julilili42/papers huggingface dataset:
Folded‐end dipole transceiver array for human whole‐brain imaging at 7 T
2021-05-12

The advancement of clinical applications of ultrahigh field (UHF) MRI depends heavily on advances in technology, including the development of new radiofrequency (RF) coil designs. Currently, the number of commercially available 7 T head RF coils is rather limited, implying a need to develop novel RF head coil designs that offer superior transmit and receive performance. RF coils to be used for clinical applications must be robust and reliable. In particular, for transmit arrays, if a transmit channel fails the local specific absorption rate may increase, significantly increasing local tissue heating. Recently, dipole antennas have been proposed and used to design UHF head transmit and receive arrays. The dipole provides a unique simplicity while offering comparable transmit efficiency and signal‐to‐noise ratio with the conventional loop design. Recently, we developed a novel array design in our laboratory using a folded‐end dipole antenna. In this work, we developed, constructed and evaluated an eight‐element transceiver bent folded‐end dipole array for human head imaging at 7 T. Driven in the quadrature circularly polarized mode, the array demonstrated more than 20% higher transmit efficiency and significantly better whole‐brain coverage than that provided by a widely used commercial array. In addition, we evaluated passive dipole antennas for decoupling the proposed array. We demonstrated that in contrast to the common unfolded dipole array, the passive dipoles moved away from the sample not only minimize coupling between the adjacent folded‐end active dipoles but also produce practically no destructive interference with the quadrature mode of the array.
The Priestly Writing(s): Scope and Nature
2021-05-12

Abstract The existence of the so-called priestly writing is one of the most important theories in the research on the formation of the Pentateuch. This essay will discuss the five most important aspects of the current debate about the priestly writing. It will address the literary character of the priestly passages, the original end of the priestly writing, the formation of the Holiness Code, the date of the priestly writing, and the overall intention of this corpus.
Does model complexity improve pricing accuracy? The case of CoCos
2021-05-12

Abstract In this study, we analyze whether model complexity improves accuracy of CoCo pricing models. We compare the out-of-sample pricing ability of four models using a broad dataset that contains all CoCos which were issued between January 1, 2013 and May 31, 2016 in euros. The regarded models include the standard model from De Spiegeleer and Schoutens (J Deriv 20:27–36, 2012), a modified version enriched by credit risk, an extended model that accounts for the effective lifetime of the CoCo, and a trading model, solely based on historic market prices but no pricing theory at all. For a normal market environment, the simple trading model provides a higher pricing accuracy than the theory-based models. Under distress, however, a theory-based model with a sufficiently high complexity is required.
De novo identification of maximally deregulated subnetworks based on multi-omics data with DeRegNet
2021-05-12

Abstract Background With a growing amount of (multi-)omics data being available, the extraction of knowledge from these datasets is still a difficult problem. Classical enrichment-style analyses require predefined pathways or gene sets that are tested for significant deregulation to assess whether the pathway is functionally involved in the biological process under study. De novo identification of these pathways can reduce the bias inherent in predefined pathways or gene sets. At the same time, the definition and efficient identification of these pathways de novo from large biological networks is a challenging problem. Results We present a novel algorithm, DeRegNet, for the identification of maximally deregulated subnetworks on directed graphs based on deregulation scores derived from (multi-)omics data. DeRegNet can be interpreted as maximum likelihood estimation given a certain probabilistic model for de-novo subgraph identification. We use fractional integer programming to solve the resulting combinatorial optimization problem. We can show that the approach outperforms related algorithms on simulated data with known ground truths. On a publicly available liver cancer dataset we can show that DeRegNet can identify biologically meaningful subgraphs suitable for patient stratification. DeRegNet is freely available as open-source software. Conclusion The proposed algorithmic framework and its available implementation can serve as a valuable heuristic hypothesis generation tool contextualizing omics data within biomolecular networks.
Benzylammonium-Mediated Formamidinium Lead Iodide Perovskite Phase Stabilization for Photovoltaics
2021-05-12

Structural, optoelectronic, photovoltaic, and supplementary characterization data for “Benzylammonium-Mediated Formamidinium Lead Iodide Perovskite Phase Stabilization for Photovoltaics”, DOI:10.1002/adfm.202101163. Figure_2_XRD.zip: Data described in Figure 2 (XRD patterns) as Origin (.opj) software file. Figure_3_NMR_data.zip: Data described in Figure 3 (NMR spectra) in the file structure of the TopSpin software, which is available from Bruker. Figure_4_spectra.zip: Data described in Figure 4 (UV-vis absorption, PL and IPCE spectra) as Origin (.opj) software files. Figure_5_PV.zip: Data described in Figure 5 (photovoltaic characterization) as Origin (.opj) software files. Figure_6_spectra.zip: Data described in Figure 6 (PLQY and TRPL) as Origin (.opj) and *.csv files. Figure_7_stability.zip: Data described in Figure 7 (stability analysis) as Origin (.opj) software files. Figure_SI.zip: Data described in the Supporting Information Figures S1, S2, S3, S5, and S6 (XRD data, reciprocal space maps, radial profiles of q-maps, UV-vis absorption spectra, PL spectra, and additional photovoltaic characterization) as Origin (.opj), text (.txt), and image (.tiff) files.
Analysis of Genomic DNA from Medieval Plague Victims Suggests Long-Term Effect of Yersinia pestis on Human Immunity Genes
2021-05-13

Abstract Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.
Reprogramming of the Caseinolytic Protease by ADEP Antibiotics: Molecular Mechanism, Cellular Consequences, Therapeutic Potential
2021-05-13

Rising antibiotic resistance urgently calls for the discovery and evaluation of novel antibiotic classes and unique antibiotic targets. The caseinolytic protease Clp emerged as an unprecedented target for antibiotic therapy 15 years ago when it was observed that natural product-derived acyldepsipeptide antibiotics (ADEP) dysregulated its proteolytic core ClpP towards destructive proteolysis in bacterial cells. A substantial database has accumulated since on the interaction of ADEP with ClpP, which is comprehensively compiled in this review. On the molecular level, we describe the conformational control that ADEP exerts over ClpP, the nature of the protein substrates degraded, and the emerging structure-activity-relationship of the ADEP compound class. On the physiological level, we review the multi-faceted antibacterial mechanism, species-dependent killing modes, the activity against carcinogenic cells, and the therapeutic potential of the compound class.
Functional Genomic Screening During Somatic Cell Reprogramming Identifies DKK3 as a Roadblock of Organ Regeneration
2021-05-13

Abstract Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf‐3 (DKK3) is identified as novel factor for organ regeneration using combined transcription‐factor‐induced reprogramming and RNA‐interference techniques. Loss of Dkk3 enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three‐germ‐layer differentiation or colony formation capacity of liver and pancreatic organoids. However, DKK3 expression levels in wildtype animals and serum levels in human patients are elevated upon injury. Accordingly, Dkk3 ‐null mice display less liver damage upon acute and chronic failure mediated by increased proliferation in hepatocytes and LGR5 + liver progenitor cell population, respectively. Similarly, recovery from experimental pancreatitis is accelerated. Regeneration onset occurs in the acinar compartment accompanied by virtually abolished canonical‐Wnt‐signaling in Dkk3 ‐null animals. This results in reduced expression of the Hedgehog repressor Gli3 and increased Hedgehog‐signaling activity upon Dkk3 loss. Collectively, these data reveal Dkk3 as a key regulator of organ regeneration via a direct, previously unacknowledged link between DKK3, canonical‐Wnt‐, and Hedgehog‐signaling.
Examining the influence of perspective and prosody on expected emotional responses to irony: Evidence from event-related brain potentials.
2021-05-13

Ironic language is typically more difficult to process and interpret than a literal equivalent, hence is assumed to serve several social and emotional functions not achieved by literal communication (such as politeness or introducing humor). Several factors may influence emotional responses to irony, such as the perspective from which the utterance is encountered (e.g., speaker vs. target) and the tone of voice (prosody) used. To examine these issues, we conducted two event-related brain potential (ERP) studies in which participants listened to scenarios describing emotional responses to either literal criticism or ironic criticism. Ironic criticism was delivered with either natural or ironic prosody. Scenarios either described an emotional response the speaker expected to elicit from the target (speaker perspective), or the target's actual emotional response (target perspective). Expected or actual emotional responses were described as either "amused" (Experiment 1) or "hurt" (Experiment 2). ERPs were calculated time-locked to the end of the ironic or literal statements, and to the audio presentation of the critical emotion words. Results showed a significant effect of perspective for amused conditions, reflected by a larger late posterior positivity for the target than speaker conditions, indicating amused responses are more expected from speaker than target perspective. This effect was not seen for hurt conditions, suggesting these are equally expected from target and speaker perspectives. The data also revealed a more negative-going ERP waveform specifically for ironic criticism delivered with ironic prosody, reflecting prosodic processing. This suggests prosody may be able to speed the identification of irony. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Severe acute respiratory Syndrome-Coronavirus-2: Can it be detected in the retina?
2021-05-13

Background/Objectives The systemic organ involvement of SARS-CoV-2 needs to be thoroughly investigated including the possibility of an ocular reservoir in humans. To examine retinal tissues and vitreous for histopathology and SARS-CoV-2 presence with regard to possible effects on the human retina and/ or vitreous. We performed histopathological analyses and quantitative (q)RT-PCR-testing for SARS-CoV-2 RNA on retinal tissues and vitreous of COVID-19 postmortem donors. Subjects/Methods Included in this study were 10 eyes of 5 deceased COVID-19 patients. The diagnosis of SARS-CoV-2 infection was confirmed via pharyngeal swabs and broncho-alveolar fluids. The highest level of personal protective equipment (PPE) and measures was employed during fluid-tissue procurement and preparation. Histopathological examinations and qRT-PCR-testing were carried out for all retinal tissues and vitreous fluids. Results The histopathological examinations revealed no signs of morphologically identifiable retinal inflammation or vessel occlusions based on hematoxylin and eosin stains. By qRT-PCRs, we detected no significant level of viral RNA in human retina and vitreous. Conclusions In this study, no significant level of SARS-CoV-2-RNA was detected in the human retinal and vitreous fluid samples of deceased COVID-19 patients. Histopathological examinations confirmed no morphological sign of damage to retinal vasculature or tissues. Further studies are needed to confirm or refute the results.
Genesis of the mafic granophyre of the Vredefort impact structure (South Africa): Implications of new geochemical and Se and Re-Os isotope data
2021-05-13

ABSTRACT This contribution is concerned with the debated origin of the impact melt rock in the central uplift of the world’s largest confirmed impact structure—Vredefort (South Africa). New major- and trace-element abundances, including those of selected highly siderophile elements (HSEs), Re-Os isotope data, as well as the first Se isotope and Se-Te elemental systematics are presented for the felsic and mafic varieties of Vredefort impact melt rock known as “Vredefort Granophyre.” In addition to the long-recognized “normal” (i.e., felsic, &amp;gt;66 wt% SiO2) granophyre variety, a more mafic (&amp;lt;66 wt% SiO2) impact melt variety from Vredefort has been discussed for several years. The hypothesis that the mafic granophyre was formed from felsic granophyre through admixture (assimilation) of a mafic country rock component that then was melted and assimilated into the superheated impact melt has been pursued here by analysis of the two granophyre varieties, of the Dominion Group lava (actually meta-lava), and of epidiorite mafic country rock types. Chemical compositions, including high-precision isotope dilution–derived concentrations of selected highly siderophile elements (Re, Os, Ir, Pt, Se, Te), and Re-Os and Se isotope data support this hypothesis. A first-order estimate, based on these data, suggests that some mafic granophyre may have resulted from a significant admixture (assimilation) of epidiorite to felsic granophyre. This is in accordance with the findings of an earlier investigation using conventional isotope (Sr-Nd-Pb) data. Moreover, these outcomes are in contrast to a two-stage emplacement model for Vredefort Granophyre, whereby a mafic phase of impact melt, derived by differentiation of a crater-filling impact melt sheet, would have been emplaced into earlier-deposited felsic granophyre. Instead, all chemical and isotopic evidence so far favors formation of mafic granophyre by local assimilation of mafic country rock—most likely epidiorite—by a single intrusive impact melt phase, which is represented by the regionally homogeneous felsic granophyre.
Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses
2021-05-13

A common hypothesis explains autism spectrum disorder (ASD) as a neurodevelopmental disorder linked to excitatory/inhibitory (E/I) imbalance in neuronal network connectivity. Mutation of genes including Met and downstream signaling components, e.g., PTEN, Tsc2 and, Rheb are involved in the control of synapse formation and stabilization and were all considered as risk genes for ASD. While the impact of Met on glutamatergic synapses was widely appreciated, its contribution to the stability of inhibitory, GABAergic synapses is poorly understood. The stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin. Here, we show in vivo and in vitro that Met is necessary and sufficient for the stabilization of GABAergic synapses via induction of gephyrin clustering. Likewise, we provide evidence for Met-dependent gephyrin clustering via activation of mTOR. Our results support the notion that deficient GABAergic signaling represents a pathomechanism for ASD.
Reassessment of ‘Chilotherium wegneri’ (Mammalia, Rhinocerotidae) from the late Miocene of Samos (Greece) and the European record of Chilotherium
2021-05-13

Chilotherium represents one of the most characteristic rhinocerotid genera during the late Miocene of Eurasia. In Europe, it is restricted to the eastern parts of the continent (Balkan Peninsula and Peri-Pontic region). In total, eight Chilotherium species have been described from European material, with Samos (Greece) representing the type locality of four of them. Herein, the type material of ‘Chilotherium wegneri’ is revisited. The type cranium is considered lost for the past half-century, but the associated mandible is still housed in the collections of the Geomuseum Münster (Germany). The ‘C. wegneri’ type mandible is redescribed and, taking into account the original illustration of the type cranium, compared to other chilotheres from Europe and Asia. Accordingly, the previously proposed synonymy of ‘C. wegneri’ and Chilotherium schlosseri, which was also initially described from the late Miocene of Samos, is further supported. Lastly, an overview of the late Miocene record of Chilotherium in Europe is provided.
Mining Indonesian Microbial Biodiversity for Novel Natural Compounds by a Combined Genome Mining and Molecular Networking Approach
2021-05-13

Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two-thirds of all clinically used antibiotics. Thus, exploiting Indonesia&amp;rsquo;s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Besides, eight putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.
DoE Optimization Empowers the Automated Preparation of Enantiomerically Pure [18F]Talazoparib and its In Vivo Evaluation as a PARP Radiotracer.
2021-05-13

PARP inhibitors are proven chemotherapeutics and serve as lead structures for the development of PARP-targeted in vivo imaging probes. Given the clinical potential of PARP imaging for the detection and stratification of various cancers, the development of novel PARP imaging probes with improved pharmacologi-cal profiles over established PARP imaging agents is warranted. Here, we present a novel 18F-labeled PARP radiotracer based on the clinically superior PARP inhibitor talazoparib. An automated radiosynthesis of [18F]talazoparib (RCY: 13 ± 3.4 %; n = 4; molar radioactivity 52 – 176 GBq/μmol) was achieved using a “Design of Experiments” (DoE) optimized copper-mediated radiofluorination reaction. The chiral product was isolated from the reaction mixture using 2D reversed-phase/chiral radio-HPLC (&gt;99% ee). (8S, 9R)-[18F]Talazoparib demonstrated PARP binding in HCC1937 cells in vitro and showed an excellent tumor-to-blood ratio in xeno-graft-bearing mice (10.2 ± 1.5). Despite expected uptake into muscle, bone, and abdominal tissue, a favorable pharmacological profile in terms of excretion, blood half-life, and target engagement was observed in the pilot in vivo study. This synthesis of [18F]talazoparib exemplifies how a DoE based tracer development pipeline can enable the radiosyntheses of clinically relevant but synthetically challenging radiolabeled compounds of high interest to the imaging community.
Uncertainty-Based Biological Age Estimation of Brain MRI Scans
2021-05-13

Age is an essential factor in modern diagnostic procedures. However,\\nassessment of the true biological age (BA) remains a daunting task due to the\\nlack of reference ground-truth labels. Current BA estimation approaches are\\neither restricted to skeletal images or rely on non-imaging modalities that\\nyield a whole-body BA assessment. However, various organ systems may exhibit\\ndifferent aging characteristics due to lifestyle and genetic factors. In this\\ninitial study, we propose a new framework for organ-specific BA estimation\\nutilizing 3D magnetic resonance image (MRI) scans. As a first step, this\\nframework predicts the chronological age (CA) together with the corresponding\\npatient-dependent aleatoric uncertainty. An iterative training algorithm is\\nthen utilized to segregate atypical aging patients from the given population\\nbased on the predicted uncertainty scores. In this manner, we hypothesize that\\ntraining a new model on the remaining population should approximate the true BA\\nbehavior. We apply the proposed methodology on a brain MRI dataset containing\\nhealthy individuals as well as Alzheimer's patients. We demonstrate the\\ncorrelation between the predicted BAs and the expected cognitive deterioration\\nin Alzheimer's patients.\\n
ABA homeostasis and long-distance translocation is redundantly regulated by ABCG ABA importers
2021-05-13

Abstract The effects of abscisic acid (ABA) on plant growth, development and response to the environment depend on local ABA concentrations. Here, we exploited a genome-scale amiRNA screen, targeting the Arabidopsis transportome, to show that ABA homeostasis is regulated by two previously unknown ABA transporters. ABCG17 and ABCG18 are localized to the plasma membranes of leaf mesophyll and stem cortex cells to redundantly promote ABA import, leading to conjugated inactive ABA sinks, thus restricting stomatal closure. ABCG17 and ABCG18 double knockdown revealed that the transporters encoded by these genes not only limit stomatal aperture size, conductance and transpiration while increasing water-use efficiency but also control ABA translocation from the shoot to the root to regulate lateral root emergence. The proposed ABCG17- and ABCG18-dependent ABA glucosyl ester shoot sink mechanism is restrained under abiotic stress conditions to further activate the ABA responses.