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Abstract The liver has the remarkable capacity to regenerate. In the clinic, regeneration is induced by portal vein embolization, which redirects portal blood flow, resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here, we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the regenerating liver. Our data unveils pervasive upregulation of genes associated with developmental processes, cellular adhesion, and inflammation in post-portal vein embolization liver, disrupted portal-central hepatocyte zonation, and altered cell subtype composition of endothelial and immune cells. Interlineage crosstalk analysis reveals mesenchymal cells as an interaction hub between immune and endothelial cells, and highlights the importance of extracellular matrix proteins in liver regeneration. Moreover, we establish tissue-scale iterative indirect immunofluorescence imaging for high-dimensional spatial analysis of perivascular microenvironments, uncovering changes to tissue architecture in regenerating liver lobules. Altogether, our data is a rich resource revealing cellular and histological changes in human liver regeneration.

Abstract Highlanders and lowlanders of Papua New Guinea have faced distinct environmental stress, such as hypoxia and environment-specific pathogen exposure, respectively. In this study, we explored the top genomics regions and the candidate driver SNPs for selection in these two populations using newly sequenced whole-genomes of 54 highlanders and 74 lowlanders. We identified two candidate SNPs under selection - one in highlanders, associated with red blood cell traits and another in lowlanders, which is associated with white blood cell count – both potentially influencing the heart rate of Papua New Guineans in opposite directions. We also observed four candidate driver SNPs that exhibit linkage disequilibrium with an introgressed haplotype, highlighting the need to explore the possibility of adaptive introgression within these populations. This study reveals that the signatures of positive selection in highlanders and lowlanders of Papua New Guinea align closely with the challenges they face, which are specific to their environments.

The subject of this paper is a description and analysis of the life and work of the extraor¬dinary personality of the exiled lawyer F. A. Mann who became an extraordinary expert in public international law, private international law, comparative law and commercial law, who, moreover, laid the foundations of monetary law as a special subject of legal doctrine. As the famous English judge, Lord Denning, would say: “Mann contributed more than anyone else to the development the science of law in our time.” Born in a German Jewish family, he studied and began an academic career in Berlin. He was then forced to flee to Great Britain, where he studied law again and became a renowned solicitor and legal scholar. His career was crowned after World War II, when he became a leading figure in international legal organizations, leaving a far-reaching influence in English and international jurisprudence. In the 1960s and 1970s, he lectured at German universities in particular, where he received the highest honours, and also influenced German jurisprudence.

AbstractIn light of pressing challenges such as climate change, real-life, participatory, adaptive, and reflexive experimental interventions have been framed as indispensable incubators for transformative change toward greater sustainability. Yet, to what extent are the promises that were attached to eco-political experimentation around the turn to the 21st Century still plausible today? In this introduction to this Special Issue on eco-political experimentation we first map the alternative that experimentation sought to be in the fields of knowledge production, governance, and civic activism and how critics responded to this agenda. We then make the case for reassessing the promises of experimentation against the backdrop of current societal constellations. These constellations include the renewed invocation of climate science as an authority that demands political action (an authority experimental knowledge production sought to decenter) and de facto return of the state and more centralized forms of governing (which experimental governance sought to go beyond). They also include the return of forms of activism that stress the importance of urgent and decisive action (which experimental action is in part an opposite to) as well as the emergence of civil society experiments in the service of exclusion if not authoritarianism (in contrast to values inclusivity and democracy that are usually attached to eco-political experimentation). The objective of this introduction, and the articles comprising this Special Issue, is to establish a sensorium for ambiguities which we regard as a precondition for experimental action that might actually achieve transformative change as opposed to merely generating hope for it.

Formative assessment is considered to be helpful in students' learning support and teaching design. Following Aufschnaiter's and Alonzo's framework, formative assessment practices of teachers can be subdivided into three practices: eliciting evidence, interpreting evidence and responding. Since students' conceptions are judged to be important for meaningful learning across disciplines, teachers are required to assess their students' conceptions. The focus of this article lies on the discussion of learning analytics for supporting the assessment of students' conceptions in class. The existing and potential contributions of learning analytics are discussed related to the named formative assessment framework in order to enhance the teachers' options to consider individual students' conceptions. We refer to findings from biology and computer science education on existing assessment tools and identify limitations and potentials with respect to the assessment of students' conceptions.

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

AbstractDespite the possibility of unintended side effects, experiments in civil society like urban gardens, sustainable housing projects, ecovillages, and so forth are associated with transformative capacities in light of an increasingly serious social-ecological crisis. The tide of the political far right, however, demonstrates that outcomes of civil society engagement undermining emancipatory sustainability are hardly just unintended effects. Therefore, I analyze the role of experimental ecopolitics for the far right by means of the example of völkisch settlers in Germany, which are diverse far-right actors practicing a strategy of rural community building. After discussing whether these practices can be understood as ecopolitical experimentation, I reflect on its tensions with far-right climate-change denialism and its relevance for future scenarios of climate politics. I suggest that despite ideological differences, far-right environmentalism of everyday corresponds with characteristic elements of experimental practices of non-far-right experimentation. Representing far-right politics beyond anti-environmentalism and denial, far-right experimentation might provide bridge building and enable potential cooptation of non-far-right experiments and participatory sustainability governance. Further, it represents an agenda of exclusive authoritarian sustainability and ethno-securitization of climate change that—as recent COVID-19 protests have indicated—has a potential for social resonance far beyond the organized far right.

Dynamically loaded structures made of thermoplastic polymers have been extensively exploited in several demanding industries. Due to the viscoelastic and thermal properties of thermoplastic polymers, self-heating is generally inevitable, especially during dynamic deformations at high frequencies. Therefore, the thermoplastic polyether ether ketone (PEEK), with its high temperature resistance and high specific strength, is a particularly ideal candidate for dynamically loaded applications. Using scanning laser Doppler vibrometry and infrared thermography, an experimental study of the vibration characteristics and the vibration-induced heating of flat-sheet PEEK specimens was carried out. The specimens were base-excited by means of a piezoelectric actuator at high frequencies in the range between 1 and 16 kHz. As a result, a maximum temperature rise of approximately 6.4 K was detected for the highest investigated excitation. A high correlation between the spatial distribution of the velocity along the beam’s axial direction and the resulting temperature increase was measured. To summarize, the occurring self-heating of PEEK due to the dissipation of vibrational energy has to be critically considered for dynamically loaded structural applications, especially areas with high displacement amplitudes, such as antinodes, which yield the highest temperature increase.

Abstract The Sound Fixing and Ranging (SOFAR) channel in the ocean allows for low frequency sound to travel thousands of kilometers, making it particularly useful for detecting underwater nuclear explosions. Suggestions that an elevated SOFAR‐like channel should exist in the stratosphere date back over half a century and imply that sources within this region can be reliably sensed at vast distances. However, this theory has not been supported with evidence of direct observations from sound within this channel. Here we show that an infrasound sensor on a solar hot air balloon recorded the first infrasound detection of a ground truth airborne source while within this acoustic channel, which we refer to as the AtmoSOFAR channel. Our results support the existence of the AtmoSOFAR channel, demonstrate that acoustic signals can be recorded within it, and provide insight into the characteristics of recorded signals. Results also show a lack of detections on ground‐based stations, highlighting the advantages of using balloon‐borne infrasound sensors to detect impulsive sources at altitude.

In this paper, we revisit the empirical observation that prices rise like rockets when input costs increase but fall like feathers when input costs decrease. The analysis draws on a novel data set that includes daily retail prices of gasoline from 12,804 stations in Germany from January 1, 2014 to December 31, 2018. Our findings based on pooled-panel asymmetric error correction models indicate that the pattern of rockets and feathers is the norm rather than the exception. Our results further show that temporal aggregation of station-level price data leads to inaccurate inferences and could account for the inconclusive findings in the literature. Keywords: Asymmetric Pricing, Market Transparency, Search Intensity, Tacit Collusion, 1. INTRODUCTION This paper revisits the debate on the asymmetric response of retail gasoline prices to crude oil price changes. Retail fuel pricing, in general, remains an area of significant [...]

Abstract Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets. Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute to pathology in modern day humans

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.

Structures made of the thermoplastic polymer polyether ether ketone (PEEK) are widely used in dynamically-loaded applications due to their high-temperature resistance and high mechanical properties. To design these dynamic applications, in addition to the well-known stiffness and strength properties the vibration-damping properties at the given frequencies are required. Depending on the application, frequencies from a few hertz to the ultrasonic range are of interest here. To characterize the frequency-dependent behavior, an experimental approach was chosen and applied to a sample polymer PEEK. The test setup consists of a piezoelectrically driven base excitation of the polymeric specimen and the non-contact measurement of the velocity as well as the surface temperature. The beam’s bending vibrations were analyzed by means of the Timoshenko theory to determine the polymer’s storage modulus. The mechanical loss factor was calculated using the half-power bandwidth method. For PEEK and a considered frequency range of 1 kHz to 16 kHz, a storage modulus between 3.9 GPa and 4.2 GPa and a loss factor between 9 × 10−3 and 17 × 10−3 were determined. For the used experimental parameters, the resulting mechanical properties were not essentially influenced by the amplitude of excitation, the duration of excitation, or thermal degrad.ation due to self-heating, but rather slightly by the clamping force within the fixation area.

Abstract Earth's ionosphere has long been targeted as a medium for remote sensing of explosive terrestrial events such as earthquakes, volcanic eruptions, and nuclear/conventional weapon detonations. Until now, the only confirmed ionospheric detections have been of very large events that were easily detectable through other traditional global sensor systems (e.g., seismic). We present the first clear, confirmed detections of relatively low yield 1‐ton TNT‐equivalent chemical explosions using pulsed Doppler radar observations of isodensity layers in the ionospheric E region. The shape and spectra of the detected waveforms closely match predictions from the acoustic ray tracing and weakly nonlinear waveform propagation models. The explosions were roughly three orders of magnitude lower yield than any previous confirmed ionospheric detection and represent the first conclusive evidence that explosions of this size can have clear impacts on the ionosphere. This technique could improve the remote detection of both anthropogenic and natural explosive events.