julilili42/papers huggingface dataset:
К истории концепта “Общество как государственное установление”: Памяти Дитриха Гайера (1928-2023)
2023-12-20

Dietrich Geyer’s article “‘Gesellschaft’ als staatliche Veranstaltung. Sozialgeschichtliche Aspekte des russischen Behördenstaats im 18. Jahrhundert,” had a significant impact on both German and American historiography, which is not the case with the Soviet historiography of the 1960-1980s. Nevertheless, late Soviet and early post-Soviet historiography was preoccupied with the same problems of the relationship between “state” and “society” in Imperial Russia and sometimes followed the line of D. Geyer’s thinking. In the 1990s, when the “grand narrative” of modernization was called into question, historians engaged in a polemic about the very productiveness of the opposition of “state” and “society” as categories of historical knowledge. They turned to the local level of late imperial Russian society, or adopted new methods of examining legislative sources, avoiding access to “backwardness” or “underdevelopment,” preferring to examine the language and rhetoric of eighteenth-century documents.
A unified data infrastructure to support large-scale rare disease research
2023-12-20

Abstract The Solve-RD project brings together clinicians, scientists, and patient representatives from 51 institutes spanning 15 countries to collaborate on genetically diagnosing (“solving”) rare diseases (RDs). The project aims to significantly increase the diagnostic success rate by co-analysing data from thousands of RD cases, including phenotypes, pedigrees, exome/genome sequencing and multi-omics data. Here we report on the data infrastructure devised and created to support this co-analysis. This infrastructure enables users to store, find, connect, and analyse data and metadata in a collaborative manner. Pseudonymised phenotypic and raw experimental data are submitted to the RD-Connect Genome-Phenome Analysis Platform and processed through standardised pipelines. Resulting files and novel produced omics data are sent to the European Genome-phenome Archive, which adds unique file identifiers and provides long-term storage and controlled access services. MOLGENIS “RD3” and Café Variome “Discovery Nexus” connect data and metadata and offer discovery services, and secure cloud-based “Sandboxes” support multi-party data analysis. This proven infrastructure design provides a blueprint for other projects that need to analyse large amounts of heterogeneous data.
Siri Hustvedt’s "The Summer Without Men" and "The Blazing World"
2023-12-20

This paper aims to analyse Siri Hustvedt’s The Summer Without Men (2011) and The Blazing World (2014) from the perspective of the female Künstlerroman or Künstlerinroman to show the convergences and divergences between Hustvedt’s contemporary artist heroines and twentieth-century ones. Through the methodological framework, I discuss Linda Huf’s study of the female artist novel and Evy Varsamopoulou’s subsequent revision of it, focusing on the protagonist’s interpersonal and social relationships. It could be concluded that Hustvedt’s portrayal of the artist heroine is still a result of living in a patriarchal system, but it opens the way for complex representations of female characters, establishing strong emotional bonds between women.
The Importance of Gender-Sensitive Health Care in the Context of Pain, Emergency and Vaccination: A Narrative Review
2023-12-21

So far, health care has been insufficiently organized in a gender-sensitive way, which makes the promotion of care that meets the needs of women and men equally emerge as a relevant public health problem. The aim of this narrative review was to outline the need for more gender-sensitive medical care in the context of pain, emergency care and vaccinations. In this narrative review, a selective search was performed in Pubmed, and the databases of the World Health Organization (WHO), the European Institute for Gender Equality and the German Federal Ministry of Health were searched. Study data indicate that there are differences between men and women with regard to the ability to bear pain. On the other hand, socially constructed role expectations in pain and the communication of these are also relevant. Studies indicate that women receive adequate pain medication less often than men with a comparable pain score. Furthermore, study results indicate that the female gender is associated with an increased risk of inadequate emergency care. In terms of vaccine provision, women are less likely than men to utilize or gain access to vaccination services, and there are gender-sensitive differences in vaccine efficacy and safety. Sensitization in teaching, research and care is needed to mitigate gender-specific health inequalities.
Disruption of a high‐pressure unit during exhumation: Example of the Cycladic Blueschist unit (Thera, Ios and Naxos islands, Greece)
2023-12-21

Abstract Reconstructing the original geometry of a high‐pressure tectonic unit is challenging but important to understand the mechanisms of mountain building. While a single nappe is subducted and exhumed, nappe‐internal thrusts may disrupt it into several subunits. The Middle‐CBU nappe of the Cycladic Blueschist Unit (Hellenide subduction orogen, Greece) shows evidence of such disruption along a Trans‐Cycladic‐Thrust (TCT), however, the timing of this thrusting is unknown. Here, we report multi‐petrological and geochronological data from the Middle‐CBU nappe from the Thera and Ios islands (Greece). Using Zr‐in‐rutile thermometry coupled with quartz‐in‐garnet elastic barometry, average P–T and phase equilibrium thermodynamic modelling, we show that garnet growth in Ios occurred during prograde metamorphism at 6.7 ± 1.4 kbar to 13.0 ± 1.6 kbar and 326 ± 20°C to 506 ± 13°C (2σ uncertainty) followed by early exhumation to 10.1 ± 0.6 kbar and 484 ± 14°C and a greenschist facies overprint at 5.7 ± 1.2 kbar and 416 ± 14°C. For Thera, we constrain peak HP conditions of 7.6 ± 1.8 kbar and 331 ± 18°C, followed by exhumation and equilibration at ~2 kbar and ~275°C using average P–T and phase equilibrium thermodynamic modelling. For Ios, Uranium‐Pb garnet geochronology provides ages of 55.7 ± 5.0 Ma (2σ uncertainties) for prograde and 40.1 ± 1.4 Ma for peak HP metamorphism. Combining our new P–T–t data from Thera and Ios islands with existing data from Naxos island, we conclude that the studied nappe segments represent remnants of a former coherent nappe. The P–T–t data define an Eocene subduction rate of 2.1 ± 1.0 km/Ma, which is distinctly slower than the current subduction rate of 40–45 km/Ma. After subduction, the exhumation of the Middle‐CBU nappe occurred during the Oligocene at different rates for different localities. The Middle‐CBU nappe of Naxos was exhumed at a rate of ~6 km/Ma, contrasting with the exhumation rate of ~3 km/Ma calculated for Ios. This result suggests that the Middle‐CBU nappe of Naxos rocks was thrust on the Ios one during the Oligocene. Using P–T–t data and assuming realistic subduction angles during the Eocene and the Oligocene, we present a 2D structural reconstruction of the Middle‐CBU nappe of these islands. This reconstruction helps to understand the mechanisms of subduction of a continental margin and its disruption during exhumation.
Identification of novel canonical and cryptic HCMV-specific T-cell epitopes for HLA-A∗03 and HLA-B∗15 via peptide-PRISM
2023-12-21

Abstract Human cytomegalovirus (HCMV) reactivation poses a substantial risk to patients receiving tranplants. Effective risk stratification and vaccine development is hampered by a lack of HCMV-derived immunogenic peptides in patients with common HLA-A∗03:01 and HLA-B∗15:01 haplotypes. This study aimed to discover novel HCMV immunogenic peptides for these haplotypes by combining ribosome sequencing (Ribo-seq) and mass spectrometry with state-of-the-art computational tools, Peptide-PRISM and Probabilistic Inference of Codon Activities by an EM Algorithm. Furthermore, using machine learning, an algorithm was developed to predict immunogenicity based on translational activity, binding affinity, and peptide localization within small open reading frames to identify the most promising peptides for in vitro validation. Immunogenicity of these peptides was subsequently tested by analyzing peptide-specific T-cell responses of HCMV-seropositive and -seronegative healthy donors as well as patients with transplants. This resulted in the direct identification of 3 canonical and 1 cryptic HLA-A∗03–restricted immunogenic peptides as well as 5 canonical and 1 cryptic HLA-B∗15–restricted immunogenic peptide, with a specific interferon gamma–positive (IFN-γ+)/CD8+ T-cell response of ≥0.02%. High T-cell responses were detected against 2 HLA-A∗03–restricted and 3 HLA-B∗15–restricted canonical peptides with frequencies of up to 8.77% IFN-γ+/CD8+ T cells in patients after allogeneic stem cell transplantation. Therefore, our comprehensive strategy establishes a framework for efficient identification of novel immunogenic peptides from both existing and novel Ribo-seq data sets.
<i>Sallekhana </i>and the End-of-Life Option of Voluntary Stopping of Eating and Drinking
2023-12-21

This article brings sallekhana, the Jain practice of fasting to death, into conversation with the practice of ‘voluntary stopping of eating and drinking’ (VSED), an end-of-life option, available in various countries for competent adults, to hasten the end of life by consciously choosing to not eat and drink. From a medical and legal point of view sallekhana can be considered a form of VSED. Although differing in terms of intent and historical context, the two practices are similar insofar that they relate to capable and sound individuals who voluntarily forego food and water until death. Showing the critical similarity between VSED and sallekhana, I argue that the grounds put forward by major medical associations and legal societies to differentiate VSED from suicide are equally applicable to the case of sallekhana. I contend that the Jain fast needs to be disentangled from the concept of suicide based on the quality of intent, but also because the process is, in theory and for some time at least, reversible, supported by loved ones and members of the larger Jain community, and dependent on the individual’s continuous and prolonged will of renouncing food and water. I also show how medical and legal authorities defend an individual’s right to VSED based on the principles of self-determination, bodily integrity, self-ownership, and respect for persons. I put forward the view to take these ethical principles into account to legally protect a Jain’s right to take the vow of sallekhana.
Constraints on flavor-diagonal non-standard neutrino interactions from Borexino Phase-II
2023-12-21

The Borexino detector measures solar neutrino fluxes via neutrino-electron elastic scattering. Observed spectra are determined by the solar- survival probability , and the chiral couplings of the neutrino and electron. Some theories of physics beyond the Standard Model postulate the existence of Non-Standard Interactions (NSI's) which modify the chiral couplings and . In this paper, we search for such NSI's, in particularly neutral-current-like interactions that modify the and couplings, using Borexino Phase II data. Standard Solar Model predictions of the solar neutrino fluxes for both high- and low-metallicity assumptions are considered. No indication of new physics is found at the level of sensitivity of the detector and constraints on the parameters of the NSI's are placed. In addition, with the same dataset the value of is obtained with a precision comparable to that achieved in reactor antineutrino experiments.
Physical activity of older children and adolescents in Germany – Results of the HBSC study 2022 and trends since 2009/10
2023-12-21

Background: Physical activity is central to health, beginning in childhood and adolescence, and regular monitoring provides important information for strategic decisions on promoting physical activity in Germany. Methods: The current survey cycle of the Health Behaviour in School-aged Children (HBSC) study gives an insight into the prevalence of the indicators daily recommended physical activity, high and low physical activity, and sporting activity among students aged between 11 and 15 for 2022. In addition, the data is compared to the survey cycles of the 2009/10, 2013/14, and 2017/18 school years and analysed over time. Results: The results of the current survey cycle show that 10.8 % of girls, 20.9 % of boys, and 12.4 % of gender diverse adolescents fulfil the daily physical activity recommendation. There are also major gender-specific differences for the other indicators. The group of gender diverse adolescents needs to be analysed further. The changes over time between 2009/10 and 2022 are relatively small. While girls' physical activity habits decreased slightly for the various indicators between 2009/10 and 2022, boys' prevalence remained relatively stable over the same period. Conclusions: Overall, in part due to the effects of the various COVID-19 lockdowns, the need for effective and population-based measures to promote physical activity in childhood and adolescence remains high.
Tropical Methods in Geometry
2023-12-21

The workshop Tropical methods in geometry was devoted to a wide discussion and exchange of ideas between the leading experts representing various points of view on the subject including tropical methods in symplectic and Lagrangian geometry, topology of real algebraic varieties and tropical homology, tropical methods in algebraic, Berkovich analytic and log geometries, refined tropical enumerative geometry and enriched counting, and algebraic geometry and matroids.
Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models
2023-12-21

The mechanisms triggering the human immunodeficiency virus type I (HIV-1) to switch the coreceptor usage from CCR5 to CXCR4 during the course of infection are not entirely understood. While low CD4 + T cell counts are associated with CXCR4 usage, a predominance of CXCR4 usage with still high CD4 + T cell counts remains puzzling. Here, we explore the hypothesis that viral adaptation to the human leukocyte antigen (HLA) complex, especially to the HLA class II alleles, contributes to the coreceptor switch. To this end, we sequence the viral gag and env protein with corresponding HLA class I and II alleles of a new cohort of 312 treatment-naive, subtype C, chronically-infected HIV-1 patients from South Africa. To estimate HLA adaptation, we develop a novel computational approach using Bayesian generalized linear mixed models (GLMMs). Our model allows to consider the entire HLA repertoire without restricting the model to pre-learned HLA-polymorphisms. In addition, we correct for phylogenetic relatedness of the viruses within the model itself to account for founder effects. Using our model, we observe that CXCR4-using variants are more adapted than CCR5-using variants (p-value = 1.34e-2). Additionally, adapted CCR5-using variants have a significantly lower predicted false positive rate (FPR) by the geno2pheno[coreceptor] tool compared to the non-adapted CCR5-using variants (p-value = 2.21e-2), where a low FPR is associated with CXCR4 usage. Consequently, estimating HLA adaptation can be an asset in predicting not only coreceptor usage, but also an approaching coreceptor switch in CCR5-using variants. We propose the usage of Bayesian GLMMs for modeling virus-host adaptation in general.
Incidental Finding of Subannular Perfused Aortic Root Abscess
2023-12-21

An 83-year-old female presented with aortic valve stenosis requiring surgery, which was diagnosed with a transthoracic echocardiography three years ago. However, the patient declined the surgery at that time due to personal reasons. Three years later she presented again with signs of dizziness and weakness and progression of the aortic valve stenosis. Cardiac catheterization and a computed tomography scan were performed before the planned surgery. Surprisingly, a huge subannular perfused abscess hole around the aortic root companying a pericardial effusion was revealed. The patient underwent an urgent aortic root replacement with a tissue valve and an aortic ascending replacement without any complications. Intraoperative inspection confirmed an active aortic root and valve endocarditis.
»Misere miser sum«. Die sprachliche Darstellung von Affekt und Emotionen junger Männer auf der Bühne der Palliata
2023-12-21

This article examines the linguistic representation of strong emotions within Roman comedy using the character of the adulescens. The detailed linguistic analysis of scenes of the three young men Calidorus (Pseudolus), Diniarchus (Truculentus), and Lysiteles (Trinummus) focuses on lexicon, syntax, morphology, prosody, and imagery. As a rule, the characters name their feelings in the beginning and explain them in detail by means of metaphors. In addition, they make use of polymetric verse and typical stylistic elements that serve to increase the pathos of the expression, such as anaphoric enumerations, amplification, rhetorical questions etc. The analysis suggests that a specific combination of these features is used to represent emotions such as miseria, ira or desperatio within the text. A final look at Terence’s Andria and Adelphoe supports the results.
Nanoparticle Interferometer by Throw and Catch
2023-12-21

Matter-wave interferometry with increasingly larger masses could pave the way to understanding the nature of wavefunction collapse, the quantum to classical transition or even how an object in a spatial superposition interacts with its gravitational field. In order to improve upon the current mass record, it is necessary to move into the nano-particle regime. In this paper we provide a design for a nano-particle Talbot-Lau matter-wave interferometer that circumvents the practical challenges of previously proposed designs. We present simulations of the expected fringe patterns that such an interferometer would produce, considering all major sources of decoherence. We discuss the practical challenges involved in building such an experiment as well as some preliminary experimental results to illustrate the proposed measurement scheme. We show that such a design is suitable for seeing interference fringes with amu SiO particles, and that this design can be extended to even amu particles by using flight times below the typical Talbot time of the system.
Apixaban versus Aspirin for Embolic Stroke of Undetermined Source
2023-12-22

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)
Pitfalls and Considerations in Determining the Potency and Mutant Selectivity of Covalent Epidermal Growth Factor Receptor Inhibitors
2023-12-22

Enzyme inhibitors that form covalent bonds with their targets are being increasingly pursued in drug development. Assessing their biochemical activity relies on time-dependent assays, which are distinct and more complex compared with methods commonly employed for reversible-binding inhibitors. To provide general guidance to the covalent inhibitor development community, we explored methods and reported kinetic values and experimental factors in determining the biochemical activity of various covalent epidermal growth factor receptor (EGFR) inhibitors. We showcase how liquid handling and assay reagents impact kinetic parameters and potency interpretations, which are critical for structure-kinetic relationships and covalent drug design. Additionally, we include benchmark kinetic values with reference inhibitors, which are imperative, as covalent EGFR inhibitor kinetic values are infrequently consistent in the literature. This overview seeks to inform best practices for developing new covalent inhibitors and highlight appropriate steps to address gaps in knowledge presently limiting assay reliability and reproducibility.
Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer
2023-12-22

Large-scale chromosomal aberrations are prevalent in human cancer, but their function remains poorly understood. We established chromosome-engineered hepatocellular carcinoma cell lines using CRISPR-Cas9 genome editing. A 33–mega–base pair region on chromosome 8p (chr8p) was heterozygously deleted, mimicking a frequently observed chromosomal deletion. Using this isogenic model system, we delineated the functional consequences of chr8p loss and its impact on metastatic behavior and patient survival. We found that metastasis-associated genes on chr8p act in concert to induce an aggressive and invasive phenotype characteristic for chr8p-deleted tumors. Genome-wide CRISPR-Cas9 viability screening in isogenic chr8p-deleted cells served as a powerful tool to find previously unidentified synthetic lethal targets and vulnerabilities accompanying patient-specific chromosomal alterations. Using this target identification strategy, we showed that chr8p deletion sensitizes tumor cells to targeting of the reactive oxygen sanitizing enzyme Nudix hydrolase 17. Thus, chromosomal engineering allowed for the identification of novel synthetic lethalities specific to chr8p loss of heterozygosity.
The keystone gut species Christensenella minuta boosts gut microbial biomass and voluntary physical activity in mice
2023-12-22

The composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family Christensenellaceae has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live C. minuta influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed C. minuta . Importantly, live C. minuta boosts the biomass of the microbiome in the gut, and a higher level of C. minuta is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the Christensenellaceae can influence host energy homeostasis and health.