Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity

Kinetic stability, defined as the rate of protein unfolding, is central to determining the functional lifetime of proteins, both in nature and in wide-ranging medical and biotechnological applications. Further, high kinetic stability is generally correlated with high resistance against chemical and thermal denaturation, as well as proteolytic degradation. Despite its significance, specific mechanisms governing kinetic stability remain largely unknown, and few studies address the rational design of kinetic stability. Here, we describe a method for designing protein kinetic stability that uses protein long-range order, absolute contact order, and simulated free energy barriers of unfolding to quantitatively analyze and predict unfolding kinetics. We analyze two β-trefoil proteins: hisactophilin, a quasi-three-fold symmetric natural protein with moderate stability, and ThreeFoil, a designed three-fold symmetric protein with extremely high kinetic stability. The quantitative analysis identifies marked differences in long-range interactions across the protein hydrophobic cores that partially account for the differences in kinetic stability. Swapping the core interactions of ThreeFoil into hisactophilin increases kinetic stability with close agreement between predicted and experimentally measured unfolding rates. These results demonstrate the predictive power of readily applied measures of protein topology for altering kinetic stability and recommend core engineering as a tractable target for rationally designing kinetic stability that may be widely applicable.
Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.
IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.
A subcritical water extract of soil grown Zingiber officinale Roscoe: Comparative analysis of antioxidant and anti-inflammatory effects and evaluation of bioactive metabolites

Introduction: Ginger (Zingiber officinale Roscoe) can scavenge free radicals, which cause oxidative damage and inflamm-ageing. This study aimed to evaluate the antioxidant and anti-inflammatory effects of soil ginger's sub-critical water extracts (SWE) on different ages of Sprague Dawley (SD) rats. The antioxidant properties and yield of SWE of soil- and soilless-grown ginger (soil ginger and soilless ginger will be used throughout the passage) were compared and evaluated. Methods: Three (young), nine (adult), and twenty-one (old) months old SD rats were subjected to oral gavage treatments with either distilled water or the SWE of soil ginger at a concentration of 200 mg/kg body weight (BW) for three months. Results: Soil ginger was found to yield 46% more extract than soilless ginger. While [6]-shogaol was more prevalent in soilless ginger, and [6]-gingerol concentration was higher in soil ginger (p < 0.05). Interestingly, soil ginger exhibited higher antioxidant activities than soilless ginger by using 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay. With ginger treatment, a reduced levels of tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) but not interleukin-6 (IL-6) were observed in young rats. In all ages of SD rats, ginger treatment boosted catalase activity while lowering malondialdehyde (MDA). Reduction of urine 15-isoprostane F2t in young rats, creatine kinase-MM (CK-MM) in adult and old rats and lipid peroxidation (LPO) in young and adult rats were also observed. Discussion: The findings confirmed that the SWE of both soil and soilless grown ginger possessed antioxidant activities. Soil ginger produced a higher yield of extracts with a more prominent antioxidant activity. The SWE of soil ginger treatment on the different ages of SD rats ameliorates oxidative stress and inflammation responses. This could serve as the basis for developing a nutraceutical that can be used as a therapeutic intervention for ageing-related diseases.
Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model

More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.
A dual-task gait test detects mild cognitive impairment with a specificity of 91.2%

Background Mild cognitive impairment (MCI) is a valuable intervention window in the progress of senile dementia, but the question of how to easily and conveniently detect MCI in the community remains unanswered. Gait performance reflects cognitive function, but how to reliably detect MCI through gait testing is still being explored. Objective To develop a dual-task gait testing method that could reliably detect MCI in the community. Methods A cross-sectional diagnostic study was conducted in 111 older adults (mean age = 72.14 ± 6.90 years) from five communities in Wuhan, China. A novel dual-task gait testing method, walking while identifying animals in pictures (AniP-DT gait test), was developed. The participants were classified into MCI or cognitively intact based on their performance on the Montreal Cognitive Assessment Scale (MoCA). Gait performance was assessed using both single-task and the AniP-DT gait test. Multiple linear regression and binary logistic regression were used to model the association between gait speed and cognitive status, and receiver operating characteristic (ROC) curve analysis was used to assess the discrimination ability. Results Compared to the cognitively intact group, the gait speed of the MCI group was lower in both single-task and the AniP-DT gait tests. The gait speed of the AniP-DT gait test was significantly associated with MoCA scores after adjusting the covariates and exhibited good discrimination ability in MCI detection (AUC = 0.814), with a specificity of 91.2%. ROC analysis of the logistic models revealed better discrimination ability of dual-task gait velocity when adjusted with age and years of education (AUC = 0.862). Conclusion The evidence in this study suggested that the AniP-DT gait test could be an easy and reliable screening tool for MCI in community older adults.
Jeans’ instability analysis of scalar field halos

In this work we present a hydrodynamic‐type model in order to study dark matter halos of galaxies. We start with the Einstein‐Hilbert Lagrangian in which we have added a complex scalar field minimally coupled to the geometry. We consider that dark matter halos are well described by the Newtonian limit of this theory. This set of equations can be written in the form of Euler equations for a fluid by making a transformation, where the self‐interaction potential of the fluid and a quantum‐like potential is present. We study the Jeans’ instability of the fluid which gives a limit for the unstable halos and is a way for computing the mass of the scalar field.
POINTS CLASSIFICATION BY A SEQUENTIAL HIGHER – ORDER MOMENTS STATISTICAL ANALYSIS OF LIDAR DATA

Abstract. The paper deals with a new sequential procedure to perform unsupervised LIDAR points classification by iteratively studying skewness and kurtosis for elevation and intensity point distribution values. After a preliminary local shape analysis of elevation and intensity point distributions, carried out from the original discrete frequencies by a non parametric estimation of the density functions, the procedure starts by choosing the category of data (elevation or intensity) to analyse at first: the choice falls on the category better showing by a testing procedure a bi or a multi clustering distribution. The first point cluster is identified by studying the distribution skewness and kurtosis variations, after removing at each step the largest data values. The selected cluster is furthermore analysed by studying higher order moments behaviour of the complementary data category. This makes possible to find out potential sub clusters of the original selected one, permitting, in this way, a more effective point classification. Successive clusters are identified by applying the same iterative procedure to the still unclassified LIDAR points. For complex point distribution shapes or for the classification of large areas, a progressive analysis method, based on the partition of the entire data set into regular subsets, is proposed. Some real numerical experiments confirm the capability of the method proposed. The classification total errors in the experiments range from a minimum value of 1,2% to a maximum value of 8,9%.
The Strategy To Increase The Purchase Intention Of Unpacked Products

: Consumer orientation toward Green Products or environmentally friendly products is one of the supporting factors for business continuity. The Green Product in this study is a refill product without packaging (unpacked product). Consumer behaviour in choosing Green Products is part of Pro-Environmental Behavior (PEB) which is largely determined by several things. This study raises several aspects: knowledge, economics, supporting facilities, packaging of the product, and environmental attitude. This research involved 124 respondents who live in Jakarta and surrounding areas. The selection of respondents was carried out by purposive sampling method, with the criteria of respondents being groups of people who were aware of the existence of refillable products without packaging. Data analysis was carried out using Structure Equation Modeling – Partial Least Square (SEM-PLS). The research reveals that all independent variables have a significant effect except for economic aspects.
The Impact Of Customer Satisfaction On Customer Loyalty Of BCA Mobile Banking

In order to meet the demands of customers who seek quick, simple, and affordable services, including banking services, businesses must adapt their methods of operation to the rapid growth of information and communication technology. This study seeks to ascertain what variables may directly affect customer loyalty in the usage of BCA mobile banking in Indonesia for millennials, as well as what factors can directly influence customer satisfaction to develop customer loyalty. Purposive sampling was used in this study's quantitative methodology, with a total sample size of 605, which was then analyzed using PLS-SEM. The results of the study stated that convenience had the greatest influence on increasing customer satisfaction. While the cost factor has no effect on increasing customer satisfaction in the use of BCA mobile banking, and responsive factor only has an effect on increasing satisfaction but does not affect customer loyalty. This provides benefits for developing BCA mobile banking.
The top-quark pair-production cross-section measurement in the dilepton final states at proton-proton collisions with √s = 7 TeV

This thesis presents the results of the top-quark pair-production (tt̄ production) cross-section measurement at proton-proton collisions with √ s = 7 TeV at the Large Hadron Collider (LHC), which is the energy frontier accelerator as of 2011. The top-quark (t-quark) is the heaviest of all known particles, and it was discovered at the Tevatron with √ s = 1.96 TeV in 1995. Owing to its largest mass, the t-quark is expected to be sensitive for new phenomena, and thus a precise measurement of the tt̄ production at the energy frontier is one of the first priorities of experimental particle physics programs. This analysis uses 0.70 fb−1 of pp collision data corresponding to production of 10 times of the tt̄ creations, which has already exceeded the number of tt̄ pairs produced at the Tevatron. The analysis extracts the tt̄ events in final states characterized by two isolated high pT leptons, a large missing transverse momentum (E T ) corresponding to two neutrinos from leptonic W boson’s decays, and jets originating from b-quarks, which are so-called “dilepton final states”. The measurement is based on the well-evaluated detector performances especially in the high intensity environment of the LHC. The following has been achieved owing to the intensive study of the detector performance: (1) the optimization of the tt̄ event selection, (2) the evaluation of the signal acceptance, and (3) the background rate estimation. Thus far, 1,400 candidate events were obtained from the pp collision data with expected the signal purity of 83%. Using the obtained samples, the cross-section is measured to be: 175 ±6 (stat.) +14 −11 (syst.) ±8 (lumi.) pb, where stat, syst, and lumi denote the statistical error, the sum of systematic errors, and the uncertainty originating from the luminosity determination, respectively. This result is in good agreement with the SM prediction of 164.6 +11.5 −15.8 pb. The uncertainty level achieved by this analysis is less than 10% and compatible to that of the SM theory. The research covers following achievements: • Confirmation of the presence of t-quark at the LHC • Establishment of the method to identify tt̄ events at the LHC pp collisions and to evaluate the background contamination • The first precise measurement of the tt̄ production rates in the dilepton final state at the 7 TeV collisions • First detailed study of the tt̄ production kinematic properties in the LHC which confirms the current particle physics Standard Model describes them well. The methods developed and the studies performed for the tt̄ cross-section measurement are applicable for other physics analyses using t-quark, e.g. a new physics search program with signatures of tt̄ + E T or tt̄+jets. The tt̄ identification method established in the present work forms the basis for these physics programs. For analyses in which the tt̄ production is a dominating background such as the supersymmetry search program, the tt̄ background can be evaluated with reference to this experimental result, and it would improve their sensitivity.
Instabilities of a buoyancy-driven system

A buoyancy-driven system can be unstable due to two different mechanisms—one mechanical and the other involving buoyancy forces. The mechanical instability is of the type normally studied in connexion with the Orr-Sommerfeld equation. The buoyancy-driven instability is rather different and is related to the ‘Coriolis’-driven instability of rotating fluids. In this paper, the stability of a buoyancy-driven system, recently called a ‘buoyancy layer’, is examined for the whole range of Prandtl numbers, s. The buoyancy-driven instability becomes increasingly important as the Prandtl number is increased and so particular interest is attached to the limit in which the Prandtl number tends to infinity. In this limit, the system is neutrally stable to first order, but second-order effects render the flow unstable at a Reynolds number of order σ-½. Consequences of the results for the stability of convection in a vertical slot are examined.
Theoretical model and simulation of the extremely short external cavity semiconductor laser

Based on the ray tracing method, the implicit expression of the output spectrum of the extremely short external cavity semiconductor Laser (ESECSL) is derived, and the output spectrum and P-I characteristic of the ESECSL are investigated. The results show that: when the length of external cavity is changed at the order of wavelength, the P-I characteristics of the ESECSL will undergo significant changes; with the variation of the external cavity length, the lasing wavelength of ESECSL will behave cyclical jump in the range of 10nm. Especially, for the external cavity length changed within the range of 40μm-70μm, the jump range of the lasing wavelength will reach the maximum. The simulations well agree with the experimental results reported.
Some conditions for rupture of polymer liquids in extension

Rupture is one of the least investigated and least understood features of the rheological behaviour of polymeric liquids. Some key experimental results on the rupture of polymer melts in uniaxial extension are discussed. Three features of experimental results for narrow molecular weight distribution (MWD) polymers may be highlighted. Firstly, steady elongational flow becomes impossible and rupture of the liquid filament occurs when and if the stored elastic (Hencky) strain reaches 0.5 units. This can be interpreted in terms of a critical Weissenberg number. Secondly, at higher rates of strain (when the elastic strain becomes more than 0.5) the relationship between limiting stress and elastic strain (at the breaking point) is linear. In this case the limiting elastic strain can become at least as high as 2. Thirdly, the strength of a fluid polymer is not a constant but may be characterised by the lifetime, or durability, t* of the filament. This leads to an empirical criterion for rupture: M=(σ3t*/η)=0.30±.
A streamline coordinate system for distorted two-dimensional shear flows

A function ϕ is derived which is constant along the orthogonal trajectories of streamlines in two-dimensional flow. In irrotational flows, ϕ reduces to the velocity potential. The pair of functions ϕ and ψ, where ψ is the stream function, are used to define a coordinate system in rotational fluid flows. Tensor methods are used to transform the equations of motion of a turbulent fluid and the equations for second moments of turbulent fluctuations to this coordinate system. Explicit extra terms appear in the transformed equations embodying the effects of streamline curvature and mean flow acceleration. These extra terms are characterized by two lengthscales which arise naturally from the transformation: the local radius of curvature of the streamline and the ‘e-folding’ distance of the mean streamwise velocity.
X-ray spectrum variations in the south-west Cygnus Loop

The Cygnus Loop is one of the nearest supernova remnants (440 pc), allowing studies of spatial variations to be carried out at high physical resolution compared with other supernova remnants. Chandra Advanced CCD Imaging Spectrometer (ACIS) observations were obtained covering the bright V-shaped region on the south-west limb. This region has strong 0.2-2 keV spectral variations seen with the ROSAT Position Sensitive Proportional Counter. The nature of the spectral variations is analysed using the ACIS observations. It is found that temperature, abundance variations and column density variations all have a significant contribution to the observed spectral variations. Fits with C, N, O (O group) elements and Ne, Na, Mg, Al, Si, S, Ar (Ne group) elements varied together are better than fits with just O and Ne varied. Large spatial variations in abundances are seen, yet the Ne group to O group ratio and the Fe group (Ca, Fe, Ni) to O group ratio are nearly constant for all of the spectra. The most natural explanation is that the elements in the region are due to supernova explosion of a star of ∼18 M ○. which predated the Cygnus Loop explosion.
Comments on “Hopf bifurcation in wakes behind a rotating and translating circular cylinder” [Phys. Fluids 8, 1972 (1996)]

Low-order Galerkin computational results [Phys. Fluids 8, 1972 (1996)] predict a decrease of vortex shedding frequency f with increasing cylinder rotation angular velocity ω, in conflict with much earlier experimental results [M.S. thesis, University of California, San Diego, 1968; AIAA J. 7, 1817 (1969)] for which f increases with increasing ω. A possible flaw in the computations is noted, and a correlation of experimental and computational results is presented.
Electrokinetic flows over inhomogeneously slipping surfaces

Recent measurements and theory suggest that some solid/liquid surfaces can exhibit slip, at times to a surprising degree. Proposed mechanisms for slip include both intrinsic molecular slip as well as “effective” slip over complex and multiphase interfaces (i.e., covered with “lubricating” nanobubbles or trapped gas pockets). Electrokinetic flow velocities can be significantly enhanced over slipping surfaces as the high shear rates within the double layer drive high slip velocities at the interface. It is not clear, however, that surfaces whose effective slip results from a macroscale average of microscopically inhomogeneous slip will exhibit the same effective slip in an electrokinetically driven system. As well, since the surface charge density is generally set by surface chemistry, one might reasonably expect the ζ potential over “slipping” regions to be different than that over nonslip surfaces. Here, we consider electrokinetic flows over inhomogeneously slipping and inhomogeneously charged surfaces th.