julilili42/papers huggingface dataset:
The large area detector onboard the eXTP mission
2022-08-31

The Large Area Detector (LAD) is the high-throughput, spectral-timing instrument onboard the eXTP mission, a flagship mission of the Chinese Academy of Sciences and the China National Space Administration, with a large European participation coordinated by Italy and Spain. The eXTP mission is currently performing its phase B study, with a target launch at the end-2027. The eXTP scientific payload includes four instruments (SFA, PFA, LAD and WFM) offering unprecedented simultaneous wide-band X-ray timing and polarimetry sensitivity. The LAD instrument is based on the design originally proposed for the LOFT mission. It envisages a deployed 3.2 m(2) effective area in the 2-30 keV energy range, achieved through the technology of the large-area Silicon Drift Detectors - offering a spectral resolution of up to 200 eV FWHM at 6 keV - and of capillary plate collimators - limiting the field of view to about 1 degree. In this paper we will provide an overview of the LAD instrument design, its current status of development and anticipated performance.
Instant disembodiment of virtual body parts
2022-08-31

Abstract Evidence from multisensory body illusions suggests that body representations may be malleable, for instance, by embodying external objects. However, adjusting body representations to current task demands also implies that external objects become disembodied from the body representation if they are no longer required. In the current web-based study, we induced the embodiment of a two-dimensional (2D) virtual hand that could be controlled by active movements of a computer mouse or on a touchpad. Following initial embodiment, we probed for disembodiment by comparing two conditions: Participants either continued moving the virtual hand or they stopped moving and kept the hand still. Based on theoretical accounts that conceptualize body representations as a set of multisensory bindings, we expected gradual disembodiment of the virtual hand if the body representations are no longer updated through correlated visuomotor signals. In contrast to our prediction, the virtual hand was instantly disembodied as soon as participants stopped moving it. This result was replicated in two follow-up experiments. The observed instantaneous disembodiment might suggest that humans are sensitive to the rapid changes that characterize action and body in virtual environments, and hence adjust corresponding body representations particularly swiftly.
How to Fight Linguistic Injustice in Science: Equity Measures and Mitigating Agents
2022-08-31

Though a common language of science allows for easier communication of the results among researchers, the use of lingua franca also comes with the cost of losing some of the diverse ideas and results arising from the plurality of languages. Following Quine’s famous thesis about the indeterminacy of translation, we elaborate on the inherent loss of diverse ideas when only one language of science is used. Non-native speakers sometimes experience epistemic injustice due to their language proficiency and consequently, their scientific insights get marginalized. Thus, it is important epistemically to include the results of all researchers independent of their native language. As a solution, we promote epistemic equity and inclusion both on the individual level and on the level of the scientific community. Epistemic equity means that researchers who suffer disadvantages because of their language skills get support from the rest of the scientific community that will compensate for their disadvantage and at the same time facilitate their epistemic inclusion. This can be achieved through the introduction of mitigating agents – the individuals and organizations that ought to serve as a communication bridge between individual researchers and the scientific community.
Wissen von Gawain
2022-08-31

Abstract With the narratological concept of a literary character existing only within the literary text, medieval literary characters pose a problem as they often appear in several texts that sometimes depict very different versions of them. Looking at King Arthur’s nephew Gawain as a character very much afflicted by this, the article suggests an approach to character that sees every single text drawing from an always-growing amount of collective knowledge about the character. Assuming that the perception of each version of the character is influenced by knowledge about the other versions, this approach sees the emergence of a complex character in medieval literature as a process that goes beyond any one single text.
A photon counting imaging detector for UV space missions
2022-08-31

We present the status of our imaging and photon counting UV-MCP detector versions, sensitive in the ultraviolet wavelength range. The detectors have a spatial resolution of 2k pixels per axis, are photon counting, have no readout noise and a very low dark rate, making it ideal for photometry and spectroscopy. The detector can be easily adapted to the requirements of different missions, e.g., only the mechanical interfaces and an electrical interface must be defined to integrate the detector, it is relatively lightweight (3 kg) and has a power consumption of only 15 W. For the sealed version of the detector, we are currently testing a sealed detector head with a cesium telluride photocathode in semitransparent mode. The open version of the detector uses a lightweight door mechanism and is currently optimized to use a KBr photocathode. Interesting advances have been made for AlGaN on MgF2 and MgO substrates. A complete h-GaN film could be grown on MgO (0 0 1), and a complete c-GaN film on MgO (1 1 0). Good crystal quality is crucial to obtain a high QE AlGaN photocathode. Finally, the challenges towards a sealed detector head with a diameter of about 8 cm are described. By rotating the detector window on the detector head during the sealing process, we were able to seal the detector. The photocathode in the sealed MCP detector is stable for at least weeks
Targeting of the human nasal microbiota by secretory IgA antibodies
2022-08-31

Abstract The human nasal microbiome is critical for health and disease, since it is associated with the occurrence of respiratory disorders and hosting of opportunistic pathogens. The host therefore protects this vulnerable mucosal barrier from infection and maintains homeostasis of the microbiota through various mechanisms, including the production of secretory IgA (sIgA) antibodies. However, we currently lack a comprehensive understanding of how sIgA affects the nasal microbiota. Through IgA-seq analysis of nasal microbiome samples and sIgA deposition experiments using nasal sIgA from healthy volunteers, we identified which bacterial genera and species are targeted by sIgA on the level of the individual host. We observed that the amount of sIgA secreted into the nasal mucosa by the host varied substantially and was negatively correlated with the bacterial density. The interaction between mucosal sIgA antibodies and the nasal microbiome was highly individual, and was not dependent on the microbiome composition, or the age or gender of the host. Importantly, we showed that for the clinically relevant opportunistic pathogen S. aureus , sIgA reactivity was in part the result of epitope-independent interaction of sIgA with the antibody binding protein SpA through binding of sIgA Fab regions. This study thereby offers a first comprehensive insight of targeting of nasal microbiota by sIgA antibodies, which may help to better understand the shaping and homeostasis of the nasal microbiome by the host and offer new targets for intervention in disease-associated microbiota.
The impact of entrepreneurial team experience on the speed of new venture internationalization
2022-08-31

Frame of the research:The international experience and orientation of the entrepreneur are one of the dominant explanations for early and accelerated new venture internationalization.We put this explanation to test by investigating the impact of multiple, nuanced dimensions of prior experience on the speed of reaching significant international sales and by extending the view from the individual to that of the team.Purpose of the paper: International entrepreneurship studies have predominantly focused on the individual's role in international expansion, neglecting the overall team experience and knowledge.This study relates a variety of experience dimensions that characterize the team to the speed of reaching significant foreign sales.Methodology: Upper Echelon theory is transferred to the context of the new, small firm and used to theorize the impact of entrepreneurial team experience on the venture's speed to reaching significant export intensity.Special attention is paid to the many facets of experiential knowledge.An OLS regression is employed on a set of 98 Italian and German new ventures.Results: Results of the OLS regression confirm the importance of the teams' industry experience, while, surprisingly, international experience exerts a significant but negative effect on the speed required to reach significant foreign sales.Experience in import-export related functions and gained in MNEs, as well as foreign language competence, do not show significant impact.Research limitations: The limited sample size does not allow to single out all experience variables.Practical implications: Practitioners and entrepreneurs who pursue fast international expansion get insight into the 'ideal' composition of the team. Originality of the paper:To the best of our knowledge, this paper is the first to empirically analyze the impact of the many dimensions of prior team experience on the speed of internationalization..
Deepfakes and Democracy (Theory): How Synthetic Audio-Visual Media for Disinformation and Hate Speech Threaten Core Democratic Functions
2022-09-01

Abstract Observers fear that deepfakes will shake the very foundations of democracy. Notwithstanding, in-depth scholarly analyses of deepfakes’ political impact are rare, and do not consider theories of democracy. This contribution helps close this research gap, drawing on Warren’s problem-oriented democracy theory, as well as theories of deliberative democracy and contributions on the role of trust in democracies. I identify three core functions of democratic systems and their normative foundations, namely empowered inclusion, collective agenda and will formation (supported by deliberation), and collective decision-making. Based on a literature and media analysis, I systematize different types of deepfakes serving either disinformation or hate speech and outline how they weaken core democratic functions and norms: Deepfakes impede citizens’ empowered inclusion in debates and decisions that affect them, e.g. by hampering efforts to hold political representatives accountable or further marginalizing certain societal groups such as women or ethnic minorities. Deepfakes also undermine collective agenda and will formation by threatening the epistemic quality of deliberation as well as citizens’ mutual empathy and respect. This culminates in a decreased legitimacy of collective decisions taken, which is additionally threatened by pervasive (but mostly speculative) fears of deepfake election manipulation. My analysis has implications for (future) governance efforts addressing deepfakes. Such efforts are increasing, e.g. on the part of social media platforms, but also (supra-)national regulatory bodies.
The Oncolytic Adenovirus XVir-N-31, in Combination with the Blockade of the PD-1/PD-L1 Axis, Conveys Abscopal Effects in a Humanized Glioblastoma Mouse Model
2022-09-01

Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required.
Bi‐Allelic COQ4 Variants Cause Adult‐Onset Ataxia‐Spasticity Spectrum Disease
2022-09-01

Abstract Background COQ4 codes for a mitochondrial protein required for coenzyme Q 10 (CoQ 10 ) biosynthesis. Autosomal recessive COQ4 ‐associated CoQ 10 deficiency leads to an early‐onset mitochondrial multi‐organ disorder. Methods In‐house exome and genome datasets (n = 14,303) were screened for patients with bi‐allelic variants in COQ4. Work‐up included clinical characterization and functional studies in patient‐derived cell lines. Results Six different COQ4 variants, three of them novel, were identified in six adult patients from four different families. Three patients had a phenotype of hereditary spastic paraparesis, two sisters showed a predominant cerebellar ataxia, and one patient had mild signs of both. Studies in patient‐derived fibroblast lines revealed significantly reduced amounts of COQ4 protein, decreased CoQ 10 concentrations, and elevated levels of the metabolic intermediate 6‐demethoxyubiquinone. Conclusion We report bi‐allelic variants in COQ4 causing an adult‐onset ataxia‐spasticity spectrum phenotype and a disease course much milder than previously reported. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement
2022-09-01

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K<sup>+</sup>/H<sup>+</sup> exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K<sup>+</sup> efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial pathologies.
Comprehensive validation of fasting-based and oral glucose tolerance test–based indices of insulin secretion against gold standard measures
2022-09-01

Introduction With pre-diabetes and diabetes increasingly recognized as heterogeneous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on oral glucose tolerance test (OGTT) and fasting measurements in comparison with gold standard methods. Research design and methods The hyperglycemic clamp extended with glucagon-like peptide 1 (GLP-1) infusion and intravenous glucose tolerance test (IVGTT), as well as OGTT, was performed in two well-phenotyped cohorts. The gold standard–derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson’s and Spearman’s correlation coefficients. The insulin-based and C-peptide-based indices were analyzed separately in different groups of glucose tolerance and the entire cohorts. Results The highest correlation coefficients were found for area under curve (AUC) (I 0-30 )/AUC (G 0-30 ), I 30 /G 30 , first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycemic clamp. AUC (I 0-120 )/AUC (G 0-120 ), BIGTT-AIR 0-60-120 , I 30 /G 30 , first-phase Stumvoll and AUC (I 0-30 )/AUC (G 0-30 ) demonstrated the strongest association with incretin-stimulated insulin response. Conclusions We have identified glucose-stimulated and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold standard measures and could be potentially used in future researches and clinical practice.
No robust online effects of transcranial direct current stimulation on corticospinal excitability
2022-09-01

Transcranial direct current stimulation (tDCS) has been used for over twenty years to modulate cortical (particularly motor corticospinal) excitability both during (online) and outlasting (offline) the stimulation, with the former effects associated to the latter. However, tDCS effects are highly variable, partially because stimulation intensity is commonly not adjusted individually (in contrast to transcranial magnetic stimulation, TMS). In Experiment 1, we therefore explored an empirical approach of personalizing tDCS intensity for the primary motor cortex (M1) based on dose-response curves (DRCs), individually relating tDCS Intensity (in steps from 0.3 to 2.0 mA) and Polarity (anodal, cathodal) to the online modulation of concurrent TMS motor evoked potentials (MEP), assessing DRC reliability across two separate days. No robust DRCs could be observed, neither at the individual nor at the group level, with the only robust effect being a (paradoxical) MEP facilitation during cathodal tDCS at 2.0 mA, but no modulation at traditional intensities of or near 1 mA. In Experiment 2, we therefore attempted to replicate the classical bidirectional online MEP modulation during 1 mA tDCS that had been reported by several of the early seminal tDCS papers. We either closely recreated stimulation parameters and temporal protocol of these original studies (Experiment 2A) or slightly modernized them according to current standards (Experiment 2B). In neither experiment did we observed any significant online MEP modulation. We conclude that an empirical titration of individually effective tDCS intensities may not be feasible as online tDCS effects do not appear to be sufficiently robust.
The Long Stare at Hercules X-1. I. Emission Lines from the Outer Disk, the Magnetosphere Boundary, and the Accretion Curtain
2022-09-01

Abstract Hercules X-1 is a nearly edge-on accreting X-ray pulsar with a warped accretion disk, precessing with a period of about 35 days. The disk precession allows for unique and changing sightlines toward the X-ray source. To investigate the accretion flow at a variety of sightlines, we obtained a large observational campaign on Her X-1 with XMM-Newton (380 ks exposure) and Chandra (50 ks exposure) for a significant fraction of a single disk precession cycle, resulting in one of the best data sets taken to date on a neutron star X-ray binary. Here we present the spectral analysis of the high state high-resolution grating and CCD data sets, including the extensive archival data available for this famous system. The observations reveal a complex Fe K region structure, with three emission line components of different velocity widths. Similarly, the high-resolution soft X-ray spectra reveal a number of emission lines of various widths. We correct for the uncertain gain of the European Photon Imaging Camera pn Timing mode spectra, and track the evolution of these spectral components with Her X-1 precession phase and observed luminosity. We find evidence for three groups of emission lines, the first of which originates in the outer accretion disk (10 5 R G from the neutron star). The second line group plausibly originates at the boundary between the inner disk and the pulsar magnetosphere (10 3 R G ). The last group is too broad to arise in the magnetically truncated disk and instead must originate very close to the neutron star surface, likely from X-ray reflection from the accretion curtain (∼10 2 R G ).
F55 Q-motor speeded tapping and pointing assessments: feasibility of a dual task design
2022-09-01

<h3>Background</h3> Quantitative digital assessments in clinical trials may increase effect sizes while reducing population sizes, resulting in more accurate and cost effective trials and less burden for participants, compared to qualitative scales. In an internship program (University of Tübingen - TüREx), we explored the feasibility of dual-task assessments using the Q-Motor devices, to amplify differentiation between HD gene carriers and healthy controls. <h3>Aims</h3> To assess feasibility of a dual-task design of Q-Motor finger tapping and target pointing task in a small cohort. <h3>Methods</h3> 10 healthy controls (non-gene carriers or status unknown) and 5 manifest and pre-manifest HD gene carriers have been enrolled in this proof-of-concept project. Participants were asked to perform three Q-Motor tasks: 1) Speeded finger tapping (non-dominant hand); 2) 3D pointing with the position tracking Polhemus Stylus to defined targets on a x-y plane installed in front of the subject in a pre-defined sequence (dominant hand); 3) Interference task, performing both tasks simultaneously. <h3>Results</h3> We found that while neither task single performed task could differentiate between the participant groups, the interference task showed good differentiation (p &lt; 0.01) between the groups for defined parameters. Specifically, HD gene carriers tended to use higher tapping forces in finger tapping, when doing target pointing simultaneously. <h3>Conclusions</h3> We found assessment of the described dual-tasks using Q-Motor devices feasible and well tolerated. While we acknowledge the limitations of the small sample size and unmatched groups, the results are encouraging and support confirmation of these findings in a larger cohort longitudinal study.