Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering of human myotubes toward a mature metabolic and contractile phenotype

Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations. We monitored the differentiation process starting from primary human CD56-positive myoblasts in the presence/absence of IGF1 in serum-free medium in daily collected samples for 10 days. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon electrical pulse stimulation following day 6. Myotubes without IGF1 were almost incapable of contraction. IGF1-treatment shifted the proteome toward skeletal muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7 and reduced MYH1/2 suggest a more oxidative phenotype further demonstrated by higher abundance of proteins of the respiratory chain and elevated mitochondrial respiration. IGF1-treatment also upregulated GLUT4 and increased insulin-dependent glucose uptake compared to myotubes differentiated without IGF1. To conclude, utilizing IGF1, we engineered human myotubes that recapitulate the physiological traits of skeletal muscle in vivo superior to established protocols and overcome limitations of previous standards. This novel “easy to use” model enables investigation of exercise on a molecular level.
Do Free Users Make Seller Pay? The Asymmetry Network Effect of Free Users on Fee Sellers in Business-to-Business Electronic Platform

With the prosperity of worldwide e-commerce, platforms generally conduct premium model to convert customer assets. Extant research has investigated the network effect at e-commerce platform, but no study to date has analyzed whether the influx of free users can stimulate sellers to pay for the membership or backfire. In the context of B2B electronic market, we examine the dynamic network effect of free users in different participation quality on fee sellers with a VAR model. The results show that (1) the rise of registered regular sellers can incite more fee sellers to pay for the membership than that of regular buyers; (2) external users attracted by advertising (search advertising and social media advertising in this paper) can impact targeted internal user base. These findings emphasize more exploration should be pay attention to the engagement quality of user base in two-sided markets, and provide guidance related to advertising strategy.
Natural thermal stress-hardening of corals through cold temperature pulses in the Thai Andaman Sea

Thermal variability can render corals stress resistant through a phenomenon coined as “stress-hardening induced by environmental priming”. Fluctuations that involve high temperature peaks have been commonly investigated, however, the effects of a stress-hardening stimulus generated by cold-water pulses has rarely been studied. Offshore island reefs in the Andaman Sea offer an ideal natural setting to study these effects, as cooling water of internal waves induce strong variability with peak intensity in January to June and absence in August to November. While western island shores are exposed to this stimulus, eastern shores remain sheltered. This study examined (1) whether corals from exposed reefs were more heat stress resistant compared to stimulus-sheltered conspecifics and (2) whether this trait can last in the absence of the stimulus. We quantified the thermal stress resistance in two ecologically important coral species, Pocillopora sp. and Porites sp. , from the two island shores, during the two seasons. Coral bleaching intensity and photosynthetic efficiency of algal symbionts were measured as response variables after a short-term heat stress assay (24-48 h, 34 °C) to assess thermal stress resistance. Stress responses of all stimulus-exposed corals were either undetectable (during the season of stimulus presence) or very weak (during stimulus absence), while corals from the stimulus-sheltered shore responded strongly to heat stress irrespective of the season. Hence, thermal resistance was overall greater in corals originating from the stimulus-exposed shore, but it was slightly diminished during the season of stimulus absence, emphasizing the relevance of stimulus recurrence in maintaining the resistance trait. We exemplify that the stimulus of fluctuating low temperature pulses successfully induced stress-hardening in corals. This suggests that priming stimuli do not necessarily need to transgress certain upper thermal thresholds, but can also touch on lower thresholds to be effective. Even more, we argue that cooling pulses might represent a safer stress-hardening regime, since warming-stress accumulation can be avoided. More research is required to obtain a better understanding of environmental priming, but current findings should encourage the development of artificial stress-hardening approaches to enhance coral resistance in reef restoration efforts.
Combined direct/indirect detection allows identification of DNA termini in diverse sequencing datasets and supports a multiple-initiation-site model for HIV plus-strand synthesis

Replication of genetic material involves the creation of characteristic termini. Determining these termini is important to refine our understanding of the mechanisms involved in maintaining the genomes of cellular organisms and viruses. Here we describe a computational approach combining direct and indirect readouts to detect termini from next-generation short-read sequencing. While a direct inference of termini can come from mapping the most prominent start positions of captured DNA fragments, this approach is insufficient in cases where the DNA termini are not captured, whether for biological or technical reasons. Thus, a complementary (indirect) approach to terminus detection can be applied, taking advantage of the imbalance in coverage between forward and reverse sequence reads near termini. A resulting metric (“strand bias”) can be used to detect termini even where termini are naturally blocked from capture or ends are not captured during library preparation (e.g., in tagmentation-based protocols). Applying this analysis to datasets where known DNA termini are present, such as from linear double-stranded viral genomes, yielded distinct strand bias signals corresponding to these termini. To evaluate the potential to analyze a more complex situation, we applied the analysis to examine DNA termini present early after HIV infection in a cell culture model. We observed both the known termini expected based on standard models of HIV reverse transcription (the U5-right-end and U3-left-end termini) as well as a signal corresponding to a previously described additional initiation site for plus-strand synthesis (cPPT [central polypurine tract]). Interestingly, we also detected putative terminus signals at additional sites. The strongest of these are a set that share several characteristics with the previously characterized plus-strand initiation sites (the cPPT and 3’ PPT [polypurine tract] sites): (i) an observed spike in directly captured cDNA ends, an indirect terminus signal evident in localized strand bias, (iii) a preference for location on the plus-strand, (iv) an upstream purine-rich motif, and (v) a decrease in terminus signal at late time points after infection. These characteristics are consistent in duplicate samples in two different genotypes (wild type and integrase-lacking HIV). The observation of distinct internal termini associated with multiple purine-rich regions raises a possibility that multiple internal initiations of plus-strand synthesis might contribute to HIV replication.
Decoded EEG Neurofeedback-Guided Cognitive Reappraisal Training for Emotion Regulation

Neurofeedback is an innovative self-training that adjusts and enhances brain function. One of the more studied application scenarios with neurofeedback training is emotion regulation. Compared with regional brain activity-informed neurofeedback techniques, neurofeedback protocols using the decoded brain states as feedback signals could make the setting of regulation targets more specific and objective. In the present study, we constructed an EEG neurofeedback-guided cognitive reappraisal training protocol for emotion regulation. Forty-two healthy participants (20 females; 22.4±2.2 years old) were recruited and were randomly assigned to either the neurofeedback group or the control group. During the training process, we calculate the real-time self-regulation performance on the evoked emotion based on the decoded emotional states and fed it back to the subjects as the feedback signal. According to our results, real-time feedback of the regulation effect helps subjects improve emotion regulation performance for emotional stimuli with low positive valence. Further analysis of selected EEG features for emotion classification revealed the neural correlates with neurofeedback training. This newly proposed neurofeedback training protocol is a promising treatment for emotion-related mental disorders, with the potential to be a low-cost and high-portability brain-based, non-invasive, neural modulation technique.
In Situ Spatial Reconstruction of Distinct Normal and Pathological Cell Populations Within the Human Adrenal Gland

The human adrenal gland consists of concentrically organized functionally distinct regions responsible for hormone production. Dysregulation of adrenocortical cell differentiation alters the proportion and organization of the functional zones of the adrenal cortex leading to disease. Current models of adrenocortical cell differentiation are based on mouse studies, but there are known organizational and functional differences between human and mouse adrenal glands. This study aimed to investigate the centripetal differentiation model in the human adrenal cortex and characterize aldosterone-producing micronodules (APMs) to better understand adrenal diseases such as primary aldosteronism. We applied spatially resolved in situ transcriptomics to human adrenal tissue sections from two individuals and identified distinct cell populations and their positional relationships. The results supported the centripetal differentiation model in humans, with cells progressing from the outer capsule to the zona glomerulosa, zona fasciculata, and zona reticularis. Additionally, we characterized two APMs in a 72-year-old female. Comparison with earlier APM transcriptomes indicated a subset of core genes, but also heterogeneity between APMs. The findings contribute to our understanding of normal and pathological cellular differentiation in the human adrenal cortex.
Diffuse electroreflectance of thin-film solar cells: Suppression of interference-related lineshape distortions

Electroreflectance (ER) is a standard method to determine the band gap of semiconductor materials that has also been applied to thin-filmsolar cells (TFSCs). However, the lineshapes in typical ER spectra of TFSCs are significantly distorted compared to the model lineshapes, which are used for spectrum evaluation. These distortions are mainly due to thin-film interferences in the stratified system. In this letter, we demonstrate that these distortions are significantly suppressed in diffuse ER (D-ER) where the diffuse instead of the specular reflection of TFSCs is evaluated. The existence of an ER signal in the diffuse reflectance is shown by two-dimensional finite-difference time-domain simulations. Experimentally, the suppression of interference-related lineshape distortions is demonstrated on a series of Cu2ZnSnSe4solar cells with different layer thicknesses and therefore different optical path lengths for interference. The same working principle is demonstrated for a Cu(In,Ga)(S,Se)2solar cell as well. The resulting lineshapes in D-ER can then be interpreted using standard analysis methods such as Aspnes' Third-Derivative Functional Form.
A Multi-stage Super DEA Efficiency Evaluation Model of COVID-19 Pandemic Transmission Performance

The COVID-19 pandemic, which first appeared in China at the end of 2019, has swept across over 220 countries, resulting in millions of infections and deaths and catastrophic economic losses. With the aim of quantitatively evaluating the spread of COVID-19 pandemic, this article constructed an output-oriented multi-stage super data envelopment analysis (DEA) model to assess the COVID-19 transmission efficiency in 117 countries and analyze the transmission characteristics and trends in different periods in Europe, Asia, Africa, and the Americas. We found that there were significant differences in the pandemic spread in different countries, with the pandemics in the United Kingdom, the United States, and Brazil being relatively more serious. However, many countries had similar pandemic transmission characteristics, such as stable or periodic transmission. Although 14.5% of the world population had been fully vaccinated as of August 1, 2021, no pandemic transmission vaccine effect has yet been directly observed.
IRAS 16293-2422: A Very Young Binary System

We present 4". 5 x 2". 5 resolution millimeter wavelength observations of the young far-infrared source IRAS 16293-2422 which resolve the continuum emission into two sources, MM 1 and MM 2. These sources coincide with known radio continuum sources and may constitute a very young binary system with a projected separation of 840 AU. Flux measurements from 18 cm to 25 μm show that the majority of the millimeter wavelength emission arises from dust within 300 AU of the individual central objects. The total dynamical mass of 1.1-1.3 M_⊙, coupled with our mass estimates for MM 1 and MM 2, suggests that the mass in circumstellar material is comparable to that of the central stellar cores. Since the stellar masses are constrained to be ≤ 0.5 M_⊙ each, it is likely that the bolometric luminosity of 30-40 L_⊙ is derived mainly from accretion of the observed circumstellar material. Maps of the J = 2, 3-1, 2 transition of SO obtained simultaneously show that this emission is centered on MM 1, with weaker emission in a clumpy distribution to the east and west. No SO emission is detected toward MM 2, indicating an upper limit to the fractional abundance which is a factor of 10 below that toward MM 1. We propose that the SO emission toward MM 1 is a result of the outflow activity associated with this source and that the outlying emission clumps trace regions of mild interaction between the outflow and the ambient cloud.
BIOMECHANICS OF STOP-JUMP LANDING AND IN-LINE SKATING JUMP LANDING

The purpose of this study was to identify the movement characteristics of lower extremities during stop-jump landing and in-line skating jump landing. Two subjects were asked to perform three jump landing tasks: stop-jump with barefoot (BF), stop-jump with ankle constrain (AC) and jump with in-line skating boots (IS). Landing movements in sagittal plane were recorded by one high speed camera. The activation of four muscles during landing was measured by EMG system. The kinematic results showed that most variables were significantly different between the three jump landing tasks, except for knee angle at ground contact. More activated rectus femoris and smaller knee flexion acceleration found in IS have been considered to be related the ACL injury. It can be concluded that in-line skating jump landing might have higher lower limbs injury risk.
Discrete-time adaptive control of continuous systems with internal and external point delays

This paper deals with the discrete-time pole and zero placement control of continuous systems with internal and external point delays when the discretization is performed through a zero order hold. This strategy of control is based on the possibility to represent the continuous system with delays as a QARMA (quasiregressive moving average) model. An approximate method based on Leverrier's algorithm for obtaining the parameters of a discrete plant model is presented. The parameters are calculated from output values at sampling points of the step response of the system. In the adaptive case, the parameters are obtained online by using the recursive least squares algorithm.
Evaluating Bias of Sequential Mixed-mode Designs Against Benchmark Surveys

This study evaluated three types of bias—total, measurement, and selection bias (SB)—in three sequential mixed-mode designs of the Dutch Crime Victimization Survey: telephone, mail, and web, where nonrespondents were followed up face-to-face (F2F). In the absence of true scores, all biases were estimated as mode effects against two different types of benchmarks. In the single-mode benchmark (SMB), effects were evaluated against a F2F reference survey. In an alternative analysis, a “hybrid-mode benchmark” (HMB) was used, where effects were evaluated against a mix of the measurements of a web survey and the SB of a F2F survey. A special reinterview design made available additional auxiliary data exploited in estimation for a range of survey variables. Depending on the SMB and HMB perspectives, a telephone, mail, or web design with a F2F follow-up (SMB) or a design involving only mail and/or web but not a F2F follow-up (HMB) is recommended based on the empirical findings.
Upper-Level Features Associated with Winter Monsoon Surges over South China

Abstract The upper-level features associated with the two kinds of winter monsoon surges over south China are studied: the easterly surge (ES) and the northerly surge (NS). The study is similar to that used by Wu and Chan, except that a broader region (0°–60°N, 70°–160°E) is considered. The outbreak of an NS is associated with a breakdown of the Siberia–Mongolia high. The upper-level features suggest that the evolution of the Siberia–Mongolia high in an NS can be related to an eastward passage of a short-wave trough and the polar jet based on the quasigeostrophic theory. The intensification of the Siberia–Mongolia high appears likely to be caused mainly by the adiabatic cooling due to rising motion associated with the trough and the polar jet passages. After the passage of the trough and the jet, the Siberia–Mongolia high breaks down in response to the sinking motion upstream of the trough, causing a surge of the northerly winds over the south China coast. For the ES, the passage of an upper ridge is obse.
Sorafenib inhibits invasion of multicellular organoids that mimic Lymphangioleiomyomatosis nodules

Lymphangioleiomyomatosis (LAM) is a debilitating, progressive lung disease with few therapeutic options, largely due to a paucity of mechanistic knowledge of disease pathogenesis. Lymphatic endothelial cells (LECs) are known to envelope and invade clusters of LAM-cells, comprising of smooth muscle α-actin and/or HMB-45 positive "smooth muscle-like cells” however the role of LECs in LAM pathogenesis is still unknown. To address this critical knowledge gap, we investigated wether LECs interact with LAM-cells to augment their metastatic behaviour of LAM-cells. We performed in situ spatialomics and identified a core of transcriptomically related cells within the LAM nodules. Pathway analysis highlights wound and pulmonary healing, VEGF signaling, extracellular matrix/actin cytoskeletal regulating and the HOTAIR regulatory pathway enriched in the LAM Core cells. We developed an organoid co-culture model combining primary LAM-cells with LECs and applied this to evaluate invasion, migration, and the impact of Sorafenib, a multi-kinase inhibitor. LAM-LEC organoids had significantly higher extracellular matrix invasion, decreased solidity and a greater perimeter, reflecting increased invasion compared to non-LAM control smooth muscle cells. Sorafenib significantly inhibited this invasion in both LAM spheroids and LAM-LEC organoids compared to their respective controls. We identified TGFβ1ι1, a molecular adapter coordinating protein-protein interactions at the focal adhesion complex and known to regulate VEGF, TGFβ and Wnt signalling, as a Sorafenib-regulated kinase in LAM-cells. In conclusion we have developed a novel 3D co-culture LAM model and have demonstrated the effectiveness of Sorafenib to inhibit LAM-cell invasion, identifying new avenues for therapeutic intervention.
Brain structure and working memory adaptations associated with maturation and aging in mice

Introduction As the population skews toward older age, elucidating mechanisms underlying human brain aging becomes imperative. Structural MRI has facilitated non-invasive investigation of lifespan brain morphology changes, yet this domain remains uncharacterized in rodents despite increasing use as models of disordered human brain aging. Methods Young (2m, n=10), middle-age (10m, n=10) and old (22m, n=9) mice were utilized for maturational (young vs. middle-age) and aging-related (middle-age vs. old mice) comparisons. Regional brain volume was averaged across hemispheres and reduced to 32 brain regions. Pairwise group differences in regional volume, residualized for total brain volume, and associations between volume and cognitive performance on the Y-maze task were tested. General linear models with total brain volume as a covariate, and logistic regression for sample wide associations were employed respectively, correcting for multiple comparisons. Structural covariance networks were generated using the R package ‘igraph’. Group differences in network centrality (degree), integration (mean distance), and segregation (transitivity, modularity) were tested across network densities (5–40%), using 5,000 (1,000 for degree) permutations with significance criteria of p<0.05 at ≥5 consecutive density thresholds. Results Widespread significant maturational changes in volume occurred in 18 brain regions, including considerable loss in isocortex regions and increases in brainstem regions and white matter tracts. The aging-related comparison yielded 6 significant changes in brain volume, including further loss in isocortex regions and increases in white matter tracts. No significant volume changes were observed across either comparison for subcortical regions. Additionally, smaller volume of the anterior cingulate area (χ2=2.325, pbh=0.044) and larger volume of the hippocampal formation (χ2=-2.180, pbh=0.044) were associated with poorer cognitive performance. Maturational network comparisons yielded significant degree changes in 9 regions, but no aging related changes, aligning with network stabilization trends in humans. Maturational decline in modularity occurred (24-29% density), mirroring human trends of decreased segregation in young adulthood, while mean distance and transitivity remained stable. Conclusions/Implications These findings offer a foundational account of age effects on brain volume, structural brain networks, and cognition in mice, informing future work in facilitating translation between rodent models and human brain aging.