Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural assessment of the full-length wild-type tumor suppressor protein p53 by mass spectrometry-guided computational modeling

The tetrameric tumor suppressor p53 represents a great challenge for 3D-structural analysis due to its high degree of intrinsic disorder (ca. 40%). We aim to shed light on the structural and functional roles of p53’s C-terminal region in full-length, wild-type human p53 tetramer and their importance for DNA binding. For this, we employed complementary techniques of structural mass spectrometry (MS) in an integrated approach with computational modeling. Our results show no major conformational differences in p53 between DNA-bound and DNA-free states, but reveal a substantial compaction of p53’s C-terminal region. This supports the proposed mechanism of unspecific DNA binding to the C-terminal region of p53 prior to transcription initiation by specific DNA binding to the core domain of p53. The synergies between complementary structural MS techniques and computational modeling as pursued in our integrative approach is envisioned to serve as general strategy for studying intrinsically disordered proteins (IDPs) and intrinsically disordered region (IDRs).
’Simple Tidy GeneCoEx’: a gene co-expression analysis workflow powered by tidyverse and graph-based clustering in R

Gene co-expression analysis is an effective method to detect groups (or modules) of co-expressed genes that display similar expression patterns, which may function in the same biological processes. Here, we present ‘Simple Tidy GeneCoEx’, a gene co-expression analysis workflow written in the R programming language. The workflow is highly customizable across multiple stages of the pipeline including gene selection, edge selection, clustering resolution, and data visualization. Powered by the tidyverse package ecosystem and network analysis functions provided by the igraph package, the workflow detects gene co-expression modules whose members are highly interconnected. Step-by-step instructions with two use case examples as well as source code are available at https://github.com/cxli233/SimpleTidy_GeneCoEx. Core Ideas An R-based workflow that performs gene co-expression analysis was developed. The workflow is based on tidyverse packages and graph theory. The workflow is highly customizable, detects tight gene co-expression modules, and generates publication quality figures. Two plant gene expression datasets were used to benchmark the workflow.
SDSS J085431.18+173730.5: THE FIRST COMPACT ELLIPTICAL GALAXY HOSTING AN ACTIVE NUCLEUS

We report the discovery of a rare compact early-type galaxy, SDSS J085431.18+173730.5 (hereafter cE_AGN). It has a half-light radius of Re = 490 pc and a brightness of Mr = −18.08 mag. Optical spectroscopy available from the Sloan Digital Sky Survey (SDSS) reveals the presence of prominent broad-line emissions with the Hα broad component width of FWHM = 2400 km s−1. The black hole (BH) mass, as estimated from the luminosity and width of the broad Hα emission, is 2.1 × 106 M ☉ ? > . With the help of surface photometry, we perform a detailed analysis of the structural properties. The observed light distribution is best modeled with a double Sérsic function. Fixing the outer component as an exponential disk, we find that the inner component has a Sérsic index of n = 1.4. Considering the inner component as bulge/spheroidal we find that cE_AGN remains consistent in both the BH mass–bulge mass relation and the BH mass–bulge Sérsic index relation. Given these observational properties, we discuss its possible origin investigating the surrounding environment where it is located.
The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus

Neutrophils are essential for host defense against Staphylococcus aureus (S. aureus). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might therefore be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular S. aureus more efficiently. N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. N-SLIT2 also enhances exocytosis of secondary granules. In a murine model of S. aureus skin and soft tissue infection (SSTI), local SLIT2 levels fall initially but increase subsequently, peaking ≈ 3 days after infection. Of note, neutralization of endogenous SLIT2 worsens SSTI. Temporal fluctuations in tissue SLIT2 levels may promote neutrophil recruitment and retention at the infection site and hasten bacterial clearance by augmenting neutrophil oxidative burst and degranulation. Collectively, these actions of SLIT2 coordinate innate immune responses to limit susceptibility to S. aureus. One-sentence summary SLIT2, a prototypic neuro-repellent, spatiotemporally coordinates host defense against Staphylococcus aureus infection.
Credit Risk Management Practices at the Branch Level of a Rural Bank

: Businesses demand credit that will be used to reinvest in their business and for which they expect to earn a return. At the same time lenders supply credit to earn a return when these companies borrow. This process of extending credit has a multiplier effect on the money supply so this is why credit is a powerful driver of any economy. The aim of the study was to examine credit risk management practices of Asante Akyem Rural Bank. The data collection was gathered through questionnaires while the bank and the staff were selected purposively. Descriptive statistics and Kendall’s Coefficient of Concordance were used to analyze the data. The result indicates the availability of credit policy, financial analysis of the borrower and poor management skills of clients affected effective credit risk management. The paper suggests that the management of the bank must review their credit policies from time to time to reflect the changing business environment. the process where consideration into the analysis of the market/industry was not a top priority to influence the credit risk management processes. High interest rate was a major challenge to borrowers while lack of proper appraisal was not an issue from the lender’s point of view. It can be concluded that credit risk management practices of Asante Akyem Rural Bank were relatively effective. The paper suggests that the management of the bank must review their credit policies from time to time to reflect the changing business environment. The need for a system to be put in place for the presentation of information about the risk exposure of the bank as this will help to regularly monitor their loan portfolios. Moreover, there is the need for regular training on effective credit management practices for the staff of the bank. This will make them effective with regards to credit management and consequently reduce portfolio at risk.
Modelling and identification for control of gas bearings — Source link

Gas bearings are popular for their high speed capabilities, low friction and clean operation, but su ﬀ er from poor damping, which poses challenges for safe operation in presence of disturbances. Enhanced damping can be achieved through active lubrication techniques using feedback control laws. Such control design requires models with low complexity, able to describe the dominant dynamics from actuator input to sensor output over the relevant range of operation. The mathematical models based on ﬁrst principles are not easy to obtain, and in many cases, they cannot be directly used for control design due to their complexity and parameter uncertainties. As an alternative, this paper presents an experimental technique for ”in situ” identiﬁcation of low complexity models of the entire rotor-bearing-actuator system. Using grey-box identiﬁcation techniques, the approach is shown to be easily applied to industrial rotating machinery with gas bearings and to allow for subsequent control design. The paper shows how piezoelectric actuators in a gas bearing are e ﬃ ciently used to perturb the gas ﬁlm for identiﬁcation over relevant ranges of rotational speed and gas injection pressure. Parameter-varying linear models are found to capture the dominant dynamics of the system over the range of operation. Based on the identiﬁed models, decentralised proportional control is designed and is shown to obtain the required damping in theory as well as in a laboratory test rig.
A divergence-free parametrization for dynamical dark energy

We introduce a new parametrization for the dark energy, led by the same idea to the linear expansion of the equation of state in scale factor a and in redshift z, which diverges neither in the past nor future and contains the same number of degrees of freedom with the former two. We present constraints of the cosmological parameters using the most updated baryon acoustic oscillation (BAO) measurements along with cosmic microwave background (CMB) data and a recent reanalysis of Type Ia supernova (SN) data. This new parametrization allowed us to carry out successive observational analyses by decreasing its degrees of freedom systematically until ending up with a dynamical dark energy model that has the same number of parameters with ΛCDM . We found that the dark energy source with a dynamical equation of state parameter equal −2/3 at the early universe and −1 today fits the data slightly better than Λ.
Surface Modification of Polymethylmethacrylate (PMMA) by Ultraviolet (UV) Irradiation and IPA Rinsing

Polymethylmethacrylate (PMMA) is commonly applied to microfluidic devices due to its excellent biocompatibility, high optical transparency, and suitability for mass production. Recently, various surface treatment methods have been reported to improve the wettability of polymers, which is directly related to adhesion. In this research, the effect of a UV irradiation technique and an IPA rinsing technique as surface treatments for PMMA is investigated regarding the water contact angle of the PMMA surface. PMMA sheets that were 1.62 mm thick and commercially available were exposed to UV light with four different exposure times. Significant decreases in the water contact angle were observed after exposure to UV light, and the lowered contact angles due to the UV irradiation increased over time. According to the measurement, the water contact angle is a function of UV exposure dose as well as storage time after UV exposure. We examined the effect of a IPA rinsing process after UV irradiation and observed an increase in the water contact angle.
Microbial alteration in marine sediments: Insights from compound-specific isotopic compositions of amino acids in subseafloor environments

The proportion of amino acids (AAs) in sediment can be used as an indicator of microbial degradation, which is primarily the product of benthic prokaryote activity. The microbial activity would be reflected with the stable isotope ratio of nitrogen (δ15N) at the time of mineralization and resynthesis of AAs. In this study, the compound-specific isotope analysis of individual AAs was used to investigate δ15N variation associated with microbial processes in marine sediment samples. Our results showed a decrease in AA concentrations in core-top sediment was accompanied by an increase in δ15N values, suggesting large 15N enrichment in buried AAs. Phenylalanine displayed an increase in δ15N from the surface to depths greater than 2 cm, whereas relatively constant δ15N values at depths below 2 cm, suggesting that microbial utilization of phenylalanine varies with depth. Glycine showed the highest relative molar contribution (from 12.1 to 36.4%), with the largest δ15N increase (from 0.8 to 8.7) in deep sediment, implying that such information can serve as a measure of AA diagenesis in sedimentary environments. Our results also indicated that the δ15N values of individual AAs in sediment reflected the microbial alteration of organic matter at water-sediment interfaces and in sub-surface environments. These findings form an important basis for interpreting the δ15N values of AAs in sediment.
Generation of red blood cells from stem cells: Achievements, opportunities and perspectives for malaria research

Parasites of the genus Plasmodium that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell. As obligate, intracellular parasites, interactions between parasite and host red blood cell components are crucial to multiple aspects of the blood stage malaria parasite lifecycle. The requirement for, and involvement of, an array of red blood cell proteins in parasite invasion and intracellular development is well established. Nevertheless, detailed mechanistic understanding of host cell protein contributions to these processes are hampered by the genetic intractability of the anucleate red blood cell. The advent of stem cell technology and more specifically development of methods that recapitulate in vitro the process of red blood cell development known as erythropoiesis has enabled the generation of erythroid cell stages previously inaccessible in large numbers for malaria studies. What is more, the capacity for genetic manipulation of nucleated erythroid precursors that can be differentiated to generate modified red blood cells has opened new horizons for malaria research. This review summarises current methodologies that harness in vitro erythroid differentiation of stem cells for generation of cells that are susceptible to malaria parasite invasion; discusses existing and emerging approaches to generate novel red blood cell phenotypes and explores the exciting potential of in vitro derived red blood cells for improved understanding the broad role of host red blood cell proteins in malaria pathogenesis.
A NEW NONPLANETARY INTERPRETATION OF THE MICROLENSING EVENT OGLE-2013-BLG-0723

Recently, the discovery of a Venus-mass planet orbiting a brown-dwarf host in a binary system was reported from the analysis of the microlensing event OGLE-2013-BLG-0723. We reanalyze the event considering the possibility of other interpretations. From this, we find a new solution where the lens is composed of two bodies, in contrast to the three-body solution of the previous analysis. The new solution better explains the observed light curve than the previous solution with Δχ2 ∼ 202, suggesting that the new solution is a correct model for the event. From the estimation of the physical parameters based on the new interpretation, we find that the lens system is composed of two low-mass stars with ∼0.2 M⊙ and ∼0.1 M⊙ and located at a distance of ∼3 kpc. The fact that the physical parameters correspond to those of the most common lens population located at a distance with a large lensing probability further supports the likelihood of the new interpretation. Considering that two dramatically different solutions can approximately explain the observed light curve, the event suggests the need for carefully testing all possible lens-system geometries.
Computational simulation of stent thrombosis induced by various degrees of stent malapposition

Percutaneous coronary intervention with stent implantation is one of the most commonly used approaches to treat coronary artery stenosis. Stent malapposition (SM) can increase the incidence of stent thrombosis, but the quantitative association between SM distance and stent thrombosis is poorly clarified. The objective of this study is to determine the biomechanical reaction mechanisms underlying stent thrombosis induced by SM and to quantify the effect of different SM severity grades on thrombosis. The thrombus simulation was performed in a continuous model based on the diffusion-convection response of blood substance transport. Simulated models included well-apposed stents and malapposed stents with various severities where the detachment distances ranged from 0 to 400 μm. The abnormal shear stress induced by SM was considered a critical contributor affecting stent thrombosis, which was dependent on changing SM distances in the simulation. The results illustrate that the proportion of thrombus volume was 1.88% at a SM distance of 75 μm (mild), 3.46% at 150 μm, and 3.93% at 400 μm (severe), but that a slight drop (3.18%) appeared at the detachment distance of 225 μm (intermediate). The results indicate that when the SM distance was less than 150 μm, the thrombus rose notably as the gap distance increased, whereas the progression of thrombogenicity weakened when it exceeded 150 μm. Therefore, more attention should be paid when SM is present at a gap distance of 150 μm. Moreover, when the SM length of stents are the same, thrombus tends to accumulate downstream towards the distal end of the stent as the SM distance increases.
The effect of employee mindfulness in the new media industry on innovative behavior: The chain mediating role of positive emotion and work engagement

Mindfulness has long been concerned and emphasized by scholars in the field of psychology, but there is still a lack of research on mindfulness in management in China. In this study, a questionnaire survey was conducted among 483 employees in the new media industry in Beijing, Shanghai, Guangzhou, Shenzhen, and Hangzhou, China. After modeling and analysis, it was found that employee mindfulness has a positive influence on innovative behavior. Employee mindfulness and innovative behavior are mediated by positive emotions. Employee mindfulness and innovative behavior are mediated by work engagement. Employee mindfulness and innovative behavior are mediated by a chain of positive emotions and work engagement. Enterprise managers should improve the level of mindfulness of employees in the new media industry through mindfulness training and courses for mindfulness training, create an organizational environment that can arouse positive emotions and improve the positive emotions of employees, pay attention to arousing the enthusiasm of the staff, and promote the innovative behavior of staff while enhancing work engagement.
Fatty acid profile driven by maternal diet is associated with the composition of human milk microbiota

Little is known regarding the impact of diet on the breast milk microbiome. We hypothesized that vegan, vegetarian, and omnivore diets would impact the human milk microbiota. We also aimed to explore associations between human milk fatty acid concentrations and microbial composition. A cross-sectional microbiome diversity analysis of human milk samples (N = 72) was performed using 16S rRNA amplicon sequencing. Human milk microbial diversity was not associated with diet type. However, analysis of microbiome in relation to fatty acid profiles revealed significant differences in the overall composition of the human milk microbiota between high (> 0.7% of total fat) and low (< 0.7%) trans-fatty acid groups (TF) (p = 0.039, pairwise PERMANOVA p = 0.035), high (> 40%) versus low (< 40%) saturated fatty acids (UniFrac p = 0.083, PERMANOVA p = 0.094), and high (>60%) versus low (<60%) unsaturated fatty acids (UF) (UniFrac p = 0.094, PERMANOVA p = 0.093). 84% of samples from omnivore mothers were in the high TF group compared to only 12% of samples from vegans. Gut-associated species (Faecalibacterium, Blautia, Roseburia and Subdoligranulum) and Lactobacillus were characteristic of both high UF and TF groups, but not the low-fat groups. Functional analysis revealed 2,4-dichlorophenol 6-monooxygenase was differentially abundant in the high UF group. Although microbiome diversity did not differ by diet type, TF breast milk content differed by diet group, highlighting the relationship between maternal diet and the microbial profile of human milk.
Novel recombinant protein flagellin A N/C attenuates experimental autoimmune encephalomyelitis by suppressing the ROS/NF-κB/NLRP3 signaling pathway

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by demyelination and neurodegeneration, for which traditional treatment offers limited relief. Microglial/macrophage modulation plays a critical role in the pathogenesis of MS. Oxygen free radical accumulation can induce axonal and nerve cell damage, and further promote MS development. We created a new recombinant protein based on flagellin from Legionella pneumophila named flagellin A with linked C- and N-terminal ends (FLaAN/C), which is an independent intellectual property of our team. We previously showed that FLaAN/C might mitigate radiation-induced damage by inhibiting inflammatory responses and oxidative stress. However, whether FLaAN/C protects against MS remains unknown. Here, we investigated the anti-inflammatory effects of FLaAN/C on mice with experimental autoimmune encephalomyelitis (EAE) induced by oligodendrocyte glycoprotein peptide 35–55 (MOG35-55). The mice were injected intraperitoneally with FLaAN/C after the onset of clinical symptoms, then clinical behavior scores and changes in body weight were recorded daily. The spinal lumbar spine in model mice was enlarged and accompanied by inflammatory cell infiltration and demyelination that were reversed by FLaAN/C. FLaAN/C also induced microglia/macrophages to generate less pro-inflammatory (CD86, iNOS, and TNF-α), and more anti-inflammatory (CD206, IL-10, and Arginase-1) cytokines. These findings suggesting that FLaAN/C promoted microglial/macrophages polarization from the inflammatory M1 to the anti-inflammatory M2 phenotype. Moreover, FLaAN/C inhibited release of the inflammatory cytokines, TNF-α, IL-8, IL-6, IL-17, and IFN-γ. These results indicated that the anti-inflammatory effect of FLaAN/C was associated with the inhibited generation of reactive oxygen species. FLaAN/C downregulated the expression of phosphorylated NF-κB-p65 and prevented downstream NLRP3 inflammasome-mediated pyroptosis. Collectively, these results indicated that FLaAN/C prevents pyroptosis by inhibiting the ROS/NF-κB/NLRP3 signaling pathway, and promotes the microglial/macrophage M1/M2 polarization that significantly alleviated inflammation in mouse models of EAE. Our findings suggested that FLaAN/C could be a promising candidate for MS therapy.
Ontology and Quantum Mechanics

The issue of ontology in quantum mechanics, or equivalently the issue of the reality of the wave function is critically examined within standard quantum theory. It is argued that though no strict ontology is possible within quantum theory, ingenious measurement schemes may still make the notion of a FAPP ontology (ontology for all practical purposes) meaningful and useful. Quanta 2014; 3: 47–66.
A low-cost wearable device for portable sequential compression therapy

In 2020, cardiovascular diseases resulted in 25% of unnatural deaths in the United States. Treatment with long-term administration of medication can adversely affect other organs, and surgeries such as coronary artery grafts are risky. Meanwhile, sequential compression therapy (SCT) offers a low-risk alternative, but is currently expensive and unwieldy, and often requires the patient to be immobilized during administration. Here, we present a low-cost wearable device to administer SCT, constructed using a stacked lamination fabrication approach. Expanding on concepts from the field of soft robotics, textile sheets are thermally bonded to form pneumatic actuators, which are controlled by an inconspicuous and tetherless electronic onboard supply of pressurized air. Our open-source, low-profile, and lightweight (140 g) device costs $62, less than one-third the cost the least expensive alternative and one-half the weight of lightest alternative approved by the US Food and Drug Administration (FDA), presenting the opportunity to more effectively provide SCT to socioeconomically disadvantaged individuals. Furthermore, our textile-stacking method, inspired by conventional fabrication methods from the apparel industry, along with the lightweight fabrics used, allows the device to be worn more comfortably than other SCT devices. By reducing physical and financial encumbrances, the device presented in this work may better enable patients to treat cardiovascular diseases and aid in recovery from cardiac surgeries.