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This article is directed towards addressing the employment related issues encountered by female workers in the gig economy in the EU. It revolves around analysing ‘the switch’ from the traditional labour market to the platform economy. It subsequently explains, by drawing comparisons, that the issues of gender inequality in the brick and mortar world are still prevalent in world of the digital platform. In fact, new challenges have emerged which are specifically related to the gig economy. Female workers are now affected by the inherent bias of algorithms. Moreover, due to the unequivocal propagation of ‘flexibility’ which is used as a weapon to glorify the gig economy; women are even more likely to be pushed into precarious work. The other prominent issues of gender inequality like the dynamics of intersectionality, the gender pay gap and hiring policies in traditional and digital platforms are also examined. Furthermore, the existing regulatory frameworks addressing these issues are discussed with the possibility of catering to the gender inequality issues in the gig economy through policy development. The article concludes with a reflection on the need for the EU to take immediate and efficacious policy measures in respect of female workers in the gig economy.
Motivated by the question of whether and how wave–wave interactions should be implemented into atmospheric gravity-wave parametrizations, the modulation of triadic gravity-wave interactions by a slowly varying and vertically sheared mean flow is considered for a non-rotating Boussinesq fluid with constant stratification. An analysis using a multiple-scale WKBJ (Wentzel–Kramers–Brillouin–Jeffreys) expansion identifies two distinct scaling regimes, a linear off-resonance regime, and a nonlinear near-resonance regime. Simplifying the near-resonance interaction equations allows for the construction of a parametrization for the triadic energy exchange which has been implemented into a one-dimensional WKBJ ray-tracing code. Theory and numerical implementation are validated for test cases where two wave trains generate a third wave train while spectrally passing through resonance. In various settings, of interacting vertical wavenumbers, mean-flow shear, and initial wave amplitudes, the WKBJ simulations are generally in good agreement with wave-resolving simulations. Both stronger mean-flow shear and smaller wave amplitudes suppress the energy exchange among a resonantly interacting triad. Experiments with mean-flow shear as strong as in the vicinity of atmospheric jets suggest that internal gravity-wave dynamics are dominated in such regions by wave modulation. However, triadic gravity-wave interactions are likely to be relevant in weakly sheared regions of the atmosphere.
With the emergence of immunotherapies, the understanding of functional HLA class I antigen presentation to T cells is more relevant than ever. Current knowledge on antigen presentation is based on decades of research in a wide variety of cell types with varying antigen presentation machinery (APM) expression patterns, proteomes and HLA haplotypes. This diversity complicates the establishment of individual APM contributions to antigen generation, selection and presentation. Therefore, we generated a novel Panel of APM Knockout Cell lines (PAKC) from the same genetic origin. After CRISPR/Cas9 genome-editing of ten individual APM components in a human cell line, we derived clonal cell lines and confirmed their knockout status and phenotype. We then show how PAKC will accelerate research on the functional interplay between APM components and their role in antigen generation and presentation. This will lead to improved understanding of peptide-specific T cell responses in infection, cancer and autoimmunity.
Cancer is the major cause of death besides cardiovascular disease. Leukaemia represents the most prevalent malignancy in children with a frequency of 30 % and is one of the ten leading types of cancer in adults. Philadelphia Chromosome-positive B-ALL (Ph+ B-ALL) is driven by the cytogenetic aberration of the reciprocal chromosomal translocation t(9;22)(q34;q11) leading to the formation of the Philadelphia chromosome with a BCR-ABL1 fusion gene. This fusion gene encodes a BCR-ABL1 oncoprotein which is characterized by a constitutively enhanced tyrosine kinase activity promoting amplified proliferation, differentiation arrest and resistance to cell death. Ph+ B-ALL is considered the most aggressive ALL subtype with a long-term survival rate in the range of only 30 % despite intensive standard of care including chemotherapy in combination with a tyrosine kinase inhibitor (TKI) followed by allogeneic stem cell transplantation after remission for clinically fit patients.
The efficacy of chemotherapy has long been mainly attributed to tumour cell toxicity while immune modulating effects have been overlooked, especially in light of known immunosuppressive properties. Accumulative evidence, however, emphasizes the ability of chemotherapeutic agents, including TKIs, to normalise or re-educate a dysfunctional tumour microenvironment (TME) resulting in enhanced anti-tumour immunity. One of the underlying mechanisms of immune modulation is the induction of immunogenic cell death (ICD). ICD is an anti-tumour agent-induced cell death modality determined by the capacity to convert cancer cells into anti-cancer vaccines. The induction of ICD relies on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells succumbing to ICD. Translocation of CALR to the cell surface, extracellular secretion of ATP and release of HMGB1 from the nucleus are key hallmarks of ICD that mediate anti-tumour immunity upon binding to antigen presenting cells resulting in a tumour antigen-specific immune response. Besides these molecular determinants, ICD is functionally defined by the inhibition of tumour growth in a vaccination assay in which mice are injected with tumour cells exposed to the potential ICD inducer in-vitro and then re-challenged with live tumour cells of the same cancer type. Both molecular and functional criteria determine the gold standard approach to assess ICD. By increasing the immunogenicity of cancer cells, ICD contributes to the restoration of immunosurveillance as an essential feature of tumour rejection, which is clinically reflected by improved therapeutic efficacy and disease outcome in patients. Therefore, identifying novel ICD inducers is an objective of interest in the context of cancer therapy.
In respect of these considerations, the aim addressed in the present work is the examination of the second-generation TKI Nilotinib for the ability to induce ICD. The thesis is set in the context of the group's research on the role of Gas6/TAM signalling within the TME regarding the pathogenesis of acute leukaemia. In in-vivo experiments of our research group it has been consistently observed that the use of Nilotinib enhances the anti-leukaemic immunity mediated by a deletion of Gas6. Against the background of increasing importance of chemotherapeutic agents as potent modulators of a dysregulated TME, it was hypothesized that Nilotinib may synergize with a Gas6-deficient environment by inducing ICD in Ph+ B-ALL cells.
In growth inhibition and Annexin V/Propidium iodide cell death assays Nilotinib was shown to induce cell death in concentration-dependent manner that occurs bimodally in terms of cell death modality ranging between apoptosis and necrosis. By ICD marker analysis, comprising flow-cytometric detection of CALR exposure, chemoluminescence-based ATP measurement and immunoblotting for HMGB1, it was found that Nilotinib-induced cell death is not accompanied by CALR exposure and ATP secretion, but is associated with the release of HMGB1. In macrophages co-culture experiments with Nilotinib-treated leukaemic cells, no relevant shift in terms of macrophages activation and polarisation was observed in either a juxtacrine or paracrine setup. In consistency with the results obtained in the in-vitro experiments, Nilotinib was not potent to elicit a protective immune response in mice within a vaccination assay.
Conclusively, Nilotinib was identified to not qualify as bona fide ICD inducer. The role of Nilotinib-induced cell death and HMGB1 release are proposed as objective for further investigation concerning the synergistic interplay between Nilotinib and a Gas6-deficient environment. Efforts addressing exploration and optimisation of the immunological potential of chemotherapeutic agents are a promising approach aimed at providing cancer patients with the best possible treatment in future.
The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
This paper contributes to the clarification of the concept of “typicality” discussed in contemporary philosophy of physics by conceiving the nomological status of a typical behaviour such as that expressed in the Second Law of Thermodynamics as a “minutis rectis law”. A brief sketch of the discovery of “typicality” shows that there were ideas of typical behaviour not only in physics but also in sociology. On this basis and in analogy to the Second Law of Thermodynamics, it is shown that the nomological status of sociological laws such as Gresham’s Law can also be conceived as “minutis rectis laws”.
The nuclear factor kappa beta (NFκB) signaling pathway plays an important role in liver homeostasis and cancer development. Tax1-binding protein 1 (Tax1BP1) is a regulator of the NFκB signaling pathway, but its role in the liver and hepatocellular carcinoma (HCC) is presently unknown. Here we investigated the role of Tax1BP1 in liver cells and murine models of HCC and liver fibrosis. We applied the diethylnitrosamine (DEN) model of experimental hepatocarcinogenesis in Tax1BP1+/+ and Tax1BP1−/− mice. The amount and subsets of non-parenchymal liver cells in in Tax1BP1+/+ and Tax1BP1−/− mice were determined and activation of NFκB and stress induced signaling pathways were assessed. Differential expression of mRNA and miRNA was determined. Tax1BP1−/− mice showed increased numbers of inflammatory cells in the liver. Furthermore, a sustained activation of the NFκB signaling pathway was found in hepatocytes as well as increased transcription of proinflammatory cytokines in isolated Kupffer cells from Tax1BP1−/− mice. Several differentially expressed mRNAs and miRNAs in livers of Tax1BP1−/− mice were found, which are regulators of inflammation or are involved in cancer development or progression. Furthermore, Tax1BP1−/− mice developed more HCCs than their Tax1BP1+/+ littermates. We conclude that Tax1BP1 protects from liver cancer development by limiting proinflammatory signaling.
This article problematizes the assumption that national policies have a direct impact on youth participation at the local level and analyses the relationships between local forms of youth participation and local and national policies. Relying on data from a EU project funded under the HORIZON 2020 programme, the article focuses on formally institutionalized settings of youth participation and elaborates local constellations of youth participation in six European cities. These constellations may be referred to as regimes of youth participation as they reflect wider structures of power and knowledge that influence the way in which young people’s practices in public spaces and their claims of being part of society are recognized. However, the analysis reveals that rather deducing it from the model of welfare regimes, such a typology needs to be developed starting from the local level and should consider the ways in which different relationships between local youth policies and national welfare states affect youth participation.
Rationale: Bronchiolitis obliterans syndrome (BOS) is a severe, chronic inflammation of the airways leading to an obstruction of the bronchioles. So far, there are only a few studies looking at the long‐term development of pulmonary impairment in children with BOS.
Objective: The objective of this study was to investigate the incidence and long‐term outcome of BOS in children who underwent allogeneic hematopoietic stem cell transplantation (HSCT).
Methods: Medical charts of 526 children undergoing HSCT in Frankfurt/Main, Germany between 2000 and 2017 were analyzed retrospectively and as a result, 14 patients with BOS were identified. A total of 271 lung functions (spirometry and body plethysmography), 26 lung clearance indices (LCI), and 46 chest high‐resolution computed tomography (HRCT) of these 14 patients with BOS were evaluated.
Results: Fourteen patients suffered from BOS after HSCT (2.7%), whereby three distinctive patterns of lung function impairment were observed: three out of 14 patients showed a progressive lung function decline; two died and one received a lung transplant. In five out of 14 patients with BOS persisted with a severe obstructive and secondarily restrictive pattern in lung function (forced vital capacity [FVC] < 60%, forced expiratory volume in 1 second [FEV1] < 50%, and FEV1/FVC < 0.7) and increased LCI (11.67‐20.9), six out of 14 patients recovered completely after moderate lung function impairment and signs of BOS on HRCT. Long‐term FVC in absolute numbers was increased indicating that the children still have lung growth.
Conclusion: Our results showed that the incidence of BOS in children is low. BOS was associated with high mortality and may lead to persistent obstructive lung disease; although, lung growth continued to exist.
“Protection of the environment“ and “sustainability“ are more significant than ever. The legal system contributes an important share to the protection of the environment. However, an overview of the German private environmental liability law shows that conventional tort law is not a suitable basis for civil liability for the environmental consequences of officially approved emissions of greenhouse gases. In general, one of the main problems of private environmental liability law lies in proving the individual causality of the conduct of an emitter, as the lawsuit of a Peruvian homeowner against a German energy company pending before the Higher Regional Court of Hamm illustratively demonstrates. The outcome of this lawsuit, which may have an outstanding significance for the status and development of private environmental liability law in Germany, is awaited with great anticipation. The article also briefly examines recent developments in private environmental liability law outside Germany and the question to what extent insurance can be an instrument to protect the environment.
This paper analyses disclosure duties in insurance contract law in Germany on the basis of questions developed in preparation of the World Congress of the International Insurance Law Association (AIDA) 2018. As risk factors are within the policyholder’s sphere of knowledge, the insurer naturally depends on gaining such knowledge from its policyholder in order to calculate and evaluate premium and risk. Legal approaches as to how the insurer may obtain relevant information and the legal consequences differ in national insurance contract laws around the globe. Taking part in this legal comparison, the paper describes the key elements of such a mechanism from a German perspective and comprises both duties of the policyholder and duties of the insurer.
As for the policyholder, these issues are differences between a duty to (spontaneously) disclose and a duty not to misrepresent as a reaction to questions of the insurer, the prerequisites and remedies of such duty, the subjective standard of the disclosure duty and a duty to notify material changes during the contract term. On the other hand, the paper also addresses an insurer’s duty to investigate, a duty to ascertain the policyholder’s understanding of the policy and a duty to inform during the contract term or after the occurrence of an insured event. In doing so, the paper offers a comprehensive and critical overview on the transfer of knowledge in the insurance (pre-)contractual relationship.
On eight species of the spider genus Synagelides Strand, 1906 from China (Araneae: Salticidae)
(2020)
Six new species of Synagelides Strand, 1906 are diagnosed and described: S. bohdanowiczi sp. nov. (♂♀), S. leigongensis sp. nov. (♂♀), S. logunovi sp. nov. (♂♀), S. subgambosus sp. nov. (♂♀), S. wuliangensis sp. nov. (♂♀) and S. xingdouensis sp. nov. (♂♀). The female of S. forkiforma Yang, Zhu & Song, 2007 and the male of S. longus Song & Chai, 1992 are described for the first time. Photos of the habitus and copulatory organs, as well as a distributional map, are provided.
Five new species of Meta Koch, 1836 (Araneae: Tetragnathidae) from Gaoligong Mountains, China
(2020)
Five new species of the genus Meta C.L. Koch, 1836 from the Gongligong Mountains, Yunnan are described: Meta hamata sp. nov. (♂♀), M. longlingensis sp. nov. (♂), M. tangi sp. nov. (♂♀), M. yani sp. nov. (♂♀) and M. yinae sp. nov. (♂♀). Detailed descriptions of somatic features and genitalic characters, photos of the body and genital organs, line drawings of the copulatory organs and distribution maps are provided.
Synaptic plasticity is the activity dependent alteration of the composition, form and strength of synapses and believed to be the underlying mechanism of learning and memory formation. While initial changes in synaptic transmission are caused by second messenger signaling pathways and rapid modifications in the cytoskeleton, to achieve stable and persistent changes at individual synapses, the expression of new mRNAs and proteins is required. The central dogma postulated that the cell body is the only source of newly synthesized proteins. For neurons, with their unique morphology, this meant that proteins would need be transported long distances, often hundreds of microns, to reach their destined locations in dendrites and at spines. To overcome this limitation, neurons have developed a strategy to regulate protein synthesis locally by distributing thousands of mRNAs into neuronal processes and use them for local protein synthesis. Ample research has demonstrated the importance of local protein synthesis to many forms of long-term synaptic plasticity. One potential regulator of mRNA localization and local translation in neurons are non-coding RNAs. Intensive work over the past decades has highlighted the importance of non-coding RNAs in many aspects of brain function. The aim of this thesis is to obtain a better understanding of the role of non-coding RNAs in synaptic function and plasticity in the murine hippocampus. For this, we focused our studies on two classes of non-coding RNAs.
In the first part of my thesis, I describe our efforts on characterizing circular RNAs, a novel and peculiar family of non-coding RNAs, in the murine hippocampus by combining high throughput RNA-Sequencing with fluorescence in situ hybridization. Furthermore, we investigated the mechanisms of circular RNA biogenesis in hippocampal neurons by temporarily inhibiting spliceosome activity and analyzing the differentially regulated circular RNAs.
A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog, but how it occurs in cities is often puzzling. If the growth rates of urban particles are similar to those found in cleaner environments (1–10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below −15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid–base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms.
This article reports an investigation of how inhibition contributes to fluid reasoning when it is decomposed into the reasoning ability, item-position, and speed components to control for possible method effects. Working memory was also taken into consideration. A sample of 223 university students completed a fluid reasoning scale, two tasks tapping prepotent response inhibition, and two working memory tasks. Fixed-links modeling was used to separate the effect of reasoning ability from the effects of item-position and speed. The goodness-of-fit results confirmed the necessity to consider the reasoning ability, item-position, and speed components simultaneously. Prepotent response inhibition was only associated with reasoning ability. This association disappeared when working memory served as a mediator. Taken together, these results reflect the inhomogeneity of what is tapped by the fluid reasoning scale on one hand and, on the other, suggest inhibition as an important component of working memory.
All extant species of the planthopper genus Limois Stål (Hemiptera: Fulgoromorpha: Fulgoridae) were studied. One new species, Limois sordida sp. nov., is described and illustrated from China. Six known species are re-described and photos and illustrations of male genitalia are provided. A key to all extant species of this genus is also given.
One individual referable to Calliopiidae G.O. Sars, 1893 was collected from a chemically reduced habitat, the hydrothermal vent systems in Okinawa Trough, and was identified as a new genus and species belonging to this family after a morphological examination. A formal description of this new species and a discussion of the relationship of the new genus within Calliopiidae are presented.
New species of Trachyderini from Mexico and Central America (Coleoptera: Cerambycidae: Cerambycinae)
(2020)
Three new trachyderine species in the subtribe Trachyderina (Coleoptera: Cerambycidae: Cerambycinae: Trachyderini) are described: Entomosterna kovariki Wappes and Santos-Silva, new species, from Belize; Gortonia sumideroensis Wappes and Santos-Silva, new species, from Mexico (Chiapas); and Sphaenothecus vandenberghei Wappes and Santos-Silva, new species, from Nicaragua. A new key to Entomosterna species, and a previous Sphaenothecus key by Chemsak and Noguera (1998) is modified to include the new species, with both provided herein.