Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease

The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue‐level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross‐sectional case–control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF‐15, IL‐6, NT‐proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide‐adenine‐dinucleotide‐hydrogen (NADH) content in skin as well as reduced passive leg movement‐induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood‐based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.
In vitro culture of reptile PGCS to preserve endangered species

Primordial germ cells (PGCs), are the source of gametes in vertebrates. There are similarities in the development of PGCs of reptiles with avian and mammalian species PGCs development. PGCs culture has been performed for avian and mammalian species but there is no report for reptilian PGCs culture. In vitro culture of PGCs is needed to produce transgenic animals, preservation of endangered animals and for studies on cell behaviour and research on fertility. Reptiles are traded as exotic pets and a source of food and they are valuable for their skin and they are useful as model for medical research. Transgenic reptile has been suggested to be useful for pet industry and medical research. In this research different aspects of PGCs development was compared in three main classes of vertebrates including mammalian, avian and reptilian species. It is proposed that a discussion on similarities between reptilian PGCs development with avian and mammalian species helps to find clues for studies of reptilian PGCs development details and finding an efficient protocol for in vitro culture of reptilian PG.
Topology, computational models, and social-cognitive complexity: Research Articles

The topology or topological structure S, respectively, of a complex system can be defined in a graph theoretical way, i.e., S ⊆ ((V × V), E), V being a set of vertices and E a set of edges. Therefore, a topological structure in this sense can be represented as a directed graph. A relation e(v1, v2), e ∈ E, v1, v2 ∈ V may represent, e.g., a social relation in a social group between group members, a cognitive (semantical or logical) relation between concepts or an economical relation between economical actors. By defining a certain topology and by adding certain rules of interaction between elements vi and vj ∈ V, one obtains a literally universal modeling schema for arbitrarily complex problems (6). This modeling schema will be applied in this article to several different problems, i.e., predictions of social group dynamical processes, the diagnosis of certain diseases via a medical diagnosis system constructed this way, and the solving of a murder case in a detective story. The schema will in some cases be extended to two levels, i.e., one element of a first level will consist of different elements itself. © 2006 Wiley Periodicals, Inc. Complexity 11:43–55, 2006This paper was submitted as an invited paper resulting from the “Understanding Complex Systems” conference held at the University of Illinois–Champaign, May 2005
Study on the Reliability of Dependence-parts Vote System Based on Copula Functions

In reliability theory,the independence is a particular state of the dependence.Reliability mathematics carries through the reliability researches of system that almost suppose that the parts are in the condition of inter-independence.This paper is based on the knowledge of the Copula function to study the reliability of vote system that consists of dependence parts and the relation between the system and copula and to show that how the dependence of parts made the reliability measure of the system.
Evaluation of a machine-learning-driven active–passive upper-limb exoskeleton robot: Experimental human-in-the-loop study

Abstract Evaluating exoskeleton actuation methods and designing an effective controller for these exoskeletons are both challenging and time-consuming tasks. This is largely due to the complicated human–robot interactions, the selection of sensors and actuators, electrical/command connection issues, and communication delays. In this research, a test framework for evaluating a new active–passive shoulder exoskeleton was developed, and a surface electromyography (sEMG)-based human-robot cooperative control method was created to execute the wearer’s movement intentions. The hierarchical control used sEMG-based intention estimation, mid-level strength regulation, and low-level actuator control. It was then applied to shoulder joint elevation experiments to verify the exoskeleton controller’s effectiveness. The active–passive assistance was compared with fully passive and fully active exoskeleton control using the following criteria: (1) post-test survey, (2) load tolerance duration, and (3) computed human torque, power, and metabolic energy expenditure using sEMG signals and inverse dynamic simulation. The experimental outcomes showed that active–passive exoskeletons required less muscular activation torque (50%) from the user and reduced fatigue duration indicators by a factor of 3, compared to fully passive ones.
Können höhere Löhne zur Überwindung des Fachkräftemangels beitragen?

Abstract Germany faces an intense debate around labor and skills shortages. The authors argue that increased competition in the labor market and consequently higher wages and better working conditions are a crucial factor to address labor scarcity. This does not mean that other measures to combat labor scarcity, such as reforms to the immigration system, provision of childcare, or tax disincentives are redundant. However, as the demographic transition will dramatically reduce labor supply, increased competition for labor is important to allocate a scarce factor more efficiently.
The Fluid Dynamics of Heart Valves: Experimental, Theoretical, and Computational Methods

The function of the valves on the left side of the heart is reviewed in Figure I, which shows schematically the pressures, flows, and valve positions of the mitral (inflow) and aortic (outflow) valves of the left ventricle. Note that the cardiac cycle can be divided into two main parts according to whether the ventricular muscle is contracting (systole) or relaxing (dias­ tole). During systole, the mitral valve is closed, the aortic valve is open� and the left ventricle forms a common chamber with the aorta. During diastole, the valve configurations are reversed, and the left ventricle forms a common chamber with the left atrium. Note that the pressure difference across the open valve is very small, and that there is no backflow except for a spurt of brief duration associated with the closure movement of the valve. The valves themselves are thin membranous leaflets. To appreciate their remarkable anatomy, see the superb drawings of Netter (1969). Better still, dissect a fresh beef heart (available from wholesale meat markets and some retail stores).
In-section Click-iT detection and super-resolution CLEM: Shedding light on nucleolar ultrastructure and S-phase progression in plants

Correlative light and electron microscopy (CLEM) is an essential tool that allows for localisation of a particular target molecule(s) and their spatial correlation with the ultrastructural map of subcellular features at the nanometer scale. Adoption of these advanced imaging methods has been limited in plant biology, due to challenges with plant tissue permeability, fluorescence labelling efficiency, indexing of features of interest throughout the complex 3D volume and their re-localization on micrographs of ultrathin cross-sections. Here, we demonstrate an imaging approach based on tissue processing and embedding into methacrylate resin followed by imaging of serial sections by both, single-molecule localization microscopy and transmission electron microscopy for correlative analysis. Importantly, we demonstrate that the use of a particular type of embedding resin is not only compatible with single-molecule localization microscopy but shows a dramatic improvement in fluorophore blinking behavior relative to the whole-mount approaches. Here we used commercially available Click-iT ethynyl-deoxyuridine cell proliferation kit to visualize the DNA replication sites of wild-type Arabidopsis thaliana seedlings, as well as FASCIATA1 and NUCLEOLIN1 mutants and applied our on-section CLEM imaging workflow for the analysis of S-phase progression and nucleolar organization in mutant plants with aberrant nucleolar phenotypes.
17 β-estradiol impedes aortic root dilation and rupture in male Marfan mice

Marfan syndrome causes a hereditary form of thoracic aortic aneurysms with dilation of the aortic root. Human and animal models suggest a worse phenotype for males compared to females with respect to aneurysm size and risk of dissection. In this study we examine the effects of 17 β-estradiol on aortic dilation and rupture in a Marfan mouse model. Marfan male mice were administered 17 β-estradiol and the growth in aortic root size along with the risk of aortic rupture or dissection with the addition of angiotensin II was measured. Transcriptomic profiling was used to identify enriched pathways from 17 β-estradiol treatment. Aortic smooth muscle cells were then treated with cytokines in order to validate the mechanism of 17 β-estradiol protection. We show that 17 β-estradiol decreased the size and rate of aortic root dilation and improved survival from rupture and dissection after treatment with angiotensin II. The Marfan transcriptome was enriched in inflammatory genes and the addition of 17 β-estradiol modulated a set of genes that function through TNFα mediated NF-κB signaling. These included many proteins known to play a role in the phenotypic shift of aortic smooth muscle cells from a contractile to a more inflammatory-like state such as Vcam-1, Mcp-1, Lgals3, Il-6, Il-1b, and C3. In addition, 17 β-estradiol suppressed the induction of these TNFα induced genes in aortic smooth muscle cells in vitro and this effect appears to be NF-κB dependent. In conclusion, 17 β-estradiol protects against the dilation and rupture of aortic roots in Marfan male mice through the inhibition of TNFα -NF-κB signaling and thus prevents the phenotypic switch of aortic smooth muscle cells from a contractile to an inflammatory state.
Role of lipid nanodomains for inhibitory FcγRIIb function

The inhibitory Fcγ receptor FcγRIIb is involved in immune regulation and is known to localize to specific regions of the plasma membrane called lipid rafts. Previous studies suggested a link between the altered lateral receptor localization within the plasma membrane and the functional impairment of the FcγRIIb-I232T variant that is associated with systemic lupus erythematosus. Here, we conducted microsecond all-atom molecular dynamics simulations and IgG binding assays to investigate the lipid nano-environment of FcγRIIb monomers and of the FcγRIIb-I232T mutant within a plasma membrane model, the orientation of the FcγRIIb ectodomain, and its accessibility to IgG ligands. In contrast to previously proposed models, our simulations indicated that FcγRIIb does not favor a cholesterol-or a sphingolipid-enriched lipid environment. Interestingly, cholesterol was depleted for all studied FcγRIIb variants within a 2-3 nm environment of the receptor, counteracting the usage of raft terminology for models on receptor functionality. Instead, the receptor interacts with lipids that have poly-unsaturated fatty acyl chains and with (poly-) anionic lipids within the cytosolic membrane leaflet. We also found that FcγRIIb monomers adopt a conformation that is not suitable for binding to its IgG ligand, consistent with a lack of detectable binding of monomeric IgG in experiments on primary immune cells. However, our results propose that multivalent IgG complexes might stabilize FcγRIIb in a binding-competent conformation. We suggest differences in receptor complex formation within the membrane as a plausible cause of the altered membrane localization or clustering and the altered suppressive function of the FcγRIIb-I232T variant. Significance Statement Our study sheds new light on the molecular mechanisms underlying the regulation of immune signaling mediated by the inhibitory Fcγ receptor (FcγRIIb). By utilizing atomistic simulations and experimental assays, we demonstrate that FcγRIIb interacts with specific lipids in the plasma membrane. Notably, our findings challenge the current view of membrane heterogeneity in immune cells, as FcγRIIb is not localized in specialized membrane domains known as rafts. Rather, we propose that receptor complex formation modulates receptor localization and conformation, thereby enabling ligand binding. Our findings have important implications for understanding how immune receptors function and communicate with each other, and may provide new opportunities for developing therapeutic strategies targeting FcγRIIb in diseases such as autoimmunity and cancer.
The stabilized supralinear network accounts for the contrast dependence of visual cortical gamma oscillations

When stimulated, neural populations in the visual cortex exhibit fast rhythmic activity with frequencies in the gamma band (30-80 Hz). The gamma rhythm manifests as a broad resonance peak in the powerspectrum of recorded local field potentials, which exhibits various stimulus dependencies. In particular, in macaque primary visual cortex (V1), the gamma peak frequency increases with increasing stimulus contrast. Moreover, this contrast dependence is local: when contrast varies smoothly over visual space, the gamma peak frequency in each cortical column is controlled by the local contrast in that column’s receptive field. No parsimonious mechanistic explanation for these contrast dependencies of V1 gamma oscillations has been proposed. The stabilized supralinear network (SSN) is a mechanistic model of cortical circuits that has accounted for a range of visual cortical response nonlinearities and contextual modulations, as well as their contrast dependence. Here, we begin by showing that a reduced SSN model without retinotopy robustly captures the contrast dependence of gamma peak frequency, and provides a mechanistic explanation for this effect based on the observed non-saturating and supralinear input-output function of V1 neurons. Given this result, the local dependence on contrast can trivially be captured in a retinotopic SSN which however lacks horizontal synaptic connections between its cortical columns. However, long-range horizontal connections in V1 are in fact strong, and underlie contextual modulation effects such as surround suppression. We thus explored whether a retinotopically organized SSN model of V1 with strong excitatory horizontal connections can exhibit both surround suppression and the local contrast dependence of gamma peak frequency. We found that retinotopic SSNs can account for both effects, but only when the horizontal excitatory projections are composed of two components with different patterns of spatial fall-off with distance: a short-range component that only targets the source column, combined with a long-range component that targets columns neighboring the source column. We thus make a specific qualitative prediction for the spatial structure of horizontal connections in macaque V1, consistent with the columnar structure of cortex.
Sinogram Domain Angular Upsampling of Sparse-View Micro-CT with Dense Residual Hierarchical Transformer and Noise-Aware Loss

Reduced angular sampling is a key strategy for increasing scanning efficiency of micron-scale computed tomography (micro-CT). Despite boosting throughput, this strategy introduces noise and artifacts due to undersampling. In this work, we present a solution to this issue, by proposing a novel Dense Residual Hierarchical Transformer (DRHT) network to recover high-quality sinograms from 2 ×, 4× and 8× undersampled scans. DRHT is trained to utilize limited information available from sparsely angular sampled scans and once trained, it can be applied to recover higher-resolution sinograms from shorter scan sessions. Our proposed DRHT model aggregates the benefits of a hierarchical-multi-scale structure along with the combination of local and global feature extraction through dense residual convolutional blocks and non-overlapping window transformer blocks respectively. We also propose a novel noise-aware loss function named KL-L1 to improve sinogram restoration to full resolution. KL-L1, a weighted combination of pixel-level and distribution-level cost functions, leverages inconsistencies in noise distribution and uses learnable spatial weights to improve the training of the DRHT model. We present ablation studies and evaluations of our method against other state-of-the-art (SOTA) models over multiple datasets. Our proposed DRHT network achieves an average increase in peak signal to noise ratio (PSNR) of 17.73dB and a structural similarity index (SSIM) of 0.161, for 8× upsampling, across the three unique datasets, compared to their respective Bicubic interpolated versions. This novel approach can be utilized to decrease radiation exposure to patients and reduce imaging time for large-scale CT imaging projects.
Roles of inflammasomes in viral myocarditis

Viral myocarditis (VMC), characterized by viral infection-induced inflammation, is a life-threatening disease associated with dilated cardiomyopathy or heart failure. Innate immunity plays a crucial role in the progression of inflammation, in which inflammasomes provide a platform for the secretion of cytokines and mediate pyroptosis. Inflammasomes are rising stars gaining increasing attention. The nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome, and the caspase-11 inflammasome are three inflammasomes that were reported to affect the process and prognosis of VMC. These inflammasomes can be activated by a wide range of cellular events. Accumulating evidence has suggested that inflammasomes are involved in different stages of VMC, including the trigger and progression of myocardial injury and remodeling after infection. In this review, we summarized the pathways involving inflammasomes in VMC and discussed the potential therapies targeting inflammasomes and related pathways.
Regulation of cleavage embryo genes upon DRP1 inhibition in mouse embryonic stem cells

Dynamic-related protein 1 (DRP1) is a key protein of mitochondrial fission. In this study, we found that inhibition of activity of DRP1 led to increased levels of cleavage embryo genes in mouse embryonic stem cells (mESCs), which might reflect a transient totipotency status derived from pluripotency. This result indicates that DRP1 inhibition in mESCs leads to a tendency to obtain a new expression profile similar to that of the 2C-like state. Meanwhile, we also noticed that the glycolysis/gluconeogenesis pathway and its related enzymes were significantly downregulated, and the key glycolytic enzymes were also downregulated in various 2C-like cells. Moreover, when DRP1 activity was inhibited from the late zygote when cleavage embryo genes started to express, development of early embryos was inhibited, and these cleavage embryo genes failed to be efficiently silenced at the late 2-cell (2C) stage. Taken together, our result shows that DRP1 plays an important role in silencing cleavage embryo genes for totipotency-to-pluripotency transition.
Co-administration of extracellular matrix-based biomaterials with neural stem cell transplantation for treatment of central nervous system injury

Injuries and disorders of the central nervous system (CNS) present a particularly difficult challenge for modern medicine to address, given the complex nature of the tissues, obstacles in researching and implementing therapies, and barriers to translating efficacious treatments into human patients. Recent advancements in neural stem cell (NSC) transplantation, endogenous neurogenesis, and in vivo reprogramming of non-neural cells into the neuronal lineage represent multiple approaches to resolving CNS injury. However, we propose that one practice that must be incorporated universally in neuroregeneration studies is the use of extracellular matrix (ECM)-mimicking biomaterials to supply the architectural support and cellular microenvironment necessary for partial or complete restoration of function. Through consideration of developmental processes including neurogenesis, cellular migration, and establishment of functional connectivity, as well as evaluation of process-specific interactions between cells and ECM components, insights can be gained to harness and modulate native and induced neurobiological processes to promote CNS tissue repair. Further, evaluation of the current landscape of regenerative medicine and tissue engineering techniques external to the neurosciences provides key perspectives into the role of the ECM in the use of stem cell-based therapies, and the potential directions future neuroregenerative approaches may take. If the most successful of these approaches achieve wide-spread adoption, innovative paired NSC-ECM strategies for neuroregeneration may become prominent in the near future, and with the rapid advances these techniques are poised to herald, a new era of treatment for CNS injury may dawn.