Graph visualization has evolved significantly over time, offering various methods to effectively represent complex data structures. This study introduces a novel force-directed algorithm for 3D data visualization, specifically tailored for commonly used datasets in linked data visualization. Leveraging the power of graph theory and methods, the algorithm aims to address the challenge of creating visually appealing and easily interpretable visualizations, which often necessitate advanced user interaction. By utilizing 3D space and the Unity Engine, the research successfully visualizes data and develops interactive visualizations, overcoming limitations of basic force-directed implementations. The main contribution of presented research is in the force-directed algorithm with springs and controlled placement as a visualization technique that combines the use of springs and attractive forces to stabilize a graph in a 3D environment. The combination of these two techniques also helps prevent the formation of a single large cluster within the graph, enhancing the overall visualization quality.

Using Directed Transfer Function (DTF) and Partial Directed Coherence (PDC) in their information version, this paper extends their theoretical framework to incorporate instantaneous Granger Causality (iGC)’s frequency domain description into a single unified perspective. We show that standard vector autoregressive models allow portraying iGC’s repercussions associated with Granger Connectivity where interactions mediated without delay between time series can be easily detected.

Labelling techniques such as electron paramagnetic resonance spectroscopy and single-molecule fluorescence resonance energy transfer, allow access to distances in the range of tens of angstroms, corresponding to the size of proteins and small to medium-sized protein complexes. Such measurements do not require long-range ordering and are therefore applicable to systems with partial disorder. Data from spin-label-based measurements can be processed into distance distributions that provide information about the extent of such disorder. Using such information in modelling presents several challenges, including a small number of restraints, the influence of the label itself on the measured distance and distribution width, and balancing the fitting quality of the long-range restraints with the fitting quality of other restraint subsets. Starting with general considerations about integrative and hybrid structural modelling, this review provides an overview of recent approaches to these problems and identifies where further progress is needed.

We present a new computing package Flagser, designed to construct the directed flag complex of a finite directed graph, and compute persistent homology for flexibly defined filtrations on the graph and the resulting complex. The persistent homology computation part of Flagser is based on the program Ripser [2], but is optimised specifically for large computations. The construction of the directed flag complex is done in a way that allows easy parallelisation by arbitrarily many cores. Flagser also has the option of working with undirected graphs. For homology computations Flagser has an Approximate option, which shortens compute time with remarkable accuracy. We demonstrate the power of Flagser by applying it to the construction of the directed flag complex of digital reconstructions of brain microcircuitry by the Blue Brain Project and several other examples. In some instances we perform computation of homology. For a more complete performance analysis, we also apply Flagser to some other data collections. In all cases the hardware used in the computation, the use of memory and the compute time are recorded.

Background: The fascial system provides an environment that enables all body systems to operate in an integrated manner and is capable of modifying its tensional state in response to the stress applied to it. Recent in vitro, animal and cadaveric studies have shown that “myofascial force transfer” (MFT) has the potential to play a major role in musculoskeletal function and dysfunction.Objective: Human evidence for the existence of invivo MFT is scarce. This scoping review attempts to gather and analyse the available evidence of the in-vivo human MFT studies in order to sustain and facilitate further research and evidence based practice in this field.Methods: A search of most major databases was conducted with relevant keywords that yielded 238 articles as of August 2020. A qualitative analysis of the studies was conducted after rating it with Oxford’s Center for Evidence –based Medicine (CEBM) scale.Result: Nineteen studies ranging from randomized controlled trials to case studies covering 540 patients were included in this review. The analysed studies were highly heterogeneous and of lower methodological quality meddling with the quantitative analysis. Ten studies are confirming a ‘most likely’ existence of MFT, eight studies confirming it as ‘likely’ and one study couldn’t confirm any MFT existence in this review.Conclusion: Findings from in vivo human studies supports the animal and cadaveric studies claiming the existence of MFT which need to be corroborated by the future high quality studies. Forthcoming studies on MFT may give answers and solutions to many of the human musculoskeletal mysteries or dysfunctions.

In a previous paper we defined the Black-and-White SAT problem which has exactly two solutions, where each variable is either true or false. We showed that Black-and-White $2$-SAT problems represent strongly connected directed graphs. We presented also the strong model of communication graphs. In this work we introduce two new models, the weak model, and the Balatonbogl\'{a}r model of communication graphs. A communication graph is a directed graph, where no self loops are allowed. In this work we show that the weak model of a strongly connected communication graph is a Black-and-White SAT problem. We prove a powerful theorem, the so called Transitions Theorem. This theorem states that for any model which is between the strong and the weak model, we have that this model represents strongly connected communication graphs as Blask-and-White SAT problems. We show that the Balatonbogl\'{a}r model is between the strong and the weak model, and it generates $3$-SAT problems, so the Balatonbogl\'{a}r model represents strongly connected communication graphs as Black-and-White $3$-SAT problems. Our motivation to study these models is the following: The strong model generates a $2$-SAT problem from the input directed graph, so it does not give us a deep insight how to convert a general SAT problem into a directed graph. The weak model generates huge models, because it represents all cycles, even non-simple cycles, of the input directed graph. We need something between them to gain more experience. From the Balatonbogl\'{a}r model we learned that it is enough to have a subset of a clause, which represents a cycle in the weak model, to make the Balatonbogl\'{a}r model more compact. We still do not know how to represent a SAT problem as a directed graph, but this work gives a strong link between two prominent fields of formal methods: SAT problem and directed graphs.

Performance of the overhead squat may affect golf swing mechanics associated with golf-related low back pain. This study investigates the difference in lumbar kinematics and joint loads during the golf downswing between golfers with different overhead squat abilities. Based on the per-formance of the overhead squat test, 21 golfers aged 18 to 30 years were divided into the highest-scoring group (HS, N=10, 1.61 ± 0.05 cm, and 68.06 ± 13.67 kg) and lowest-scoring group (LS, N=11, 1.68 ± 0.10 cm, and 75.00 ± 14.37 kg). Data collection used a motion analysis system, two force plates, and TrackMan. OpenSim software was used to simulate the joint loads for each lum-bar joint. An independent t-test was used for statistical analysis. Compared to golfers demonstrat-ing limitations in the overhead squat test, golfers with better performance in the overhead squat test demonstrated significantly greater angular extension displacement on the sagittal plane, smaller lumbar extension angular velocity, and smaller L4-S1 joint shear force. Consequently, the overhead squat test is found to be a useful index to reflect lumbar kinematics and joint loading patterns during the downswing, and provides a good training guide reference for reducing the risk of a golf-related low back injury

The Casimir–Lifshitz friction force and the heating rates of two metal plates with a narrow vacuum gap between them during nonrelativistic motion of one of them are calculated analytically and numerically within the framework of fluctuation electrodynamics. Changes in material properties are taken into account using the Bloch-Grüneisen and modified Bloch-Grüneisen (with finite residual resistance) resistivity models within the Drude approximation. It is shown that identical plates with the same initial temperature have the same heating rate, determined by the power of the friction force, and the possibility of measuring the friction force from the heating kinetics of nonmagnetic metal plates with temperatures of 1–10 K is substantiated.

This letter attempts to find splashing height of liquid-filled container drop impact to a solid surface by dimensional analysis (DA). Two solutions were obtained by both traditional DA and directed DA without solving any governing equations. It is found that the directed DA can provide much more useful information than the traditional one. This study shows that the central controlling parameter is called splash number $\mathrm{Sp}=\mathrm{Ga} \mathrm{La}^\beta=(\frac{gR^3}{\nu^2})(\frac{\sigma R}{\rho \nu^2})^\beta$, which is the collective performance of each quantity. The splash height is given by $ \frac{h}{H}=(\frac{\rho\nu^2}{\sigma R})^\alpha f[\frac{gR^3}{\nu^2}(\frac{R\sigma}{\rho\nu^2})^\beta]=\frac{1}{\mathrm{La}^\alpha}f(\mathrm{Ga}\cdot \mathrm{La}^\beta)$. From the physics of the splashing number, we can have a fair good picture on the physics of the liquid splashing as follows: the jets propagation will generate vortex streets from the container bottom due to sudden pressure increasing from drop impact (water-hammer effect), which will travel along the container sidewall to the centre of the container and subsequently excite a gravity wave on the liquid surface. The interaction between the gravitational force, surface force and viscous force is responsible for creating droplet splash at the liquid surface.

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed to symptoms relief, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from repurposing of specific compounds with known antiviral activity to the screening of libraries and of natural compounds. The identified antiviral candidates include drugs targeting viral components (structural proteins and enzymes), as well as cellular ones. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein gene vp3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential for infectivity. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

Extraversion, a Big Five personality trait, has been identified as a significant factor in COVID-19 positive coping—yet, relevant research is conflicting. Studies have not situated the influence of extraversion within a geographical and historical context. Thus, a sound base is lacking for assessing when opposing results regarding extraversion and COVID-19 positive coping are likely to result. Furthermore, extraversion with respect to COVID-19 coping has not been considered concerning other-directed learning in contrast to self-directed learning. To establish a sufficiently sound base, an examination of the range of high-ranking Google Scholar results on extraversion and COVID-19 coping from different countries during the pandemic’s various waves—pre and post vaccine introduction—is undertaken. The same are then considered for insights into public opinion. Following, extraversion is compared with other-directed learning and differentiated from self-directed learning. An understanding is thus presented for assessing when extraversion will necessarily be an effective personality trait for COVID-19 positive coping and when it will not. Extraversion’s effect will be found inherently inconsistent for identifying COVID-19 positive coping as a result, because of its dependence on other-directed learning. The conclusion: COVID-19 positive coping stability is contingent on personal values that guide self-directed learning, rather than other-directed extraversion.

This study introduces a novel computational approach for testing conditional independence (BB CI test) within causal Directed Acyclic Graphs (DAGs), leveraging Bayesian non-parametric bootstrap and machine learning techniques. Our method offers an alternative for validating the assumptions underpinning causal DAGs. Through simulation studies and an industrial case analysis, we demonstrate the test procedure in accurately assessing conditional independence, comparing it with the Generalized Covariance Measure (GCM) test. Our findings suggest that the BB CI test is advantageous in scenarios where existing methods may falter due to violations of model assumptions. This research contributes to the causal inference literature by providing a computational tool for researchers and practitioners to validate causal models.

The Collatz conjecture is a well-known number theory puzzle that states that every positive integer would eventually converge to the trivial cycle of 1, 2, 1, 2,... when repeatedly exposed to a particular transformation. In this transformation, even numbers are divided in half, odd numbers are tripled, and one is added. In this study, we present a new method for creating a directed graph and using it to display and analyze Collatz sequences. Our technique creates what we call a Collatz directed graph by joining an endless number of simple directed graphs, each of which corresponds to a natural number. We show by careful mathematical analysis that all positive integers are included in this Collatz directed graph. Moreover, we give an evidence that verifies the Collatz conjecture by showing that the sole cycle in this graph is the trivial cycle of 1, 2, 1, 2,... We also prove that there is no sequence that diverges to infinity in this graph. Our results provide insights into the fundamental structure of Collatz sequences and further our knowledge of the Collatz conjecture .

This paper proposes a contact force controller for a constrained flexible manipulator in three-dimensional motion. This controller used the conversion formula obtained empirically and experimental results showed the effectiveness of the proposed contact force controller. First, the manipulator was operated with the tip of the second link restrained, then, time response of the root strain, joint angles and contact force were used to derive the relational between the three quantities. The effectiveness of the relational expression was verified by conducting a target contact force tracking experiment by inputting the angle from the relational expression. The contact force control using the strain feedback method was proposed with the strain amount estimated from the target contact force as the target value, and its effectiveness was verified by experiments. From the results obtained, controller using the strain feedback method was designed for the purpose of controlling the contact force at the tip of a flexible manipulator with two links and three degrees of freedom that performs three-dimensional spatial motion, and its effectiveness was shown by comparison with the contact force feedback method.

The thesis proposes a argument that a mass point moving in a horizontal circle on the Earth's surface can generate a radial centrifugal force of the Earth's center of mass, thus realizing an unconventional anti-gravity path. And through the theoretical analysis of the difference in the distribution of gravitational acceleration at different latitudes caused by the rotation of the earth, and the centrifugal force of a mass point moving in a horizontal circle on the earth's surface is analyzed, the validity of the argument is demonstrated. At the same time, the paper puts forward two possible basic principles, and makes theoretical analysis and demonstration. Conceive of the concrete experimental verification of principle two is proposed. Four technical schemes for antigravity ascent are proposed and basic analysis is made. On the premise of not fully considering the practical technical ability, it is theoretically proved that three of them have realistic operability and development potential. In theory, this paper opens up a different way of anti-gravity for human beings, which will bring new ideas and prospects for human beings to get rid of the bondage of gravity.

Prostate cancer lung metastasis represents a clinical conundrum due to their implication of advanced disease progression and the complexities they introduce in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, the review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, the review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Catheter-based revascularization procedures developed as an alternative of systemic thrombolysis for patients at intermediate-high and high-risk pulmonary embolism. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow up. Secondary endpoints were short- and mid-term changes in echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high risk PE (86%), mostly female (57%), median age 66.5 years (IQR 56-74), and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 hours and at follow up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74) while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, oh whom 4.9% were BARC 3. Preliminary results from USAT IH-PE registry showed low incidence of PH, improvement in RV function and a safe profile.

Routing a person through a traffic network presents a tension between selecting a fixed route that is easy to navigate and selecting an aggressively adaptive route that minimizes the expected travel time. We propose to create non-aggressive adaptive routes in the middle-ground seeking the best of both these extremes. Specifically, these routes still adapt to changing traffic conditions, however we limit the number of adjustments made in the route. This improves the user experience, by providing a continuum of options between saving travel time and minimizing navigation. We design strategies to model single and multiple route adjustments, and investigate enumerative techniques to solve these models. To alleviate the intractability with handling real-life traffic data, we develop efficient algorithms with easily computable lower and upper bounds. We finally present computational experiments highlighting the benefits of limited adaptability in terms of reducing the expected travel time.

Re-shaping of thermodynamics with the graph theory and Ramsey theory is suggested. Maps built of thermodynamic states are addressed. Thermodynamic states may be attainable and non-attainable by the thermodynamic process in the system of constant mass. We address the following question how large should be a graph describing connections between discrete thermodynamic states to guarantee the appearance of thermodynamic cycles? The Ramsey theory supplies the answer to this question. Direct graphs emerging from the chains of irreversible thermodynamic processes are considered. In any complete directed graph, representing the thermodynamic states of the system the Hamiltonian path is found. Transitive thermodynamic tournaments are addressed. The entire transitive thermodynamic tournament built of irreversible processes does not contain a cycle of length 3, or in other words, the transitive thermodynamic tournament is acyclic and contains no directed thermodynamic cycles.

For any positive integer n ≥ 2, the Erdős-Straus Conjecture claims that the Diophantine equation 4/n = 1/x + 1/y + 1/z has a solution where x, y, z are also positive integers. In this paper, a directed network based on this equation is generated, with properties such as its average clustering coefficient, average path length, degree distributions, and largest strongly connected component analysed to reveal some underlying trends about the nature of the conjecture. Potential connections between different numbers, that result from satisfying a source-solution relationship for this equation, are described using the appropriate number-theoretic interpretations wherever possible, while conjectures backed by these trends are made in other instances. Additionally, a directed configuration model is used to show that the origin of several results is the degree sequence of the network. Metrics relating to the prime number nodes, specifically their in and out degrees, are also explored to yield some intriguing observations. On the whole, the aim is to highlight the viability of complex networks as a computational tool to study this general class of problems pertaining to fixed-length unit fraction splits.

High-frequency neuroelectric signals like electroencephalography (EEG) or magnetoencephalography (MEG) provide a unique opportunity to infer causal relationships between local activity of brain areas. While causal inference is commonly performed through Classical Granger causality (GC) based on multivariate autoregressive models, this method may encounter important limitations (e.g. data paucity) in the case of high dimensional data from densely connected systems like the brain. Additionally, physiological signals often present long-range dependencies which commonly require high autoregressive model orders / number of parameters. We present a generalization of autoregressive models for GC estimation based on Wiener-Volterra decompositions with Laguerre polynomials as basis functions. In this basis, the introduction of only one additional global parameter allows to capture arbitrary long dependencies without increasing model order, hence retaining model simplicity, linearity and ease of parameters estimation. We validate our method in synthetic data generated from families of complex, densely connected networks and demonstrate superior performance as compared to classical GC. Additionally, we apply our framework to studying the directed human brain connectome through MEG data from 89 subjects drawn from the Human Connectome Project (HCP) database, showing that it is able to reproduce current knowledge as well as to uncover previously unknown directed influences between cortical and limbic brain regions.

The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a “break test” depends on the tester’s force rise and the patient’s ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers’ force profiles is required for valid application. The study examined the force profiles of n=29 testers (n=9 experiences (Exp), n=8 little experienced (LitExp), n =12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient’s reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj=0.029), the ratio of starting to maximum force (padj=0.005) and the normalized mean Euclidean distances between the 10 trials (padj=0.015). The slope is significantly higher in Exp vs. LitExp (p=0.006) and Beg (p=0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. That highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required – a suggestion is given.

Atomic force microscopes are used, beside their principal function as surface imaging tools, in surface manipulation and measurement of interfacial properties. In particular, they can be modified to measure lateral friction forces that occur during the sliding of the tip against the underlying substrate. However, the shape, size, and deformation of the tips profoundly affect the measurements in a manner that is difficult to predict. In this work, we investigate the contribution of these effect to the magnitude of the lateral forces during sliding. The surface substrate is chosen to be few-layer AB-stacked graphene surface whereas the tip is initially constructed from face-centered cubic gold. In order to separate the effect of deformation from shape, rigid tips of three different shapes were considered first, namely a cone, a pyramid and a hemisphere. The shape was seen to dictate all aspects of the interface during sliding, from temperature dependence to stick-slip behavior. Deformation was investigated next by comparing a rigid hemispherical tip to one of identical shape and size but with all but the top three layers of atoms free to move. The deformation, as also verified by an indentation analysis, occurs by means of the lower layers collapsing on the upper ones, thereby increasing the contact area. This collapse mitigates the friction force and decreases it with respect to the rigid tip for the same vertical distance. Finally, the size effect is studied by means of calculating the friction forces for a much larger hemispherical tip whose atoms are free to move. In this case, the deformation is found to be much smaller but the stick-slip behavior is much more clearly seen.

Temperature dependent entropic force acting between the straight direct current I and the linear system (string with length of L) of N elementary non-interacting magnets/spins μ is reported. The system of elementary magnets is supposed to be in the thermal equilibrium with the infinite thermal bath T. The entropic force at large distance from the current is given by Fmagnen=Nμ02μ2I24π2kBTr3 , where r is the distance between the edge of the string and the current I, and kB is the Boltzmann constant; (r≫L is adopted). The entropic magnetic force is the repulsion force. The entropic magnetic force scales as Fmagnen~1T , which is unusual for entropic forces. The effect of “entropic pressure” is predicted for the situation when the source of the magnetic field is embedded into the continuous media, comprising elementary magnets/spins.

Genetic diversity is the foundation of evolutionary resilience, adaptive potential, and the flourishing vitality of living organisms, serving as the cornerstone for robust ecosystems and the continuous evolution of life on Earth. The landscape of directed evolution, a powerful biotechnological tool inspired by natural evolutionary processes, has undergone a transformative shift propelled by innovative strategies for generating genetic diversity. This shift is fuelled by several factors, encompassing the utilization of advanced toolkits like CRISPR-Cas and base editors, enhanced comprehension of biological mechanisms, cost-effective custom oligo pool synthesis, and the seamless integration of artificial intelligence and automation. This comprehensive review looks into the myriad methodologies employed for constructing gene libraries, both in vitro and in vivo, categorized into three major classes: random mutagenesis, focused mutagenesis, and DNA recombination. The objectives of this review are threefold: firstly, to present a panoramic overview of recent advances in genetic diversity creation, secondly, to inspire novel ideas for further innovation in the genetic diversity generation, and thirdly, to provide a valuable resource for individuals entering the field of directed evolution.

The contemporary landscape of education is witnessing a paradigm shift towards innovative instructional methods, with the flipped learning approach gaining considerable attention. The purpose of this research was to investigate the impact of the flipped learning approach on students' perception and acceptance throughout an entire semester in the 'Introduction to Programming with Java' course, using a research design with a quantitative approach, ultimately aiming to inform educational practice and advance our knowledge of innovative teaching methods in higher education. This study was conducted at a university with 174 students involved, divided into two groups, 87 students in the experimental group and 87 students in the control group. The data collected through the scales were analyzed by using descriptive and inferential statistical analysis techniques in statistical software. At the end of the measurements, the technology acceptance level and self-directed learning perceptions of engineering students who received education with flipped learning were high. The results suggest that educators should consider students' readiness for self-directed learning when implementing the flipped learning approach and focus on creating an environment that supports their autonomy and engagement. This research offers valuable guidance for instructors, curriculum designers, and educational policymakers seeking to enhance the effectiveness of flipped learning in higher education courses.

Defects in low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. Defective LDLR in hepatocytes leads to increased blood cholesterol level that damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully comprehended. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSC) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-EC), we detected the LDLR protein predominantly in its mature form, while iPSC-EC from patients with FH display reduced level of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of iPSC-EC with mutant LDLR revealed a unique transcriptome profile comprising downregulated genes related to monocarboxylic acid transport, exocytosis and cell adhesion, as well as upregulated signaling pathways of cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increases susceptibility of endothelial cells to inflammation and oxidative stress. This, combined with elevated extrinsic cholesterol levels, may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies related to FH.

The term new genomic techniques (NGTs), is an umbrella term to describe a variety of techniques that can alter the genetic material of an organism and that have emerged or have been developed since 2001, when the existing genetically modified organism (GMO) legislation was adopted. The analytical framework to detect GMOs in Europe is a established single harmonized procedure which is mandatory for authorization of GM food and feed, thus generating reliable, transparent and effective labelling scheme for GMO products. However, NGT products challenge the implementation and enforcement of the current regulatory system in the EU, relating in particular to the detection of NGT products that contain no foreign genetic material. Consequently, current detection methods will fail to meet minimum performance requirements. Although existing detection methods may be able to detect and quantify even small alterations in the genome, this does not necessarily confirm the distinction between products resulting from NGTs subject to the GMO legislation and other products. Therefore, this study provides a stepwise approach for the in silico prediction of PCR systems specificity by testing a bioinformatics pipeline for amplicon and primer set searches in current genomic databases. We have tested our methodology in two mutant genotypes produced by CRISPR/Cas9 in Arabidopsis thaliana. Overall, our results demonstrated that the single PCR system developed for the identification of a nucleotide insertion in the grf1-3 genotype has sufficient hits in the databases that would not allow discrimination of this mutanted event. Differently, the second mutated genotype grf8-61 which contains a -3bp deletion, found no matches in the sequence variant database. Our approach is the first step in decision making on PCR system and modification of them for empirical testings.

Directed acyclic graphs (DAGs) are nonparametric causal path diagrams that have substantial utility as principled representations of disease and healthcare pathways, and of the underlying ‘data generating mechanisms’ these pathways involve. As such, DAGs provide a valuable bridge between: the aetiological knowledge, operational insight and professional experience on which clinical training and practice depend; and the more abstract epistemological and analytical considerations required to extract robust statistical insight from health and healthcare data. DAGs are nonetheless vulnerable to imperfect biomedical paradigms, partial clinical knowledge and limited empirical data. DAGs drawn under such circumstances offer limited scope for statistical insight free from cognitive, analytical or inferential bias if: they misrepresent the data generating mechanisms involved; or ignore the important role that omitted variables (whether measured, unmeasured or unacknowledged) might play therein. To address these weaknesses and broaden the appeal and application of DAGs, this chapter provides ten simple steps that educators can use to improve the analytical competence and statistical confidence of the healthcare students, qualified practitioners and experienced researchers they support. These steps use temporal logic to draw DAGs so as to: reduce reliance on uncertain knowledge, incomplete information, flawed assumptions or guesswork; and avoid, mitigate or acknowledge the errors and biases that each of these incur. The chapter comprises an accessible, non-technical overview of the perspective and thoughtfulness required to generate temporally coherent DAGs as objective representations of the probabilistic causal paths involved in context-specific data generating mechanisms. It encourages a focus on those variables operating as potential sources of analytical or inferential bias when estimating the plausible, probabilistic causal relationship between two pre-specified variables; and specifically addresses the challenges posed by: omitted; time-variant; non-asynchronous; and temporally obscure variables. The chapter includes a worked example based on a published clinical study to demonstrate how each of the steps required to generate temporally-informed DAGs can be applied to: critically appraise the analytical decisions made during applied healthcare research; and inform the decisions required when designing, undertaking and analysing primary and secondary, prospective and retrospective research. The appendices include a summary of ten recommendations for improving the reporting and interrogability of DAGs and DAG-informed analyses.

The origins of directed acyclic graphs (DAGs) date back to the emergence of ‘graph theory’ in the early 1700s (Biggs et al. 1986). DAGs are conceptual or literal, diagrammatic representations of causal paths between variables which are constructed – as their name suggests – on the basis of two over-riding principles: first, that all causal paths are ‘directed’ (i.e. for each pair of variables, only one can represent the cause, while the other must be its consequence); and second, that no direct cyclical paths, or indirect cyclical pathways (comprising sequences of consecutive paths) are allowed, such that no consequence can be considered its own direct or indirect cause (hence ‘acyclic’; Law et al., 2012). As such DAGs reflect the knowledge, presumptions, assumptions and/or speculation of the analyst(s) concerned regarding the causal relationships between each of the variables included therein. Current convention dictates that variables are represented as nodes/vertices, and that any causal paths between variables are represented as directed arcs/edges/lines, often in the form of arrows (see Figure 1). Although each arc indicates the presence and direction of a known/presumed/assumed/speculative causal relationship between the two variables concerned, drawing an arc does not require the sign, magnitude, precision or shape of the relationship to be known or declared (Tennant et al., 2021). In this respect, DAGs provide a simple, uncomplicated, accessible and entirely nonparametric approach for postulating causal relationships amongst any variables of interest even when these are uncertain, unknown or entirely speculative (Ellison, 2020). Nonetheless, as a result of the parametric constraints imposed by the presence/absence of possible arcs within any given DAG, these also reflect and support a number of more sophisticated statistical applications which make it possible to use DAGs to inform the design of multivariable statistical models that reflect the causal structure(s) involved – albeit without the need to know or understand the mathematical technicalities on which these are based (Lewis and Kuerbis, 2016). These features make DAGs attractive cognitive, educational and analytical tools for strengthening the epistemological, theoretical and empirical basis of causal inference, and there has been a recent proliferation in the use of DAGs across a range of applied scientific disciplines (e.g. Knight and Winship, 2013), and an associated upsurge in analytical methods training (e.g. Elwert, 2011; Gilthorpe, 2017; Hernán 2018; Roy, 2021; Hünermund, 2021). This Chapter reflects on a decade of delivering medical statistics training to undergraduate medical students at the University of Leeds between 2012-2021 in which the third year research, evaluation and special studies module (‘RESS3’) has used DAGs to support the development of applied statistical skills relevant to the extended student-selected research and evaluation projects (ESREP) students undertake in their fourth and final years (Ellison, 2021; Ellison et al., 2014a,b). Based on successive iterations of the structure and content of the RESS3 module, together with notes made during formal and informal planning and review meetings with module leads, lecturers, tutors and students, we draw on the claims and criticisms made of DAGs in the epidemiological literature to identify a number of explicit strengths (and associated, often implicit. weaknesses) that are central to their use in prediction and causal inference modelling. While using DAGs requires (and benefits from) a clear understanding of their non-parametric nature and parametric implications, the weaknesses of DAGs seem likely to reflect both: the challenges inherent in the modelling of data generating processes when these are imperfectly understood; and troublesome cognitive and heuristic tendencies common to all analytical tools – in which the tool facilitates the task in hand by reducing the necessity (and benefits of) exploring uncertainties and identifying assumptions. These, more epistemological considerations appear particularly challenging for medical undergraduates to grasp (Ellison, 2021), but also appear poorly understood by many established analysts and clinical epidemiologists (Ellison, 2020).

Directed energy deposition (DED) is an efficient method to fabricate functionally graded materials (FGMs) with gradient composition and complex structures, allowing for local tailoring of properties instead of the costly need for extraneous welds and joints. In this study, a FGM from stainless steel to Inconel alloy was successfully fabricated using the powder-based laser DED. A very refined grain structure has been observed in at the composition with 75 wt.% Inconel alloy content, which also exhibits the highest (entropy). For the first time, the post heat treatments, microstructure and aging precipitation behaviors of FGMs were systematically studied via experimental characterization and computation, to elucidate their effects on the gradient smoothing and mechanical properties. The diffusion and segregation of Ni, Nb and Ti elements underly the transformation mechanism between Laves, δ, γ’ and γ’’ phases during precipitation. Homogenization on FGMs not only eliminates the heterogeneity inherited from the AM process, but also provides a practical way to smoothen the gradient on composition and microstructure for the eventual good gradient properties. It has a direct influence on the following precipitation behaviors in the FGM, which highly relies on the diffusion degree of the elements in the matrix and grain boundaries. The high-throughput thermodynamic modeling and kinetic modeling were exploited to evaluate the experimental microstructure and address computational uncertainty using different thermodynamic conditions and databases, which enables an accelerated design through local tailoring of process-structure-property relationships to develop new functional materials.

Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet to be established. Methods: We evaluated the safety and efficacy of adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. Results: Among the 1,849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received intracoronary infusion of tissue plasminogen activator during primary PCI (CDT group), whereas 222 did not receive (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p=0.53; 7.3% vs. 2.3%, p=0.11; and 12.6% vs. 17.5%, p=0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6%; CDT group and 87.4%; non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p<0.01). However, the final rates improved considerably without significant difference (90.3% vs. 97.4%, p=0.14). Conclusions: For STEMI patients with high thrombus burden, adjunctive CDT is safe and effective for improving coronary flow. CDT resulted in favorable coronary flow even after unsatisfactory aspiration thrombectomy.

Genetic switches can be utilized for many purposes in synthetic biology including the assembly of complex genetic circuits to achieve sophisticated cellular systems and the construction of biosensors for real-time monitoring of intracellular metabolite concentrations. Although genetic switches have mainly been developed in prokaryotes to date, eukaryotic genetic switches are increasingly being reported as both rational and irrational engineering technologies mature. In this review, we describe genetic switches in yeast based on synthetic transcription factors and/or synthetic promoters. We also discuss directed evolution technologies for the rapid and robust construction of yeast genetic switches.

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

This paper proposes a multi-terminal adaptive collaborative operation method to solve the problem of unstable internal force tracking in clamping and handling unknown objects by multi-terminal robots. In the proposed method, the internal command force changes the complex internal force control problem into an internal force tracking problem from multi-slave to master. Moreover, we develop an algorithm for multi-slave setups to estimate object stiffness and motion uncertainty in the direction of the internal command force according to Lyapunov theory. Finally, the impedance control generates a reference trajectory for the multi-slave to maintain the desired internal force and track the master’s motion. Several experiments are conducted on a self-made robot equipped. The experimental results show that the oscillation amplitude of each slave end is less than 1 mm, the directional oscillation amplitude is less than 1 degree during the tracking of the desired commanded internal force. For objects with low stiffness, the error of the commanded internal force is less than 1 N (6%) per slave. The error in tracking the commanded internal force for objects with high stiffness is less than 2 N (8%). The results prove the feasibility and effectiveness of the proposed method.

The translocator protein (TSPO) is a transmembrane protein present in the three domains of life. Its functional quaternary structure consists of one or more subunits. In mouse, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the mouse protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the mouse protein.

Force reduction is one of the most important benefit of applying ultrasonic vibration on milling. However, most of studies so far are limited to experimental investigation. In the current study, an analytical predictive model on cutting forces in ultrasonic vibration-assisted milling is proposed. The three types of tool-workpiece criteria are considered based on the instantaneous position and velocity of tool center. Type I criterion indicates that there is no contact if the instantaneous velocity is opposite to tool rotation direction. Type II criterion checks whether the vibration displacement is larger than the instantaneous uncut chip thickness. Type III criterion considers the overlaps between current and previous tool paths due to vibration. If none of these criteria is satisfied, milling forces are nonzero. Then the calculation is performed by transforming milling and tool geometry configuration to orthogonal cutting at each instant. The orthogonal cutting forces are predicted through the exhaustive search of shear angle and calculation of shear flow stress on tool-chip interface. The axial force is then calculated based on tool geometry, and the milling forces in feed, cutting, and axial directions are calculated after coordinate transformation. The proposed predictive force model in ultrasonic vibration-assisted milling is validated through comparison to experimental measurements on Aluminum alloy 2A12. The predicted values are able to match the measured milling forces with high accuracy of average difference of 13.6% in feed direction and 13.8% in cutting direction.

We present a Quantum Space Model (QSM) of cosmic evolution based on the theory that space consists of energy quanta which participates in the evolution of the universe. It shows that Dark Energy is the energy of space which causes its accelerating expansion. We used the Friedmann equations to trace the history of the cosmos from a time before the Big Bang to its ultimate end. The universe started from a quantum size volume of space with high energy density.Quantum fluctuations triggered the release of energy in a Big Bang at very high temperature and pressure. It then expanded and cooled undergoing phase transitions to radiation, fundamental particles, and matter. Matter grew into galaxies, and was further consolidated by gravity into Dark Energy Stars/Black Holes, ending in a Big Crunch at about 1.380 trillion years, thus bringing the universe back to its initial state. It can stay in a Deep Feeeze inside a Black Hole and through fluctuations or other mechanism may start a new cycle in its life with a new Bang. If the Law of Conservation of Energy is universal, then the cosmos is eternal. Space and energy are equivalent just as matter and energy are. This is well founded in Planck’s energy equation. They are the two most fundamental quantities in the universe that govern cosmic evolution. The two principal long range forces are the gravitational force and the space force.The latter could be the fifth force in the universe. They may provide the clockwork mechanism that operates our eternal cyclic universe.

The material flow dynamic and velocity distribution on the melted domain surface play a crucial role on the joint quality and formation of welding defects. In this study, authors investigated the effects of the low and high currents of plasma arc welding on the material flow and thermodynamics of molten pool and its relationship to the welding defects. The high-speed video camera (HSVC) was used to observe the convection of the melted domain and welded-joint appearance. Furthermore, to consider the Marangoni force activation, the temperature on the melted domain was measured by a thermal HSVC. The results revealed that the velocity distribution on the weld surface was higher than that inside the molten weld pool due to the difference of the massive density between the air and the steel. Moreover, in the case of low welding current (80A) the convection speed of molten was faster than that of the high welding current case (160A) owing to the difference of main driving forces direction and strength, which leading to undercut and humping defects on the weld surface and excessive convex (burn-through) defect at the bottom weld side, respectively. The medium welding current (120A) had two convection patterns with the main flow in backward direction, which resulted in better welding quality without defect. The interaction between the shear force and Marangoni force played a solid state on the convection and heat transportation processes in the plasma arc welding process.

Many studies discuss carbon-based materials because of the versatility of its element. They include different opinions for scientific problems and discuss fairly at convincing and compelling levels within the scope and application. A gas-state carbon atom converts into various states depending on its conditions of processing. The electron transfer mechanism in the gas-state carbon atom is responsible to convert it into various states, namely, graphite, nanotube, fullerene, diamond, lonsdaleite and graphene. The shape of ‘energy trajectory’ enables transferring electrons from the left- and right-sides of an atom is like a parabola. That ‘energy trajectory’ is linked to states (filled state and suitable nearby unfilled state) where force-exertion along the poles of transferring electrons is remained balance. So, the mechanism of originating different states of a gas-state carbon atom is under the involvement of energy first. This is not the case for atoms executing confined inter-state electron-dynamics as the force is involved first. Graphite-, nanotube- and fullerene-state atoms ‘partially evolve partially develop’ (form) their structures. These possess one-dimensional, two-dimensional and four-dimensional ordering of atoms, respectively. Their structural formation also comprises ‘energy curve’ having a shape-like parabola. Transferring suitable filled state electron to suitable nearby unfilled state is under a balance force exerting along the poles. The graphite structure under only attained-dynamics of atoms can also be formed but in two-dimension. Here, binding energy between graphite-state carbon atoms is for a small difference of exerting forces along their opposite poles. Structural formation in diamond, lonsdaleite and graphene atoms involve energy to gain required infinitesimal displacements of electrons through which they maintain orientationally-controlled exerting forces along dedicated poles. In this study, the growth of diamond is found to be south to east-west (ground) where atoms bound ground to south. Thus, diamond atoms merge for a tetra-electron ground to south topological structure. Lonsdaleite atoms merge for a bi-electron ground to just-south topological structure. The growth of graphene is found to be north to ground where atoms bound ground to north. Thus, graphene atoms merge for a tetra-electron ground to north topological structure. Glassy carbon exhibits layered-topological structure where, tri-layers of gas-, graphite- and lonsdaleite-state atoms successively bind in repetitive order. Nanoscale hardness is also sketched based on different force-energy behaviors of different state carbon atoms. Here, structure evolution in each carbon state atom explores its own science.

STRAS (Single access Transluminal Robotic Assistant for Surgeons) is a flexible robotic system based on the Anubis® platform of Karl Storz for application to intra-luminal surgical procedures. It consists of three cable-driven systems, one endoscope serving as guide and two inserted instruments. The flexible and bendable instruments have three degrees of freedom and can be teleoperated by a single user via two specially designed master interfaces. In this research, a pair of specific sensor gloves, which ergonomically fit to the master handles of the system was designed and the forces applied by one expert and one novice user during system-specific task execution in a simulator task (4-step-pick-and-drop) were compared. The results show that user expertise is not only reflected by shorter task execution times but also, more importantly, by specific differences in handgrip force profiles for specific sensor locations on anatomically relevant parts of the fingers and hand controlling the surgical instruments of the robotic master/slave system.

Organizational skills are a set of cognitive abilities responsible for goal-directed behaviors. While they are moderately studied in clinical settings, the assessment of organizational skills in the general population remains under-studied. This paper presents the new Durand Organizational Skills Questionnaire (DOSQ), which was developed to examine the factors associated with organizational abilities in the general population. Exploratory factor analysis, validated by a confirmatory factor analysis, suggests eight factors: Work Organization, Communication Clarity, Punctuality, Goal-Oriented Behavior, Assiduity, Workspace Organization, Strategies, and Attentiveness. Three studies using samples from the general population provided evidence for the reliability and validity of the DOSQ’s scores. Overall, the results suggest that the DOSQ offers a valid approach to measuring organizational skills in the general population.

Polyvinyl Alcohol (PVA)/ Graphene Quantum Dots (GQDs) polymer nanocomposite films have been prepared, and the relationship between their structural, thermal and nanoscale morphologi-cal properties, and their photoluminescent response, has been investigated. Although according to X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Thermal Analysis (DTA) the incorporation of GQDs does not significantly affect the percentage crystallinity of the PVA matrix, for a range of added GQD concentrations, Atomic Force Micros-copy (AFM) showed the formation of islands with apparent crystalline morphology on the surface of the PVA/GQD films, with GQD presumably acting as a nucleating agent for island growth. The incorporation of GQD also led to the formation of characteristic surface pores with increased stiffness and frictional contrast, according to Ultrasonic Force Microscopy (UFM) and Frictional Force Microscopy (FFM) data. The photoluminescence (PL) spectra of the films were found to de-pend both on the amount of GQD incorporated and on the film morphology. For GQD loads > 1,2wt%, a GQD-related band was observed at ~ 1650 cm-1 in FT-IR, along with an increase in the PL band at lower energy. For a load of ~2wt% GQD, the surface morphology was characterized by extended cluster aggregates with lower stiffness and friction than the surrounding matrix, and the PL signal decreased.

The literature offers limited information on the effect of obesity on the rate of force development, a critical parameter for mobility in older adults. The objectives of this study were; to explore the influence of obesity on RFD in older adults and to examine the association between this neuromuscular parameter and walking speed. 42 older adults were classified into two groups: the control group (CG, n=22; age=81.13±4.02 years; Body mass index (BMI)=25.13±3.35 kg/m²), and the obese group (OG, n=20; age=77.71±2.95 years; BMI=34.46±3.25 kg/m²). Walking speed (m/s) was measured using the 10-meter walking test. Neuromuscular parameters of the plantar flexors were evaluated during a maximal voluntary contraction test using a dynamometer. The RFD was calculated from the linear slop of the force – time curve in two phases: from the onset of the contraction to 50 ms (RFD50-100) and from 100 to 200 ms (RFD100-200). The gait speed was lower in the OG compared to the CG (p

This paper is the third application-oriented paper based on the "unified theory of forces" and also addresses the shortcomings of previous research in fully explaining the origin and nature of the weak force. The main conclusions of this paper are as follows: (1) It is argued that neutrinos are generated by the gravitational field, and their generation mechanism is similar to the radiation of photons from electron orbital transitions. Particles undergoing orbital transitions in a gravitational field will emit neutrinos. (2) We rigorously derive the energy formula for neutrinos and demonstrate that the energy formula for neutrinos does not comply with the Planck energy formula. Neutrinos with higher energy have longer wavelengths and are more easily observed in experiments.

Objectives The aim of this study was to measure the magnitude of forces in the joints of the lower limb whilst running barefoot and compare them to the forces generated whilst wearing running shoes with a thick midsole.MethodsTwenty-three volunteers who utilised running as their main sport or a training aid ran as training aid were included in this study. Each volunteer would run down a fourteen-meter-long corridor both barefoot and with running shoes. Forces for joints of the lower limb were collected using a Vicon motion analysis system and force plates. The joint forces for the ankles, knees and hips were taken as the largest joint force experienced during the stance phase and then averaged over five running trials.ResultsThere was significant reduction in the joint forces for the ankles, knees, and hips when barefoot running compared to the shod condition.ConclusionBarefoot running could be utilised to prevent both acute and degenerative injuries of the lower limb.

The model of T4 phage, Lambda phage and Escherichia coli is often used in research on virus-host interactions. This paper reports for the first time the thermodynamic driving force of biosynthesis, catabolism and metabolism for the three organisms, on the M9 medium. Moreover, the influence of activities of nutrients and metabolic products is analyzed. All three organisms were found to have very similar Gibbs energies of metabolism. Moreover, since they share the same catabolism, their Gibbs energies of catabolism are identical. However, Gibbs energies of biosynthesis differ. The calculated thermodynamic properties have been used to explain the coexistence of both bacteria and phages in a dynamic equilibrium in natural ecosystems.

The electric field is enormously more powerful than the gravitational field. However, in our normal experience there is no electric field, the electric force is missing. How is it that when you get to larger and larger scales the gravitational field is extremely important whereas the electric field becomes less and less important [1]? This paper proposes a model to explain why gravitation dominates at a larger scale.

Purposely slow velocity resistance exercise (i.e., 10 s concentric and eccentric phases) is a popular training method, but limits the loads that can be lifted (e.g., <50% 1 RM). This study compared the biomechanical properties of purposely slow velocity (SLOW) and traditional resistance exercise (TRAD) that uses maximal lifting velocities. Healthy resistance-trained men (n=5) performed two testing sessions (barbell squat and bench press) in random-order; a SLOW session (1 set x 10 repetitions at 28% 1 RM, 10 s concentric & eccentric), and a TRAD session (3 x 10 at 70% 1 RM, controlled eccentric and maximal concentric). A force plate and linear position transducer were used to collect kinetic and kinematic data for every repetition of both protocols (α = 0.05). For both exercises, both concentric and eccentric mean force (N) and power (W) for each repetition was greater for TRAD. When the entire training session (squat + bench press) was examined, SLOW exhibited greater time under tension, while TRAD produced greater work (J) and impulse (N·s). Contrary to suggestions in both the lay and scientific literature, purposely slow resistance exercise produced less force, power, and work than traditional velocity resistance exercise.

This paper first explains the theory of the origin of force from a new perspective, explaining that the origin of all forces is caused by the "missing of energy in the time dimension" (non-conservation in a certain period of time), and constructs a unified theory of force on this basis. Then, through the unified theory of force, the following phenomena are reinterpreted: (1) The common origin of the inverse square law of gravitation and electromagnetic force; (2) The origin of the repulsive force of electrons and protons at small distances; (3) The mystery of the rotation curve of galaxies and the new explanation of "dark matter"; (4) explain the origin of the magnetic field; (5) Predict that moving magnets have the same radiation effect as charged particles (electron magnetic moments also have radiation effects); (6) Reinterpret Maxwell's displacement current; (7) Reinterpret synchrotron radiation and bremsstrahlung; (8) Explain that the strong and weak forces are short-range forces; (9) Predict the true structure of black holes and the origin of gravitational waves;(10) Possible explanation for the origin of the speed of light.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

The combination of wet-lab experimental data on multi-site combinatorial mutations and machine learning is an innovative method in protein engineering. In this study, we present an improved innovative sequence–activity relationship (innov'SAR) methodology based on novel descriptors and digital signal processing (DSP) to construct a predictive model. In this improved approach, 21 experimental (R)-selective amine transaminases from Aspergillus terreus (AT-ATA) were used as an input to predict higher thermostability than that predicted using the existing data. We successfully improved the determination coefficient (R2) of the model from 0.66 to 0.92. In addition, root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were estimated and conformation analysis based on molecular dynamics simulations was performed to verify the enhanced thermal stability of the screened mutants. The improved innov'SAR algorithm enhanced the predictive accuracy, suggesting a method for modifying the stability of AT-ATA, which may help in directed evolutionary screening and open up new avenues for protein engineering.

Despite of over 20 years of community directed treatment with ivermectin (CDTI), a high prevalence of onchocerciasis and onchocerciasis-associated epilepsy were observed in rural villages in Mahenge, Tanzania. Therefore, we assessed the knowledge, attitude and practice about onchocerciasis in four rural villages in the Mahenge area. This was a qualitative study conducted between June and July 2019. Eleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Most participants were aware about symptoms of onchocerciasis using local terminologies such as “ukurutu/rough dry skin” and “kuwashwa/itching”. A small proportion of people did not take ivermectin during CDTI for fear of adverse reactions such as itching and swelling. Some men believed that ivermectin may decrease libido. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision by the NTD coordinators. In conclusion, ivermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasis-associated morbidity and by improving supervision during CDTI.

A large variety of molecular interactions occurs between biomolecular components in cells. When one or a cascade of molecular interactions results in a regulatory effect, by one component onto a downstream component, a so-called ‘causal interaction’ takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g., gene regulation) need to be described with a careful appreciation of molecular interactions that occur between entities. A proper description of this information enables archiving, sharing, and reuse by humans and for computational science. Various representations of causal relationships between biological components are currently used in a variety of resources. Here, we propose a checklist that accommodates current representations, and call it the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while assuring uniformity and interoperability of the data across resources.

Background: The rate of force development (RFD) plays a pivotal role not only in preventing falls but also in ensuring successful completion of many functional tasks that demand swift muscle power rather than prolonged strength. Despite its importance, there is limited compre-hensive research on the relationship between RFD and walking speed, especially in older adults with Sarcopenic Obesity (SO). Objective: to investigate the influence of obesity on neuromuscular markers in older adults with SO and to assess the relationship between neuromuscular markers and gait speed in older adults with SO. Methods: a cohort of 42 participants was categorized based on their BMI into two groups: the sarcopenic non-obese group (CG, n=22; age=81.13±4.02; BMI=25.13±3.35) and the sarcopenic obese group (SOG, n=20; age=77.71±2.95; BMI=34.46±3.25). Gait speed was measured using a 10-meter test. Additionally, the isometric strength of the plantar flexor muscles was assessed during maximal voluntary contractions. Absolute Peak force (aPeak, N) were documented at intervals of 50 ms (a50, N), 100 ms (a100, N), and 200 ms (a200, N), subsequently normalized to body mass (r50, r100, r200, N). The RFD was derived in two phases: from the start of the contraction to 50 ms (RFD50-100) and from 100 to 200 ms (RFD100-200) and calculated from the linear slop of the force – time curve (Δ force/Δ time). Conclusion: Obesity negatively impacts neuromuscular markers in older adults. Notably, RFD emerges as the dominant factor influencing gait speed, accounting for an impressive 51% of its variability, far surpassing the impact of relative peak force. This underscores the imperative of evaluating neuromuscular health in older adults with SO to provide insights into mobility out-comes.

Cancer cells exhibit aberrant extracellular matrix mechanosensing due to altered expression of mechanosensory cytoskeletal proteins. Aberrant mechanosensing of the tumor microenvironment (TME) by cancer cells has been shown to be associated with cancer development and progression. Recent studies show that altered mechanosensing changes the mechanobiological properties of cells, and, in turn, cells become susceptible to mechanical perturbations. Due to an increasing understanding of cell biomechanics and cellular machinery, several approaches have emerged to target the mechanobiological properties of cancer cells and cancer-associated cells to inhibit cancer growth and progression. In this review, we summarize the progress that happened in the development of mechano-based approaches to target cancer by interfering with the cellular mechanosensing machinery and overall TME.

Impact force and maximum velocity are important indicators of kick efficiency in fighting activities. Therefore, this systematic review compared the front kick (FK) and roundhouse kick (RK), including maximal and impact force, maximum velocity, maximum angular velocity, and execution time, at different target types and experience levels. The Web of Science, SportDiscus, and PubMed were systematically searched from January 1982 to May 2022, according to PRISMA guidelines. The normalized kicking values were compared using one-way ANOVA. Eighteen articles, including FK with a pooled sample of 113 elite men, 109 sub-elite men, and 46 novices, and 25 articles, including RK with a sample of 238 elite men, 143 sub-elite men, and 27 novice men, fulfilled the inclusion criteria. The primary findings were that the impact forces of FK were higher than RK for the novice, sub-elite, and elite groups by 47% (p<0.01), 92% (p<0.01), and 120% (p<0.01), respectively. Moreover, the maximum foot velocity of RK was faster than FK for the sub-elite and elite groups by 44% (p<0.01) and 48% (p<0.01), respectively. The Elite group had 65% (p<0.01) higher knee extension angular velocity within RK than FK, and 138% (p<0.01) higher hip extension angular velocity within FK than RK.

Tolman VII solution \citep{ref-journal 2} is an exact analytic solution to the Einstein field equations describing the space-time of a static spherically symmetric distribution of matter. The solution has been shown to be capable of describing the interior of compact objects like neutron stars. Generalized \cite{ref-journal 13} and modified \cite{ref-journal 10} versions of the solution are also available in the literature, which have been subsequently developed to accommodate more realistic descriptions of neutron stars. The stability of the modified Tolman VII solution has recently been analyzed by Posada {\em et al} \cite{ref-journal 9 }, who evaluated a critical value of the adiabatic index above which the stellar configuration becomes unstable against radial oscillations. In this paper, making use of the generalized version of the Tolman VII solution, we prescribe an upper bound on the compactness ($M/R$) beyond which the star becomes unstable. Our investigation is based on the stability analysis of a star against radial oscillations developed by Chandrasekhar \cite{ref-journal 1}. The analysis brings out to attention the role of a particular model parameter in the generalized Tolman VII solution which can be linked to the inhomogeneity of the matter distribution vis-a-vis equation of state (EOS).

The detection and enrichment of circulating melanoma cells is a challenge as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers that predict progress and therapeutic response. We here analyzed the elasticity of A375 melanoma cells applying force spectroscopy and a microfluidic method. To identify and eventually separate circulating tumor cells, it is crucial to precisely know their physical properties. First, we used standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of measurement with a tip, we then used cantilevers without a tip to press on the cells over a large area. The resulting Young’s moduli are slightly lower and vary less without tip presumably because of the inhomogeneity of the cells. Finally, we implemented our microfluidic method. We measured single cell elasticity by analyzing its deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress strain diagram. The results from microfluidic deformation analysis were in accordance with the results from force spectroscopy. The microfluidic method provides advantages over conventional methods, since it is less invasive and less likely to harm the cell during the measurement, and the whole cell is measured as one entity without contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows to predict the overall elastic behavior of the whole inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulation melanoma cells in the clinical practice.

Classical laws of friction suggest that friction force is proportional to the normal load and independent of the nominal contact area. As a great improvement in this subject, it is now widely accepted that friction force is proportional to the real area in contact, and much work has been conducted based on this hypothesis. In present study, this hypothesis will be carefully revisited by measuring the friction force and real contact area in-site and real-time at both normal loading and unloading stages. Our experiments reveal that the linear relation always holds between friction force and normal load. However, for the relation between friction force and real contact area, the linearity holds only at the loading stage while fails at the unloading stage. This study may improve our understanding of the origin of friction.

As the coproduct of steelmaking, steelmaking slag, volumetrically expansive-prone without treatment, has been satisfactorily used as an aggregate base course material in highway construction. Although numerous technical reports and papers have revealed that steel slag aggreged using in rigid matrixes, the end product, paving block, non-structural concrete, for example, possesses superb strength and durability properties, the application of steel slag aggregate as a concrete aggregate is currently prohibited in highway construction. Naturally, researchers explore the practicality of use of steel slag, how to connect the laboratory experiment results to the end-product behavior, and further convert the research results into real construction? For all nontraditional or secondary materials utilization, the procedure of laboratory material examination, lab and field trial test are critical. To generalize the utilization, usability criteria establishment is necessary. This paper tries to use step-by-step method and plain language to explain how the volumetrically expansion can be simulated in lab testing apparatus, and based on the model, the mathematical deduction can result in a numerical usability criterion for steel slag use as a coarse aggregate in concrete (a rigid material). Therefore the paper is composed four main parts, laboratory test methods to examine the expansion force resulted from steel slag; converting the measured expansion force in a given volume of mass aggregate to the expansion (body) force of a single particle; modeling of slag and end material disruption; and a usability criterion from numerical deduction for the use of expansive-prone coarse slag in concrete or other rigid matrices. The paper provides the solutions to answer the above questions. Through the mathematical and mechanical modeling, provides the potential criteria that could result in specifications and guidance establishment for broad volumetric expansive-prone slags.

To quantify damage to reinforced concrete (RC) column members after an earthquake, an engineer needs to know the maximum applied force that was generated by the earthquake. Therefore, in this work, piezoceramic transducers are used to detect the applied force on an RC column member under dynamic loading. To investigate the use of post-embedded piezoceramic sensors in detecting the force that is applied to RC columns, eight full-size RC column specimens with various failure modes are tested under specific earthquake loadings. Post-embedded piezoceramic sensors are installed at a range of depths (70-80 mm) beneath the surface of a column specimen to examine the relationship between the signals that are obtained from them and the force applied by the dynamic actuator. The signals that are generated by the post-embedded piezoceramic sensors, which correlate with the applied force, are presented. These results indicate that the post-embedded piezoceramic sensors have great potential as tools for measuring the maximum applied force on an RC column in an earthquake. Restated, signals that are obtained from post-embedded piezoceramic sensors on an RC column in an earthquake can be used to determine the applied force and corresponding damage or residual seismic capacity.

Laser-Powder Directed Energy Deposition (DED-LB/Powder) is an additive manufacturing process that is gaining popularity in the manufacturing industry due to its numerous advantages, particularly in repairing operations. However, its application is often limited to case studies due to some critical issues that need to be addressed, such as the degree of internal porosity. This paper investigates the effect of the most relevant process parameters of the DED-LB/Powder process on the level and distribution of porosity. Results indicate that, among the process parameters examined, porosity is less affected by travel speed and more influenced by powder mass flow rate and laser power. Additionally, a three-dimensional finite element transient model was introduced, which was able to predict the development and location of lack-of-fusion pores along the building direction.

Abstract: CRISPR/Cas systems are used for genome editing, both in basic science and in bio-technology. At the same time, CRISPR/Cas editors have several limitations, including insufficient specificity leading to "off-targets" and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have been obtained now, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cere-visiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.

Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients from developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMC) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMC, most monocytes/macrophages became foamy cells that overproduce NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMC were exposed to Mtb, a subset of macrophages quickly captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFN-gamma. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria to degrade them, markedly activated caspase-1 and elicited a potent IFNgamma/cytotoxic response. In rabb-gammaits immunized with the same bacteria, fluvastatin therapy increased the tuberculin test response. We conclude that statins enhance macrophage effectiveness to control Mtb supported by adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

Solidification cracking is a major obstacle when joining dissimilar alloys using additive manufacturing. In this work, location-specific solidification cracking susceptibility has been investigated using an integrated computational materials engineering (ICME) approach for a graded alloy formed by mixing P91 steel and Inconel 740H superalloy. An alloy derived from a mixture of 26 wt.% P91 steel and 74 wt.% Inconel 740H, with high configurational and total entropy, was fabricated using wire-arc additive manufacturing. Microstructure characterization revealed intergranular solidification cracks, which increased in length along with the build height. With inputs from experiments, such as secondary dendrite arm spacing, the DICTRA (diffusion-controlled transformations) module within the Thermo-Calc software was used to model location-specific solidification cracking susceptibility. The top region, with the highest cooling rate, has the highest solidification cracking susceptibility and is in good agreement with the experimentally observed crack length. From Scheil simulations, it was deduced that pronounced segregation of Nb and Cu within the cracks increased the solidification range by suppressing the solidus temperature. The overall solidification cracking susceptibility and freezing range was highest for the 26 wt.% P91 alloy amongst the mixed compositions between P91 steel and 740H superalloy, proving that solidification characteristics play a major role in alloy design for additive manufacturing.

This study is a synthesis of 159 articles that were selected for their relevance to comprehend key aspects of the Massive Open Online Courses (MOOCs) phenomenon, from a discourse analysis perspective. Since 2011, MOOCs are expanding worldwide so that the number of subscribers outpointed 101 million at the end of 2018. This paper explores the question whether the MOOCs are the embodiment of the global one-world classroom or whether, instead, they represent a low-cost alternative tailored to a segment that doesn´t have enough time or resources to attend a brick-and-mortar college. In addition, the review tackles the link between motivation and low completion rates. Finally, we discuss the need to devise better methods to assess the pedagogical value of MOOCs.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

Based on the panel data from 31 provinces in China from 2012 to 2020, this paper uses the TOPSIS method to measure the development level of the digital economy and environmental quality. Then, a coupled coordination degree model is used to analyse the relationship between the digital economy and environmental quality. Kernel density estimation and the Dagum Gini coefficient method were used to reveal the dynamic evolution trend of the coupled coordination level between the digital economy and environmental quality and the regional trends of coupled indicators. Finally, the dynamics of the above relations were explored with an econometric model. The results show that the coupled coordination degree of the digital economy and environmental quality displays obvious regional heterogeneity, and the national coordination level exhibits dynamic convergence characteristics. The heterogeneity of the coupled coordination degree of the two systems in the eastern region has decreased year by year, except in the western region, the central region and the northeast region, where an upwards trend is observed. Overall, the Gini coefficient of the coupled coordination degree between the digital economy and environmental quality displays a certain downwards trend. The level of economic development, technological innovation level, industrial structure, degree of opening to the outside world, degree of environmental regulation, marketization index and financial development level have a positive influence on the coupled coordination of the digital economy and environmental quality. Environmental regulation is the core driver of the coupling of the two systems, and the economic development level, technological innovation level, industrial structure and degree of openness are the other major drivers. Therefore, in the processes of digital economy transformation and environmental governance, all regions should focus on balanced development between regions to optimize the overall efficiency of the two systems, consider external influence, enhance internal capabilities, and promote the coordination and co-development of the two systems.

We studied the magnetostriction coefficients, λs, Curie temperature, Tc, and their dependence on annealing conditions in Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 amorphous glass-coated microwires with rather different character of hysteresis loops. A positive λs≈20x10-6is observed in as-prepared Fe47Ni27Si11B13C2, while low and negative λs ≈-0.3x10-6 is ob-tained for Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 microwire. Annealing affects the magnetostriction coeffi-cients and Curie temperatures, Tc, of both Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 glass-coated microwires in a similar way. Observed dependencies of hysteresis loops, λs and Tc on annealing conditions are discussed in terms of superposition of internal stresses relaxation and structural relaxation of studied microwires. We observed linear λs dependence on applied stress, σ, in both studied microwires. A decrease with applied stress is observed for Co-rich mi-crowires with negative magnetostriction coefficient. In contrast, a linear increase of the magne-tostriction coefficient with applied stress is observed for Fe-Ni- rich microwires with positive magnetostriction coefficient. Observed results are discussed in terms of influence of internal stresses and short range atomic rearrangements induced by annealing on hysteresis loops, magnetostriction coefficients and Curie temperatures of studied microwires.

When a suspension passes through a high-frequency standing sound wave, the particles it contains are manipulated by acoustic forces. In a one-dimensional sound field, these forces lead to a planar arrangement of the particles and the formation of agglomerates. It is known that the combination of these forces and depth filtration can be utilized to significantly increase the filter efficiency of coarse-pored media. So far, this concept has only been used in microfluidics. In this paper, we present the results of a scaled-up filtration channel to test the viability of the industrial application of acoustically assisted filtration systems for the removal of microparticles. The influences of acoustic power input, flow rate, and the porosity of the filter media are investigated. In addition to verifying the scalability, a significant decrease in the large particle fraction in the outflow of the channel was observed when a high-power sound field is applied. Furthermore, the formed agglomerates tend to rise to the fluid surface. The floating particles mostly consist of a large particle fraction.

The need for miniaturized shear force sensors is expanding, particularly for biomedical applications. Examples include measuring interfacial shear stresses between a human and an external device (e.g., footwear or a prosthesis). However, there are considerable challenges in designing a shear sensor for these applications due to the need for a small package, low power requirements, and resistance to interference from motion artifact and electromagnetic fields. This paper presents the design, fabrication, and characterization sensor that measures two-axis shear force by detecting displacement between a color panel and a red, green, and blue light-sensing photodiode. The sensor response to applied displacements and forces was characterized under benchtop testing conditions. We also present the design of a prototype wireless version of the sensor for integration into footwear. The sensor exhibited strong agreement with gold standard measurements for two axis shear displacements (R2>0.99, RMSE≤5.0 µm) and forces (R2>0.99, RMSE≤0.94 N). This performance, along with the sensor’s scalability, miniaturized form, and low power requirements make it well-suited a variety of biomedical applications.

Unpaid family caregivers must consider the economic trade-off between caregiving and paid employment. Prior literature has suggested labour force participation (LFP) to decline with caregiving intensity, but no study has evaluated this relationship by accounting for the presence of both kinks and discontinuities. Here we used respondents of the China Health and Retirement Longitudinal Study baseline survey who were non-farming, of working-age (aged 45-60) and had a young grandchild and/or a parent/parent-in-law. For women and men separately, a caregiving threshold-adjusted probit model was used to assess the association between LFP and weekly unpaid caregiving hours. Instrumental variables were used to rule out the endogeneity of caregiving hours. Of the 3,718 respondents in the analysis, for men, LFP was significantly and inversely associated with caregiving that involved neither discontinuities nor kinks. For women, a kink was identified at the caregiving threshold of 8 hours per week such that before 8 hours, each caregiving hour was associated with an increase of 0.0257 in the marginal probability of LFP, but each hour thereafter was associated with a reduction of 0.0014 in the marginal probability of LFP. These results have implications for interventions that simultaneously advance policies of health, social care and labour force.

The entropic gravity conception proposes that what has been traditionally interpreted as unobserved dark matter might be merely the product of quantum effects. These effects would produce a novel sort of positive energy that translates into dark matter via $E=mc^2$. In the case of axions, this perspective as been shown to yield quite sensible, encouraging results [DOI:10.13140/RG.2.2.17894.88641] . There, a simple Schrodinger mechanism was utilized, in which his celebrated equation is solved with a potential function based on the microscopic Verlinde's entropic force advanced in [Physica A {\bf 511} (2018) 139]. In this effort we revisit such technique with regards to fermions' behavior (specifically, baryons).

Domain walls were studied for permalloy wires with different depth trenches (500 nm wide, 30 nm thick, 7.5 µm long, the depth of the trench was 0, 4, 5, 8, 10, 12 and 15nm). Permalloy (Ni80Fe20) wires were fabricated by electron beam lithography and Ar ion milling. When the depth of trench is smaller than 12 nm, the switching field (Hs) is increasing with the deeper trench. However, the depth of trench is bigger than half depth of thickness, the Hs is decreasing with the deeper trench. We believed that Hs increased as the trench depth increased was because the magnetic diploes force increased between the magnetic poles on two sides of the trench. The domains of the wires were divided by the trenches and the domain walls were pinned on the trenches these were confirmed by magnetic force microscopy images.

In the manufacturing industry, cutting tool failure is a probable fault which causes damage to the cutting tools, workpiece quality and unscheduled downtime. It is very important to develop a reliable and inexpensive intelligent tool wear monitoring system for use in cutting processes. A successful monitoring system can effectively maintain machine tools, cutting tool and workpiece. In the present study, the tool condition monitoring system has been developed for Die steel (H13) milling process. Effective design of experiment and robust data acquisition system ensured the machining forces impact in the milling operation. Also, ANFIS based model has been developed based on cutting force-tool wear relationship in this research which has been implemented in the tool wear monitoring system. Prediction model shows that the developed system is accurate enough to perform an online tool wear monitoring system in the milling process.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

The research proposes a self-directed paradigm with self-design using the existing technology with LMS modules, discussions, and self-tests. The research establishes its criteria for assurance of teaching and learning known as 7x2C for the compliance of content, and appearance along with other criteria for the analysis. The above technology of web and LMS is tested for a business course that is technology-oriented in creating an experiential learning system for Covid-19 awareness. Similarly, among other ideas, an environment for educating learners about diabetes and obesity has been designed. The project is known as Sunchoke with its theme of Grow, Eat, and Heal. The educators can use their technology and apply self-directed pedagogy to transform this approach to their customized ways by using their content and rubrics.

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modified putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 to 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.

Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

Hybrid machine tools combining additive and subtractive processes have arisen as a solution to the increasing manufacture requirements, boosting the potentials of both technologies, while compensating and minimizing their limitations. Nevertheless, the idea of hybrid machines is relatively new and there is a notable lack of knowledge in the field. Therefore, in the present paper, an insight into the advancements of hybrid machines is given, identifying their real capabilities, together with the latest developments from an industrial context. In addition, the current situation and future perspectives of hybrid machines from the point of view of process planning, monitoring and inspection are discussed. Finally, the challenges that must be overcome and the opportunities that the hybrid machines will provide in the forthcoming years are presented.

The article outlines a creative approach by fusing ideas from fuzzy contractions, graph mappings, and Kannan mappings to create a brand-new notion known as "Kannan-graph-fuzzy contraction." This combination of concepts makes it possible to create a unique framework for resolving real-world issues controlled by nonlinear models. It is anticipated that using Kannan-graph-fuzzy contractions will offer a fresh approach to discussing solution existence in situations where these ideas overlap. This strategy might have a significant impact on a lot of real-world applications, proving how practical multidisciplinary techniques are for tackling issues in the real world originating from technology and engineering. The article includes several illustrated examples based on computer simulations, making the results more explicit.

Background: Coronavirus disease (COVID-19) has caused one of the worst global pandemics in recent decades. It has disrupted education systems worldwide, leading to a forced shift from traditional face-to-face to blended or fully distanced learning, requiring a higher level of student readiness for self-directed learning (SDL) and a more internal locus of control (LOC). Objective: This study explored the relationship between locus of control and level of readiness for SDL among Saudi nursing students and whether the COVID-19 pandemic has impacted this relation-ship. Methods: a cross-sectional correlational descriptive study was conducted to survey 277 Saudi nursing students enrolled in the bachelor program at one of the reputable universities in Saudi Arabia. An E-questionnaire containing two scales, the Self-Directed Learning Readiness Scale for Nursing Education, and the Locus of Control Scale, was used to collect data in addition to the selected participants’ characteristics. Results: Nursing students had a moderate-to-low level of readiness for SDL (mean = 144.0), and the majority had an external LOC. There was a significant association between the locus of control and level of readiness for self-directed learning (r = 0.19*, p = 0.001), and the internal locus of control was more significantly associated with self-directed learning (r = 0.22*, p = 0.0001) than with external locus of control. Conclusion: The study findings indicate a propensity of respondents towards an external locus of control, whereas most of the respondents’ reported levels of readiness ranged between low and moderate across all dimensions of self-directed learning. This study was not registered.

Alzheimer's disease is a multifactorial neurodegenerative disorder, with Acetylcholinesterase, Butyrylcholinesterase, Beta secretase, Glycogen Synthase Kinase beta and Monoamine oxidase B playing central role in it's pathogenesis. Therefore, this research aims to discover potential curative multitarget drugs derived from African natural products capable of addressing the multifactorial characteristics of the disease. In silico approaches were used to filter a 880 african natural compounds library based on selected pharmacokinetic properties. Molecular docking against the five aforementioned proteins, followed by Molecular Mechanics with Generalised Born and Surface Area Solvation scoring for the top compounds were used to assess binding. Density Functional Theory studies were used to assess electronic transitions. Pharmacokinetic filters resulted in 200 compounds, of which only five were selected after molecular docking. Density Functional Theory and Molecular Mechanics with Generalised Born and Surface Area Solvation scoring resulted in 3 potential multitarget compounds. Compound 157 (ZINC000095485950) showed triple-target inhibitory activity against Butyrylcholinesterase, Glycogen Synthase Kinase beta and Beta-secretase, while compounds 159 (ZINC000095485952) and 696 (ZINC000039144622) showed dual-target inhibitory activity against Butyrylcholinesterase and Glycogen Synthase Kinase beta. Molecular dynamics simulation and further experimental assessments are suggested.

Laser Powder Directed Energy Deposition (LP-DED) is an Additive Manufacturing process in which a laser beam is used to generate a melt pool onto a substrate. The additional material, in form of powder material, is fed into the generated melt pool and a raised track is obtained. The LP-DED process is very powerful for different applications such as the repair operations and the production of functionally graded material, however the application is still limited and one of the main reasons is related to the lack of knowledge in the physics of the process mechanisms. The process is influenced by a huge number of parameters and three main mechanisms can be identi-fied. These mechanisms are the powder flow, the generation of the molten pool and the solidifica-tion process and for each of these mechanisms the process parameters have a different relevance. In this paper, a review of the main mechanisms and the relationship between the process parame-ters and the outcome of each step of the process is presented.

Diabetic foot is a serious complication that poses significant risks for diabetic people. The resulting reduction in protective sensitivity in the plantar region requires early detection to prevent the imminent ulceration and amputation. The primary method employed for evaluating this sensitivity loss is the 10 g f Semmes-Weinstein monofilament test, commonly used as a first-line procedure. However, the lack of calibration in existing devices often introduces decision errors due to unreliable feedback. In this paper, a new equipment designed to address these limitations and enhance the assessment of the sensitivity loss using the 10 g f monofilament is introduced. The proposed system automates metrological verification and evaluation processes, ensuring accurate and reliable results. Furthermore, it simulates the practitioner’s procedure, serving both as a valuable training tool and a means to provide force-feedback information. An analytical model of the monofilament buckling and deflection is also presented. The obtained results showed that the tested monofilaments had a very high error compared to the 10 g f declared by the manufacturers. It is aimed, by introducing this advanced equipment, to improve the precision and reliability of assessing the sensitivity loss. The integration of automated verification, simulation capabilities, and precise measurements shows great promise for diabetic patients, reducing the likelihood of adverse outcomes such as ulceration and amputation.

The complex dynamics of the neocortex, the outermost layer of the brain, have been a subject of intense research in neuroscience. Recent studies have suggested that magnetic fields generated by neuronal activity may play a significant role in neocortical dynamics. This paper presents a simplified mathematical model that explores the hypothesized interactions between magnetic dynamos, nondissipative systems, Hamiltonian equations, and the Lorenz force in the context of neocortical dynamics. The proposed model is based on a set of coupled Hamiltonian equations inspired by the Lorenz system, a well-known chaotic dynamical system. The generalized coordinates in the model represent the magnetic field components, while the generalized momenta are related to the electric field components or other relevant quantities. The Hamiltonian equations describe the conservative dynamics of the system, and the coupling terms in the equations are interpreted as representing the interactions between the magnetic and electric field components, analogous to the Lorenz force in electromagnetism. The model is implemented using Python, and the Hamiltonian equations are numerically solved using the odeint function from the scipy.integrate module. The resulting dynamics of the magnetic field components are visualized using matplotlib. While the model is highly simplified and does not capture the full complexity of neocortical dynamics, it serves as a starting point for investigating the potential role of magnetic dynamos and Lorenz force interactions in the brain. The paper discusses the limitations of the current model and highlights the need for further refinements, such as incorporating more realistic biological constraints, considering energy dissipation and compensation mechanisms, and validating the model against experimental data. Future work should focus on developing a more comprehensive and biologically plausible model that integrates the latest findings from neuroscience, physics, and computational modeling. By presenting this simplified Hamiltonian model, the paper aims to stimulate further research and discussion on the potential significance of magnetic dynamos and Lorenz force interactions in neocortical dynamics. The model provides a framework for exploring these hypothesized mechanisms and may guide future experimental and theoretical investigations in this emerging field of neuroscience

The ageing global population and changing labor force participation are having a profound impact on state pension programs worldwide, including Malaysia. However, the effects of an ageing workforce and declining fertility rates are having a significant impact on future trends in labor force participation and the duration of retirement. This paper presents an innovative examination of labor force participation rate (LFPR) forecasting within the context of an aging workforce, utilizing the Lee-Carter and Cairns-Blake Dowd stochastic models, traditionally applied to mortality data. By adapting these models to LFPR data, the study offers a novel perspective on predicting workforce participation trends and understanding the dynamics of retirement planning from year 2001 to 2047. Additionally, by incorporating the mortality forecasts from the United Nations, the research navigates through the complexities of applying actuarial methods to labor economics, revealing differentiated pathways for male and female participation in the labor market and the anticipated length of retirement. This study offers a unique comparison between the Lee-Carter and the Cairns-Blake-Dowd (CBD) LFPR models. It focuses on fitting and forecasting the LFPR of senior employees aged 50 to 64. The results highlighted discrepancies among models that demonstrated evidence of model risk for extended retirement duration.

This paper focuses on improving the tracking accuracy for servo systems and increasing the contouring performance of precision machining. The dynamic friction during precision machining is analyzed using the LuGre model. The dynamic and static parameters in the friction model are efficiently and accurately identified using the improved Drosophila Swarm Algorithm based on cross-mutation. The friction tracking error can be deduced by the friction state space and an expression is derived. To compensate for the tracking error caused by friction, a feedforward compensation control is designed to avoid signal lag in traditional friction controllers. Furthermore, the factors of multi-axis parameter mismatching that impact the machining profile accuracy are analyzed for multi-axis control. An adaptive cross-coupled control-based pre-compensation strategy of contour error is designed to reduce both the tracking error and the contour error. The effectiveness of the proposed method is validated through several experiments, which demonstrate a remarkable improvement in tracking performance and contour accuracy.

Real-time multi-axis distributed tactile sensing is a critical capability if robots are to perform stable gripping and dexterous manipulation, as it provides crucial information about the sensor-object interface. In this paper, we present an optical-based 6-axis tactile sensor designed in a fingertip shape for robotic dexterous manipulation. The distributed sensor can precisely estimate local XYZ force and displacement at ten distinct locations, and provide global XYZ force and torque measurements. Its compact size, comparable to that of a human thumb, and minimal thickness allow seamless integration onto existing robotic fingers, eliminating the need for complex modifications to the gripper. The proposed sensor design uses a simple, low-cost fabrication method. Moreover, the optical transduction approach uses light angle and intensity sensing to infer force and displacement from deformations of individual sensing units that form the overall sensor, providing distributed 6-axis sensing. The local force precision at each sensing unit in the X, Y, and Z axes is 20.89 mN, 19.19 mN, and 43.22 mN, respectively, over an local force range of approximately ±1.5 N in X and Y and 0 to -2 N in Z. The local displacement precision in the X, Y and Z axes is 56.70 μm, 50.18 μm and 13.83 μm, respectively, over a local displacement range of ±2 mm in the XY directions and 0 to -1.5mm in Z (i.e., compression). Additionally, the sensor can measure global torques, Tx, Ty and Tz, with a precision of of 1.90 N-mm, 1.54 N-mm and 1.26 N-mm, respectively. The fabricated design is showcased by integrating it with an OnRobot RG2 gripper and illustrating real-time measurements during in simple demonstration task which generate changing global forces and torques.

The world population is aging, which along with recent shifts in the labor force participation (LFP), is having a significant longevity influence on state pension programs across the board, including Canada, Finland, Japan, and Germany. Except Japan, these countries have set their statutory re-tirement age at 65, but the impact of aging workforce and declined fertility rates create wonders on the estimate future trends in the LFP, as well as the length of retirement. In this study, we fit the LFP rates of these countries, representing continents from Asia, Europe and North America among the OECD countries, using the Lee-Carter and Cairns-Blake-Dowd (CBD) stochastic models. The es-timates are then used for the projection of future LFP rates (1989-2066), and by combining the mortality forecasts from the United Nations, we project the expected length of retirement (1989-2066). This study provided a novel comparison between the Lee-Carter and the CBD LFP models by fitting and forecasting the LFP rates of senior employees between 50- to 74-year-olds. The results revealed disparities between models that provided proof of the presence of model risk for longer retirement durations. The study findings emphasized the importance for decision-makers in pension industry to have awareness of potential risks and limits associated with the LFP models. The Lee-Carter model outperformed the CBD model even though the CBD model is known for its ac-curate prediction in higher ages. Population aging should be considered in any analysis of the long-term viability of pensions, together with the participation rate trends for a sustainable labor market future.

In this paper, a mathematical and physical interpretation of the length and the angle of the catenary curve made by the anchor chains was implemented, and the safety of an anchored vessel was reviewed. So far, holding force has been calculated approximately when the angle of the catenary curve of the anchor chain to the seafloor is 0°. In this study, the holding force equation was strictly derived for the case of anchor dragging. In addition, the equations for the angle and length of the catenary curve were mathematically derived when the anchor dragging occurs. The holding force equation derived in this paper are expected to help provide guidelines in vessel design or increase the safety of anchoring.

Viroids represent the simplest, but are also among the most interesting life-like forms. They represent a great problem in agriculture. Moreover, pathogens similar to viroids, such as the hepatitis Delta virus represent a risk for human health. Viroids encode no proteins, but are still able to hijack their host cells’ metabolism to perform multiplication. This paper attempts to reply three questions about viroids. First, how can viroids hijack their host cells’ metabolism, even though they encode no proteins to achieve this? Second, what advantages do viroids have from their simplicity? Third, what can viroids, as the simplest life-like forms, tell us about life as a natural phenomenon? These questions are discussed from the perspective of biothermodynamics. In order to do this, elemental composition, biosynthesis reactions and standard thermodynamic properties of viroids have been determined and analyzed.

Holding an object by clamping force is a fundamental phenomena, layered or laminated architectures with internal sliding features are essential mechanism in natural and man-made structural system. In this paper, we combine the layered architecture and clamping mechanism to form a multilayered clamp and study the clamping force with internal friction. Our investigations show that the clamping force and energy dissipation are very mich depend on the number of layers, its geometry and elasticity, as well as internal friction. The central goal of studying the covered book is not only to predict the clamping force of the clamp, but also as a representative case to help finding some clue on the universal behaviours of multilayered architectures with internal friction.

Granular superconductivity at high temperatures in graphite can emerge at certain two-dimensional (2D) stacking faults (SFs) between regions with twisted (around the c-axis) or untwisted crystalline regions with Bernal (ABA...) and/or rhombohedral (ABCABCA...) stacking order. One way to observe experimentally such 2D superconductivity is to measure the frozen magnetic flux produced by a permanent current loop that remains after removing an external magnetic field applied normal to the SFs. Magnetic force microscopy was used to localize and characterize such a permanent current path found in one natural graphite sample out of ∼50 measured graphite samples of different origins. The position of the current path drifts with time and roughly follows a logarithmic time dependence similar to the one for flux creep in type II superconductors. We demonstrate that a ≃10nm deep scratch on the sample surface at the position of the current path causes a change in its location. A further scratch was enough to irreversibly destroy the remanent state of the sample at room temperature. Our studies clarify some of the reasons for the difficulties of finding a trapped flux in remanent state at room temperature in graphite samples with SFs.

In this paper, we have shown the electronic circuit equivalence of a mechanical system consists of two oscillators coupled with each other. The mechanical design has the effects of the magnetic, resistance forces and the spring constant of the system is periodically varying. We have shown that the system’s state variables, such as the displacements and the velocities, under the effects of different forces, lead to some nonlinear behaviors, like a transition from the fixed point attractor to the chaotic attractor through the periodic and quasi-periodic attractors. We have constructed the equivalent electronic circuit of this mechanical system and have verified the numerically obtained behaviors using the electronic circuit.

During operation, the support bracket is the main part to withstand the axial loads of the pumped storage unit. Moreover, the effects of axial loads including the hydraulic thrust of runner flow and the weight of runner body may cause the support bracket deformation and fatigue damage. For the safe and stable operation, the simulation of the axial force and the structural analysis of the support bracket of a pumped storage unit was carried out in this paper. The CFD simulation result has revealed the variation rule of the axial force in different operating conditions. Using ANSYS Mechanical, the static stresses and deformation of support bracket with axial loads were calculated. The results release the location and variations of maximum stress and maximum deformation caused by the axial loads. By comparing the predicted maximum axial force with the admission force calculated by the structural analysis, it is found that the axial force of the researched machine is within the safe range. This study provides the reference for the safety and stable operation of the pumped storage unit.