julilili42/papers huggingface dataset:
Stability of black holes with non-minimally coupled scalar hair to the Einstein tensor
2022-05-30

Abstract General relativity admits a plethora of exact compact object solutions. The augmentation of Einstein’s action with non-minimal coupling terms leads to modified theories with rich structure, which, in turn, provide non-trivial solutions with intriguing phenomenology. Thus, assessing their viability under generic fluctuations is of utmost importance for gravity theories. We consider static and spherically-symmetric solutions of a Horndeski subclass which includes a massless scalar field non-minimally coupled to the Einstein tensor. Such theory possesses second-order field equations and admits an exact black hole solution with scalar hair. Here, we study the stability of such solution under axial gravitational perturbations and find that it is linearly stable. The qualitative features of the ringdown waveform depend solely on the ratio of the two available parameters of spacetime, namely the black hole mass m and the non-minimal coupling strength <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mi>l</mml:mi> <mml:mi>η</mml:mi> </mml:msub> </mml:math> . Finally, we demonstrate the gravitational-wave ringdown transitions between three distinct patterns as the ratio <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>m</mml:mi> <mml:mo>/</mml:mo> <mml:msub> <mml:mi>l</mml:mi> <mml:mi>η</mml:mi> </mml:msub> </mml:mrow> </mml:math> increases; a state which is dominated by photon-sphere excitations and maintains a typical quasinormal ringdown, an intermediate long-lived state which exhibits gravitational-wave echoes and, finally, a state where the ringdown and echoes are depleted rapidly to turn to an exponential tail.
Geomorphology and shallow sub-sea-floor structures underneath the Ekström Ice Shelf, Antarctica
2022-05-30

Abstract. The Ekström Ice Shelf is one of numerous small ice shelves that fringe the coastline of western Dronning Maud Land, East Antarctica. Reconstructions of past ice-sheet extent in this area are poorly constrained, due to a lack of geomorphological evidence. Here, we present a compilation of geophysical surveys in front of and beneath the Ekström Ice Shelf, to identify and interpret evidence of past ice-sheet flow, extent and retreat. The sea floor beneath the Ekström Ice Shelf is dominated by an incised trough, which extends from the modern-day grounding line onto the continental shelf. Our surveys show that mega-scale glacial lineations cover most of the mouth of this trough, terminating 11 km away from the continental shelf break, indicating the most recent minimal extent of grounded ice in this region. Beneath the front ∼30 km of the ice shelf measured from the ice shelf edge towards the inland direction, the sea floor is characterised by an acoustically transparent sedimentary unit, up to 45 m thick. This is likely composed of subglacial till, further corroborating the presence of past grounded ice cover. Further inland, the sea floor becomes rougher, interpreted as a transition from subglacial tills to a crystalline bedrock, corresponding to the outcrop of the volcanic Explora Wedge at the sea floor. Ice retreat in this region appears to have happened rapidly in the centre of the incised trough, evidenced by a lack of overprinting of the lineations at the trough mouth. At the margins of the trough uniformly spaced recessional moraines suggest ice retreated more gradually. We estimate the palaeo-ice thickness at the calving front around the Last Glacial Maximum to have been at least 305 to 320 m, based on the depth of iceberg ploughmarks within the trough and sea level reconstructions. Given the similarity of the numerous small ice shelves along the Dronning Maud Land coast, these findings are likely representative for other ice shelves in this region and provide essential boundary conditions for palaeo ice-sheet models in this severely understudied region.
Future Directions for Chemosensory Connectomes: Best Practices and Specific Challenges
2022-05-30

Ecological chemosensory stimuli almost always evoke responses in more than one sensory system. Moreover, any sensory processing takes place along a hierarchy of brain regions. So far, the field of chemosensory neuroimaging is dominated by studies that examine the role of brain regions in isolation. However, to completely understand neural processing of chemosensation, we must also examine interactions between regions. In general, the use of connectivity methods has increased in the neuroimaging field, providing important insights to physical sensory processing, such as vision, audition, and touch. A similar trend has been observed in chemosensory neuroimaging, however, these established techniques have largely not been rigorously applied to imaging studies on the chemical senses, leaving network insights overlooked. In this article, we first highlight some recent work in chemosensory connectomics and we summarize different connectomics techniques. Then, we outline specific challenges for chemosensory connectome neuroimaging studies. Finally, we review best practices from the general connectomics and neuroimaging fields. We recommend future studies to develop or use the following methods we perceive as key to improve chemosensory connectomics: (1) optimized study designs, (2) reporting guidelines, (3) consensus on brain parcellations, (4) consortium research, and (5) data sharing.
Reflectometry curves (XRR and NR) and corresponding fits for machine learning
2022-05-30

This is a compiled dataset of raw X-ray reflectivity (XRR, reflectometry) measurements together with corresponding fit parameters, intentionally published to use as training or test data for machine learning models. (The authors aim to include NR data in further versions of this dataset and plan to include other substrates and materials for XRR. Contributions welcome!) <br> <strong>An interactive documentation can be found in <em>"README.html"</em> or at https://schreiber-lab.github.io/reflectometry-dataset.</strong> Data structure All data is provided in an hdf5 file, following NeXus convention with respect to the provided metadata in the hdf5 attributes. Some datesets have been measured in-situ and therefore there are stacks of curves that correspond to the different layer thicknesses of the same material on top of SiOx. The measured data is provided under experimental and the corresponding fit parameters under fit. Additional information is collected in metadata. Where to find the dataset and how to contribute Have a look at github and zenodo. In case you wish to contribute further curves to this dataset or have ideas how to improve the dataset or where else to deposit it, please contact the authors at softmatter AT ifap.uni-tuebingen.de.
Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8+ T Cells
2022-05-31

Abstract Effector CD8+ T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, T cells must acquire metabolic traits enabling sustained effector function at the tumor site to elicit a robust antitumor immune response. Here, we report that IL12-stimulated CD8+ T cells have elevated intracellular acetyl CoA levels and can maintain IFNγ levels in nutrient-deprived, tumor-conditioned media (TCM). Pharmacological and metabolic analyses demonstrated an active glucose–citrate–acetyl CoA circuit in IL12-stimulated CD8+ T cells supporting an intracellular pool of acetyl CoA in an ATP-citrate lyase (ACLY)–dependent manner. Intracellular acetyl CoA levels enhanced histone acetylation, lipid synthesis, and IFNγ production, improving the metabolic and functional fitness of CD8+ T cells in tumors. Pharmacological inhibition or genetic knockdown of ACLY severely impaired IFNγ production and viability of CD8+ T cells in nutrient-restricted conditions. Furthermore, CD8+ T cells cultured in high pyruvate–containing media in vitro acquired critical metabolic features of IL12-stimulated CD8+ T cells and displayed improved antitumor potential upon adoptive transfer in murine lymphoma and melanoma models. Overall, this study delineates the metabolic configuration of CD8+ T cells required for stable effector function in tumors and presents an affordable approach to promote the efficacy of CD8+ T cells for adoptive T-cell therapy. Significance: IL12-mediated metabolic reprogramming increases intracellular acetyl CoA to promote the effector function of CD8+ T cells in nutrient-depleted tumor microenvironments, revealing strategies to potentiate the antitumor efficacy of T cells.
Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3
2022-05-31

Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.
Arabidopsis PFA-DSP-Type Phosphohydrolases Target Specific Inositol Pyrophosphate Messengers
2022-05-31

Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With a cyclic array of phosphate esters and diphosphate groups around <i>myo</i>-inositol, these molecular messengers possess the highest charge density found in nature. Recent work deciphering inositol pyrophosphate biosynthesis in <i>Arabidopsis</i> revealed important functions of these messengers in nutrient sensing, hormone signaling, and plant immunity. However, despite the rapid hydrolysis of these molecules in plant extracts, very little is known about the molecular identity of the phosphohydrolases that convert these messengers back to their inositol polyphosphate precursors. Here, we investigate whether <i>Arabidopsis</i> Plant and Fungi Atypical Dual Specificity Phosphatases (PFA-DSP1-5) catalyze inositol pyrophosphate phosphohydrolase activity. We find that recombinant proteins of all five <i>Arabidopsis</i> PFA-DSP homologues display phosphohydrolase activity with a high specificity for the 5-β-phosphate of inositol pyrophosphates and only minor activity against the β-phosphates of 4-InsP<sub>7</sub> and 6-InsP<sub>7</sub>. We further show that heterologous expression of <i>Arabidopsis</i> PFA-DSP1-5 rescues wortmannin sensitivity and deranged inositol pyrophosphate homeostasis caused by the deficiency of the PFA-DSP-type inositol pyrophosphate phosphohydrolase Siw14 in yeast. Heterologous expression in <i>Nicotiana benthamiana</i> leaves provided evidence that <i>Arabidopsis</i> PFA-DSP1 also displays 5-β-phosphate-specific inositol pyrophosphate phosphohydrolase activity <i>in planta</i>. Our findings lay the biochemical basis and provide the genetic tools to uncover the roles of inositol pyrophosphates in plant physiology and plant development.
4-Chlorophenyl-N-furfuryl-1,2,4-triazole Methylacetamides as Significant 15-Lipoxygenase Inhibitors: an Efficient Approach for Finding Lead Anti-inflammatory Compounds
2022-05-31

Lipoxygenases (LOXs) are a class of enzymes that catalyze the production of pro-inflammatory mediators, such as leukotrienes and lipoxins, via an arachidonic acid cascade as soon as they are released from the membrane phospholipids after tissue injury. In continuation of our efforts in search for new LOX inhibitors, a series of chlorophenyl-furfuryl-based 1,2,4-triazole derivatives were prepared and evaluated for their 15-LOX inhibitory activities. A simple precursor, 4-chlorobenzoic acid (<b>a</b>), was consecutively transformed into benzoate (<b>1</b>), hydrazide (<b>2</b>), semicarbazide (<b>3</b>), and <i>N</i>-furfuryl 5-(4-chlorobenzyl)-4<i>H</i>-1,2,4-triazole (<b>4</b>), which when further merged with electrophiles (<b>6a-o</b>) resulted in end products (<b>7a-o</b>). The structural elucidations of the newly synthesized compounds (<b>7a-o</b>) were carried out by Fourier transform infrared, <sup>1</sup>H-, <sup>13</sup>C NMR spectroscopy, EI-MS, and HR-EI-MS spectrometry. The inhibitive capability of compounds (<b>7a-o</b>) on soybean 15-LOX was performed in vitro using the chemiluminescence method. The compounds <b>7k</b>, <b>7o</b>, <b>7m</b>, <b>7b,</b> and <b>7i</b> demonstrated potent activities (IC<sub>50</sub> 17.43 ± 0.38, 19.35 ± 0.71, 23.59 ± 0.68, 26.35 ± 0.62, and 27.53 ± 0.82 μM, respectively). These compounds revealed 79.5 to 98.8% cellular viability as measured by the MTT assay at 0.25 mM concentration. The structure-activity relationship (SAR) studies showed that the positions and the nature of substituents bonded to the phenyl ring are important in the determination of 15-LOX inhibitory activities. ADME, in silico, and density functional theory studies supported the evidence as yet another class of triazoles with potential lead properties in search for anti-LOX compounds with a safe gastrointestinal safety profile for various inflammatory diseases. Further work is in progress on the synthesis of more derivatives in search for anti-inflammatory agents.
Primary choice of estrogen and progestogen as components for HRT: a clinical pharmacological view
2022-05-31

Prescribing hormone replacement therapy (HRT) requires consideration of the selection of its two components, the estrogen and the progestogen. In terms of the estrogen, the decision is mainly whether to use estradiol (E2) or conjugated equine estrogens (CEE). These are the components needed to efficiently treat climacteric symptoms or/and prevent osteoporosis, currently the only labeled indications. There is still controversy regarding the adequate dosages comparing E2 and CEE; however, the consensus is that the differences in the efficacy of E2 and CEE are not a real issue. Therefore, other criteria have to be used. The first reason to add the progestogen is to avoid the development of endometrial cancer (i.e. to achieve 'endometrial safety'). Any available 'fixed-combined' HRT preparation has to be tested for sufficient endometrial efficacy, because the first question the health authorities ask before product registration relates to endometrial safety. We can generally rely on the endometrial safety of these fixed-combined products. However, it could be that we want to use 'free' combinations, which are necessary if we use transdermal E2 (patches, gel, spray), but also to individualize schedules, for example when treating bleeding problems. The question here is how to attain knowledge about the endometrial efficacy of the different progestogens and how to monitor therapy. We will try to answer these two questions from a 'clinical pharmacology' point of view, as a discipline which preferably considers pharmacological properties, but also relating to clinical practice, to achieve individualized therapy with optimal efficacy, best tolerability and minimal risks.
[(CH3)Al(CH2)]12: Methylaluminomethylene (MAM‐12)
2022-05-31

Abstract The molecular structure of enigmatic “poly(aluminium‐methyl‐methylene)” (first reported in 1968) has been unraveled in a transmetalation reaction with gallium methylene [Ga 8 (CH 2 ) 12 ] and AlMe 3 . The existence of cage‐like methylaluminomethylene moieties was initially suggested by the reaction of rare‐earth‐metallocene complex [Cp* 2 Lu{( μ ‐Me) 2 AlMe 2 }] with excess AlMe 3 affording the deca‐aluminium cluster [Cp* 4 Lu 2 ( μ 3 ‐CH 2 ) 12 Al 10 (CH 3 ) 8 ] in low yield (Cp*=C 5 Me 5 ). Treatment of [Ga 8 (CH 2 ) 12 ] with excess AlMe 3 reproducibly gave the crystalline dodeca‐aluminium complex [(CH 3 ) 12 Al 12 ( μ 3 ‐CH 2 ) 12 ] (MAM‐12). Revisiting a previous approach to “poly(aluminium‐methyl‐methylene” by using a (C 5 H 5 ) 2 TiCl 2 /AlMe 3 (1 : 100) mixture led to amorphous solids displaying solubility behavior and spectroscopic features similar to those of crystalline MAM‐12. The gallium methylene‐derived MAM‐12 was used as an efficient methylene transfer reagent for ketones.
Revisiting the high-mass transfer close binary star system AU Monocerotis
2022-05-31

Context. AU Monocerotis is an eclipsing, double-lined spectroscopic binary with a period of 11 days that is in a state of extreme mass transfer, consisting of a main sequence B-type embedded in a thick accretion disk fed by a Roche lobe overflowing evolved G-type companion. It is also one of the double periodic variable Algol-type binaries. Aims. Our aim is to study the accretion environment and the origin of the long cycle in the system. We present revised properties of the gainer by including contributions from the accretion disk and its boundary layer, because the absorption lines used in previous works to estimate the parameters were contaminated by the disk absorption. Methods. We performed a multiwavelength spectroscopic study using archival high-resolution IUE ultraviolet (1200–3200 Å) spectra and optical spectra (from about 3700–9000 Å) from FEROS, HARPS, and SOPHIE. Results. Using the optical He I lines and the UV Si III, C II, Si IV lines, we derived new parameters for the temperature, gravity, and rotational velocity of the B star. The IUE spectra delineate a stratified environment around the gainer, with spectral lines such as O I, Mg II, Al II, and Si II formed in the outer accretion disk and a pseudo-photospheric boundary layer that alters the spectrum. Phase-limited discrete outflows, detected in the time-dependent absorption, trace the stream impact site and the disturbance it creates downstream in the disk. The long-term variability is due to changes in the accretion disk structure and circumstellar environment. Enhanced systemic mass outflow is observed at long cycle maximum, reaching at least 1000 km s −1 . Conclusions. These results highlight the complex interplay between physical mechanisms that regulate the evolution of strongly interacting mass-exchanging binary stars.
Reflexive Saccades Used for Objective and Automated Measurements of Contrast Sensitivity in Selected Areas of Visual Field
2022-05-31

Assessment of CS using reflexive saccades extends the portfolio of suggested eye movement-based tests, allowing objective examination across the VF, which might be helpful especially in the early detection of various eye diseases.
Discontinuing atovaquone/proguanil prophylaxis ad-hoc post-exposure and during-travel dose-sparing prophylactic regimens against P. falciparum malaria: An update with pointers for future research
2022-05-31

Further research would be needed if the research question is considered of sufficient importance to facilitate evidence-based decision-making to modify current guidelines, as efficacy studies in travellers are fraught with confounders. We recommend human challenge trials to study abbreviated AP regimens pertaining to malaria chemoprophylaxis as they allow for rational, subject number, time- and cost-saving trial designs.
Improved preoperative risk stratification in endometrial carcinoma patients: External validation of the ENDORISK Bayesian network model in a large population-based case series
2022-05-31

Abstract Purpose Preoperative risk stratification of newly diagnosed endometrial carcinoma (EC) patients has been hindered by only moderate prediction performance for many years. Recently ENDORISK, a Bayesian network model, showed high predictive performance. It was the aim of this study to validate ENDORISK by applying the model to a population-based case series of EC patients. Methods ENDORISK was applied to a retrospective cohort of women surgically treated for EC from 2003-2013. Prediction accuracy for LNM as well as 5-year DSS was investigated. The model’s overall performance was quantified by the Brier score, discriminative performance by area under the curve (AUC). Results A complete data set was evaluable from 247 patients. 78.1% cases were endometrioid histotype. The majority of patients (n=156;63.2%) had stage IA disease. Overall, positive lymph nodes were found in 20(8.1%) patients. Using ENDORISK predicted probabilities, most (n=156;63.2%) patients have been assigned to low or very low risk group with a false-negative rate of 0.6%.AUC for LNM prediction was 0.851 (95% confidence interval [CI] 0.761-0.941) with a Brier score of 0.06. For 5-year DSS the AUC was 0.698 (95% CI 0.595-0.800) as Brier score has been calculated 0.09. Conclusions We were able to successfully validate ENDORISK for prediction of LNM and 5-year DSS. Next steps will now have to focus on ENDORISK performance in daily clinical practice. In Addition, incorporating TCGA-derived molecular subtypes will be of key importance for future extended use. This study may support further promoting of data-based decision-making tools for personalized treatment of EC.