ/ψe+e−=59±14 and NJ/ψμ+μ−=1364±53. We present dσJ/ψ/dy for the two rapidity regions under study and, for the forward-y range, d2σJ/ψ/dydpt in the transverse momentum domain 0<pt<8 GeV/c. The results are compared with previously published results at s=7 TeV and with theoretical calculations.
Identical neutral kaon pair correlations are measured in √s=7 TeV pp collisions in the ALICE experiment. One-dimensional Ks0Ks0 correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the a0/f0 resonance. Ks0Ks0 correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, mT, as seen in ππ correlations in pp collisions and in heavy-ion collisions. Transverse mass scaling is observed between the Ks0Ks0 and ππ radii. Also, the first observation is made of the decay of the f2′(1525) meson into the Ks0Ks0 channel in pp collisions.
A measurement of the multi-strange Ξ− and Ω− baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for inelastic proton–proton collisions at a centre-of-mass energy of 7 TeV. The transverse momentum (pT) distributions were studied at mid-rapidity (|y|<0.5) in the range of 0.6<pT<8.5 GeV/c for Ξ− and Ξ¯+ baryons, and in the range of 0.8<pT<5 GeV/c for Ω− and Ω¯+. Baryons and antibaryons were measured as separate particles and we find that the baryon to antibaryon ratio of both particle species is consistent with unity over the entire range of the measurement. The statistical precision of the current data has allowed us to measure a difference between the mean pT of Ξ− (Ξ¯+) and Ω− (Ω¯+). Particle yields, mean pT, and the spectra in the intermediate pT range are not well described by the PYTHIA Perugia 2011 tune Monte Carlo event generator, which has been tuned to reproduce the early LHC data. The discrepancy is largest for Ω− (Ω¯+). This PYTHIA tune approaches the pT spectra of Ξ− and Ξ¯+ baryons below pT<0.85 GeV/c and describes the Ξ− and Ξ¯+ spectra above pT>6.0 GeV/c. We also illustrate the difference between the experimental data and model by comparing the corresponding ratios of (Ω−+Ω¯+)/(Ξ−+Ξ¯+) as a function of transverse mass.
Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV
(2012)
The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations.
Harmonic decomposition of two particle angular correlations in Pb–Pb collisions at √sNN=2.76 TeV
(2012)
Angular correlations between unidentified charged trigger (t) and associated (a) particles are measured by the ALICE experiment in Pb–Pb collisions at √sNN=2.76 TeV for transverse momenta 0.25<pTt,a<15 GeV/c, where pTt>pTa. The shapes of the pair correlation distributions are studied in a variety of collision centrality classes between 0 and 50% of the total hadronic cross section for particles in the pseudorapidity interval |η|<1.0. Distributions in relative azimuth Δϕ≡ϕt−ϕa are analyzed for |Δη|≡|ηt−ηa|>0.8, and are referred to as “long-range correlations”. Fourier components VnΔ≡〈cos(nΔϕ)〉 are extracted from the long-range azimuthal correlation functions. If particle pairs are correlated to one another through their individual correlation to a common symmetry plane, then the pair anisotropy VnΔ(pTt,pTa) is fully described in terms of single-particle anisotropies vn(pT) as VnΔ(pTt,pTa)=vn(pTt)vn(pTa). This expectation is tested for 1⩽n⩽5 by applying a global fit of all VnΔ(pTt,pTa) to obtain the best values vn{GF}(pT). It is found that for 2⩽n⩽5, the fit agrees well with data up to pTa∼3–4 GeV/c, with a trend of increasing deviation as pTt and pTa are increased or as collisions become more peripheral. This suggests that no pair correlation harmonic can be described over the full 0.25<pT<15 GeV/c range using a single vn(pT) curve; such a description is however approximately possible for 2⩽n⩽5 when pTa<4 GeV/c. For the n=1 harmonic, however, a single v1(pT) curve is not obtained even within the reduced range pTa<4 GeV/c.
The ALICE Collaboration reports the measurement of the relative J/ψ yield as a function of charged particle pseudorapidity density dNch/dη in pp collisions at √s=7 TeV at the LHC. J/ψ particles are detected for pt>0, in the rapidity interval |y|<0.9 via decay into e+e−, and in the interval 2.5<y<4.0 via decay into μ+μ− pairs. An approximately linear increase of the J/ψ yields normalized to their event average (dNJ/ψ/dy)/〈dNJ/ψ/dy〉 with (dNch/dη)/〈dNch/dη〉 is observed in both rapidity ranges, where dNch/dη is measured within |η|<1 and pt>0. In the highest multiplicity interval with 〈dNch/dη(bin)〉=24.1, corresponding to four times the minimum bias multiplicity density, an enhancement relative to the minimum bias J/ψ yield by a factor of about 5 at 2.5<y<4 (8 at |y|<0.9) is observed.
We show from first principles the emergence of classical Boltzmann equations from relativistic nonequilibrium quantum field theory as described by the Kadanoff–Baym equations. Our method applies to a generic quantum field, coupled to a collection of background fields and sources, in a homogeneous and isotropic spacetime. The analysis is based on analytical solutions to the full Kadanoff–Baym equations, using the WKB approximation. This is in contrast to previous derivations of kinetic equations that rely on similar physical assumptions, but obtain approximate equations of motion from a gradient expansion in momentum space. We show that the system follows a generalized Boltzmann equation whenever the WKB approximation holds. The generalized Boltzmann equation, which includes off-shell transport, is valid far from equilibrium and in a time dependent background, such as the expanding universe.
We present, in the framework of the interacting hadron resonance gas, an evaluation of thermodynamical quantities. The interaction is modelled via a correction for the finite size of the hadrons. We investigate the sensitivity of the model calculations on the radius of the hadrons, which is a parameter of the model. Our calculations for thermodynamical quantities as energy and entropy densities and pressure are confronted with predictions using the lattice Quantum Chromodynamics (QCD) formalism.
Herbal hepatotoxicity is a rare and poorly described disease because reported cases are mostly scattered and lack an appropriate causality assessment. We now describe in detail the clinical picture of herbal hepatotoxicity by extracts of Greater Celandine (GC), syn. Chelidonium majus L. from the Papaveraceae family, which contain more than 20 ingredients including various biologically active isoquinoline alkaloids. For this purpose, we analyzed and reviewed published cases of 16 patients from various European countries. In all patients, herbal hepatotoxicity was of probable and highly probable causality for GC, using the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences). GC associated hepatotoxicity usually has an acute clinical course exhibiting a hepatocellular pattern of injury and is correlated to an idiosyncratic reaction with its metabolic subtype. Jaundice combined with high values of serum aminotransferases was present in virtually all cases with favourable outcome despite severe clinical course. In conclusion, GC hepatotoxicity is a typical herbal hepatotoxicity with a sound causality track for GC, but there is uncertainty regarding the respective causative compound(s). The present detailed review of GC hepatotoxicity may serve as an example for clinical causality assessments of future cases of liver injury due to other herbs.
Background. Spontaneous reports of herb induced liver injury (HILI) represent a major regulatory issue, and it is in the interest of pharmacovigilance to identify and quantify previously unrecognized adverse reactions and to confirm or refute false positive signals of safety concerns. In a total of 13 spontaneous cases, liver disease has initially been attributed to the use of Pelargonium sidoides (PS), a plant from the South African region. Water/ethanol extracts derived from its roots are available as registered herbal drugs for the treatment of upper respiratory tract infections including acute bronchitis. Objectives. The present study examines whether and to what extent treatment by PS was associated with the risk of liver injury in these spontaneous cases. Study design: Overall, 13 spontaneous cases with primarily suspected PS hepatotoxicity were included in the study. Their data were submitted to a thorough clinical evaluation that included the use of the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences) to assess causality levels. These scales are liver specific, validated for liver toxicity, structured and quantitative.
Results. None of the 13 spontaneous cases of liver disease generated a positive signal of safety concern, since causality for PS could not be established on the basis of the applied CIOMS scales in any of the assessed patients. Confounding variables included comedication with synthetic drugs, major comorbidities, low data quality, lack of appropriate consideration of differential diagnoses, and multiple alternative diagnoses. Among these were liver injury due to comedication, acute pancreatitis and cholangitis, acute cholecystitis, hepatic involvement following lung contusion, hepatitis in the course of virus and bacterial infections, ANA positive autoimmune hepatitis, and other preexisting liver diseases. In the course of the case assessments and under pharmacovigilance aspects, data and interpretation deficits became evident. Possible improvements include appropriate data quality of cases in spontaneous reports, case assessment by skilled specialists, use of a validated liver specific causality assessment method, and inclusion only of confirmed cases into the final regulatory case database.
Conclusions. This study shows lack of hepatotoxicity by PS in all 13 spontaneous cases as opposed to initial judgment that suggested a toxic potential of PS. Major shortcomings emerged in the pharmacovigilance section that require urgent improvements.
Hadron production and their suppression in Pb+Pb collisions at LHC at a center-of-mass energy of sNN=2.76 TeV are studied within a multiphase transport (AMPT) model whose initial conditions are obtained from the recently updated HIJING 2.0 model. The centrality dependence of charged hadron multiplicity dNch/dη at midrapidity was found quite sensitive to the largely uncertain gluon shadowing parameter sg that determines the nuclear modification of the gluon distribution. We find final-state parton scatterings reduce considerably hadron yield at midrapidity and enforces a smaller gluon shadowing to be consistent with dNch/dη data at LHC. With such a constrained parton shadowing, charged hadron and neutral pion production over a wide transverse momenta range are investigated in AMPT. Relative to nucleon–nucleon collisions, the particle yield in central heavy ion collisions is suppressed due to parton energy loss. While the calculated magnitude and pattern of suppression is found consistent with that measured in Au+Au collisions at sNN=0.2 TeV at RHIC, at the LHC energy the suppression is overpredicted which may imply the medium formed at LHC is less opaque than expected from simple RHIC extrapolations. Reduction of the QCD coupling constant αs by ∼30% in the higher temperature plasma formed at LHC as compared to that at RHIC was found to reproduce the measured suppression at LHC.
The ALICE experiment has measured low-mass dimuon production in pp collisions at √s=7 TeV in the dimuon rapidity region 2.5<y<4. The observed dimuon mass spectrum is described as a superposition of resonance decays (η,ρ,ω,η′,ϕ) into muons and semi-leptonic decays of charmed mesons. The measured production cross sections for ω and ϕ are σω(1<pt<5 GeV/c,2.5<y<4)=5.28±0.54(stat)±0.49(syst) mb and σϕ(1<pt<5 GeV/c,2.5<y<4)=0.940±0.084(stat)±0.076(syst) mb. The differential cross sections d2σ/dydpt are extracted as a function of pt for ω and ϕ. The ratio between the ρ and ω cross section is obtained. Results for the ϕ are compared with other measurements at the same energy and with predictions by models.
he first measurements of the invariant differential cross sections of inclusive π0 and η meson production at mid-rapidity in proton–proton collisions at s=0.9 TeV and s=7 TeV are reported. The π0 measurement covers the ranges 0.4<pT<7 GeV/c and 0.3<pT<25 GeV/c for these two energies, respectively. The production of η mesons was measured at s=√7 TeV in the range 0.4<pT<15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the π0 spectrum at s=0.9 TeV, overestimate those of π0 and η mesons at s=√7 TeV, but agree with the measured η/π0 ratio at s=√7 TeV.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
The ALICE Collaboration has made the first measurement at the LHC of J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at sNN=2.76 TeV. The J/ψ is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 μb−1. The cross section for coherent J/ψ production in the rapidity interval −3.6<y<−2.6 is measured to be dσJ/ψcoh/dy=1.00±0.18(stat)−0.26+0.24(syst) mb. The result is compared to theoretical models for coherent J/ψ production and found to be in good agreement with those models which include nuclear gluon shadowing.
2. Workshop der AG "Erzählforschung" und der AG "Rezeption und Inter-textualität" im Rahmen der Kooperation des Zentrums für Graduiertenstudien (ZGS) der Bergischen Universität Wuppertal und der Graduiertenschule Kultur- und Sozialwissenschaften (GSKS) der Albert-Ludwigs-Universität Freiburg, 21. und 22. April 2012, Bergische Universität Wuppertal.
The transitional nucleus 154Gd was investigated using a combination of a photon scattering experiment and a γγ-coincidence study following the β decay of 154Tb. A novel decay channel from the scissors mode to the band head of the β-band was observed. Its transition strength B(M1; 1sc+ → 0β+) was determined. An IBM-2 calculation reveals a correlation of this decay channel and the shape phase transition between spherical and deformed nuclei.
We introduce a top-down stylized model to analyse the impact of a transition to a European power system based only on wind and solar power. Wind and solar power generation is calculated from high-resolution weather data and based on the country specific electricity demand alone, we introduce a model of the conventional power system that facilitates simple spatio-temporal modelling of its macroscopic behavior without direct reference to the underlying technological, economical, and political development in the system. Using this model, we find that wind and solar power generation can replace conventional power generation and power capacity to a large degree if power transmission across the continent is made possible.
Preface
(2012)
The so-called extended linear sigma model is a chiral model with (pseudo)scalar and (axial-)vector mesons. It is based on the requirements of (global) chiral symmetry and dilatation invariance. The purpose of this model is the description of the hadron phenomenology up to 1.7 GeV. We present the latest theoretical results, which show a good agreement with the experiment.
We study primary and secondary reactions induced by 600 MeV proton beams in monolithic cylindrical targets made of natural tungsten and uranium by using Monte Carlo simulations with the Geant4 toolkit [1–3]. Bertini intranuclear cascade model, Binary cascade model and IntraNuclear Cascade Liège (INCL) with ABLA model [4] were used as calculational options to describe nuclear reactions. Fission cross sections, neutron multiplicity and mass distributions of fragments for 238U fission induced by 25.6 and 62.9 MeV protons are calculated and compared to recent experimental data [5]. Time distributions of neutron leakage from the targets and heat depositions are calculated.
These proceedings will cover various studies of hadronic resonances within the UrQMD transport model. After a brief explanation of the model, various observables will be highlighted and the chances for resonance reconstruction in hadronic channels will be discussed. Possible signals of chiral symmetry restoration will be investigated for feasibility.
The status of the analysis of electron-positron pairs measured by ALICE in pp collisions at √s = 7 TeV and central Pb-Pb collisions at √sNN = 2.76 TeV is presented. Key questions and the main challenges of the analysis are discussed on the basis of first raw invariant mass spectra for both collision systems.
Resonances from PHSD
(2012)
The multi-strange baryon and vector meson resonance production in relativistic nucleus-nucleus collisions is studied within the parton-hadron-string dynamics (PHSD) approach which incorporates explicit partonic degrees-of-freedom in terms of strongly interacting quasiparticles (quarks and gluons) in line with an equation-of-state from lattice QCD as well as the dynamical hadronization and hadronic collision dynamics in the final reaction phase. We find a significant effect of the partonic phase on the production of multi-strange antibaryons at SPS energies due to a slightly enhanced pair production from massive time-like gluon decay and a larger formation of antibaryons in the hadronization process. We, futhermore, obtain a visible in-medium effects in the low mass dilepton sector from dynamical vector-meson spectral functions from SIS to SPS energies whereas at RHIC and LHC energies such medium effects become more moderate. In the intermediate mass regime from 1.1 to 3 GeV pronounced traces of the partonic degrees of freedom are found at SPS energies which superseed the hadronic (multi-meson) channels as well as the correlated and uncorrelated semi-leptonic D-meson decays. The dilepton production from the strongly interacting quark-gluon-plasma (sQGP) becomes already visible at top SPS energies and more pronounced at RHIC and LHC energies.
New results on the differential cross section in deuteron-proton elastic scattering are obtained at the deuteron kinetic energy of 2.5 GeV with the HADES spectrometer. The angular range of 69° – 125° in the center of mass system is covered. The obtained results are compared with the relativistic multiple scattering model calculation using the CD-Bonn deuteron wave function. The data at fixed scattering angles in the c.m. are in qualitative agreement with the constituent counting rules prediction.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
We present results on hadronic resonance production in high energy nuclear collisions from the UrQMD hybrid model. In particular we are interested in the effect of the final hadronic stage on the properties of resonances observable at RHIC and LHC experiments. We investigate weather these observable properties can be used to pinpoint the transition energy density from the QGP phase to the hadronic phase.
Wenn man an die Stelle des Titels "Georg Büchner und seine Zeit" "Georg Büchner in seiner Zeit" setzt, hat man den Unterschied der Lebenszeit Büchners (1813-1837) und seiner Wirkung über einen umfassenderen Zeitraum im Blick. Diese doppelte Perspektive versucht der Essay durchzuhalten: Er fragt zunächst, wie es möglich wurde, dass ein junger Mann, der mit 24 Jahren starb, nicht nur als Schriftsteller, sondern auch als Wissenschaftler und Revolutionär eine herausragende Rolle spielen konnte. Anschließend werden zwei avantgardistische Alternativen zu den von Büchner gewählten Dramenstoffen Danton und Woyzeck fiktiv vorgeführt.
This article deals with the difficulty of translating institution names. The translation of institution names from one language into another plays an important role at the translation of official documents. Institution names are stronger conventionalised than other proper names, because the judicial system is determined by the appropriate public institutions. The names of institutions arose in each speech community related to the judicial tradition and the legal history, which must be taken into account at translating them from one language into another and thus from one legal system into another. This article points out the difficulties that arise at different levels when translating institution names, it presents the advantages and disadvantages of the solutions offered so far in the specialized literature and proposes a surrogate solution.
This paper discusses and analyses the importance of oral history in offering a true image of reality. Referring to the tragic destiny of the German ethnic group in Romania after the second world war – their deportation in the Soviet Union – it presents an excerpt of the narration of contemporary witnesses.
At the beginning of the 1970s, the literature in German language from Romania went through a radical process of change that transformed a largely epigonic and obedient literature into a dynamic, original and subversive one. The following paper analyses the context, the causes, and the mechanisms of this innovative period.
The motif of the „sun wedding“, which has its origin in ancient mythology, can also be found in the Romanian folk ballad The sun and the moon, where the action takes place around the conflict with etiological meaning of the love between brother and sister. So, the ballad tries to explain some natural phenomena and tries to answer the question, why the sun never meets the moon in its way across the sky. Masterpiece of Romanian folk poetry, the ballad of the sun wedding with the moon raised the interest of German translators, who proved the size of their talent by translating the ballad in German and by popularizing it among the German readers in the country and abroad. The present study analyses the variants of translation of five authors in different centuries (the 19th and the 20th century) and aims to highlight the difficulties, the solutions and the takeovers of the time, as a result of the authors’ wish to translate the original text as accurately as possible and as close as possible to the spirit of the Romanian folk poetry.
Fascinated by the exotic India, Mircea Eliade decided to explore closely the culture and its subtleties. In 1929 he received a scholarship for five years to study the culture and religions of India under the guidance of the illustrious scholar Surendranah Dasgupta. During the time spent in the master‘s house, Eliade gets to know his daughter Maitreyi, whom he falls in love with and they will experience a beautiful and exciting love affair. This relationship will subsequently be the subject of the novel with the same name. Unique case in the history of world literature, the novel Maitreyi will receive a reply over the years, still under the form of a fascinating narration, whose author is the main character Maitreyi Devi herself. It Does Not Die (Love never dies, in Romanian translation; Die Liebe stirbt nicht, in German translation) will become the platform that will host the narrative duel of Eliade the author become character, and Maitreyi Devi, the character, who became author. In our analytical approach we tried to render the ways in which this intercultural dialogue at a distance was perceived in the German linguistic area.
This study intends to analyze the barely known literary personality of Carmen Sylva, the first Romanian queen. Since Carmen Sylva was a German-born princess, yet lived almost her entire life in the Romanian cultural environment, the main point of this paper is to analyze the idea of writing while being split between two different cultures. Carmen Sylva’s self-assumed role of cultural mediator is in this respect obvisouly worth mentioning. However the main question of this study lies not necessarily in the role, but rather in the place of this writer with two homelands. Did she indeed manage to become a cultural mediator or was she her entire life nothing more than an outsider?
The aim of the present paper is to describe the geographic diffusion of the family name Pfaff in Germany, starting from the telephone directory of 2005 and retracing the historic linguistic phenomena that led to the formation of this name. Pfaff (mhd. phaffe, md. paffe, nd. pape, southern German Pfaffe “priest” or “churchman”) is explained both as an agnomen and as the name of a profession. Our map represents an addition to the maps that have already appeared in dtv – Atlas Namenkunde (1999), Duden-Familiennamen (2005) and Deutscher Familiennamenatlas (2011), for it additionally and thoroughly renders not? only the geographic diffusion of the family name Pfaff in Germany but also in Transylvania, where the name also exists. [this surname also exists in Transylvania]. The type Pfaff (5056 telephone addresses) is spread all over Germany, but we notice two areas of high frequency: one, according to our expectations, in the southern part of the Benrath Line and on the right of the Germersheim Line, but also on the left of the latter, especially in the rectangle Koblenz – Kassel – Hof – Frankfurt and also in south-western Germany (in Schwarzwald –The Black Forest). The northern version Pape, approximately twice more frequent than Pfaff(e), did not adapt to standard German, due to the negative connotations of the appellative Pfaffe, Pfaffen, which appeared at the same time as the Church Reform in the 16th century. In some places in Transylvania, the surname Pfaff was replaced with the version Prediger. The appellative Pfaffe and the family name Pfaff (in the Saxon language – the Romanian “limba sãseascã”: faf, pfaf ) contributed to the formation of different rural toponyms in Transylvania. The surname Pfaff is spread not only in the German linguistic space, but also in areas where ethnic Germans live (France, Luxembourg, Belgium, Holland, Poland, Romania, USA, Canada, Argentina). In Romania, there are very few Pfaff surnames in telephone books for the 2008-2009 period, due to the massive migration of the German ethnics to Germany after 1990.
This study indicates research areas from the perspective of the German and Romanian language phraseology, areas that are exemplified within the phraseosemantic field of „communication”. The analysis of the current state of research indicates the partial or complete lack of preoccupation, on the one hand, with the metaphorization process and the predominance of the conceptual metaphors in the two languages or the dominance of some components and their analysis from a cultural-specific point of view, and, on the other hand, with the systematization of morphosyntactic or semantic restrictions.
Translation exercises have always played an important role in teaching/learning foreign languages, ever since the Grammar-Translation method was developed. However, with the emergence of the communicative language teaching in the 70s which focussed on communicative competence as the ultimate goal of language learning, they were considered to be obsolete and inefficient. The present article suggests that the utility of translation – not only where teaching foreign languages is concerned, but also within the field of German studies – should be reassessed, showing that both ”pedagogical” as well as ”communicative” translation can support and improve the study of German language, literature and culture, increase students‘ awareness of both German language and their mother tongue and furthermore contribute to the enrichment of their general knowledge.
The current article deals with the feedback issue in the study of foreign languages, both from the perspective of traditional learning, as well as from the perspective of computer assisted learning. The possibilities and limits, advantages and disadvantages of each case are presented and compared, and the new demands and opportunities on the educational - and job market are being mentioned.
The present study researches the literary materializations of the Heimat visions as they emerge from Herta Müller’s Atemschaukel and Aglaja Veteranyi’s Warum das Kind in der Polenta kocht. The Heimat concepts are narratologically constructed both as Erinnerungsräume and as imaginary geographies. Usage of these notions will be made according to the definitions of Aleida Assmann respectively Doris Bachmann-Medick. Heimat is seen as a space from the past, which is projected with the force of the memories in the present having an imaginary geography, that can be articulated on three aspects associated with this concept: shelter, food and possessions.
The present interview is rooted in the diverse aspects of interculturalism and of Romanian-German literary convergence – landmarks of both the works of fiction and non-fiction of the German author hailing from Sibiu. Special emphasis is placed upon the collection of essays Einen Halt suchen (En. In search of stability) and upon its translations from the Romanian into German, the main scope of the interview being to highlight the author’s opinions about the aforementioned aspects.
This paper proposes to analyse contrastively the phraseological expressions which include proper names in German and Romanian languages and also, to interpret them as cultural elements that generate problems when trying to translate them. It is intended to establish equivalence relations between the onimical expressions of the two languages, suggesting, where it will be the case, the translation strategies.
German language in Romania is being strongly influenced by Romanian, the majority language. In the field of secondary and higher education linguistic interferences that come from Romanian touch types or names of educational institutions, types of didactic activities, types of assessment and examination.
The current article presents the various functions which are allotted to the foreign language learning in the broader context of the globalization, not only regarding the economical international exchanges, but also from the perspective of the development of personality and of the capacity of understanding different cultures and mentalities – which can play an essential role in the good understanding and peaceful living among the people. Based on these considerations, suggestions are made, regarding the necessity of a reevaluation of the place which the foreign languages teaching is recognized in the curriculum of the various branches of study.
The Romanian poet and essayist Ion Pillat (1891-1945) ranks among the relatively often translated writers of his generation (authors who were active during the interwar period). His works have kept the attention of the German readership several times: Two volumes by Ion Pillat, which appeared in 1943 and 1976 (containing translations by Konrad Richter and Bernhard Capesius, respectively by Wolf von Aichelburg), as well as varied publications in anthologies and other publications have contributed to the spread of his work in Germany and Austria. The author offers an overview of the existing translations and, in the end, refers to his own attempts at translating Ion Pillat’s poetry into German.
This succint introduction to Radu Vancu, the young poet and university lecturer invited to the reading organized by the Department of German Studies as part of its annual scientific conference, offers some biographical and exegetical points of reference for the author’s literary and professional evolution. For instance, there is the apprenticeship (rather a “friendshipin-love”) with the venerated master: the poet, gifted translator and man of culture Mircea Ivãnescu, whom he praises in his doctoral thesis as ”the poet of absolute discretion”. Then there is his editing activity at the “Transilvania” Cultural Journal, a publication of original critical and essayistic writings. His forceful, resourceful and sensitive lyrical work shows two dominant themes: on the one hand, the traumatising early loss of his father, and on the other hand, the birth and growing-up of his son Sebastian, for whom the poet builds, with endless affection and humour, a magical livresque universe, populated by fabulous creatures.
This article discusses one of many possible strategies that translators use in rendering an idiom from a L1 to a L2, i.e. the verbatim or the literal translation. The points of view according to this strategy differ very much among the researchers: some treat them as semantic false friends. Based on the replies to a questionnaire that was handed out to 10 Romanian native speakers, one could state that the context in which the literal translation of a source-idiom is situated plays an important role for the understanding of the text. Beyond that, the translation of an idiom cannot be judged only by virtue of the denotative meaning – the pragmatic function of the translation as a whole is just as important. The questionnaire was compiled of literal translations of Swedish idioms into Romanian (from different translations of different novels). The article further discusses some of the text examples from this questionnaire and describes some of the phenomena related to idioms which hinder the so-called idiom-understanding and which probably led to misinterpretation and a failed literal translation.
The four novels of Cătălin Dorian Florescu (Wunderzeit, Der kurze Weg nach Hause, Der blinde Masseur, Zaira) analysed here are interpreted in relation to the chronotope, a term developed by Michail Bachtin meaning the connectedness of time and space in narrative. Space knows two opposite dimensions in Florescu’s works: the West (Switzerland, USA) and the East (Romania). The Romanian space is represented by three different images corresponding to three different periods: Romania between the two world wars, during the communist period and after 1989. The main characters are Romanians who leave their country of origin during the communist period, hoping that they will find a better life in the West. After the revolt in 1989, the characters return to the space of their childhood, where they could find themselves and happiness once again. There are analyzed different aspects of the aesthetic space Romania: exotic space, space of discovery of oneself, spiritual space of traditions, but also space of disappointment and of perils. Space is in close connection with movement, the movement of the protagonists from one dimension to another, which is also the basis of the plot.
"Spieglein, Spieglein an der Wand ..." : das Diminutiv im Überzetzungsvergleich Deutsch-Rumänisch
(2012)
The paper presents some aspects connected to the system of diminution in German and Romanian, by offering a comparative analysis of the German version of the fairy tale “Snow White” and six Romanian translations of the text. The focus lies on the ways in which the nouns in the text are marked as ‘diminutives’ in German (mainly by adding suffixes, the synthetic diminutives) and the equivalences suggested by the Romanian translators. Although the category ‘diminution’ is common to both languages, there are significant differences in the way it is linguistically expressed. A main part of the paper is devoted to these differences and their reflection in the text.
Ever since their settlement in the Maramureș at the end of the 18th century, the Zipser Germans have been living in close relation to the other linguistic groups (Romanians, Hungarians, Ruthenians, Jews, and Roma/Sinti) in Viºeu de Sus. Thus a multi-/intercultural and multilingual society has emerged under all social, economic and cultural aspects of life. These intercultural interactions can be observed especially on the level of the language. This article tries to identify and analyse some borrowings from Romanian and Hungarian into the Zipser German dialect from the lexical, semantic and syntactic perspective of transference.
The paper discusses the request of the Jewish Middle/ Middle-East-European immigrants for images, impressions, feelings and memories from their native lands, which Aaron Lebedeff masterfully captured in his American-Jewish musicals. The paper focuses on multiculturalism and multilingualism in overlapping regions of extended cultural areas, particularly in territories along the borders of Middle/Middle-East-European states, which don’t form any abrupt cultural barriers. Using the example of a in our time in Jewish milieus worldwide frequently played quadrilingual song from Aaron Lebedeff about Romania (with the German translation of the complete version from 1925), the paper conveys the role of Yiddish as a major dialect of the German as a worldwide carrier of this language as well.
The meaning of the verb „heischen“ occurs in standard German in special context only, especially in poetic language. In some Rhenish idioms of the German language space this lexeme is documented with the same meaning as in the Transylvanian Saxon idiom. Notable is the meaning “to woo”, “to ask for the bride’s hand” and idioms with a special wording that is specific to the Transylvanian-Saxon idiom only. This case study exemplifies how Transylvanian Saxon, removed from the German language space, is handling the linguistic thesaurus brought over centuries ago via emigration from the old country and how it adds its own meanings through a mixture and balance of language, a phenomenon specific to the colonial idioms.
Julian/Jutta Schutting, as a self-conscious author, understands the literary activity as a common and democratic act of creation, performed both by the writer as well as by the reader, thus revealing and connecting the multitude of associative meanings of the literary artifact. Until 1989, until her transformation, the writing of Jutta Schutting was a “secret therapy for survival,” by means of which the troubled existence was to be overcome through the creative power and the originality of her work. Back then she described her art as a “hybrid life … neither … nor…, both … and …,” an attempt to transform the personal inner conflict into curative fictional models. This “neither … nor … - both … and …” situation illustrates the androgynous attitude towards this kind of fictionalized models, this tonality being also supported at the stylistic level that escapes any formalist framework of the genre literature. “Gralslicht. Ein Theaterlibretto” [“The Grail’s Light. A TheatreLibretto“] was published in 1989 by Residenz-Publishing House and is explicitly “composed” as a modern interpretation of Wagner’s “Parsifal” in the typical manner of Schutting. The language ceases to be referential and becomes almost exclusively self-referential, because the dialogues do not rely on a situation of communication [communication situation], but are to be regarded as an interactive exchange of monologues. The female character “Kundry” is almost completely absent from the stage [at the level of the stage] and becomes evident only in the dramatic game between the two male characters that regard her and her duality as the principle of the eternal feminine. Kundry remains active only at the textual level and becomes a life example and a pretext in the love-chastity debate between Parsifal and Don Giovanni.
The following essay illustrates the extraordinary love story between Clemens Rescher and Rodica Neagoie. These key characters are representative figures for the nation they belong to. Clemens is a Transylvanian Saxon and Rodica a Romanian. Despite all contradictions, they fall in love, spend time together, travel to the Black Sea and plan their future. Even though they are bound to each other by strong feelings, this love cannot overcome all the preset cultural, ethnic and social obstacles. Clemens and Rodica become the victims of the world they live in.
The paper aims at presenting the Boer Wars (1881–1882 and 1899–1902) as they are reflected in „Siebenbürgisch-Deutsches Tageblatt”, the most important daily newspaper of the Transylvanian Saxons. From the beginning of the second conflict, the Saxons felt great sympathy for the Boers, because they considered them relatives due to their Germanic roots. They also drew a parallel between the Boers’ fight for independence and their own fight against the attempt of forced Hungarization by the authorities from Budapest. In the newspaper there were published not only articles about the armed conflicts but also contributions on the way of life and the habits of the Boers. A novel on the topic of the “Jameson Raid” which took place on New Year’s Eve 1895/1896 was also published. During the “Second Boer War” the Saxons created “Associations of Boer Friends” aimed to help their “brothers” from South Africa who lived in great misery.
Margarethe Sindel-Alberti is a rather unknown 20th century writer from Transilvania. Being a member of the German minority it is very unusual for her to write a story about Romanian protagonists. Also unusual is the fact that she writes about a kind of secret initiation of a young girl who is guided by her grandmother how to deal with sexuality. Our analysis makes a referance to the psychoanalytic interpretation of the tale “Little Red Hood” as we find it in the works of Siegmund Freud and to the interpretation as an initiation tale as it is considered by Vladimir Propp. Margarethe Sindel is considered to be outstanding for her geographical space and time writing about a feminist subject and a different culture than her own.
Two Romanian authors, Nora Iuga and Carmen Francesca Banciu have published their impressions about the German capital Berlin. Nora Iuga stayed there twice for a limited period of time (in 2000 and in 2010), whereas Carmen Francesca Banciu decided to live in Berlin after her scholarship there ended in 1991. This is why Carmen Francesca Banciu’s writing changed together with the changing city, which was then under construction not only literally but also in a figurative way integrating new influences due to the opening of Eastern Europe after the end of its isolation during the Cold War. She is one of those new elements which reshape Berlin adding new and different perspectives to its cultural life. Banciu publishes her impressions in Berlin ist mein Paris. Nora Iuga, on the other hand, remains nothing but a visitor. Her ideas about the City and about the Germans in general change a lot during her stays in Berlin. In the end, she leaves for Bucharest with new impressions, which are released in Romania in her book Berlinul meu e un monolog.