julilili42/papers huggingface dataset:
Functional and structural characterization of PII‐like protein CutA does not support involvement in heavy metal tolerance and hints at a small‐molecule carrying/signaling role
2020-06-29

The PII‐like protein CutA is annotated as being involved in Cu 2+ tolerance, based on analysis of Escherichia coli mutants. However, the precise cellular function of CutA remains unclear. Our bioinformatic analysis reveals that CutA proteins are universally distributed across all domains of life. Based on sequence‐based clustering, we chose representative cyanobacterial CutA proteins for physiological, biochemical, and structural characterization and examined their involvement in heavy metal tolerance, by generating CutA mutants in filamentous Nostoc sp. and in unicellular Synechococcus elongatus . However, we were unable to find any involvement of cyanobacterial CutA in metal tolerance under various conditions. This prompted us to re‐examine experimentally the role of CutA in protecting E. coli from Cu 2+ . Since we found no effect on copper tolerance, we conclude that CutA plays a different role that is not involved in metal protection. We resolved high‐resolution CutA structures from Nostoc and S. elongatus . Similarly to their counterpart from E. coli and to canonical PII proteins, cyanobacterial CutA proteins are trimeric in solution and in crystal structure; however, no binding affinity for small signaling molecules or for Cu 2+ could be detected. The clefts between the CutA subunits, corresponding to the binding pockets of PII proteins, are formed by conserved aromatic and charged residues, suggesting a conserved binding/signaling function for CutA. In fact, we find binding of organic Bis‐Tris/MES molecules in CutA crystal structures, revealing a strong tendency of these pockets to accommodate cargo. This highlights the need to search for the potential physiological ligands and for their signaling functions upon binding to CutA. Databases Structural data are available in Protein Data Bank (PDB) under the accession numbers 6GDU , 6GDV , 6GDW , 6GDX , 6T76 , and 6T7E .
Psychosocial stress reactivity habituates following acute physiological stress
2020-06-29

Abstract Acute and chronic stress are important factors in the development of mental disorders. Reliable measurement of stress reactivity is therefore pivotal. Critically, experimental induction of stress often involves multiple “hits” and it is an open question whether individual differences in responses to an earlier stressor lead to habituation, sensitization, or simple additive effects on following events. Here, we investigated the effect of the individual cortisol response to intravenous catheter placement (IVP) on subsequent neural, psychological, endocrine, and autonomous stress reactivity. We used an established psychosocial stress paradigm to measure the acute stress response ( Stress ) and recovery ( PostStress ) in 65 participants. Higher IVP‐induced cortisol responses were associated with lower pulse rate increases during stress recovery ( b = −4.8 bpm, p = .0008) and lower increases in negative affect after the task ( b = −4.2, p = .040). While the cortisol response to IVP was not associated with subsequent specific stress‐induced neural activation patterns, the similarity of brain responses Pre‐ and PostStress was higher IVP‐cortisol responders ( t [64] = 2.35, p = .022) indicating faster recovery. In conclusion, preparatory stress induced by IVP reduced reactivity in a subsequent stress task by modulating the latency of stress recovery. Thus, an individually stronger preceding release of cortisol may attenuate a second physiological response and perceived stress suggesting that relative changes, not absolute levels are crucial for stress attribution. Our study highlights that considering the entire trajectory of stress induction during an experiment is important to develop reliable individual biomarkers.
Assisting students’ writing with computer-based concept map feedback: A validation study of the CohViz feedback system
2020-06-29

CohViz is a feedback system that provides students with concept maps as feedback on the cohesion of their writing. Although previous studies demonstrated the effectiveness of CohViz, the accuracy of CohViz remains unclear. Thus, we conducted two comprehensive validation studies to assess the accuracy of CohViz in terms of its reliability and validity. In a reliability study, we compared the concept maps generated by CohViz with concept maps generated by four human expert raters based on a text corpus comprising students' explanatory texts (N = 100). Regarding the depiction of cohesion gaps, we obtained high accordance between the CohViz concept maps and the concept maps generated by the human expert raters. However, CohViz tended to overestimate the number of relations within the concept maps. In a validity study, we examined the validity of CohViz and compared central features of the CohViz concept maps with convergent linguistic features and divergent linguistic features based on a Wikipedia text corpus (N = 1020). We found medium to high agreement with the convergent cohesion features and low agreement with the divergent features. Together, these findings suggest that CohViz can be regarded as an accurate feedback system to provide feedback on the cohesion of students' writing.
Hybrid Modelling of Transarterial Chemoembolisation Therapies (TACE) for Hepatocellular Carcinoma (HCC)
2020-06-29

Abstract We extend an agent-based multiscale model of vascular tumour growth and angiogenesis to describe transarterial chemoembolisation (TACE) therapies. The model accounts for tumour and normal cells that are both nested in a vascular system that changes its structure according to tumour-related growth factors. Oxygen promotes nutrients to the tissue and determines cell proliferation or death rates. Within the extended model TACE is included as a two-step process: First, the purely mechanical influence of the embolisation therapy is modelled by a local occlusion of the tumour vasculature. There we distinguish between partial and complete responders, where parts of the vascular system are occluded for the first and the whole tumour vasculature is destroyed for the latter. In the second part of the model, drug eluding beads (DEBs) carrying the chemotherapeutic drug doxorubicin are located at destroyed vascular locations, releasing the drug over a certain time-window. Simulation results are parameterised to qualitatively reproduce clinical observations. Patients that undergo a TACE-treatment are categorised in partial and complete responders one day after the treatment. Another 90 days later reoccurance or complete response are detected by volume perfusion computer tomography (VPCT). Our simulations reveal that directly after a TACE- treatment an unstable tumour state can be observed, where regrowth and total tumour death have the same likeliness. It is argued that this short time-window is favorable for another therapeutical intervention with a less radical therapy. This procedure can shift the outcome to more effectiveness. Simulation results with an oxygen therapy within the unstable time-window demonstrate a potentially positive manipulated outcome. Finally, we conclude that our TACE model can motivate new therapeutical strategies and help clinicians analyse the intertwined relations and cross-links in tumours.
Simultaneous Monitoring of Molecular Thin Film Morphology and Crystal Structure by X-ray Scattering
2020-06-29

Hybrid materials of π-conjugated molecular semiconductors combined with two-dimensional (2D) materials exhibit a significant potential for novel (opto)electronics. The overall characteristics of molecular growth, such as molecular packing, crystallographic structure, and morphology, determine the specific application. The growth studies are thus key for understanding and improving these systems. So far, a simultaneous real-time study of the thin film morphology evolution along with its crystalline phase on a 2D substrate has not been performed. Here, we report on an additional feature of surface-sensitive grazing-incidence wide-angle X-ray scattering (GIWAXS). We show that refraction induced multiple scattering effects can be employed to reveal the morphology-related growth modes of a thin organic layer on a 2D underlayer together with the crystallographic structure and molecular orientation. A thorough description of the dynamic scattering effects is provided, allowing a detailed study of the Bragg peak splitting in the out-of-plane direction. We discuss the influence of the material-related parameters, such as stress and growth type, on the mutual position of the split peaks during the growth. Furthermore, we show that the time-resolved GIWAXS enables the observation of the electron density variation in real time. Our findings should be considered as a general feature of GIWAXS that can be applied to various types of thin films, where the temporal evolution of morphology, molecular arrangement, and crystallographic structure are of interest.
Rare genital malformations in women’s health research: sociodemographic, regional, and disease-related characteristics of patients with Mayer-Rokitansky-Küster-Hauser syndrome
2020-06-29

Abstract Background The Mayer-Rokitansky-Küster-Hauser syndrome, MRKHS, is a rare (orphan) disease characterized by the aplasia or hypoplasia of the uterus and the vagina. In women's health research, little is known as to how much care provision for patients with MRKHS takes into account their socio-demographic together with their clinical characteristics. This work examines the patients’ socio-demographic characteristics, highlighting issues of inappropriate and deficient provision of care. Methods The study was carried out as part of the larger TransCareO project and included a group of N =129 MRKHS patients who underwent surgery between 2008 and 2012. Using a specially developed questionnaire, we analyzed MRKHS patients’ data found both in the clinical documentation of the Department for Women's Health, University Hospital of Tübingen and the patient surveys of the Center for Rare Genital Malformations (CRGM/ ZSGF). Patients who took part in interviews were compared with non-respondents. Results Patient respondents and non-respondents did not differ as to the parameters of interest. In most cases, primary amenorrhea was reported as an admission reason. In 24% of patients, a medical intervention (hymenal incision or hormone treatment) already occurred before admission to the Center in Tübingen and proper diagnosis of MRKHS. About one third received in advance inappropriate treatment. During the therapy, more than half of the patients were in a solid partnership. 10% of the family anamneses documented the occurrence of urogenital malformations. Conclusions Care provision for MRKHS patients is largely characterized by delayed proper diagnosis and in part, by inappropriate treatment attempts; there are also indications of regional differences. Anamnestic clues such as an asymptomatic amenorrhea or renal abnormalities of unclear origin still fail to result early enough in referral to a center on the basis of suspected MRKHS diagnosis. Urogenital malformations in the family are more common in patients than in the general population. For patients, a wide range of burdens are associated with the diagnosis. Abnormalities compared to their female peers occur, for instance, in the partnership status: MRKHS patients have more rarely a partner.
The reaction of imidazo[1,5-a]pyridines with ninhydrin revisited
2020-06-29

Abstract The synthesis of 2,2′-(Imidazo[1,5- a ]pyridine-1,3-diyl)bis(2-hydroxy-1 H -indene-1,3(2 H )-dione) ( 11 ) is achieved by reaction of imidazo[1,5- a ]pyridine ( 7 ) with two equivalents of ninhydrin ( 1 ) at room temperature. The structure of this new 1,3-bis-adduct 11 is evidenced from HRMS and NMR spectral data and confirmed by single-crystal X-ray crystallography. Employment of equimolar amounts of 1 and 7 gave a separable mixture of the respective 1- and 3-monomeric adducts ( 9 , 10 ).
Revision of the occurrence of muskox (Ovibos moschatus Zimmermann 1780) from the Gravettian of Arbreda Cave (Serinyà, northeastern Iberian Peninsula): new insights for the study of Iberian cold‐adapted faunas
2020-06-29

During the Last Glacial cycle ( MIS 4 to MIS 2), the isthmic Pyrenees mountain range acted as a biogeographical barrier, effectively restricting faunal exchanges to its western and eastern terminations. The study of the composition of megaherbivore communities has revealed the transitional character of the Cantabrian region (northwest Iberian Peninsula) during the MIS 3, between western European cold faunas and southern Iberian temperate faunas. In the Catalan area (northeastern Iberian Peninsula), cold‐adapted faunas are frequently recorded during the cold pulses of MIS 3 and MIS 2, albeit to a lesser extent. In the present paper, we provide the first direct evidence of a muskox record in the Iberian Peninsula, together with a morphometric study and the results of collagen δ 13 C and δ 15 N analysis. The results reveal that the Arbreda specimen fits biometrically within the Late Holocene Umingmak specimens (Banks Island, Canada). Moreover, its isotopic values fall into the range of Late Pleistocene Mammoth steppe muskoxen, which indicates a typical ecological behaviour for muskox. Indeed, it suggests a niche partitioning of this cold‐adapted specimen in relation to other Gravettian Iberian fauna. Chronologically, this occurrence is interpreted as an isolated southward expansion of the biogeographical limits of muskox during the Greenland Stadial 4, in the latest MIS 3.
A shortcut in forward genetics: concurrent discovery of mutant phenotype and causal mutation in Arabidopsis M2 families via MAD-mapping
2020-06-29

ABSTRACT Forward genetics is a powerful tool to establish phenotype-genotype correlations in virtually all areas of plant biology and has been particularly successful in the model plant Arabidopsis. This approach typically starts with a phenotype in an M2 mutant, followed by identifying a causal DNA change in F2 populations resulting from a cross between the mutant and a wildtype individual. Ultimately, two additional generations are needed to pinpoint causal DNA changes upon mutant identification. We postulated that genome-wide allele frequency distributions within the mutants of M2 families facilitate discrimination of causal versus non-causal mutations, essentially eliminating the need for F2 populations. In a proof-of-principle experiment, we aimed to identify signalling components employed by the executor-type resistance ( R ) protein, Bs4C, from pepper ( Capsicum pubescens ). In a native setting, Bs4C is transcriptionally activated by and mediates recognition of the transcription activator-like effector AvrBs4 from the bacterial pathogen Xanthomonas . Arabidopsis containing an estradiol-inducible Bs4C transgene was used in a conditionally lethal screen to identify second-site suppressor mutations. Whole genome sequencing was used for M 2 mutant a llele-frequency d istribution (MAD) mapping in three independent M2 families. MAD-mapping uncovered that all three families harboured mutations in XRN4 , a novel component of executor R protein pathways. Our work demonstrates that causal mutations observed in forward genetic screens can be identified immediately in M2 families instead of derived F2 families. Notably, the timesaving concept of MAD mapping should be applicable to most crop species and will advance the appeal of forward genetics beyond applications in fundamental research. SIGNIFICANCE Forward genetics has uncovered numerous genes that govern plant immune reactions. This procedure relies on mutant plants with modified immune reactions followed by identification of causal DNA changes in derived F2 progeny. We developed a novel forward genetics concept where causal DNA changes are identified in the initial M2 mutants, making time consuming establishment of F2 populations obsolete. To confirm the feasibility of the concept, we mutagenized transgenic Arabidopsis seeds containing the cell death executing resistance gene Bs4C from pepper. Whole-genome sequencing of identified mutant families that lack a Bs4C -dependent cell death revealed the XRN4 gene as a novel component of Bs4C -dependent cell death. This confirms our hypothesis that causal mutations can be identified directly within phenotypically selected mutant families.
The More Economic Judicature: How the General Court has Recalibrated the Merger Gauge
2020-06-29

In its judgment of May 28, 2020, CK Telecoms UK Investments Ltd v. Commission, the EU General Court (GC) has made several fundamental observations on the construal of the SIEC-test with regard to horizontal mergers. The GC embraces a more economic approach, while tightening the standard of proof, and demanding stricter and more coherent principles for the concepts of closeness of competition, and of important competitive force. With respect to the analysis of upward pricing pressures (UPP), the judgment calls for a differentiated analysis of efficiencies within the framework of the theory of harm, rather than considering efficiencies solely as a defense. In our article, we conclude that the judgment should be endorsed for identifying weak spots in the current enforcement architecture, and for providing convincing approaches for a recalibration of the SIEC test.
The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation
2020-06-30

Abstract The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.
Vowel deletion in two Aymara varieties
2020-06-30

Aymara vowels delete under predictable phonotactic, syntactic, and morphophonemic conditions. We provide a detailed description of each of these processes, with special attention to morphophonemic vowel deletion. In this process, specific suffixes trigger the deletion of the preceding vowel, with no obvious phonological or semantic conditioning. This is both the most common type of vowel deletion in Aymara, and the most unusual one in cross-linguistic terms. We compare vowel deletion in Contemporary Aymara (Coler 2014) and Historical Aymara as attested in the 17th century (e.g. Bertonio 1612a) and reveal that both varieties delete vowels as a result of processes arising from phonotactic and morphophonemic motivation, though some processes of syntactic vowel deletion were not widespread in the historical variety. Notably, while morphophonemic vowel deletion was attested in both Contemporary and Historical Aymara, the suffixes which are lexically pre-specified to delete the preceding vowel are often different in the two varieties. Further, Historical Aymara lacks accusative inflection marking with subtractive disfixation, which is an important and typologically unusual aspect of Contemporary Aymara nominal morphology. In light of the typological rarity of morphophonemic vowel deletion (and disfixation in particular), we expect this description to be of interest to typologists.
Determining the Pace and Magnitude of Lake Level Changes in Southern Ethiopia Over the Last 20,000 Years Using Lake Balance Modeling and SEBAL
2020-06-30

The Ethiopian rift is known for its diverse landscape, ranging from arid and semi-arid savannahs to high and humid mountainous regions. Lacustrine sediments and paleo-shorelines indicate water availability fluctuated dramatically from deep fresh water lakes, to shallow highly alkaline lakes, to completely desiccated lakes. To investigate the role lakes have played through time as readily available water sources to humans, an enhanced knowledge of the pace, character and magnitude of these changes is essential. Hydro-balance models are used to calculate paleo-precipitation rates and the potential pace of lake level changes. However, previous models did not consider changes in hydrological connectivity during humid periods in the rift system, which may have led to an overestimation of paleo-precipitation rates. Here we present a comprehensive hydro-balance modeling approach that simulates multiple rift lakes from the southern Ethiopian Rift (lakes Abaya, Chamo, and paleo-lake Chew Bahir) simultaneously, considering their temporal hydrological connectivity during high stands of the African Humid Period (AHP, ~15–5 ka). We further used the Surface Energy Balance Algorithm for Land (SEBAL) to calculate the evaporation of paleo-lake Chew Bahir's catchment. We also considered the possibility of an additional rainy season during the AHP as previously suggested by numerous studies. The results suggest that an increase in precipitation of 20–30% throughout the southern Ethiopian Rift is necessary to fill paleo-lake Chew Bahir to its overflow level. Furthermore, it was demonstrated that paleo-lake Chew Bahir was highly dependent on the water supply from the upper lakes Abaya and Chamo and dries out within ~40 years if the hydrological connection is cut off and the precipitation amount decreases to present day conditions. Several of such rapid lake level fluctuations, from a freshwater to a saline lake, might have occurred during the termination of the AHP, when humid conditions were less stable. Fast changes in fresh water availability requires high adaptability for humans living in the area and might have exerted severe environmental stress on humans in a sub-generational timescale.
Enhanced two-photon photoluminescence assisted by multi-resonant characteristics of a gold nanocylinder
2020-06-30

Abstract Multi-resonant plasmonic simple geometries like nanocylinders and nanorods are highly interesting for two-photon photoluminescence and second harmonic generation applications, due to their easy fabrication and reproducibility in comparison with complex multi-resonant systems like dimers or nanoclusters. We demonstrate experimentally that by using a simple gold nanocylinder we can achieve a double resonantly enhanced two-photon photoluminescence of quantum dots, by matching the excitation wavelength of the quantum dots with a dipolar plasmon mode, while the emission is coupled with a radiative quadrupolar mode. We establish a method to separate experimentally the enhancement factor at the excitation and at the emission wavelengths for this double resonant system. The sensitivity of the spectral positions of the dipolar and quadrupolar plasmon resonances to the ellipticity of the nanocylinders and its impact on the two-photon photoluminescence enhancement are discussed.