julilili42/papers huggingface dataset:
Remote Testing of the Familiar Word Effect With Non-dialectal and Dialectal German-Learning 1–2-Year-Olds
2021-12-02

Variability is pervasive in spoken language, in particular if one is exposed to two varieties of the same language (e.g., the standard variety and a dialect). Unlike in bilingual settings, standard and dialectal forms are often phonologically related, increasing the variability in word forms (e.g., German Fuß “foot” is produced as [fus] in Standard German and as [fs] in the Alemannic dialect). We investigate whether dialectal variability in children’s input affects their ability to recognize words in Standard German, testing non-dialectal vs. dialectal children. Non-dialectal children, who typically grow up in urban areas, mostly hear Standard German forms, and hence encounter little segmental variability in their input. Dialectal children in turn, who typically grow up in rural areas, hear both Standard German and dialectal forms, and are hence exposed to a large amount of variability in their input. We employ the familiar word paradigm for German children aged 12–18 months. Since dialectal children from rural areas are hard to recruit for laboratory studies, we programmed an App that allows all parents to test their children at home. Looking times to familiar vs. non-familiar words were analyzed using a semi-automatic procedure based on neural networks. Our results replicate the familiarity preference for non-dialectal German 12–18-month-old children (longer looking times to familiar words than vs. non-familiar words). Non-dialectal children in the same age range, on the other hand, showed a novelty preference. One explanation for the novelty preference in dialectal children may be more mature linguistic processing, caused by more variability of word forms in the input. This linguistic maturation hypothesis is addressed in Experiment 2, in which we tested older children (18–24-month-olds). These children, who are not exposed to dialectal forms, also showed a novelty preference. Taken together, our findings show that both dialectal and non-dialectal German children recognized the familiar Standard German word forms, but their looking pattern differed as a function of the variability in the input. Frequent exposure to both dialectal and Standard German word forms may hence have affected the nature of (prelexical and/or) lexical representations, leading to more mature processing capacities.
Glucose-1,6-bisphosphate, a key metabolic regulator, is synthesized by a distinct family of α-phosphohexomutases widely distributed in prokaryotes
2021-12-02

Abstract The reactions of α-D-phosphohexomutases (αPHM) are ubiquitous, key to primary metabolism and essential for several processes in all domains of life. The functionality of these enzymes relies on an initial auto-phosphorylation step which requires the presence of α-D-glucose-1,6-bisphosphate (Glc-1,6-BP). While well investigated in vertebrates, the origin of this activator compound in bacteria is unknown. Here we show that the Slr1334 protein from the unicellular cyanobacterium Synechocysitis sp. PCC 6803 is a Glc-1,6-BP-synthase. Biochemical analysis revealed that Slr1334 efficiently converts fructose-1,6-bisphosphate (Frc-1,6-BP) and α-D-glucose-1-phosphate/α-D-glucose-6-phosphate into Glc-1,6-BP and also catalyzes the reverse reaction. As inferred from phylogenetic analysis, the slr1334 product belongs to a primordial subfamily of αPHMs that is present especially in deeply branching bacteria and also includes human commensals and pathogens. Remarkably, the homologue of Slr1334 in the human gut bacterium Bacteroides salyersiae catalyzes the same reaction, suggesting a conserved and essential role for the members of this αPHM subfamily.
Novel corrections to the momentum sum rule for nuclear structure functions
2021-12-02

We address novel features of deep inelastic lepton scattering on nuclei at small Bjorken variable xB j. In this regime the lepton-nuclear cross section involves the interference between the standard lepton-quark scattering amplitude for the deep inelastic scattering (DIS) process on a single nucleon and a two-step process where diffractive scattering on a first nucleon combines with the amplitude for DIS on a second nucleon. The phases associated with the t-channel exchanges to the diffractive amplitude can produce either a destructive or constructive quantum-mechanical interference of the one-step and two-step amplitudes. This provides a mechanism regulating the respective amounts of shadowing suppression and anti-shadowing enhancement at low xB j. Furthermore, the standard leading-twist operator product and handbag diagram analyses of the forward virtual Compton amplitude on the nucleus are inapplicable, barring a conventional probabilistic interpretation. A main observable consequence is the impossibility of extracting momentum and spin sum rules from nuclear structure functions. We present numerical predictions supporting this picture and test them against DIS neutrino-nucleus and charged-lepton-nucleus scattering data.
Fluorescence blinking in MoS2 atomic layers by single photon energy transfer
2021-12-02

Abstract The quantum optical phenomena, such as single photon emission, in two-dimensional (2D) transition metal dichalcogenides (TMDCs) have triggered extensive researches on 2D material-based quantum optics and devices. By far, most reported quantum optical emissions in TMDCs are based on atomic defects in the material or the local confinement of excitons by introducing local stain or potential. In contrast, energy transfer between two materials could also manipulate the photon emission behaviors in materials, even at the single photon level. Along with the single-photon emission nature of zero-dimensional (0D) quantum dots (QDs) at room temperature, constructing a 0D-2D hybrid heterostructure may provide an effective way to regulate the quantum states related optical emissions of TMDCs. Here, we report on fluorescence blinking, a quantum phenomenon, from MoS2 atomic layers in QD/ MoS2 heterostructure at room temperature. We demonstrate the single-photon nature of the QDs in heterostructures by second-order photon correlation measurements. Based on the transient PL spectroscopy and PL time trajectories, we attribute the fluorescence blinking behavior in MoS2 to the single photon energy transfer from QD to MoS2. Our work opens the possibility to achieve correlated quantum emitters in TMDCs at room temperature by controlling the energy transfer between QD and TMDCs.
NamZ1 and NamZ2 from the oral pathogen Tannerella forsythia are peptidoglycan processing exo-β-N-acetylmuramidases with distinct substrate specificity
2021-12-02

ABSTRACT The Gram-negative periodontal pathogen Tannerella forsythia is inherently auxotrophic for N -acetylmuramic acid (MurNAc), which is an essential carbohydrate constituent of the peptidoglycan (PGN) of the bacterial cell wall. Thus, to build up its cell wall, T. forsythia strictly depends on the salvage of exogenous MurNAc or sources of MurNAc, such as polymeric or fragmentary PGN, derived from cohabiting bacteria within the oral microbiome. In our effort to elucidate how T. forsythia satisfies its demand for MurNAc, we recognized that the organism possesses three putative orthologs of the exo-β- N -acetylmuramidase BsNamZ from Bacillus subtilis , which cleaves non-reducing end, terminal MurNAc entities from the artificial substrate pNP-MurNAc and the naturally-occurring disaccharide substrate MurNAc-β-1,4- N -acetylglucosamine (GlcNAc). TfNamZ1 and TfNamZ2 were successfully purified as soluble, pure recombinant His 6 -fusions and characterized as exo-lytic β- N -acetylmuramidases with distinct substrate specificities. The activity of TfNamZ1 was considerably lower compared to TfNamZ2 and BsNamZ, in the cleavage of pNP-MurNAc and MurNAc-GlcNAc. When peptide-free PGN glycans were used as substrates, we revealed striking differences in the specificity and mode of action of these enzymes, as analyzed by mass spectrometry. TfNamZ1, but not TfNamZ2 or BsNamZ, released GlcNAc-MurNAc disaccharides from these glycans. In addition, glucosamine (GlcN)-MurNAc disaccharides were generated when partially N-deacetylated PGN glycans from B. subtilis 168 were applied. This characterizes TfNamZ1 as a unique disaccharide-forming exo-lytic β- N -acetylmuramidase (exo-disaccharidase), and, TfNamZ2 and BsNamZ as sole MurNAc monosaccharide-lytic exo-β- N -acetylmuramidases. IMPORTANCE Two exo-β- N -acetylmuramidases from T. forsythia belonging to glycosidase family GH171 ( www.cazy.org ) were shown to differ in their activities, thus revealing a functional diversity within this family: NamZ1 releases disaccharides (GlcNAc-MurNAc/GlcN-MurNAc) from the non-reducing ends of PGN glycans, whereas NamZ2 releases terminal MurNAc monosaccharides. This work provides a better understanding of how T. forsythia may acquire the essential growth factor MurNAc by the salvage of PGN from cohabiting bacteria in the oral microbiome, which may pave avenues for the development of anti-periodontal drugs. On a broad scale, our study indicates that the utilization of PGN as a nutrient source, involving exo-lytic N -acetylmuramidases with different modes of action, appears to be a general feature of bacteria, particularly among the phylum Bacteroidetes.
First eROSITA study of nearby M dwarfs and the rotation-activity relation in combination with TESS
2021-12-03

We present the first results with the ROentgen Survey with an Imaging Telescope Array (eROSITA) on board the Russian Spektrum-Roentgen-Gamma mission, and we combine the new X-ray data with observations with the Transiting Exoplanet Survey Satellite (TESS). We used the SUPERBLINK proper motion catalog of nearby M dwarfs as input sample to search for eROSITA and TESS data. We extracted Gaia DR2 data for the full M dwarf catalog, which comprises ~9000 stars, and we calculated the stellar parameters from empirical relations with optical/IR colors. Then we cross-matched this catalog with the eROSITA Final Equatorial Depth Survey (eFEDS) and the first eROSITA all-sky survey (eRASS1). After a meticulous source identification in which we associated the closest Gaia source with the eROSITA X-ray detections, our sample of M dwarfs is defined by 687 stars with SpT = K5..M7 (673 from eRASS1 and 14 from eFEDS). While for eRASSl we used the data from the source catalog provided by the eROSITA_DE consortium, for the much smaller eFEDS sample, we performed the data extraction, and we analyzed the X-ray spectra and light curves. This unprecedented data base for X-ray emitting M dwarfs allowed us to place a quantitative constraint on the mass dependence of the X-ray luminosity, and to determine the change in the activity level with respect to pre-main-sequence stars. TESS observations are available for 489 of 687 X-ray detected M dwarfs. By applying standard period search methods, we were able to determine the rotation period for 180 X-ray detected M dwarfs. This is about one-forth of the X-ray sample. With the joint eROSITA and TESS sample, and combining it with our compilation of historical X-ray and rotation data for M dwarfs, we examined the mass dependence of the saturated regime of the rotation-activity relation. A first comparison of eROSITA hardness ratios and spectra shows that 65% of the X-ray detected M dwarfs have coronal temperatures of ~0.5 keV. We performed a statistical investigation of the long-term X-ray variability of M dwarfs by comparing the eROSITA measurements to those obtained ~30 yr earlier during the ROSAT all-sky survey (RASS). Evidence for X-ray flares is found in various parts of our analysis: directly from an inspection of the eFEDS light curves, in the relation between RASS and eRASSl X-ray luminosities, and in a subset of stars that displays hotter X-ray emission than the bulk of the sample according to the hardness ratios. Finally, we point out the need to obtain X-ray spectroscopy for more M dwarfs to study the coronal temperature-luminosity relation, which is not well constrained by our eFEDS results.
Working memory capacity of crows and monkeys arises from similar neuronal computations
2021-12-03

Complex cognition relies on flexible working memory, which is severely limited in its capacity. The neuronal computations underlying these capacity limits have been extensively studied in humans and in monkeys, resulting in competing theoretical models. We probed the working memory capacity of crows ( Corvus corone ) in a change detection task, developed for monkeys ( Macaca mulatta ), while we performed extracellular recordings of the prefrontal-like area nidopallium caudolaterale. We found that neuronal encoding and maintenance of information were affected by item load, in a way that is virtually identical to results obtained from monkey prefrontal cortex. Contemporary neurophysiological models of working memory employ divisive normalization as an important mechanism that may result in the capacity limitation. As these models are usually conceptualized and tested in an exclusively mammalian context, it remains unclear if they fully capture a general concept of working memory or if they are restricted to the mammalian neocortex. Here, we report that carrion crows and macaque monkeys share divisive normalization as a neuronal computation that is in line with mammalian models. This indicates that computational models of working memory developed in the mammalian cortex can also apply to non-cortical associative brain regions of birds.
Multi-Material 3D Printing of a Customized Sports Mouth Guard: Proof-of-Concept Clinical Case
2021-12-03

A multilayer mouth guard is known to have the best protective performance. However, its manufacturing in a digital workflow may be challenging with regards to virtual design and materialization. The present case demonstrates a pathway to fabricate a multilayer individualized mouth guard in a fully digital workflow, which starts with intraoral scanning. A free-form CAD software was used for the virtual design. Two various CAM techniques were used, including Polyjet 3D printing of rubber-like soft material and silicone printing using Drop-on-Demand technique. For both methods the outer layer was manufactured from more rigid materials to facilitate its protective function; the inner layer was printed from a softer material to aid a better adaptation to mucosa and teeth. Both 3D printed multilayer mouth guards showed a clinically acceptable fit and were met with patient appraisal. Their protective capacities must be evaluated in further clinical studies.
mTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in Energy Metabolism Caused by FH Loss in RPE Cells
2021-12-03

Age-related macular degeneration (AMD) is a complex degenerative disease of the retina with multiple risk-modifying factors, including aging, genetics, and lifestyle choices. The combination of these factors leads to oxidative stress, inflammation, and metabolic failure in the retinal pigment epithelium (RPE) with subsequent degeneration of photoreceptors in the retina. The alternative complement pathway is tightly linked to AMD. In particular, the genetic variant in the complement factor H gene (CFH), which leads to the Y402H polymorphism in the factor H protein (FH), confers the second highest risk for the development and progression of AMD. Although the association between the FH Y402H variant and increased complement system activation is known, recent studies have uncovered novel FH functions not tied to this activity and highlighted functional relevance for intracellular FH. In our previous studies, we show that loss of CFH expression in RPE cells causes profound disturbances in cellular metabolism, increases the vulnerability towards oxidative stress, and modulates the activation of pro-inflammatory signaling pathways, most importantly the NF-kB pathway. Here, we silenced CFH in hTERT-RPE1 cells to investigate the mechanism by which intracellular FH regulates RPE cell homeostasis. We found that silencing of CFH results in hyperactivation of mTOR signaling along with decreased mitochondrial respiration and that mTOR inhibition via rapamycin can partially rescue these metabolic defects. To obtain mechanistic insight into the function of intracellular FH in hTERT-RPE1 cells, we analyzed the interactome of FH via immunoprecipitation followed by mass spectrometry-based analysis. We found that FH interacts with essential components of the ubiquitin-proteasomal pathway (UPS) as well as with factors associated with RB1/E2F signalling in a complement-pathway independent manner. Moreover, we found that FH silencing affects mRNA levels of the E3 Ubiquitin-Protein Ligase Parkin and PTEN induced putative kinase (Pink1), both of which are associated with UPS. As inhibition of mTORC1 was previously shown to result in increased overall protein degradation via UPS and as FH mRNA and protein levels were shown to be affected by inhibition of UPS, our data stress a potential regulatory link between endogenous FH activity and the UPS.
Predicting the functional effects of voltage-gated potassium channel missense variants with multi-task learning
2021-12-03

Abstract Purpose Variants in genes encoding voltage-gated potassium channels are associated with a broad spectrum of neurological diseases including epilepsy, ataxia, and intellectual disability. Knowledge of the resulting functional changes, characterized as overall ion channel gain- or loss-of-function, is essential to guide clinical management including precision medicine therapies. However, for an increasing number of variants, little to no experimental data is available. New tools are needed to evaluate variant functional effects. Methods We catalogued a comprehensive dataset of 959 functional experiments across 19 voltage-gated potassium channels, leveraging data from 782 unique disease-associated and synthetic variants. We used these data to train a taxonomy-based multi-task learning support vector machine (MTL-SVM), and compared performance to a baseline of standard SVMs. Results MTL-SVM maintains channel family structure during model training, improving overall predictive performance (mean balanced accuracy 0.729 ± 0.029, AU-ROC 0.757 ± 0.039) over baseline (mean balanced accuracy 0.645 ± 0.041, AU-ROC 0.710 ± 0.074). We can obtain meaningful predictions even for channels with few known variants ( KCNC1, KCNQ5 ). Conclusion Our model enables functional variant prediction for voltage-gated potassium channels. It may assist in tailoring current and future precision therapies for the increasing number of patients with ion channel disorders.
Antiviral Drugs Against Influenza Virus
2021-12-03

Vaccination is the first choice to protect against influenza. However, the vaccine must be adjusted annually, and effectiveness is consistently only 50% or less. Since the vaccination rate is on average below 50%, only roughly 25% of the population is protected by vaccination. Therefore, antiviral drugs are important for therapeutic intervention. Moreover, in the case of a pandemic, especially in the early stages, when no vaccine is yet available, we are completely dependent on antiviral drugs. In this chapter, the currently available drugs for the therapy of influenza or those that are in clinical development will be presented.
High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study
2021-12-04

Abstract Background The rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue. Objective To determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types. Design Comprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers. Patients Deceased with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Collections of 29 vaccinees which were analyzed and compared to 141 nonvaccinated control cases. Results Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within the organism in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008). Vaccinated cases also showed high viral loads, reaching Ct values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. A fatal course after vaccination occurred in only 14% of all COVID-19 deceased in Augsburg. Limitations Restricted number of cases Conclusions Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions. Interestingly, we observed striking virus dissemination in our case study, which may indicate a decreased ability to eliminate the virus in patients with an impaired immune system. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Funding source This work was supported by the German Registry of COVID-19 Autopsies ( www.DeRegCOVID.ukaachen.de ) and funded by the Federal Ministry of Health (ZMVI1-2520COR201), the Federal Ministry of Education and Research within the framework of the network of university medicine (DEFEAT PANDEMICs, 01KX2021), and the German Federal Ministry of Food and Agriculture through the Federal Office for Agriculture and Food (project ZooSeq, grant number 2819114019).
Receptor Activator of NF-κB (RANK) Confers Resistance to Chemotherapy in AML and Associates with Dismal Disease Course
2021-12-04

Although treatment options of acute myeloid leukemia (AML) have improved over the recent years, prognosis remains poor. Better understanding of the molecular mechanisms influencing and predicting treatment efficacy may improve disease control and outcome. Here we studied the expression, prognostic relevance and functional role of the tumor necrosis factor receptor (TNFR) family member Receptor Activator of Nuclear Factor (NF)-κB (RANK) in AML. We conducted an experimental ex vivo study using leukemic cells of 54 AML patients. Substantial surface expression of RANK was detected on primary AML cells in 35% of the analyzed patients. We further found that RANK signaling induced the release of cytokines acting as growth and survival factors for the leukemic cells and mediated resistance of AML cells to treatment with doxorubicin and cytarabine, the most commonly used cytostatic compounds in AML treatment. In line, RANK expression correlated with a dismal disease course as revealed by reduced overall survival. Together, our results show that RANK plays a yet unrecognized role in AML pathophysiology and resistance to treatment, and identify RANK as “functional” prognostic marker in AML. Therapeutic modulation of RANK holds promise to improve treatment response in AML patients.