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Mit "Stirners Einzigem" ist das Buch 'Der Einzige und sein Eigentum' von Max Stirner gemeint, das gegen Ende des Vormärz erschien. Das Buch war ein Skandalon, ein paradoxes Skandalon allerdings, weil es ideengeschichtlich dort am eingreifendsten wirksam wurde, wo die Reaktion verborgen und indirekt blieb, bei Marx und Nietzsche. Ich habe den diffusen Status des 'Einzigen', der sich daraus ergab und den er, obwohl kein Mangel an Sekundärliteratur herrscht, im Grunde bis heute behielt, in einer Wirkungsgeschichte dargestellt und diese mit einem sprechenden Neologismus eine Re(pulsions- und De)zeptionsgeschichte genannt.
Auf die Repulsionsgeschichte des Einzigen gemünzt ist das "Vade retro!" im Titel, denn eine Reihe durchaus bedeutender Denker sahen in Stirners Ideen tatsächlich den Inbegriff des Bösen, Teuflischen bzw. "aufgeklärterweise" den Einbruch des Tierischen, Unmenschlichen, Barbarischen, Zerstörerischen in die kulturelle Welt. Einige waren dabei so entschieden, dass sie ihre philosophische Position wesentlich - wenngleich undeklariert - in Abwehr von Stirners Ideen entwickelten.
Ich werde - nach einer biografischen Skizze zu Leben und Werk Stirners - diese Repulsionsgeschichte in ihren markanteren Stationen wie in einem Parcours durchlaufen, um zu zeigen, dass diese Bezeichnung adäquat ist. Die mit ihr verwobene Dezeptionsgeschichte, also die das Inhaltliche betreffenden Täuschungen, Selbsttäuschungen und Verdrängungen der Abwehrenden, können hier nur beiläufig zur Sprache kommen.
In fast jedem autoritär regierten Staat werden von den Machthabern Maßnahmen wie Repressalien und Strafen ergriffen, die die erwünschten Verhaltensweisen der Menschen erzwingen und diese dazu bringen sollen, sich einer bestimmten Ideologie unterzuordnen. Die Kunst ist ein besonders empfindlicher Bereich des öffentlichen Lebens und entzieht sich zumindest teilweise diesen Methoden. Eine Kontrolle über die Künstler und ihr Schaffen erfordert seitens der Staatsgewalt deshalb meistens ein subtileres Instrumentarium. Aber auch andere, "weiche" Faktoren haben einen Einfluss auf das politische Verhalten der Künstler und die Gestaltung der Kunstinhalte.
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays. We identified 451 TAL1 target genes in K562 cells. Furthermore, we analysed the regulation of one of these genes, the catalytic subunit beta of protein kinase A (PRKACB), during megakaryopoiesis of K562 and primary human CD34+ stem cell/progenitor cells. We found that TAL1 together with hematopoietic transcription factors RUNX1 and GATA1 binds to the promoter of the isoform 3 of PRKACB (Cβ3). During megakaryocytic differentiation a coactivator complex on the Cβ3 promoter, which includes WDR5 and p300, is replaced with a corepressor complex. In this manner, activating chromatin modifications are removed and expression of the PRKACB-Cβ3 isoform during megakaryocytic differentiation is reduced. Our data uncover a role of the TAL1 complex in controlling differential isoform expression of PRKACB. These results reveal a novel function of TAL1, RUNX1 and GATA1 in the transcriptional control of protein kinase A activity, with implications for cellular signalling control during differentiation and disease.
Midkine is a pleiotropic factor, which is involved in angiogenesis. However, its mode of action in this process is still ill defined. The function of midkine in arteriogenesis, the growth of natural bypasses from pre-existing collateral arteries, compensating for the loss of an occluded artery has never been investigated. Arteriogenesis is an inflammatory process, which relies on the proliferation of endothelial cells and smooth muscle cells. We show that midkine deficiency strikingly interferes with the proliferation of endothelial cells in arteriogenesis, thereby interfering with the process of collateral artery growth. We identified midkine to be responsible for increased plasma levels of vascular endothelial growth factor A (VEGFA), necessary and sufficient to promote endothelial cell proliferation in growing collaterals. Mechanistically, we demonstrate that leukocyte domiciled midkine mediates increased plasma levels of VEGFA relevant for upregulation of endothelial nitric oxide synthase 1 and 3, necessary for proper endothelial cell proliferation, and that non-leukocyte domiciled midkine additionally improves vasodilation.
The data provided on the role of midkine in endothelial proliferation are likely to be relevant for both, the process of arteriogenesis and angiogenesis. Moreover, our data might help to estimate the therapeutic effect of clinically applied VEGFA in patients with vascular occlusive diseases.
Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.
New results are presented of the 234U neutron-induced fission cross section, obtained with high accuracy in the resonance region by means of two methods using the 235U(n,f) as reference. The recent evaluation of the 235U(n,f) obtained with SAMMY by L. C. Leal et al. (these Proceedings), based on previous n_TOF data [1], has been used to calculate the 234U(n,f) cross section through the 234U/235U ratio, being here compared with the results obtained by using the n_TOF neutron flux.
The impact of the incorporation of a non-natural amino acid (NNAA) on protein structure, dynamics, and ligand binding has not been studied rigorously so far. NNAAs are regularly used to modify proteins post-translationally in vivo and in vitro through click chemistry. Herein, structural characterisation of the impact of the incorporation of azidohomoalanine (AZH) into the model protein domain PDZ3 is examined by means of NMR spectroscopy and X-ray crystallography. The structure and dynamics of the apo state of AZH-modified PDZ3 remain mostly unperturbed. Furthermore, the binding of two PDZ3 binding peptides are unchanged upon incorporation of AZH. The interface of the AZH-modified PDZ3 and an azulene-linked peptide for vibrational energy transfer studies has been mapped by means of chemical shift perturbations and NOEs between the unlabelled azulene-linked peptide and the isotopically labelled protein. Co-crystallisation and soaking failed for the peptide-bound holo complex. NMR spectroscopy, however, allowed determination of the protein-ligand interface. Although the incorporation of AZH was minimally invasive for PDZ3, structural analysis of NNAA-modified proteins through the methodology presented herein should be performed to ensure structural integrity of the studied target.
The transporter associated with antigen processing (TAP) selectively translocates antigenic peptides into the endoplasmic reticulum. Loading onto major histocompatibility complex class I molecules and proofreading of these bound epitopes are orchestrated within the macromolecular peptide-loading complex, which assembles on TAP. This heterodimeric ABC-binding cassette (ABC) transport complex is therefore a major component in the adaptive immune response against virally or malignantly transformed cells. Its pivotal role predestines TAP as a target for infectious diseases and malignant disorders. The development of therapies or drugs therefore requires a detailed comprehension of structure and function of this ABC transporter, but our knowledge about various aspects is still insufficient. This review highlights recent achievements on the structure and dynamics of antigenic peptides in complex with TAP. Understanding the binding mode of antigenic peptides in the TAP complex will crucially impact rational design of inhibitors, drug development, or vaccination strategies.
Background: Supracondylar fractures of the humerus are a common injury in pediatric traumatology. The most common operative therapy is closed reduction and percutaneous pinning using K-wires. Common complications associated with this entity are neurovascular lesions, especially of the brachial artery and the median nerve.
Methods: We report two cases of patients treated in our trauma-center with supracondylar fracture of the humerus (AO IV°) and neurovascular complications.
Results: Both patients underwent open revision and recovered completely in their further course.
Conclusion: We recommend detailed neurovascular examination initially and after reposition of the fracture. The threshold for open reduction in cases of irreducible fractures should be low. In the presence of neurovascular impairment an open revision is mandatory, even months after the initial Trauma.
Background: The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs.
Methods: Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA pulldown and immunoprecipitation, mass spectrometry, microarray, several knockdown approaches, CRISPR-Cas9, assay for transposase-accessible chromatin sequencing, and chromatin immunoprecipitation in human umbilical vein endothelial cells. Patient samples from lung and tumors were studied for MANTIS expression.
Results: A search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, here termed MANTIS, as the most strongly regulated lncRNA. Controlled by the histone demethylase JARID1B, MANTIS was downregulated in patients with idiopathic pulmonary arterial hypertension and in rats treated with monocrotaline, whereas it was upregulated in carotid arteries of Macaca fascicularis subjected to atherosclerosis regression diet, and in endothelial cells isolated from human glioblastoma patients. CRISPR/Cas9-mediated deletion or silencing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of endothelial cells in response to shear stress. Mechanistically, the nuclear-localized MANTIS lncRNA interacted with BRG1, the catalytic subunit of the switch/sucrose nonfermentable chromatin-remodeling complex. This interaction was required for nucleosome remodeling by keeping the ATPase function of BRG1 active. Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding.
Conclusion: MANTIS is a differentially regulated novel lncRNA facilitating endothelial angiogenic function.
Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity.
Following up on earlier investigations, the present paper analyzes construct validity of the impostor phenomenon. It examines the question whether the impostor phenomenon is a homogeneous construct or whether different types of persons with impostor self-concept can be distinguished on the basis of related characteristics. The study was conducted with professionals in leadership positions exhibiting a pronounced impostor self-concept (n = 183). Cluster-analytic procedures indicated the existence of two different types: one group which, in line with the literature (e.g., Clance, 1985), possessed traits classified as fairly unfavorable (“true impostors”) and another group which can be described as largely unencumbered (“strategic impostors”). The present study suggests two types of impostorism: “True” impostors characterized by the negative self-views associated with the construct definition, and more “strategic” impostors who seem to be less encumbered by self-doubt. It is assumed that “strategic impostors” are characterized by a form of deliberate self-presentation. Therefore, the impostor self-concept cannot principally be viewed as a dysfunctional personality style. This distinction should be more carefully considered in further research and in therapeutic interventions.
Monte Carlo (MC) simulations are an essential tool to determine fundamental features of a neutron beam, such as the neutron flux or the γ-ray background, that sometimes can not be measured or at least not in every position or energy range. Until recently, the most widely used MC codes in this field had been MCNPX and FLUKA. However, the Geant4 toolkit has also become a competitive code for the transport of neutrons after the development of the native Geant4 format for neutron data libraries, G4NDL. In this context, we present the Geant4 simulations of the neutron spallation target of the n_TOF facility at CERN, done with version 10.1.1 of the toolkit. The first goal was the validation of the intra-nuclear cascade models implemented in the code using, as benchmark, the characteristics of the neutron beam measured at the first experimental area (EAR1), especially the neutron flux and energy distribution, and the time distribution of neutrons of equal kinetic energy, the so-called Resolution Function. The second goal was the development of a Monte Carlo tool aimed to provide useful calculations for both the analysis and planning of the upcoming measurements at the new experimental area (EAR2) of the facility.
The spent fuel of current nuclear reactors contains fissile plutonium isotopes that can be combined with 238U to make mixed oxide (MOX) fuel. In this way the Pu from spent fuel is used in a new reactor cycle, contributing to the long-term sustainability of nuclear energy. The use of MOX fuels in thermal and fast reactors requires accurate capture and fission cross sections. For the particular case of 242Pu, the previous neutron capture cross section measurements were made in the 70's, providing an uncertainty of about 35% in the keV region. In this context, the Nuclear Energy Agency recommends in its “High Priority Request List” and its report WPEC-26 that the capture cross section of 242Pu should be measured with an accuracy of at least 7–12% in the neutron energy range between 500 eV and 500 keV. This work presents a brief description of the measurement performed at n_TOF-EAR1, the data reduction process and the first ToF capture measurement on this isotope in the last 40 years, providing preliminary individual resonance parameters beyond the current energy limits in the evaluations, as well as a preliminary set of average resonance parameters.
La risa es uno de los temas menos estudiados en la obra de Walter Benjamin; sin embargo, constituye una de las claves para la comprensión de lo que el crítico alemán consideró que podría ser una politización del arte. En este artículo tratamos de desgranar el lugar de la risa en la teoría estética y política de Benjamin a partir de su conferencia «El autor como productor». Desde ese punto nos proponemos introducir su lectura de Bertolt Brecht, así como su polémica con Theodor W. Adorno.
The recent recolonisation of the Central European lowland (CEL) by the grey wolf (Canis lupus) provides an excellent opportunity to study the effect of founder events on endoparasite diversity. Which role do prey and predator populations play in the re-establishment of endoparasite life cycles? Which intrinsic and extrinsic factors control individual endoparasite diversity in an expanding host population? In 53 individually known CEL wolves sampled in Germany, we revealed a community of four cestode, eight nematode, one trematode and 12 potential Sarcocystis species through molecular genetic techniques. Infections with zoonotic Echinococcus multilocularis, Trichinella britovi and T. spiralis occurred as single cases. Per capita endoparasite species richness and diversity significantly increased with population size and changed with age, whereas sex, microsatellite heterozygosity, and geographic origin had no effect. Tapeworm abundance (Taenia spp.) was significantly higher in immigrants than natives. Metacestode prevalence was slightly higher in ungulates from wolf territories than from control areas elsewhere. Even though alternative canid definitive hosts might also play a role within the investigated parasite life cycles, our findings indicate that (1) immigrated wolves increase parasite diversity in German packs, and (2) prevalence of wolf-associated parasites had declined during wolf absence and has now risen during recolonisation.
We compute the fermion spin distribution in the vortical fluid created in off-central high energy heavy-ion collisions. We employ the event-by-event (3+1)D viscous hydrodynamic model. The spin polarization density is proportional to the local fluid vorticity in quantum kinetic theory. As a result of strong collectivity, the spatial distribution of the local vorticity on the freeze-out hyper-surface strongly correlates to the rapidity and azimuthal angle distribution of fermion spins. We investigate the sensitivity of the local polarization to the initial fluid velocity in the hydrodynamic model and compute the global polarization of Λ hyperons by the AMPT model. The energy dependence of the global polarization agrees with the STAR data.
Vom 14. bis zum 16. September 2017 fanden am Institut für Germanistik der Universität Wrocław die VI. Linguistischen Treffen unter dem Titel 'Grenzen der Sprache, Grenzen der Sprachwissenschaft' statt. Die Treffen wurden vom Lehrstuhl für Deutsche Sprache und Lehrstuhl für Angewandte Linguistik veranstaltet
O Direito liberal procede da ideia kantiana de um acordo de arbítrios conforme uma lei de liberdade externa, assegurando a ideia de um radicalismo pós-religioso de legitimidade e sem fundamentos metafísicos (Nozick). Habermas aproveita os sentidos do Direito liberal de Nozick e Kant, liberdade e não fundacionismo e associa a crítica ao Direito socialista a uma visão construtiva que, assim como Rawls (e seu pluralismo razoável), busca pensar as pretensões de um Direito democrático no espaço público. Superando a dicotomia socialista-liberal do século XX, Habermas busca manter a democracia e a pós-metafísica como elementos de um Direito pluralista que através do procedimentalismo institucionalizador das conquistas do espaço público movido pela razão comunicativa, possa assegurar as pretensões de legitimação da liberdade com as necessárias visões da “Teoria Crítica” sobre a legitimação da democracia no capitalismo tardio, preservando as autonomias pública e privada da tradição republicana e liberal de Kant.
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha (PDGFRA) is thought to be essential for the derivation and maintenance of mouse XEN cell lines. Here, we have re-evaluated this requirement for PDGFRA. We derived multiple PDGFRA-deficient XEN cell lines from postimplantation and preimplantation embryos of a PDGFRA-GFP knockout strain. We also converted PDGFRA-deficient embryonic stem cell lines into XEN cell lines chemically by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of our 12 PDGFRA-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, PDGFRA is not essential for the derivation and maintenance of XEN cell lines.
Referenz und Prominenz
(2017)
Background: Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors’ and/or patients’ side or be caused by the healthcare system. To assess whether patients’ concepts and attitudes are really an implementation barrier for AG, we analysed the patients’ perspective of a “good asthma therapy” and contrasted their wishes with current recommendations.
Methods: Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached. Inclusion criteria were an asthma diagnosis and age above 18. FG sessions were recorded audio-visually and analysed via a mapping technique and content analysis performed according to Mayring (supported by MAXQDA®). Participants’ speech times and the proportion of time devoted to different themes were calculated using the Videograph System® and related to the content analysis.
Results: Thirteen men and 24 women aged between 20 and 77 from rural and urban areas attended five FG. Some patients had been recently diagnosed with asthma, others years previously or in childhood. The following topics were addressed: (a) concern about or rejection of therapy components, particularly corticosteroids, which sometimes resulted in autonomous uncommunicated medication changes, (b) lack of time or money for optimal treatment, (c) insufficient involvement in therapy choices and (d) a desire for greater empowerment, (e) suboptimal communication between healthcare professionals and (f) difficulties with recommendations conflicting with daily life. Primarily, (g) participants wanted more time with doctors to discuss difficulties and (h) all aspects of living with an impairing condition.
Conclusions: We identified some important patient driven barriers to implementing AG recommendations. In order to advance AG implementation and improve asthma treatment, the patients’ perspective needs to be considered before drafting new versions of AG. These issues should be addressed at the planning stage.
Trial registration: DRKS00000562 (German Clinical Trials Registry).
In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 106 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice. Local and systemic tumor growth were monitored by regular hrUS, μCT and MRI examinations. Cells engrafted in all mice and gave rise to exponentially growing, solid tumors. All imaging techniques allowed to detect orthotopic tumors and to precisely calculate their volumes. While tumors appeared homogenously radiolucent in μCT, hrUS and MRI allowed for a better visualization of intratumoral structures and surrounding soft tissue. Examination time was the shortest for hrUS, followed by μCT and MRI. Tumor volumes determined by hrUS, μCT and MRI showed a very good correlation with each other and with caliper measurements at autopsy. 10 animals developed pulmonary metastases being well detectable by μCT and MRI. In conclusion, each technique has specific strengths and weaknesses, so the one(s) best suitable for a specific experiment may be chosen individually.
To study the implications of highly space-demanding organic moieties on the properties of self-assembled monolayers (SAMs), triptycyl thiolates and selenolates with and without methylene spacers on Au(111) surfaces were comprehensively studied using ultra-high vacuum infrared reflection absorption spectroscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy and thermal desorption spectroscopy. Due to packing effects, the molecules in all monolayers are substantially tilted. In the presence of a methylene spacer the tilt is slightly less pronounced. The selenolate monolayers exhibit smaller defect densities and therefore are more densely packed than their thiolate analogues. The Se–Au binding energy in the investigated SAMs was found to be higher than the S–Au binding energy.
The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.
Mistakes in translation of messenger RNA into protein are clearly a detriment to the recombinant production of pure proteins for biophysical study or the biopharmaceutical market. However, they may also provide insight into mechanistic details of the translation process. Mistakes often involve the substitution of an amino acid having an abundant codon for one having a rare codon, differing by substitution of a G base by an A base, as in the case of substitution of a lysine (AAA) for arginine (AGA). In these cases one expects the substitution frequency to depend on the relative abundances of the respective tRNAs, and thus, one might expect frequencies to be similar for all sites having the same rare codon. Here we demonstrate that, for the ADP-ribosylation factor from yeast expressed in E. coli, lysine for arginine substitutions frequencies are not the same at the 9 sites containing a rare arginine codon; mis-incorporation frequencies instead vary from less than 1 to 16%. We suggest that the context in which the codons occur (clustering of rare sites) may be responsible for the variation. The method employed to determine the frequency of mis-incorporation involves a novel mass spectrometric analysis of the products from the parallel expression of wild type and codon-optimized genes in 15N and 14N enriched media, respectively. The high sensitivity and low material requirements of the method make this a promising technology for the collection of data relevant to other mis-incorporations. The additional data could be of value in refining models for the ribosomal translation elongation process.
Human beings are assumed to possess an approximate number system (ANS) dedicated to extracting and representing approximate numerical magnitude information. The ANS is assumed to be fundamental to arithmetic learning and has been shown to be associated with arithmetic performance. It is, however, still a matter of debate whether better arithmetic skills are reflected in the ANS. To address this issue, Chinese and German adults were compared regarding their performance in simple arithmetic tasks and in a non-symbolic numerical magnitude comparison task. Chinese participants showed a better performance in solving simple arithmetic tasks and faster reaction times in the non-symbolic numerical magnitude comparison task without making more errors than their German peers. These differences in performance could not be ascribed to differences in general cognitive abilities. Better arithmetic skills were thus found to be accompanied by a higher speed of retrieving non-symbolic numerical magnitude knowledge but not by a higher precision of non-symbolic numerical magnitude representations. The group difference in the speed of retrieving non-symbolic numerical magnitude knowledge was fully mediated by the performance in arithmetic tasks, suggesting that arithmetic skills shape non-symbolic numerical magnitude processing skills.
Identification of unique cardiolipin and monolysocardiolipin species in Acinetobacter baumannii
(2017)
Acidic glycerophospholipids play an important role in determining the resistance of Gram-negative bacteria to stress conditions and antibiotics. Acinetobacter baumannii, an opportunistic human pathogen which is responsible for an increasing number of nosocomial infections, exhibits broad antibiotic resistances. Here lipids of A. baumannii have been analyzed by combined MALDI-TOF/MS and TLC analyses; in addition GC-MS analyses of fatty acid methyl esters released by methanolysis of membrane phospholipids have been performed. The main glycerophospholipids are phosphatidylethanolamine, phosphatidylglycerol, acyl-phosphatidylglycerol and cardiolipin together with monolysocardiolipin, a lysophospholipid only rarely detected in bacterial membranes. The major acyl chains in the phospholipids are C16:0 and C18:1, plus minor amounts of short chain fatty acids. The structures of the cardiolipin and monolysocardiolipin have been elucidated by post source decay mass spectrometry analysis. A large variety of cardiolipin and monolysocardiolipin species were found in A. baumannii. Similar lysocardiolipin levels were found in the two clinical strains A. baumannii ATCC19606T and AYE whereas in the nonpathogenic strain Acinetobacter baylyi ADP1 lysocardiolipin levels were highly reduced.
HADES is a multi-purpose charged-particle detector operated at the SIS18 synchrotron located at the GSI Helmholtz Center for Heavy Ion Research in Darmstadt, Germany. The provided ion beam energies of 1-2 A GeV are the lowest of all currently running heavy-ion experiments and result in the highest baryo-chemical potentials at freeze-out in case of Au+Au collisions. At this Quark Matter conference we presented results from Au+Au collisions at sNN=2.4GeV. The created system exhibits a very clear hierarchy in hadron yields, with about 100 protons, 10 pions, 10−2 kaons and 10−4 antikaons per event. The HADES program focuses on four main observables: (subthreshold) strangeness production, particle flow and its anisotropies, virtual photon emission and net-proton number fluctuations.
GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced. Loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells did not recapitulate any of the phenotypes observed in GPR116-ELTD1 double deficient mice, indicating that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.
Progressive neurodegenerative diseases plague millions of individuals both in the United States and across the world. The current pathology of progressive neurodegenerative tauopathies, such as Alzheimer’s disease (AD), Pick’s disease, frontotemporal dementia (FTD), and progressive supranuclear palsy, primarily revolves around phosphorylation and hyperphosphorylation of the tau protein. However, more recent evidence suggests acetylation of tau protein at lysine 280 may be a critical step in molecular pathology of these neurodegenerative diseases prior to the tau hyperphosphorylation. Secondary injury cascades such as oxidative stress, endoplasmic reticulum stress, and neuroinflammation contribute to lasting damage within the brain and can be induced by a number of different risk factors. These injury cascades funnel into a common pathway of early tau acetylation, which may serve as the catalyst for progressive degeneration. The post translational modification of tau can result in production of toxic oligomers, contributing to reduced solubility as well as aggregation and formation of neurofibrillary tangles, the hallmark of AD pathology. Chronic Traumatic Encephalopathy (CTE), caused by repetitive brain trauma is also associated with a hyperphosphorylation of tau. We postulated acetylation of tau at lysine 280 in CTE disease could be present prior to the hyperphosphorylation and tested this hypothesis in CTE pathologic specimens. We also tested for ac-tau 280 in early stage Alzheimer’s disease (Braak stage 1). Histopathological examination using the ac tau 280 antibody was performed in three Alzheimer's cases and three CTE patients. Presence of ac-tau 280 was confirmed in all cases at early sites of disease manifestation. These findings suggest that tau acetylation may precede tau phosphorylation and could be the first "triggering" event leading to neuronal loss. To the best of our knowledge, this is the first study to identify acetylation of the tau protein in CTE. Prevention of tau acetylation could possibly serve as a novel target for stopping neurodegeneration before it fully begins. In this study, we highlight what is known about tau acetylation and neurodegeneration.
Lieblingsbild
(2017)
Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance
(2017)
Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed.
In this work, largely based on [J. L. Albacete, A. Soto-Ontoso, Hot spots and the hollowness of proton-proton interactions at high energies, arXiv:1605.09176; J. L. Albacete, H. Petersen, A. Soto-Ontoso, Correlated wounded hot spots in proton-proton interactions, arXiv:1612.06274], we present a novel initial state geometry for proton-proton interactions. We rely on gluonic hot spots as effective degrees of freedom whose transverse positions inside the proton are correlated. We explore the impact of these non-trivial spatial correlations on the eccentricity and triangularity of the system following a Monte Carlo Glauber approach.
The measurement of concentrations of drugs and endogenous substances is widely used in basic and clinical pharmacology research and service tasks. Using data science‐derived visualizations of laboratory data, it is demonstrated on a real‐life example that basic statistical exploration of laboratory assay results or advised standard visual methods of data inspection may fall short in detecting systematic laboratory errors. For example, data pathologies such as generating always the same value in all probes of a particular assay run may pass undetected when using standard methods of data quality check. It is shown that the use of different data visualizations that emphasize different views of the data may enhance the detection of systematic laboratory errors. A dotplot of single data in the order of assay is proposed that provides an overview on the data range, outliers and a particular type of systematic errors where similar values are wrongly measured in all probes.
The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.
Background: To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients’ performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain.
Methods: We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2–4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain.
Results: Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate.
Conclusions: Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.
Wer durch eine Stadt wie Venedig geht, sieht, dass die Zeit überall ihre Spuren hinterlässt. Der britische Kunsthistoriker John Ruskin nennt diese Spuren in seinem 1851 bis 1853 publizierten Reisebericht 'The Stones of Venice' "time stains" und macht darin eindrücklich darauf aufmerksam, dass Spuren der Zeit ästhetisch betrachtet werden können, obwohl sie kein Produkt des Menschen, sondern zunächst einmal eines der Zeit sind. Vor diesem Hintergrund drängt sich die Frage auf, ob und inwiefern die Zeit als Gestalterin ästhetischer Objekte begriffen werden kann und wie sie dieses Potenzial in Konkurrenz zu kulturellen Gestaltungsabsichten erfüllt.
Zur Beantwortung dieser Frage lassen sich die im Kontext der Ruinenästhetik geführten Diskussionen und das seit einigen Jahren zu verzeichnende neue Interesse am Naturschönen folgendermaßen verbinden und zuspitzen: Die Zeit muss als gegenkulturelle Gestalterin der Lebenswelt genauer ins Visier und als ästhetisches Subjekt ernst genommen werden. Der Beitrag reiht sich damit in die seit einigen Jahren Konjunktur verzeichnende ästhetische Auseinandersetzung mit der Zeit ein. Dort ist bislang versäumt worden, dezidiert nach der ästhetischen Gestaltungskraft von Zeit zu fragen, während man die kulturelle Gestaltbarkeit von Zeit betont hat.
Nicht selten waren es im Übrigen dieselben Autoren, die zunächst mit heftig-expressiven Worten den Krieg herbeigeredet hatten; die ihn als existenzielles, ästhetisches und erotisches Überwältigungserlebnis feierten und die – zumal nach den blutigen Ernüchterungen von Langemarck und anderen Schlachterlebnissen in der Frühphase des Ersten Weltkriegs – sein Zerstörungswerk und die mit ihm verbundenen materiellen und ideellen Katastrophen entsetzt und erschüttert, leidenschaftlich und in messianisch-erlösungsgieriger Manier zu verbannen versuchten. Die sog. expressionistische Generation ist für diese "Ambivalenz" das immer wieder zitierte Beispiel; auch wenn der Terminus "Ambivalenz" in meiner Sicht für einen solchen Wandel vom Kriegstaumel zum Pazifismus eigentümlich euphemistisch klingt. Ich möchte im Folgenden an einigen Beispielen den rhetorischen und thematischen, den stilistischen und den analytischen Überschwang veranschaulichen, mit dem Autoren und Autorinnen vor, während und nach dem Ersten Weltkrieg die Gewalt der Zerstörung entweder ersehnten oder beklagten, bejubelten oder betrauerten (vgl. Buelens 2014). Das Spektrum von hierfür möglichen Autoren und Texten, Positionen und Publikationen ist viel zu groß, als dass die folgenden Überlegungen Anspruch auf Repräsentativität erheben könnten; mit der getroffenen Auswahl soll gleichwohl der hier interessierende Konnex zwischen Wortgewalt und Kriegserfahrung möglichst aussagekräftig vergegenwärtigt werden.
Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders.
Empreende-se aqui uma leitura de Viagem à Itália, de Goethe, menos como uma obra autobiográfica do que como uma das muitas narrativas enciclopédicas do autor, em que relatos de diferentes dicções e propósitos são reunidos sob motivos e sugestões comuns. Aqui, busca-se identificar esse fio condutor sob a percepção goethiana das formas. Sob o termo, entendemos tanto as formas naturais quanto artísticas, assim como os objetos e ritos da religião católica, trazidas pela experiência italiana.
Biomaterials are widely used in guided bone regeneration (GBR) and guided tissue regeneration (GTR). After application, there is an interaction between the host immune system and the implanted biomaterial, leading to a biomaterial-specific cellular reaction. The present review focuses on cellular reactions to numerous biomaterials in vivo with consideration of different implantation models and microenvironments in different species, such as subcutaneous implantation in mice and rats, a muscle model in goats and a femur model in rabbits. Additionally, cellular reactions to different biomaterials in various clinical indications within the oro-maxillofacial surgical field were considered. Two types of cellular reactions were observed. There was a physiological reaction with the induction of only mononuclear cells and a pathological reaction with the induction of multinucleated giant cells (MNGCs). Attention was directed to the frequently observed MNGCs and consequences of their appearance within the implantation region. MNGCs have different subtypes. Therefore, the present review addresses the different morphological phenotypes observed within the biomaterial implantation bed and discusses the critical role of MNGCs, their subtypes and their precursors as well as comparing the characteristics and differences between biomaterial-related MNGCs and osteoclasts. Polymeric biomaterials that only induced mononuclear cells underwent integration and maintained their integrity, while polymeric biomaterials that induced MNGCs underwent disintegration with material breakdown and loss of integrity. Hence, there is a question regarding whether our attention should be directed to alternative biological concepts, in combination with biomaterials that induce a physiological mononuclear cellular reaction to optimize biomaterial-based tissue regeneration.
Systemic lupus erythematosus (SLE) is a chronic disease characterized by progressive tissue damage. In recent decades, novel treatments have greatly extended the life span of SLE patients. This creates a high demand for identifying the overarching symptoms associated with SLE and developing therapies that improve their life quality under chronic care. We hypothesized that SLE patients would present dysphonic symptoms. Given that voice disorders can reduce life quality, identifying a potential SLE-related dysphonia could be relevant for the appraisal and management of this disease. We measured objective vocal parameters and perceived vocal quality with the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched healthy controls. SLE patients also filled a questionnaire reporting perceived vocal deficits. SLE patients had significantly lower vocal intensity and harmonics to noise ratio, as well as increased jitter and shimmer. All subjective parameters of the GRBAS scale were significantly abnormal in SLE patients. Additionally, the vast majority of SLE patients (29/36) reported at least one perceived vocal deficit, with the most prevalent deficits being vocal fatigue (19/36) and hoarseness (17/36). Self-reported voice deficits were highly correlated with altered GRBAS scores. Additionally, tissue damage scores in different organ systems correlated with dysphonic symptoms, suggesting that some features of SLE-related dysphonia are due to tissue damage. Our results show that a large fraction of SLE patients suffers from perceivable dysphonia and may benefit from voice therapy in order to improve quality of life.
Köşker 2015 yılında yayımlanan "Yabancı Dil Öğretiminde Kültür Aktarımı: Fransız Dili Örneği" başlıklı makalesinde geçmişten günümüze süregelen hedeflerin aksine dil öğrenmenin temel amacının artık öğrenilen dili konuşan kişilerle yazılı veya sözlü iletişim kurabilmek olduğunu belirtmiş, ancak Zeuner (1997) gibi o da konuşma ve anlama üzerine kurulu yazılı ve sözlü iletişim yetisini kullanabilmek için sadece dilbilgisi kurallarını bilmenin yetmediğini, bunun yanı sıra etkileşime girilen kişilerin yaşadıkları topluma ilişkin kültürel değerler hakkında da bilgi sahibi olmak ve dili konuşanların sözel olmayan mesajlarını da anlamak gerektiğini vurgulamıştır. Köşker ve Zeuner'in bu görüşlerinden hareketle bu çalışmada Milli Eğitim Bakanlığı Talim ve Terbiye Kurulu Başkanlığının 2016-2017 öğretim yılından itibaren 5 (beş) yıl süreyle ders kitabı olarak kabul ettiği ve okullarda 2016-2017 eğitim-öğretim yılında yaygın olarak kullanılan Türkiye'de hazırlanmış ve basılmış olan Schritt für Schritt Deutsch Ortaöğretim A1.1 Düzeyi Almanca Ders Kitabı (Çelen Öztürk, 2016) içerdiği kültürel öğeler bakımından Tomková'nın (1992) ve Arıkan ve Saraç'ın (2010) geliştirmiş oldukları ölçütler doğrultusunda mercek altına alınmış ve veriler betimsel analiz yöntemi ile çözümlenerek, yorumlanmıştır. Veriler, Schritt für Schritt Deutsch Ortaöğretim A1.1 Düzeyi Almanca Ders Kitabında hedef dilin konuşulduğu ülkenin günlük yaşamına ve kültürüne ilişkin Türkçede 'Ülke Bilgisi' olarak karşılık bulan Landeskunde kavramı bağlamında coğrafi, tarihsel, sayısal, istatistiksel vs. gibi bilgilere yer verildiğini, bunun ötesinde öğrencilerin hedef dil kültürel öğeleri görmelerini ve duymalarını ve bu yolla zihinlerinde hayal edebilmelerini sağlayan ve kendi kültürü ile hedef dilin kültürünü karşılaştırabileceği ve empati kurabileceği düzenlemelere gidildiğini, ancak gerek 'Kültürlerarasılık' kavramı bağlamında yapılması öngörülen etkinliklerin gerekse ‘Ülke Bilgisi’ olarak karşılık bulan Landeskunde kavramı bağlamında sunulan coğrafi, tarihsel, sayısal, istatistiksel vs. gibi bilgilerin sayıca oldukça sınırlı olduğunu ortaya koymuştur. Araştırma kitapta yabancı olanı doğru anlayabilmek için mutlaka bilinmesi gereken hedef dilin konuşulduğu ülkeye has kültürel değerlere çok az değinildiğini ve erek dili konuşanların sözel olmayan mesajlarını da anlayabilme becerisini de geliştirecek türde düzenlemelere gidilmesi gerektiğini ortaya koymuştur.
Objective: The aim of this study was to evaluate and compare the efficacy of single-treatment cooled and uncooled microwave ablation in thyroid nodules.
Methods: Eighteen patients (11 women) with an average age of 62 years (range: 41–80) with 18 cold, mainly solid or solid thyroid nodules were treated with cooled or uncooled microwave ablation. Pain during the treatment was measured on a 10-point score. Side effects revealed by ultrasound or patients’ complaints were documented. Laboratory data was evaluated before, 24 h and three months after MWA. Nodule volumes were measured before and three months after MWA.
Results: Cooled MWA was better tolerated than uncooled MWA. A significant reduction of thyroid nodule volume was observed in all cases. The reduction after cMWA was higher (40%) than after uMWA (29%). Pain intensity during cMWA was significantly lower than after uMWA. CMWA and uMWA led to a significant decrease of nodule blood circulation and echogenicity and to a significant increase of nodule elasticity. Thyroid function remained intact in all cases. The energy (kJ/s) administered into the nodules in relation to the ablation time during cMWA was higher than during uMWA.
Conclusions: CMWA leads to a slightly higher but statistically not significant nodule volume reduction than uMWA. Patient comfort during cMWA is higher than during uMWA. The risk of unintended side effects is less in cMWA. A Single-treatment provides sufficient results.
Background: Oral anticoagulation therapy (OAT) is a challenge in general practice, especially for high-risk groups such as the elderly. Insufficient patient knowledge about safety-relevant aspects of OAT is considered to be one of the main reasons for complications. The research question addressed in this manuscript is whether a complex intervention that includes practice-based case management, self-management of OAT and additional patient and practice team education improves patient knowledge about anticoagulation therapy compared to a control group of patients receiving usual care (as a secondary objective of the Primary Care Management for Optimised Antithrombotic Treatment (PICANT) trial).
Methods: The cluster-randomised controlled PICANT trial was conducted in 52 general practices in Germany, between 2012 and 2015. Trial participants were patients with a long-term indication for oral anticoagulation. A questionnaire was used to assess knowledge at baseline, after 12, and after 24 months. The questionnaire consists of 13 items (with a range of 0 to 13 sum-score points) covering topics related to intervention. Differences in the development of patient knowledge between intervention and control groups compared to baseline were assessed for each follow-up by means of linear mixed-effects models.
Results: Seven hundred thirty-six patients were included at baseline, of whom 95.4% continued to participate after 12 months, and 89.3% after 24 months. The average age of patients was 73.5 years (SD 9.4), and they mainly suffered from atrial fibrillation (81.1%). Patients in the intervention and control groups had similar knowledge about oral anticoagulation at baseline (5.6 (SD 2.3) in both groups). After 12 months, the improvement in the level of knowledge (compared to baseline) was significantly larger in the intervention group than in the control group (0.78 (SD 2.5) vs. 0.04 (SD 2.3); p = 0.0009). After 24 months, the difference between both groups was still statistically significant (0.6 (SD 2.6) vs. -0.3 (SD 2.3); p = 0.0001).
Conclusion: Since this intervention was effective, it should be established in general practice as a means of improving patient knowledge about oral anticoagulation.
Trial registration: Current controlled trials ISRCTN41847489; Date of registration: 13/04/2012
The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of the interaction remain elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with coevolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted in a novel structural model that rationalizes previous experimental observations. We identify an evolutionarily conserved interaction surface formed by helix II of the DnaJ J-domain and a structurally contiguous region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter-domain linker, and the β-basket of the substrate binding domain.
This paper presents an analysis of the novel 'Die fremde Frau' by the writer Paul Zifferer (1879-1929) who came from Bystřice pod Hostýnem in Moravian Wallachia. It is a largely unknown, late naturalistic text which addresses national and social issues that were topical at the end of the 19th century. The novel offers a critical reflection on both bourgeois society and national tensions in Moravian Wallachia. It oscillates between conservativism and revolution, between historical authenticity and fiction. Moreover, the analysis shows that German literature from Moravian Wallachia deserves a serious and comprehensive exploration - as does Paul Zifferer's work, especially in the context of German or Austrian naturalism and aesthetic modernism.
Genetic factors and mechanisms underlying food allergy are largely unknown. Due to heterogeneity of symptoms a reliable diagnosis is often difficult to make. Here, we report a genome-wide association study on food allergy diagnosed by oral food challenge in 497 cases and 2387 controls. We identify five loci at genome-wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the cytokine gene cluster at 5q31.1, the filaggrin gene, the C11orf30/LRRC32 locus, and the human leukocyte antigen (HLA) region. Stratifying the results for the causative food demonstrates that association of the HLA locus is peanut allergy-specific whereas the other four loci increase the risk for any food allergy. Variants in the SERPINB gene cluster are associated with SERPINB10 expression in leukocytes. Moreover, SERPINB genes are highly expressed in the esophagus. All identified loci are involved in immunological regulation or epithelial barrier function, emphasizing the role of both mechanisms in food allergy.
Heute am 14. Dezember kommt der Film "Leaning into the Wind" über den britischen Landart Künstler Andy Goldsworthy in die Kinos. Exklusiv stand der Regisseur Thomas Riedelsheimer bei der Vorpremiere am vergangenen Samstag seinem Publikum Rede und Antwort. Bereits 2001 hatten Goldsworthy und Riedelsheimer einen Film über das Schaffen des außergewöhnlichen Künstlers produziert. Nach 16 Jahren knüpfen sie nun an die Erfolgsgeschichte von damals an und schaffen 90 Minuten eindrucksvolles Bildmaterial, das durch seine vielfältigen Kameraeinstellungen ein umfassendes und intimes Porträt des Künstlers und seiner nahezu symbiotischen Arbeit in und mit der Natur kreiert. ...
Der Anarchismus stellt eine Form des Gefühls der Grenzenlosigkeit dar. Ob der politische Anarchismus auf dieser affektiven Basis entsteht oder einen anderen Ursprung hat, sei zunächst dahingestellt. Wie ist es aber möglich, dass sich dieses Gefühl immer wieder entwickelt, ohne sein Ziel - die Grenzenlosigkeit - je erreichen zu können? Um diese Frage zu beantworten, möchte ich an der Wurzel dieses Gefühls ansetzen. Oft gründet das Gefühl überbordender Freiheit im Gefühl des Behütetseins bzw. des Schutzes, in dem man nur allmählich zum Wunsch der Überschreitung kommt, weil die Grenzen nicht fühlbar waren, innerhalb derer sich das Kind in seiner familiären Tätigkeitssphäre noch unbewusst bewegte. Gerade die Abwesenheit eines Kanons von Verhaltensregeln ermöglichte es dem Kind, den Fallen und Inklinationen transgenerationaler Verhaltensanweisungen gegenüber noch frei zu bleiben. In dieser Grenzferne des Kindes - sowie auch im Zustand der Resignation mancher Erwachsenen, die ihr Ziel nicht erreichen konnten und aufgeben mussten - kann das gedeihen, was jene "Lehre von der Freiheit als Grundlage der menschlichen Gesellschaft" erahnen lässt, die Erich Mühsams sozialistischer Prägung als sittlicher Zustand und geistige Welt gegolten hatte. Gesetzesferne bedeutet aber noch keine intendierte Gesetzlosigkeit.
Aus der Gesetzesferne trifft das Kind vielmehr allmählich auf die Regularien, die diese Gesetzesferne durch soziale Entitäten ablösen wollen. Die Grenzferne des Kindes hatte aber bereits tiefergreifend seine Handlungsauffassung geprägt. Im Folgenden möchte ich die These entwickeln, nach der ein Element des Anarchismus eine schon früh ansetzende Gefühlsform ist.
This paper presents a follow-up study of Markovits et al.’s (2014) comparison of large samples of Greek employees before and at the onset of the economic crisis. Now at the crisis’ peak, we again sampled data from 450 employees about their job satisfaction, organizational commitment, regulatory focus, and burnout. Overall, compared to the two samples before, employees’ job attitudes further decrease with lower normative and higher continuance commitment, lower (extrinsic and intrinsic) job satisfaction and both lower promotion and (somewhat surprisingly) even lower prevention orientation. Expanding previous studies, results show that satisfaction and commitment are also related to burnout and that those participants who are currently employed but had experienced personal unemployment during the crisis showed more negative attitudes and higher burnout.
Ziel der vorliegenden Arbeit ist die Vorstellung einer Übersicht über die Moose und Moosgesellschaften der Kalkrasen sowie der angrenzenden Vegetationstypen im Muschelkalkgebiet des unteren Unstruttales in der Umgebung von Zscheiplitz zwischen Laucha und Freyburg/Unstrut. Bedeutungsvoll sind in einem Kalksteinbruch, in verschiedenen Trocken- und Halbtrockenrasen sowie Xerothermgebüschen die epilithischen, photophytischen Assoziationen Orthotricho anomali-Grimmietum pulvinatae, Grimmietum orbicularis, das seltene Grimmietum tergestinae, die sciophytischen Gesellschaften Homomallietum incurvati und die Homalothecium sericeum-Gesellschaft. Auf Kalkböden gedeihen häufig das Tortelletum inclinatae, vereinzelt das Barbuletum convolutae, in den Fugen der Kalkbänke das Weissietum crispatae und Aloinetum rigidae mit Aloina obliquifolia. Auf der Borke lebender Laubgehölze wachsen vereinzelt das Orthotrichetum fallacis, Syntrichio latifoliae-Leskeetum polycarpae, lokal das Ulotetum crispae, Syntrichietum pulvinatae und Orthotrichetum pallentis. Alle Gesellschaften sind durch zahlreiche Vegetationsaufnahmen in 11 Tabellen dargestellt. Insgesamt wurden 21 Moosgesellschaften und 104 Moosarten (7 Lebermoose, 97 Laubmoose) nachgewiesen. Die Diskussion betrifft die bryogeographische Situation in der Umgebung von Zscheiplitz sowie die Lebensformen, Lebensstrategien und Reproduktionsstrategien der Moose und Moosgesellschaften.
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation of the receptor-interacting protein kinases 1 and 3 (RIPK1/3) in a necrosome complex, eventually leading to the phosphorylation and relocation of mixed lineage kinase domain like protein (MLKL). Using a high-content screening of small compounds and FDA-approved drug libraries, we identified the anti-cancer drug Sorafenib tosylate as a potent inhibitor of TNF-dependent necroptosis. Interestingly, Sorafenib has a dual activity spectrum depending on its concentration. In murine and human cell lines it induces cell death, while at lower concentrations it inhibits necroptosis, without affecting NF-κB activation. Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 and MLKL. Moreover, it inhibits RIPK1 and RIPK3 kinase activity. In vivo Sorafenib protects against TNF-induced systemic inflammatory response syndrome (SIRS) and renal ischemia–reperfusion injury (IRI). Altogether, we show that Sorafenib can, next to the reported Braf/Mek/Erk and VEGFR pathways, also target the necroptotic pathway and that it can protect in an acute inflammatory RIPK1/3-mediated pathology.
Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC) count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL) and myeloperoxidase+ tumor-associated neutrophils (TANs) in patients with anal squamous cell carcinoma (ASCC) treated with definitive chemoradiotherapy (CRT). After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001) and N-stage (p < 0.001), and predicted for worse distant-metastasis-free survival (p = 0.006), disease-free-survival (DFS, p = 0.029), and overall survival (p = 0.013). Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014), whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028). Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039), albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.
O reconhecimento é um conceito normativo. Ao reconhecermos alguém como portador de determinadas características ou capacidades, reconhecemos seu status normativo e estamos assumindo responsabilidade por tratar este alguém de determinada forma. O não reconhecimento, neste caso, pode significar privação de direitos e marginalização; em uma democracia pode impossibilitar indivíduos ou grupos de desfrutar o ideal igualitário democrático, por exemplo. Nas últimas três décadas, a reflexão sobre esta categoria se aprofundou e assumiu maior importância no debate entre liberalismo e comunitarismo em paralelo às demandas, por vezes pelas conquistas, de grupos e minorias (LGBTQIA, portadores de necessidades especiais, feministas, indígenas, étnicos, etc.) que se sentem não reconhecidos e se engajam em movimentos políticos através de lutas por reconhecimento. Retomaremos, aqui, o desenvolvimento do conceito de “eticidade” empreendido por Axel Honneth em Luta por reconhecimento (1992), obra fundamental para a reflexão sobre o tema. O autor situa sua teoria no meio termo entre a moral kantiana e as éticas comunitaristas: sua concepção é formal por entender que normas universais são condições de algumas possibilidades, mas é substantiva por se orientar pelo fim da autorrealização humana.
We present a method that enables the identification and analysis of conformational Markovian transition states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented by using both analytical models and examples from MD simulations of the benchmark system helix-forming peptide Ala5, and of larger, biomedically important systems: the 15-lipoxygenase-2 enzyme (15-LOX-2), the epidermal growth factor receptor (EGFR) protein, and the Mga2 fungal transcription factor. The analysis of 15-LOX-2 uses data generated exclusively from biased umbrella sampling simulations carried out at the hybrid ab initio density functional theory (DFT) quantum mechanics/molecular mechanics (QM/MM) level of theory. In all cases, our method automatically identifies the corresponding transition states and metastable conformations in a variationally optimal way, with the input of a set of relevant coordinates, by accurately reproducing the intrinsic slowest relaxation rate of each system. Our approach offers a general yet easy-to-implement analysis method that provides unique insight into the molecular mechanism and the rare but crucial (i.e., rate-limiting) transition states occurring along conformational transition paths in complex dynamical systems such as molecular trajectories.
Red-billed tropicbirds (Phaethon aethereus) are distributed throughout the tropical waters of the Eastern Pacific, the Northwest Indian Ocean and the Atlantic Ocean; in the latter, the species is represented by P. a. mesonauta (Del Hoyo et al. 1992). The brown booby (Sula leucogaster) is the species with the largest distribution within the Sulidae (Patterson et al. 2011) with breeding sites across the Atlantic, Indian and Pacific oceans (Morris-Pocock et al. 2010).
We performed an intercomparison of river discharge regulated by dams under four meteorological forcings among five global hydrological models for a historical period by simulation. This is the first global multimodel intercomparison study on dam-regulated river flow. Although the simulations were conducted globally, the Missouri–Mississippi and Green–Colorado Rivers were chosen as case-study sites in this study. The hydrological models incorporate generic schemes of dam operation, not specific to a certain dam. We examined river discharge on a longitudinal section of river channels to investigate the effects of dams on simulated discharge, especially at the seasonal time scale. We found that the magnitude of dam regulation differed considerably among the hydrological models. The difference was attributable not only to dam operation schemes but also to the magnitude of simulated river discharge flowing into dams. That is, although a similar algorithm of dam operation schemes was incorporated in different hydrological models, the magnitude of dam regulation substantially differed among the models. Intermodel discrepancies tended to decrease toward the lower reaches of these river basins, which means model dependence is less significant toward lower reaches. These case-study results imply that, intermodel comparisons of river discharge should be made at different locations along the river's course to critically examine the performance of hydrological models because the performance can vary with the locations.
The 236U isotope plays an important role in nuclear systems, both for future and currently operating ones. The actual knowledge of the capture reaction of this isotope is satisfactory in the thermal region, but it is considered insufficient for Fast Reactor and ADS applications. For this reason the 236U(n, γ) reaction cross-section has been measured for the first time in the whole energy region from thermal energy up to 1 MeV at the n_TOF facility with two different detection systems: an array of C6D6 detectors, employing the total energy deposited method, and a FX1 total absorption calorimeter (TAC), made of 40 BaF2 crystals. The two n_TOF data sets agree with each other within the statistical uncertainty in the Resolved Resonance Region up to 800 eV, while sizable differences (up to ≃ 20%) are found relative to the current evaluated data libraries. Moreover two new resonances have been found in the n_TOF data. In the Unresolved Resonance Region up to 200 keV, the n_TOF results show a reasonable agreement with previous measurements and evaluated data.
The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data.
In 2006, the Task Force of the European Society of Cardiology published its consensus document on the use of autologous cell therapy for repair of the heart. Since then, there have been numerous clinical trials and analyses performed to establish the role of autologous cell therapy in the treatment of both acute and chronic cardiac disease. The majority of these studies have been Phase II clinical trials. Phase III clinical trials of autologous cell therapy have been launched (e.g. BAMI), which marks the successful progression of clinical investigation of autologous cell therapy in heart disease. The Task Force has reviewed its 2006 recommendations and the developments in this area of research and proposes updated recommendations for the future of autologous cell therapy in the heart. This article does not duplicate the many reviews on stem cells and the heart but gives considered recommendations based on the experience from the last 10 years.
There is mounting evidence that aerobic exercise has a positive effect on cognitive functions in older adults. To date, little is known about the neurometabolic and molecular mechanisms underlying this positive effect. The present study used magnetic resonance spectroscopy and quantitative MRI to systematically explore the effects of physical activity on human brain metabolism and grey matter (GM) volume in healthy aging. This is a randomised controlled assessor-blinded two-armed trial (n=53) to explore exercise-induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age >65) were allocated to a 12-week individualised aerobic exercise programme intervention (n=29) or a 12-week waiting control group (n=24). The main outcomes were the change in cerebral metabolism and its association to brain-derived neurotrophic factor (BDNF) levels as well as changes in GM volume. We found that cerebral choline concentrations remained stable after 12 weeks of aerobic exercise in the intervention group, whereas they increased in the waiting control group. No effect of training was seen on cerebral N-acetyl-aspartate concentrations, nor on markers of neuronal energy reserve or BDNF levels. Further, we observed no change in cortical GM volume in response to aerobic exercise. The finding of stable choline concentrations in the intervention group over the 3 month period might indicate a neuroprotective effect of aerobic exercise. Choline might constitute a valid marker for an effect of aerobic exercise on cerebral metabolism in healthy aging.
Marcel Proust musste bekanntlich einiges dafür tun, um die Aufregung zu lindern, die im Freundes- und Bekanntenkreis aufgekommen ist, wenn es um die Durchschaubarkeit biografischer Vorbilder für die eine oder andere seiner Figuren ging. Die Tatsache, dass der Autor die eigene Homosexualität von der Erzählerfigur auf andere Protagonisten gleichsam umgelenkt hat, spielt dabei eine zwar wichtige, aber nicht die entscheidende Rolle. Statt biografischem Voyeurismus kommt es darauf an, die Bewegungen, die zwischen Fiktion und Realität in beiden Richtungen verlaufen, genau zu erfassen.
Gerade die Unauffälligkeit, mit der es ihm gelingt, Gegebenheiten der Zeitgeschichte im Kontext der aristokratischen Zusammenkünfte als Teil der erfundenen Welt erscheinen zu lassen, gehört zu den fesselndsten Zügen des Romans 'In Swanns Welt‘. Eine in diesem Zusammenhang jedenfalls sehr bemerkenswerte Figur ist diejenige der Königin von Neapel. Sie gehört im fünften Teil des Romans "La Prisonnière" (erschienen 1923) zu denjenigen Gästen, die Baron Charlus in die Gesellschaft eingeladen hat, die die Verdurins veranstalten.
One of the notable features of penguin evolution is the occurrence of very large species in the early Cenozoic, whose body size greatly exceeded that of the largest extant penguins. Here we describe a new giant species from the late Paleocene of New Zealand that documents the very early evolution of large body size in penguins. Kumimanu biceae, n. gen. et sp. is larger than all other fossil penguins that have substantial skeletal portions preserved. Several plesiomorphic features place the new species outside a clade including all post-Paleocene giant penguins. It is phylogenetically separated from giant Eocene and Oligocene penguin species by various smaller taxa, which indicates multiple origins of giant size in penguin evolution. That a penguin rivaling the largest previously known species existed in the Paleocene suggests that gigantism in penguins arose shortly after these birds became flightless divers. Our study therefore strengthens previous suggestions that the absence of very large penguins today is likely due to the Oligo-Miocene radiation of marine mammals.
Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications.
La connaissance du potentiel et de la productivité d'une ressource est une donnée nécessaire à l'élaboration d'une bonne politique de sa gestion. La structure et la productivité des peuplements à Acacia seyal Del. et à Acacia senegal (L) Willd.ont été étudiées dans les formations naturelles de Massenya au Tchad. Sur la base de 32 placeaux de 900 m2 , le diamètre et la hauteur de tous les individus d’espèces ligneuses ont été mesurés. Pour des espèces adultes à port arbustif, le diamètre est mesuré à 50 cm du sol. Les individus juvéniles sont simplement comptés et rangés en classe de hauteur. L’étude de la structure des peuplements et de deux espèces d’Acacia a été réalisée à travers le nombre de tiges à l’hectare et les classes de diamètre. L’Indice de Valeur d’Importance (IVI) a été utilisée pour apprécier la prédominance des espèces sur le site. La productivité des peuplements en gomme a été évaluée en fonction de la production moyenne d’un arbre qui était de 250 g. Les peuplements à Acacia de Massenya sont très denses (619 ± 269 tiges/ha), mais à surface terrière faible (7,10 ± 1,20 m²/ ha) due à un grand nombre d’individus de petit diamètre (11,1 ± 2,2 cm). Ce sont des peuplements généralement arbustif (hauteur de 5,2 ± 0,9 m) avec un bon potentiel de juvéniles (408 ± 267 tiges/ha) pouvant se régénérer naturellement. Toutefois, Acacia seyal semble plus apte à coloniser d’autres milieux qu’Acacia senegal. Sur les sept espèces qui prédominent sur le site, Acacia seyal et Acacia senegal réalisent des IVI plus élevés (respectivement 79 et 54). Les espèces à bon potentiel de régénération sont Acacia seyal (65 ± 8 juv./ha), Acacia senegal (58 ± 10 juv./ha) et Guiera senegalensis (51 ± 8 juv./ha). La production annuelle de gomme est estimée à 56 ± 6 kg/ha de gomme friable (à Acacia seyal) et 41 ± 5 kg/ha de gomme dure (à A. senegal).
If Third World women form ‘the bedrock of a certain kind of global exploitation of labour,’ as Chandra Mohanty argues, how can our theoretical definitions of exploitation account for this? This paper argues that liberal theories of exploitation are insufficiently structural and that Marxian accounts are structural but are insufficiently intersectional. What we need is a structural and intersectional definition of exploitation in order to correctly identify global structural exploitation. Drawing on feminist, critical race/post-colonial and post-Fordist critiques of the Marxist definition and the intersectional accounts of Maria Mies and Iris Marion Young, this paper offers the following definition of structural exploitation: structural exploitation refers to the forced transfer of the productive powers of groups positioned as socially inferior to the advantage of groups positioned as socially superior. Global structural exploitation is a form of global injustice because it is a form of oppression.
Soil frequently occurs as a contaminant on numerous sea, land and air transport pathways. It can carry unwanted invasive species, is widely recognized as a biosecurity risk, and is usually strictly regulated by biosecurity authorities. However, little is known about relative risk levels between pathways, thus authorities have limited capability to identify and target the riskiest soil pathways for management. We conducted a an experiment to test the hypotheses that biosecurity risks from soil organisms will increase both with declining transport duration and with increasing protection from environmental extremes. Soil was collected from two sites, a native forest remnant and an orchard, and stored on, in and under sea containers, or in cupboards, and assayed after 0, 3, 6 and 12 months for bacteria, fungi, nematodes and seeds. Results showed that viability of Pseudomonas spp., bacteria, nematodes and plants declined over 12 months, irrespective of soil source. Also, mortality of most biota was higher when exposed to sunlight, moisture and desiccation than when protected. However, bacterial and fungal numbers were higher in exposed environments, possibly due to ongoing colonization of exposed soil by airborne propagules. The results were consistent with our observations of organisms in soil intercepted from airports and sea ports, and indicated there is potential to rank risks from transported soils based partly on transport duration and environmental exposure. This would help authorities to optimally allocate management resources according to pathway-specific risks.
A compreensão histórica de literatura no primeiro romantismo alemão decorre, entre outros aspectos, dos escritos de Winckelmann, Herder, Lessing, assim como da relação dialética entre o clássico e o romântico estabelecida por Goethe e Schiller. Nesse contexto, a aproximação antitética entre o antigo e o romântico tem um papel central na determinação das principais teorias românticas de literatura. O artigo investiga e discute a importância da antinomia entre o antigo e o moderno na constituição e desenvolvimento das teorias literárias de Friedrich Schlegel no primeiro romantismo alemão
Ebenso wie Pierre Bourdieu ist sein Schüler Loïc Wacquant einer der selten gewordenen Intellektuellen, die ihre Profession, die Soziologie, nutzen um soziale Ungleichheiten und gesellschaftliche Machtverhältnisse nicht nur zu analysieren, sondern auch versuchen, damit auf öffentliche Debatten zu einzuwirken. Daher ist Wacquants Aufsatz nicht nur als eine interessante Diskussion der Frage, ob Bourdieus Werk in der Stadtsoziologie angemessen und korrekt verwendet werde, zu verstehen. Der in dem Text formulierte Appell, Bourdieus Arbeit auch innerhalb der Stadtsoziologie stärker anzuwenden, ist – vor dem Hintergrund zunehmender sozialer Ungleichheit, Armut, Marginalisierung und einem Aufschwung des Rechtspopulismus – eine Forderung nach einer soziologischen Betrachtung dieser Probleme in der Stadt. Was kann nun also das Werk von Pierre Bourdieu zur Analyse der heutigen sozialen Probleme in der Stadt in Deutschland beitragen?
Ilse Aichingers 'Spiegelgeschichte' ist einer der schon früh zum Klassiker avancierten Prosatexte der österreichischen Nachkriegsliteratur. Nachdem Aichinger seit Anfang des Jahres 1948 gut eineinhalb Jahre daran gearbeitet hatte, erschien der Text erstmals in drei Fortsetzungen im August 1949 in der Wiener Tageszeitung, 1952 folgte die Publikation in der Rede unter dem Galgen betitelten Ausgabe von Hans Weigel. Isoliert man das erzählte Geschehen aus der von einer anonymen Du-Stimme anachronisch erzählten Analepse, erzählt man die spiegelverkehrt vergebenen Informationen im Text also 'realistisch' nach, so hat man es zunächst mit einem recht simplen plot zu tun: Eine junge Frau erlebt mit dem frühen Verlust ihrer Mutter und der damit einhergehenden Verantwortung für ihre jüngeren Brüder eine schwere Kindheit, verliebt sich, träumt von einer guten Zukunft, wird ungewollt schwanger und lässt von einer Kurpfuscherin eine Abtreibung vornehmen, an deren Folgen sie stirbt. Aichinger verweigert ihrer Geschichte aber einen solchermaßen linearen Verlauf und unterminiert alle traditionellen "Parameter der realistisch-mimetischen Schreib- und Leseweise", indem sie logische wie chronologische Denkmuster aushebelt. Ihre Geschichte beginnt mit einem Irrealis, nämlich der Imagination des Tot-Seins: Die im Krankenhaus im Sterben liegende Protagonistin antizipiert die eigene Begräbnissituation, schickt sich selbst aus ihrem Grab wieder hinaus und vergegenwärtigt sich ihr Leben stationsweise raffend jeweils gegenchronologisch vom Grab, über die Leichenhalle, das Sterbebett, die Abtreibung, die Liebesgeschichte, den ersten Geschlechtsverkehr, die Schulzeit und die Kindheit bis zu ihrer Geburt.
Este escrito reconstruye la problematización que Wellmer hace del planteamiento adorniano sobre el hundimiento de la metafísica y su articulación con una eventual alternativa estética para, inmediatamente, explorar la propuesta integral de la tercera Escuela de Frankfurt en torno a la eticidad democrática, sustentable desde los planteamientos de Dubiel, Honneth y Wellmer, como alternativa para una superación de las aporías que Adorno y la primera Escuela de Frankfurt no logran superar, categoría que nos remite en Habermas a su noción del patriotismo constitucional donde adquiere toda su proyección política postconvencional la eticidad democrática y que concurre en la figura de una opinión pública contestataria, que tanto Habermas como Nancy Fraser han querido fundamentar, como opción contra hegemónica y potencialmente emancipatoria en las sociedades en conflicto, para finalmente articular lo anterior con el talante cosmopolita del republicanismo que enfatiza, desde Nussbaum, Bohman y de nuevo Fraser, la perspectiva transnacional que las aspiraciones emancipatorias pueden tener en un mundo global, cuyas sinergias confluyen y concretan no solo estrategias de convivencia democrática nacionales e internacionales sino además, a través de las mismas, la superación concreta —no meramente ética o estética— de fenómenos de autoritarismo político y alienación social, en tanto mediación idónea, aunque parcial, de reconciliación en las sociedades complejas.
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.
AirCore-HR : a high-resolution column sampling to enhance the
vertical description of CH₄ and CO₂
(2017)
An original and innovative sampling system called AirCore was presented by NOAA in 2010 (Karion et al., 2010). It consists of a long ( > 100 m) and narrow (< 1 cm) stainless steel tube that can retain a profile of atmospheric air. The captured air sample has then to be analyzed with a gas analyzer for trace mole fraction. In this study, we introduce a new AirCore aiming to improve resolution along the vertical with the objectives to (i) better capture the vertical distribution of CO2 and CH4, (ii) provide a tool to compare AirCores and validate the estimated vertical resolution achieved by AirCores. This (high-resolution) AirCore-HR consists of a 300 m tube, combining 200 m of 0.125 in. (3.175 mm) tube and a 100 m of 0.25 in. (6.35 mm) tube. This new configuration allows us to achieve a vertical resolution of 300 m up to 15 km and better than 500 m up to 22 km (if analysis of the retained sample is performed within 3 h). The AirCore-HR was flown for the first time during the annual StratoScience campaign from CNES in August 2014 from Timmins (Ontario, Canada). High-resolution vertical profiles of CO2 and CH4 up to 25 km were successfully retrieved. These profiles revealed well-defined transport structures in the troposphere (also seen in CAMS-ECMWF high-resolution forecasts of CO2 and CH4 profiles) and captured the decrease of CO2 and CH4 in the stratosphere. The multi-instrument gondola also carried two other low-resolution AirCore-GUF that allowed us to perform direct comparisons and study the underlying processing method used to convert the sample of air to greenhouse gases vertical profiles. In particular, degrading the AirCore-HR derived profiles to the low resolution of AirCore-GUF yields an excellent match between both sets of CH4 profiles and shows a good consistency in terms of vertical structures. This fully validates the theoretical vertical resolution achievable by AirCores. Concerning CO2 although a good agreement is found in terms of vertical structure, the comparison between the various AirCores yields a large and variable bias (up to almost 3 ppm in some parts of the pro- files). The reasons of this bias, possibly related to the drying agent used to dry the air, are still being investigated. Finally, the uncertainties associated with the measurements are assessed, yielding an average uncertainty below 3 ppb for CH4 and 0.25 ppm for CO2 with the major source of uncertainty coming from the potential loss of air sample on the ground and the choice of the starting and ending point of the collected air sample inside the tube. In an ideal case where the sample would be fully retained, it would be possible to know precisely the pressure at which air was sampled last and thus to improve the overall uncertainty to about 0.1 ppm for CO2 and 2 ppb for CH4
New neutron cross section measurements of minor actinides have been performed recently in order to reduce the uncertainties in the evaluated data, which is important for the design of advanced nuclear reactors and, in particular, for determining their performance in the transmutation of nuclear waste. We have measured the 241Am(n,γ) cross section at the n_TOF facility between 0.2 eV and 10 keV with a BaF2 Total Absorption Calorimeter, and the analysis of the measurement has been recently concluded. Our results are in reasonable agreement below 20 eV with the ones published by C. Lampoudis et al. in 2013, who reported a 22% larger capture cross section up to 110 eV compared to experimental and evaluated data published before. Our results also indicate that the 241Am(n,γ) cross section is underestimated in the present evaluated libraries between 20 eV and 2 keV by 25%, on average, and up to 35% for certain evaluations and energy ranges.
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3+ T cell phenotype showed up to 85% cell surface expression of the respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK cells showed, that engineered cells exhibited diminished in vitro expansion, retained WT CIK cell phenotype with higher percentages of differentiated effector memory/effector cells. Activating natural killer (NK) cell receptor NKG2D-restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated significantly increased cytotoxicity against ErbB2-positive targets, including primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and efficiently lysed tumor cell monolayers as well as 3D tumor spheroids.
Here, we demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for the recognition and elimination of tumor cells expressing ErbB2, which we identified as a targetable antigen on high-risk STS cells.
Abrupt switches between different tenses (past-to-present, present-to-past) are known from oral narratives and medieval literature in Romance languages, but there is little consensus about their function and interpretation. In this study, we combine corpus-linguistic tools with experimental methods and quantitative analysis to shed light on the use of tense switches in a medieval Icelandic prose text (Hrafnkels saga freysgoða). Specifically, we part-of-speech tagged all words in Hrafnkels saga freysgoða and then determined where verbs exhibit tense switches. In a second step, we had 19 subjects mark all parts in the saga they consider climactic so as to study the overall as well as subject-specific correlations between climaxness and tense switches. In the vast majority of subjects, we observe the expected correlation, and for most of these it is significant. We discuss the findings with regard to their implications for tense switching as a performative device and the position of sagas on an orality-literacy continuum.
The article presents in its first part approaches to the concept of text genres and some milestones in the evolution of text linguistics. The aim of this linguistics consists in the research of different ways of constructing texts, regardles of style and genre. Starting from the premise that some textual elements are indices for the text genres, the article exposes some observations regarding delimitations between text genres and research approaches from the intercultural and interdisciplinary perspective.
Risk culture during the last 2000 years - from an aleatory society to the illusion of risk control
(2017)
The culture of risk is 2000 years old, although the term “risk” developed much later. The culture of merchants making decisions under uncertainty and taking the individual responsibility for the uncertain future started with the Roman “Aleatory Society”, continued with medieval sea merchants, who made business “ad risicum et fortunam”, and sustained to the culture of entrepreneurs in times of industrialisation and dynamic economic changes in the 18th and 19th century. For all long-term commercial relationships, the culture of honourable merchants with personal decision-making and individual responsibility worked well. The successful development of sciences, statistics and engineering within the last 100 years led to the conjecture that men can “construct” an economical system with a pre-defined “clockwork” behaviour. Since probability distributions could be calculated ex-post, an illusion to control risk ex-ante became a pattern in business and banking. Based on the recent experiences with the financial crisis, a “risk culture” should understand that human “Strength of Knowledge” is limited and the “unknown unknown” can materialise. As all decisions and all commercial agreements are made under uncertainty, the culture of honourable merchants is key to achieve trust in long-term economic relations with individual responsibility, flexibility to adapt and resilience against the unknown.
Relativistic jets from active galactic nuclei (AGN) often display a non-uniform structure and are, under certain conditions, susceptible to a number of instabilities. An interesting example is the development of non-axisymmetric, Rayleigh-Taylor type instabilities in the case of differentially rotating two-component jets, with the toroidal component of the magnetic field playing a key role in the development or suppression of these instabilities. We have shown that higher magnetization leads to stability against these non-axisymmetric instabilities. Using ray-casting on data from relativistic MHD simulations of two-component jets, we now investigate the effect of these instabilities on the synchrotron emission pattern from the jets. We recover many well known trends from actual observations, e.g., regarding the polarization fraction and the distribution of the position angle of the electric field, in addition to a different emitting region, depending on the stability of the jet.
The terrestrial fern Hypolepis distans (Dennstaedtiaceae) is recorded as indigenous to New Zealand and Tasmania. The fern was not known from New South Wales or the Australian mainland until recently. This paper reports on the recent discovery of the species at Macquarie Pass in the Illawarra area on the south-eastern edge of the Central Tablelands Botanical Subdivision of New South Wales. Its ecology and conservation needs are discussed.
Background: The Aedes (Stegomyia) albopictus subgroup includes 11 cryptic species of which Ae. albopictus is the most widely distributed. Its global expansion associated with a documented vector competence for several emerging arboviruses raise obvious concerns in the recently colonized regions. While several studies have provided important insights regarding medical importance of Ae. albopicus, the investigations of the other sibling species are scarce. In Asia, indigenous populations within the Ae. albopictus subgroup can be found in sympatry. In the present study, we aimed to describe and compare molecular, morphological and bacterial symbionts composition among sympatric individuals from the Ae. albopictus subgroup inhabiting a Vietnamese protected area.
Results: Based on morphological structure of the cibarial armarture, we identified a cryptic species in the forest park at Bù Gia Mập in the south-eastern region of Vietnam. Analysis of nuclear (ITS1-5.8S-ITS2) and mitochondrial (cox1, nad5) markers confirmed the divergence between the cryptic species and Ae. albopictus. Analysis of midgut bacterial microbiota revealed a strong similarity among the two species with a notable difference; contrary to Ae. albopictus, the cryptic species did not harbour any Wolbachia infection.
Conclusions: These results could reflect either a recent invasion of Wolbachia in Ae. albopictus or alternatively a loss of this symbiont in the cryptic species. We argue that neglected species of the Ae. albopictus subgroup are of main importance in order to estimate variation of host-symbionts interactions across evolution.
Aproximadamente cinquenta universidades brasileiras possuem algum tipo de estudo de Língua Alemã, sendo que dezessete delas oferecem a graduação em Letras com habilitação em Alemão, bacharelado ou licenciatura. O objetivo deste trabalho é analisar as crenças e ex-pectativas dos estudantes de Letras/Alemão a respeito do curso que frequentam, a partir da rea-lização de uma investigação em uma universidade pública do Estado do Paraná, em 2016. Com base em um questionário respondido por 18 alunos do Curso de Letras desta instituição, busca-mosidentificar os motivos que os levaram a optar pela licenciatura em Letras/Alemão e suas perspectivas de desenvolvimento profissional. A fundamentação teórica advém da perspectiva dos estudos de crenças discentes (SILVA 2007; BARCELOS2001), mais especificamente dos es-tudos de crenças de alunos acerca da aprendizagem de línguas estrangeiras. A metodologia da pesquisa corresponde a um paradigma híbrido (KUCKARTZ 2014, 2016 e MAYRING 2015), com características de pesquisa qualitativa e quantitativa. Como resultado da pesquisa, entre outros aspectos, observou-se que a maioria dos alunos optou pelo curso de Letras/Alemão como forma de aprender essa língua e no futuro atuarem profissionalmente nessa área, seja no campo da Linguística, da Literatura ou da Tradução.
High precision measurement of the radiative capture cross section of 238U at the n_TOF CERN facility
(2017)
The importance of improving the accuracy on the capture cross-section of 238U has been addressed by the Nuclear Energy Agency, since its uncertainty significantly affects the uncertainties of key design parameters for both fast and thermal nuclear reactors. Within the 7th framework programme ANDES of the European Commission three different measurements have been carried out with the aim of providing the 238U(n,γ) cross-section with an accuracy which varies from 1 to 5%, depending on the energy range. Hereby the final results of the measurement performed at the n_TOF CERN facility in a wide energy range from 1 eV to 700 keV will be presented.
The aim of this work is to provide a precise and accurate measurement of the 238U(n,γ) reaction cross section in the energy region from 1 eV to 700 keV. This reaction is of fundamental importance for the design calculations of nuclear reactors, governing the behavior of the reactor core. In particular, fast reactors, which are experiencing a growing interest for their ability to burn radioactive waste, operate in the high energy region of the neutron spectrum. In this energy region most recent evaluations disagree due to inconsistencies in the existing measurements of up to 15%. In addition, the assessment of nuclear data uncertainty performed for innovative reactor systems shows that the uncertainty in the radiative capture cross section of 238U should be further reduced to 1–3% in the energy region from 20 eV to 25 keV. To this purpose, addressed by the Nuclear Energy Agency as a priority nuclear data need, complementary experiments, one at the GELINA and two at the n_TOF facility, were proposed and carried out within the 7th Framework Project ANDES of the European Commission. The results of one of these 238U(n,γ) measurements performed at the n_TOF CERN facility are presented in this work. The γ-ray cascade following the radiative neutron capture has been detected exploiting a setup of two C6D6 liquid scintillators. Resonance parameters obtained from this work are on average in excellent agreement with the ones reported in evaluated libraries. In the unresolved resonance region, this work yields a cross section in agreement with evaluated libraries up to 80 keV, while for higher energies our results are significantly higher.
Background: Electrical stimulation (ES) has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation.
Methods: In the present study we exposed rat bone marrow- (BM-) and adipose tissue- (AT-) derived mesenchymal stem cells (MSCs) to direct current electrical stimulation (DC ES) and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points.
Results: Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES.
Discussion: This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.
Der viel diskutierte Begriff der "Multinormativität" steht heute in Konkurrenz zu dem des "Rechtspluralismus" und der "Diversität" des Rechts. Alle drei Begriffe verfügen nicht über eine inhaltliche und funktionale Eindeutigkeit und zeigen kein bestimmtes Verhältnis zu- und untereinander. Eine sehr vage Gemeinsamkeit solcher "Rechtspluralitäten" besteht allein in deren Unterscheidung oder Abweichung vom Gegenbegriff einer "Rechtseinheit" bzw. der ideal gedachten Einheit der Rechtsordnung, wie sie von den Kodifikatoren des Privatrechts im Zeitalter der Aufklärung versucht wurde zu verwirklichen. In einem solchen Spannungsverhältnis zwischen Einheitlichkeit oder Vielfalt gesellschaftlicher und staatlicher Rechtsgestaltung steht jedes organisierte Gemeinwesen. Das ist eine historische Erfahrung, die sich seit der römischen Antike in der rechtssystematischen Einteilung in ein "ius universale " und "ius speciale/particulare" zeigt. In der aktuellen Diskussion scheint "Multinormativität" als der umfassendere Begriff für die Rechtevielfalt gebraucht zu werden. In der rechtstheoretisch orientierten Literatur kann man je nach disziplinärer Einteilung bis zu sieben "Rechtspluralismen" unterscheiden, die die Definitionsnot und sprachliche Bedeutungsvielfalt nachdrücklich belegen. Dieser "Pluralismus" kann durch Rechte oder auch "Rechts-Ordnungen" in der Interaktion zwischen einer herrschenden und einer alternativen "Rechts-Ordnung" bestimmt sein. Die Konkretisierungsbedürftigkeit von "Rechtspluralismus" und "Multinormativität" haben diese beiden Begriffe auch gemeinsam mit dem geläufigen Nachbarbegriff der pluralen "Rechtsquellen", die als Sammelbezeichnung für die Grundlagen rechtlicher Entscheidungen fungieren. Multinormativität kann heute als eine extensive Variante von "Rechtsquellenvielfalt" oder "Rechtsvielfalt" gesehen werden, beschränkt sich jedoch nicht auf die Dimension der rechtlichen Entscheidungsgrundlagen, sondern erweitert diese auch auf die Vielzahl möglicher außerrechtlicher entscheidungsrelevanter "Normen". Das ist der Grund, weshalb heute der Begriff des "normative pluralism" dem des "legal pluralism" vorgezogen wird, um auch das "phenomenon of law beyond the state" in den Griff zu bekommen. In der deutschen Literatur ist heute das beliebte Bild und der vielgebrauchte Begriff der "Rechtsquellen" höchst umstritten, da in ihm mehr das "fließende" Element höchst mobiler rechtlicher Ordnungsinstrumente zum Ausdruck kommt als die Bestimmtheit und Sicherheit rechtlicher Normangebote. Luhmann bezeichnete die eine Rechtspluralität indizierende Rechtsquellenlehre als ein "mehrschichtiges Theoriegebäude mit schwankenden Fundamenten" und Esser sprach sogar von den "doktrinären Peinlichkeiten", vor die sich die Rechtsquellenlehre gestellt sah und gestellt sieht. Multinormativität löst heute weitgehend den "Rechtsquellen"-Begriff ab, indem er ihn vor dem Hintergrund internationaler politischer Praxis und Erfahrungen überlagert und ausweitet. ...
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
The challenges posed by climate and land use change are increasingly complex, with ever-increasing and accelerating impacts on the global environmental system. The establishment of an internationally harmonized, integrated, and long-term operated environmental monitoring infrastructure is one of the major challenges of modern environmental research. Increased efforts are currently being made in Europe to establish such a harmonized pan-European observation infrastructure, and the European network of Long-Term Ecological Research sites – LTER-Europe – is of particular importance. By evaluating 477 formally accredited LTER-Europe sites, this study gives an overview of the current distribution of these infrastructures and the present condition of long-term environmental research in Europe. We compiled information on long-term biotic and abiotic observations and measurements and examined the representativeness in terms of continental biogeographical and socio-ecological gradients. The results were used to identify gaps in both measurements and coverage of the aforementioned gradients. Furthermore, an overview of the current state of the LTER-Europe observation strategies is given. The latter forms the basis for investigating the comparability of existing LTER-Europe monitoring concepts both in terms of observational design as well as in terms of the scope of the environmental compartments, variables and properties covered.
In diesem Beitrag wird korpusbasiert, qualitativ und aus kontrastiver Sicht anhand ausgewählter Einzelbeispiele untersucht, welchen Beitrag die Frame-Semantik bei der Analyse konzeptueller Metaphern im aktuellen Migrationsdiskurs in der deutschen und italienischen Presse leisten kann. Sie macht es möglich, unterschiedliche Perspektivierungen bei der Betrachtung des Phänomens herauszukristallisieren, da semantische Frames ein facettenreiches Angebot für den Blickwinkel der Betrachtung bereitstellen. Auch Metaphern selbst besitzen diese Eigenschaft der Perspektivierung, vor allem auch solche, die charakteristisch für einen kulturspezifischen Kontext stehen. Zu den Möglichkeiten, die der Einsatz von Metaphern bietet, zählt vor allem der "Highlighting und Hiding"-Effekt (LAKOFF/JOHNSON 1980), indem Metaphern bestimmte Aspekte betonen oder verdunkeln. Um welche es sich dabei im Einzelnen handelt, hängt von mehreren Faktoren ab, wie zum Beispiel der politischen Orientierung von Journalisten oder Politikern oder der wirtschaftlichen Lage eines Landes.
In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity.
O intuito deste trabalho é destacar a importância do escrito juvenil Traumland para a formação do poeta Georg Trakl, por meio de uma leitura cerrada do texto. Sob a forma de uma lembrança do narrador, esse breve relato apresenta uma experiência de iniciação ou perda da inocência oriunda da percepção do mal no mundo, concentrado na figura de uma prima doente, Maria. O conflito entre o anseio romântico (Sehnsucht) pleno de expectativas e entusiasmo e essa realidade aterradora, vivenciado como uma quebra no sentimento (Stimmung) de harmonia cósmica, impulsiona uma transformação no sentimento e na visão de mundo do protagonista, que metaforicamente pode ser lida como a transição de uma poética puramente romântica para uma poética mais sintonizada com as exigências do século XX, especialmente no sentido da dimensão reconhecida ao mal irremediável, que não pode ser completamente romantizado.
Kaum eine geistes- und kulturwissenschaftliche Disziplin hat in Italien in solchem Ausmaß unter Selbstdarstellungs- und Rechtfertigungszwang gestanden und sich über so heftige Widerstände hinwegsetzen müssen wie die Komparatistik. Ein Leserbrief des Literaturwissenschaftlers Armando Gnisci, der in den 1980er- und 1990er-Jahren die Szene der italienischen Komparatistik wesentlich geprägt, aber nur marginal bis ins neue Jahrtausend mitbestimmen konnte, gibt einen konzis-kritischen – wenn auch leicht polemischen – Einblick in das, was seit dem letzten state of the art aus dem Jahre 1991 auf dem Gebiet der Allgemeinen und Vergleichenden Literaturwissenschaft in Italien passiert ist. Entlang dieser Linie verlief nämlich die wichtigste Front im Streit zwischen den Nationalphilologen und den Komparatisten. Gniscis Schreiben mit dem programmatischen wie suggestiven Titel "Comparatisti e italianisti, le due tribù" [Komparatisten und Italianisten, die beiden Stämme] – erschienen am 21. März 2004 in der Kulturbeilage Domenica – ist ein Rundumschlag gegen die seinerzeit in Italien weitverbreitete Ansicht, die Allgemeine und Vergleichende Literaturwissenschaft als "sub-category of Italian literature departments" zu betrachten.
We study platform design in online markets in which buying involves a (nonmonetary) cost for consumers caused by privacy and security concerns. Firms decide whether to require registration at their website before consumers learn relevant product information. We derive conditions under which a monopoly seller benefits from ex ante registration requirements and demonstrate that the profitability of registration requirements is increased when taking into account the prospect of future purchases or an informational value of consumer registration to the firm. Moreover, we consider the effectiveness of discounts (store credit) as a means to influence the consumers’ registration decision. Finally, we confirm the profitability of ex ante registration requirements in the presence of price competition.
We study the effect of the chiral symmetry restoration (CSR) on heavy-ion collisions observables in the energy range sNN=3–20GeV within the Parton-Hadron-String Dynamics (PHSD) transport approach. The PHSD includes the deconfinement phase transition as well as essential aspects of CSR in the dense and hot hadronic medium, which are incorporated in the Schwinger mechanism for particle production. Our systematic studies show that chiral symmetry restoration plays a crucial role in the description of heavy-ion collisions at sNN=3–20GeV, realizing an increase of the hadronic particle production in the strangeness sector with respect to the non-strange one. Our results provide a microscopic explanation for the horn structure in the excitation function of the K+/π+ ratio: the CSR in the hadronic phase produces the steep increase of this particle ratio up to sNN≈7GeV, while the drop at higher energies is associated to the appearance of a deconfined partonic medium. Furthermore, the appearance/disappearance of the horn structure is investigated as a function of the system size. We additionally present an analysis of strangeness production in the (T,μB)-plane (as extracted from the PHSD for central Au+Au collisions) and discuss the perspectives to identify a possible critical point in the phase diagram.
Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIα were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution.