Miracle-dz/UniFAR-FTUs huggingface dataset:
Osaka feedback model: isolated disc galaxy simulations

We study various implementations of supernova feedback model and present the results of our `Osaka feedback model' using isolated galaxy simulations performed by the smoothed particle hydrodynamics (SPH) code {\small GADGET-3}. Our model is a modified version of Stinson et al.'s work, and we newly add the momentum kick for SN feedback rather than only thermal feedback. We incorporate the physical properties of SN remnants from the results of Chevalier and McKee \& Ostriker, such as the effective radius of SN bubble and the remnant life-time, in the form of Sedov-Taylor (ST)-like solutions with the effect of radiative cooling. Our model utilizes the local, physical parameters such as density and temperature of the ISM rather than galactic or halo properties to determine the galactic wind velocity or mass-loading factor. The Osaka model succeeds in self-regulating star formation, and naturally produces galactic outflow with variable velocities depending on the local environment and available SN energy as a function of time.An important addition to our previous work by Aoyama et al. is the implementation of the {\small CELib} chemistry library which allows us to deal with the time-dependent input of energy and metal yields for type Ia \& II supernovae (SNe) and asymptotic giant branch (AGB) stars. As initial tests of our model, we apply it to isolated galaxy simulations, and examine various galactic properties and compare with observational data including metal abundances.
Nonpolar III-nitride vertical-cavity surface-emitting lasers incorporating an ion implanted aperture

We report on our recent progress in improving the performance of nonpolar III-nitride vertical-cavity surface-emitting lasers (VCSELs) by using an Al ion implanted aperture and employing a multi-layer electron-beam evaporated ITO intracavity contact. The use of an ion implanted aperture improves the lateral confinement over SiNx apertures by enabling a planar ITO design, while the multi-layer ITO contact minimizes scattering losses due to its epitaxially smooth morphology. The reported VCSEL has 10 QWs, with a 3 nm quantum well width, 1 nm barriers, a 5 nm electron-blocking layer, and a 6.95- λ total cavity thickness. These advances yield a single longitudinal mode 406 nm nonpolar VCSEL with a low threshold current density (∼16 kA/cm2), a peak output power of ∼12 μW, and a 100% polarization ratio. The lasing in the current aperture is observed to be spatially non-uniform, which is likely a result of filamentation caused by non-uniform current spreading, lateral optical confinement, contact resistance, and.
The Structure of cold dark matter halos

High resolution N-body simulations show that the density profiles of dark matter halos formed in the standard CDM cosmogony can be fit accurately by scaling a simple “universal” profile. Regardless of their mass, halos are nearly isothermal over a large range in radius, but significantly shallower than r -2 near the center and steeper than r -2 in the outer regions. The characteristic overdensity of a halo correlates strongly with halo mass in a manner consistent with the mass dependence of the epoch of halo formation. Matching the shape of the rotation curves of disk galaxies with this halo structure requires (i) disk mass-to-light ratios to increase systematically with luminosity, (ii) halo circular velocities to be systematically lower than the disk rotation speed, and (iii) that the masses of halos surrounding bright galaxies depend only weakly on galaxy luminosity. This offers an attractive explanation for the puzzling lack of correlation between luminosity and dynamics in observed samples of binary galaxies and of satellite companions of bright spiral galaxies, suggesting that the structure of dark matter halos surrounding bright spirals is similar to that of cold dark matter halos.
Disentangling contact and ensemble epistasis in a riboswitch

Mutations introduced into macromolecules often exhibit epistasis, where the effect of one mutation alters the effect of another. Knowledge of the mechanisms that lead to epistasis is important for understanding how macromolecules work and evolve, as well as for effective macromolecular engineering. Here we investigate the interplay between “contact epistasis” (epistasis arising from physical interactions between mutated residues) and “ensemble epistasis” (epistasis that occurs when a mutation redistributes the conformational ensemble of a macromolecule, thus changing the effect of the second mutation). We argue that the two mechanisms can be distinguished in allosteric macromolecules by measuring epistasis at differing allosteric effector concentrations. Contacts give rise to epistasis in the microscopic equilibrium constants describing the conformational ensemble. Ensemble epistasis manifests in thermodynamic observables, such as the energy of ligand binding or enzyme activation, that depend on the concentration of allosteric effector. Using this framework, we experimentally investigated the origins of epistasis in three mutant cycles introduced into the adenine riboswitch aptamer domain. We found evidence for both contact and ensemble epistasis in all cycles. Further, we found that the two mechanisms of epistasis can interact with each other. For example, in one mutant cycle we observe contact epistasis of 6 kcal/mol attenuated by the ensemble to only 1.5 kcal/mol in the final thermodynamic observable. Finally, our work yields simple heuristics for identifying contact and ensemble epistasis using limited experimental measurements. Statement of significance Mutations to protein or RNA molecules often have different effects when introduced individually versus together. To understand and engineer biological macromolecules, we must identify the mechanistic origins of this phenomenon. Here, we measured the interplay between direct, physical interactions between mutations (“contact epistasis”) and indirect interactions mediated by conformational ensembles (“ensemble epistasis”). We introduced pairs of mutations into an RNA molecule that transitions between several different conformations. We found epistasis arising from both contacts and the ensemble, and that the two mechanisms could synergize with one another. Our work reveals that one must consider the effects of mutations on multiple conformations to understand epistasis and suggests a few rules-of-thumb for disentangling contact and ensemble epistasis in other macromolecules.
Spectrum preserving tilings enable sparse and modular reference indexing

The reference indexing problem for k-mers is to pre-process a collection of reference genomic sequences ℛ so that the position of all occurrences of any queried k-mer can be rapidly identified. An efficient and scalable solution to this problem is fundamental for many tasks in bioinformatics. In this work, we introduce the spectrum preserving tiling (SPT), a general representation of ℛ that specifies how a set of tiles repeatedly occur to spell out the constituent reference sequences in ℛ. By encoding the order and positions where tiles occur, SPTs enable the implementation and analysis of a general class of modular indexes. An index over an SPT decomposes the reference indexing problem for k-mers into: (1) a k-mer-to-tile mapping; and (2) a tile-to-occurrence mapping. Recently introduced work to construct and compactly index k-mer sets can be used to efficiently implement the k-mer-to-tile mapping. However, implementing the tile-to-occurrence mapping remains prohibitively costly in terms of space. As reference collections become large, the space requirements of the tile-to-occurrence mapping dominates that of the k-mer-to-tile mapping since the former depends on the amount of total sequence while the latter depends on the number of unique k-mers in ℛ. To address this, we introduce a class of sampling schemes for SPTs that trade off speed to reduce the size of the tile-to-reference mapping. We implement a practical index with these sampling schemes in the tool pufferfish2. When indexing over 30,000 bacterial genomes, pufferfish2 reduces the size of the tile-to-occurrence mapping from 86.3GB to 34.6GB while incurring only a 3.6× slowdown when querying k-mers from a sequenced readset. Supplementary materials Sections S.1 to S.8 available online at https://doi.org/10.5281/zenodo.7504717 Availability pufferfish2 is implemented in Rust and available at https://github.com/COMBINE-lab/pufferfish2.
The endogenous modulation of visual plasticity in human adults

The adult human visual system can exhibit a degree of neuroplastic change under the right conditions which has implications for future treatments to recover vision loss that have occurred in infancy. The exogenous factors that promote neuroplastic change have been the focus of human psychophysical, electrophysiological and neuroimaging research over the last decade. What has not been considered is the importance of endogenous factors. In this study we modulate the neural oscillations that determines the internal neural state to demonstrate that endogenous factors play a critical role in not only baseline contrast sensitivity but also the extent to which the adult visual system can undergo neuroplastic change in binocular balance.
Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration

The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we defined the epithelial and mesenchymal subsets of the epicardium. We further identified a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by ptx3a and col12a1b expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and pdgfra+hapln1a+ mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocked heart regeneration through reduced Nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
Evidence for an one-step mechanism of endosymbiont-induced thelytoky in the parasitoid wasp, Muscidifurax uniraptor

Wolbachia manipulates host reproduction in various haplodiploid insect species, in which fertilized eggs normally develop into diploid females while unfertilized eggs develop into haploid males. Females infected with a thelytoky-inducing Wolbachia produce diploid daughters from unfertilized eggs (thelytoky), but in some infected species diploid males spontaneously occur in low numbers. This suggests that diploidization and feminization are induced separately. In the Wolbachia-infected thelytokous parasitoid wasp, Muscidifurax uniraptor, occasional males have been found but with unknown ploidy. Therefore, we studied the mechanism of Wolbachia-induced thelytoky in M. uniraptor in the context of sex determination. We started by feeding different concentrations of tetracycline (antibiotic) to M. uniraptor females to gradually reduce the Wolbachia titre. We found that a decreased Wolbachia titre leads to an increased proportion of haploid male offspring, but we found no diploid males. Next, we studied the effect of Wolbachia infection on the expression and splicing of the sex determination genes transformer (Mutra) and transformer-2 (Mutra2) in female ovaries and conclude that Wolbachia does neither affect the expression nor the splicing of Mutra and Mutra2. We then measured Mutra and Mutra2 expression levels in developing zygotes at different time points and found a two-fold Mutra expression increase in Wol+ compared to Wol-. Finally, we used the sexually reproducing sister species, Muscidifurax raptorellus and artificially created triploid females to determine whether diploidization is sufficient for feminization. These triploid females, when virgin, produced haploid sons and diploid daughters, showing that in Muscidifurax feminization solely depends on ploidy level. This strongly suggests that Wolbachia only needs to induce diploidization and that bi-allelic Mutra expression is sufficient for female development.
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders

SLC29A3, also known as ENT3, is a lysosomal transmembrane protein that transports nucleosides from the lysosomes to the cytoplasm1. Loss-of-function mutations in SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs2,3. However, little is known about the mechanism through which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3−/− mice was demonstrated to depend on TLR7, which senses a combination of nucleosides and oligoribonucleotides4,5. TLR7 responded to lysosomal nucleoside storage and enhanced proliferation of Ly6Chi CX3CR1low immature monocytes and their maturation into Ly6Clow phagocytes in Slc29a3−/− mice. Because accumulated nucleosides primarily originated from cell corpse phagocytosis, TLR7 in immature monocytes recognized nucleoside storage as lysosomal stress and increased phagocyte numbers. This non-inflammatory compensatory response is referred to as the TLR7 stress response where Syk, GSK3β, β-catenin, and mTORC1 serve as downstream signalling molecules. In SLC29A3 disorders, histiocytosis accompanies inflammation6,7. Nucleoside storage failed to induce pro-inflammatory cytokine production in Slc29a3−/− mice, but enhanced ssRNA-dependent pro-inflammatory cytokine production in Ly6Chi classical monocytes and peripheral macrophages, not proliferating immature monocytes. Patient-derived monocytes harbouring G208R SLC29A3 mutation showed higher survival and proliferation in the presence of M-CSF and produced larger amounts of IL-6 upon ssRNA stimulation than did those derived from healthy subjects. A TLR8 antagonist inhibited the survival/proliferation of patient-derived macrophages. These results demonstrated that TLR7/8 responses to lysosomal nucleoside stress drive SLC29A3 disorders.
Effect of age and sex on gene expression-based radiation biodosimetry using mouse peripheral blood

Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24hr later and subjected to whole genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ± 0.75 Gy (R^2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex. However, inclusion of age and sex as biological factors is essential for effectively predicting radiation injury and for developing radiation medical countermeasures.
Siphonophore community biodiversity and spatio-temporal distribution concerning the oceanographic parameters in the Patagonian Fjord Ecosystem during the winter season

This study describes the spatial distribution and abundance of siphonophores concerning oceanographic variables (temperature, salinity, and dissolved oxygen) in the northern Chilean Patagonian Fjord Ecosystem, from Guafo Passage (43º30'S) to Elefantes Gulf (46º40'S) during the winter of 2012. Twelve species were identified, ten belonging to suborder Calycophorae and two assigned to suborder Physonectae. The species Chelophyes appendiculata and Sphaeronectes gamulini are new records for this study area. Dominant species were Muggiaea atlantica (63.15%), Lensia conoidea (21.85%), and Sphaeronectes koellikeri (9.91%). Species richness showed a negative latitudinal gradient, and the highest densities were found in North Moraleda Channel (5316 ind 1000 m -3 ) and the lowest in South Moraleda Channel, near Elefantes Gulf (71 ind 1000 m -3 ). Some species showed a significant and positive association with some oceanographic variables, e.g., M. atlantica showed a positive association with dissolved oxygen, L. conoidea with temperature and negative association with dissolved oxygen, Sphaeronectes fragilis , S. koellikeri, and C. appendiculata showed a positive association with salinity. Eudoxids (sexual reproductive stage) were found for M. atlantica , L. conoidea, and Dimophyes arctica, indicating that the PFE conditions are suitable for some siphonophore species even in winter.
Influence of mindfulness levels on emotional regulation, depression, anxiety and stress dimensions in a Brief Intervention Program in candidates for the OAB exam

In this study, a six-meeting mindfulness intervention was conducted with Brazilian Bar Association (OAB) exam applicants, with 42 participants. This is a quantitative, correlational and explanatory research. Linear regression showed explanatory power between the awareness dimension and the consciousness and clarity dimensions of emotional regulation in the pre and post-intervention. In the pre-test, the acceptance dimension correlates with Strategies, Non-acceptance and Impulse; in the post-test, Acceptance extends its explanatory power to all dimensions of emotional regulation. This study also points to a significant increase between the explanatory power of acceptance and the grand total of the emotional regulation scale. The correlation with depression, anxiety and stress was also up to acceptance, highlighting the increase in explanatory power regarding stress, in the post-test.
An evaluation of biomass burning aerosol mass, extinction, and size distribution in GEOS using observations from CAMP2Ex

Abstract. Biomass burning aerosol impacts aspects of the atmosphere and Earth system through direct and semi-direct effects, as well as influencing air quality. Despite its importance, the representation of biomass burning aerosol is not always accurate in numerical weather prediction and climate models or reanalysis products. Using observations collected as part of the Cloud, Aerosol and Monsoon Processes Philippines Experiment (CAMP2Ex) in August through October of 2019, aerosol concentration and optical properties are evaluated within the Goddard Earth Observing System (GEOS) and its underlying aerosol module, GOCART. In the operational configuration, GEOS assimilates aerosol optical depth observations at 550 nm from AERONET and MODIS to constrain aerosol fields. Particularly for biomass burning aerosol, without the assimilation of aerosol optical depth, aerosol extinction is underestimated compared to observations collected in the Philippines region during the CAMP2Ex campaign. The assimilation process adds excessive amounts of carbon to account for the underestimated extinction, resulting in positive biases in the mass of black and organic carbon, especially within the boundary layer, relative to in situ observations from the Langley Aerosol Research Group Experiment. Counteracting this, GEOS is deficient in sulfate and nitrate aerosol just above the boundary layer. Aerosol extinction within GEOS is a function of the mass of different aerosol species, the ambient relative humidity, the assumed spectral optical properties, and particle size distribution per species. The relationship between dry and ambient extinction in GEOS reveals that hygroscopic growth is too high within the model for biomass burning aerosol. An additional concern lies in the assumed particle size distribution for GEOS, which has a single mode radius that is too small for organic carbon. Variability in the observed particle size distribution for biomass burning aerosol within a single flight also illuminates the fact that a single assumed particle size distribution is not sufficient and that for a proper representation, a more advanced aerosol module within GEOS may be necessary.
Serum cytokines predict efficacy and toxicity, but are not useful for disease monitoring in lung cancer treated with PD-(L)1 inhibitors

Introduction PD-(L)1 inhibitors (IO) have improved the prognosis of non-small-cell lung cancer (NSCLC), but more reliable predictors of efficacy and immune-related adverse events (irAE) are urgently needed. Cytokines are important effector molecules of the immune system, whose potential clinical utility as biomarkers remains unclear. Methods Serum samples from patients with advanced NSCLC receiving IO either alone in the first (1L, n=46) and subsequent lines (n=50), or combined with chemotherapy (ICT, n=108) were analyzed along with age-matched healthy controls (n=15) at baseline, after 1 and 4 therapy cycles, and at disease progression (PD). Patients were stratified in rapid progressors (RP, progression-free survival [PFS] <120 days), and long-term responders (LR, PFS >200 days). Cytometric bead arrays were used for high-throughput quantification of 20 cytokines and other promising serum markers based on extensive search of the current literature. Results Untreated NSCLC patients had increased levels of various cytokines and chemokines, like IL-6, IL-8, IL-10, CCL5, G-CSF, ICAM-1, TNF-RI and VEGF (fold change [FC]=1.4-261, p=0.026-9x10-7) compared to age-matched controls, many of which fell under ICT (FC=0.2-0.6, p=0.014-0.002), but not under IO monotherapy. Lower baseline levels of TNF-RI were associated with longer PFS (hazard ratio [HR]= 0.42-0.54; p=0.014-0.009) and overall survival (HR=0.28-0.34, p=0.004-0.001) after both ICT and IO monotherapy. Development of irAE was associated with higher baseline levels of several cytokines, in particular of IL-1β and angiogenin (FC=7-9, p=0.009-0.0002). In contrast, changes under treatment were very subtle, there were no serum correlates of radiologic PD, and no association between dynamic changes in cytokine concentrations and clinical outcome. No relationship was noted between the patients’ serologic CMV status and serum cytokine levels. Conclusions Untreated NSCLC is characterized by increased blood levels of several pro-inflammatory and angiogenic effectors, which decrease under ICT. Baseline serum cytokine levels could be exploited for improved prediction of subsequent IO benefit (in particular TNF-RI) and development of irAE (e.g. IL-1β or angiogenin), but they are not suitable for longitudinal disease monitoring. The potential utility of IL-1/IL-1β inhibitors in the management and/or prevention of irAE in NSCLC warrants investigation.