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Im Mittelpunkt der Dissertation steht die Untersuchung der Sprachförderkompetenz von Grundschullehrkräften aus linguistischer Perspektive. Dabei geht es um Grundschullehrkräfte, die in der vorschulischen Sprachförderung, v.a. von Kindern mit Deutsch als früher Zweitsprache (DaZ), im Rahmen sogenannter Vorlaufkurse in Hessen tätig sind. Anhand von zwei zentralen Dimensionen professioneller Kompetenz, dem Wissen und dem Handeln, werden in zwei empirischen Studien anhand einer Gruppe von 10 Lehrkräften der Umfang des sprachlichen Fachwissens und verschiedene Eigenschaften des sprachlichen Handelns in der Interaktion mit DaZ-Kindern im Vorlaufkurs untersucht. Zudem werden mögliche Zusammenhänge zwischen Wissen und Handeln sowie Unterschiede und Gemeinsamkeiten hinsichtlich beider Dimensionen zu pädagogischen Fachkräften aus dem Elementarbereich geprüft.
Background: Physiologically-based population pharmacokinetic modeling (popPBPK) coupled with in vitro biopharmaceutics tools such as biorelevant dissolution testing can serve as a powerful tool to establish virtual bioequivalence and set clinically relevant specifications. One of several applications of popPBPK modeling is in the emerging field of virtual bioequivalence (VBE), where it can be used to streamline drug development by implementing model-informed formulation design and to inform regulatory decision-making e.g., with respect to evaluating the possibility of extending BCS-based biowaivers beyond BCS Class I and III compounds in certain cases.
Methods: In this study, Naproxen, a BCS class II weak acid was chosen as the model compound. In vitro biorelevant solubility and dissolution experiments were performed and the resulting data were used as an input to the PBPK model, following a stepwise workflow for the confirmation of the biopharmaceutical parameters. The naproxen PBPK model was developed by implementing a middle-out approach and verified against clinical data obtained from the literature. Once confidence in the performance of the model was achieved, several in vivo dissolution scenarios, based on model-based analysis of the in vitro data, were used to simulate clinical trials in healthy adults. Inter-occasion variability (IOV) was also added to critical physiological parameters and mechanistically propagated through the simulations. The various trials were simulated on a “worst/best case” dissolution scenario and average bioequivalence was assessed according to Cmax, AUC and tmax.
Results: VBE results demonstrated that naproxen products with in vitro dissolution reaching 85% dissolved within 90 minutes would lie comfortably within the bioequivalence limits for Cmax and AUC. Based on the establishment of VBE, a dissolution “safe space” was designed and a clinically relevant specification for naproxen products was proposed. The interplay between formulation-related and drug-specific PK parameters (e.g., t1/2) to predict the in vivo performance was also investigated.
Conclusion: Over a wide range of values, the in vitro dissolution rate is not critical for the clinical performance of naproxen products and therefore naproxen could be eligible for BCS-based biowaivers based on in vitro dissolution under intestinal conditions. This approach may also be applicable to other poorly soluble acidic compounds with long half-lives, providing an opportunity to streamline drug development and regulatory decision-making without putting the patient at a risk.
(1) Background: Oncological gastrectomy requires complex multidisciplinary management. Clinical pathways (CPs) can potentially facilitate this task, but evidence related to their use in managing oncological gastrectomy is limited. This study evaluated the effect of a CP for oncological gastrectomy on process and outcome quality. (2) Methods: Consecutive patients undergoing oncological gastrectomy before (n = 64) or after (n = 62) the introduction of a CP were evaluated. Assessed parameters included catheter and drain management, postoperative mobilization, resumption of diet and length of stay. Morbidity, mortality, reoperation and readmission rates were used as indicators of outcome quality. (3) Results: Enteral nutrition was initiated significantly earlier after CP implementation (5.0 vs. 7.0 days, p < 0.0001). Readmission was more frequent before CP implementation (7.8% vs. 0.0%, p = 0.05). Incentive spirometer usage increased following CP implementation (100% vs. 90.6%, p = 0.11). Mortality, morbidity and reoperation rates remained unchanged. (4) Conclusions: After implementation of an oncological gastrectomy CP, process quality improved, while indicators of outcome quality such as mortality and reoperation rates remained unchanged. CPs are a promising tool to standardize perioperative care for oncological gastrectomy
In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.
Rethinking superdeterminism
(2020)
Quantum mechanics has irked physicists ever since its conception more than 100 years ago. While some of the misgivings, such as it being unintuitive, are merely aesthetic, quantum mechanics has one serious shortcoming: it lacks a physical description of the measurement process. This “measurement problem” indicates that quantum mechanics is at least an incomplete theory—good as far as it goes, but missing a piece—or, more radically, is in need of complete overhaul. Here we describe an approach which may provide this sought-for completion or replacement: Superdeterminism. A superdeterministic theory is one which violates the assumption of Statistical Independence (that distributions of hidden variables are independent of measurement settings). Intuition suggests that Statistical Independence is an essential ingredient of any theory of science (never mind physics), and for this reason Superdeterminism is typically discarded swiftly in any discussion of quantum foundations. The purpose of this paper is to explain why the existing objections to Superdeterminism are based on experience with classical physics and linear systems, but that this experience misleads us. Superdeterminism is a promising approach not only to solve the measurement problem, but also to understand the apparent non-locality of quantum physics. Most importantly, we will discuss how it may be possible to test this hypothesis in an (almost) model independent way.
Despite the popularity of the term Positive Psychological Coaching within the literature, there is no consensus as to how it should be defined (framed) or what the components of a positive coaching “model” should include. The aim of this systematic review was to define positive psychological coaching and to construct a clear demarcated positive psychological coaching model based on the literature. A systematic literature review led to the extraction of 2,252 records. All records were screened using specific inclusion/exclusion criteria, which resulted in the exclusion of records based on duplicates (n = 1,232), titles (n = 895), abstracts (n = 78), and criteria violations (n = 23). Twenty-four academic, peer-reviewed publications on positive psychological coaching were included. Data relating to conceptual definitions and coaching models/phases/frameworks were extracted and processed through thematic content analysis. Our results indicate that positive psychological coaching can be defined as a short to medium term professional, collaborative relationship between a client and coach, aimed at the identification, utilization, optimization, and development of personal strengths and resources in order to enhance positive states, traits and behaviors. Utilizing Socratic goal setting and positive psychological evidence-based approaches to facilitate personal growth, optimal functioning, enhanced wellbeing, and the actualization of people's potential. Further, eight critical components of a positive psychological coaching model were identified and discussed. The definition and coaching process identified in this study will provide coaches with a fundamental positive psychological framework for optimizing people's potential.
Tigers are indisputably in danger of extinction due to habitat loss and demand for their parts. Tigers are extirpated in the wild from every country bar one in mainland East and Southeast Asia. Although consumption of tiger products is known to be established in China, less is known about demand for tiger products in Southeast Asia. In this study, we investigate tiger product demand in Vietnam, a major illegal wildlife consumer country. There has been little research into consumption, in particular the level of use, the products being consumed, variation in use of products between areas, and the motivations of consuming tiger products. Through a quantitative survey of 1120 individuals, we show that use of tiger products could be as high as ~11% of the sample in both urban centers of Vietnam, Hanoi and Ho Chi Minh City. Tiger bone glue is the predominant product used, for medicinal purposes. In Hanoi, it is generally purchased by the individual for self-use, while in Ho Chi Minh City it is generally purchased as a gift. In both cities, individuals were generally highly satisfied with the product, indicating entrenched belief in efficacy among consumers. Ultimately, our results show that tiger product use is relatively pervasive. We suggest that conservation organizations should focus on behavior change campaigns that are informed by the results here, and that are specific to each area and to the specific use of tiger product glue for medicine. By reducing demand, beleaguered tiger populations will have a greater chance of stabilization and eventual growth.
Metasomatic evolution of coesite-bearing diamondiferous eclogite from the Udachnaya Kimberlite
(2020)
A coesite-bearing diamondiferous eclogite from the Udachnaya kimberlite (Daldyn field, Siberian craton) has been studied to trace its complex evolution recorded in rock-forming and minor mineral constituents. The eclogite sample is composed of rock-forming omphacite (60 vol%), garnet (35 vol%) and quartz/coesite (5 vol%) and contains intergranular euhedral zoned olivine crystals, up to 200 µm long, coexisting with phlogopite, orthopyroxene, clinopyroxene (secondary), K-feldspar, plagioclase, spinel, sodalite and djerfisherite. Garnet grains are zoned, with a relatively homogeneous core and a more magnesian overgrowth rim. The rim zones further differ from the core in having higher Zr/Y (6 times that in the cores), ascribed to interaction with, or precipitation from, a kimberlite-related melt. Judging by pressure-temperature estimates (~1200 °C; 6.2 GPa), the xenolith originated at depths of ~180–200 km at the base of the continental lithosphere. The spatial coexistence of olivine, orthopyroxene and coesite/quartz with K-Na-Cl minerals in the xenolith indicates that eclogite reacted with a deep-seated kimberlite melt. However, Fe-rich olivine, orthopyroxene and low-pressure minerals (sodalite and djerfisherite) likely result from metasomatic reaction at shallower depths during transport of the eclogite by the erupting kimberlite melt. Our results demonstrate that a mixed eclogitic-peridotitic paragenesis, reported previously from inclusions in diamond, can form by interaction of eclogite and a kimberlite-related melt.
Background: Re-treatment in patients with a chronic hepatitis C virus (HCV) infection and a previous failure to direct-acting antiviral (DAA) treatment remains a challenge. Therefore, we investigated the success rate of treatment and re-treatment regimens used at our center from October 2011 to March 2018.
Methods: A retrospective analysis of DAA-based HCV therapies of 1096 patients was conducted. Factors associated with a virological relapse were identified by univariable and multivariable logistic regression, treatment success of the re-treatment regimens was evaluated by an analysis of sustained virological response (SVR) rates in patients with a documented follow-up 12 weeks after the end of treatment.
Results: Of 1096 patients treated with DAA-based regimens, 91 patients (8%) were lost to follow-up, 892 of the remaining 1005 patients (89%) achieved an SVR12. Most patients (65/113, 58%) who experienced a virological relapse received an interferon-based DAA regimen. SVR rates were comparable in special cohorts like liver transplant recipients (53/61, 87%) and people with a human immunodeficiency virus (HIV) coinfection (41/45, 91%). On multivariable analysis, interferon-based DAA therapy was associated with treatment failure (odds ratio 0.111, 95%-confidence interval 0.054–0.218) among others. One hundred seventeen patients with multiple DAA treatment courses were identified, of which 97 patients (83%) experienced a single relapse, but further relapses after two (18/117, 15%) or even three (2/117, 2%) treatment courses were also observed. Eighty-two of 96 (85%) re-treatment attempts with all-oral DAA regimens were successful after an initial treatment failure.
Conclusion: Overall, DAA re-treatments were highly effective in this real-world cohort and only a minority of patients failed more than two treatment courses. Switching to–or addition of–a new drug class seem to be valid options for the re-treatment of patients especially after failure of an interferon-based regimen.
A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.
The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Objective: Severely injured patients frequently develop an immunological imbalance following the traumatic insult, which might result in infectious complications evoked by a persisting immunosuppression. Regulatory T cells (Tregs) maintain the immune homeostasis by suppressing proinflammatory responses, however, their functionality after trauma is unclear. Here, we characterized the role of Tregs in regulating the proliferation of CD4+ lymphocytes in traumatized patients (TP). Methods: Peripheral blood was obtained daily from 29 severely injured TP (Injury Severity Score, ISS ≥16) for ten days following admission to the emergency department (ED). Ten healthy volunteers (HV) served as controls. The frequency and activity of Tregs were assessed by flow cytometry. Proliferation of CD4+ cells was analyzed either in presence or absence of Tregs, or after blocking of either IL-10 or IL-10R1. Results: The frequencies of CD4+CD25high and CD4+CD25+CD127− Tregs were significantly decreased immediately upon admission of TP to the ED and during the following 10 post-injury days. Compared with HV CD4+ T cell proliferation in TP increased significantly upon their admission and on the following days. As expected, CD4+CD25+CD127− Tregs reduced the proliferation of CD4+ cells in HV, nevertheless, CD4+ proliferation in TP was increased by Tregs. Neutralization of IL-10 as well as blocking the IL-10R1 increased further CD4+ T cell proliferation in Tregs-depleted cultures, thereby confirming an IL-10-mediated mechanism of IL-10-regulated CD4+ T cell proliferation. Neutralization of IL-10 in TP decreased CD4+ T cell proliferation in Tregs-depleted cultures, whereas blocking of the IL-10R1 receptor had no significant effects. Conclusions: The frequency of Tregs in the CD4+ T lymphocyte population is reduced after trauma; however, their inductiveness is increased. The mechanisms of deregulated influence of Tregs on CD4+ T cell proliferation are mediated via IL-10 but not via the IL-10R1.
Survivin is a drug target and its suppressant YM155 a drug candidate mainly investigated for high-risk neuroblastoma. Findings from one YM155-adapted subline of the neuroblastoma cell line UKF-NB-3 had suggested that increased ABCB1 (mediates YM155 efflux) levels, decreased SLC35F2 (mediates YM155 uptake) levels, decreased survivin levels, and TP53 mutations indicate YM155 resistance. Here, the investigation of 10 additional YM155-adapted UKF-NB-3 sublines only confirmed the roles of ABCB1 and SLC35F2. However, cellular ABCB1 and SLC35F2 levels did not indicate YM155 sensitivity in YM155-naïve cells, as indicated by drug response data derived from the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) databases. Moreover, the resistant sublines were characterized by a remarkable heterogeneity. Only seven sublines developed on-target resistance as indicated by resistance to RNAi-mediated survivin depletion. The sublines also varied in their response to other anti-cancer drugs. In conclusion, cancer cell populations of limited intrinsic heterogeneity can develop various resistance phenotypes in response to treatment. Therefore, individualized therapies will require monitoring of cancer cell evolution in response to treatment. Moreover, biomarkers can indicate resistance formation in the acquired resistance setting, even when they are not predictive in the intrinsic resistance setting.
Although the big tobacco companies offer the same cigarette brands across countries, little is known about the potential regional differences of the particulate matter (PM) emissions of apparently equal brands. PM emissions of three cigarette brands (Marlboro Gold, Winston Red resp. Classic, Parliament Platinum resp. Night Blue) from the United Arab Emirates (UAE) and Germany were analysed. Second-hand smoke was produced in a 2.88 m3 measuring cabin by an automatic environmental tobacco smoke emitter. PM size fractions PM10, PM2.5, and PM1 were detected in real-time using laser aerosol spectrometry. Depending on the PM fraction Marlboro cigarettes from UAE showed 33%–35% higher PM amounts. Moreover, Winston cigarettes from UAE showed distinctly higher PM values (28–31%) than the German counterparts. The “lighter” Parliament from UAE emitted 3%–9% more PM than the German one. The measured mean PM10 values laid between 778 and 1163 µg/m3 (mean PM2.5: 777–1161 µg/m3; mean PM1: 724–1074 µg/m3). That means smoking in enclosed rooms causes massive PM burden. The PM emission of equal or similar tobacco products from different countries can differ distinctly. Hence, the declaration of PM emission values, besides nicotine, tar, and carbon monoxide amounts, should be obligatory worldwide. Furthermore, complete information about the ingredients and production processes of tobacco products should be provided to health officials and the public. This can help to minimise or ban substances or product designs that make smoking even more harmful, and to enhance the awareness of the risks of smoking.
Rezension zu: Heinrich Schlange-Schöningen, Hieronymus. Eine historische Biographie (Darmstadt 2018)
(2020)
The paper examines the application of the category of ‘populism’ to Athenian democracy. Unlike previous works on the subject, which have focused on the fifth century, it studies the fourth, where the tradition is much better, since we can refer to contemporary public speeches. It shows that, despite some parallels on the lexical level, 'populist’ strategies matching the criteria of modern political science cannot be identified in Athenian political communication and interprets this result in its historical context.
Enthält 2 Teile:
Oliva Menozzi: Introduction S. 1-10
Gloria Adinolfi, Silvano Agostini, Valentina Belfiore, Rodolfo Carmagnola, Maria Violeta Carniel, Vincenzo d’Ercole, Rocco D’Errico, Maria Giorgia Di Antonio, Eugenio Di Valerio, Maria Emilia Masci, Maria CristinaMancini, Oliva Menozzi, Donato Palumbo, Ilaria Zelante: Le metodologie, il team risultati preliminari del digital imaging. S. 11-52
IFLS-Journal. Nr. 25, 2020
(2020)
Das Working Paper bietet die zusammenfassende Stellungnahme von Prof. Volker Wieland zum Ankaufprogramm der Europäischen Zentralbank für Anleihen des öffentlichen Sektors (Public Sector Purchase Programme, PSPP) am Bundesverfassungsgericht am 30.07.2019. Dabei liegt der Schwerpunkt auf der Frage der Einordnung des PSPP als monetäre, geldpolitische Maßnahme und der Verhältnismäßigkeit des Programms und seiner Umsetzung. Ebenfalls wird kurz auf die weiteren Fragen zur Umsetzung, insbesondere Ankündigung, Begrenzung und Abstand zum Primärmarkt für Staatsanleihen eingegangen.
The European Commission is trying to reboot the CMU project: The High-Level Forum on Capital Markets Union – a group of 28 selected experts from industry, academia and civil society – is expected to submit policy recommendations by the end of May 2020 which will feed into the Commission’s new CMU agenda. This contribution is largely based on a letter to the High-Level Forum that gives feedback on the Interim Report published in February. There, we introduce a comprehensive approach to distinguish, from a functional finance perspective, between the ‘game changers’ and what is nice to have. We highlight the importance of common and consistent supervisory practices across Member States and recommend building up a European Securities and Exchange Commission (E-SEC) according to the American model.
We study how the Eurosystem Collateral Framework for corporate bonds helps the European Central Bank (ECB) fulfill its policy mandate. Using the ECBs eligibility list, we identify the first inclusion date of both bonds and issuers. We find that due to the increased supply and demand for pledgeable collateral following eligibility, (i) securities lending market trading activity increases, (ii) eligible bonds have lower yields, and (iii) the liquidity of newly-issued bonds declines, whereas the liquidity of older bonds is una↵ected/improves. Corporate bond lending relaxes the constraint of limited collateral supply, thereby making the market more cohesive and complete. Following eligibility, bond-issuing firms reduce bank debt and expand corporate bond issuance, thus increasing overall debt size and extending maturity.
The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker by an active ester of the catalyst. However, this procedure was low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts can be expected when the catalyst is attached to a strong 5’ closing base pair and when the oligonucleotide contains several LNA units that are equally distributed in the strand. However, when placed in the 5’ position, LNA building blocks tend to diminish the specificity of RNA cleavage.
RNA-protein complexes (RNPs) are essential components in a variety of cellular processes, and oftentimes exhibit complex structures and show mechanisms that are highly dynamic in conformation and structure. However, biochemical and structural biology approaches are mostly not able to fully elucidate the structurally and especially conformationally dynamic and heterogeneous nature of these RNPs, to which end single molecule Förster resonance energy transfer (smFRET) spectroscopy can be harnessed to fill this gap. Here we summarize the advantages of strategic smFRET studies to investigate RNP dynamics, complemented by structural and biochemical data. Focusing on recent smFRET studies of three essential biological systems, we demonstrate that investigation of RNPs on a single molecule level can answer important functional questions that remained elusive with structural or biochemical approaches alone: The complex structural rearrangements throughout the splicing cycle, unwinding dynamics of the G-quadruplex (G4) helicase RHAU, and aspects in telomere maintenance regulation and synthesis.
Brutalität ist der Kunst Richard Jacksons inhärent. Sie zeigt sich jedoch nicht nur in der Darstellung sich bekriegender Enten oder in dem Blick auf eine augenscheinlich schmerzhafte und chaotische Geburt, sondern in etwas anderem. Etwas, das sich direkt vor unseren Augen abspielt, aber unbenannt bleibt. Ein Kommentar.
Communication sounds are ubiquitous in the animal kingdom, where they play a role in advertising physiological states and/or socio-contextual scenarios. Human screams, for example, are typically uttered in fearful contexts and they have a distinctive feature termed as “roughness”, which depicts amplitude fluctuations at rates from 30–150 Hz. In this article, we report that the occurrence of fast acoustic periodicities in harsh sounding vocalizations is not unique to humans. A roughness-like structure is also present in vocalizations emitted by bats (species Carollia perspicillata) in distressful contexts. We report that 47.7% of distress calls produced by bats carry amplitude fluctuations at rates ~1.7 kHz (>10 times faster than temporal modulations found in human screams). In bats, rough-like vocalizations entrain brain potentials and are more effective in accelerating the bats’ heart rate than slow amplitude modulated sounds. Our results are consistent with a putative role of fast amplitude modulations (roughness in humans) for grabbing the listeners attention in situations in which the emitter is in distressful, potentially dangerous, contexts.
A growing body of experimental syntactic research has revealed substantial variation in the magnitude of island effects, not only across languages but also across different grammatical constructions. Adopting a well-established experimental design, the present study examines island effects in Spanish using a speeded acceptability judgment task. To quantify variation across grammatical constructions, we tested extraction from four different types of structure (subjects, complex noun phrases, adjuncts and interrogative clauses). The results of Bayesian mixed effects modelling showed that the size of island effects varied between constructions, such that there was clear evidence of subject, adjunct and interrogative island effects, but not of complex noun phrase island effects. We also failed to find evidence that island effects were modulated by participants’ working memory capacity as measured by an operation span task. To account for our results, we suggest that variability in island effects across constructions may be due to the interaction of syntactic, semantic-pragmatic and processing factors, which may affect island types differentially due to their idiosyncratic properties.
The third dataset dedicated to the Open Guided Waves platform aims at carbon fiber composite plates with an additional omega stringer at constant temperature conditions. The two structures used in this work are representative for real aircraft components. Comprehensive measurements were recorded in order to study (I) the impact of the omega stringer on guided wave propagation, and (II) elliptical reference damages of different sizes located at three separate positions on the structure. Measurements were recorded for narrowband excitation (5-cycle toneburst with varying carrier frequencies) and broadband excitation (using chirp waveforms). The paper presents the results of a technical validation including numerical modelling, and enables further research, for example related to probability of detection (POD) analysis.
Vegetation responds to drought through a complex interplay of plant hydraulic mechanisms, posing challenges for model development and parameterization. We present a mathematical model that describes the dynamics of leaf water-potential over time while considering different strategies by which plant species regulate their water-potentials. The model has two parameters: the parameter λ describing the adjustment of the leaf water potential to changes in soil water potential, and the parameter Δψww describing the typical ‘well-watered’ leaf water potentials at non-stressed (near-zero) levels of soil water potential. Our model was tested and calibrated on 110 time-series datasets containing the leaf- and soil water potentials of 66 species under drought and non-drought conditions. Our model successfully reproduces the measured leaf water potentials over time based on three different regulation strategies under drought. We found that three parameter sets derived from the measurement data reproduced the dynamics of 53% of an drought dataset, and 52% of a control dataset [root mean square error (RMSE) < 0.5 MPa)]. We conclude that, instead of quantifying water-potential-regulation of different plant species by complex modeling approaches, a small set of parameters may be sufficient to describe the water potential regulation behavior for large-scale modeling. Thus, our approach paves the way for a parsimonious representation of the full spectrum of plant hydraulic responses to drought in dynamic vegetation models.
Obtaining sufficient numbers of functional natural killer (NK) cells is crucial for the success of NK-cell-based adoptive immunotherapies. While expansion from peripheral blood (PB) is the current method of choice, ex vivo generation of NK cells from hematopoietic stem and progenitor cells (HSCs) may constitute an attractive alternative. Thereby, HSCs mobilized into peripheral blood (PB-CD34+) represent a valuable starting material, but the rather poor and donor-dependent differentiation of isolated PB-CD34+ cells into NK cells observed in earlier studies still represents a major hurdle. Here, we report a refined approach based on ex vivo culture of PB-CD34+ cells with optimized cytokine cocktails that reliably generates functionally mature NK cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. To further enhance NK cell expansion, we generated K562 feeder cells co-expressing 4-1BB ligand and membrane-anchored IL-15 and IL-21. Co-culture of PB-derived NK cells and NK cells that were ex-vivo-differentiated from HSCs with these feeder cells dramatically improved NK cell expansion, and fully compensated for donor-to-donor variability observed during only cytokine-based propagation. Our findings suggest mobilized PB-CD34+ cells expanded and differentiated according to this two-step protocol as a promising source for the generation of allogeneic NK cells for adoptive cancer immunotherapy.
Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity. Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1–22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected. Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred. Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.
Nightly selection of resting sites and group behavior reveal antipredator strategies in giraffe
(2020)
This study presents the first findings on nocturnal behavior patterns of wild Angolan giraffe. We characterized their nocturnal behavior and analyzed the influence of ecological factors such as group size, season, and habitat use. Giraffe were observed using night vision systems and thermal imaging cameras on Okapuka Ranch, Namibia. A total of 77 giraffe were observed during 24 nights over two distinct periods—July–August 2016 (dry season) and February–March 2017 (wet season). Photoperiod had a marked influence on their activity and moving behavior. At dusk, giraffe reduced the time spent moving and increasingly lay down and slept at the onset of darkness. Body postures that likely correspond to rapid eye movement (REM) sleep posture (RSP) were observed 15.8 ± 18.3 min after giraffe sat down. Season had a significant effect with longer RSP phases during the dry season (dry: 155.2 ± 191.1 s, n = 79; wet: 85.8 ± 94.9 s, n = 73). Further analyses of the influence of social behavior patterns did not show an effect of group size on RSP lengths. When a group of giraffe spent time at a specific resting site, several individuals were alert (vigilant) while other group members sat down or took up RSP. Simultaneous RSP events within a group were rarely observed. Resting sites were characterized by single trees or sparse bushes on open areas allowing for good visibility in a relatively sheltered location.
According to the free radical theory of aging, reactive oxygen species (ROS) have been proposed to be a major cause of aging for a long time. Meanwhile, it became clear that ROS have diverse functions in a healthy organism. They act as second messengers, and as transient inhibitors of phosphatases and others. In fact, their detrimental role is highly dependent on the context of their production. NADPH oxidases (Nox) have been discovered as a controllable source of ROS. NoxO1 enables constitutive ROS formation by Nox1 by acting as a constitutively active cytosolic subunit of the complex. We previously found that both Nox1 and NoxO1 were highly expressed in the colon, and that NoxO1-/- deficiency reduces colon health. We hypothesized that a healthy colon potentially contributes to longevity and NoxO1 deficiency would reduce lifetime, at least in mouse. In contrast, here we provide evidence that the knockout of NoxO1 results in an elongated life expectancy of mice. No better endothelial function, nor an improved expression of genes related to longevity, such as Sirt1, were found, and therefore may not serve as an explanation for a longer life in NoxO1 deficiency. Rather minor systemic differences, such as lower body weight occur. As a potential reason for longer life, we suggest better DNA repair capacity in NoxO1 deficient mice. Although final fatal DNA damage appears similar between wildtype and NoxO1 knockout animals, we identified less intermediate DNA damage in colon cells of NoxO1-/- mice, while the number of cells with intact DNA is elevated in NoxO1-/- colons. We conclude that NoxO1 deficiency prolongs lifetime of mice, which correlates with less intermediate and potentially fixable DNA damage at least in colon cells.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
In power systems, flow allocation (FA) methods enable to allocate the usage and costs of the transmission grid to each single market participant. Based on predefined assumptions, the power flow is split into isolated generator-specific or producer-specific sub-flows. Two prominent FA methods, Marginal Participation (MP) and Equivalent Bilateral Exchanges (EBEs), build upon the linearized power flow and thus on the Power Transfer Distribution Factors (PTDFs). Despite their intuitive and computationally efficient concepts, they are restricted to networks with passive transmission elements only. As soon as a significant number of controllable transmission elements, such as high-voltage direct current (HVDC) lines, operate in the system, they lose their applicability. This work reformulates the two methods in terms of Virtual Injection Patterns (VIPs), which allows one to efficiently introduce a shift parameter q to tune contributions of net sources and net sinks in the network. In this work, major properties and differences in the methods are pointed out, and it is shown how the MP and EBE algorithms can be applied to generic meshed AC-DC electricity grids: by introducing a pseudo-impedance ω¯ , which reflects the operational state of controllable elements and allows one to extend the PTDF matrix under the assumption of knowing the current flow in the system. Basic properties from graph theory are used to solve for the pseudo-impedance in dependence of the position within the network. This directly enables, e.g., HVDC lines to be considered in the MP and EBE algorithms. The extended methods are applied to a low-carbon European network model (PyPSA-EUR) with a spatial resolution of 181 nodes and an 18% transmission expansion compared to today’s total transmission capacity volume. The allocations of MP and EBE show that countries with high wind potentials profit most from the transmission grid expansion. Based on the average usage of transmission system expansion, a method of distributing operational and capital expenditures is proposed. In addition, it is shown how injections from renewable resources strongly drive country-to-country allocations and thus cross-border electricity flows.
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
Competition anxiety has been demonstrated to decrease sports performance while increasing burnout risk. To date, its degree in CrossFit (CF) is unknown. The present study, therefore, examines competition fear and relevant coping skills as well as potential correlates of both in individuals participating in CF events. A total of n = 79 athletes answered a battery of three questionnaires (competition fear index, athletic coping skills inventory, mindfulness attention awareness scale). Substantial levels of anxiety, particularly regarding the somatic dimension of the competition fear index, were reported. The most pronounced coping skill was freedom of worry. While age or level of competition showed no/very small associations with survey data, sex was correlated to the psychological characteristics: women reported higher competition fears and lower coping skill levels (p > 0.05). Competition fears are highly prevalent in CF athletes and the preventive value of population-specific interventions, particularly in females, should be investigated in future trials.
We study the influence of the baryon chemical potential μB on the properties of the Quark–Gluon–Plasma (QGP) in and out-of equilibrium. The description of the QGP in equilibrium is based on the effective propagators and couplings from the Dynamical QuasiParticle Model (DQPM) that is matched to reproduce the equation-of-state of the partonic system above the deconfinement temperature Tc from lattice Quantum Chromodynamics (QCD). We study the transport coefficients such as the ratio of shear viscosity η and bulk viscosity ζ over entropy density s, i.e., η/s and ζ/s in the (T,μ) plane and compare to other model results available at μB=0 . The out-of equilibrium study of the QGP is performed within the Parton–Hadron–String Dynamics (PHSD) transport approach extended in the partonic sector by explicitly calculating the total and differential partonic scattering cross sections based on the DQPM and the evaluated at actual temperature T and baryon chemical potential μB in each individual space-time cell where partonic scattering takes place. The traces of their μB dependences are investigated in different observables for symmetric Au + Au and asymmetric Cu + Au collisions such as rapidity and mT -distributions and directed and elliptic flow coefficients v1,v2 in the energy range 7.7 GeV ≤sNN−−−−√≤200 GeV.
Background: Body dysmorphic disorder (BDD) is characterized by an excessive preoccupation with one or more perceived flaws in one’s own appearance. Previous studies provided evidence for deficits in configural and holistic processing in BDD. Preliminary evidence suggests abnormalities at an early stage of visual processing. The present study is the first examining early neurocognitive perception of the own face in BDD by using electroencephalography (EEG). We investigated the face inversion effect, in which inverted (upside-down) faces are disproportionately poorly processed compared to upright faces. This effect reflects a disruption of configural and holistic processing, and in consequence a preponderance of featural face processing.
Methods: We recorded face-sensitive event-related potentials (ERPs) in 16 BDD patients and 16 healthy controls, all unmedicated. Participants viewed upright and inverted (upside-down) images of their own face and an unfamiliar other face, each in two facial emotional expressions (neutral vs. smiling). We calculated the early ERP components P100, N170, P200, N250, and the late positive component (LPC), and compared amplitudes among both groups.
Results: In the early P100, no face inversion effects were found in both groups. In the N170, both groups exhibited the common face inversion effects, with significantly larger N170 amplitudes for inverted than upright faces. In the P200, both groups exhibited larger inversion effects to other (relative to own) faces, with larger P200 amplitudes for other upright than inverted faces. In the N250, no significant group differences were found in face processing. In the LPC, both groups exhibited larger inversion effects to other (relative to own) faces, with larger LPC amplitudes for other inverted than upright faces. These overall patterns appeared to be comparable for both groups. Smaller inversion effects to own (relative to other) faces were observed in none of these components in BDD, relative to controls.
Conclusions: The findings suggest no evidence for abnormalities at all levels of early face processing in our observed sample of BDD patients. Further research should investigate the neural substrates underlying BDD symptomatology.
Die vorliegende Studie versucht einen Beitrag zur Erforschung von Implementationsmöglichkeiten des bilingualen Sprachvermögens von Schüler*innen mit Migrationshintergrund für den Regelschulkontext zu leisten, indem ein bilinguales Interaktionsangebot beim Peer-Learning für türkisch-deutschsprachig aufwachsende Schüler*innen der dritten und vierten Klasse in einem quasi-experimentellen Setting unter Verwendung von Mixed Methods untersucht wird.
This open access book presents a unique collection of practical examples from the field of pharma business management and research. It covers a wide range of topics such as: "Brexit and its Impact on pharmaceutical Law - Implications for Global Pharma Companies", "Implementation of Measures and Sustainable Actions to Improve Employee's Engagement", "Global Medical Clinical and Regulatory Affairs (GMCRA)", and "A Quality Management System for R&D Project and Portfolio Management in a Pharmaceutical Company".
The chapters are summaries of master’s theses by "high potential" Pharma MBA students from the Goethe Business School, Frankfurt/Main, Germany, with 8-10 years of work experience and are based on scientific know-how and real-world experience. The authors applied their interdisciplinary knowledge gained in 22 months of studies in the MBA program to selected practical themes drawn from their daily business.
We study how the Eurosystem Collateral Framework for corporate bonds helps the European Central Bank (ECB) fulfill its policy mandate. Using the ECBs eligibility list, we identify the first inclusion date of both bonds and issuers. We find that due to the increased supply and demand for pledgeable collateral following eligibility, (i) securities lending market trading activity increases, (ii) eligible bonds have lower yields, and (iii) the liquidity of newly-issued bonds declines, whereas the liquidity of older bonds is unaffected/improves. Corporate bond lending relaxes the constraint of limited collateral supply, thereby making the market more cohesive and complete. Following eligibility, bond-issuing firms reduce bank debt and expand corporate bond issuance, thus increasing overall debt size and extending maturity.
WiWi news [1/2020]
(2020)