Miracle-dz/UniFAR-FTUs huggingface dataset:
Stochasticity in multi-phosphorylation and quasi steady state approximation in stochastic simulation

Quantitative and qualitative nature of chemical noise propagation in a network of chemical reactions depend crucially on the topology of reaction networks. Multisite reversible phosphorylation-dephosphorylation of target proteins is one such recurrently found topology in various cellular networks regulating key functions in living cells. Here we analytically calculated the stochasticity in multistep reversible chemical reactions by determining variance of phosphorylated species at the steady state using linear noise approximation. We investigated the dependence of variance on the rate parameters in the reaction chain and the number of phosphorylation sites on the species. Assuming a quasi steady state approximation on the multistep reactions, originating from the disparity in time scales in the network, we propose a simulation scheme for coupled chemical reactions to improve the computational efficiency of stochastic simulation of the network. We performed case studies on signal transduction cascade and positive feedback loop with bistability to show the accuracy and efficiency of the method.
Newly developed method for the determination of sitagliptin phosphate using rubeanic acid as a precipitating agent via the use of ISNAG continues flow fluorimeter

A new, a simple, sensitive and fast developed method for the estimation of sitagliptin phosphate in pure and pharmaceutical drugs (tablet). This method based on the reaction between sitagliptin phosphate and rubeanic acid to form reddish-black ppt, using ISNAG-Fluorimeter analyzer via the measure of diverged light at 90° from radiation sourcewhich is used a range of high intensity ultraviolet 184.9 nm & 253.7 nm by low-pressure mercury lamp while detector cell can detect at 410-1150 nm. The resultant of diverged light by an interaction between incident photons and precipitated particles giving rise to a longer wavelength that the detector can detected. Chemical and physical parameters were studied and optimized. The calibration graph was linear in the range of (0.03-13 ) mmol.L−1 , with correlation coef icient ( r )= 0.9881 ,linearity percentage r%= 97.64 , L.O. D = 0. 7848μg/sample and RSD lower than 0.6% for (3&7 ) mmol.L−1 ( eight replicates) concentration of sitagliptin phosphate. This method was successfully applied for the determination of sitagliptin phosphate in two different companies of pharmaceutical drugs. A comparisonwasmadebetween thenewlydevelopedmethod analysiswith the classical method (UV-spectrophotometer by measuring of absorbance ) using standard addition method via the use of t-test, it was noticed that there was no signi icant difference between two methods at %95 con idence level.
Individual‐based models forecast the spread and inform the management of an emerging riverine invader

Mounting ecological impacts of invasive species on freshwater ecosystems are among the greatest challenges confronting ecologists and decision‐makers in conserving biodiversity and ecosystem function. Tools to slow the proliferation of aquatic invasive species are still needed to guide the allocation of limited resources more effectively and efficiently once a species is already established. Here we develop mechanistic models to recreate the invasion history of the rusty crayfish Faxonius rusticus in the John Day River (JDR) basin, forecast its future distribution, and evaluate the management efficiency of, and trade‐offs among, population control actions.
Examining effectiveness of teaching business ethics: An experimental assessment

Abstract The authors examine impact of ethics education on decision making of students who had successfully credited a recently instituted course on business ethics in their Bachelor of Commerce program. Designing an experiment that provides both the opportunity and incentive to act unfairly, they assess effectiveness of the ethics education and examine the extent to which ethical values are actually internalized. The authors test ethical conduct of the students using a novel adaption of the unscrambled-anagram exercise. They further compare unethical behavior of the students with academic grades and religiosity. Regardless of the grades earned, misreporting rates are nearly the same. The authors find that sociocultural religious values do impact the ethical behavior.
CFD-CFD coupling: A novel method to develop a fast urban microclimate model

Computational fluid dynamics (CFD) technique is well-known for its powerful capability of modelling the cross-ventilation. CFD is broadly coupled with energy simulation programmes, such as EnergyPlus, to expand its application in building energy calculation. During the coupling process, iterative calculation is required to improve the accuracy of the coupling method, which means the scale of the model should be designed with extra care so that the simulation can be practical in terms of computational cost. A coarse-resolution mesh (here denoted as CFDc) cannot properly represent the required local environment to study the underlying physics. However, a fine-resolution CFD microclimate model (here denoted as CFDf), which includes both indoor and outdoor spaces, always requires a large number of cells to capture the complexities of environment; this makes the coupling procedure a challenging problem. This study aims to propose an innovative, high-resolution and computationally cost-effective CFDf-CFDc model to overcome this gap. The full-scale CFDf works in an off-line manner at the preliminary simulation stage and generates detailed flow parameters at the interfaces for CFDc. At the dynamic stage of the simulation, CFDc participates in the coupling procedure with the other tools, for example, building energy simulation (BES) tool (e.g. EnergyPlus). The coupling of CFDf-CFDc-BES is about 200 times faster than an ordinary coupled CFDf-BES method with a significantly quicker and more stable achievement in the convergence.
A latitudinal gradient in herbivore resistance in common sunflower, Helianthus annuus (Asteraceae)

Background and aims – The intensity of herbivory is expected to decline with increasing latitude. As herbivory varies spatially and over time, a reliable method of assessing the intensity of herbivory is to examine the degree of herbivore resistance in the plant community. Latitudinal gradients in resistance to herbivory were examined in wild populations of common sunflower, Helianthus annuus. Materials and methods – Seeds from 23 different latitudes, ranging from 20 to 44°N, were obtained from the USDA’s Germplasm Resources Information Network. Plants were grown in a greenhouse for nine weeks. At that time, the size (height, leaf length, number of leaves) and resistance of each plant to herbivory (determined through a bioassay using a generalist herbivore, Helicoverpa zea was assessed. Key results – Resistance to herbivory decreased significantly with latitude, while plant size, as indicated by height, was positively correlated with latitude and negatively correlated with both temperature and resistance to herbivory. Conclusion – Populations from lower latitudes exhibited elevated resistance to herbivory and slower growth, suggesting first, that herbivory is more intense at lower latitudes and second, that there is a tradeoff between growth and defense.
Seafloor mapping based on multibeam echosounder bathymetry and backscatter data using Object-Based Image Analysis: a case study from the Rewal site, the Southern Baltic

Abstract Seafloor mapping is a fast developing multidisciplinary branch of oceanology that combines geophysics, geostatistics, sedimentology and ecology. One of its objectives is to isolate distinct seabed features in a repeatable, fast and objective way, taking into consideration multibeam echosounder (MBES) bathymetry and backscatter data. A large-scale acoustic survey was conducted by the Maritime Institute in Gdańsk in 2010 using Reson 8125 MBES. The dataset covered over 20 km2 of a shallow seabed area (depth of up to 22 m) in the Polish Exclusive Economic Zone within the Southern Baltic. Determination of sediments was possible based on ground-truth grab samples acquired during the MBES survey. Four classes of sediments were recognized as muddy sand, very fine sand, fine sand and clay. The backscatter mosaic created using the Angular Variable Gain (AVG) empirical method was the primary contribution to the image processing method used in this study. The use of the Object-Based Image Analysis (OBIA) and the Classification and Regression Trees (CART) classifier makes it possible to isolate the backscatter image with 87.5% overall and 81.0% Kappa accuracy. The obtained results confirm the possibility of creating reliable maps of the seafloor based on MBES measurements. Once developed, the OBIA workflow can be applied to other spatial and temporal scenes.
Rational Discovery of Dual-Action Multi-Target Kinase Inhibitor for Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

Although remarkable progresses have been made in the cancer treatment, existing anti-cancer drugs are associated with increasing risk of heart failure, variable drug response, and acquired drug resistance. To address these challenges, for the first time, we develop a novel genome-scale multi-target screening platform 3D-REMAP that integrates data from structural genomics and chemical genomics as well as synthesize methods from structural bioinformatics, biophysics, and machine learning. 3D-REMAP enables us to discover marked drugs for dual-action agents that can both reduce the risk of heart failure and present anti-cancer activity. 3D-REMAP predicts that levosimendan, a drug for heart failure, inhibits serine/threonine-protein kinase RIOK1 and other kinases. Subsequent experiments confirm this prediction, and suggest that levosimendan is active against multiple cancers, notably lymphoma, through the direct inhibition of RIOK1 and RNA processing pathway. We further develop machine learning models to identify cancer cell-lines and patients that may respond to levosimendan. Our findings suggest that levosimendan can be a promising novel lead compound for the development of safe and effective multi-targeted cancer therapy, and demonstrate the potential of genome-wide multi-target screening in designing polypharmacology and drug repurposing for precision medicine. Author Summary Multi-target drug design (a.k.a targeted polypharmacology) has emerged as a new strategy for discovering novel therapeutics that can enhance therapeutic efficacy and overcome drug resistance in tackling multi-genic diseases such as cancer. However, it is extremely challenging for conventional computational tools that are either receptor-based or ligand-based to screen compounds for selectively targeting multiple receptors. Existing multi-target drug design mainly focuses on compound screening against receptors within the same gene family but not across different gene families. Here, we develop a new computational tool 3D-REMAP that enables us to identify chemical-protein interactions across fold space on a genome scale. The genome-scale chemical-protein interaction network allows us to discover dual-action drugs that can bind to two types of targets simultaneously, one for mitigating side effect and another for enhancing the therapeutic effect. Using 3D-REMAP, we predict and subsequently experiments validate that levosimendan, a drug for heart failure, is active against multiple cancers, notably, lymphoma. This study demonstrates the potential of genome-wide multi-target screening in designing polypharmacology and drug repurposing for precision medicine.
Computational Study of Desynchronization of Fast‐Spiking Interneurons at Macroscopic Gamma Oscillations

There are typically two distinct types of single‐neuron dynamics, known as Class I and Class II. Fast‐spiking (FS) neurons are a type of Class II neuron, which tend to exhibit periodic spikes in the gamma frequency. Although the population dynamics of Class I neurons are well elucidated with the Fokker‐Planck equation (FPE), much remains unknown about the population dynamics of Class II neurons. This is because the population model of Class II neurons typically leads to a high‐dimensional FPE that is hard to analyze. The modified theta (MT) model is one of the simplest mathematical models of Class I neurons, which possesses voltage‐dependent dynamics and has advantages in the analysis of population dynamics. In this study, we propose two approximation methods to derive a one‐dimensional FPE for FS interneurons using the framework of MT transformation. One method is mean‐field approximation of the variable related to adaptation; the other is semi‐adiabatic approximation of the variable. We confirm the firing characteristics of a single neuron in these approximated models match well to that of the original model proposed by Izhikevich. For the populational dynamics of the gamma oscillation, FPEs with these approximations make it possible to identify the region where Class II neuron firings synchronize. Bifurcation analyses of two FPEs show that semi‐adiabatic approximation fits better to the numerical results than mean‐field approximation. FPE with semi‐adiabatic approximation better illustrates the fact that a population of FS interneurons has a narrower region of gamma oscillation than that of Class I neurons. Moreover, analysis with semi‐adiabatic approximation of a population composed of both Class I and FS interneurons has a narrower region of synchronization with an increase in the FS interneuron ratio. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons

Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson‘s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson’s disease.
An improved dealiasing scheme for the fourth‐order Runge‐Kutta method: Formulation, accuracy and efficiency analysis

In this paper, the Random Phase Shift Method (RPSM) dealiasing scheme has been developed with the classical fourth‐order explicit Runge‐Kutta (RK4) method. This scheme is implemented in different benchmark problems to verify its numerical accuracy and computational efficiency where strong gradients are present in the solution. The propagation of aliasing errors through the substeps of RK4 is derived to show the existence of the residual aliasing error terms which results in mild smoothing effect without dissipating the small‐scale flow structures. Smoothness and numerical stability in the solutions obtained from the RPSM scheme also remain well preserved even at under‐resolved conditions. Numerical results agree well with the analytical and the computed solutions from previous studies. RPSM scheme shows a slight delay in the formation of numerical singularity for the inviscid flows but the filtering‐based schemes suffer from early blow‐up problem. We observe that this scheme displays better resolving ability than higher‐order exponential smoothing spectral filter scheme in capturing the strong fronts accurately even at just resolved spatial grid resolutions. Three‐dimensional truncation‐based dealiasing scheme, spherical truncation (SPT) shows vortices generated due to the parasitic currents in the solution of the inviscid three‐dimensional Taylor Green (TG) vortex flows. RPSM displays only the accurate isocontours of vortical field at nearly same computational expenses as the SPT scheme.
Parallel structure of six wheel-legged robot trajectory tracking control with heavy payload under uncertain physical interaction

This paper aims on the trajectory tracking of the developed six wheel-legged robot with heavy load conditions under uncertain physical interaction. The accuracy of trajectory tracking and stable operation with heavy load are the main challenges of parallel mechanism for wheel-legged robots, especially in complex road conditions. To guarantee the tracking performance in an uncertain environment, the disturbances, including the internal friction, external environment interaction, should be considered in the practical robot system. ,In this paper, a fuzzy approximation-based model predictive tracking scheme (FMPC) for reliable tracking control is developed to the six wheel-legged robot, in which the fuzzy logic approximation is applied to estimate the uncertain physical interaction and external dynamics of the robot system. Meanwhile, the advanced parallel mechanism of the electric six wheel-legged robot (BIT-NAZA) is presented. ,Co-simulation and comparative experimental results using the BIT-NAZA robot derived from the developed hybrid control scheme indicate that the methodology can achieve satisfactory tracking performance in terms of accuracy and stability. ,This research can provide theoretical and engineering guidance for lateral stability of intelligent robots under unknown disturbances and uncertain nonlinearities and facilitate the control performance of the mobile robots in a practical system.
Probabilistic fatigue model for cast alloys of aero engine applications

PurposeThe purpose of this study is to address the complexity involved in computing the fatigue life of casted structure with porosity effects in aero engine applications. The uncertainty of porosity defects is addressed by introducing probabilistic models.Design/methodology/approachOne major issue of casted aluminium alloys in the application of aerospace industries is their internal defects such as porosities, which are directly affecting the fatigue life. Since there is huge cost and time effort involved in understanding the effect of fatigue life in terms of the presence of the internal defects, a probabilistic fatigue model approach is applied in order to define the realistic fatigue limit of the casted structures for the known porosity fractions. This paper describes the probabilistic technique to casted structures with measured porosity fractions and its relation to their fatigue life. The predicted fatigue life for various porosity fractions and dendrite arm spacing values is very well matching with the experimentally predicted fatigue data of the casted AS7G06 aluminium alloys with measured internal defects. The probabilistic analysis approach not only predicts the fatigue life limit of the structure but also provides the limit of fatigue life for the known porosity values of any casted aluminium bearing support structure used in aero engines.FindingsThe probabilistic fatigue model for addressing porosity in casting structure is verified with experimental results.Research limitations/implicationsThis is grey area in aerospace and automotive industry.Originality/valueThis work is original and not published anywhere else.
n+-p-p+ Silicon Solar Cell Base Optimum Thickness Determination under Magnetic Field

Base optimum thickness is determined for a front illuminated bifacial silicon solar cell n+-p-p+ under magnetic field. From the magneto transport equation relative to excess minority carriers in the base, with specific boundary conditions, the photocurrent is obtained. From this result the expressions of the carrier’s recombination velocity at the back surface are deducted. These new expressions of recombination velocity are plotted according to the depth of the base, to deduce the optimum thickness, which will allow the production, of a high short-circuit photocurrent. Calibration relationships of optimum thickness versus magnetic field were presented according to study ranges. It is found that, applied magnetic field imposes a weak thickness material for solar cell manufacturing leading to high short-circuit current.
Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous protrusions that enable the direct transfer of various cargo between cells. Here we show that TNTs are formed between leukemic and bone marrow stromal cells. Fluorescence confocal microscopy with 3D reconstructions, correlative light-electron microscopy and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated that the stromal cells stimulate TNT-mediated vesicle transfer towards leukemic cells. Transfer of vesicular cargo from stromal cells correlated with increased resistance to anti-leukemic treatment. Moreover, specific sets of proteins with a potential role in survival and the drug response were transferred within these vesicles. Altogether, we found that TNTs are involved in the leukemia-stroma cross-talk and the stroma-mediated cytoprotection of leukemic cells. Our findings implicate TNT connections as a possible target for therapeutic interventions within the leukemia microenvironment to attenuate stroma-conferred protection.
Are Non-Perennial Rivers Considered as Valuable and Worthy of Conservation as Perennial Rivers?

Non-perennial rivers, watercourses that cease to flow at some point in time and space, are widespread globally but often lack effective protections. Although it is thought that these ecosystems are undervalued by society, empirical studies exploring people’s perceptions of non-perennial rivers are uncommon. We carried out an image-based survey at three U.S. universities to measure students’ perception of riverscapes according to seven characteristics: aesthetics, naturalness, habitat for biodiversity, habitat for fish, need of human intervention, importance for human well-being, and conservation value. Our results showed that non-perennial rivers are generally considered less valuable and worthy of conservation than their perennial counterparts. Furthermore, several factors influenced peoples’ perception of non-perennial rivers, including where they live, their educational history, how often they visit rivers, their leisure activities, and whether they live close to a river. Our findings suggested the need to improve people’s perceptions of non-perennial rivers as a step toward increased protection for these ecosystems. This current challenge demands combined actions by researchers from diverse disciplines and professionals working from different perspectives, including policymakers and educators.
Complete mitochondrial genome of Cyllorhynchites ursulus (Coleoptera: Rhynchitidae)

Abstract The complete mitochondrial genome of Cylloryhunchites ursulus was sequenced for the first time from its whole body using the next-generation sequencing method. This mitogenome was 14,508 base pairs in length, containing 13 protein-coding genes, 20 transfer RNA genes, and two ribosomal RNA genes. Its overall A, C, G, and T contents were 37.8, 17.8, 11.1, and 33.4%, respectively. Its A + T content (71.2%) was higher than G + C content. The phylogenetic result showed that although C. ursulus is a species of family Rhynchitidae, its phylogenetic position is closely related to family Attlabidae.