Miracle-dz/UniFAR-FTUs huggingface dataset:
Geometry‐derived statistical significance: A probabilistic framework for detecting true positive findings in MRI data

The false discovery rate (FDR) procedure does not incorporate the geometry of the random field and requires high statistical power at each voxel, a requirement not satisfied by the limited number of participants in imaging studies. Topological FDR, threshold free cluster enhancement (TFCE), and probabilistic TFCE improve statistical power by incorporating local geometry. However, topological FDR requires specifying a cluster defining threshold and TFCE requires specifying transformation weights.
Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase

Significance Using a variety of biophysical tools, we present evidence of a cooperative protein restructuring that originates at a defined protein–water interface to provide the thermal activation driving the active site hydrogen tunneling in soybean lipoxygenase (SLO). An atomistic understanding of how classical motions within the protein scaffold may control the active site quantum properties becomes apparent when the substrate linoleic acid is modeled into available X-ray structures for SLO. A dynamical model of enzyme catalysis is presented that combines distributed conformational ensembles with site-specific thermal initiation of the chemical reaction.
Bursts of relativistic electrons from Jupiter observed in interplanetary space with the time variation of the planetary rotation period

Bursts of Jovian electrons in the energy range 3–30 MeV have been detected to distances of the order of 1 AU from the planet. The duration of each burst was about 2–3 days, and the maximum intensity increased with increasing distance from the sun. These events could not be correlated with known solar activity. The conclusion that these electrons originated at Jupiter and were accelerated within the Jovian magnetosphere is based on the following observations of three of these bursts. (1) The power spectrum of the temporal variations of the 6- to 30-MeV electron flux showed a persistent peak at Jupiter's rotation frequency, 2.8×10−5 Hz (corresponding to the 10-hour rotation period) out to distances >108 km from the planet; (2) the slope, or spectral, index, of the differential energy spectrum measured as a function of time displayed the 10-hour cyclic variation in the value of the index, which was earlier discovered by our group as being characteristic of the electrons within the Jovian magnetosphere; (3) the value of the spectral index was anticorrelated with the flux level of the 6- to 30-MeV electrons, an effect that was found inside the magnetosphere on the inbound pass; (4) the 10-hour variations of both the spectral index and the number density observed in the bursts analyzed so far are in phase with the corresponding variations inside the Jovian magnetosphere for R ≳ 50 RJ; and (5) overall, the bursts were anisotropic, their direction of propagation being toward the sun along the average interplanetary magnetic field. We also note that the particles in the bursts propagated across the average interplanetary magnetic field to reach Pioneer 10, and we discuss some of the implications. The analysis of these events provides a new tool for the study of the propagation of particles in the interplanetary medium.
Developmental trajectories of sensitivity to threat in children and adolescents predict larger medial frontal theta differentiation during response inhibition

Abstract Sensitivity to threat (ST) is thought to be a hallmark of the onset and maintenance of anxiety, which often manifests behaviorally as withdrawal, increased arousal and hypervigilant monitoring of performance. The current study investigated whether longitudinal trajectories of ST were linked to medial frontal (MF) theta power dynamics, a robust marker of performance monitoring. Youth (N = 432, Mage = 11.96 years) completed self-report measures of threat sensitivity annually for 3 years. A latent class growth curve analysis was used to identify distinct profiles of threat sensitivity over time. Participants also completed a GO/NOGO task while electroencephalography was recorded. We identified three threat sensitivity profiles: (i) high (n = 83), (ii) moderate (n = 273) and (iii) low ( n= 76). Participants in the high threat sensitivity class had greater levels of MF theta power differentiation (NOGO-GO) compared to participants in the low threat sensitivity class, indicating that consistently high threat sensitivity is associated with neural indicators of performance monitoring. Of concern, both hypervigilant performance monitoring and threat sensitivity have been associated with anxiety; thus, youth with high threat sensitivity may be at risk for the development of anxiety.
A chromosome-scale high-contiguity genome assembly of the cheetah (Acinonyx jubatus)

The cheetah (Acinonyx jubatus, SCHREBER 1775) is a large felid and is considered the fastest land animal. Historically, it inhabited open grassland across Africa, the Arabian Peninsula, and southwestern Asia; however, only small and fragmented populations remain today. Here, we present a de novo genome assembly of the cheetah based on PacBio continuous long reads and Hi-C proximity ligation data. The final assembly (VMU_Ajub_asm_v1.0) has a total length of 2.38 Gb, of which 99.7% are anchored into the expected 19 chromosome-scale scaffolds. The contig and scaffold N50 values of 96.8 Mb and 144.4 Mb, respectively, a BUSCO completeness of 95.4% and a k-mer completeness of 98.4%, emphasize the high quality of the assembly. Furthermore, annotation of the assembly identified 23,622 genes and a repeat content of 40.4%. This new highly contiguous and chromosome-scale assembly will greatly benefit conservation and evolutionary genomic analyses and will be a valuable resource, e.g., to gain a detailed understanding of the function and diversity of immune response genes in felids.
Query evaluation with constant delay

This thesis is concentrated around the problem of query evaluation. Given a query q and a database D it is to compute the set q(D) of all tuples in the output of q on D. However, the set q(D) may be larger than the database itself as it can have a size of the form n^l where n is the size of the database and l the arity of the query. It can therefore require too many of the available resources to compute it entirely. The main focus of this thesis is a particular solution to this problem: a scenario where in stead of just computing, we are interested in enumerating q(D) with constant delay. Intuitively, this means that there is a two-phase algorithm working as follows: a preprocessing phase that works in time linear in the size of the database, followed by an enumeration phase outputting one by one all the elements of q(D) with a constant delay (which is independent from the size of the database) between any two consecutive outputs. Additionally, four more problems related to enumeration are also considered in the thesis. These are model-checking (where the query q is boolean), counting (where one wants to compute just the size |q(D)| of the output set), testing (where one is interested in an efficient test for whether a given tuple belongs to the output of the query or not) and j-th solution (where, one wants to be able to directly access the j-th element of q(D)). The results presented in the thesis address the above problems with respect to: - first-order queries over the classes of structures with bounded degree, - monadic second-order queries over the classes of structures with bounded treewidth, - first-order queries over the classes of structures with bounded expansion.
Safety evaluation of immune checkpoint inhibitors combined with chemotherapy for the treatment of small cell lung cancer: A meta‐analysis of randomized controlled trials

The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first‐line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. The present study evaluated the tolerability of immune‐based combinations in the first‐line treatment of SCLC.
T 2 orientation anisotropy mapping of articular cartilage using qMRI

Objective. To provide orientation-independent MR parameters potentially sensitive to articular cartilage degeneration by measuring isotropic and anisotropic components of T 2 relaxation, as well as 3D fiber orientation angle and anisotropy via multi-orientation MR scans. Approach. Seven bovine osteochondral plugs were scanned with a high angular resolution of thirty-seven orientations spanning 180° at 9.4 T. The obtained data was fitted to the magic angle model of anisotropic T 2 relaxation to produce pixel-wise maps of the parameters of interest. Quantitative Polarized Light Microscopy (qPLM) was used as a reference method for the anisotropy and fiber orientation. Main results. The number of scanned orientations was found to be sufficient for estimating both fiber orientation and anisotropy maps. The relaxation anisotropy maps demonstrated a high correspondence with qPLM reference measurements of the collagen anisotropy of the samples. The scans also enabled calculating orientation-independent T 2 maps. Little spatial variation was observed in the isotropic component of T 2 while the anisotropic component was much faster in the deep radial zone of cartilage. The estimated fiber orientation spanned the expected 0°–90° in samples that had a sufficiently thick superficial layer. The orientation-independent magnetic resonance imaging (MRI) measures can potentially reflect the true properties of articular cartilage more precisely and robustly. Significance. The methods presented in this study will likely improve the specificity of cartilage qMRI by allowing the assessment of the physical properties such as orientation and anisotropy of collagen fibers in articular cartilage.
Near-infrared electroluminescent devices based on colloidal HgTe quantum dot arrays

Crystalline 4.6 nm HgTe quantum dots, stabilized by 1-thioglycerol ligands, were synthesized by wet chemical methods. Room-temperature photoluminescence spectra of the dots, both in solution and as solid arrays, exhibited near-infrared emission. Light-emitting devices were fabricated by deposition of quantum dot layers onto glass∕indium tin oxide (ITO)∕3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates followed by top contacting with evaporated aluminum. Room-temperature near-infrared electroluminescence from 1mm2 ITO∕PEDOT∕HgTe∕Al devices, centered at ∼1600nm, with an external quantum efficiency of 0.02% and brightness of 150nW∕mm2 at 50 mA and 2.5 V was achieved.
ChatGPT in Clinical Toxicology

ChatGPT has recently been shown to pass the United States Medical Licensing Examination (USMLE). We tested ChatGPT (Feb 13, 2023 release) using a typical clinical toxicology case of acute organophosphate poisoning. ChatGPT fared well in answering all of our queries regarding it.
TOT in combination with solifenacin or intravaginal prasterone in postmenopausal women with mixed urinary incontinence: A retrospective analysis in 112 patients

The aim of this study was to compare the efficacy of the transobturator tape (TOT) procedure combined with solifenacin (TOT‐S) or prasterone (TOT‐P) in postmenopausal women affected by mixed urinary incontinence (MUI) with a predominant stress urinary incontinence component.
Optical State Changes in the X-Ray-quiescent Black Hole A0620–00

We present optical and infrared photometry of the soft X-ray transient A0620–00, obtained by the SMARTS and YALO consortia, spanning the period 1999-2007. Although A0620–00 was X-ray quiescent throughout this period, our data show three distinct optical states, characterized by magnitude, color, and aperiodic variability. In particular, we find that in what we call the “passive” state, A0620–00 exhibits no observable aperiodic variability on any timescale longer than our exposure length. The existence of these states may explain the differences between phased light curves observed by previous authors. We suggest that in order to obtain the purest ellipsoidal light curves, passive-state data should be used in future studies of ellipsoidal variability.
Moisture Transport, Lower-Tropospheric Stability, and Decoupling of Cloud-Topped Boundary Layers

Abstract Decoupling during the “Lagrangian” evolution of a cloud-topped boundary layer advected equatorward by the trade winds in an idealized eastern subtropical ocean is studied using a mixed-layer model (MLM). The sea surface temperature is gradually warmed while the free tropospheric sounding remains unchanged, causing the boundary layer to deepen, the surface relative humidity to decrease, and surface latent heat fluxes to increase. Diurnally averaged insolation is used. For entrainment closures in which entrainment rate is related to a large-eddy convective velocity scale w*, the MLM predicts an increasingly prominent layer of negative buoyancy fluxes below cloud base as the sea surface temperature warms. Decoupling of the mixed layer can be inferred when the MLM-predicted negative buoyancy fluxes become too large for the internal circulations to sustain. The authors show that decoupling is mainly driven by an increasing ratio of the surface latent heat flux to the net radiative cooling in the cloud.
The selective estrogen receptor modulator clomiphene inhibits sterol biosynthesis in Arabidopsis thaliana

Sterols are produced via complex, multistep biosynthetic pathways involving similar enzymatic conversions in plants, animals and fungi, yielding a variety of sterol metabolites with slightly different chemical properties to exert diverse and specific functions. The role of plant sterols has been studied in the context of cell biological processes, signaling and overall plant development, mainly based on mutants. Due to their essential nature, genetic interference with their function causes pleiotropic developmental defects. An important alternative is to use a pharmacological approach. However, the current toolset for manipulating sterol biosynthesis in plants remains limited. Here, we probed a collection of inhibitors of mammalian cholesterol biosynthesis to identify new inhibitors of plant sterol biosynthesis. We provide evidence that imidazole-type fungicides, bifonazole, clotrimazole and econazole inhibit the obtusifoliol 14α-demethylase CYP51, that is highly conserved among eukaryotes. Surprisingly, we found that the selective estrogen receptor modulator, clomiphene, inhibits sterol biosynthesis, in part by inhibiting the plant-specific cyclopropyl-cycloisomerase CPI1. These results demonstrate that rescreening of the animal sterol biosynthesis pharmacology is an easy approach for identifying novel inhibitors of plant sterol biosynthesis. Such molecules can be used as entry points for the development of plant-specific inhibitors of sterol biosynthesis that can be used in agriculture.
Conserved auxin signalling synergism through the canonical and ETT-mediated pathways promotes gynoecium development in members of the Brassicaceae

Gynoecium polarity establishment is regulated by auxin, a phytohormone whose signal is transduced through several pathways. The relationship between the ETT and canonical TIR1/AFB pathways, and their relevance for carpel development beyond Arabidopsis thaliana, have not been investigated. The data presented here show that the expression patterns of canonical and ETT-mediated signalling components, and phenotypes of higher order mutants are shared between Arabidopsis and Capsella rubella. tir1 afb2 ett mutants partially phenocopy ett arf4 double mutants, suggesting a role for AUXIN RESPONSE FACTOR 4 (ARF4) in the integration of canonical and ETT-mediated signalling. Comparative transcriptomics revealed that the auxin-independent mis-regulation of YABBY genes correlate with patterning defects observed in Arabidopsis ett arf4 mutants. Together, the data presented suggest conserved synergism between canonical and ETT-mediated pathways in gynoecium polarity establishment in the Brassicaceae. Finally, the data suggest that ETT/ARF4 function to prevent the auxin-induced expression of a range of targets in Arabidopsis, consistent with activator-repressor ARF antagonism, and implying that the maintenance of auxin insensitivity by repressive ARFs is important for a range of biological processes. Summary Statement Here the relationship between canonical and ETT-mediated auxin signalling machineries is investigated in Arabidopsis and Capsella revealing conserved synergism between these two pathways in Brassicaceae with distinct fruit shapes.
Molecular Adverse Outcome Pathways: towards the implementation of transcriptomics data in risk assessments

Adverse Outcome Pathways (AOPs) are designed to provide mechanistic insights into toxicological processes after exposure to a stressor and facilitate the replacement of animal studies with in vitro testing systems. Starting with a Molecular Initiating Event (MIE) and ending with an Adverse Outcome, the sequence of Key Events (KEs) spans across biological levels, but the majority of KEs in AOP-Wiki describe molecular and cellular processes. That suggests that established transcriptome-wide studies can be used to validate or measure a multitude of KEs simultaneously and be a goldmine of useful information about cellular responses. Currently, in toxicology, omics technologies are not widely applied in risk assessments of chemicals because of their complexity and lack of consensus on aspects such as standardization, analysis and interpretation. Given their value in hypothesis generation and ability to provide a vast amount of information about a biological response, the challenge lies in the acceptance of using transcriptomics data in regulatory risk assessments. We here introduce molecular AOPs to define the connections between KEs of the AOP-Wiki and curated biological pathways in WikiPathways, thereby providing a new method for the analysis and interpretation of transcriptomics data to identify KE activation. To study this, we performed case studies on liver steatosis and mitochondrial complex I inhibition, for which molecular AOPs were developed and public transcriptomics datasets were selected. Upon extension of the molecular AOP networks in Cytoscape, we mapped and analysed transcriptomics data, and calculated an enrichment score for individual KEs. Further interpretation of the data was done through the visualisation of the data on the specific molecular pathways. Two molecular AOPs were developed and KEs were linked to the appropriate molecular pathways, allowing a detailed exploration of molecular processes with the selected transcrip-tomics datasets. This has shown us that we can verify the activation of specific MIEs and KEs, and assess progression across the AOP in the steatosis case study through variables in exposure time and dose. These case studies have shown that transcriptomics data can be used for identifying the potential activation of KEs. However, it is also clear that extensive datasets are required to fully test the capabilities of molecular AOPs, and the process of linking molecular pathways and KEs can be challenging, not always allowing one-to-one mapping. While proven valuable to analyse and understand transcriptomic data, pathways linked to KEs appear to show inconsistent levels of activation and should be looked into and refined. More case studies are required to optimize the approaches used for the development and use of molecular AOPs with transcriptomics datasets.
Spatiotemporal Regulation of De Novo and Salvage Purine Synthesis during Brain Development

Visual Abstract The levels of purines, essential molecules to sustain eukaryotic cell homeostasis, are regulated by the coordination of the de novo and salvage synthesis pathways. In the embryonic central nervous system (CNS), the de novo pathway is considered crucial to meet the requirements for the active proliferation of neural stem/progenitor cells (NSPCs). However, how these two pathways are balanced or separately used during CNS development remains poorly understood. In this study, we showed a dynamic shift in pathway utilization, with greater reliance on the de novo pathway during embryonic stages and on the salvage pathway in postnatal–adult mouse brain. The pharmacological effects of various purine synthesis inhibitors in vitro and the expression profile of purine synthesis enzymes indicated that NSPCs in the embryonic cerebrum mainly use the de novo pathway. Simultaneously, NSPCs in the cerebellum require both the de novo and the salvage pathways. In vivo administration of de novo inhibitors resulted in severe hypoplasia of the forebrain cortical region, indicating a gradient of purine demand along the anteroposterior axis of the embryonic brain, with cortical areas of the dorsal forebrain having higher purine requirements than ventral or posterior areas such as the striatum and thalamus. This histologic defect of the neocortex was accompanied by strong downregulation of the mechanistic target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase (S6K)/S6 signaling cascade, a crucial pathway for cell metabolism, growth, and survival. These findings indicate the importance of the spatiotemporal regulation of both purine pathways for mTORC1 signaling and proper brain development.
OprF impacts Pseudomonas aeruginosa biofilm matrix eDNA levels in a nutrient-dependent manner

The biofilm matrix is composed of exopolysaccharides, eDNA, membrane vesicles, and proteins. While proteomic analyses have identified numerous matrix proteins, their functions in the biofilm remain understudied compared to the other biofilm components. In the Pseudomonas aeruginosa biofilm, several studies have identified OprF as an abundant matrix protein and, more specifically, as a component of biofilm membrane vesicles. OprF is a major outer membrane porin of P. aeruginosa cells. However, current data describing the effects of OprF in the P. aeruginosa biofilm is limited. Here we identify a nutrient-dependent effect of OprF in static biofilms, whereby ΔoprF cells form significantly less biofilm than wild type when grown in media containing glucose or low sodium chloride concentrations. Interestingly, this biofilm defect occurs during late static biofilm formation and is not dependent on the production of PQS, which is responsible for outer membrane vesicle production. Furthermore, while biofilms lacking OprF contain approximately 60% less total biomass than those of wild type, the number of cells in these two biofilms is equivalent. We demonstrate that P. aeruginosa ΔoprF biofilms with reduced biofilm biomass contain less eDNA than wild-type biofilms. These results suggest that the nutrient-dependent effect of OprF is involved in the maintenance of mature P. aeruginosa biofilms by retaining eDNA in the matrix. IMPORTANCE Many pathogens form biofilms, which are bacterial communities encased in an extracellular matrix that protects them against antibacterial treatments. The roles of several matrix components of the opportunistic pathogen Pseudomonas aeruginosa have been characterized. However, the effects of P. aeruginosa matrix proteins remain understudied and are untapped potential targets for antibiofilm treatments. Here we describe a conditional effect of the abundant matrix protein OprF on late-stage P. aeruginosa biofilms. A ΔoprF strain formed significantly less biofilm in low sodium chloride or with glucose. Interestingly, the defective ΔoprF biofilms did not exhibit fewer resident cells but contained significantly less extracellular DNA (eDNA) than wild type. These results suggest that OprF is involved in matrix eDNA retention in mature biofilms.