Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigations into the Tectonics of Uranian and Saturnian Icy Satellites

Miranda, a ~470-km-diameter Uranian icy satellite, has a surface that exhibits evidence of a complex tectonic history. Tectonic structures are mostly localized in three regions termed coronae, but also form a rift system inferred to be global in extent. Ridges within the boundary of Arden Corona, and those that make up the 340° Chasma, part of the global rift system, have been interpreted as normal fault blocks. Using Voyager data, we test the hypothesis that these Arden Corona faults, as well as those at the northern edge of the 340o Chasma, are listric in geometry. For this testing, we use four geometric criteria for listric faults: (1) progressive down-dip decrease in fault scarp dip, (2) progressive down-dip increase in back-tilted face slope, (3) concavity of the exposed scarp surface, and (4) presence of a rollover structure. Results of this analysis support the hypothesis that the faults within the Arden Corona boundary are listric in geometry, but do not strongly support the hypothesis for the faults within the 340 ̊ Chasma. By analogy with terrestrial structures, the listric character of faults within the Arden Corona boundary suggests the presence of a subsurface detachment. This detachment likely occurred at Miranda’s brittle-ductile transition zone at the time of faulting. Measurements of the Arden Corona fault system geometry are used to estimate depths to the proposed brittleductile transition zone at the time of faulting, resulting in values of 6.7 – 9.0 km. Those depths in turn are used to estimate a thermal gradient of 6 – 25 K km and a surface heat flux of 31 – 112 mW m. The weaker evidence of a listric geometry for the faults of the 340 ̊ Chasma suggests that those faults did not interact with a brittle-ductile transition at the time of their formation. Our estimated thermal gradient of the Arden Corona region is consistent with a previous heating event on Miranda that was as significant as Europa’s current resonance-induced tidal heating. This heating event may be associated with a hypothesized previous tidal resonance of Miranda with Umbriel and/or Ariel.
Resistance in Enteric Shigella and nontyphoidal Salmonella: emerging concepts

Purpose of review The emergence of globally resistant enteric Shigella and nontyphoidal Salmonella strains (NTS) has limited the selection of effective drugs, which has become a major challenge for the treatment of infections. The purpose of this review is to provide the current opinion on the antimicrobial-resistant enteric Shigella and nontyphoidal Salmonella. Recent findings Enteric Shigella and NTS are resistant to almost all classes of antimicrobials in recent years. Those with co-resistance to ciprofloxacin, azithromycin and ceftriaxone, the first-line antibiotics for the treatment of infectious diarrhoea have emerged worldwide. Some of them have caused interregional and international spread by travel, trade, MSM, and polluted water sources. Several strains have even developed resistance to colistin, the last-resort antibiotic used for treatment of multidrug-resistant Gram-negative bacteria infections. Summary The drug resistance of enteric Shigella and NTS is largely driven by the use of antibiotics and horizontal gene transfer of mobile genetic elements. These two species show various drug resistance patterns in different regions and serotypes. Hence treatment decisions for Shigella and Salmonella infections need to take into consideration prevalent antimicrobial drug resistance patterns. It is worth noting that the resistance genes such as blaCTX,mph, ermB, qnr and mcr, which can cause resistance to ciprofloxacin, cephalosporin, azithromycin and colistin are widespread because of transmission by IncFII, IncI1, IncI2 and IncB/O/K/Z plasmids. Therefore, continuous global monitoring of resistance in Shigella and Salmonella is imperative.
Marshalling the Potential of Auger Electron Radiopharmaceutical Therapy

Visual Abstract Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 “Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments” at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.
The North Pacific Gyre Oscillation

Decadal variability in the North Pacific is typically described by the Pacific Decadal Oscillation (PDO). While many aspects of Pacific climate anomalies are associated with the PDO, variations of oceanic salinity, nutrients and the ecosystem off the coast of North America are independent of the PDO. A 50+ year ocean hindcast in the North-East Pacific suggests that the North Pacific Gyre Oscillation (NPGO; Di Lorenzo et al. 2008), the second empirical orthogonal function of sea surface height, reproduces these time series in the California Current and Alaskan Gyre. The mode describes a spin-up (or down) of the subtropical and Alaskan gyres, and an acceleration of the North Pacific Current. Associated sea surface temperature patterns are similar to the Victoria Mode, the second EOF of North Pacific surface temperature anomalies. With a lag of a few years, the NPGO is linked to strength of Kuroshio Extension via Rossby wave dynamics. The NPGO is the oceanic expression of the North Pacific Oscillation, a dipole sea level pressure pattern that results from intrinsic atmospheric mid-latitude variability and interactions with the El Nino/Southern Oscillation.
Dynamic applicability domain (dAD): compound–target binding affinity estimates with local conformal prediction

Abstract Motivation Increasing efforts are being made in the field of machine learning to advance the learning of robust and accurate models from experimentally measured data and enable more efficient drug discovery processes. The prediction of binding affinity is one of the most frequent tasks of compound bioactivity modelling. Learned models for binding affinity prediction are assessed by their average performance on unseen samples, but point predictions are typically not provided with a rigorous confidence assessment. Approaches, such as the conformal predictor framework equip conventional models with a more rigorous assessment of confidence for individual point predictions. In this article, we extend the inductive conformal prediction framework for interaction data, in particular the compound–target binding affinity prediction task. The new framework is based on dynamically defined calibration sets that are specific for each testing pair and provides prediction assessment in the context of calibration pairs from its compound–target neighbourhood, enabling improved estimates based on the local properties of the prediction model. Results The effectiveness of the approach is benchmarked on several publicly available datasets and tested in realistic use-case scenarios with increasing levels of difficulty on a complex compound–target binding affinity space. We demonstrate that in such scenarios, novel approach combining applicability domain paradigm with conformal prediction framework, produces superior confidence assessment with valid and more informative prediction regions compared to other ‘state-of-the-art’ conformal prediction approaches. Availability and implementation Dataset and the code are available on GitHub (https://github.com/mlkr-rbi/dAD).
AIM (Angular Indication Measurement)- Visual Acuity: An adaptive, self-administered, and generalizable vision assessment method used to measure visual acuity

This proof-of-concept study introduces Angular Indication Measurement and applies it to VA (AIM-VA). First, we compared the ability of AIM-VA and ETDRS to detect defocus and astigmatic blur in 22 normally-sighted adults. Spherical and cylindrical lenses (±0.00D, +0.25D, +0.50D, +0.75D, +1.00D, +2.00D and +0.50D, +1.00D, +2.00D each at 0°, 90°, 135°, respectively) in the dominant eye induced blur. Second, we compared repeatability over two tests of AIM-VA and ETDRS. A 2-way-ANOVA showed a main effect for defocus-blur and test with no interaction. A 3-way-ANOVA for the astigmatism experiment revealed main effects for test type, blur, and direction and with no interactions. Planned multiple comparisons showed AIM had greater astigmatic-induced VA loss than ETDRS. Bland-Altman plots showed small bias and no systematic learning effect for either test type and improved repeatability with >2 adaptive steps for AIM-VA. AIM-VA’s ability to detect defocus was comparable with that of an ETDRS letter chart and showed greater sensitivity to astigmatic blur, and AIM-VA’s repeatability is comparable with ETDRS when using 2 or more adaptive steps. AIM’s self-administered orientation judgment approach is generalizable to interrogate other visual functions, e.g., contrast, color, motion, stereo-vision.
R-loops and Topoisomerase 1 facilitate formation of transcriptional DSBs at gene bodies of hypertranscribed cancer genes

DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employed advanced techniques to map DSBs, R-loops, and Topoisomerase 1 cleavage complex (TOP1cc) and re-analyzed ChIP-seq and DRIP-seq data to comprehensively investigate the interplay between transcription, DSBs, Topoisomerase 1 (TOP1), and R-loops. Our findings revealed the presence of DSBs at highly expressed genes enriched with TOP1 and R-loops, indicating their crucial involvement in transcription-associated genomic instability. Depletion of R-loops and TOP1 specifically reduced DSBs at highly expressed genes, uncovering their pivotal roles in transcriptional DSB formation. By elucidating the intricate interplay between TOP1cc trapping, R-loops, and DSBs, our study provides novel insights into the mechanisms underlying transcription-associated genomic instability. Moreover, we establish a link between transcriptional DSBs and early molecular changes driving cancer development. Notably, our study highlights the distinct etiology and molecular characteristics of driver mutations compared to passenger mutations, shedding light on the potential for targeted therapeutic strategies. Overall, these findings deepen our understanding of the regulatory mechanisms governing DSBs in hypertranscribed genes associated with carcinogenesis, opening avenues for future research and therapeutic interventions.
Depicting the landscape of gut microbial-metabolic interaction and microbial-host immune heterogeneity in deficient and proficient DNA mismatch repair colorectal cancers

Background Accumulating evidence has indicated the role of gut microbiota in remodeling host immune signatures, but various interplays underlying colorectal cancers (CRC) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) remain poorly understood. This study aims to decipher the gut microbiome-host immune interactions between dMMR and pMMR CRC. Method We performed metagenomic sequencing and metabolomic analysis of fecal samples from a cohort encompassing 455 participants, including 21 dMMR CRC, 207 pMMR CRC, and 227 healthy controls. Among them, 50 tumor samples collected from 5 dMMR CRC and 45 pMMR CRC were conducted bulk RNA sequencing. Results Pronounced microbiota and metabolic heterogeneity were identified with 211 dMMR-enriched species, such as Fusobacterium nucleatum and Akkermansia muciniphila, 2 dMMR-depleted species, such as Flavonifractor plautii, 13 dMMR-enriched metabolites, such as retinoic acid, and 77 dMMR-depleted metabolites, such as lactic acid, succinic acid, and 2,3-dihydroxyvaleric acid. F. plautii was enriched in pMMR CRC and it was positively associated with fatty acid degradation, which might account for the accumulation of dMMR-depleted metabolites classified as short chain organic acid (lactic acid, succinic acid, and 2,3-dihydroxyvaleric acid) in pMMR CRC. The microbial-metabolic association analysis revealed the characterization of pMMR CRC as the accumulation of lactate induced by the depletion of specific gut microbiota which was negatively associated with antitumor immune, whereas the nucleotide metabolism and peptide degradation mediated by dMMR-enriched species characterized dMMR CRC. MMR-specific metabolic landscapes were related to distinctive immune features, such as CD8+ T cells, dendritic cells and M2-like macrophages. Conclusions Our mutiomics results delineate a heterogeneous landscape of microbiome-host immune interactions within dMMR and pMMR CRC from aspects of bacterial communities, metabolic features, and correlation with immunocyte compartment, which infers the underlying mechanism of heterogeneous immune responses.
Fiber-reinforced polyvinyl alcohol hydrogel via in situ fiber formation

Abstract Polyvinyl alcohol (PVA) hydrogels have been extensively investigated for drug release, artificial cartilage, biosensing, and other applications owing to their good chemical stability, biocompatibility, high water absorption, and ease of processing. However, the conventional hydrogel preparation method is complex and energy-intensive, and the mechanical performance of the pure PVA hydrogel is poor, which severely limits its application in related fields. In this study, a PVA hydrogel was functionally modified using polybutylene succinate (PBS) nanofibers prepared using in situ fiber-forming technology to fabricate a PBS-enhanced PVA composite hydrogel. The strength of the PBS/PVA hydrogel fabricated in this study is 3.88 MPa, which is 4.94 times that of the pure PVA hydrogel; thus, the strength of the hydrogel was effectively improved. The hydrogel preparation method used in this study is novel and straightforward. Moreover, the resulting materials are biodegradable and non-toxic. Compared to conventional methods, this method has the advantages of conserving resources and being environmentally friendly.
Toxicity of source-oriented ambient submicron particulate matter

8 Executive Summary . 9 Chapter 1-Introduction. 1-1 References.1-3 Chapter 2-Conditional Sampling for Source-Oriented Toxicological Studies using a Single Particle Mass Spectrometer. 2-1 Abstract . 2-2 Introduction.2-3 Experimental Design.2-3 Results and Discussion . 2-6 References.2-12 Supporting Information.2-21 Chapter-3-A High-Efficiency, Low-Bias Method for Extracting Particulate Matter from Filter and Impactor Substrates. 3-
Mechanical force regulates ligand binding and function of PD-1

Immune checkpoint blockade targeting PD-1 shows great success in cancer therapy. However, the mechanism of how ligand binding initiates PD-1 signaling remains unclear. As prognosis markers of multiple cancers, soluble PD-L1 is found in patient sera and can bind PD-1, but fails to suppress T cell function. This and our previous observations that T cells exert endogenous forces on PD-1– PD-L2 bonds prompt the hypothesis that mechanical force might be critical to PD-1 triggering, which is missing in the soluble ligand case due to the lack of mechanical support afforded by surface-anchored ligand. Here we show that PD-1 function is eliminated or reduced when mechanical support on ligand is removed or dampened, respectively. Force spectroscopic analysis reveals that PD-1 forms catch bonds with both PD-Ligands <7 pN where force prolongs bond lifetime, but slip bonds >8 pN where force accelerates dissociation. Steered molecular dynamics finds PD-1–PD-L2 complex very sensitive to force due to the two molecules’ “side-to-side” binding via β sheets. Pulling causes relative rotation and translation between the two molecules by stretching and aligning the complex along the force direction, yielding new atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced new interactions maintain the same binding affinity but display lower rupture force, shorter bond lifetime, reduced tension, and most importantly, impaired capacity to suppress T cell activation. Our results uncover a mechanism for cells to probe the mechanical support of PD-1–PD-Ligand bonds using endogenous forces to regulate PD-1 triggering.
The Spatial Patterns and Determinants of Cerebrospinal Fluid Circulation in the Human Brain

The circulation of cerebrospinal fluid (CSF) is essential for maintaining brain homeostasis and clearance, and impairments in its flow can lead to various brain disorders. Recent studies have shown that CSF circulation can be interrogated using low b-value diffusion magnetic resonance imaging (low-b dMRI). Nevertheless, the spatial organization of intracranial CSF flow dynamics remains largely elusive. Here, we developed a whole-brain voxel-based analysis framework, termed CSF pseudo-diffusion spatial statistics (CΨSS), to examine CSF mean pseudo-diffusivity (MΨ), a measure of CSF flow magnitude derived from low-b dMRI. We showed that intracranial CSF MΨ demonstrates characteristic covariance patterns by employing seed-based correlation analysis. Importantly, we applied non-negative matrix factorization analysis to further elucidate the covariance patterns of CSF MΨ in a hypothesis-free, data-driven way. We identified distinct CSF spaces that consistently displayed unique pseudo-diffusion characteristics across multiple imaging datasets. Our study revealed that age, sex, brain atrophy, ventricular anatomy, and cerebral perfusion differentially influence MΨ across these CSF spaces. Notably, individuals with anomalous CSF flow patterns displayed incidental findings on multimodal neuroradiological examinations. Our work sets forth a new paradigm to study CSF flow, with potential applications in clinical settings.
Season, not long-term warming, affects the relationship between ecosystem function and microbial diversity

Across biomes, soil biodiversity promotes ecosystem functions. However, whether this relationship will be maintained under climate change is uncertain. Here, using two long-term warming experiments, we investigated how warming affects the relationship between ecosystem functions and microbial diversity across seasons, soil horizons, and warming duration. The soils in these warming experiments were heated +5 °C above ambient for 13 or 28 years. We measured seven different ecosystem functions representative of soil carbon cycling, soil nitrogen cycling, or nutrient pools. We also surveyed bacterial and fungal community diversity. We found that the relationship between ecosystem function and bacterial diversity and the relationship between ecosystem function and fungal diversity was unaffected by warming or warming duration. Ecosystem function, however, was significantly affected by season, with autumn samples having higher function than summer samples. Our findings further emphasize that season is a consistent driver of ecosystem function and that this is maintained even under simulated climate change. Importance Soils perform a variety of ecosystem functions, and soil microbial communities with higher diversity tend to promote the performance of these functions. Yet, biodiversity loss due to climate change threatens this relationship. Long-term global change studies provide the opportunity to examine the trajectory of the effects of climate change. Here, we utilized two long-term warming experiments, where soils have been heated +5 °C above ambient temperature for 13-28 years, to understand how increased temperatures affect the relationship between ecosystem function and soil microbial diversity. We observed that the effects of increased temperature on the relationship between bacterial diversity and ecosystem function were season-specific. This work emphasizes the role that environmental conditions, such as season, have on modulating effects of climate change. Additionally, these findings demonstrate the value of long-term ecological research in furthering our understanding of climate change.
EWSR1’s visual modalities are defined by its association with nucleic acids and RNA polymerase II

We report systematic analysis of endogenous EWSR1’s cellular organization. We demonstrate that EWSR1, which contains low complexity and nucleic acid binding domains, is present in cells in faster and slower-recovering fractions, indicative of a protein undergoing both rapid exchange and longer-term interactions. The employment of complementary high-resolution imaging approaches shows EWSR1 exists in in two visual modalities, a distributed state which is present throughout the nucleoplasm, and a concentrated state consistent with the formation of foci. Both EWSR1 visual modalities localize with nascent RNA. EWSR1 foci concentrate in regions of euchromatin, adjacent to protein markers of transcriptional activation, and significantly colocalize with phosphorylated RNA polymerase II. Interestingly, EWSR1 and FUS, another FET protein, exhibit distinct spatial organizations. Our results contribute to bridging the gap between our understanding of the biophysical and biochemical properties of FET proteins, including EWSR1, their functions as transcriptional regulators, and the participation of these proteins in tumorigenesis and neurodegenerative disease. SUMMARY Rajan et al. report the visualization of endogenous EWSR1. EWSR1 exists in two visual modalities in the nucleoplasm, one distributed and one as foci. Both EWSR1 modalities localize with nascent RNA. EWSR1 foci concentrate in regions of euchromatin and colocalize with phosphorylated RNA polymerase II.
Uncertainty propagation using copulas in a 3D stereo matching pipeline

This contribution presents a concrete example of uncertainty propagation in a stereo matching pipeline. It considers the problem of matching pixels between pairs of images whose radiometry is uncertain and modeled by possibility distributions. Copulas serve as dependency models between variables and are used to propagate the imprecise models. The propagation steps are detailed in the simple case of the Sum of Absolute Difference cost function for didactic purposes. The method results in an imprecise matching cost curve. To reduce computation time, a sufficient condition for conserving possibility distributions after the propagation is also presented. Finally, results are compared with Monte Carlo simulations, indicating that the method produces envelopes capable of correctly estimating the matching cost.