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Horizontal penetration in granular media: effect of intruder shape, depth, orientation, and material density on penetration forces
No full textUnderstanding the mechanics of horizontal penetration is fundamental for the development of new burrowing techniques for subsurface characterization/monitoring, infrastructure construction, and the exploration of extreme environments. This contribution uses 3D discrete element simulations and 1-g physical model tests to study the effects of tip shape, intruder depth, soil density, and tip orientation on the drag, lift, and lateral forces that develop during horizontal penetration. The intruder tips tested include the standard CPT tip and three tip morphologies optimized in a prior research study to reduce drag and/or lift forces. The data generated reveal that using the optimized tips can reduce drag forces by up to 45% (compared to a standard cone penetration conical tip). The lift forces are depth-dependent, suggesting that a single intruder geometry cannot yield minimum lift for all depths. The penetration forces increase nonlinearly with penetration depth, indicating a transition between shallow and deep failure mechanisms. The penetration forces increase with soil density due to the increase in the peak friction angle of the material. Tip rotation effectively changes the lateral/vertical forces during penetration. Still, continuous measurement and adaptation are needed to account for instrument compliance, soil variability, and path deviations
Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets
No full textBackground & Aims
Liver sinusoidal endothelial cells (LSECs) are highly specialized components of the hepatic vascular niche, regulating liver function and disease pathogenesis through angiocrine signaling. Recently, we identified GATA4 as a key transcription factor controlling LSEC development and protecting against liver fibrosis. As the transcription factor c-Maf was strongly downregulated in Gata4-deficient LSECs, we hypothesized that c-Maf might be an important downstream effector of GATA4 in LSEC differentiation and liver fibrogenesis.
Methods
Clec4g-iCre/Maffl/fl (MafLSEC-KO) mice with LSEC-specific Maf deficiency were generated and liver tissue was analyzed histologically. LSECs were isolated for bulk RNA-seq, ATAC-seq, and single-cell (sc) RNA-seq analysis. MafLSEC-KO livers were analyzed after MASH diet feeding. The expression of MAF and its targets was analyzed in published human scRNA-seq data.
Results
Endothelial Maf deficiency resulted in perisinusoidal liver fibrosis (Sirius red 0.46% vs. 2.92%; p <0.05) without affecting metabolic liver zonation, accompanied by a switch from sinusoidal to continuous endothelial cell identity, which was aggravated upon MASH diet feeding (p <0.01). Furthermore, endothelial Maf deficiency caused LSEC proliferation (p <0.05) and expression of profibrotic angiocrine factors including Pdgfb, Igfbp5, Flrt2, and Cxcl12, among which FLRT2 (p <0.01) and CXCL12 (p <0.001) activated hepatic stellate cells in vitro. scRNA-seq revealed replacement of zonated LSEC subpopulations with capillarized, proliferative, sprouting and secretory endothelial cell subsets that promote liver fibrogenesis and angiogenesis. This fundamental dysregulation of LSEC gene expression and differentiation was caused by changes in chromatin accessibility and transcription factor activity following loss of Maf. Notably, endothelial MAF expression was also significantly reduced in human cirrhotic livers (p <0.0001).
Conclusions
Hepatic endothelial c-Maf protects against metabolic dysfunction-associated steatohepatitis-like liver fibrosis and regulates endothelial differentiation and zonation by controlling chromatin opening
Stable distance regression via spatial–frequency state space model for robot-assisted endomicroscopy
No full textPurpose
Probe-based confocal laser endomicroscopy (pCLE) is a noninvasive technique that enables the direct visualization of tissue at a microscopic level in real time. One of the main challenges in using pCLE is maintaining the probe within a working range of micrometer scale. As a result, the need arises for automatically regressing the probe–tissue distance to enable precise robotic tissue scanning.
Methods
In this paper, we propose the spatial frequency bidirectional structured state space model (SF-BiS4D) for pCLE probe–tissue distance regression. This model advances traditional state space models by processing image sequences bidirectionally and analyzing data in both the frequency and spatial domains. Additionally, we introduce a guided trajectory planning strategy that generates pseudo-distance labels, facilitating the training of sequential models to generate smooth and stable robotic scanning trajectories. To improve inference speed, we also implement a hierarchical guided fine-tuning (GF) approach that efficiently reduces the size of the BiS4D model while maintaining performance.
Results
The performance of our proposed model has been evaluated both qualitatively and quantitatively using the pCLE regression dataset (PRD). In comparison with existing state-of-the-art (SOTA) methods, our approach demonstrated superior performance in terms of accuracy and stability.
Conclusion
Our proposed deep learning-based framework effectively improves distance regression for microscopic visual servoing and demonstrates its potential for integration into surgical procedures requiring precise real-time intraoperative imaging
Differences in fMRI-based connectivity during abstinence or interventions between heroin-dependent individuals and healthy controls
No full textThe substantial personal, societal, and economic impacts of opioid addiction drive research investigating how opioid addiction affects the brain, and whether therapies attenuate addiction-related metrics of brain function. Evaluating the connectivity between brain regions is a useful approach to characterise the effects of opioid addiction on the brain. This work is a systematic narrative review of studies investigating the effect of abstinence or interventions on connectivity in people who are dependent on heroin (HD) and healthy controls (HC). We found that HD typically showed weaker connectivity than HC between three functional networks: the Executive Control Network, Default Mode Network, and the Salience Network. Abstinence and Transcranial Magnetic Stimulation (TMS) both attenuated differences in connectivity between HD and HC, often by strengthening connectivity in HD. We observed that increased connectivity due to abstinence or TMS consistently related to decreased craving/risk of relapse. Using these findings, we present an “urge and action framework” relating therapeutic factors contributing to craving/relapse, connectivity results, and neurobiological models of HD. To inform future research, we critically assessed the impact of study design and analysis methods on study results. We conclude that the weaker between-network connectivity in HD and HC and its relationship to craving/relapse merits further exploration as a biomarker and target for therapeutic interventions
Longitudinal assessment of sexual behavior and relationship quality during the first year of the COVID-19 pandemic in Britain: findings from a longitudinal population survey (Natsal-COVID)
No full textWhile the impact of social restrictions on sexual and romantic life early in the COVID-19 pandemic has been widely studied, little is known about impacts beyond the initial months. We analyzed responses from 2,098 British adults (aged 18–59) taking part in the Natsal-COVID study (Waves 1 and 2). Participants were recruited via a web panel and surveyed twice: four months and one year after the start of the UK’s first national lockdown (July 2020 and March 2021). Changes in the prevalence and frequency of participants’ physical and virtual sexual behaviors between the two surveys were analyzed using multinomial logistic regression. Changes in the quality of intimate relationships were modeled using logistic regression for the 1,407 participants in steady relationships, adjusting for age, gender, and relationship status. The reported prevalence of any sexual activity amongst the full sample increased over the study period (from 88.1% to 91.5%, aOR = 1.50, 95% CI 1.23–1.84). Increases were observed for physical (aOR = 1.41, 95% CI 1.15–1.74) and virtual (aOR = 1.20, 95% CI 1.07–1.34) activities, particularly masturbation (aOR 1.53, 95% CI 1.37–1.72). Increases were larger for men than women. The proportion of participants in steady relationships whose relationship scored as “lower quality” increased (from 23.9% to 26.9%, aOR = 1.28, 95% CI 1.10–1.49). These findings have implications for understanding sexual health needs during disasters and planning sexual health service priorities following the pandemic
Mechanistic pathways underlying genetic predisposition to atrial fibrillation are associated with different cardiac phenotypes and cardioembolic stroke risk
No full textBACKGROUND:
Genome-wide association studies have clustered candidate genes associated with atrial fibrillation (AF) into biological pathways reflecting different pathophysiological mechanisms. We investigated whether these pathways associate with distinct intermediate phenotypes and confer differing risks of cardioembolic stroke.
METHODS:
Three distinct subsets of AF-associated genetic variants, each representing a different mechanistic pathway, that is, the cardiac muscle function and integrity pathway (15 variants), the cardiac developmental pathway (25 variants), and the cardiac ion channels pathway (12 variants), were identified from previous AF genome-wide association studies. Using genetic epidemiological methods and large-scale datasets such as UK Biobank, deCODE, and GIGASTROKE, we investigated the associations of these pathways with AF-related cardiac intermediate phenotypes, which included electrocardiogram parameters (≈16 500 electrocardiograms), left atrial and ventricular size and function (≈36 000 cardiac magnetic resonance imaging scans), and relevant plasma biomarkers (N-terminal pro-B-type natriuretic peptide, ≈70 000 samples; high-sensitivity troponin I and T, ≈87 000 samples), as well as with subtypes of ischemic stroke (≈11 000 cases).
RESULTS:
Genetic variants representing distinct AF-related mechanistic pathways had significantly different effects on several AF-related phenotypes. In particular, the muscle pathway was associated with a longer PR interval (P for heterogeneity between pathways [Phet]=1×10−10), lower left atrial emptying fraction (Phet=5×10−5), and higher N-terminal pro-B-type natriuretic peptide (Phet=2×10−3) per log-odds higher risk of AF compared with the developmental and ion-channel pathways. In contrast, the ion-channel pathway was associated with a lower risk of cardioembolic stroke (Phet=0.04 in European, and 7×10−3 in multiancestry populations) compared with the other pathways.
CONCLUSIONS:
Genetic variants representing specific mechanistic pathways for AF are associated with distinct intermediate cardiac phenotypes and a different risk of cardioembolic stroke. These findings provide a better understanding of the etiological heterogeneity underlying the development of AF and its downstream impact on disease and may offer a route to more targeted treatment strategies
An augmented shadowing algorithm for calculating the sensitivity of time-average quantities of chaotic systems
No full textWe apply the non-intrusive least-squares shadowing (NILSS) method to a newly proposed augmented tangent system in order to calculate the sensitivity of time-average quantities of chaotic dynamical systems to parameter variations. The original tangent system is augmented with an additional equation that acts as a low-pass filter, leaving low frequencies unaffected while filtering out high frequencies. A linear damping term is also added to the original tangent system; the term is activated at high frequencies but vanishes at low frequencies. The method introduces two new parameters, the damping coefficient and the time-scale of the filter. Their values can be estimated from the properties of the dynamical system. We evaluate the performance of the proposed algorithm in the Kuramoto–Sivashinsky equation and the Kolmogorov flow system. The number of non-negative Lyapunov exponents (NNLEs) of the augmented system is generally smaller than that of the original system, and this accelerates the sensitivity calculations. Comparisons with the standard NILSS demonstrate the accuracy of the method at a reduced computational cost. The proposed algorithm is more scalable compared to existing approaches and can be applied to sensitivity analysis as well as optimisation and control of complex, large-scale dynamical systems, including turbulent flows
Free probability, path developments and signature kernels as universal scaling limits
No full textRandom developments of a path into a matrix Lie group GN have recently been used to construct signature-based kernels on path space. Two examples include developments into GL(N ; R) and U (N ; C), the general linear and unitary groups of dimension N . For the former, Muça Cirone et al. showed that the signature kernel is obtained via a scaling limit of developments with Gaussian vector fields. The second instance was used by Lou et al. to construct a metric between probability measures on path space. We present a unified treatment to obtaining large N limits by leveraging the tools of free probability theory. An important conclusion is that the limiting kernels, while dependent on the choice of Lie group, are nonetheless universal limits with respect to how the development map is randomised. For unitary developments, the limiting kernel is given by the contraction of a signature against the monomials of freely independent semicircular random variables. Using the Schwinger-Dyson equations, we show that this kernel can be obtained by solving a novel quadratic functional equation. We provide a convergent numerical scheme for this equation, together with rates, which does not require computation of signatures themselves
Investigating the effect of lithiation on polycrystalline NMC811 Li-ion battery cathode cracking using in situ SEM micromechanical testing
No full textThe mechanical degradation of polycrystalline NMC811 cathode particles during electrochemical cycling was investigated using in situ powder compression and nanoindentation. The research demonstrates a significant reduction in particle strength upon the first delithiation, with only partial recovery upon (re)lithiation. Continuous cycling within the normal operating window leads to further mechanical degradation, likely due to cracking and potential rock-salt layer formation. This method can be applied to other materials chemistries and used as a reliable and quick method to quantify the mechanical stability of other spherical particles exposed to electrochemical cycling
The effect of micro and nano scale phenomena on system level design and engineering of hybrid pemfc systems
No full textHybrid PEMFC vehicles are an important technological solution in the electrification of transport and the viability of sustainable systems. The degradation of Lithium Ion batteries used in this application is heavily dependent on the thermal management of the system, as well as the ratio between total storage capacity and peak power required. These are also inherently linked in implementation due to the non-isotropic thermal conductivity of the devices, and so de-coupling their impact on long term performance is impossible in situ. To better understand the separate contributions, as well as the interaction between these two parameters with respect to degradation, custom cells composed of a single layer of active material were commissioned. These were then mounted in a custom rig for the purpose of ensuring uniform temperature across all of the active material, and cycled at a variety of temperatures and discharge rates. The results show that above a threshold discharge rate the degradation is significantly accelerated, as well as the shift between degradation modes across a range of temperatures. In addition, the specific power of a PEMFC can be increased by use of current perturbation, a well known technique. However, the mechanism through which this acts is poorly understood, as well as the implementation being rudimentary. A custom PEMFC system was built to demonstrate that modern automotive style PEMFC designs do still benefit from this technique, and that the parameters of the perturbation can be optimised in operando to yield greater benefit. Finally,the voltage response during and after a perturbation was measured at significantly higher sample rate than any present in the literature, giving greater insight into both the mechanism through which the technique acts, as well as informing more elegant future implementations to minimise drawbacks, such as accelerated catalyst and GDL degradation due to frequent voltage cycling.Open Acces