julilili42/papers huggingface dataset:
Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver
2022-07-26

Abstract Activation of the constitutive androstane receptor (CAR) may induce adaptive but also adverse effects in rodent liver, including the induction of drug-metabolizing enzymes, transient hepatocellular proliferation, and promotion of liver tumor growth. Human relevance of CAR-related adverse hepatic effects is controversially debated. Here, we used the chimeric FRG-KO mouse model with livers largely repopulated by human hepatocytes, in order to study human hepatocytes and their response to treatment with the model CAR activator phenobarbital (PB) in vivo. Mice received an intraperitoneal injection with 50 mg/kg body weight PB or saline, and were sacrificed after 72–144 h. Non-repopulated FRG-KO mice were used as additional control. Comprehensive proteomics datasets were generated by merging data obtained by targeted as well as non-targeted proteomics approaches. For the first time, a novel proteomics workflow was established to comparatively analyze the effects of PB on human and murine proteins within one sample. Analysis of merged proteome data sets and bioinformatics data mining revealed comparable responses in murine and human hepatocytes with respect to nuclear receptor activation and induction of xenobiotic metabolism. By contrast, activation of MYC, a key regulator of proliferation, was predicted only for mouse but not human hepatocytes. Analyses of 5-bromo-2′-deoxyuridine incorporation confirmed this finding. In summary, this study for the first time presents a comprehensive proteomic analysis of CAR-dependent effects in human and mouse hepatocytes from humanized FRG-KO mice. The data support the hypothesis that PB does induce adaptive metabolic responses, but not hepatocellular proliferation in human hepatocytes in vivo.
Diversity by Design?
2022-07-26

The unreflected promotion of diversity as a value in social interactions --- including in technology-mediated ones --- risks emphasizing the benefits of inclusion without recognizing the potential harm of failing to protect vulnerable individuals or account for the empowerment of marginalized groups. Adopting the position that technology is not value-neutral, we seek to answer the question of how technology-mediated social platforms can accommodate diversity by design by balancing the often tension-ridden principles of protection and inclusion. In this paper, we present our research program, developed strategy, as well as first analyses and results. Building on approaches from scenario analysis and Value Sensitive Design, we identify key arguments for a "diversity by design''-agenda. Furthermore, we discuss how these arguments can be operationalized and implemented in a diversity-aware chatbot and provide a critical reflection on the limits and drawbacks of the proposed approach.
Northward expansion of the westerlies over glacial southeastern Australia: evidence from semi-arid lunette dunes, temperate basalt plains, and wind modelling
2022-07-26

It has long been hypothesized that the last glacial maximum (LGM) oversaw cold, arid, windy climates across southern Australia, and that these were driven by intensification and northward expansion of mid-latitude westerly circulation. Moreover, it was recently suggested that Australia experienced an extended LGM which began several millennia before the global peak. Aeolian sedimentary deposits provide key evidence for these hypotheses, and climate modelling an alternative means to test them. As yet, however, combined approaches to reconstructing glacial environments on the continent are scarce. Here we provide new evidence for westerly wind regimes across glacial southeastern Australia. We confirm active transverse lunette deposition at c. 29 ka and c. 23–19 ka in the semi-arid Willandra Lakes, and identify aeolian sand incursions to Spring Creek on the temperate Western Victorian Volcanic Plains from c. 29 ka. The Spring Creek deposits contain a surprising quantity of sand-sized quartz given the basalt setting, which we propose to be allochthonous and likely transported some distance. The site lies more than 50 km east and south of dunefields which were active at the same time and may have contributed sediment via long distance transport. We investigate the hypothesis for northward glacial expansion of westerly winds by combining our sediment records with aeolian particle transport simulations. We find that LGM near-surface winds were dominated by stronger, more focussed westerly air flow across southeastern Australia, compared with presently more diffuse wind regimes. Our results suggest stronger potential for LGM eastward distal sand transport onto the basalt plains, coeval with enhanced aeolian activity in the semi-arid Australian dunefields. Our combined reconstruction of aeolian deposition and trajectory modelling confirms the extended LGM hypothesis and indicates a northward migration of westerly winds over southeastern Australia during this period.
Do we know and do we care? Algorithms and Attitude towards Conversational User Interfaces: Comparing Chatbots and Voice Assistants
2022-07-26

As conversational user interfaces (CUIs) are increasingly integrated into daily life, ethical and societal concerns about integrated content filtering algorithms emerge. In addressing these concerns, it is essential to know how aware and knowledgeable society is of the algorithms it encounters using CUIs and the extent to which this impacts the attitude towards these technologies. In this survey study, we made a first attempt to measure and compare participants' algorithm awareness of chatbots and voice assistants. Further, we assessed the effect of algorithm literacy on the attitude towards CUIs and possible interaction effects with technology acceptance. Lastly, we compared previous and future usage purposes for chatbots and voice assistants. We found higher algorithm awareness for voice assistants than for chatbots. No correlation between algorithm literacy and attitude towards either chatbots or voice assistants was found. An additional personal-level factor, technology acceptance, did not affect this relationship. The results show that participants preferred using voice assistants for task completion and social purposes over chatbots, while getting information was equally preferred between chatbots and voice assistants. Considering its societal relevance, we want to encourage more research on algorithmic awareness and understanding in the field of CUI and its cognitive and behavioral effects.
SRG/eROSITA micrometeoroid hits and effects
2022-07-26

Micrometeoroids are micron-sized dust particles orbiting at hypervelocities of a few tens of kilometers per second. Impacts on sensitive x-ray astronomical devices in space can degrade their performance and even lead to fatal loss of at least parts of their functionality, like in the case of two CCDs of the EPIC MOS1 camera aboard XMM-Newton. We summarize here the main parameters and effects of such micrometeoroid impacts on x-ray astronomical instrumentation in space, to serve as quick reference on this subject, e.g. for subsequent comparative studies. In particular, we list all related SRG/eROSITA events registered during the first two years of operations at the sun-Earth L2 point. None of these seven events has lead to any failure or significant reduction of instrument performance. Only bright pixels and column segments developed. They were either set to bad onboard or could be cured by computation of new offset maps or commanding of higher thresholds for individual pixels. Only one case was clearly associated with an intense optical light flash. Finally, we compare the number of registered events to predictions from interplanetary dust models of sporadic meteoroids from the interplanetary dust cloud and cometary meteoroid streams. The modelled dust fluxes for approximately 1 <i>μ</i>m sized sporadic particles are in rough agreement with the number of events registered by eROSITA, while cometary meteoroid streams can most likely be excluded as origin of eROSITA hits.
Accelerated and Quantitative 3D Semisolid MT/CEST Imaging using a Generative Adversarial Network (GAN-CEST)
2022-07-26

Purpose: To substantially shorten the acquisition time required for quantitative 3D chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at 3 different sites, using 3 different scanner models and coils. A generative adversarial network supervised framework (GAN-CEST) was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. Results: The GAN-CEST 3D acquisition time was 42-52 seconds, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 seconds. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r &gt; 0.97, NRMSE &lt; 1.5%). GAN-CEST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3.8 1.3% and 4.6 1.3%, respectively, and SSIM of 96.3 1.6% and 95.0 2.4%, respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE &lt; 7% and SSIM &gt; 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-CEST has demonstrated improved performance and reduced noise compared to MRF. Conclusion: GAN-CEST can substantially reduce the acquisition time for quantitative semisolid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.
Flexible and efficient simulation-based inference for models of decision-making
2022-07-27

Inferring parameters of computational models that capture experimental data is a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.
A deep spectromorphological study of theγ-ray emission surrounding the young massive stellar cluster Westerlund 1
2022-07-27

Context. Young massive stellar clusters are extreme environments and potentially provide the means for efficient particle acceleration. Indeed, they are increasingly considered as being responsible for a significant fraction of cosmic rays (CRs) that are accelerated within the Milky Way. Westerlund 1, the most massive known young stellar cluster in our Galaxy, is a prime candidate for studying this hypothesis. While the very-high-energy γ -ray source HESS J1646−458 has been detected in the vicinity of Westerlund 1 in the past, its association could not be firmly identified. Aims. We aim to identify the physical processes responsible for the γ -ray emission around Westerlund 1 and thus to understand the role of massive stellar clusters in the acceleration of Galactic CRs better. Methods. Using 164 h of data recorded with the High Energy Stereoscopic System (H.E.S.S.), we carried out a deep spectromorphological study of the γ -ray emission of HESS J1646−458. We furthermore employed H I and CO observations of the region to infer the presence of gas that could serve as target material for interactions of accelerated CRs. Results. We detected large-scale (∼2° diameter) γ -ray emission with a complex morphology, exhibiting a shell-like structure and showing no significant variation with γ -ray energy. The combined energy spectrum of the emission extends to several tens of TeV, and it is uniform across the entire source region. We did not find a clear correlation of the γ -ray emission with gas clouds as identified through H I and CO observations. Conclusions. We conclude that, of the known objects within the region, only Westerlund 1 can explain the majority of the γ -ray emission. Several CR acceleration sites and mechanisms are conceivable and discussed in detail. While it seems clear that Westerlund 1 acts as a powerful particle accelerator, no firm conclusions on the contribution of massive stellar clusters to the flux of Galactic CRs in general can be drawn at this point.
Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
2022-07-27

Background: Variants in the phospholipase C gamma 2 (PLCG2) gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. Linking the clinical phenotype with the genotype is relevant in making the final diagnosis. Methods: This is a single center case series of five related patients (4–44 years), with a history of autoinflammation and immune dysregulation. Clinical and laboratory characteristics were recorded and a literature review of APLAID/PLAID was performed. Results: All patients had recurrent fevers, conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold-induced urticaria and recurrent airway infections. Hearing loss was detected in two patients. Inflammatory parameters were slightly elevated during flares. Unswitched B-cells were decreased. Naïve IgD+CD27− B-cells and unswitched IgD+CD27+ B-cells were decreased; switched IgD-CD27+ B-cells were slightly increased. T-cell function was normal. Genetic testing revealed a heterozygous missense variant (c.77C&gt;T, p.Thr26Met) in the PLCG2 gene in all patients. Genotype and phenotype characteristics were similar to previously published PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies) patients. Furthermore, they displayed characteristics for both PLAID and APLAID (recurrent infections, abdominal pain/diarrhea) with normal T-cell function. Conclusion: The heterozygous missense PLCG2 gene variant (c.77C&gt;T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.
A multiple sulfur record of super-large volcanic eruptions in Archaean pyrite nodules
2022-07-27

Archaean supracrustal rocks carry a record of mass-independently fractionated S that is interpreted to be derived from UV-induced photochemical reactions in an oxygen-deficient atmosphere. Experiments with photochemical reactions of SO2 gas have provided some insight into these processes. However, reconciling experimental results with the multiple S isotopic composition of the Archaean sedimentary record has proven difficult and represents one of the outstanding issues in understanding the Archaean surface S-cycle. We present quadruple S isotope data (32S, 33S, 34S, 36S) for pyrite from Mesoarchaean carbonaceous sediments of the Dominion Group, South Africa, deposited in an acidic volcanic lake, which help reconcile observations from the Archaean sedimentary record with the results of photochemical experiments. The data, which show low S/S ratios (mostly ≪ 1) and very negative S/S ratios (−4 and lower), contrast with the composition of most Archaean sedimentary sulfides and sulfates, having S/ (the so-called ‘Archaean reference array’), but match those of modern photochemical sulfate aerosols produced in the stratosphere, following super-large volcanic eruptions, and preserved in Antarctic ice. These data are also consistent with the results of UV-irradiation experiments of SO2 gas at variable gas pressure. The S isotope composition of the Dominion Group pyrite is here interpreted to reflect the products of photolysis in a low-oxygen-level atmosphere at high SO2 pressure during large volcanic eruptions, mixed with Archaean ‘background’ (having a composition broadly similar to the Archaean reference array) S pools. It is inferred that high sedimentation rates in a terrestrial basin resulted in an instantaneously trapped input of atmospheric S during short-lasted depositional intervals, which faithfully represents transient photochemical signals in comparison with marine sedimentary records.
Projective measurements can probe non-classical work extraction and time-correlations
2022-07-27

We demonstrate an experimental technique to characterize genuinely nonclassical multi-time correlations using projective measurements with no ancillae. We implement the scheme in a nitrogen-vacancy center in diamond undergoing a unitary quantum work protocol. We reconstruct quantum-mechanical time correlations encoded in the Margenau-Hills quasiprobabilities. We observe work extraction peaks five times those of sequential projective energy measurement schemes and in violation of newly-derived stochastic bounds. We interpret the phenomenon via anomalous energy exchanges due to the underlying negativity of the quasiprobability distribution.
“For me, it's just a piece of freedom”—Increased empowerment through physical activity promotion among socially disadvantaged women
2022-07-27

Introduction Community-based participatory research (CBPR) is an effective health promotion approach for reaching socially disadvantaged groups. However, there is limited evidence on how such interventions and their effects can be reproduced across time and place. The present study examines the effects of BIG (i.e., movement as an investment in health), a long-standing German CBPR project. Since 2005, BIG has aimed to empower women in difficult life situations to increase control over their health determinants and reduce social inequalities by promoting physical activity. One of BIG's key features is its implementation in several German municipalities since 2005. This study explores (a) whether participation could change women's empowerment, and (b) how increased empowerment affects other areas of women's lives. Methods With a total of 63 interviewees (i.e., 40 participating women, 7 trainers, 3 project coordinators, and 13 stakeholders), we conducted 53 semi-structured qualitative interviews in five BIG communities between 2007 and 2011. Some interviews were conducted with two people simultaneously. The interview guide contained questions on various dimensions of empowerment (e.g., project engagement, increased self-efficacy, and developed competencies). Framework analysis was used for the analytical process. Results BIG contributed to women's empowerment in various ways, including increased self-efficacy, social network promotion, competency development, and increased motivation to change physical activity behavior. Women who took on added tasks and became more involved in project planning also strengthened their organizational empowerment. Furthermore, increased empowerment had a positive influence on the women's quality of life, family, and professional lives. Conclusion The novel findings helped in understanding the effects of a complex empowerment-based approach that promoted physical activity among women in difficult life situations. Future research should focus on the long-term effects of these programs and their transferability to other sites. Further effort is necessary in the area of public health policy.
From up-toning intensifying particle to scalar focus particle
2022-07-27

Abstract The paper proposes a new developmental path from up-toning intensifying particle to additive scalar focus particle based on a diachronic corpus analysis of the German focus particles zumal ‘especially’, gar ‘even’, and sogar ‘even’. The meaning shift took place about 1600 and was facilitated by shared morpho-syntactic and semantic properties of the source and target meanings. Critical (ambiguous) and isolating contexts play a crucial role in the study. The data indicate the occurrence of two types of critical contexts, a syntactically motivated one and a semantically motivated one. Furthermore, the new developmental path is argued to follow a general cross-linguistic tendency of additive scalar focus particles to develop from scalar expressions in a broader sense.
Release of the pre-assembled naRNA-LL37 composite DAMP re-defines neutrophil extracellular traps (NETs) as intentional DAMP webs
2022-07-27

Abstract Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs), the primary human leukocyte population. NETs trap and kill microbes but have also been linked to inflammation, e.g. atherosclerosis, arthritis or psoriasis by unknown mechanisms. We here characterize naRNA (NET-associated RNA), as a new canonical, abundant, and unexplored inflammatory NET component. naRNA, upon release by NET formation, drove further NET formation in naïve PMN, and induced macrophage and keratinocyte activation via TLR8 in humans and Tlr13 in mice, in vitro and in vivo. Importantly, in vivo naRNA strongly drove skin inflammation, whereas genetic ablation of RNA sensing drastically ameliorated psoriatic skin inflammation. Rather than accidentally assembling with LL37 on the NET, naRNA was intracellularly pre-associated in resting neutrophils as a ‘composite DAMP’, thus highlighting NET formation as a DAMP release process. This re-defines sterile NETs as an intentionally inflammatory agent, signaling and amplifying neutrophil activation. Moreover, in the many conditions previously linked to NETs and extracellular RNA, TLR-mediated naRNA sensing emerges as both potential cause and new intervention target. Graphical abstract Created with biorender.com
Complete Genome Sequence of the Collinolactone Producer Streptomyces sp. Strain Gö40/10
2022-07-27

The actinomycete Streptomyces sp. strain Gö40/10 has the potential to produce a range of secondary metabolites, one of which is collinolactone, a compound with neuroprotective properties and potential for pharmaceutical applications. The genome was sequenced with Oxford Nanopore Technologies MinION and Illumina MiSeq systems and consists of a single 9,635,564-nucleotide linear chromosome.