julilili42/papers huggingface dataset:
Antibacterial Synnepyrroles from Human-Associated Nocardiopsis sp. Show Protonophore Activity and Disrupt the Bacterial Cytoplasmic Membrane
2022-09-30

Actinobacteria have traditionally been an important source of bioactive natural products, although many genera remain poorly explored. Here, we report a group of distinctive pyrrole-containing natural products, named synnepyrroles, from <i>Nocardiopsis synnemataformans</i>. Detailed structural characterization by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy combined with isotope-labeling experiments revealed their molecular structures and biosynthetic precursors acetate, propionate, aspartate, and (for branched analogues) valine. The biosynthetic data points toward an unusual pathway for pyrrole formation via condensation of aspartate with diverse fatty acids that give rise to a unique pyrrole-3,4-dicarboxylate core and variable linear or terminally branched alkyl side chains. In addition, the bioactivity and mode of action of synnepyrrole A were characterized in <i>Bacillus subtilis</i>. Orienting assessment of the phenotype of synnepyrrole A-treated bacteria by high-resolution microscopy suggested the cytoplasmic membrane as the target structure. Further characterization of the membrane effects demonstrated dissipation of the membrane potential and intracellular acidification indicative of protonophore activity. At slightly higher concentrations, synnepyrrole A compromised the barrier function of the cytoplasmic membrane, allowing the passage of otherwise membrane-impermeable dye molecules.
Ivermectin treatment in rosacea: How novel smartphone technology can support monitoring rosacea‐associated signs and symptoms
2022-09-30

Rosacea lessens patients' quality of life not only by visible symptoms like erythema, papules, and pustules but also by invisible symptoms like stinging, burning, and dryness. Ivermectin 1% cream has recently been introduced as an efficient therapy for papules and pustules in rosacea patients. To investigate the potential of ivermectin 1% cream to improve rosacea-associated erythema and invisible symptoms by combining established questionnaires with the novel photography and analysis tool Scarletred®Vision. We performed an open monocentric pilot study including 25 Caucasian patients presenting with moderate to severe rosacea with erythema, less than 10 papules and/or pustules, and ≥ 15 Demodex mites/cm2 . Patients applied 1 g of ivermectin 1% cream (Soolantra®) once a day for ≥16 weeks. Skin symptoms were recorded at baseline, week 8 and ≥ week 16. Grade of erythema was determined by clinician erythema assessment (CEA) and patient self-assessment (PSA). Severity of invisible skin symptoms (stinging and/or burning, dryness, itching) were assessed by questionnaire. Erythema and skin texture were additionally quantified using Scarletred®Vision. Ivermectin 1% cream significantly reduced invisible symptoms of rosacea (stinging and/or burning, dryness: p < 0.0001; itching p < 0.001; at ≥16 weeks). Analysis with Scarletred®Vision confirmed CEA and PSA results for improvement of erythema (p < 0.0001; at ≥16 weeks) and skin roughness (p < 0.001; at ≥16 weeks). Treatment with ivermectin 1% cream is efficient in treating not only rosacea-associated papules and pustules but also erythema and invisible skin symptoms.
Inflammatory Surrogate Parameters for Predicting Ifosfamide-Induced Neurotoxicity in Sarcoma Patients
2022-09-30

Sarcomas compromise a heterogenous group of tumors of a mesenchymal origin. Although treatment options in many solid tumors have evolved over the past decades, the treatment of advanced sarcoma is still based on conventional chemotherapeutic agents. Beside anthracyclines, alkylating agents such as ifosfamide are frequently used in sarcoma treatment. However, treatment with ifosfamide can cause severe dose- and treatment-limiting side effects, such as ifosfamide-induced neurotoxicity (IIN). Especially in sarcoma, consecutive risk assessment analyses investigating the individual factors associated with the increased incidence in IIN, remain insufficient so far. In this retrospective analysis, we investigated 172 sarcoma patients treated with ifosfamide. Out of 172 patients, 49 patients (28.5%) developed IIN. While gender, age, histologic origin, and tumor stage were not associated with the occurrence of IIN, infusion times, simultaneous radiotherapy, and concomitant use of opioids or anticonvulsants affected the risk of developing IIN. Sarcoma patients with IIN showed an alteration in several inflammatory markers, including a lower lymphocyte count, hemoglobin levels, and calcium levels, as well as elevated GGT, sodium, and CRP levels. Remarkably, the occurrence of IIN was associated with a worse prognosis regarding progression free and overall survival. In addition, high CTCAE grades were negatively associated with overall survival in sarcoma. The observation that an inflammatory state is associated with an increased risk of IIN in sarcoma patients can be used prospectively to further investigate the relationship of inflammation and IIN. In addition, the easily accessible blood markers used in our study to predict IIN can be incorporated into clinical decision making.
Learning with phenotypic similarity improves the prediction of functional effects of missense variants in voltage-gated sodium channels
2022-09-30

Abstract Background Missense variants in genes encoding voltage-gated sodium channels are associated with a spectrum of severe diseases affecting neuronal and muscle cells, the so-called sodium channelopathies. Variant effects on the biophysical function of the channel correlate with clinical features and can in most cases be categorized as an overall gain- or loss-of-function. This information enables a timely diagnosis, facilitates precision therapy, and guides prognosis. Machine learning models may be able to rapidly generate supporting evidence by predicting variant functional effects. Methods Here, we describe a novel multi-task multi-kernel learning framework capable of harmonizing functional results and structural information with clinical phenotypes. We included 62 sequence- and structure-based features such as amino acid physiochemical properties, substitution radicality, conservation, protein-protein interaction sites, expert annotation, and others. We harmonized phenotypes as human phenotype ontology (HPO) terms, and compared different measures of phenotypic similarity under simulated sparsity or noise. The final model was trained on whole-cell patch-clamp recordings of 375 unique non-synonymous missense variants each expressed in mammalian cells. Results Our gain- or loss-of-function classifier outperformed both conventional baseline and state-of-the-art methods on internal validation (mean accuracy 0.837 ± 0.035, mean AU-ROC 0.890 ± 0.023) and on an independent set of recently described variants (n = 30, accuracy 0.967, AU-ROC 1.000). Model performance was robust across different phenotypic similarity measures and largely insensitive to phenotypic noise or sparsity. Localized multi-kernel learning offered biological insight and interpretability by highlighting channels with implicit genotype-phenotype correlations or latent task similarity for downstream analysis. Conclusions Learning with phenotypic similarity makes efficient use of clinical information to enable accurate and robust prediction of variant functional effects. Our framework extends the use of human phenotype ontology terms towards kernel-based methods in machine learning. Training data, pre-trained models, and a web-based graphical user interface for the model are publicly available.
Effects of age and sex on outcomes of the Q-Motor speeded finger tapping and grasping and lifting tests-findings from the population-based BiDirect Study
2022-09-30

Background Q-Motor is a suite of motor tests originally designed to assess motor symptoms in Huntington's disease. Among others, Q-Motor encompasses a finger tapping task and a grasping and lifting task. To date, there are no systematic investigations regarding effects of variables which may affect the performance in specific Q-Motor tests per se , and normative Q-Motor data based on a large population-based sample are not yet available. Objective We investigated effects of age and sex on five selected Q-Motor outcomes representing the two core Q-Motor tasks speeded finger tapping and grasping and lifting in a community sample of middle-aged to elderly adults. Furthermore, we explored effects of the potentially mediating variables educational attainment, alcohol consumption, smoking status, and depressive symptoms. Moreover, we explored inter-examiner variability. Finally, we compared the findings to findings for the Purdue Pegboard test. Methods Based on a sample of 726 community-dwelling adults and using multiple (Gaussian) regression analysis, we modeled the motor outcomes using age, sex, years in full-time education, depressive symptoms in the past seven days, alcohol consumption in the past seven days, and smoking status as explanatory variables. Results With regard to the Q-Motor tests, we found that more advanced age was associated with reduced tapping speed, male sex was associated with increased tapping speed and less irregularity, female sex was associated with less involuntary movement, more years of education were associated with increased tapping speed and less involuntary movement, never smoking was associated with less involuntary movement compared to current smoking, and more alcohol consumed was associated with more involuntary movement. Conclusion The present results show specific effects of age and sex on Q-Motor finger tapping and grasping and lifting performance. In addition, besides effects of education, there also were specific effects of smoking status and alcohol consumption. Importantly, the present study provides normative Q-Motor data based on a large population-based sample. Overall, the results are in favor of the feasibility and validity of Q-Motor finger tapping and grasping and lifting for large observational studies. Due to their low task-complexity and lack of placebo effects, Q-Motor tests may generate additional value in particular with regard to clinical conditions such as Huntington's or Parkinson's disease.
Do Output-Dependent Prizes Alleviate the Sabotage Problem in Tournaments?
2022-09-30

We investigate whether tournament prizes that depend on joint output (“variable prize tournaments”) can alleviate the sabotage problem which is otherwise inherent in tournament structures. In a game-theoretical model with three contestants, we compare fixed-prize tournaments with tournaments where prizes depend on contestants’ joint output. Our analysis suggests that the incentives to sabotage in a fixed-prize tournament may be counteracted in a variable-prize tournament such that contestants no longer sabotage, but help one another. We empirically test the implications of our model with the help of a classroom experiment where we compare participants’ choices in a fixed-prize treatment (FP) with those of a variable-prize treatment (VP) in a between-subjects design. Given our parametrization, we expect efforts to be identical in both treatments, and we expect sabotage in the FP treatment and no sabotage in the VP treatment. In accordance with the model, we find that participants in the fixed-prize tournament sabotage one another, whereas participants in the variable-prize tournament help one another. At the same time, participants’ effort levels do not vary between the two treatments.
The complete chloroplast genome of the endangered species garra de león [Bomarea ovallei (Phil.) Ravenna] from Chile
2022-09-30

Bomarea ovallei (Phil.) Ravenna (2n=2x=18) is an endangered endemic species that inhabits only a small part of the coast of the Atacama region. We describe the structure, gene composition and phylogeny of the complete chloroplast sequence of this elusive species. The chloroplast genome consists of 155,018 bp, with typical quadripartite structures: a large single copy region (LSC) of 84,132 bp, a small single copy region (SSC) of 17,794 bp, and two inverted repeat regions (IRs) contain 26,546 bp. One hundred and thirty-four genes were identified out of which 84 coding genes, 8 rRNA, 38 tRNA and 4 pseudogenes. B. ovallei chloroplast resembles chloroplasts from seven species of the order Liliales in length and structure and is most similar to Bomarea edulis (BP=100). The average nucleotide variability (Pi) of 0.00254 between these two Bomarea species is moderate. Nine loci with increased variability were identified: rps16-trnQ, atpF, trnL, ndhC-trnV, rbcL, psbJ, rpl32-trnL, ndhD and ycf1. These loci could be used as DNA markers for classification and evaluation studies in Bomarea populations.
TRoponin of Unknown origin in STroke evaluated by multi-component cardiac Magnetic resonance Imaging – The TRUST-MI study
2022-09-30

Aims Increased high-sensitive cardiac troponin I (hs-cTnI) levels are common in patients with acute ischemic stroke. However, only a minority demonstrates culprit lesions on coronary angiography, suggesting other mechanisms, e.g., inflammation, as underlying cause of myocardial damage. Late Gadolinium Enhancement (LGE)-cardiac magnetic resonance (CMR) with mapping techniques [T1, T2, extracellular volume (ECV)] allow the detection of both focal and diffuse myocardial abnormalities. We investigated the prevalence of culprit lesions by coronary angiography and myocardial tissue abnormalities by a comprehensive CMR protocol in troponin-positive stroke patients. Methods and results Patients with troponin-positive acute ischemic stroke and no history of coronary artery disease were prospectively enrolled. Coronary angiography and CMR (LGE, T1 + T2 mapping, ECV) were performed within the first days of the acute stroke. Twenty-five troponin-positive patients (mean age 62 years, 44% females) were included. 2 patients (8%) had culprit lesions on coronary angiography and underwent percutaneous coronary intervention. 13 patients (52%) demonstrated LGE: (i) n = 4 ischemic, (ii) n = 4 non-ischemic, and (iii) n = 5 ischemic AND non-ischemic. In the 12 LGE-negative patients, mapping revealed diffuse myocardial damage in additional 9 (75%) patients, with a high prevalence of increased T2 values. Conclusions Our data show a low prevalence of culprit lesions in troponin-positive stroke patients. However, &amp;gt; 50% of the patients demonstrated myocardial scars (ischemic + non-ischemic) by LGE-CMR. Mapping revealed additional myocardial abnormalities (mostly inflammatory) in the majority of LGE-negative patients. Therefore, a comprehensive CMR protocol gives important insights in the etiology of troponin which might have implications for the further work-up of troponin-positive stroke patients.
Neural representations of the content and production of human vocalization
2022-09-30

Abstract Speech, as the spoken form of language, is fundamental for human communication. The phenomenon of covert inner speech implies a functional independence of speech content and motor production. However, it remains unclear how a flexible mapping between speech content and production is achieved on the neural level. To address this, we recorded magnetoencephalography (MEG) in humans performing a rule-based vocalization task. On each trial, vocalization content (one of two vowels) and production form (overt or covert) were instructed independently. Using multivariate pattern analysis, we found robust neural information about vocalization content and production, mostly originating from speech areas of the left hemisphere. Production signals dynamically transformed upon presentation of the content cue, whereas content signals remained largely stable throughout the trial. In sum, our results show dissociable neural representations of vocalization content and production in the human brain and provide new insights into the neural dynamics underlying human vocalization.
Rosenzweig and Luther. The Concept of Faith in the Perspective of «New Thinking» and Bible Translation
2022-09-30

In his “The Star of Redemption”, Rosenzweig engages not only in an argument with philosophy, but also with theology. Next to Augustine and Friedrich Schleiermacher Martin Luther was a counterpart in whose face he developed his dialogical “new thinking”. The essay takes up the traces of this dispute in the letters to focus here on Rosenzweig's reading of Ricarda Huch's “Luther’s Faith”. This literary picture is then related in a sketch to Luther's Reformation theology as it emerges from contemporary research. In a next step, the “Star” is interpreted as a book that, on the one hand, owes much to a previous reception of Luther, but on the other hand, also shows the Reformator's thinking in a new light. Finally, the late writings on the problem of translation come into view in order to justify Rosenzweig’s “Verdeutschung” of the Hebrew Bible, undertaken together with Buber, to Luther’s “German Bible”.
CLSM data of 1st instar larva of Dilar montanus
2022-09-30

The 1st instar larva of<em> Dilar montanus </em>Yang was mounted between two cover slips with double-sided tape spacers in a drop of methyl-salicylate and scanned from both sides with an argon laser emitting light of 488 – 579 nm wave length using a Zeiss LSM 880. The obtained datasets were stitched together using the “align manually with landmarks” tool of the TrackEM plugin for ImageJ and exported as a .tiff images stack. The voxel size for the dataset is 1.489 μm x 1.489 μm x 8.277 μm.
CLSM data of 1st instar larva of Dilar montanus
2022-09-30

&amp;lt;p&amp;gt;The 1st instar larva of&amp;lt;em&amp;gt; Dilar montanus &amp;lt;/em&amp;gt;Yang was mounted between two cover slips with double-sided tape spacers in a drop of methyl-salicylate and scanned from both sides with an argon laser emitting light of 488 &amp;ndash; 579 nm wave length using a Zeiss LSM 880. The obtained datasets were stitched together using the &amp;ldquo;align manually with landmarks&amp;rdquo; tool of the TrackEM plugin for ImageJ and exported as a .tiff images stack. The voxel size for the dataset is 1.489 &amp;micro;m x 1.489 &amp;micro;m x 8.277 &amp;micro;m.&amp;lt;/p&amp;gt;
The X-Ray Polarization View of Mrk 421 in an Average Flux State as Observed by the Imaging X-Ray Polarimetry Explorer
2022-10-01

Abstract Particle acceleration mechanisms in supermassive black hole jets, such as shock acceleration, magnetic reconnection, and turbulence, are expected to have observable signatures in the multiwavelength polarization properties of blazars. The recent launch of the Imaging X-Ray Polarimetry Explorer (IXPE) enables us, for the first time, to use polarization in the X-ray band (2–8 keV) to probe the properties of the jet synchrotron emission in high-synchrotron-peaked BL Lac objects (HSPs). We report the discovery of X-ray linear polarization (degree Π x = 15% ± 2% and electric vector position angle ψ x = 35° ± 4°) from the jet of the HSP Mrk 421 in an average X-ray flux state. At the same time, the degree of polarization at optical, infrared, and millimeter wavelengths was found to be lower by at least a factor of 3. During the IXPE pointing, the X-ray flux of the source increased by a factor of 2.2, while the polarization behavior was consistent with no variability. The higher level of Π x compared to longer wavelengths, and the absence of significant polarization variability, suggest a shock is the most likely X-ray emission site in the jet of Mrk 421 during the observation. The multiwavelength polarization properties are consistent with an energy-stratified electron population, where the particles emitting at longer wavelengths are located farther from the acceleration site, where they experience a more disordered magnetic field.
Prospects for detecting the diffuse supernova neutrino background with JUNO
2022-10-01

Abstract We present the detection potential for the diffuse supernova neutrino background (DSNB) at the Jiangmen Underground Neutrino Observatory (JUNO), using the inverse-beta-decay (IBD) detection channel on free protons. We employ the latest information on the DSNB flux predictions, and investigate in detail the background and its reduction for the DSNB search at JUNO. The atmospheric neutrino induced neutral current (NC) background turns out to be the most critical background, whose uncertainty is carefully evaluated from both the spread of model predictions and an envisaged in situ measurement. We also make a careful study on the background suppression with the pulse shape discrimination (PSD) and triple coincidence (TC) cuts. With latest DSNB signal predictions, more realistic background evaluation and PSD efficiency optimization, and additional TC cut, JUNO can reach the significance of 3σ for 3 years of data taking, and achieve better than 5σ after 10 years for a reference DSNB model. In the pessimistic scenario of non-observation, JUNO would strongly improve the limits and exclude a significant region of the model parameter space.
X-Ray Polarization Detection of Cassiopeia A with IXPE
2022-10-01

Abstract We report on a ∼5 σ detection of polarized 3–6 keV X-ray emission from the supernova remnant Cassiopeia A (Cas A) with the Imaging X-ray Polarimetry Explorer (IXPE). The overall polarization degree of 1.8% ± 0.3% is detected by summing over a large region, assuming circular symmetry for the polarization vectors. The measurements imply an average polarization degree for the synchrotron component of ∼2.5%, and close to 5% for the X-ray synchrotron-dominated forward shock region. These numbers are based on an assessment of the thermal and nonthermal radiation contributions, for which we used a detailed spatial-spectral model based on Chandra X-ray data. A pixel-by-pixel search for polarization provides a few tentative detections from discrete regions at the ∼ 3 σ confidence level. Given the number of pixels, the significance is insufficient to claim a detection for individual pixels, but implies considerable turbulence on scales smaller than the angular resolution. Cas A’s X-ray continuum emission is dominated by synchrotron radiation from regions within ≲10 17 cm of the forward and reverse shocks. We find that (i) the measured polarization angle corresponds to a radially oriented magnetic field, similar to what has been inferred from radio observations; (ii) the X-ray polarization degree is lower than in the radio band (∼5%). Since shock compression should impose a tangential magnetic-field structure, the IXPE results imply that magnetic fields are reoriented within ∼10 17 cm of the shock. If the magnetic-field alignment is due to locally enhanced acceleration near quasi-parallel shocks, the preferred X-ray polarization angle suggests a size of 3 × 10 16 cm for cells with radial magnetic fields.
Thermodynamics of quantum-jump trajectories of open quantum systems subject to stochastic resetting
2022-10-01

We consider Markovian open quantum systems subject to stochastic resetting, which means that the dissipative time evolution is reset at randomly distributed times to the initial state. We show that the ensuing dynamics is non-Markovian and has the form of a generalized Lindblad equation. Interestingly, the statistics of quantum-jumps can be exactly derived. This is achieved by combining techniques from the thermodynamics of quantum-jump trajectories with the renewal structure of the resetting dynamics. We consider as an application of our analysis a driven two-level and an intermittent three-level system. Our findings show that stochastic resetting may be exploited as a tool to tailor the statistics of the quantum-jump trajectories and the dynamical phases of open quantum systems.