Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these ...systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR-Cas9 scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore clonality and lineage dynamics during cerebral organoid development and identify a time window of fate restriction as well as variation in neurogenic dynamics between progenitor neuron families. We also establish long-term four-dimensional light-sheet microscopy for spatial lineage recording in cerebral organoids and confirm regional clonality in the developing neuroepithelium. We incorporate gene perturbation (iTracer-perturb) and assess the effect of mosaic TSC2 mutations on cerebral organoid development. Our data shed light on how lineages and fates are established during cerebral organoid formation. More broadly, our techniques can be adapted in any iPSC-derived culture system to dissect lineage alterations during normal or perturbed development.
We compared the effects of two resistance training (RT) programs only differing in the repetition velocity loss allowed in each set: 20% (VL20) vs 40% (VL40) on muscle structural and functional ...adaptations. Twenty‐two young males were randomly assigned to a VL20 (n = 12) or VL40 (n = 10) group. Subjects followed an 8‐week velocity‐based RT program using the squat exercise while monitoring repetition velocity. Pre‐ and post‐training assessments included: magnetic resonance imaging, vastus lateralis biopsies for muscle cross‐sectional area (CSA) and fiber type analyses, one‐repetition maximum strength and full load‐velocity squat profile, countermovement jump (CMJ), and 20‐m sprint running. VL20 resulted in similar squat strength gains than VL40 and greater improvements in CMJ (9.5% vs 3.5%, P < 0.05), despite VL20 performing 40% fewer repetitions. Although both groups increased mean fiber CSA and whole quadriceps muscle volume, VL40 training elicited a greater hypertrophy of vastus lateralis and intermedius than VL20. Training resulted in a reduction of myosin heavy chain IIX percentage in VL40, whereas it was preserved in VL20. In conclusion, the progressive accumulation of muscle fatigue as indicated by a more pronounced repetition velocity loss appears as an important variable in the configuration of the resistance exercise stimulus as it influences functional and structural neuromuscular adaptations.
The relaxation behavior of two lignins (Alcell organosolv, OSL, and hydroxypropyl modified Kraft, ML) and bio-based thermoplastic polyurethane (TPU) blends have been studied by Differential scanning ...calorimetry (DSC), Dynamic-mechanical analysis (DMA) and Dielectric relaxation spectroscopy (DRS). The effect of blending on the glass and local relaxation processes as a function of composition, frequency, and temperature has been assessed. The dielectric spectra were resolved into dipolar relaxations as well as conductive processes for differing blend compositions. Characteristic relaxation times, activation energies and dielectric relaxation strengths of lignin/xTPU blends were also investigated. It was found that blending suppresses the α-relaxation process of the blends compared to virgin TPU. On the other hand, while the position of the β-relaxation was not influenced by blending, a reduction of the activation energies, Ea, of this process was observed in the lignin/xTPU blends. Finally, changes are observed in the conductivity behavior of both blends, with conductivity processes more favorable for the OSL/xTPU blends.
This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery ...as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s).
•Machine Learning (ML) models were used to simulate in real-time the biomechanical behavior of the breast.•Three ML models were trained with data from Finite Element (FE) simulations.•Four experiments were designed to validate and study the models' performance.•The mean error in the prediction of the nodal displacements was under 3 mm.•The time needed for breast compression prediction was under 0.5 s.
•Machine learning (ML) to model the liver biomechanical behaviour during breathing.•ML is much faster than the popular FEM, allowing real-time soft tissue modelling.•Modelling scheme able to predict ...deformation for a new load and a new liver.•ML regression models were used: three tree-based methods and two simpler ones.•Good prediction performance was obtained: all samples with an error under 1 mm.
Progress in biomechanical modelling of human soft tissue is the basis for the development of new clinical applications capable of improving the diagnosis and treatment of some diseases (e.g. cancer), as well as the surgical planning and guidance of some interventions. The finite element method (FEM) is one of the most popular techniques used to predict the deformation of the human soft tissue due to its high accuracy. However, FEM has an associated high computational cost, which makes it difficult its integration in real-time computer-aided surgery systems. An alternative for simulating the mechanical behaviour of human organs in real time comes from the use of machine learning (ML) techniques, which are much faster than FEM. This paper assesses the feasibility of ML methods for modelling the biomechanical behaviour of the human liver during the breathing process, which is crucial for guiding surgeons during interventions where it is critical to track this deformation (e.g. some specific kind of biopsies) or for the accurate application of radiotherapy dose to liver tumours. For this purpose, different ML regression models were investigated, including three tree-based methods (decision trees, random forests and extremely randomised trees) and other two simpler regression techniques (dummy model and linear regression). In order to build and validate the ML models, a labelled data set was constructed from modelling the deformation of eight ex-vivo human livers using FEM. The best prediction performance was obtained using extremely randomised trees, with a mean error of 0.07 mm and all the samples with an error under 1 mm. The achieved results lay the foundation for the future development of some real-time software capable of simulating the human liver deformation during the breathing process during clinical interventions.
•High surface area Fe2O3 (208m2g−1) prepared using a hard template method.•Fe2O3 formed by aggregation of nanocrystals prepared by soft chemistry.•Mesoporous Fe2O3 are very active for the combustion ...of VOCs (propane and toluene).•Soft chemistry higher reducibility than hard template method.•The type of VOC influences the nature of the most active catalysts.
The total oxidation of two representative VOCs, propane and toluene, has been studied using mesoporous α-Fe2O3 catalysts. Different preparation methods have been followed leading to mesoporous materials with different characteristics. Whilst a mesoporous catalyst formed by aggregation of nanocrystals has been produced by soft chemistry using oxalic acid as precipitating agent, a mesoporous material with crystalline walls have been prepared by a nanocasting route using a hard template. These catalysts have been characterized by several physicochemical techniques: XRD, N2 adsorption, TPR, XPS, TEM, HR-TEM, SAED and EDX. Among the different α-Fe2O3 catalysts synthesized differences not only in the surface area and morphology have been observed but also in the lattice parameter, in the concentration of oxygen defects for VOCs adsorption and in the reducibility. In the case of the toluene oxidation it has been observed that the catalytic activity is highest for the catalysts prepared by a nanocasting route, which presents a very high surface area of 208m2g−1. Conversely, for propane oxidation the most active catalyst resulted to be the mesoporous nanocrystalline catalyst formed by aggregation. In this case, a direct relationship between reducibility and catalytic activity normalized per surface area has been observed. The differences between toluene and propane oxidation can be tentatively ascribed to different reaction mechanisms to be accounted for.
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored ...a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.
We performed a comprehensive demographic study of the CO extent relative to dust of the disk population in the Lupus clouds in order to find indications of dust evolution and possible correlations ...with other disk properties. We increased the number of disks of the region with measured
R
CO
and
R
dust
from observations with the Atacama Large Millimeter/submillimeter Array to 42, based on the gas emission in the
12
CO
J
= 2−1 rotational transition and large dust grains emission at ~0.89 mm. The CO integrated emission map is modeled with an elliptical Gaussian or Nuker function, depending on the quantified residuals; the continuum is fit to a Nuker profile from interferometric modeling. The CO and dust sizes, namely the radii enclosing a certain fraction of the respective total flux (e.g.,
R
68%
), are inferred from the modeling. The CO emission is more extended than the dust continuum, with a
R
68%
CO
/
R
68%
dust
median value of 2.5, for the entire population and for a subsample with high completeness. Six disks, around 15% of the Lupus disk population, have a size ratio above 4. Based on thermo-chemical modeling, this value can only be explained if the disk has undergone grain growth and radial drift. These disks do not have unusual properties, and their properties spread across the population’s ranges of stellar mass (
M
⋆
), disk mass (
M
disk
), CO and dust sizes (
R
CO
,
R
dust
), and mass accretion of the entire population. We searched for correlations between the size ratio and
M
⋆
,
M
disk
,
R
CO
, and
R
dust
: only a weak monotonic anticorrelation with the
R
dust
is found, which would imply that dust evolution is more prominent in more compact dusty disks. The lack of strong correlations is remarkable: the sample covers a wide range of stellar and disk properties, and the majority of the disks have very similar size ratios. This result suggests that the bulk of the disk population may behave alike and be in a similar evolutionary stage, independent of the stellar and disk properties. These results should be further investigated, since the optical depth difference between CO and dust continuum might play a major role in the observed size ratios of the population. Lastly, we find a monotonic correlation between the CO flux and the CO size. The results for the majority of the disks are consistent with optically thick emission and an average CO temperature of around 30 K; however, the exact value of the temperature is difficult to constrain.
Context.
The High Resolution Telescope (HRT) of the Polarimetric and Helioseismic Imager on board the Solar Orbiter spacecraft (SO/PHI) and the Helioseismic and Magnetic Imager (HMI) on board the ...Solar Dynamics Observatory (SDO) both infer the photospheric magnetic field from polarised light images. SO/PHI is the first magnetograph to move out of the Sun–Earth line and will provide unprecedented access to the Sun’s poles. This provides excellent opportunities for new research wherein the magnetic field maps from both instruments are used simultaneously.
Aims.
We aim to compare the magnetic field maps from these two instruments and discuss any possible differences between them.
Methods.
We used data from both instruments obtained during Solar Orbiter’s inferior conjunction on 7 March 2022. The HRT data were additionally treated for geometric distortion and degraded to the same resolution as HMI. The HMI data were re-projected to correct for the 3° separation between the two observatories.
Results.
SO/PHI-HRT and HMI produce remarkably similar line-of-sight magnetograms, with a slope coefficient of 0.97, an offset below 1 G, and a Pearson correlation coefficient of 0.97. However, SO/PHI-HRT infers weaker line-of-sight fields for the strongest fields. As for the vector magnetic field, SO/PHI-HRT was compared to both the 720-second and 90-second HMI vector magnetic field: SO/PHI-HRT has a closer alignment with the 90-second HMI vector. In the weak signal regime (< 600 G), SO/PHI-HRT measures stronger and more horizontal fields than HMI, very likely due to the greater noise in the SO/PHI-HRT data. In the strong field regime (≳600 G), HRT infers lower field strengths but with similar inclinations (a slope of 0.92) and azimuths (a slope of 1.02). The slope values are from the comparison with the HMI 90-second vector. Possible reasons for the differences found between SO/PHI-HRT and HMI magnetic field parameters are discussed.
Poly(vinylpyrrolidone-co-butyl acrylate) samples with different proportions of monomers were prepared as tractable and hydrophilic materials. An analysis of the intermolecular interactions between ...the polymer groups was carried out by FTIR. The dependence of the CO bands (lactam and pendant butyl ester) with the composition suggests a strong interaction between the lactam groups. They exert an important influence in the molecular mobility, which was studied by DSC and DRS. A single narrow glass transition temperature (T g) is observed in each random copolymer, consistent with a single phase of low compositional nanoheterogeneity. The dependence of the T g with the composition suggests significant interactions between polymer components. The dielectric spectra show γ, β, and α relaxations in increasing order of temperature, followed by conductive contributions. The apparent activation energies for secondary relaxations have similar values for all the samples. The γ-process is related to the local motions of the butyl units and the β-process is a Johari–Golstein secondary relaxation that is related to the local motions of the pyrrolidone group together with the motion of polymer backbone segments.
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