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Die Arbeit untersucht die Ad-hoc-Publizität unter der Geltung der MAR. In der Arbeit werden zuerst das Informationsmodell auf dem Kapitalmarkt und die Erforderlichkeit und Notwendigkeit der Regulierung des Kapitalmarkts durch gesetzliche Informationspflichten analysiert. Mithilfe eines Rückblicks auf die Entwicklung der Ad-hoc-Publizität in den Rechtsnormen wird ihr Sinn und Zweck untersucht. Die rechtlichen Anforderungen an Ad-hoc-Publizität unter der Geltung der MAR werden in einem weiteren Schritt untersucht. Der Schwerpunkt liegt dabei auf den Tatbestandsmerkmalen der Ad-hoc-Publizitätspflicht und dem Aufschub der Veröffentlichung. Darüber hinaus werden die Rechtsfolgen im Falle von Pflichtverstößen, insbesondere Anspruchsgrundlagen nach §§ 97, 98 WpHG analysiert. Im Hinblick auf die Ad-hoc-Publizität nach dem chinesischen Recht werden ihre historische Entwicklung in Rechtsnormen und ihr Sinn und Zweck untersucht. Eine dogmatische Analyse der Ad-hoc-Publizitätspflicht und der Rechtsfolgen beim Pflichtverstoß nach dem geltenden chinesischen Recht wird dann durchgeführt. Schließlich wird die Ad-hoc-Publizität nach der MAR und dem chinesischen Recht verglichen.
Im rechtsvergleichenden Teil der Untersuchung identifiziert der Verfasser bestimmte Besonderheiten und Defizite im chinesischen Recht. Den Regelungsansätzen der beiden Rechtssysteme liegen unterschiedliche rechtpolitische Zielsetzungen zugrunde. In der EU und in Deutschland steht der Konnex zum Insiderhandel im Vordergrund, denn diesem wird durch die Ad-Hoc Meldung der Boden entzogen. In China handelt es sich bei der Ad-hoc-Publizität konzeptionell eher um einen Annex zur Regelpublizität. Damit geht Hand in Hand, dass die Verfolgung zivilrechtlicher Ansprüche aufgrund falscher Ad-hoc-Meldungen in China der behördlichen Genehmigung bedarf. Der Verfasser macht auf dieser Grundlage Vorschläge zur (behutsamen) Rechtsfortbildung in China nach europäischem Vorbild.
This inventory intends to provide updated numbers of vascular plants occurring in Cyprus. Currently, 1649 indigenous taxa (species and subspecies) are known to occur in Cyprus. In addition 254 taxa belong to various categories of neophytes. The endemism rate of the indigenous flora amounts to 8.55 %, i. e. 141 taxa, while 33 species and subspecies belong to the category of near-endemic for which Cyprus bears significant responsibility for their conservation.
The recently described Phelipanche hedypnoidis from the Orobanche (Phelipanche) ramosa group has been found in Cyprus for the first time. So far, it is known only from one site at the south coast. Hedypnois rhagadioloides as host plant is confirmed. To meet the demands of a more traditional generic treatment the new combination Orobanche hedypnoidis is proposed.
Further noteworthy records of vascular plants in Cyprus (1997–2018) and some status clarifications
(2019)
This paper deals with specimen-based records of 74 taxa, most of them having a scattered occurrence or restricted distribution range in Cyprus. The following taxa are new to Cyprus or have been found in the wild for the first time: Aristida adscensionis subsp. adscensionis, Buglossoides incrassata subsp. splitgerberi, Cenchrus setaceus, Chenopodium rubrum, Gazania rigens, Malus domestica, Mespilus germanica, Mirabilis jalapa, Pyrus communis, Sambucus nigra and Spartium junceum. The new combination Urtica cypria (H. Lindb.) Hand for the endemic nettle species is proposed.
Tradescantia fluminensis is an invasive weed that has been recorded for the first time in Cyprus. The species occurs in river banks, mainly under shady conditions. It has been recorded in three sites, always at low density: Marathasa river (Lefkosia district), Kargotis river (Lefkosia district), Kryos river (Lemesos district).
The influence of temperature is regarded as particularly important for a structural health monitoring system based on ultrasonic guided waves. Since the temperature effect causes stronger signal changes than a typical defect, the former must be addressed and compensated for reliable damage assessment. Development of new temperature compensation techniques as well as the comparison of existing algorithms require high-quality benchmark measurements. This paper investigates a carbon fiber reinforced plastic (CFRP) plate that was fully characterized in previous research in terms of stiffness tensor and guided wave propagation. The same CFRP plate is used here for the analysis of the temperature effect for a wide range of ultrasound frequencies and temperatures. The measurement data are a contribution to the Open Guided Waves (OGW) platform: http://www.open-guided-waves.de. The technical validation includes initial results on the analysis of phase velocity variations with temperature and exemplary damage detection results using state-of-the-art signal processing methods that aim to suppress the temperature effect.
AMPA receptors and interacting proteins are importantly involved in mediating stress-dependent plasticity. Previously we reported that GluA1-containing AMPA receptors and their interaction with PDZ-proteins are required for the experience-dependent expression of behavioral despair in the forced swim test. However, it is unclear if the expression of GluA1-containing AMPA receptors is affected by this type of behavior. Here we investigated in wild type mice, whether hippocampal gene or protein levels of GluA1 or associated PDZ proteins is altered following forced swim stress. We show that expression of Dlg4 (the gene coding for PSD-95) was strongly reduced after two days of forced swimming. In contrast, levels of Dlg1, Gria1, and Gria2 (coding for SAP97, GluA1, and GluA2 respectively) were not affected after one or two days of forced swimming. The changes in gene expression largely did not translate to the protein level. These findings indicate a limited acute effect of forced swim stress on the expression of the investigated targets and suggest that the acute involvement of GluA1-containing AMPA receptors tor forced swim behavior is a result of non-genomic mechanisms.
Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2–3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period.
Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the “door-to-needle” time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire.
Interventions: We are applying a multi-level intervention in cooperation with three “STREAM multipliers” from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2–3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings.
Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and often has a poor prognosis. The present study investigated the role of the low affinity nerve growth factor receptor CD271 as a putative therapy target in HNSCC. Neurotrophins that bind to CD271 also have a high affinity for the tropomyosin receptor kinase family (Trk), consisting of TrkA, TrkB, and TrkC, which must also be considered in addition to CD271. A retrospective study and functional in vitro cell line tests (migration assay and cell sorting) were conducted in order to evaluate the relevance of CD271 expression alone and with regard to Trk expression. CD271 and Trks were heterogeneously expressed in human HNSCC. The vast majority of tumors exhibited CD271 and TrkA, whereas only half of the tumors expressed TrkB and TrkC. High expression of CD271-positive cells predicted a bad clinical outcome of patients with HNSCC and was associated with distant metastases. However, the human carcinomas that also expressed TrkC had a reduced correlation with distant metastases and better survival rates. In vitro, CD271 expression marked a subpopulation with higher proliferation rates, but proliferation was lower in tumor cells that co-expressed CD271 and TrkC. The CD271 inhibitor LM11A 31 suppressed cell motility in vitro. However, neither TrkA nor TrkB expression were linked to prognosis or cell proliferation. We conclude that CD271 is a promising candidate that provides prognostic information for HNSCC and could be a putative target for HNSCC treatment.
Background: Outcomes of catheter ablation of atrial fibrillation (AF) are variable and the predictors of success require further elucidation since the identification of correctable risk factors could help to optimize therapy. We aimed to assess the impact of body mass index (BMI) in the overall safety and efficacy of catheter ablation of AF, with emphasis on the use of cryoballoon ablation and novel oral anticoagulants.
Methods and Results: There were 2497 consecutive patients undergoing catheter ablation of AF in 7 European high volume centers were stratified according to BMI (normal weight <25 kg/m2, pre‐obese 25–30 kg/m2, obesity 30–35 kg/m2, and morbid obesity ≥35 kg/m2) and comparisons of procedural outcomes evaluated. Pre‐obese and obese patients presented more comorbidities (hypertension, diabetes mellitus, and sleep apnea), and had higher rates of non‐paroxysmal AF ablation procedures. The rate of atrial 12‐month arrhythmia relapse increased alongside with BMI (35.2%, 35.7%, 43.6%, and 48.0% P<0.001). During a median follow‐up of 18.8 months (interquartile range 11–28), after adjusting for all baseline differences, BMI was an independent predictor of relapse (hazard ratio=1.01 per kg/m2; 95% CI 1.01–1.02; P=0.002), adding incremental predictive value to obstructive sleep apnea. BMI was not a predictor for any of the reported complications. Using novel oral anticoagulants and cryoballoon ablation was safe and efficacy was comparable with vitamin‐K antagonists and radiofrequency ablation.
Conclusions: Obese patients present with a more adverse comorbidity profile, more advanced forms of AF, and have lower chances of being free from AF relapse after ablation. Use of novel oral anticoagulants and cryoballoon ablation may be an option in this patient group.
In vivo functional diversity of midbrain dopamine neurons within identified axonal projections
(2019)
Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.
Intact-cell maldi-tof mass spectrometry for the authentication of drug-adapted cancer cell lines
(2019)
The use of cell lines in research can be affected by cell line misidentification. Short tandem repeat (STR) analysis is an effective method, and the gold standard, for the identification of the genetic origin of a cell line, but methods that allow the discrimination between cell lines of the same genetic origin are lacking. Here, we use intact cell MALDI-ToF mass spectrometry analysis, routinely used for the identification of bacteria in clinical diagnostic procedures, for the authentication of a set of cell lines consisting of three parental neuroblastoma cell lines (IMR-5, IMR-32 and UKF-NB-3) and eleven drug-adapted sublines. Principal component analysis (PCA) of intact-cell MALDI-ToF mass spectrometry data revealed clear differences between most, but not all, of the investigated cell lines. Mass spectrometry whole-cell fingerprints enabled the separation of IMR-32 and its clonal subline IMR-5. Sublines that had been adapted to closely related drugs, for example, the cisplatin- and oxaliplatin-resistant UKF-NB-3 sublines and the vincristine- and vinblastine-adapted IMR-5 sublines, also displayed clearly distinctive patterns. In conclusion, intact whole-cell MALDI-ToF mass spectrometry has the potential to be further developed into an authentication method for mammalian cells of a common genetic origin.
Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.
Inflammatory activation of astroglia adds to the pathology of various neurological diseases. Astrocytes respond to microglia-derived cytokines such as interleukin-1α (IL-1α) with enhanced inflammatory signaling. This provokes pro-inflammatory gene expression of, among others, the eicosanoid-generating enzyme prostaglandin endoperoxide synthase 2 (Ptgs2). Whereas metabolic regulation of innate immune cell inflammatory responses is intensely studied, pathways related to how metabolism modulates inflammatory signaling in astrocytes are underexplored. Here, we examined how mitochondrial oxidative phosphorylation affects inflammatory responses towards IL-1α and tumor necrosis factor α in neonatal rat astrocytes. Blocking respiratory complex I and III or adenosine triphosphate (ATP) synthase did not affect activation of inflammatory signaling by IL-1α, but did elicit differential effects on inflammatory gene mRNA expression. Remarkably, mRNA and protein expression of Ptgs2 by IL-1α was consistently up-regulated when oxidative phosphorylation was inhibited. The increase of Ptgs2 resulted from mRNA stabilization. Mitochondrial inhibitors also increased IL-1α-triggered secretion of eicosanoids, such as prostaglandin E2, prostaglandin F2α, and 6-keto-prostaglandin F1α, as assessed by liquid chromatography/mass spectrometry. Mechanistically, attenuating oxidative phosphorylation elevated adenosine monophosphate (AMP) and activated AMP-activated protein kinase (AMPK). AMPK silencing prevented Ptgs2 up-regulation by mitochondrial inhibitors, while AMPK activators recapitulated Ptgs2 mRNA stability regulation. Our data indicate modulation of astrocyte inflammatory responses by oxidative metabolism, with relevance towards eicosanoid production.
Background: Receiving a cancer diagnosis can be a major life event which causes distress even years after primary treatment.
Aim: To examine the prevalence of distress in older patients with cancer (OPCs) up until 5 years post-diagnosis, and identify predictors present at time of diagnosis. Results are compared with reference groups of middle-aged patients with cancer (MPCs) and older patients without a cancer diagnosis (OPs).
Design & setting: OPCs, MPCs, and OPs participated in a longitudinal cohort study in Belgium and the Netherlands by filling in questionnaires at designated time points from 2010–2019.
Method: Data from 541 patients were analysed using multivariable logistic regression analyses.
Results: At baseline, 40% of OPCs, 37% of MPCs, and 17% of OPs reported distress. After 5 years, 35% of OPCs, 23% of MPCs, and 25% of OPs reported distress. No significant predictors for long-term distress in OPCs and OPs were found. For MPCs, it was found that baseline distress (odds ratio [OR] 2.94; 95% confidence intervals [CI] = 1.40 to 6.19) and baseline fatigue (OR 4.71; 95% CI = 1.81 to 12.31) predicted long-term distress.
Conclusion: Distress is an important problem for people with cancer, with peaks at different moments after diagnosis. Feelings of distress are present shortly after diagnosis but they decrease quickly for the majority of patients. In the long term, however, OPCs in particular appear to be most at risk for distress. This warrants extra attention from primary healthcare professionals, such as GPs who are often patients’ first medical contact point. More research into risk factors occurring later in an illness trajectory might shed more light on predictors for development of long-term distress.
Wie man weiß, zählt der Sozialstaat der Industrieepoche zu den ganz großen Innovationen in der Institutionengeschichte. Es entsteht ausgehend vom europäischen Norden und Westen und schnell mit kontinentalen und globalen Dimensionen ein hochkomplexes Geflecht aus Organisationen, aus juridischen und nicht-juridischen Normen und aus sozialen Praktiken, das auf die große – für das Schicksal der kapitalistischen Ordnung mitentscheidende – Herausforderung der "sozialen Frage" antwortet. Dabei ist dieses Gefüge nicht strukturell einheitlich, sondern durch erhebliche nationale Variation geprägt. Darüber hinaus entstehen die Institutionen im Rahmen der Einzelstaaten in keiner Weise gleichzeitig, sondern auf einer langgestreckten Zeitachse. Dieser Befund der hochgradigen Varianz kennzeichnet den Sektor der industriellen Beziehungen, in dem kollektive Akteure wesentliche Aufgaben des Sozialstaats "übernehmen", in einer besonders intensiven Weise. Es ist dieser Bereich, auf den wir sogleich näher eingehen. Im Weiteren kommt es auf dem Kontinent mit dem Aufstieg nicht-demokratischer Regime und deren Versionen des Sozialstaats zu einer zusätzlichen Komplizierung. Und schließlich tritt die neue Makrostruktur – ihren genetischen Raum überschreitend – alsbald im globalen Rahmen in Erscheinung. Ihre weltweiten Wirkungen sind immens, wie das 100-jährige Jubiläum der ILO unterstreichen mag. Und die Rückwirkungen und Irritationen vor allem aus neuen dynamischen Zentren des demokratisch verfassten Kapitalismus, zunächst der USA und dann auch Japans, sind es nicht minder. ...
Introduction: An overview of the requirements for the head of a surgical department in Germany should be given.
Materials and methods: A retrospective literature research on surgical professional policy publications of the last 10 years in Germany was conducted.
Results: Surveys show that commercial influences on medical decisions in German hospitals have today become an everyday, predominantly negative, actuality. Nevertheless, in one survey, 82.9% of surgical chief physicians reported being very satisfied with their profession, compared with 61.5% of senior physicians and only 43.4% of hospital specialists. Here, the chief physician is challenged. Only 70% of those surveyed stated that they could rely on their direct superiors when difficulties arose at work, and only 34.1% regarded feedback on the quality of their work as sufficient. The high distress rate in surgery (58.2% for all respondents) has led to a lack in desirability and is reflected in a shortage of qualified applicants for resident positions. In various position papers, surgical residents (only 35% describe their working conditions as good) demand improved working conditions. Chief physicians are being asked to facilitate a suitable work-life balance with regular working hours and a corporate culture with participative management and collegial cooperation. Appreciation of employee performance must also be expressed. An essential factor contributing to dissatisfaction is that residents fill a large part of their daily working hours with non-physician tasks. In surveys, 70% of respondents stated that they spend up to ≥3 h a day on documentation and secretarial work.
Discussion: The chief physician is expected to relieve his medical staff by employing non-physician assistants to take care of non-physician tasks. Transparent and clearly structured training to achieve specialist status is essential. It has been shown that a balanced work-life balance can be achieved for surgeons. Family and career can be reconciled in appropriately organized departments by making use of part-time and shift models that exclude 24-h shifts and making working hours more flexible.
The artworks of the Peruvian artist Carlos Runcie Tanaka, who has his British and Japanese Roots combined in his surname, refer to pre-Columbian ceramics and traditional Peruvian, Japanese and European practices. He represented Peru in ARCOmadrid 2019, the 12th Havana Biennial, the XXVI Sao Paulo Biennial, the 49th Venice Biennale, and the I Bienal Iberoamericana de Lima. In August, we sat down to talk about music, the past, the present, and the future. We discussed how all references of time can be combined into one material.
By studying pre-Columbian ceramics, researchers have developed several interpretations about the lifestyle and cosmovision of the ancient Peruvian people. Many of the techniques and motifs included in these traditional practices are still being passed on to communities throughout the country today. This ancestral knowledge is a fundamental element of identity. Therefore, ceramic is a material that has made the generation of historical discourse and the preservation of cultural memory possible. At the same time, ceramics are connected to aspects of our daily life. As objects of daily use (such as mugs, plates and bowls) they contribute to the fulfillment of basic needs. They are also included in ritual and funerary practices. In conclusion, the use of ceramics can be understood not only in a practical sense, but in an artistic sense as well.
Therapy of acute myeloid leukemia (AML) is unsatisfactory. Histone deacetylase inhibitors (HDACi) are active against leukemic cells in vitro and in vivo. Clinical data suggest further testing of such epigenetic drugs and to identify mechanisms and markers for their efficacy. Primary and permanent AML cells were screened for viability, replication stress/DNA damage, and regrowth capacities after single exposures to the clinically used pan-HDACi panobinostat (LBH589), the class I HDACi entinostat/romidepsin (MS-275/FK228), the HDAC3 inhibitor RGFP966, the HDAC6 inhibitor marbostat-100, the non-steroidal anti-inflammatory drug (NSAID) indomethacin, and the replication stress inducer hydroxyurea (HU). Immunoblotting was used to test if HDACi modulate the leukemia-associated transcription factors β-catenin, Wilms tumor (WT1), and myelocytomatosis oncogene (MYC). RNAi was used to delineate how these factors interact. We show that LBH589, MS-275, FK228, RGFP966, and HU induce apoptosis, replication stress/DNA damage, and apoptotic fragmentation of β-catenin. Indomethacin destabilizes β-catenin and potentiates anti-proliferative effects of HDACi. HDACi attenuate WT1 and MYC caspase-dependently and -independently. Genetic experiments reveal a cross-regulation between MYC and WT1 and a regulation of β-catenin by WT1. In conclusion, reduced levels of β-catenin, MYC, and WT1 are molecular markers for the efficacy of HDACi. HDAC3 inhibition induces apoptosis and disrupts tumor-associated protein expression.
Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function.
Purpose: The aim of this study is to record material- and surface-dependent heat dissipation during the process of inserting implants into native animal bone. Materials and Methods: Implants made of titanium and zirconium that were identical in macrodesign were inserted under controlled conditions into a bovine rib tempered to 37 °C. The resulting surface temperature was measured on two bone windows by an infrared camera. The results of the six experimental groups, ceramic machined (1), sandblasted (2), and sandblasted and acid-etched surfaces (3) versus titanium implants with the corresponding surfaces (4, 5, and 6) were statistically tested. Results: The average temperature increase, 3 mm subcrestally at ceramic implants, differed with high statistical significance (p = 7.163 × 10−9, resulting from group-adjusted linear mixed-effects model) from titanium. The surface texture of ceramic implants shows a statistical difference between group 3 (15.44 ± 3.63 °C) and group 1 (19.94 ± 3.28 °C) or group 2 (19.39 ± 5.73 °C) surfaces. Within the titanium implants, the temperature changes were similar for all surfaces. Conclusion: Within the limits of an in vitro study, the high temperature rises at ceramic versus titanium implants should be limited by a very slow insertion velocity.
The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.
Narratives 2.0 : a multi-dimensional approach to semi-public storytelling in WhatsApp voice messages
(2019)
Based on a corpus of voice message narratives in German WhatsApp group chats, the present study contributes to research on social media storytelling in that it focusses on stories of personal experience which are embedded in a communication platform which favours a continuous dialogic exchange, narrated to well-defined non-anonymous publics and multimodal (comprised of visual and audible posting types). To capture the characteristics of this type of social media storytelling, the paper argues that Ochs and Capps’ (2001) dimensional model originally developed for conversational narratives (including the dimensions of tellability, tellership, embeddedness, linearity, moral stance) should be expanded by the dimensions of publicness, multimodality and sequencing. The prototype of storytelling in WhatsApp group chats is based on recent personal experiences; it is related by a single teller as an initial, sequentially non-embedded and linearly organised “big package” story (in a single voice message sometimes introduced by a text message containing an abstract); other group members routinely document their evaluative stances in rather conventionalised text message responses in the semi-public group space.
This contribution aims to describe privacy, publicness and anonymity as essential analytic dimensions for media linguistic research. The dimensions are not inherent in and predetermined by the technical features and forms of communication provided by mobile devices, but are used by the participants as an orientation grid for shaping their online and offline practices in and with mobile media. Considering both mobile device use in the public realm and the dissemination of increasingly private content in social media (which is said to lead to ‘blurred boundaries’ between the private and the public), the paper provides a brief overview of the main developments in mobile media research: Studies adopting various approaches – e. g. sociological-ethnographic, linguistic and media studies – illustrate how publicness, privacy and anonymity are actively shaped and brought about by mobile media users in face-to-face and remote social encounters. As this shows that publicness, privacy and anonymity are still relevant concepts for users, future media linguistics studies should focus on the dynamic multimodal practices by which they are contextualized and accomplished.
Die peripartale Depression tritt während der Schwangerschaft und in den 12 Monaten nach der Geburt auf. Zusätzlich zu Symptomen einer depressiven Episode ist die peripartale Depression durch schwangerschafts- oder kindbezogene Symptome wie infantizidale Vorstellungen, Gefühlslosigkeit gegenüber dem Kind, Versagensängste oder Insuffizienzgefühle als Mutter gekennzeichnet. Die Prävalenz liegt bei 7 bis 10 % präpartal und 7 bis 20 % postpartal. Folge ist ein erhöhtes Risiko für frühzeitige Wehentätigkeit, geringes Geburtsgewicht, intrauterine Wachstumsstörungen, Verhaltensstörungen und gestörte kognitive Entwicklung des Kindes. Außerdem steigt die Wahrscheinlichkeit für Mutter und Kind, im weiteren Leben erneut an einer Depression zu erkranken. Therapieoptionen stehen insbesondere psychotherapeutische Verfahren wie Interpersonelle Psychotherapie und Kognitive Verhaltenstherapie und eine antidepressive Therapie zur Verfügung.
Ziel der Arbeit war es, die Publikationen zu Depression und Schwangerschaft nach szientometrischen Kriterien zu analysieren und Charakteristika und Tendenzen der Forschung zu erkennen und zu interpretieren.
Nach Definition des Suchbegriffes wurden mithilfe der Datenbank Web of Science bzw. Web of Science Core Collection alle Publikationen zu Depression im Rahmen der Schwangerschaft von 1900 bis 2012 inklusive aller bibliometrischer Daten analysiert. Die Daten wurden nach Bereinigung hinsichtlich qualitativer Gesichtspunkte und szientometrischer Parameter wie Zitierungen, Zitationsrate und modifiziertem h-Index der Publikationen, Autoren, Institutionen und Nationen untersucht. Dabei wurden zusätzlich Genderaspekte und sozioökonomische Faktoren berücksichtigt.
Insgesamt wurden 7.330 Veröffentlichungen zu Pregnancy and Depression analysiert. 95,9 % davon waren in englischer Sprache veröffentlicht. Seit 1982 konnte eine kontinuierliche Zunahme der jährlichen Publikationen verzeichnet werden. Die Zahl der Zitierungen stieg seit 1979 ebenso jährlich an. Dabei sank die Zitationsrate seit 1990. Besonders viele Arbeiten wurden im Journal of Affective Disorders und im Archives of Womens Mental Health veröffentlicht. Unter den Forschungseinrichtungen fielen die Harvard University und St. George’s, University of London durch besonders viele Publikationen auf.
Wichtigste Wissenschaftsstandorte waren die USA, Großbritannien, Australien und Kanada, was sich in den meisten Publikationen, Zitierungen und den höchsten modifizierten h Indizes äußerte, gefolgt von meist europäischen Staaten. Unter Berücksichtigung sozioökonomischer Faktoren ergaben sich mehrere Besonderheiten: Die skandinavischen Staaten Norwegen, Schweden und Finnland finden sich unter den produktivsten Ländern nach Bereinigung um die Bevölkerungszahl. Nationen mit mittlerem und niedrigem Einkommen (Low- and middle income countries = LAMICs) wie Pakistan, Südafrika und Äthiopien leisten einen relevanten Beitrag zur Forschung, berücksichtigt man das Bruttoinlandsprodukt oder die Zahl der Wissenschaftler. Internationale Kooperation dieser Nationen entstanden insbesondere mit Großbritan-nien. Durch diese Zusammenarbeit wurde einerseits auf die höhere Prävalenz von Perinataler Depression in Entwicklungs und Schwellenländern hingewiesen. Andererseits wurde die schwangerschaftsassoziierte Depression als wichtiges Element von Global Mental Health anerkannt.
Seit 1992 veröffentlichen pro Jahr mehr Frauen als Männer zu Peripartaler Depression. Die weibliche Autorenschaft liegt bei 63 %. Unter den produktivsten Wissenschaftlern sind 8 Autorinnen und 6 Autoren. Die produktivsten Autoren sind die US Amerikanerin K.L. Wisner und die Britin L. Murray. Letztere wurde am häufigsten zitiert und führt die Liste der modifizierten h Indizes mit einem Wert von 68 an. Für den britischen Autor und Begründer des Screening-Instruments Edinburgh Postnatal Depression Scale (EPDS) J.L. Cox wurde die höchste Zitationsrate berechnet.
Im Gegensatz zu Veröffentlichungen in gynäkologischen Fachzeitschriften oder szientometrischen Arbeiten zu psychiatrischen Erkrankungen wie Schizophrenie ist der Frauenanteil in allen untersuchten Teilbereichen dem Männeranteil überlegen. Einzige Ausnahme ist die Letztautorenschaft. Diese Ergebnisse stellen eine Besonderheit dar, da eine weibliche Dominanz der Wissenschaft im Schnittbereich zwischen Psychiatrie, Psychosomatik, Psychologie und Frauenheilkunde bisher nicht beschrieben ist.
Comprehensive landscape of active deubiquitinating enzymes profiled by advanced chemoproteomics
(2019)
Enzymes that bind and process ubiquitin, a small 76-amino-acid protein, have been recognized as pharmacological targets in oncology, immunological disorders, and neurodegeneration. Mass spectrometry technology has now reached the capacity to cover the proteome with enough depth to interrogate entire biochemical pathways including those that contain DUBs and E3 ligase substrates. We have recently characterized the breast cancer cell (MCF7) deep proteome by detecting and quantifying ~10,000 proteins, and within this data set, we can detect endogenous expression of 65 deubiquitylating enzymes (DUBs), whereas matching transcriptomics detected 78 DUB mRNAs. Since enzyme activity provides another meaningful layer of information in addition to the expression levels, we have combined advanced mass spectrometry technology, pre-fractionation, and more potent/selective ubiquitin active-site probes with propargylic-based electrophiles to profile 74 DUBs including distinguishable isoforms for 5 DUBs in MCF7 crude extract material. Competition experiments with cysteine alkylating agents and pan-DUB inhibitors combined with probe labeling revealed the proportion of active cellular DUBs directly engaged with probes by label-free quantitative (LFQ) mass spectrometry. This demonstrated that USP13, 39, and 40 are non-reactive to probe, indicating restricted enzymatic activity under these cellular conditions. Our extended chemoproteomics workflow increases depth of covering the active DUBome, including isoform-specific resolution, and provides the framework for more comprehensive cell-based small-molecule DUB selectivity profiling.
Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.
Critique, and especially radical critique of reason, is under pressure from two opponents. Whereas the proponents of "post-critical" or "acritical" thinking denounce critique as an empty and self-righteous repetition of debunking, the decriers of "post-truth" accuse critique of having helped to bring about our current "post-truth" politics. Both advocate realism as a limit critique must respect, but Vogelmann defends the claim that we urgently need radical critiques of reason because they offer a more precise diagnosis of the untruths in politics the two opponents of critique are rightfully worried about. Radical critiques of reason are possible, he argues, if we turn our attention to the practices of criticizing, if we refrain from a sovereign epistemology, and if we pluralize reason without trivializing it. In order to demonstrate the diagnostic advantage of radical critiques of reason, he briefly analyzes the political and epistemic strategy at work in two exemplary untruths in politics.
Critique, and especially radical critique of reason, is under pressure from two opponents. Whereas the proponents of "post-critical" or "acritical" thinking denounce critique as an empty and self-righteous repetition of debunking, the decriers of "post-truth" accuse critique of having helped to bring about our current "post-truth" politics. Both advocate realism as a limit critique must respect, but I will defend the claim that we urgently need radical critiques of reason because they offer a more precise diagnosis of the untruths in politics the two opponents of critique are rightfully worried about. Radical critiques of reason are possible, I argue, if we turn our attention to the practices of criticizing, if we refrain from a sovereign epistemology, and if we pluralize reason without trivializing it. In order to demonstrate the diagnostic advantage of radical critiques of reason, I briefly analyze the political and epistemic strategy at work in two exemplary untruths in politics.
Background and Aims: Vitamin D has an inhibitory role in the inflammatory signaling pathways and supports the integrity of the intestinal barrier. Due to its immunomodulatory effect, vitamin D plays a role in chronic inflammatory bowel disease (IBD) and a deficiency is associated with an increased risk for a flare. We aimed to investigate to what extent the 25-hydroxyvitamin D (25(OH)D3) level correlates with disease activity and whether a cut-off value can be defined that discriminates between active disease and remission. Methods: Patients with IBD, treated at the University Hospital Frankfurt were analyzed retrospectively. The 25(OH)D3 levels were correlated with clinical activity indices and laboratory chemical activity parameters. A deficiency was defined as 25(OH)D3 levels <30 ng/mL. Results: A total of 470 (257 female) patients with IBD were included, 272 (57.9%) with Crohn’s disease (CD), 198 (42.1%) with ulcerative colitis (UC). The median age of the patients was 41 (18–84). In 283 patients (60.2%), a vitamin D deficiency was detected. 245 (53.6%) patients received oral vitamin D supplementation, and supplemented patients had significantly higher vitamin D levels (p < 0.0001). Remission, vitamin D substitution, and male gender were independently associated with the 25(OH)D3 serum concentration in our cohort in regression analysis. A 25(OH)D3 serum concentration of 27.5 ng/mL was the optimal cut-off value. Conclusion: Vitamin D deficiency is common in IBD patients and appears to be associated with increased disease activity. In our study, vitamin D levels were inversely associated with disease activity. Thus, close monitoring should be established, and optimized supplementation should take place.
The multifaceted p21 (Cip1/Waf1/CDKN1A) in cell differentiation, migration and cancer therapy
(2019)
Loss of cell cycle control is characteristic of tumorigenesis. The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein. p21 is transcriptionally controlled by p53 and p53-independent pathways. Its expression is increased in response to various intra- and extracellular stimuli to arrest the cell cycle ensuring genomic stability. Apart from its roles in cell cycle regulation including mitosis, p21 is involved in differentiation, cell migration, cytoskeletal dynamics, apoptosis, transcription, DNA repair, reprogramming of induced pluripotent stem cells, autophagy and the onset of senescence. p21 acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications. In the present review, we briefly mention the general functions of p21 and summarize its roles in differentiation, migration and invasion in detail. Finally, regarding its dual role as tumor suppressor and oncogene, we highlight the potential, difficulties and risks of using p21 as a biomarker as well as a therapeutic target.
Introduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT.
Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset.
Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses.
Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.
Introduction: Our aim was to highlight the characteristics of pediatric Meckel's diverticulum with a special focus on its complications.
Methods: We report a group of seven patients with Meckel's diverticulum and its resection from the Department of Pediatric Surgery between 2012 and 2017. We reviewed all patient records, clinical presentation, and intraoperative findings. The diagnosis was confirmed by surgery and pathology. For a systematic literature review, we used PubMed, Medline and Google Scholar search engines to locate articles containing terms such as Meckel's diverticulum, children, pediatric, complications and symptomatic. We included article reporting on case series in English and German on pediatric patients only.
Results: All included patients (n = 7) were symptomatic. Some patients showed isolated symptoms, and others presented with a combination of symptoms that consisted of abdominal pain, bloody stool or vomiting. The median age of our seven cases was 3.5 years, including 4 male and 3 female patients. Intestinal obstruction was the most common complication; it was seen in 5 out of 7 patients (intussusception in 4 cases, volvulus in 1 case). Ectopic gastric tissue was identified in 3 cases, and inclusion of pancreatic tissue was observed in 1 case. The literature review identified 8 articles for a total of 641 patients aged between 1 day and 17 years and a male:female ratio of 2.6:1. From this group, 528 patients showed clinical symptoms related to Meckel's diverticulum. The most common symptom was abdominal pain and bloody stool. The most common surgical finding in symptomatic patients was intestinal obstruction (41%), followed by intestinal hemorrhage (34%). Complications such as perforation (10%) and diverticulitis (13%) were less frequently reported. Heterotopic tissue was confirmed on histopathology in 53% of all patients enclosing gastric, pancreatic, and both gastric and pancreatic mucosae. In one case, large intestine tissue could be found. Overall, one death was reported.
Conclusion: The presented case series and literature review found similar clinical presentations and complications of Meckel's diverticulum in children. Intestinal obstruction and bleeding are more frequent than inflammation in pediatric Meckel's diverticulum. Bowel obstruction is the leading cause for complicated Meckel's diverticulum in patients younger than 12 years.
About 200 years ago, legal concepts based on the idea of formal equality prevailed. Over the last 150 years, however, the law has tried on a large scale to establish substantive equality, or at least to alleviate social and economic imbalances. To this day, the law which has undertaken this task has grown in scope and become increasingly differentiated. It has become one of the most important components of modern legal systems and has a history with its own distinctive contours. The terms used to summarise the corresponding legal materials are manifold: law of the welfare state, law of the provident state (état providence) (François Ewald), social law, social welfare law, etc. ...
The use of contractual engineering to create channels of credit intermediation outside of the realm of banking regulation has been a recurring activity in Western financial systems over the last 50 years. After the financial crisis of 2007 and 2008, this phenomenon, at that time commonly referred to as ‘shadow banking’, evoked a large-scale regulatory backlash, including several specific regulatory constraints being placed on non-bank financial institutions (NBFI). This paper proposes a different avenue for regulators to keep regulatory arbitrage under control and preserve sufficient space for efficient financial innovation. Rather than engaging in the proverbial race between hare and hedgehog that is emerging with increasingly specific regulation of particular contractual arrangements, this paper argues for a normative approach to supervision. We outline this approach in detail by showing that regulators should primarily analyse the allocation of tail risk inherent in the respective contractual arrangements. Our paper proposes to assign regulatory burdens equivalent to prudential banking regulation, in case these arrangements become only viable through indirect or direct access to an (ad hoc) public backstop. In order to make the pivotal assessment, regulators will need information about recent contractual innovations and their risk-allocating characteristics. According to the scholarship on regulatory networks serving as communities of interpretation, we suggest in particular how regulators should structure their relationships with semi-public gatekeepers such as lawyers, auditors and consultants to keep abreast of the real-world implications of evolving transactional structures. This paper then uses the rise of credit funds as a non-bank entities economically engaged in credit intermediation to apply this normative framework, pointing to recent contractual innovations that call for more regulatory scrutiny in a multipolar regulatory dialogue.
The article analyses how the decrees of the Council of Trent regarding marriage were used by the Church of Rome as a tool to contrast mixed marriages in Early Modern Europe. It investigates how these decrees were evaded by local churches in order to administer a practice of confessional coexistence impossible to eradicate, and how they were manipulated by actors – even Protestants – to put an end to undesirable unions. It also presents the interpretation that the Church of Rome made of the Tametsi to resolve the age-old issue of mixed marriages in the Low Countries, issuing the Benedictine Declaration, later applied to other contexts with a strong Protestant presence – above all out-side Europe. Although the Council of Trent claimed to have fixed a homogeneous and flawless nuptial ritual, the various local practices did not always adapt to it. Indeed, they bypassed it; sometimes refused it. This led parish priests and missionaries to turn to Rome for the resolution of concrete cases. The decisions taken for individual cases became a normative reference point. It was produced by the continuous interaction and negotiation with local churches and went on in fact to profoundly influence the sacramental rituality of marriages, which Tametsi had claimed were fixed and immutable.
Worldwide, academics and practitioners are developing ‘planning-oriented’ approaches to reduce the negative impacts of car traffic for more sustainable urban and transport development. One such example is the design of car-reduced neighborhoods, although these are controversial issues in the hegemonic ‘system’ of automobility. Despite the reduction of emissions and frequent recognition as ‘best practice examples’, ‘planning-critical’ research questions the underlying objectives and narratives of such sustainable developments. Our study contributes to this research perspective by improving the understanding of narratives that emerge along with car-reduced housing developments. For this purpose, we analyze two car-reduced neighborhoods in the City of Darmstadt (Germany) by conducting interviews with different actors involved in the planning and implementation processes. Our investigation reveals that the development of car-reduced neighborhoods (i) is consciously embedded in the context of sustainability, (ii) is characterized by power relations, (iii) follows normative indicators, and (iv) does not always correspond to lived realities. Altogether, the traced narratives of car-reduced neighborhoods are embedded in the overarching debate on sustainability, while at the same time revealing the dependence of society on the automobile. Thus, the hegemonic ‘system’ of automobility—although it is beginning to crack—continues to exist.
The 100th anniversary of the Weimar Constitution’s promulgation has brought a number of new stimuli to a historiography that has for a long time focused largely on the Weimar Republic’s failure. Two prominent recent publications – Udo Di Fabio’s study and a collective volume edited by Horst Dreier und Christian Waldhoff – are reviewed in this issue by the Brazilian constitutional historian Marcelo Neves. His review and the last months’ public debate on the merits and flaws of the Weimar Constitution in Germany, which was framed by current concerns about the state of Western democracies, show to what extent constitutional history is always also a conversation about the present. ...
Background: We aimed to investigate the potential effects of a 4-week motor–cognitive dual-task training on cognitive and motor function as well as exercise motivation in young, healthy, and active adults.
Methods: A total of 26 participants (age 25 ± 2 years; 10 women) were randomly allocated to either the intervention group or a control group. The intervention group performed a motor–cognitive training (3×/week), while the participants of the control group received no intervention. Before and after the intervention period of 4 weeks, all participants underwent cognitive (d2-test, Trail Making Test) and motor (lower-body choice reaction test and time to stabilization test) assessments. Following each of the 12 workouts, self-reported assessments (rating of perceived exertion, enjoyment and pleasant anticipation of the next training session) were done. Analyses of covariances and 95% confidence intervals plotting for between group and time effects were performed.
Results: Data from 24 participants were analysed. No pre- to post-intervention improvement nor a between-group difference regarding motor outcomes (choice-reaction: F = 0.5; time to stabilization test: F = 0.7; p > 0.05) occurred. No significant training-induced changes were found in the cognitive tests (D2: F = 0.02; Trail Making Test A: F = 0.24; Trail Making Test B: F = 0.002; p > 0.05). Both enjoyment and anticipation of the next workout were rated as high.
Discussion: The neuro-motor training appears to have no significant effects on motor and cognitive function in healthy, young and physically active adults. This might be explained in part by the participants’ very high motor and cognitive abilities, the comparably low training intensity or the programme duration. The high degree of exercise enjoyment, however, may qualify the training as a facilitator to initiate and maintain regular physical activity. The moderate to vigorous intensity levels further point towards potential health-enhancing cardiorespiratory effects.
During the drafting process from the 1920s to 1940s, the Weimar Constitution (WRV) played a decisive role in shaping Chinese social(-ist) con- stitutions, especially the part related to the social- economic issue. Through the lens of cultural trans- lation, this paper seeks to explain how the WRV was adapted, reinterpreted, and recontextualized throughout several rounds of constitution making in China. By focusing on the roles played by the translators, legislators, and interpreters, this paper discusses how the social rights created by the WRV were translated into the fundamental policy of the 1947 Constitution of the Republic of China. More- over, regarding »policy« as the legal instrument for regulating the social-economic life, and even broader fields, it triggers the modern transforma- tion of Chinese meritocracy and reinforces the national legal tradition depicted in its modern form. To some extent, this case study on cultural translation of constitutional law discloses the mechanism, both temporarily and spatially, for the intercultural communication of the normative information.
Background: Although anterior cruciate ligament (ACL) tear-prevention programs may be effective in the (secondary) prevention of a subsequent ACL injury, little is known, yet, on their effectiveness and feasibility. This study assesses the effects and implementation capacity of a secondary preventive motor-control training (the Stop-X program) after ACL reconstruction.
Methods and design: A multicenter, single-blind, randomized controlled, prospective, superiority, two-arm design is adopted. Subsequent patients (18–35 years) with primary arthroscopic unilateral ACL reconstruction with autologous hamstring graft are enrolled. Postoperative guideline rehabilitation plus Classic follow-up treatment and guideline rehabilitation plus the Stop-X intervention will be compared. The onset of the Stop-X program as part of the postoperative follow-up treatment is individualized and function based. The participants must be released for the training components. The endpoint is the unrestricted return to sport (RTS) decision. Before (where applicable) reconstruction and after the clearance for the intervention (aimed at 4–8 months post surgery) until the unrestricted RTS decision (but at least until 12 months post surgery), all outcomes will be assessed once a month. Each participant is consequently measured at least five times to a maximum of 12 times. Twelve, 18 and 24 months after the surgery, follow-up-measurements and recurrence monitoring will follow. The primary outcome assessement (normalized knee-separation distance at the Drop Jump Screening Test (DJST)) is followed by the functional secondary outcomes assessements. The latter consist of quality assessments during simple (combined) balance side, balance front and single-leg hops for distance. All hop/jump tests are self-administered and filmed from the frontal view (3-m distance). All videos are transferred using safe big content transfer and subsequently (and blinded) expertly video-rated. Secondary outcomes are questionnaires on patient-reported knee function, kinesiophobia, RTS after ACL injury and training/therapy volume (frequency – intensity – type and time). All questionnaires are completed online using the participants’ pseudonym only.
Group allocation is executed randomly. The training intervention (Stop-X arm) consists of self-administered home-based exercises. The exercises are step-wise graduated and follow wound healing and functional restoration criteria. The training frequency for both arms is scheduled to be three times per week, each time for a 30 min duration. The program follows current (secondary) prevention guidelines.
Repeated measurements gain-score analyses using analyses of (co-)variance are performed for all outcomes.
Trial registration: German Clinical Trials Register, identification number DRKS00015313. Registered on 1 October 2018.
You wait ages for a bus, the saying goes, and then two (or three) come along at once. A similar feeling set in when Oxford University Press published two volumes on legal history in its Oxford Handbooks series within the space of four weeks last year. They are a welcome addition to the prestigious and well-established series that now boasts hundreds of volumes, including around 50 on history and over three dozen on law. The latter do not only cover established sub-disciplines of legal studies, such as jurisprudence and philosophy of law (2002), comparative law (2006, 2nd ed. 2019), international trade law (2009), the law of the sea (2015), European Union law (2015), criminal law (2014) and intellectual property (2018), but also more recent and emerging fields, including international environmental law (2007), empirical legal research (2010), behavioural economics and law (2014), international adjudication (2013), international climate change law (2016) and law and economics (3 vols., 2017). The Handbooks have become increasingly specialised with titles focusing on narrow topics such as individual national constitutions (USA, 2015; India, 2016; Canada, 2017) and important, but nevertheless discrete legal issues, for example, US health law (2017) and the sources of international law (2017). The obvious question was why, nearly two decades after the launch of the series, there was such a thing as an Oxford Handbook of American Sports Law (2018) but still no volume on the history of law. The absence of such a title was all the more striking in light of the publication of books in the series dealing with individual fields of legal history, such as the Oxford Handbook of the History of International Law (2012), the Oxford Handbook of Roman Law and Society (2016), the Oxford Handbook of Carl Schmitt (2017) and the Oxford Handbook of English Law and Literature, 1500–1700 (2017). ...
Den Auftakt zum Oxford Handbook of European Legal History machen fünf Beiträge, die unter der Überschrift "Approaches to European Legal History: Historiography and Methods" versammelt sind. Um sie in Beziehung zu setzen, habe ich im Folgenden drei Fragenkomplexe formuliert, die die gemeinsamen Aspekte dieses Quintetts abbilden. Die Beiträge werden in der Reihenfolge ihres Auftretens im Handbuch referiert. Zur Vermeidung von Redundanzen haben die Nachgeordneten im Wiederholungsfalle der Argumente das Nachsehen und werden "nur" als Verweis genannt.
Light-matter interaction in the strong coupling regime is of profound interest for fundamental quantum optics, information processing and the realization of ultrahigh-resolution sensors. Here, we report a new way to realize strong light-matter interaction, by coupling metamaterial plasmonic "quasi-particles" with photons in a photonic cavity, in the terahertz frequency range. The resultant cavity polaritons exhibit a splitting which can reach the ultra-strong coupling regime, even with the comparatively low density of quasi-particles, and inherit the high Q-factor of the cavity despite the relatively broad resonances of the Swiss-cross and split-ring-resonator metamaterials used. We also demonstrate nonlocal collective interaction of spatially separated metamaterial layers mediated by the cavity photons. By applying the quantum electrodynamic formalism to the density dependence of the polariton splitting, we can deduce the intrinsic transition dipole moment for single-quantum excitation of the metamaterial quasi-particles, which is orders of magnitude larger than those of natural atoms. These findings are of interest for the investigation of fundamental strong-coupling phenomena, but also for applications such as ultra-low-threshold terahertz polariton lasing, voltage-controlled modulators and frequency filters, and ultra-sensitive chemical and biological sensing.
For reasons of curiosity, we perused the two recent Oxford handbooks on legal history looking for discussions of digital methods in legal history. One of the fundamental decisions to be made when organizing such a handbook is defining which methodological approaches deserve an article of their own and which ones are to be understood rather as cross-cutting themes to be discussed in the context of many articles dedicated to other things. In the case of digital methods in legal history, this decision seems to have been a tough one – at one point, you can find a curious reference to a "chapter on 'Legal History and Digital Humanities'" (OHBLH 354), but in the final publication there is no such text.
However, discussing digital methods in the context of other subjects has, in our opinion, the disadvantage that more systematic, methodological arguments cannot really be developed. Put more concretely, the most "substantial" contributions regarding digital methods are, for whatever reason, those on "The Intellectual History of Law" by Assaf Likhovski, on "Taking the Long View" by Paul D. Halliday, on "Quantitative Legal History" by Daniel Klerman, and on "Indian Law" by Mitra Sharafi, all of which are in the Oxford Handbook on Legal History. (Equally surprising, there is no mention of digital methods at all in Angela Fernandez’s "Legal History as The History of Legal Texts".) However, even these articles do not really "discuss" digital methods, rather they merely refer to them (and to some projects) as contributions of sorts to their respective fields of interest.
Thus, if you are looking for digital methods in those handbooks, you can hardly find more than some namedropping passages where things like "digital mapping […], network analysis […], text analysis" (OHBLH 845f.) are mentioned, together with references to example projects where they have been employed but without any explanation as to:
–why these methods are mentioned and not others,
–what they are doing, to which end and under what circumstances,
–what, possibly transformative, impact these methods have on the (respective sub-) field of legal history, and
–what a scholar considering to apply these methods should be aware of.
While the space for this is limited, the present Forum contribution tries to mitigate the scarcity of such discussions by presenting and discussing a few textual analyses that make use – for demonstration purposes – of digital methods. Some other methods of analysis, network analysis, and geo-mapping (among others), cannot be covered here, but we provide a link to an online bibliography where you can find them applied to legal history or a related domain, and discussed critically. A general discussion of digital perspectives beyond concrete methods of analysis concludes this contribution.
State-of-the-art climate models contain, to a significant degree, empirical components. In particular, subgrid-scale (SGS) parameterizations are usually highly tuned against observations or high-resolution model data. While this enables the models to minimize the error during hindcasts, it is not guaranteed that it yields a benefit for climate projections because of climate change. In this thesis the Fluctuation-Dissipation theorem (FDT) is used to update the statistics of the system in the presence of an external forcing. If the empirical parameters are tuned objectively to the data (i.e., they depend on the statistics of the data), then they might be updated with the FDT. This ansatz is tested within a framework of a semi-empirical model (SEM) based on the leading variance patterns of a quasigeostrophic three-layer model (QG3LM) and supplemented by a purely data-driven parameterization. We show that the FDT is able to successfully update the tuning parameters of the data-driven SGS closure, resulting in a systematic improvement in model performance in comparison to an untreated SEM. Ideally, SGS parameterizations should contain little to no tuning parameters. Thus, complementary to the FDT approach we investigate a stochastic SGS closure constrained by first principles that is calculated using the stochastic mode reduction (SMR). The SMR allows for an analytic derivation of the SGS closure from the model equations while requiring only minimal tuning. We successfully apply the SMR to the QG3LM and construct the reduced stochastic model (RSM). Furthermore, we show that the RSM is more robust against an external forcing than the SEM. Additionally, we find that, under appropriate conditions, the FDT is able to update the empirical parts of the RSM. Yet, only for the response in mean streamfunction the RSM provides useful results, while the response in covariance of the streamfunction is incorrect for most cases. Nevertheless, we obtain a remarkably accurate response in both moments for the RSM in an idealized setting. In combination with the results of the FDT study this indicates that the considered RSM is too low dimensional and encourages us to investigate the response of larger RSMs in the future.
Five decades of US, UK, German and Dutch music charts show that cultural processes are accelerating
(2019)
Analysing the timeline of US, UK, German and Dutch music charts, we find that the evolution of album lifetimes and of the size of weekly rank changes provide evidence for an acceleration of cultural processes. For most of the past five decades, number one albums needed more than a month to climb to the top, nowadays an album is in contrast top ranked either from the start, or not at all. Over the last three decades, the number of top-listed albums increased as a consequence from roughly a dozen per year, to about 40. The distribution of album lifetimes evolved during the last decades from a log-normal distribution to a power law, a profound change. Presenting an information–theoretical approach to human activities, we suggest that the fading relevance of personal time horizons may be causing this phenomenon. Furthermore, we find that sales and airplay- based charts differ statistically and that the inclusion of streaming affects chart diversity adversely. We point out in addition that opinion dynamics may accelerate not only in cultural domains, as found here, but also in other settings, in particular in politics, where it could have far reaching consequences.
The presence of moral theology and scholasticism in the recently published Oxford Handbook of Legal History and Oxford Handbook of European Legal History is very limited. The first volume aims to be iconoclastic. It explicitly does not seek to provide a kind of global historical account but instead presents some of the innovative methodological perspectives guiding current legal historical research. Thomas Duve, writing about the contribution of the School of Salamanca to the theorization of a certain framework of "indigenous rights" during the period of colonial domination, is thus the only contributor to this volume who mentions moral theology. In the Handbook of European Legal History, there are two articles on important scholastic contributions to legal history that also deal with the influence of Salamanca and related scholastic authors to equally wide fields of legal thinking. Wim Decock discusses authors of the second scholasticism in the context of the law of property and obligations (611–632), and David Ibbetson writes on natural law (566–582). In the following, I will focus on Ibbetson’s chapter, which only partially matches the ambitious intended aims of the volume editors (Pihlajamäki, Dubber, Godfrey): to "chart the landscape of contemporary research" and to show the global impact that European legal systems had "from the fifteenth century onwards". ...
Background: Patients with chronic kidney disease (CKD) have considerable cardiovascular morbidity and mortality. Aortic stiffness is an independent predictor of cardiovascular risk and related to left ventricular remodeling and heart failure. Myocardial fibrosis is the pathophysiological hallmark of the failing heart.
Methods and results: An observational study of consecutive CKD patients (n = 276) undergoing comprehensive clinical cardiovascular magnetic resonance imaging. The relationship between aortic stiffness, myocardial fibrosis, left ventricular remodeling and the severity of chronic kidney disease was examined. Compared to age-gender matched controls with no known kidney disease (n = 242), CKD patients had considerably higher myocardial native T1 and central aortic PWV (p ≪ 0.001), as well as abnormal diastolic relaxation by E/e′ (mean) by echocardiography (p ≪ 0.01). A third of all patients had LGE, with similar proportions for the presence and the (ischaemic and non-ischaemic) pattern between the groups. PWV was strongly associated with and age, NT-proBNP and native T1 in both groups, but not with LGE presence or type; the associations were amplified in severe CKD stages. In multivariate analyses, PWV was independently associated with native T1 in both groups (p ≪ 0.01) with near two-fold increase in adjusted R2 in the presence of CKD (native T1 (10 ms) R2, B(95%CI) CKD vs. non-CKD 0.28, 0.2(0.15–0.25) vs. 0.18, 0.1(0.06–0.15), p ≪ 0.01).
Conclusions: Aortic stiffness and interstitial myocardial fibrosis are interrelated; this association is accelerated in the presence of CKD, but independent of LGE. Our findings reiterate the significant contribution of CKD-related factors to the pathophysiology of cardiovascular remodeling.
Partant des conditions de mise en place de l’une des dernières commissions d’historiens bilatérales en date – à savoir la commission germano-italienne en 2008 – et du constat de la nature à la fois ambigüe et excessive des attentes formulées à son encontre, cet ouvrage collectif dirigé par deux historiens du temps présent (l’Allemand Christoph Cornelißen et l’Italien Paolo Pezzino) place au cœur de la réflexion la figure de l’historien confronté à une demande d’expertise croissante dans le contexte de l’après guerre froide. Il examine les usages pratiques (voire politiques) des savoirs académiques historiques et leurs effets sur les standards de production de ces savoirs assurant la légitimité professionnelle et sociale des historiens. ...
Das hochwertig ausgestattete Buch vereint elf der im Jahre 2017 in Goslar gehaltenen Vorträge zum Jubiläum der tausendsten Wiederkehr des Geburtstages Heinrichs III. Der Rezensent beteiligte sich in dieser Reihe mit einem Beitrag, der wegen seiner umfangreichen Thematik ("Das salische Reich und Europa zur Zeit Kaiser Heinrichs III.") nicht in eine Kurzfassung gegossen werden konnte, was hier der Fairness halber bemerkt werden muss. ...
Introduction: Vacuolization is a frequently found morphological feature in acute myeloid leukemia (AML) blasts. Subcellular origin and biological function as well as prognostic impact are currently unknown. The aim of this study was to evaluate whether vacuolization correlates with clinically relevant AML features.
Materials & methods: Bone marrow smears of patients diagnosed with AML at the University Hospital Frankfurt between January 2011 and August 2013 were analyzed for blast vacuolization and correlated with clinically relevant AML features. Patients undergoing standard induction chemotherapy were further analyzed for molecular and cytogenetic features as well as treatment response and survival.
Results: 14 of 100 patients diagnosed with AML receiving standard induction chemotherapy had evidence of blast vacuolization. Positivity for vacuolization correlated with a CD15 positive immunophenotype and with a higher incidence of high-risk AML according to the European LeukemiaNet risk stratification. AML patients with blast vacuolization had a poor blast clearance after standard induction chemotherapy and poor survival.
Discussion: In conclusion, our findings demonstrate that vacuolization can easily be determined in myeloid leukemia blasts and may be a useful biomarker to predict AML risk groups as well as early treatment response rates and survival.
Masha Bruskina wurde im Jahr 1924 in Minsk als Jüdin geboren und genoss eine gute Bildung. Doch als sie gerade einmal 17 Jahren alt war, brach der Krieg über die Sowjetunion herein und es dauerte bloß sechs Tage, bis die deutschen Truppen die Stadt einnahmen. Bruskina war als überzeugte Kommunistin schon im jungen Alter Leiterin einer Pioniereinheit und doch gezwungen, im Minsker Ghetto zu leben. In dem Unwillen ihr Schicksal hinzunehmen, wechselte sie auf die sogenannte "arische Seite" und gab sich als Nichtjüdin aus: Sie färbte ihre Haare und nahm den Namen ihrer Mutter an. Bald darauf schloss sie sich dem im Untergrund operierenden Minsker Widerstand an und arbeite als Krankenschwester, um sowjetische Soldaten in einem Krankenhaus zu versorgen und ihnen bei der Flucht zu helfen. Sie schmuggelte zivile Kleidung und Medikamente, zudem eine Kamera, mit der sie gefälschte Ausweise herstellte. Waren die Soldaten wieder auf den Beinen, führten die anderen Widerständler sie durch die Wälder zur Partisanenbewegung. ...
The focus of this paper are space-improvements of programs, which are transformations that do not worsen the space requirement during evaluations. A realistic theoretical treatment must take garbage collection method into account. We investigate space improvements under the assumption of an optimal garbage collector. Such a garbage collector is not implementable, but there is an advantage: The investigations are independent of potential changes in an implementable garbage collector and our results show that the evaluation and other similar transformations are space-improvements.
Uni-Highlights Oktober 2019 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Facebook’s proposal to create a global digital currency, Libra, has generated a wide discussion about its potential benefits and drawbacks. This note contributes to this discussion and, first, characterizes similarities and dissimilarities of Libra’s building blocks with existing institutions. Second, the note discusses open questions about Libra which arise from this characterization and, third, potential future developments and their policy implications. A central issue is that Libra raises considerable questions about its role in and impact on the international monetary and financial system that should be addressed before policymakers and regulators give Libra the green light.
The identification of heat stress (HS)-resilient germplasm is important to ensure food security under less favorable environmental conditions. For that, germplasm with an altered activity of factors regulating the HS response is an important genetic tool for crop improvement. Heat shock binding protein (HSBP) is one of the main negative regulators of HS response, acting as a repressor of the activity of HS transcription factors. We identified a TILLING allele of Solanum lycopersicum (tomato) HSBP1. We examined the effects of the mutation on the functionality of the protein in tomato protoplasts, and compared the thermotolerance capacity of lines carrying the wild-type and mutant alleles of HSBP1. The methionine-to-isoleucine mutation in the central heptad repeats of HSBP1 leads to a partial loss of protein function, thereby reducing the inhibitory effect on Hsf activity. Mutant seedlings show enhanced basal thermotolerance, while mature plants exhibit increased resilience in repeated HS treatments, as shown by several physiological parameters. Importantly, plants that are homozygous for the wild-type or mutant HSBP1 alleles showed no significant differences under non-stressed conditions. Altogether, these results indicate that the identified mutant HSBP1 allele can be used as a genetic tool in breeding, aiming to improve the thermotolerance of tomato varieties.
leporello #1
(2019)
Function of p21 (Cip1/Waf1/CDKN1A) in migration and invasion of cancer and trophoblastic cells
(2019)
Tumor progression and pregnancy have several features in common. Tumor cells and placental trophoblasts share many signaling pathways involved in migration and invasion. Preeclampsia, associated with impaired differentiation and migration of trophoblastic cells, is an unpredictable and unpreventable disease leading to maternal and perinatal mortality and morbidity. Like in tumor cells, most pathways, in which p21 is involved, are deregulated in trophoblasts of preeclamptic placentas. The aim of the present study was to enlighten p21’s role in tumorigenic choriocarcinoma and trophoblastic cell lines. We show that knockdown of p21 induces defects in chromosome movement during mitosis, though hardly affecting proliferation and cell cycle distribution. Moreover, suppression of p21 compromises the migration and invasion capability of various trophoblastic and cancer cell lines mediated by, at least partially, a reduction of the extracellular signal-regulated kinase 3, identified using transcriptome-wide profiling, real-time PCR, and Western blot. Further analyses show that downregulation of p21 is associated with reduced matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2. This work evinces that p21 is involved in chromosome movement during mitosis as well as in the motility and invasion capacity of trophoblastic and cancer cell lines.
Truffle fungi are well known for their enticing aromas partially emitted by microbes colonizing truffle fruiting bodies. The identity and diversity of these microbes remain poorly investigated, because few studies have determined truffle-associated bacterial communities while considering only a small number of fruiting bodies. Hence, the factors driving the assembly of truffle microbiomes are yet to be elucidated. Here we investigated the bacterial community structure of more than 50 fruiting bodies of the black truffle Tuber aestivum in one French and one Swiss orchard using 16S rRNA gene amplicon high-throughput sequencing. Bacterial communities from truffles collected in both orchards shared their main dominant taxa: while 60% of fruiting bodies were dominated by α-Proteobacteria, in some cases the β-Proteobacteria or the Sphingobacteriia classes were the most abundant, suggesting that specific factors (i.e., truffle maturation and soil properties) shape differently truffle-associated microbiomes. We further attempted to assess the influence in truffle microbiome variation of factors related to collection season, truffle mating type, degree of maturation, and location within the truffle orchards. These factors had differential effects between the two truffle orchards, with season being the strongest predictor of community variation in the French orchard, and spatial location in the Swiss one. Surprisingly, genotype and fruiting body maturation did not have a significant effect on microbial community composition. In summary, our results show, regardless of the geographical location considered, the existence of heterogeneous bacterial communities within T. aestivum fruiting bodies that are dominated by three bacterial classes. They also indicate that factors shaping microbial communities within truffle fruiting bodies differ across local conditions.
Lipoxygenases (LOXs) catalyze the stereo-specific peroxidation of polyunsaturated fatty acids (PUFAs) to their corresponding hydroperoxy derivatives. Human macrophages express two arachidonic acid (AA) 15-lipoxygenating enzymes classified as ALOX15 and ALOX15B. ALOX15, which was first described in 1975, has been extensively characterized and its biological functions have been investigated in a number of cellular systems and animal models. In macrophages, ALOX15 functions to generate specific phospholipid (PL) oxidation products crucial for orchestrating the nonimmunogenic removal of apoptotic cells (ACs) as well as synthesizing precursor lipids required for production of specialized pro-resolving mediators (SPMs) that facilitate inflammation resolution. The discovery of ALOX15B in 1997 was followed by comprehensive analyses of its structural properties and reaction specificities with PUFA substrates. Although its enzymatic properties are well described, the biological functions of ALOX15B are not fully understood. In contrast to ALOX15 whose expression in human monocyte-derived macrophages is strictly dependent on Th2 cytokines IL-4 and IL-13, ALOX15B is constitutively expressed. This review aims to summarize the current knowledge on the regulation and functions of ALOX15 and ALOX15B in human macrophages.
Iodo(triphenyl)silane
(2019)
The molecular structure of the title compound, C18H15ISi, which crystallizes in the space group C2/c, does not exhibit any unusual features. Two weak C—H⋯π interactions may help to consolidate the packing. The present structure is not isostructural with the known Ph3SiX (X = F, Cl or Br) compounds.
This review summarizes studies of protection against singlet oxygen and radical damage by carotenoids. The main focus is on how substitutions of the carotenoid molecules determine high antioxidant activities such as singlet oxygen quenching and radical scavenging. Applied assays were carried out either in vitro in solvents or with liposomes, and in a few cases with living organisms. In the latter, protection by carotenoids especially of photosynthesis against light- and UV-stress is of major importance, but also heterotrophic organisms suffer from high light and UV exposure which can be alleviated by carotenoids. Carotenoids to be compared include C30, C40 and C50 molecules either acyclic, monocyclic or bicyclic with different substitutions including sugar and fatty acid moieties. Although some studies are difficult to compare, there is a tendency towards mono and bicyclic carotenoids with keto groups at C-4/C-4’ and the longest possible polyene structure functions to act best in singlet oxygen quenching and radical scavenging. Size of the carotenoid and lipophilic substituents such as fatty acids seem to be of minor importance for their activity but hydroxyl groups at an acyclic end and especially glycosylation of these hydroxyl groups enhance carotenoid activity.
Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86, and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429, and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in Drosophila melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.
The lipid status in patients with ulcerative colitis : Sphingolipids are disease-dependent regulated
(2019)
The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids. Sphingolipids impact cell–cell contacts and function as second messengers. We collected blood and colon tissue samples from UC patients and healthy controls and investigated the sphingolipids and other lipids by LC-MS/MS or LC-QTOFMS. The expression of enzymes of the sphingolipid pathway were determined by RT-PCR and immunohistochemistry. In inflamed colon tissue, the de novo-synthesis of sphingolipids is reduced, whereas lactosylceramides are increased. Reduction of dihydroceramides was due to posttranslational inhibition rather than altered serine palmitoyl transferase or ceramide synthase expression in inflamed colon tissue. Furthermore, in human plasma from UC-patients, several sphinglipids change significantly in comparison to healthy controls. Beside sphingolipids free fatty acids, lysophosphatidylcholines and triglycerides changed significantly in the blood of colitis patients dependent on the disease severity. Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for UC. Several lipids changed significantly in the blood, which might be used as biomarkers for disease control; however, diet-related variabilities need to be considered.
From a global viewpoint, a lot of time is spent within the indoor air compartment of vehicles. A German study on mobility has revealed that, on average, people spend 45 minutes per day inside vehicles. In recent years the number of cars has increased to around 43 million vehicles in private households. This means that more than one car can be used in every household. The ratio has been growing, especially in eastern Germany and rural areas. "Overall and especially outside the cities, the car remains by far number one mode of transport, especially in terms of mileage". Therefore, numerous international studies have addressed different aspects of indoor air hygiene, in the past years. In this paper, meaningful original studies on car indoor air pollution, related to VOCs, COx, PMs, microbials, BFRs, OPFRs, cigarettes, electronic smoking devices, high molecular weight plasticizer, and NOx are summarized in the form of a review. This present review aimed to summarize recently published studies in this important field of environmental medicine and points to the need for further studies with special recommendations for optimizing the interior air hygiene.
Environmental niche modelling is an acclaimed method for estimating species’ present or future distributions. However, in marine environments the assembly of representative data from reliable and unbiased occurrences is challenging. Here, we aimed to model the environmental niche and distribution of marine, parasitic nematodes from the Pseudoterranova decipiens complex using the software Maxent. The distribution of these potentially zoonotic species is of interest, because they infect the muscle tissue of host species targeted by fisheries. To achieve the best possible model, we used two different approaches. The land distance (LD) model was based on abiotic data, whereas the definitive host distance (DHD) model included species-specific biotic data. To assess whether DHD is a suitable descriptor for Pseudoterranova spp., the niches of the parasites and their respective definitive hosts were analysed using ecospat. The performance of LD and DHD was compared based on the variables’ contribution to the model. The DHD-model clearly outperformed the LD-model. While the LD-model gave an estimate of the parasites’ niches, it only showed the potential distribution. The DHD-model produced an estimate of the species’ realised distribution and indicated that biotic variables can help to improve the modelling of data-poor, marine species.
Abiotic formation of n-alkane hydrocarbons has been postulated to occur within Earth's crust. Apparent evidence was primarily based on uncommon carbon and hydrogen isotope distribution patterns that set methane and its higher chain homologues apart from biotic isotopic compositions associated with microbial production and closed system thermal degradation of organic matter. Here, we present the first global investigation of the carbon and hydrogen isotopic compositions of n-alkanes in volcanic-hydrothermal fluids hosted by basaltic, andesitic, trachytic and rhyolitic rocks. We show that the bulk isotopic compositions of these gases follow trends that are characteristic of high temperature, open system degradation of organic matter. In sediment-free systems, organic matter is supplied by surface waters (seawater, meteoric water) circulating through the reservoir rocks. Our data set strongly implies that thermal degradation of organic matter is able to satisfy isotopic criteria previously classified as being indicative of abiogenesis. Further considering the ubiquitous presence of surface waters in Earth’s crust, abiotic hydrocarbon occurrences might have been significantly overestimated.
Der betongraue Bunker ist von Zwangsarbeitern der Nationalsozialisten im Zweiten Weltkrieg errichtet worden. Geplant war er als Luftschutzbunker für die Mitarbeiter und Kunden der Reichsbahn, damit sie sich im Ernstfall vom nah gelegenen Bahnhof, dem heutigen Bahnhof Friedrichstrasse, vor dem Bombenhagel retten konnten; bis zu 2.500 Menschen finden darin Platz. Nach dem Ende des Zweiten Weltkrieges wurde der Bunker sehr unterschiedlich genutzt: Zuerst diente er als Kriegsgefängnis der Roten Armee, danach als Lager für Textilien und anschließend für Südfrüchte, was ihm den Namen „Bananenbunker“ einbrachte. Nach dem Mauerfall ging das Gebäude in den Besitz des Bundes über und die Kultur Berlins zog ein: Erst in Form eines Techno-Clubs, in welchem auch Theaterstücke aufgeführt wurden, bis der Bund das Gebäude vorerst schloss. Der Werbeagentur-Inhaber Christian Boros erwarb zusammen mit seiner Frau Karen Boros den Bunker schließlich und baute ihn fünf Jahre lang um: Seit 2008 werden die Kunstwerke aus Boros’ privater Kunstsammlung präsentiert. ...
To prepare for an impending event of unknown temporal distribution, humans internally increase the perceived probability of event onset as time elapses. This effect is termed the hazard rate of events. We tested how the neural encoding of hazard rate changes by providing human participants with prior information on temporal event probability. We recorded behavioral and electroencephalographic (EEG) data while participants listened to continuously repeating five-tone sequences, composed of four standard tones followed by a non-target deviant tone, delivered at slow (1.6 Hz) or fast (4 Hz) rates. The task was to detect a rare target tone, which equiprobably appeared at either position two, three or four of the repeating sequence. In this design, potential target position acts as a proxy for elapsed time. For participants uninformed about the target’s distribution, elapsed time to uncertain target onset increased response speed, displaying a significant hazard rate effect at both slow and fast stimulus rates. However, only in fast sequences did prior information about the target’s temporal distribution interact with elapsed time, suppressing the hazard rate. Importantly, in the fast, uninformed condition pre-stimulus power synchronization in the beta band (Beta 1, 15–19 Hz) predicted the hazard rate of response times. Prior information suppressed pre-stimulus power synchronization in the same band, while still significantly predicting response times. We conclude that Beta 1 power does not simply encode the hazard rate, but—more generally—internal estimates of temporal event probability based upon contextual information.
Sulforaphane is a natural substance found in cruciferous vegetables such as broccoli or cabbage. There are promising results for a number of tumor entities regarding the potential anti-carcinogenic effects of sulforaphane. The experiments designed for this study were performed on prostate carcinoma cells. The aim was to investigate the influence of sulforaphane on the growth behaviour of prostate cancer cells.
Designed as an in-vitro-model, prostate carcinoma cell lines DU145 and PC3 were used in the study. The experiments can be roughly divided into two categories:
• Regulation of cell growth: After the growth inhibitory effect of sulforaphane has been confirmed (MTT test), the proliferation rate (BrdU assay) and apoptosis rate (apoptosis assay) of the cells were measured under the influence of sulforaphane. Studies on clonogenic growth completed this series of experiments.
• Regulation of the cell cycle: After determining the impact of sulforaphane on the phases of the cell cycle (cell cycle assay), the cell cycle-relevant proteins of the cyclin-CDK-axis, the CDK inhibitors p19 and p27 as well as the acetylated histones aH3 and aH4 were analysed (Western Blot).
An additional MTT test was performed to determine a possible induction of resistance by long-term sulforaphane exposure. In addition, the expression profile of CD44 subtypes v4, v5 and v7 under the influence of sulforaphane has been investigated by FACS analysis.
The growth and proliferation rate as well as the clonogenic growth of the prostate carcinoma cells were shown to be inhibited under the influence of sulforaphane in a concentration-dependent manner. Induction of apoptosis has not occurred. The treatment with sulforaphane resulted in a concentration-dependent G2/M arrest of the cell cycle. The level of expression of cyclins A and B and of CDKs 1 and 2 has increased due to sulforaphane exposure. The level of expression of pCDKs has decreased except for a slight increase in pCDK 2 in the DU145 cell line. The CDK inhibitors p19 and p27 were elevated, except for a reduction of p27 in the PC3 cell line. The level of expression of acetylated histones aH3 and aH4 has increased due to sulforaphane treatment. Indications for induction of resistance by long-term use of sulforaphane were not found. Treatment with sulforaphane resulted in an increased expression level of the CD44 subtypes v4, v5 and v7 in a concentration- and time-dependent manner.
The test results fit into the existing findings. The exact processes and relationships of the modes of action are not yet sufficiently understood. Nevertheless, it can be stated that sulforaphane can trigger anticarcinogenic mechanisms at the molecular level also in prostate cancer. Therefore, sulforaphane could eventually be used in clinical practice, whether prophylactically or therapeutically. Further studies, also in clinical settings on humans, are therefore necessary.
Nukleäre Rezeptoren sind ligandenaktivierte Transkriptionsfaktoren, die das pharmazeutische Interesse als Zielstrukturen für antientzündliche Wirkstoffe und andere Indikationen erwecken. Entzündungen werden durch Noxen physikalischer, chemischer oder mikrobiologischer Art hervorgerufen. Dabei reagiert das geschädigte Gewebe mit zahlreichen Vorgängen, die vaskuläre und zelluläre Reaktionen mit Immunantworten verknüpfen und nach der Wiederherstellung des ursprünglichen Zustands streben. Bei andauernder Wirkung können Entzündungen jedoch in einen schädlichen Prozess umschlagen, sodass in solchen Fällen eine therapeutische Intervention Notwendigkeit erlangt. Ziel dieser Arbeit war es deshalb, neue Liganden nukleärer Rezeptoren als Kandidaten für antientzündliche Wirkstoffe zu identifizieren.
Leber X Rezeptoren (LXRs) sind Zielstrukturen für entzündliche und neurodegenerative Erkrankungen mit antiphlogistischem Potenzial. Zur Identifikation neuer LXR-Liganden wurde eine Datenbank mit zugelassenen Wirkstoffen mithilfe einer selbstorganisierenden Karte (SOM) auf Interaktion mit LXR gescreent. Die Retinoid X Rezeptor (RXR)-Agonisten Alitretinoin (37) und Bexaroten (38) konnten in der anschließenden in vitro Charakterisierung als potente duale LXRalpha/LXRbeta-Partialagonisten mit moderater Aktivierungseffizienz bestätigt werden. Während 37 und 38 synthetische LXR-Vollagonisten partiell antagonisierten, führten sie mit dem endogenen Partialagonisten 22(R)-Hydroxycholesterol (4) zur additiven Aktivierung von LXR. Die Charakterisierung von Alitretinoin (37) und Bexaroten (38) als duale LXR/RXR-Agonisten liefert nicht nur eine weitere Erklärung für in klinischen Studien beobachtete Nebenwirkungen, sondern könnte auch den Startpunkt zur Entwicklung neuer antientzündlicher LXR- und dualer LXR/RXR-Liganden bieten.
Der Peroxisomen Proliferator-aktivierte Rezeptor (PPAR) gamma ist ein nukleärer Rezeptor, der neben der Steigerung der Insulinsensitivität auch antientzündliche Effekte aufweist. Auf Grundlage seiner Y-förmigen und fettsäuremimetischen Struktur konnte das Urikosurikum Lesinurad (47) als PPARgamma-Partialagonist in vitro charakterisiert werden. Im Gegensatz zu PPARgamma-Vollagonisten wie Pioglitazon (31) oder Rosiglitazon (32) induzierte 47 nicht die Differenzierung muriner 3T3-L1 Zellen in reife Adipozyten, aber erhöhte in der humanen Leberzellkarzinomzelllinie HepG2 die Expression von Genen, welche die Insulinsensitivität und den Fettsäureabbau steigern könnten. Folglich erwies sich Lesinurad (47), das bei der Pharmakotherapie von Gicht Anwendung findet, als selektiver PPARgamma-Modulator (sPPARgammaM) ohne adipogene Nebenwirkungen. Insbesondere Patienten mit Komorbiditäten wie Diabetes mellitus Typ 2 oder anderen Erkrankungen des metabolischen Syndroms könnten von einer Behandlung mit 47 profitieren. Inwiefern PPARgamma an der Auflösung von Entzündungen bei Gicht beteiligt ist, bleibt in zukünftigen Studien zu klären.
Synthetische RXR-Agonisten haben ein vielversprechendes Potenzial zur Behandlung entzündlicher neurodegenerativer Erkrankungen, das jedoch von nachteiligen Eigenschaften dieser Rexinoide beeinträchtigt wird. Durch ein pharmakophorbasiertes Screening einer fokussierten Substanzbibliothek aus Fettsäuremimetika konnte ein fortschrittliches RXR-Ligandgerüst identifiziert werden. Eine geeignete Synthesestrategie wurde etabliert und die Leitstrukturen durch systematisches Studium der Struktur-Wirkungsbeziehung (SAR) optimiert. In vitro Experimente wie Reportergenassays und die Quantifizierung der Zielgenexpression bestätigten die RXR-partialagonistische Aktivität der dabei entwickelten nanomolaren Verbindung 89. Mit seiner hohen Selektivität, gesteigerten wässrigen Löslichkeit sowie reduzierter Lipophilie und Toxizität könnte 89 die Probleme bisheriger synthetischer RXR-Agonisten überwinden. Seine Präferenz von RXRgamma hinsichtlich der Aktivierungseffizienz könnte richtungsweisend für die Entwicklung subtypselektiver Liganden sein.
Die nichtalkoholische Steatohepatitis (NASH) ist eine Leberentzündung, die aus einer Steatose hervorgehen kann und deren multifaktorielle Natur eine hohe therapeutische Effizienz erfordert. Diese könnte durch duale Modulation der nukleären Rezeptoren Farnesoid X Rezeptor (FXR) und PPARdelta mit antientzündlichen Eigenschaften und unterschiedlichem Wirkprinzip erreicht werden. Zur Validierung dieses Ansatzes mit synergistischem Potenzial sollten duale PPARdelta/FXR-Agonisten ausgehend von einer in früheren Studien des Arbeitskreises identifizierten Leitstruktur mit moderater Potenz entwickelt werden. Dazu wurde ein fünfstufiges Verfahren zur Synthese von Derivaten der Leitstruktur erarbeitet und die Derivate hinsichtlich ihrer Aktivität auf den Zielstrukturen in vitro evaluiert. In systematischen SAR-Studien wurden dabei Strukturmotive charakterisiert, welche die Wirksamkeit und Maximalaktivierung auf PPARdelta und FXR steigerten. Darüber hinaus konnten Modifikationen identifiziert werden, welche eine Selektivität über PPARalpha und PPARgamma gewährten. Die Kombination dieser vorteilhaften Gruppen und Substituenten könnte neue Wirkstoffkandidaten zur Behandlung von NASH hervorbringen.
Insgesamt wurden in dieser Arbeit zahlreiche Wirkstoffe und Wirkstoffkandidaten erfolgreich als Liganden nukleärer Rezeptoren mit antientzündlichem Potenzial identifiziert. Alitretinoin (37) und Bexaroten (38) können als Leitstruktur zur Entwicklung neuer selektiver LXR- oder dualer LXR/RXR-Agonisten dienen. Die PPARgamma-partialagonistische Aktivität von Lesinurad (47) könnte einen Fortschritt in der Therapie von Gicht mit metabolischen Begleiterkrankungen bewirken. Zudem könnten im Zuge dieser Arbeit synthetisierte Serien von RXR- und dualen PPARdelta/FXR-Partialagonisten neue Therapieoptionen bei neurodegenerativen Erkrankungen oder NASH ermöglichen.
Human readers have the ability to infer knowledge from text, even if that particular information is not explicitly stated. In this thesis, we address the phenomena of text-level implicit information and outline novel automated methods for its recovery.
The main focus of this work is on two types of unexpressed content that arises between sentences (implicit discourse relations) and within sentences (implicit semantic roles).
Traditional approaches mostly rely on costly rich linguistic features, e.g., sentiment or frame-based lexicons, and require heuristics or manual feature engineering.
As an improvement, we propose a collection of generic resource-lean methods, implemented in the form of statistical background knowledge or by means of neural architectures.
Our models are largely language-independent and produce state-of-the-art performance, e.g., in the classification of Chinese implicit discourse relations, or the detection of locally covert predicative arguments in free texts.
In novel experiments, we quantitatively demonstrate that both types of implicit information are mutually dependent insofar as, for instance, some implicit roles directly correlate with implicit discourse relations of similar properties.
We show that implicit information processing further benefits downstream applications and demonstrate its applicability to the higher-level task of narrative story understanding.
In the conclusion of the dissertation, we argue for the need of implicit information processing in order to realize the goal of true natural language understanding.
Die wissenschaftliche Vernetzung, Betreuung und Unterstützung in der Promotionsphase steht im Zentrum dieser Forschungsarbeit, für die eine soziale Netzwerkanalyse (SNA) zur Karriereentwicklung in einem Bildungsforschungsprogramm in Deutschland durchgeführt wurde. Als Ausgangsproblem wird die schwierige Situation der unsicheren beruflichen Perspektiven Promovierter aufgegriffen.
Die Arbeit beschäftigt sich mit der Frage, wie Promovierende sowohl eine hohe fachliche Qualifikation erreichen, die für eine wissenschaftliche Karriere erforderlich ist, als auch eine gute Vernetzung in der wissenschaftlichen Gemeinschaft aufbauen können, um sich Chancen für die nächsten Karriereschritte zu eröffnen. Aus der Perspektive der Promovierten werden Chancen und Risiken der Vernetzung behandelt, um Überlegungen zu förderlichen und hinderlichen Aspekten der Betreuung und Unterstützung anzustellen.
Die Ergebnisse dieser Forschungsarbeit zeigen auf, welche Bedeutung soziale Netzwerke in der Berufsbiografie haben können und wie wissenschaftliches und soziales Kapital für die Karriere genutzt werden kann. Dazu richtet sich die erziehungswissenschaftliche Perspektive auf Prozesse des Wissenserwerbs und gemeinschaftlicher Lernprozesse, die zur Qualifizierung dienen und unterschiedliche Modelle von Betreuung umfassen. Im Verlauf der Promotionsphase und der weiteren wissenschaftlichen Karriere beginnen die Promovierenden auf der Wissensgrundlage ihres Studiums als Neulinge ihre erste umfangreiche empirische Forschungsarbeit. Sie werden durch die Mitarbeit im Projekt und ihre Beteiligung an Aktivitäten an die Arbeitsweisen in der Wissenschaft herangeführt. Von einer solchen eher randständigen Position aus erwerben sie Wissen, lernen hinzu, tauschen sich mit fortgeschrittenen WissenschaftlerInnen aus und sammeln eigene Erfahrungen. Nach einiger Zeit weiterer Qualifizierung und größerer Sichtbarkeit in der wissenschaftlichen Gemeinschaft können sie Positionen näher am Zentrum ihres Forschungsgebiets einnehmen, die auf ihren Kenntnissen und ihrer zunehmenden fachlichen und methodischen Expertise beruhen.
Neue Erkenntnisse über Betreuungsmodelle sind hilfreich, denn die Betreuung orientiert sich mal stark an dem klassischen Lehrer-Schüler-Modell (Individualbetreuung) oder an einer gemeinsamen Betreuung in einer Forschungsgruppe (Gruppenbetreuung). Die Untersuchung der Bedeutung von sozialem Kapital und situiertem Lernen in der Qualifikationsphase dient dazu, die Vernetzung von Promovierten in ihrer späteren akademischen Karriere zu analysieren.
Transposable elements (TEs) are replicating genetic elementst hat comprise up to 50% of mammalian genomes. A specific class of TEs are retrotransposons that proliferate by transcription into a RNA intermediate, followed by genomic reintegration into another locus (so called “copy & paste” mechanism). Due to the lack of removal mechanisms and very rare parallel insertions, the presence of TE insertions at ortholgous genomic loci in multiple taxa provides a virtually homoplasy free phylogenetic marker. So far, developing phylogenetically informative markers from TE insertions has been a tedious work of testing hundreds of putative candidate loci in a trial-and error approach with low success rate. Hence, phylogenetic studies using TE insertions were often limited to a few dozen markers.
Recently, genome sequencing of multiple species using reference-mapping allowed the identification of genome-scale datasets of TE insertions. and made the ad-hoc development of phylogenetic informative markers possible. However, genome scale TE detection methods have rarely been applied to non model organisms in which data availability and quality is comparably limited. In this thesis, I developed the TeddyPi pipeline (TE detection and discovery for phylogenetic inference), a software tool that made it possible to obtain reliable genome-scale TE insertion data from low-coverage genomes. This was achieved by integrating the data from multiple TE and structural variation callers as well as applying a stringent filtering pipeline to exclude low-quality insertion calls. Whole-genome sequencing datasets of bears (Ursidae) and baleen whales (Mysticeti) were used to apply TE based phylogenetic inference and evaluate the method in comparison to sequence-based phylogenomic analyses.
In the bear genomes, TeddyPi identified 150,513 high-quality transposable element (TE) insertions, which allowed me to reconstruct the evolutionary history of bears despite extensive phylogenetic conflict (Lammers et al., 2017). The large number of detected TE insertions made also detailed network analyses possible that visualize the phylogenetic conflict. Experimental polymerase chain reaction (PCR) assays validated up to 93 % of the computationally identified TE loci and demonstrated the high accuracy of the dataset underlying the phylogenetic analyses.
Second, I present the initial genome sequencing of six baleen whales and a detailed investigation of their evolutionary history using TE insertions and established sequence-based phylogenomic methods. The taxon sampling of baleen whales included iconic species like the blue whale (Balaneoptera musculus) or the humpback whale (Megaptera novaengliae) (Árnason et al., 2018). A sequence-based reconstruction of the baleen whale species tree solved the long-debated phylogenetic position of the gray whale (Echrichtius robustus) within rorquals (Balaneopteridae) for the first time with high statistical support. Furthermore, the genome data made it possible to identify large extent of phylogenetic conflict for divergences during the radiation of rorquals that occurred 7-10 million years ago (Ma).
The phylogenomic analyses of 91,589 TE insertions in the whale genomes confirmed the sequence-based topology (Lammers et al., 2019). The quantification of phylogenetic signals obtained from the TE insertions revealed a high degree of discordance for the divergence of the gray whale and rorquals. Despite the large genome-scale dataset, statistical tests showed only marginal support for a bifurcating divergence of gray whales and the rorqual species. The limited statistical support for a strictly bifurcating tree obtained from genome-scale datasets of thousands of markers demonstrates the importance for including phylogenetic networks for displaying evolutionary divergences.
In conclusion, this thesis shows that identification of TE insertions from whole-genome resequencing provides plentiful and accurate phylogenomic markers. For the application in non model organisms, I provide a easy-to-use software to integrate multiple datasets from TE and structural variation callers in order to obtain reliable and ascertainment-bias free datasets. Detecting genome-scale datasets of TE insertions in two case studies demonstrates the applicability of this marker system for phylogenetic reconstruction and inferring phylogenetic conflict.
Nominal modification in language production: Extraposition of prepositional phrases in german
(2019)
In my dissertation, I investigate the phenomenon of extraposition of PP out of NP in German in language production. Four production experiments, using the method of production of memory, and three experiments testing the acceptability of extraposition were conducted. In extraposition, a constituent is realized in a position to the right of what would be considered the canonical position. A special case is extraposition out of a nominal phrase (NP), in which a constituent is moved out of NP to the end of the utterance. The example in (1a) illustrates the canonical version, in which a prepositional phrase (PP) is adjacent to its head noun. In (1b) the PP is extraposed out of NP to the right edge of the sentence.
(1) a. Gestern hat eine Frau mit einer lauten, schrillen Stimme angerufen.
b. Gestern hat eine Frau angerufen mit einer lauten, schrillen Stimme.
There are two main aspects to consider: the length of the extraposed constituent (the PP), and the length of the intervening material. Experiment 1 investigated the influence of constituent length on extraposition. The hypothesis is that longer and more complex constituents are harder to produce and are therefore produced towards the end of the utterance. In the experiment, PPs of three different lengths (2-3, 5-6, 9-11 words) had to be reproduced in either adjacent or extraposed position. As to the length of the intervening material, the hypothesis is that sentences with more intervening material between head noun and extraposed PP will tend to be reproduced with the PP in adjacent position to the head noun. In order to test this hypothesis, the length of the intervening material (1, 2 and 4 words) was manipulated in Experiment 2. The same material was used in an acceptability experiment, using the method of magnitude estimation (Experiment 5).
Previous studies found that extraposition is preferred over verbal material only, thus Experiment 3 investigated the influence of different lengths of purely verbal intervening material. Experiment 4 was concerned with the differences between PP and RC extraposition in production.
Experiment 6 and 7 used Likert scales to assess the acceptability of extraposition. Experiment 6 investigated whether the acceptability of extraposition is influenced by the definiteness status of the NP out of which is extraposed and if a soft constraint for definiteness can be found for PP extraposition in German. Experiment 7 asked if the inner structure of the extraposed constituent (PP only vs. PP+RC) influences its acceptability. An extraposed PP that includes an RC should be "heavier" than a PP without an RC, since the number of phrasal nodes is higher. If indeed heavier constituents are realized at the end of an utterance, the acceptability of an extraposed PP that includes an RC should be higher than that of an extraposed PP without one.
The results of the production experiments show that sentences are mostly reproduced in their original linear sequence, which suggests that extraposed position seems to be just as canonical as adjacent position, especially when extraposition takes place over verbal material only. With regard to constituent length, in extraposed position long PPs are shortened less often, supporting the hypothesis that longer and more complex constituents tend to be produced at the end of the utterance. Recency effects were found for intervening material as participants dropped intervening material rather than change syntactic position of constituents. The length and type of the intervening material is important with respect to how much intervening material is acceptable. Verb clusters were not shortened in sentences with extraposed PPs, however, 1⁄3 of adverbs and 1⁄2 of PP adverbials including a lexical NP were shortened to „verb only“. Extraposed PPs are more often reproduced in adjacent position than adjacent PPs are reproduced in extraposed position. However, the position of RCs is more often changed from adjacent to extraposed than from extraposed to adjacent.
While producing extraposed PPs seems not to be any more difficult than producing adjacent ones, adjacent constituents are consistently rated higher than extraposed constituents in grammaticality judgment tasks. This is in line with findings of Konieczny (2000) on German RC extraposition. The number of phrasal nodes, as suggested by Rickford et al. (1995), did not have an influence on the acceptability of extraposition, while the length of the constituent, measured in words, seems to play a role. Definiteness had no effect on adjacent PPs, but when the PP was extraposed, sentences with an indefinite antecedent were rated higher than sentences with a definite antecedent. This suggests that there is a "soft constraint" for definiteness with regard to PP extraposition out of NP in German.
Buchbesprechungen
(2019)
Es werden folgende Publikation rezensiert: Daniel Barthélémy (Hrsg.): Pl@ntNet; Bunzel-Drüke et al.: Naturnahe Beweidung und Natura 2000; Martina D'Ascola: 50 sagenhafte Naturdenkmale in Hessen; Hessisches Landesamt für Naturschutz, Umwelt und Geologie: Guter Heinrich, Pfingst-Nelke, Färber-Scharte & Co. Hessische Verantwortungsarten – Teil 1.
Die von Wolfgang Ludwig hinterlassene Pflanzensammlung im Marburger Herbar wurde aufbereitet und dokumentiert. Vorgestellt werden Belege aus der in über 70 Jahren (1938–2010) entstandenen Sammlung, die für die hessische Flora bislang nicht bekannt waren sowie Belege zu inzwischen ausgestorbenen, sehr seltenen oder sonstigen bemerkenswerten Arten.
Das Naturschutzgebiet Kühkopf-Knoblochsaue mit 2 400 ha überflutbarer Aue eignet sich in dem potenziellen Wildreben-Verbreitungsgebiet in Deutschland (Oberrheingebiet zwischen Freiburg und Wiesbaden) aktuell bei weitem am besten zum Wiederaufbau überlebensfähiger, ausreichend heterozygoter Wildrebenbestände. Nach einer ersten Wiederansiedlung 2013 mit 65 Genotypen und 121 ausgebrachten wurzelnackten Pflanzen mit Draht-Verbissschutz wurden 2016 in einer zweiten Wiederansiedlungsmaßnahme 551 Wilde Weinreben (78 Genotypen) an 12 Standorten gepflanzt. Es handelte sich hierbei um zweijährige Topfpflanzen, die ohne Verbissschutz gepflanzt wurden. Ein Jahr nach der Pflanzung war eine durchschnittliche Überlebensrate von 69 % zu konstatieren. Die Überlebensraten variieren an den Standorten zwischen 55 und 87 %. 75 von Wildschweinen herausgewühlte Wilde Weinreben wurden wieder eingepflanzt; die Überlebensrate kann somit noch über 69 % steigen.
Bei einer Prüfung von 153 Gewässern in Frankfurt am Main wurden neben den heimischen Typha-Arten Typha angustifolia und T. latifolia Verwilderungen von Typha shuttleworthii und Pflanzungen von Typha laxmannii gefunden. Auch Typha ×glauca die Hybride zwischen Typha angustifolia und T. latifolia wurde mehrfach gefunden.
Im Rahmen der Kartierung der Gefäßpflanzenflora des Vor-, Hochund kammnahen Hintertaunus wurde im Jahre 2004 ein großer Bestand des für Deutschland bislang selten erwähnten Doronicum ×willdenowii entdeckt. Da sich die Art bis heute nicht nur gehalten, sondern vermehrt hat, besteht offensichtlich ein Trend zur lokalen Einbürgerung.
Im Jahr 2008 wurden im Hochtaunus zwei Vorkommen der für diesen Bereich in der Literatur bisher nicht erwähnten Süßdolde (Myrrhis odorata) entdeckt. Beide haben sich bis heute (2017) in dicht geschlossenen, einmal im Jahr gemähten Pflanzenbeständen gehalten. Die Art besitzt also offensichtlich das Potential zur Einbürgerung, wobei man angesichts der relativ geringen Bestandesgröße noch nicht von einem gesicherten Trend zur Einbürgerung sprechen darf. Beide Pflanzenbestände sind saumartig ausgebildet, wobei der Aspekt auch von typischen Saumarten bestimmt wird. Der für Saumgesellschaften auffallend hohe Anteil an Wiesenarten dürfte darauf zurückzuführen sein, dass beide Säume einmal im Jahr gemäht werden.
Um dem neuen Forschungsstand zu Luthers geistlichem Mentor im Augustinerorden endlich zum Durchbruch zu verhelfen, edieren Dohna und Wetzel u. a. Akten aus dem Häresie-Verfahren des Erzbischofs von Salzburg gegen den Augustiner Agricola. Staupitz, der ein Gutachten lieferte, hat sich keineswegs von der lutherischen Bewegung distanziert. Er blieb seiner frühreformatorischen Theologie treu und vermied eine Verurteilung. Agricola musste keineswegs fliehen, er wurde freigelassen. Während andernorts schon Scheiterhaufen brannten, hatten Reformkatholiken hier noch Platz in der abendländischen Kirche.
SAFE Newsletter : 2019, Q3
(2019)