Miracle-dz/UniFAR-FTUs huggingface dataset:
Kindlin‐1 drives early steps of breast cancer metastasis

Dear Editor, Kindlin-1 plays a major role in the activation of integrins [1]. Kindlin-1 is often overexpressed in cancers. Kindlin-1 overexpression has been associated with a higher propensity of breast cancer patients to metastasize to the lungs [2, 3]. Furthermore, Kindlin-1 depletion in mouse models was found to inhibit tumor growth and lung metastasis [3, 4]. However, the underlying mechanisms remain poorly explored. We used the 4T1 mouse model to unravel the causal role of Kindlin-1 in breast cancer. This model comprises of four syngeneic tumor cell lines, including the nonmetastatic 168FARN and the highly metastatic 4T1 cells [5]. We previously demonstrated that Kindlin-1 was only expressed in the 4T1 cells [3]. We now investigated whether Kindlin-1 expression in the 168FARN cells is sufficient to enhance their metastatic capacities (Supplementary Materials). We ectopically expressedKindlin-1 in 168FARNcells and determined the status of β1-integrin activity. Consistent with previous studies [4, 6, 7], adhesion to extracellular matrix substrates was enhanced in Kindlin-1 expressing cells (hereafter cited as Kind1-cells) as compared to control cells (a three-fold increase on laminin, P < 0.001) (Figure 1A). We then evaluated the binding of Kind1-cells to a fibronectin fragment (FN7-10), harboring the integrinbinding RGD motif. We observed that Kindlin-1 enhanced integrin binding to the fibronectin fragment (Figure 1B). Moreover, Kindlin-1 induced the activation of β1-integrin as shown by increased levels of the active form of the protein specifically detected by the 9EG7 antibody on the cell surface (Figure 1C,D). In agreement with previous works [7], Kindlin-1 enhanced cell spreading as measured by the area of the cells (1240 versus 556 μm2, P < 0.001), and Kind1-cells exhibited a reorganized actin cytoskeleton into stress fibers (Supplementary Figure S1A-B). Furthermore, Kindlin-1 triggered the phosphorylation of Src at Tyr416
Human body models for validation studies of deep hyperthermia

Hyperthermia is a therapeutic technique used to enhance the efficacy of radiotherapy and chemotherapy in the treatment of oncological pathologies, by way of a temperature increase of 41–43°C in the target region. To validate hyperthermia devices, as well as the numerical codes used to simulate hyperthermia treatments, simple phantoms are used. This article considers the influence of phantoms’ geometry, dimensions, and considered organs, on the electromagnetic power absorption. Aim of the study was to evaluate the representativeness of such simple phantoms in terms of the power absorbed by the organs target of deep hyperthermia treatments (i.e., uterus and bladder). In particular, attention was posed on the influence of the visceral fat on the distribution of the absorbed power among the different organs. Results show that geometry and dimension does not influence the distribution of the absorbed power among the different tissues/organs (the maximum difference is 4% in the bladder). However, neglecting the presence of visceral fat greatly changes the electromagnetic power absorbed by the target organs, leading to a 23% increase of the percentage power absorbed in the uterus with respect to the complete model. This percent value corresponded to an increase in the volume‐averaged SAR of 140%.
Inhibition of Biofilm Formation and Virulence Factors of Cariogenic Oral Pathogen Streptococcus mutans by Shikimic Acid

Natural products are an important and cost-effective source for screening antimicrobial agents. Here, we identified one compound, shikimic acid, from Illicium verum extract, exhibiting antimicrobial activity against S. mutans proliferation. It also inhibits biofilm formation of this bacteria through decreasing Gtf expression and EPS synthesis. Furthermore, this compound exhibits no significant cytotoxicity at its MIC against S. mutans, providing evidence for its clinical application. ABSTRACT Streptococcus mutans is known as an important oral pathogen causing dental caries, a widespread oral infectious disease. S. mutans synthesize exopolysaccharide (EPS) using glucosyltransferases (Gtfs), resulting in biofilm formation on the tooth surface. Bacterial cells in the biofilms become strongly resistant to a harsh environment, such as antibiotics and host defense mechanisms, making biofilm-based infections difficult to eliminate. Discovering novel antibiofilm agents, especially from natural products, helps to develop effective strategies against this kind of diseases. The present study investigated the inhibitory effect of shikimic acid (SA), one abundant compound derived from Illicium verum extract, on the biofilm formation of S. mutans. We found SA can reduce the EPS synthesized by this oral pathogen and modulate the transcription of biofilm formation related genes, leading to fewer bacterial cells in its biofilm. SA also interacted with cell membrane and membrane proteins, causing damage to bacterial cells. Ex vivo testing of biofilm formation on bovine teeth showed SA strongly decreased the number of S. mutans cells and the number of EPS accumulated on dental enamel surfaces. Moreover, SA exhibits almost no toxicity to human oral cells evaluated by in vitro biocompatibility assay. In conclusion, shikimic acid exhibits remarkable antibiofilm activity against S. mutans and has the potential to be further developed as a novel anticaries agent. IMPORTANCE Natural products are an important and cost-effective source for screening antimicrobial agents. Here, we identified one compound, shikimic acid, from Illicium verum extract, exhibiting antimicrobial activity against S. mutans proliferation. It also inhibits biofilm formation of this bacteria through decreasing Gtf expression and EPS synthesis. Furthermore, this compound exhibits no significant cytotoxicity at its MIC against S. mutans, providing evidence for its clinical application.
Treg suppression of immunity within inflamed allogeneic grafts

CD4+Foxp3+ regulatory T cells (Tregs) restrain inflammation and immunity. However, the mechanisms underlying Treg suppressor function in inflamed nonlymphoid tissues remain largely unexplored. Here, we restricted immune responses to nonlymphoid tissues and used intravital microscopy to visualize Treg suppression of rejection by effector T cells (Teffs) within inflamed allogeneic islet transplants. Despite their elevated motility, Tregs preferentially contacted antigen-presenting cells (APCs) over Teffs. Interestingly, Tregs specifically targeted APCs that were extensively and simultaneously contacted by Teffs. In turn, Tregs decreased MHC-II expression on APCs and hindered Teff function. Last, we demonstrate that Treg suppressive function within inflamed allografts required ectonucleotidase CD73 activity, which generated the antiinflammatory adenosine. Consequently, CD73–/– Tregs exhibited fewer contacts with APCs within inflamed allografts compared with WT Tregs, but not in spleen. Overall, our findings demonstrate that Tregs suppress immunity within inflamed grafts through CD73 activity and suggest that Treg-APC direct contacts are central to this process.
A Community-Informed Virtual World-Based Cardiac Rehabilitation Program as an Extension of Center-Based Cardiac Rehabilitation

This study assessed the feasibility and acceptability of a novel virtual world-based CR (VWCR) program, Destination Rehab, as an extension of a conventional center-based CR program. The VWCR program is a feasible, highly acceptable, and innovative platform to potentially influence health behaviors and CV risk and may increase accessibility to disadvantaged populations with higher CV disease burdens. Purpose: Innovative methods for delivering cardiac rehabilitation (CR) that provide strategies to circumvent the mounting barriers to traditional CR have the potential to widen access to a well-established secondary prevention strategy. Our study assesses the feasibility and acceptability of a novel virtual world-based CR (VWCR) program, Destination Rehab, as an extension of a conventional center-based CR program. Methods: Adult cardiac patients hospitalized at Mayo Clinic hospitals with a diagnosis for CR and ≥1 modifiable, lifestyle risk factor target—sedentary lifestyle (<3 hr physical activity/wk), unhealthy diet (<5 servings fruits and vegetables/d), or current smoking (>1 yr)—were recruited. Patients participated in an 8-wk health education program using a virtual world (VW) platform from a prior proof-of-concept study and a post-intervention focus group. Primary outcome measures included feasibility and acceptability. Secondary outcome measures included changes from baseline to post-intervention in cardiovascular (CV) health behaviors and biometrics, CV health knowledge, and psychosocial factors. Results: Of the 30 enrolled patients (age 59.1 ± 9.7 yr; 50% women), 93% attended ≥1 session and 71% attended ≥75% of sessions. The overall VWCR experience received an 8 rating (scale 0-10) and had high acceptability. Clinically relevant trends were noted in CV health behaviors and biometrics, although not statistically significant. Conclusions: The VWCR program is a feasible, highly acceptable, and innovative platform to potentially influence health behaviors and CV risk and may increase accessibility to disadvantaged populations with higher CV disease burdens.
Early Changes in Striatal Activity and Motor Kinematics in a Huntington's Disease Mouse Model

Huntington's disease is a progressive neurodegenerative disorder with no disease‐modifying treatments. Patients experience motor, cognitive, and psychiatric disturbances, and the dorsal striatum is the main target of neurodegeneration. Mouse models of Huntington's disease show altered striatal synaptic signaling in vitro, but how these changes relate to behavioral deficits in vivo is unclear.
Multivariate data analysis : a global perspective

1 Introduction: Models and Model Building Section I Understanding and Preparing for Multivariate Analysis 2 Cleaning and Transforming Data 3 Factor Analysis Section II Analysis Using Dependece Techniques 4 Simple and Multiple Regression Analysis 5 Canonical correlation 6 Conjoint analysis 7 Multiple Discriminant Analysis and Logistic Regression 8 ANOVA and MANOVA Section III Analysis using Interdependence Techniques 9 Group data and Cluster Analysis 10 MDS and Correspondence Analysis Structural Equation Modeling 11 SEM: An Introduction 12 Application of SEM
Further Study on a PWM Current-Source-Converter-Based Wind Energy Conversion System Considering the DC-Link Voltage

Previous research on the series-connected pulsewidth modulation current-source-converter-based offshore wind energy conversion system is conducted without considering the effects of the independent control of offshore converters and the cables connected between offshore converters and between offshore and onshore converters. In the present work, a further study on the system is conducted taking these factors into consideration. First, the equivalent circuit of the system is derived, based on which two items are selected to evaluate the performance of the system: the dc-link current and the dc-link voltage. Second, both the dc-link current and the dc-link voltage are derived and analyzed, and the worst case is quantitatively and qualitatively defined. Third, the performance of the system with dc filters is investigated. Finally, both simulation and laboratory-scale experiments are provided.
Age-Associated Neurological Complications of COVID-19: A Systematic Review and Meta-Analysis

The outbreak of the novel and highly infectious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in hundreds of millions of infections and millions of deaths globally. Infected individuals that progress to coronavirus disease-19 (COVID-19) experience upper and lower respiratory complications that range in severity and may lead to wide-spread inflammation and generalized hypoxia or hypoxemia that impacts multiple organ systems, including the central and peripheral nervous systems. Since the SARS-CoV-2 outbreak, multiple reports continue to emerge that detail neurological symptoms, ranging from relatively mild (e.g., impaired taste and/or smell) to severe (e.g., stroke), suggesting SARS-CoV-2 may be neurotropic and/or contribute to nervous system injury through direct and/or indirect mechanisms. To gain insight into the types of neurological complications associated with SARS-CoV-2 infection and their possible relationship with age, sex, COVID-19 severity, and comorbidities, we performed a systematic review of case reports and series published in 2020 – April 4, 2021 of infected patients with neurological manifestations. Meta-analyses were conducted using individual patient data from reports where these data could be extracted. Here, we report neurological injury occurs across the lifespan in the context of infection, with and without known comorbidities, and with all disease severities, including asymptomatic patients. Older individuals, however, are more susceptible to developing life-threatening COVID-19 and cerebrovascular disease (CVD), such as stroke. A mild but inverse correlation with age was seen with CNS inflammatory diseases, such as encephalitis, as well as taste and/or smell disorders. When reported, increased age was also associated with comorbid cardiovascular risk factors, including hypertension, diabetes mellitus, and lipid disorders, but not with obesity. Obesity did correlate with development of critical COVID-19. Discussion into potential pathophysiological mechanisms by which neurological symptoms arise and long-term consequences of infection to the nervous system is also provided.
Energy yield modelling of perovskite/silicon two-terminal tandem PV modules with flat and textured interfaces

Perovskite/silicon tandem photovoltaics have emerged as a new technology for highly efficient and inexpensive photovoltaics (PV). In order to maximize the energy yield (EY) and reduce the cost of generated electricity, light management concepts are of key importance for this technology. This numerical study provides a systematic EY analysis, evaluating and predicting the improvement in the EY of perovskite/silicon (Si) two-terminal (2T) PV modules employing micron-scale random pyramids at the front and/or rear surface of the PV module. The 2T tandem PV module architectures comprise an optically thick encapsulant and a module front cover glass with an anti-reflection coating. The EY is studied at various locations in the USA with different climate zones. For a perovskite top solar cell with a bandgap of around 1.72 eV, the perovskite/Si 2T tandem PV modules with textured front and rear surfaces yield the highest relative enhancement in EY of around 26–28% compared to that of a state-of-the-art crystalline Si single-junction reference. The relative enhancement in the EY of planar and rear side textured perovskite/Si 2T tandem PV modules is lower (planar: 12–14% and rear side textured: 19–22%). Finally, the EY of the textured perovskite/Si tandem PV module is investigated with respect to the bandgap of the perovskite top solar cell. Overall, this study highlights the great promise of perovskite/Si 2T tandem PV modules under realistic irradiation conditions and emphasizes the importance of light management textures for maximizing the EY of this technology.
Disproportionate collapse analysis of mid-rise cross-laminated timber buildings

Abstract This paper investigates the structural behaviour of a twelve-storey Cross-Laminated Timber (CLT) building subjected to sudden removal of internal and external ground floor loadbearing walls, and computes the probability of disproportionate collapse. Analyses are carried out at three different structural idealisations, accounting for feasibility and complexity of finite elements models to understand their performance at: (i) the global, (ii) the component and (iii) the connection level. Focus is devoted on force and deformation-demands obtained from nonlinear dynamic analyses of the building. The demands are compared against the supply from common CLT panel sizes and the rotational stiffness (k) of the joints, detailed with off-the-shelf angle brackets and self-tapping screws. The study demonstrates that the applied forces and deformations required to develop resistance mechanisms are too large to be supplied by the proposed element and connection designs, if an internal ground floor wall is removed. The considered building has a probability of failure as high as 32% if designed without considerations of the complexities associated with disproportionate collapse. Consequently, to resist the effects of internal wall removal, the floors need to be redesigned and improved structural detailing with sufficient strength, stiffness and ductility is necessary to trigger collapse resistance mechanisms.
Modeling of the Two-Dimensional Flow Caused by Sea Conditions and Wind Stresses on the Example of Dead Vistula

Abstract The article presents the results of two-dimensional modeling of flows caused by the sea conditions and wind stresses on the example of Dead Vistula. Based on the available bathymetric data, a numerical model of the river section was created, which was supplemented with data on the position of the water table depending on hydrometeorological conditions. To describe the flow field in steady conditions, a simplified model of two-dimensional flow in the form of the bi-harmonic Helmholtz equation for the current function has been adopted, taking into account additional impacts caused by wind stresses on the water surface. Then the current function was converted into the velocity vector components. This equation, supplemented with appropriate boundary conditions, has been solved numerically using the finite difference method. On the basis of the available literature, 4 variants of hydrometeorological conditions were adopted, depending on the direction and strength of wind and sea conditions. The obtained results were compared with the results of published measurements taken on the studied section of the river. These calculations were the basis for the implementation of a two-dimensional model of the spread of pollutants in the studied section of the Dead Vistula.
IFNγ-primed periodontal ligament cells regulate T-cell responses via IFNγ-inducible mediators and ICAM-1-mediated direct cell contact

Periodontal ligament (PDL) cells help maintain tissue homeostasis by balancing PDL tissue inflammation and regeneration. However, the mechanisms by which interferon γ (IFNγ) modulate this process are not yet fully understood. The present study aimed to examine the effect of primed and non-primed PDL cells with IFNγ on the viability and differentiation of T lymphocytes and its functional consequences. The results showed that IFNγ-primed PDL cells possessed enhanced immunosuppression by suppressing T-lymphocyte viability and directing T-lymphocyte differentiation towards a higher T helper (Th) Th2/Th1 ratio. Suppression of T-cell viability was mainly mediated by IFNγ-inducible secreted mediators, which was prevented in the presence of direct cell contact, probably by intercellular adhesion molecule-1 (ICAM-1)-induced PI3 K-mediated transforming growth factor β1 expression in PDL cells. By contrast, ICAM-1 activation augmented IFNγ-induced IFNγ and interleukin-6 expression in PDL cells, which in turn modulated T-cell differentiation. The resulting interaction between these two cell types activated macrophage and suppressed osteoclast differentiation. In conclusion, the results have shown, for the first time to our knowledge, that primed and non-primed PDL cells with IFNγ differentially control T-cell responses via IFNγ-inducible mediators and ICAM-1-mediated direct cell contact, suggesting the role of PDL cells in shifting an inflammatory phase towards a regenerative phase.
Compression principle and Zipf’s Law of brevity in infochemical communication

Compression has been presented as a general principle of animal communication. Zipf’s Law of brevity is a manifestation of this postulate and can be generalized as the tendency of more frequent communicative elements to be shorter. Previous works supported this claim, showing evidence of Zipf’s Law of brevity in animal acoustical communication and human language. However, a significant part of the communicative effort in biological systems is carried out in other transmission channels, such as those based on infochemicals. To fill this gap, we seek, for the first time, evidence of this principle in infochemical communication by analysing the statistical tendency of more frequent infochemicals to be chemically shorter and lighter. We analyse data from the largest and most comprehensive open-access infochemical database known as Pherobase, recovering Zipf’s Law of brevity in interspecific communication (allelochemicals) but not in intraspecific communication (pheromones). Moreover, these results are robust even when addressing different magnitudes of study or mathematical approaches. Therefore, different dynamics from the compression principle would dominate intraspecific chemical communication, defying the universality of Zipf’s Law of brevity. To conclude, we discuss the exception found for pheromones in the light of other potential communicative paradigms such as pressures on successful communication or the Handicap principle.
Making Sense of Childcare Instability Among Families with Low Incomes: (Un)desired and (Un)planned Reasons for Changing Childcare Arrangements

Childcare instability can negatively affect family well-being. Yet not all childcare changes are bad for families. This qualitative study (N = 85) examines work, family, provider, and subsidy-related factors contributing to childcare changes among families with low incomes. We focus on the desirability—the extent to which parents wanted to leave their provider—and the planned nature of childcare changes—the extent to which parents anticipated the change and had time to plan. We find that although nearly all desired changes were planned, undesired changes were both planned and unplanned. Planning was important but not enough for finding care that aligned with family needs, and undesired changes, especially sudden changes, were often driven by the loss of a childcare subsidy, sometimes accompanied by a job loss. We discuss how these findings can help researchers and policymakers understand the implications of complex childcare trajectories for family well-being and early care and education policy.
Investigation of axial thrust deviation between the theory and experiment for high-speed mine submersible pump

In this article, three types of high-speed mine submersible pumps were designed and experimented. During the reliability performance test, the axial thrust balancing device of GFQ150-700 was overloaded and damaged due to an unsuitable designed value of axial thrust. The designed hydraulic axial thrust with the actual value is compared in this article, and the reason for axial thrust deviation is discussed. Results show that axial thrust of the theoretical calculation is close to the numerical simulation value at a certain extent. GFQ100-1000 obtains the maximum theoretical axial thrust, while the maximum simulated value is produced in GFQ150-700, and that is corroborated by experiments. The axial blade force is related to the pump stage and area differences between the blade suction and pressure surface. Due to the increasing stage in GFQ100-1000, the axial blade force increases to a remarkable value in an opposite direction with respect to GFQ150-700. The opposite blade force offsetting other hydraulic forces in GFQ100-1000 is responsible for the maximum hydraulic axial thrust emerges in GFQ150-700 instead of GFQ100-1000.