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This paper provides a complete characterization of optimal contracts in principal-agent settings where the agent's action has persistent effects. We model general information environments via the stochastic process of the likelihood-ratio. The martingale property of this performance metric captures the information benefit of deferral. Costs of deferral may result from both the agent's relative impatience as well as her consumption smoothing needs. If the relatively impatient agent is risk neutral, optimal contracts take a simple form in that they only reward maximal performance for at most two payout dates. If the agent is additionally risk-averse, optimal contracts stipulate rewards for a larger selection of dates and performance states: The performance hurdle to obtain the same level of compensation is increasing over time whereas the pay-performance sensitivity is declining.
"Naming Gender" von Susanne Oelkers (2003) ist die erste Studie, die sich eingehend mit der Geschlechtskennzeichnung von Rufnamen befasst. Für die Herstellung und Darstellung von Geschlecht stellt nicht nur Sprache generell, sondern zuvörderst das Namensystem ein zentrales Zeichensystem zur Verfügung. Namen haben damit beträchtlichen Anteil an Ordnungsstiftung und Komplexitätsreduktion. Die deutsche Onomastik hat sich bis 2003 kaum für die soziale Differenz Gender interessiert, sie hat die linguistische und soziologische Genderforschung nicht rezipiert. Umgekehrt haben auch Genderlinguistik und Soziologie die Personennamen weitgehend übersehen (von Lindemann 1996 und Gerhards 2003 abgesehen). Dies steht der Relevanz entgegen, die Namen für die Etablierung und Prozessierung der Geschlechterordnung haben. Selbst Sprachen ohne jegliche grammatische Genus- oder Gendermarkierung können mit ihren Rufnamen Geschlecht indizieren (z.B. Finnisch und Estnisch, die nicht einmal bei den Personalpronomen der 3. Person Geschlecht markieren).
Based on the concept of oxidative stress, reactive oxygen species (ROS) have been incriminated as the drivers behind almost every cardiovascular pathology. Redox alterations are, however, omnipresent bystanders to changes in cellular activity state. Even when ROS levels are altered, their contribution to pathology is not necessarily causal. Researchers should hesitate to engage in global ROS measurements and rather aim on identifying individual molecular targets of redox regulation.
Objectives: The SAVI-TF (Symetis ACURATE neo Valve Implantation Using Transfemoral Access) registry was initiated to study the ACURATE neo transcatheter heart valve in a large patient population treated under real-world conditions.
Background: The self-expanding, supra-annular ACURATE neo prosthesis is a transcatheter heart valve that gained the Conformité Européene mark in 2014, but only limited clinical data are available so far.
Methods: This prospective, multicenter registry enrolled 1,000 patients at 25 European centers who were followed for 1 year post-procedure.
Results: Mean patient age was 81.1 ± 5.2 years; mean logistic European System for Cardiac Operative Risk Evaluation I score, European System for Cardiac Operative Risk Evaluation II score, and Society of Thoracic Surgeons score were 18.1 ± 12.5%, 6.6 ± 7.5%, and 6.0 ± 5.6%, respectively. At 1 year, 8.0% (95% confidence interval [CI]: 6.3% to 9.7%) of patients had died, 2.3% (95% CI: 1.3% to 3.2%) had disabling strokes, and 9.9% (95% CI: 8.1% to 11.8%) had permanent pacemaker implantations. Through 1 year, 5 reinterventions (0.5%; 95% CI: 0.1% to 1.0%) were performed: 3 valve-in-valve and 2 surgical aortic valve replacements. Mean effective orifice area was 1.84 ± 0.43 cm2, mean gradient was 7.3 ± 3.7 mm Hg, and greater than mild paravalvular leakage was observed in 3.6% of patients.
Conclusions: Transfemoral implantation of the ACURATE neo prosthesis resulted in favorable 1-year clinical and echocardiographic outcomes with very low mortality and new pacemaker rates.
Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.
Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation.
Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.
Conclusions: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.
Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.
Background: A diagnosis of post-traumatic stress disorder (PTSD) requires the identification of one or more traumatic events, designated the index trauma, which serves as the basis for assessment of severity of PTSD. In patients who have experienced more than one traumatic event, severity may depend on the exact definition of the index trauma. Defining the index trauma as the worst single incident may result in PTSD severity scores that differ from what would be seen if the index trauma included multiple events.
Objective: This study aimed to investigate the impact of the definition of the index trauma on PTSD baseline severity scores and treatment outcome.
Method: A planned secondary analysis was performed on data from a subset (N = 58) of patients enrolled in a trial evaluating the efficacy of a 12 week residential dialectical behavioural therapy programme for PTSD related to childhood abuse (DBT-PTSD). Assessments of the severity of PTSD were conducted at admission, at the end of the 12 week treatment period, and at 6 and 12 weeks post-treatment, using the Clinician-Administered PTSD Scale. The index trauma was defined with respect to both the worst single incident and up to three qualitatively distinct traumatic events.
Results: When the index trauma included multiple traumas, PTSD severity scores were significantly higher and improvements from pre- to post-treatment were significantly lower than when the index trauma was defined as the worst single incident.
Conclusions: In patients with PTSD who have experienced multiple traumas, defining the index trauma as the worst single incident may miss some aspects of clinically relevant symptomatology, thereby leading to a possibly biased interpretation of treatment effects. In DBT-PTSD, treatment effects were lower when the index trauma included multiple traumatic events. More research is needed to determine the impact of the various index trauma definitions on the evaluation of other trauma-focused treatments.
Objectives: In the AURA3 trial, individuals received osimertinib 80 mg once daily or chemotherapy for advanced non-small cell lung cancer. Here, we explore patient-reported symptoms possibly related to treatment.
Materials and methods: AURA3 was an open-label, randomized phase III trial involving 419 patients. As part of the trial’s exploratory objectives, individuals were asked to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) electronically, first weekly for 18 weeks and then every 3 weeks for up to 57 weeks, subject to the availability of validated local-language versions (English, German, Japanese and Spanish versions were available).
Results: In total, 161 patients (38%; 102 receiving osimertinib, 59 receiving chemotherapy) provided data for PRO-CTCAE analyses (mean age: 64 years; 63% women). Diarrhea was reported more commonly with osimertinib than with chemotherapy, and was mostly graded as occurring rarely or occasionally. Decreased appetite was reported less commonly with osimertinib than with chemotherapy. The proportion of patients reporting nausea changed little from baseline with osimertinib and increased with chemotherapy. Few patients reported vomiting. Both nausea and vomiting were generally graded as mild in severity. Fatigue was reported less commonly with osimertinib than with chemotherapy, and was mostly graded as mild or moderate. Of patients reporting fatigue, the proportion grading it as interfering at least ‘somewhat’ with their usual or daily activities was lower with osimertinib than with chemotherapy.
Conclusion: Symptoms were generally mild and not frequent, with some differences in symptom patterns between the two treatment groups. The results support and complement the AURA3 trial data and give insight into patients’ experience with treatment.
Effects of single-point acupuncture (HT7) in the prevention of test anxiety : results of a RCT
(2018)
Background: The number of students using neuro enhancement to improve their performance and to prevent test anxiety is increasing. The acupuncture point Heart 7 (HT7) has been described as being prominent in reducing states of anxiety.
Methods: We conducted a randomized placebo-controlled, two-armed pilot trial to investigate the efficacy of a single-point acupuncture treatment at bilateral HT7 compared to sham laser acupuncture on test anxiety. Test anxiety was induced applying the standardised protocol of the Trier Social Stress Test. Outcome measures included saliva samples analysed for cortisol and amylase, anxiety questionnaires and heart rate variability.
Results: Twenty-five male subjects (age 28 ± 5 years) were allocated to either verum acupuncture (n = 12) or sham laser acupuncture (n = 13). Cortisol peaked 20 min after the stress test (2-fold, 18.11 ± 2 nmol/l) and amylase 10 min after (2-fold, 259 ± 49 U/ml) with no difference between groups. There were no differences between groups regarding either anxiety questionnaires or physiological parameters. Compared to reference data (3-fold increase in cortisol), increase in stress hormones and heart rate seemed somewhat reduced.
Conclusions: Acupuncture may be a possible approach for the treatment of anxiety. Due to the lack of a no control treatment group, we cannot determine the magnitude of possible specific needle effects at HT7 to promote specific effects in the neuroendocrine system. Finally this study only examines the efficacy of a single time treatment.
kurz und kn@pp news : Nr. 43
(2018)
The liver as the biggest endocrine gland of the human body plays a central role in many metabolic pathways such as detoxification, storage of carbohydrates and distribution of lipids. As the liver receives blood supply from the gut by the portal vein, liver cells are often challenged with high concentrations of nutrients and components of our commensal microbiota. Therefore, the immune system of the liver induces a tolerant state, meaning no or low inflammatory reactions to those constant stimuli. Yet, as various pathogens target the liver, the hepatic immune system also needs the capability to induce strong immune responses quickly. Chronical damage to the liver, which can be caused by alcohol, pathogens or toxins, might lead to liver cirrhosis, where the amount of functional liver tissue is decreased dramatically. This pathology can worsen and lead to acute-on-chronic liver failure, whose high mortality is due to high inflammation and multi-organ failure. Interleukin-7 is a cytokine known for its pro-survival functions especially in lymphopoiesis. However, it is also very important for maintenance of mature immune cells in the liver. As mouse experiments have demonstrated an induction of Interleukin-7 in the liver as a response to bacterial lipopolysaccharide, we aimed to characterize the role of Interleukin-7 in hepatic immunoregulation in both health and disease.
The experiments were mostly based on in vitro approaches. Induction of Interleukin-7 in liver cells was analyzed using ELISA, quantitative PCR, and Immunoblotting. Knockdown of signal transduction components was performed by siRNA transfection. Primary immune cells isolated from healthy donor buffy coat were studied for their ability to respond to Interleukin-7. Activation of downstream signal transduction was assessed by Immunoblotting. Functional consequences of Interleukin-7 signaling, such as alterations in cellular metabolism, cellular survival and endotoxin tolerance, were studied in monocyte-derived macrophages. Finally, serum concentrations of Interleukin-7 and frequencies of Interleukin-7 receptor positive immune cells were quantified in patients with compensated or decompensated liver cirrhosis or acute-on-chronic liver failure.
Interleukin-7 expression could be observed in human hepatic cell lines and primary hepatic sinusoidal endothelial cells when stimulated with IFNα or IFNγ, but not IFNλ. IRF-1 was identified as a key regulator of Interleukin-7 expression, as its transcription, translation and nuclear translocation were induced and enhanced upon IFNα or IFNγ, but not IFNλ treatment. We identified LPS-primed macrophages as innate immune target cells of Interleukin-7, which responded by an inhibitory phosphorylation of GSK3. This signal transduction led to enhanced production of pro-inflammatory cytokines and abolished endotoxin tolerance. In parallel, cellular fitness was reduced as demonstrated by reduced intracellular ATP concentration and intracellular WST-1 staining. Finally, we could identify components of the in vitro signal transduction also in liver cirrhosis patients. However, Interleukin-7 serum concentrations were significantly in liver cirrhosis patients compared to healthy controls. In addition, the frequencies of Interleukin-7 receptor positive immune cell populations differed in patients and controls.
We identify Interleukin-7 as a pro-inflammatory cytokine in hepatic immunoregulation. It is part of a cascade where its induction is regulated by type I and type II Interferons and mainly restricted by the presence of IRF1. We demonstrate the importance of Interleukin-7 also for innate immune cells, where the abolishment of endotoxin tolerance may provide an interesting strategy of liver cirrhosis patients. In addition, reduced viability of macrophages in response to Interleukin-7 is a striking contrast to the well-described survival functions in lymphocytes. The decrease of serum Interleukin-7 levels and alterations of Interleukin-7 receptor positive immune cell populations suggest an important role for Interleukin-7 also in the diseased liver. Due to the identified mechanisms of action, Interleukin-7 may be an interesting candidate for immunotherapeutic approaches of liver cirrhosis and acute-on-chronic liver failure.
Eastern boundary upwelling provides the conditions for high marine productivity in the Canary Current System off NW-Africa. Despite its considerable importance to fisheries, knowledge on this marine ecosystem is only limited. Here, parasites were used as indicators to gain insight into the host ecology and food web of two pelagic fish species, the commercially important species Trichiurus lepturus Linnaeus, 1758, and Nealotus tripes Johnson, 1865. Fish specimens of T. lepturus (n = 104) and N. tripes (n = 91), sampled from the Canary Current System off the Senegalese coast and Cape Verde Islands, were examined, collecting data on their biometrics, diet and parasitisation. In this study, the first parasitological data on N. tripes are presented. T. lepturus mainly preyed on small pelagic Crustacea and the diet of N. tripes was dominated by small mesopelagic Teleostei. Both host species were infested by mostly generalist parasites. The parasite fauna of T. lepturus consisted of at least nine different species belonging to six taxonomic groups, with a less diverse fauna of ectoparasites and cestodes in comparison to studies in other coastal ecosystems (Brazil Current and Kuriosho Current). The zoonotic nematode Anisakis pegreffii occurred in 23% of the samples and could pose a risk regarding food safety. The parasite fauna of N. tripes was composed of at least thirteen species from seven different taxonomic groups. Its most common parasites were digenean ovigerous metacercariae, larval cestodes and a monogenean species (Diclidophoridae). The observed patterns of parasitisation in both host species indicate their trophic relationships and are typical for mesopredators from the subtropical epi- and mesopelagic. The parasite fauna, containing few dominant species with a high abundance, represents the typical species composition of an eastern boundary upwelling ecosystem.
Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab. Serum HMGB1 levels were significantly higher in a subset of the PDX collection, which exhibited slower tumor growth during subsequent passages than tumors with low HMGB1 serum levels. Pre-treatment PDX serum HMGB1 levels also correlated with response to systemic treatment: PDX models with high HMGB1 levels predicted response to bevacizumab. Taken together, we provide for the first time evidence that the damage associated molecular pattern biomarker HMGB1 can predict response to systemic treatment with bevacizumab. Our data support the future evaluation of HMGB1 as a predictive biomarker for bevacizumab sensitivity in patients with renal cell carcinoma.
Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode the cis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affecting RON exon 11 skipping, which corresponds to the pathological isoform RON∆165. Importantly, the effects correlate with RON alternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.
When mapping eye-movement behavior to the visual information presented to an observer, Areas of Interest (AOIs) are commonly employed. For static stimuli (screen without moving elements), this requires that one AOI set is constructed for each stimulus, a possibility in most eye-tracker manufacturers' software. For moving stimuli (screens with moving elements), however, it is often a time-consuming process, as AOIs have to be constructed for each video frame. A popular use-case for such moving AOIs is to study gaze behavior to moving faces. Although it is technically possible to construct AOIs automatically, the standard in this field is still manual AOI construction. This is likely due to the fact that automatic AOI-construction methods are (1) technically complex, or (2) not effective enough for empirical research. To aid researchers in this field, we present and validate a method that automatically achieves AOI construction for videos containing a face. The fully-automatic method uses an open-source toolbox for facial landmark detection, and a Voronoi-based AOI-construction method. We compared the position of AOIs obtained using our new method, and the eye-tracking measures derived from it, to a recently published semi-automatic method. The differences between the two methods were negligible. The presented method is therefore both effective (as effective as previous methods), and efficient; no researcher time is needed for AOI construction. The software is freely available from https://osf.io/zgmch/.
Predicting the requirement for renal replacement therapy in intensive care patients with sepsis
(2018)
Sepsis is one of the most frequent causes of acute kidney injury (AKI) in critically ill patients, with initial organ impairment often followed by dysfunction in other systems. Renal dysfunction may therefore represent one facet in the evolution towards multiple organ dysfunction syndrome (MODS) or, alternatively, may be indicative of system-wide endothelial damage caused by hyperinflammation and a positive fluid balance. Whilst numerous biomarkers have been investigated to predict renal replacement therapy (RRT) requirement, including NGAL, TIMP-2 and IGFBP-7, mid-regional proadrenomedullin (MR-proADM) may also be of interest due to its involvement in capillary leakage, endothelial dysfunction and the initial stages of multiple organ failure development. ...
Im Jahr 1564 veröffentlicht der Ulmer Militärexperte und -schriftsteller Leonhard Fronsperger die Schrift "Von dem Lob deß Eigen Nutzen", in der er darlegt, dass die konsequente Verfolgung des eigenen Nutzens als individuelle Handlungsmaxime im Ergebnis zu einer Förderung des Gemeinwohls führt. Das etwas mehr als hundert Seiten umfassende Werk wird in Frankfurt am Main, einem Zentrum des europäischen Buchdrucks und -handels, verlegt und findet Erwähnung im ersten veröffentlichten Katalog der Frankfurter Buchmesse. Fronsperger präsentiert seine für die damalige Zeit durchaus revolutionäre These in der Form eines satirischen Enkomions und unterlegt sie mit einer umfangreichen Gesellschaftsanalyse. Er stellt fest, dass die politischen Herrschaftsformen, die gesellschaftlichen Institutionen und die wirtschaftlichen Handelsbeziehungen auf einer konsequenten Verfolgung des eigenen Nutzens aller Akteure beruhen und dass sich die von der Kirche geforderte Ausrichtung des individuellen Handelns am Gemeinwohl in der Realität nicht finden lässt. Vielmehr hält er die Kritik der Theologen am egoistischen Handeln des Einzelnen für falsch, empfindet er doch den Staat, Wirtschaft und Gesellschaft im Großen und Ganzen als gut funktionierend.
Im Folgenden dokumentieren wir zunächst die Biografie des Autors, die Entstehung und Verbreitung des Werks und seine besondere literarische Form. Anschließend diskutieren wir die zentrale These in drei verschiedenen geistesgeschichtlichen Kontexten, die jeweils von besonderer Bedeutung für die Herausbildung der neuzeitlichen Gesellschafts- und Wirtschaftstheorien sind. Erkenntnis- und staatstheoretisch weist Fronspergers Werk deutliche Parallelen zu den Analysen auf, die Niccolò Machiavelli und später Giovanni Botero in Italien zur Bedeutung der auf den individuellen fürstlichen Interessen basierenden Staatsräson bzw. zu den Triebkräften erfolgreicher Stadtentwicklung vorlegten. Markante Unterschiede gibt es dagegen zu den Ansichten der deutschsprachigen Reformatoren im Anschluss an Luther, die zwar die Unterscheidung zwischen geistlicher und weltlicher Sphäre propagieren und damit die Entwicklung einer eigenständigen Moral für das Wirtschaftsleben befördern, dort allerdings mehrheitlich die Orientierung am "Gemeinen Nutzen" propagieren. Indem Fronsperger dagegen die Verfolgung des Eigennutzes fordert, nimmt er wirtschafts- und gesellschaftstheoretische Einsichten über das Wesen und die Auswirkungen der Arbeitsteilung vorweg, die erst 150 Jahre und später von Bernard Mandeville und Adam Smith in England und Schottland formuliert wurden. Das Werk Fronspergers bietet damit ein herausragendes Beispiel dafür, wie sich aus dem Zusammenspiel von wirtschaftlichem Erfolg, einem realistischen Menschenbild und manchen Aspekten der Reformation in deren Folge ein neues normatives Verständnis von den Antriebskräften ökonomischer und gesellschaftlicher Dynamik entwickelt, das später als der "Geist des Kapitalismus" bezeichnet wird.
Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus. We show that the dynamics of Q is redox-state-dependent, and that quinol, QH2, moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica. We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.
The retinal rod pathway, featuring dedicated rod bipolar cells (RBCs) and AII amacrine cells, has been intensely studied in placental mammals. Here, we analyzed the rod pathway in a nocturnal marsupial, the South American opossum Monodelphis domestica to elucidate whether marsupials have a similar rod pathway. The retina was dominated by rods with densities of 338,000–413,000/mm². Immunohistochemistry for the RBC-specific marker protein kinase Cα (PKCα) and the AII cell marker calretinin revealed the presence of both cell types with their typical morphology. This is the first demonstration of RBCs in a marsupial and of the integration of RBCs and AII cells in the rod signaling pathway. Electron microscopy showed invaginating synaptic contacts of the PKCα-immunoreactive bipolar cells with rods; light microscopic co-immunolabeling for the synaptic ribbon marker CtBP2 confirmed dominant rod contacts. The RBC axon terminals were mostly located in the innermost stratum S5 of the inner plexiform layer (IPL), but had additional side branches and synaptic varicosities in strata S3 and S4, with S3-S5 belonging to the presumed functional ON sublayer of the IPL, as shown by immunolabeling for the ON bipolar cell marker Gγ13. Triple-immunolabeling for PKCα, calretinin and CtBP2 demonstrated RBC synapses onto AII cells. These features conform to the pattern seen in placental mammals, indicating a basically similar rod pathway in M. domestica. The density range of RBCs was 9,900–16,600/mm2, that of AII cells was 1,500–3,260/mm2. The numerical convergence (density ratio) of 146–156 rods to 4.7–6.0 RBCs to 1 AII cell is within the broad range found among placental mammals. For comparison, we collected data for the Australian nocturnal dunnart Sminthopsis crassicaudata, and found it to be similar to M. domestica, with rod-contacting PKCα-immunoreactive bipolar cells that had axon terminals also stratifying in IPL strata S3-S5.
Die Verknüpfung des Fahrrades mit dem Öffentlichen Verkehr (ÖV) kann den Umweltverbund stärken, den Übergang von einem Verkehrssystem auf das andere erleichtern und eine attraktive Alternative zum motorisierten Individualverkehr schaffen. Die vorliegende Arbeit repräsentiert den zweiten umfassenden Projektbericht innerhalb des Forschungsprojektes „Verbesserte Integration des Fahrrads in den öffentlichen Verkehr – Systematische Erschließung von Handlungsoptionen und Bewertung von Best-Practices“. Im ersten Projektbericht (ebenfalls in dieser Arbeitspapierreihe erschienen – Nr. 15) wurden die Entwicklungen der letzten Jahre in den infrastrukturellen Themenfeldern Fahrradmitnahme, Fahrradverleihsysteme und Fahrradabstellanlagen aufgearbeitet und Fragen zu Kommunikation und Marketing der Angebote sowie zu Möglichkeiten der fortschreitenden Digitalisierung zur verbesserten Integration von Fahrrad und Öffentlichem Verkehr diskutiert. Darauf aufbauend werden im vorliegenden Bericht die Ergebnisse vertiefender Fallstudien dargestellt, mit dem Ziel, Erfolgsfaktoren und Hemmnisse für die Integration von Fahrrad mit Öffentlichem Verkehr aufzuzeigen und in einem späteren Schritt daraus Handlungsempfehlungen zur Stärkung dieser Integration für Kommunen und Verkehrsanbieter geben zu können. Für die Fallstudien wurden solche Beispiele ausgewählt, die einen Vorbildcharakter haben und als nachahmenswert für andere Städte und Regionen gelten können bzw. aus denen sich Erkenntnisse für die Stärkung der Integration von Fahrradverkehr mit dem ÖV ziehen lassen. Zudem sollten die verschiedenen infrastrukturellen Themenfelder abgedeckt sein. Neben einer Darstellung der jeweils fallspezifischen Besonderheiten wird zu jedem Fallbeispiel das Betreiber- und Geschäftsmodell dargestellt und es erfolgt eine Bewertung, die sowohl die Sicht der Betreiber als auch die der Nutzenden beachtet.
Folgende Fallbeispiele werden behandelt:
Die hessischen Verkehrsverbünde Rhein-Main-Verkehrsverbund (RMV) und Nordhessischer Verkehrsverbund (NVV) bieten eine kosten- und sperrzeitfreie Mitnahmeregelung für Fahrräder an.
Das MVGmeinRad Mainz ist als Fahrradverleihsystem ein Teil des kommunalen ÖPNV-Unternehmens.
Zu den Fahrradabstellanlagen an Bahnhöfen wurden in der Fallstudie drei unterschiedlich große Anlagen einbezogen: Dein Radschloss des Verkehrsverbundes Rhein-Ruhr (VRR) für kleine, das Radhaus Offenburg für mittelgroße und die Radstation Düsseldorf für große Standorte.
München wurde schließlich für eine kommunale Strategie zur verbesserten Verknüpfung von Fahrrad und Öffentlichem Verkehr ausgewählt, da dort eine Vielzahl von Maßnahmen zur Stärkung der Fahrradmobilität sichtbar sind.
SAFE Newsletter : 2018, Q3
(2018)
Die am Ende des 19. Jahrhunderts in Frankreich entstandene Décadence hatte einen wichtigen Einfluss auf europäische Literaturen. Charles Baudelaire, Paul Bourget, Hermann Bahr und Friedrich Nietzsche sind unter den Vertretern dieser literarischen Bewegung aufzuzählen. Die Wirkung der Décadence auf derzeitige türkische Literatur ist aus vielen Werken erkennbar. Yakup Kadris frühe Werke tragen auch klare Spuren der 'Décadence'. In seinem Roman 'Yaban' – obwohl es ein realistischer Roman ist – sind viele dekadente Eigenschaften zu betrachten. Der große Abgrund zwischen den türkischen Intellektuellen und den Dörfern ist ein wichtiges Thema des Werkes. Der Protagonist Ahmet Celâl beschließt nach dem Ersten Weltkrieg in einem kleinen Dorf Anatoliens zu leben. Durch seine Erfahrungen und Beziehungen mit den Dörflern treten zahlreiche dekadente Eigenschaften der Dörfler und des Protagonisten in Vordergrund. Ahmet Celâl konfrontiert die Einsamkeit, Krankheiten, Hilflosigkeit, Entfremdung und allerart soziokulturellen Verfall im Dorf, was die dekadente Seite des Dorfes zeigt. Andererseits sind seine dekadenten Haltungen wie Zurückgezogenheit, Übertreibung der Hässlichkeit und Schönheit, Widrigkeit, Verschönerung des Todes und Pessimismus im Werk zu sehen. In dieser Arbeit wird eine kurze Information über die Dekadenz und deren Vertreter vermittelt. Anhand der Décadence-Auffassungen von Nietzsche, Bourget und Bahr werden dekadente Motive in Yakup Kadris Roman Yaban dargestellt.
Das Ziel dieser Arbeit ist es, die Dekadenz als literarische Vorlage in den Werken von Tezer Özlü und Hugo von Hofmannsthal zu untersuchen. Hierbei wird der Tod in den Werken 'Die kalten Nächte der Kindheit' und 'Das Märchen der 672. Nacht' mit Hilfe der hermeneutischen Methode analysiert. Anhaltspunkt für die Analyse ist die Dekadenzdichtung nach Bourget und Bahr. Bourgets Vergleich der Gesellschaft mit Organismen und deren Verfall im Falle einer Verweigerung der Kooperation sind neben Bahrs Romantik der Nerven, Hang nach dem Künstlichen, Sucht nach dem Mystischen und letztlich dem Zug ins Ungeheure und Schrankenlose Hauptuntersuchungskriterien bei der Motivselektion. Die ausgesuchten Motive werden in Passagen ausgeschnitten und den dekadenten Vorgaben gemäß interpretiert und kontrastiv verglichen. Man sieht, dass die Dekadenzdichtung nicht zeitengebunden ist, da beide Werke verschiedenen Epochen angehören. Was sie vereint, ist einzig und allein der Hang zur Abweichung, wie auch Huysmanns Roman A rebours es sagt, nämlich gegen den Strich.
Hofmannsthal ist vom Orient fasziniert. In seinem lyrischen Drama "Hochzeit der Sobeide" wie in vielen seiner Werke und Erzählungen sind Einflüsse der orientalischen Kultur auffällig. Der Handlungsort des Dramas "Die Hochzeit der Sobeide" ist eine alte Stadt im Königreich Persien. Dass der orientalische Schauplatz hier eine dekorative Bedeutung hat, bestätigt eine spätere Version, in der die Geschichte von Persien nach Ragusa verlegt wird. Aus der Stadt in Persien wird dann eine italienische Kaufmannsrepublik. Dennoch stellt sich die Frage: Warum die Geschichte zunächst im Orient spielt. Mein Beitrag wird die Deutung orientalischer Spuren in dem Theaterstück thematisieren.
Background: Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells (NPCs), especially their biological behavior under the influence of exogenous stem cells, specifically the gene expression and regulation pattern. In the present study, we aimed to determine messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), which are differentially expressed during the co-culturing process with adipose-derived mesenchymal stem cells (ASCs) and to explore the involved signaling pathways and the regulatory networks.
Methods: We compared degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA-mRNA microarray analysis. Based on these data, we investigated the significantly regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were demonstrated to be involved in IDD were chosen; we investigated their theoretic regulatory importance associated with our microarray data.
Results: We found 632 lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716 probes. We then confirmed the microarray data by real-time PCR. Furthermore, we demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176 significantly enriched pathways, such as the mitogen-activated protein kinase (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network was constructed for the significantly changed mRNAs and lncRNAs. Also, the competing endogenous RNA (ceRNA) network was built.
Conclusion: Our results present the first comprehensive identification of differentially expressed lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and outline the gene expression regulation pattern. These may provide valuable information for better understanding of stem cell therapy and potential candidate biomarkers for IDD treatment.
Background: The rate of caesarean sections increased in the last decades to about 30% of births in western populations. Many caesarean sections are electively planned without an urgent medical reason for mother or child. Especially in women with a foregoing caesarean section, the procedure is planned early. An early caesarean section though may harm the newborn. Our aim is to evaluate the gestational time point after the 37th gestational week (after prematurity = term) of performing an elective caesarean section with the lowest morbidity for mother and child.
Methods: This is an update of a systematic review previously carried out on behalf of the German Federal Ministry of Health. We will perform a systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary outcome is the rate of admissions to the neonatal intensive care unit in early versus late term neonates. We will include (quasi) randomized controlled trials and cohort studies. The studies should include pregnant women who have an elective caesarean section at term. We will screen titles and abstracts and the identified full texts of studies for eligibility. Risk of bias will be assessed with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks will be performed independently by two reviewers. Data will be extracted in beforehand piloted extraction tables. A dose-response meta-analysis will be performed.
Discussion: Our aim is to reach a higher validity in the assessment of the time point of elective caesarean sections by performing a meta-analysis to support recommendations for clinical practice. We assume to identify less randomized controlled trials but a large number of cohort studies analyzing the given question. We will discuss similarities and differences in included studies as well as methodological strengths and weaknesses.
Systematic review registration: PROSPERO CRD42017078231
Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics.
Background/Aims: Sphingosine 1-phosphate (S1P) is considered as a key molecule regulating various cell functions including cell growth and death. It is produced by two sphingosine kinases (SK) denoted as SK-1 and SK-2. Whereas SK-1 has been extensively studied and has been appointed a role in promoting cell growth, the function of SK-2 is controversial, and both pro-proliferative and pro-apoptotic functions have been suggested. In this study we investigated whether renal mesangial cells isolated from transgenic mice overexpressing the human Sphk2 gene (hSK2-tg) showed an altered cell response towards growth-inducing and apoptotic stimuli.
Methods: hSK2-tg mice were generated by using a Quick KnockinR strategy. Renal mesangial cells were isolated by a differential sieving method and further cultivated in vitro. Lipids were quantified by mass spectrometry. Protein expression was determined by Western blot analysis, cell proliferation was determined by 3H-thymidine incorporation, and apoptosis was determined by a DNA fragmentation ELISA.
Results: We show here that kidneys and mesangial cells from hSK2-tg mice express the hSK2 as well as the endogenous mouse mSK2. hSK2 and mSK2 predominantly resided in the cytosol of quiescent transgenic cells. However, S1P accumulated strongly in the nucleus and only minimally in the cytosol of transgenic cells. Functionally, hSK2-tg cells proliferated less than control cells under normal growth conditions and were also more sensitive towards stress-induced apoptosis. On the molecular level, this was reflected by reduced ERK and Akt/PKB activation, and upon staurosporine treatment, by a sensitized mitochondrial pathway as manifested by reduced anti-apoptotic Bcl-XL expression and increased cleavage of caspase-9, downstream caspase-3 and PARP-1.
Conclusion: Altogether, these data demonstrate that SK-2 exerts an antiproliferative and apoptosis-sensitizing effect in renal mesangial cells which suggests that selective inhibitors of SK-2 may promote proliferation and reduce apoptosis and this may have impact on the outcome of proliferation-associated diseases such as mesangioproliferative glomerulonephritis.
Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma
(2018)
Glioblastoma (GB) is the most frequent primary brain tumor in adults with a dismal prognosis despite aggressive treatment including surgical resection, radiotherapy and chemotherapy with the alkylating agent temozolomide. Thus far, the successful implementation of the concept of targeted therapy where a drug targets a selective alteration in cancer cells was mainly limited to model diseases with identified genetic drivers. One of the most commonly altered oncogenic drivers of GB and therefore plausible therapeutic target is the epidermal growth factor receptor (EGFR). Trials targeting this signaling cascade, however, have been negative, including the phase III OSAG 101-BSA-05 trial. This highlights the need for further patient selection to identify subgroups of GB with true EGFR-dependency. In this retrospective analysis of treatment-naïve samples of the OSAG 101-BSA-05 trial cohort, we identify the EGFR signaling activity markers phosphorylated PRAS40 and phosphorylated ribosomal protein S6 as predictive markers for treatment efficacy of the EGFR-blocking antibody nimotuzumab in MGMT promoter unmethylated GBs. Considering the total trial population irrespective of MGMT status, a clear trend towards a survival benefit from nimotuzumab was already detectable when tumors had above median levels of phosphorylated ribosomal protein S6. These results could constitute a basis for further investigations of nimotuzumab or other EGFR- and downstream signaling inhibitors in selected patient cohorts using the reported criteria as candidate predictive biomarkers.
In the insect brain, the mushroom body is a higher order brain area that is key to memory formation and sensory processing. Mushroom body (MB) extrinsic neurons leaving the output region of the MB, the lobes and the peduncle, are thought to be especially important in these processes. In the honeybee brain, a distinct class of MB extrinsic neurons, A3 neurons, are implicated in playing a role in learning. Their MB arborisations are either restricted to the lobes and the peduncle, here called A3 lobe connecting neurons, or they provide feedback information from the lobes to the input region of the MB, the calyces, here called A3 feedback neurons. In this study, we analyzed the morphology of individual A3 lobe connecting and feedback neurons using confocal imaging. A3 feedback neurons were previously assumed to innervate each lip compartment homogenously. We demonstrate here that A3 feedback neurons do not innervate whole subcompartments, but rather innervate zones of varying sizes in the MB lip, collar, and basal ring. We describe for the first time the anatomical details of A3 lobe connecting neurons and show that their connection pattern in the lobes resemble those of A3 feedback cells. Previous studies showed that A3 feedback neurons mostly connect zones of the vertical lobe that receive input from Kenyon cells of distinct calycal subcompartments with the corresponding subcompartments of the calyces. We can show that this also applies to the neck of the peduncle and the medial lobe, where both types of A3 neurons arborize only in corresponding zones in the calycal subcompartments. Some A3 lobe connecting neurons however connect multiple vertical lobe areas. Contrarily, in the medial lobe, the A3 neurons only innervate one division. We found evidence for both input and output areas in the vertical lobe. Thus, A3 neurons are more diverse than previously thought. The understanding of their detailed anatomy might enable us to derive circuit models for learning and memory and test physiological data.
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
Despite being an essential consideration when deciding rule changes, injury prevention strategies, and athlete development models, there is little epidemiological data of U18 field hockey player injuries–something explicitly referred to in the 2015 International Olympic Committee’s Consensus Statement on Youth Athlete Development. The aim of this study was to quantify incidence and characteristics of injuries in elite youth field hockey players during a major international tournament. Standardized reporting forms detailing time, location on pitch, mechanism and anatomical location of injury were completed for new musculoskeletal conditions resulting in a time stoppage by the umpire and where a player was noticeably affected by an injury for up to 20 s regardless of time stoppage. Injury incidence was 1.35 and 2.20 injuries/match or 53 and 86 injuries per 1000 player match hours for boys (B) and girls (G) respectively; girls were over three times more likely to have a minor injury. Most injuries were contusions due to being hit by the ball or stick (B: 12, G: 27), with high numbers of injuries to the torso (B: 8) and head/face (G: 7). Injuries during the penalty corner (B: 3, G: 4) were to the lower limb and hand, and boys were less likely to wear facial protection (B: 65.9%, G: 86.4%). Results form an essential initial dataset of injuries in U18 field hockey players. Current reporting protocols under-report injuries and must be addressed by the international governing body. The high number of head/face injuries, particularly in females, requires further investigation.
Introduction: The clinical management of breech presentations at term is still a controversially discussed issue among clinicians. Clear predictive criteria for planned vaginal breech deliveries are desperately needed to prevent adverse fetal and maternal outcomes and to reduce elective cesarean section rates. The green-top guideline considers an estimated birth weight of 3.8 kg or more an indication to plan a cesarean section despite the lack of respective evidence.
Objective: To compare maternal and neonatal outcome of vaginal intended breech deliveries of births with children with a birth weight of 2.5 kg– 3.79 kg and children with a birth weight of 3.8 kg and more.
Design: Prospective cohort study.
Sample: All vaginal intended deliveries out of a breech position of newborns weighing between 2.5 kg and 4.5 kg at the Obstetrics department at Goethe University Hospital Frankfurt from January 2004 until December 2016
Methods: Neonatal and maternal outcome of a light weight group (LWG) (< 3.8 kg) was compared to and a high weight group (HWG) (≥ 3.8 kg) using Pearson’s Chi Square test and Fishers exact test. A logistic regression analysis was performed to detect an association between cesarean section rates, fetal outcome and the birth weight.
Results: No difference in neonatal morbidity was detected between the HWG (1.8%, n = 166) and the LWG (2.6%, n = 888). Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 1.57 (95% CI 1.29–1.91, p<0.0001). In vaginal deliveries, a high birth weight was not associated with an increased risk of maternal birth injuries (LWG in vaginal deliveries: 74.3%, HWG in vaginal deliveries: 73.6%; p = 0.887; OR = 1.9 (95% CI 0.9–1.1))
Conclusion: A fetal weight above 3.79 kg does not predict increased maternal or infant morbidity after delivery from breech presentation at term. Neither the literature nor our analyses document evidence for threshold of estimated birth weight that is associated with maternal and/or infant morbidity. However, patients should be informed about an increased likelihood of cesarean sections during labor when attempting vaginal birth from breech position at term in order to reach an informed shared decision concerning the birth strategy. Further investigations in multi center settings are needed to advance international guidelines on vaginal breech deliveries in the context of estimated birth weight and its impact on perinatal outcome.
Marie Wrona präsentiert in ihrem Beitrag "Ist das ein Komma oder kann das weg? - Topologische Felder und Kommasetzung. Erste empirische Befunde" ein Experiment zur Kommadidaktik. Sie untersucht, inwiefern sich die Kommasetzungskompetenz von SchülerInnen verbessert, wenn diese mithilfe des topologischen Feldermodells vermittelt wird, das auf der Verbklammer im Deutschen aufbaut, anstatt wie bei traditionellen Ansätzen mithilfe von Signalwörtern wie Subjunktionen. Die SchülerInnen lernten, das finite Verb zu bestimmen und so zu entscheiden, ob ein Komma gesetzt werden muss oder nicht. Nach der Unterrichtseinheit setzten die SchülerInnen v.a. deutlich weniger falsche Kommata
Johanna Hartwig beschäftigt sich mit der Deklination entlehnter Farbadjektive wie lila, orange und rosa ("Gibt es denn jetzt lilane Kühe oder nicht? - Einflussfaktoren auf den Gebrauch indeklinabler Farbadjektive"). Diese Adjektive wurden ursprünglich nicht flektiert (das lila/rosa Haus). Hartwig führt ein Produktionsexperiment durch, um zu überprüfen, inwiefern die Frequenz und die Endung eines Adjektivs Einfluss auf dessen Flexion nehmen. Dabei stellt sie fest, dass frequente Adjektive zur Flexion neigen, jedoch auch die Endung eine Rolle spielt. So bleiben Adjektive auf [a] wie bspw. lila trotz hoher Frequenz unflektiert. Adjektive auf Frikativ weisen hingegen umso mehr Flexion auf, je frequenter sie sind. Für seltene Adjektive (creme) konnte Hartwig eine Vermeidungsstrategie feststellen: Creme wurde in ihrem Experiment am häufigsten in ein Derivat (cremefarben) umgewandelt, das eine Flexion des Adjektivs ermöglicht (das cremefarbene Haus).
Wie Hashtags bei Twitter als Teile von Komposita verwendet werden, zeigt Markus Majewski in seinem Beitrag #Erdogan-Diktatur - Hashtags als Elemente von Substantivkomposita in politischen Tweets. Als Grundlage dient ihm das Korpus aus Tweets von SpitzenpolitikerInnen der großen Parteien während des Wahlkampfs, in dem er alle Substantivkomposita mit einem Hashtag als Bestandteil wie #Energiewende auf funktionale, graphematische und strukturelle Aspekte untersucht. Insbesondere bei der Schreibung der Komposita zeigt sich eine große Kreativität. Zudem lassen sich Twitter-spezifische Kommunikationsfunktionen der Hashtag-Erstglieder beobachten.
Für den Wandel und die Variation der Präposition wegen interessieren sich Lea Heese und Fabiola Kaiser in ihrem Beitrag "Die menschliche Zunge ist faul. Assoziationen zu der Verwendungsweise der Präposition wegen mit dem Genitiv und dem Dativ". Wegen schwankt im Standard-deutschen zwischen Genitiv- und Dativrektion. Obwohl sie seit langem existiert, wird die Dativvariante von SprecherInnen oftmals als Zeichen für Sprachverfall gedeutet. Heese und Kaiser erhoben mithilfe einer Onlineumfrage Daten zum Gebrauch der Präposition in informellen und formellen Registern sowie Assoziationen zu den beiden Varianten. Wie bereits das Titelzitat des Beitrags zeigt, wird der Dativ unter anderem als Zeichen für Nachlässigkeit interpretiert.
Carlotta J. Hübener diskutiert in ihrem Beitrag "Nicht/keinen/kein Fußball spielen? - Inkorporationsprozesse in Substantiv-Verb-Verbindungen" Inkorporationprozesse bei Substantiv-Verb-Verbindungen wie bspw. Fußball spielen. Hierbei fokussiert sie auf die Negation: Während kein(en) Fußball spielen einen Hinweis darauf gibt, dass Fußball noch als eigenständiges Substantiv interpretiert wird, ist nicht Fußball spielen ein Indiz dafür, dass Fußball und spielen als eine konzeptionelle Einheit wahrgenommen werden. Kein negiert nämlich Nomen (Ich mag keinen Spinat), während nicht Verben negiert (Ich hab‘ noch nicht gegessen). Hübener überprüft in ihrem Beitrag anhand des Deutschen Referenzkorpus, inwiefern Frequenz, Idiomatik und Individuiertheit Einfluss auf die Negation von Substativ-Verb-Verbindungen nehmen können.
Brit Schwerin nimmt sich in ihrem Artikel "die bisher jedermann unbekannt gewesen [ist/war/sei/wäre] -Zum Rückgang des ersparten Finitums in Nebensätzen des frühen Neuhochdeutsch" des Phänomens der afiniten Nebensätze an, die in der Frühen Neuzeit im deutschen Sprachraum weit verbreitet waren. Ihre Analyse von Nebensätzen mit und ohne finites Verb in Texten aus dem 17. und 18. Jh. ergibt, dass der Rückgang der afiniten Konstruktionen in Verbindung mit dem Bedürfnis nach eindeutiger Markierung grammatischer Kategorien wie Tempus und Modus steht. Die diachronen Studien decken somit Sprachwandel auf verschiedenen Ebenen ab.
Wie sich Konzessivkonnektoren im 18. und 19. Jh. entwickelt haben, untersuchen Lisa Bürgerhoff, Jana Giesenschlag, Linda Kunow und Alexandra Kern für ihren Beitrag "Von ob ich schon wanderte zu obschon ich wanderte?! - Eine Korpusuntersuchung zur Konzessivität von 1700-1900". Ihre Untersuchungen im Deutschen Textarchiv zeigen unter anderem einen Zusammenhang zwischen der Zusammenschreibung der Konnektoren und einer eindeutig konzessiven Lesart, der für obschon, obgleich, obwohl und obzwar allerdings unterschiedlich stark ist. Auch die Faktizität der Teilsätze und das Auftreten verstärkender Partikeln sind für die Entwicklung der ob-Gruppe von Bedeutung. Als eindeutigste und frequenteste Konzessivkonnektoren stellen sich insgesamt obwohl und vor allem obzwar heraus.
Mit der mittelhochdeutschen Nebensilbenabschwächung beschäftigt sich Tanja Stevanovićs Beitrag "Wo sind die vollen Vokale geblieben? Eine Untersuchung möglicher Einflussfaktoren auf die Nebensilbenabschwächung". Dafür hat sie in einer Korpusuntersuchung im Referenzkorpus Mittelhochdeutsch schwache Verben analysiert, die trotz der fortschreitenden Nebensilbenabschwächung noch im Mittelhochdeutschen Vollvokale in Endsilben aufweisen.
Lena Schnee analysiert in ihrem Beitrag "Eingenordet - Morphologische Assimilation mittelniederdeutscher Lehnwörter im Altnordischen" die Liste mittelniederdeutscher Entlehnungen im Altnordischen Etymologischen Wörterbuch und zeigt, wie die mittelniederdeutschen Wörter, die in der Hansezeit in die skandinavischen Sprachen entlehnt wurden, an das Altnordische angepasst wurden. Dabei wendet sie ein Transderivationsmodell an, um die morphologische Assimilation nicht nur von ganzen Lexemen, sondern auch von Affixen und Wortstämmen nachzuvollziehen. Schnees Untersuchung ergibt, dass bei der Entlehnung in das Altnordische hauptsächlich die Affixe adaptiert wurden. Die mittelniederdeutschen Affixe wurden überwiegend durch native oder entlehnte altnordische ersetzt, was darauf hinweist, dass die Morphemgrenzen und Wortbildungselemente bei der Entlehnung als solche erkannt wurden. Als Erklärung hierfür führt Schnee die typologische Ähnlichkeit der beiden Sprachen an.
Die hier abgedruckten Beiträge sind in einem Lehrprojekt zum Thema "Wie verändern wir Sprache?" entstanden. Das im Rahmen des Universitätskollegs 2.0 aus Mitteln des BMBF geförderte Projekt fand vom Sommersemester 2017 bis zum Wintersemester 2017/18 an der Universität Hamburg statt. Insgesamt 17 Studierende beschäftigten sich über ein Jahr hinweg mit aktuellen und historischen Sprachwandelphänomenen und führten eigene empirische Forschungsprojekte durch, die sie auf der studentischen Tagung am 1.-3. Februar 2018 präsentierten. Die Beiträge beschäftigen sich aus diachroner sowie synchroner Perspektive mit Sprachvariation und -wandel.
Diyalog 2018/1
(2018)
Im Fachbereich der Deutschen Literatur äußert sich der erste Artikel zur Autorinszenierung in Rolf Schneiders Erzählung "Metamorphosen". Eine Deutung orientalischer Spuren in Hofmannsthals lyrischem Drama "Die Hochzeit der Sobeide" bildet den Schwerpunkt des zweiten Artikels dieser Rubrik. Im dritten Beitrag dieses Fachbereichs geht es um das Leben und Schreiben von Wolfgang Hilbig und die Schwierigkeiten ein Mann zu sein. Der vierte Beitrag stellt "Leutnant Gustl" als eine repräsentative Figur für die Identitätdefizite in der Gesellschaft in den Mittelpunkt. Erich Maria Remarques Roman "Im Westen nichts Neues" bildet den Ausgangspunkt für die Analyse von 'Kriegstrauma' als eine der bedeutendsten Herausforderungen in der Antikriegsliteratur, was im fünften Beitrag der Rubrik Deutsche Literatur nachgelesen werden kann. Dem Fachbereich Komparatistik sind zwei Artikel zuzuordnen. Der erste stellt anhand eines episch dekadenten Dialogs einen dekadenten Vergleich des Todes in den Werken von Tezer Kıral und Hugo von Hofmannsthal in den Mittelpunkt. Im zweiten Beitrag erfolgt eine Analyse des Romans 'Yaban' von Yakup Kadri im Sinne der Dekadenz. Sieben Beiträge bearbeiten Themen aus der Erziehungswissenschaft bzw. aus dem DaF-Bereich. Überlegungen hinsichtlich der Vermittlung von Speicherstrategien beim Lernen mit der Wortliste des Goethe-Zertifikats B1 bilden den Fokus des ersten Beitrags dieser Rubrik. Der zweite Beitrag präsentiert Ergebnisse einer Studie zur fehleranalytischen Kompetenz der Studenten/innen in der Deutschlehrerausbildung. Der dritte Artikel analysiert und bewertet Sprachlernspiele in dem Lehrwerk 'MOMENT MAL 1' und 'MOMENT MAL 2'. Der vierte Beitrag dieses Fachbereichs ist in Türkisch verfasst und stellt Überlegungen zur Entwicklung von digitalen Spielen und zu gamifizierten Anwendungen in dem Fremdsprachenunterricht in den Mittelpunkt. Ebenfalls in Türkisch verfasst ist der fünfte Aufsatz, der bei der Lehre von Türkisch als Zweitsprache Nutzen aus den Modellen und Erfahrungen thematisiert, die bei der Vermittlung von Deutsch als zweite Sprache mit in Deutschland lebendenden Migranten gemacht worden sind. Thema des sechsten Artikels ist die Erforschung von Stereotypen in DaF- und TRaF-Lehrwerken und ihr Potenzial als Störfaktor oder Impulsgeber. Der letzte Beitrag des Bereichs Erziehungswissenschaft bzw. DaF fokussiert eine korpusbasierte Studie am Beispiel der Germanistikstudenten der Ege Universität, in der die pragmatisch-diskursive Fähigkeit in den mündlichen Prüfungsgesprächen analysiert wird. Dem Bereich Translationswissenschaft sind vier Aufsätze zugehörig. In dem ersten Beitrag wird eine empirische Studie präsentiert, die die Rolle sprachlicher und kultureller Kompetenz in der "Funktionalen Übersetzung" zum Thema hat. In Türkisch verfasst ist der zweite Artikel dieser Rubrik, der Maßstäbe der Textwahl im Übersetzungsunterricht behandelt. Informationen zur Konzeption des Türkischen Übersetzerlexikons werden im dritten Aufsatz gegeben. Der in Türkisch verfasste vierte Beitrag dieses Fachbereichs gibt einen allgemeinen Überblick über ins Türkische übersetzte deutsche Literatur. Der Forum-Teil ist dem in Türkisch verfassten Beitrag vorbehalten, der mit Edmund Husserl in Bezug auf das Museum des 11. Septembers als Erinnerungszeichen die Suche nach Sinn fokussiert. In der Rubrik Berichte werden im Rückblick Informationen zu zwei Konferenzen mitgeteilt. In dem ersten Tagungsbericht wird die Stärke und Rolle der deutschen Sprache in Mitteleuropa betont, so, wie sie in einer linguistischen Konferenz vermittelt worden ist. In dem zweiten Tagungsbericht werden Erfahrungen und Informationen zum XI. Internationalen Kongress der Germanisten Rumäniens wiedergegeben. Neben den Aufsätzen und Berichten gibt es in dieser Ausgabe auch eine in Türkisch geschriebene Rezension zum Werk "Lernabenteuer Deutsch - Das Geheimnis der Himmelsscheibe".
Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.