Miracle-dz/UniFAR-FTUs huggingface dataset:
The Utilisation of Interactive Simulations in the Teaching and Learning of a Grade 10 Chemistry Topic: A Case in the North West province of South Africa: The utilisation of interactive simulations in Chemistry

This study focussed on the utilisation of interactive simulations in the teaching and learning of a Grade 10 Chemistry topic (three states of matter [TSM]) – specifically sub-microscopic behaviour of particles – in the South African context. In this study, the utilisation of PhET interactive simulations is twofold: (i) for conceptual understanding of TSM; (ii) and for administering a practical experiment. The overarching theoretical framework underpinning this study is experiential learning theory. In order to understand and capture in-depth data, it was ideal to adopt an interpretive, exploratory qualitative case study approach rather than a quantitative approach. This study was conducted in one of the nine educational provinces (North West) of South Africa, where the authors reside, hence convenience sampling was employed to select the province. Two in-service Grade 10 Physical Sciences teachers from two rural secondary schools were purposively selected from one of the four educational districts in the North West province. A code-to-theory model was used to analyse the data. The main findings of this study showed that, despite the advantages of PhET interactive simulations to promote conceptual understanding and allowing for the administration of TSM laboratory experiments, interactive simulations may result in misconceptions. It is recommended that PhET interactive simulations be utilised for effective teaching and learning of abstract concepts and conceptual understanding of sub-microscopic behaviour of particles in TSM.
Examining the role of Dash Robot in Fourth-grade English as a Medium of Instruction using the UTAUT model

The subjects of this study are fourth-grade students in a primary school in Hsinchu City. This study uses the WLRC 2021 competition topics as the content of the EMI (English as a Medium of Instruction) curriculum in the fourth-grade computer science course to explore students’ English learning attitudes. Through the mode of group cooperation, students can share exploration together and increase their ability to communicate and interact with peers. In terms of research methods, the "UTAUT-based Expectation situation questionnaire" is used to test the learning attitude, and to aid understanding of the students' expected learning attitude. The study showed high expectations in the pre-test questionnaire scores, and the post-test questionnaire scores also improved significantly after the course, confirming that the expectations were exceeded. This research aims to cultivate the basic concepts of programming for primary school students in Taiwan, and it strengthens students' basic English ability and combines technology, language, and interpersonal relationships to build the foundation of children's learning ability in school. It is expected that the findings of this study will help to measure primary school students in finding innovative learning aids in the language learning mode.
GENERALIZED CENTER METHOD FOR MULTIOBJECTIVE ENGINEERING OPTIMIZATION

Abstract This paper presents a new approach to multiobjective engineering optimization: the generalized center method (GCM). A multiobjective problem is solved by calculating the centers of a sequence of level sets. These sets comprise intersections of the original constraints and level constraints imposed on objective functions. In view of the different dimensions and conflicting nature of multiple objectives, some scaling and trade-off procedures are implemented. Several engineering optimization examples are given to demonstrate the effectiveness of the proposed method.
Glucocorticoids negatively relate to body mass on the short-term in a free-ranging ungulate

Environmental fluctuations force animals to adjust glucocorticoids (GCs) secretion and release to current conditions. GCs are a widely used proxy of an individual stress level. While short-term elevation in GCs is arguably beneficial for fitness components, previous studies have documented that the relationship between long-term baseline GCs elevation and fitness components can vary according to ecological and individual factors and according to the life-history of the species studied. Using longitudinal data on roe deer (Capreolus capreolus) from two populations facing markedly different environmental contexts, we tested whether baseline GC levels negatively correlate with body mass – a trait positively associated with demographic individual performance – on the short- to long-term. In support, higher baseline GC concentrations were associated to lighter body mass, both measured during the same capture event, in adults of both populations. Overall, we showed that despite the marked environmental and demographic differences between populations and despite the between-sex differences in life history (i.e. reproductive tactics), the relationship between body mass and GCs is consistent across environmental contexts, but might differ according to the life history stage of an individual. This work opens promising perspectives to further explore the relationship between GC and fitness-related traits according to life history stages in free-ranging mammals across seasonal and environmental contexts. The timing and context-dependence of GC levels highlight the complexity of studying stress responses in the wild.
Superconducting properties of vanadium films

Studies on superconducting thin films of vanadium for determining the influence of production parameters are performed. The critical temperature Tc is determined as a function of the film thickness and the dependence of the critical magnetic field Hc∥ and Hc⟂ on the reduced temperature is measured. Moreover the dependence of the critical magnetic field and the critical current density on the angle are measured and the film constants λ, ξ, and x are determined. The experimental values are compared with values, which are calculated from the Ginsburg-Landau theory.
Smooth pursuit eye movements contribute to anticipatory force control during mechanical stopping of moving objects

When stopping a closing door or catching an object, humans process the motion of inertial objects and apply reactive limb force over short period to interact with them. One way in which the visual system processes motion is through extraretinal signals associated with smooth pursuit eye movements (SPEM). We conducted three experiments to investigate how SPEM contribute to anticipatory and reactive hand force modulation when interacting with a virtual object moving in the horizontal plane. We hypothesized that SPEM signals are critical for timing motor responses, anticipatory control of hand force, and task performance. Participants held a robotic manipulandum and attempted to stop an approaching simulated object by applying a force impulse (area under force-time curve) that matched the object’s virtual momentum upon contact. We manipulated the object’s momentum by varying either its virtual mass or its speed under free gaze or constrained gaze conditions. We examined gaze variables, timing of hand motor responses, anticipatory force control, and overall task performance. Our results show that when SPEM were constrained, anticipatory modulation of hand force prior to contact decreased. However, constraining SPEM did not seem to affect the timing of the motor response or the task performance. Together, these results suggest that SPEM may be important for anticipatory control of hand force prior to contact and may also play a critical role in anticipatory stabilization of limb posture when humans interact with moving objects. New and Noteworthy We show for the first time that smooth pursuit eye movements (SPEM) play a role in modulation of anticipatory control of hand force to stabilize posture against contact forces. SPEM are critical for tracking moving objects, facilitate processing motion of moving objects, and are impacted during aging and in many neurological disorders, such as Alzheimer’s disease and Multiple Sclerosis. These results provide a novel basis to probe how changes in SPEM could contribute to deficient limb motor control in older adults and patients with neurological disorders.
Sema7A and Sema4D Heterodimerization is Essential for Membrane Targeting and Neocortical Wiring

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving intellectual disability, speech delay, epilepsy and craniofacial defects. We show that Satb2 controls neuronal migration and axonal outgrowth by inducing the expression of the GPI-anchored protein, Sema7A. We find that heterodimerization with Sema4D increases targeting of Sema4D to the membrane and is required for Sema7A function. Finally, we report that membrane localization and pos- translational modification of the Sema7A-Sema4D complex is disrupted by a novel de novo mutation in Sema4D (Q497P) that is associated with epilepsy in humans. GRAPHICAL ABSTRACT HIGHLIGHTS Sema7A is a direct Satb2 target that drives neuronal migration and axon outgrowth Sema7A exerts its effect by heterodimerizing with Sema4D at neurites and growth cones Sema7A increases cell surface localization of Sema4D De novo human Sema4D-Q497P mutation causes epilepsy, inhibits post-translational processing & surface localization eTOC Sema7A is a direct target of the transcription factor Satb2. Sema7A promotes normal migration and axon outgrowth in cortical neurons by modulating reverse signaling via Sema4D. These processes are dependent on Sema7A-Sema4D heterodimerization and membrane localization; insufficient transcription of Sema7A or incomplete glycosylation of Sema4D inhibit this progression.
Smooth muscle-derived adventitial progenitor cells promote key cell type transitions controlling plaque stability in atherosclerosis in a Klf4-dependent manner

We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM cells localize throughout the vessel wall and atherosclerotic plaques, where they primarily differentiate into fibroblasts, SMCs, or remain in a stem-like state. Klf4 knockout specifically in AdvSca1-SM cells induced transition to a more collagen-enriched myofibroblast phenotype compared to WT mice. Additionally, Klf4 depletion drastically modified the phenotypes of non-AdvSca1-SM-derived cells, resulting in more contractile SMCs and atheroprotective macrophages. Functionally, overall plaque burden was not altered with Klf4 depletion, but multiple indices of plaque vulnerability were reduced. Collectively, these data support that modulating the AdvSca1-SM population confers increased protection from the development of unstable atherosclerotic plaques.
Rationally designed protein bandpass filters for controlling cellular signaling with chemical inputs

Biological mechanisms that rely on signal integration and processing are fundamental for cell function. These types of capabilities are analogous to those found in electronic circuits where individual components perform operations on input signals. In electronics, bandpass filters are crucial components to narrow frequencies within a specified range and reject frequencies outside of that range. However, no generalizable protein-based components are currently available to mimic such processes in engineered biological systems, representing an unmet need in controllable modules. Here, we propose a rational design approach to create protein-based chemically responsive bandpass filters (CBP) which pass chemical concentrations within a range and reject concentrations outside of that range, showing an OFF-ON-OFF regulatory pattern. The CBPs were designed using structure-based approaches where we created a heterodimeric construct which the assembly is triggered by low concentration of a small-molecule, and this interaction is inhibited at high concentrations of the drug, effectively creating a bandpass filter. The CBPs have a multidomain architecture where we used known drug-receptors, a computationally designed protein binder and small-molecule inhibitors. Owing to the modularity of the system, each domain of the CBPs can be rationally fine-tuned to optimize its performance, including bandwidth, maximum response, cutoff concentration and fold changes. These CBPs were used to regulate cell surface receptor signaling pathways showing the capability to control cellular activities in engineered cells.
Development of White Matter Fiber Covariance Networks Supports Executive Function in Youth

The white matter architecture of the human brain undergoes substantial development throughout childhood and adolescence, allowing for more efficient signaling between brain regions that support executive function. Increasingly, the field understands grey matter development as a spatially and temporally coordinated mechanism that follows hierarchically organized gradients of change. While white matter development also appears asynchronous, previous studies have largely relied on anatomical atlases to characterize white matter tracts, precluding a direct assessment of how white matter structure is spatially and temporally coordinated. Here, we leveraged advances in diffusion modeling and unsupervised machine learning to delineate white matter fiber covariance networks comprised of structurally similar areas of white matter in a cross-sectional sample of 939 youth aged 8-22 years. We then evaluated associations between fiber covariance network structural properties with both age and executive function using generalized additive models. The identified fiber covariance networks aligned with the known architecture of white matter while simultaneously capturing novel spatial patterns of coordinated maturation. Fiber covariance networks showed heterochronous increases in fiber density and cross section that generally followed hierarchically organized temporal patterns of cortical development, with the greatest increases in unimodal sensorimotor networks and the most prolonged increases in superior and anterior transmodal networks. Notably, we found that executive function was associated with structural features of limbic and association networks. Taken together, this study delineates data-driven patterns of white matter network development that support cognition and align with major axes of brain maturation.
ADAM10 mediates macroglial cell fate decisions in the developing brain

ADAMs (a disintegrin and metalloproteinase) are transmembrane proteins with cell adhesion and protease activities that contain disintegrin and metalloproteinase domains. ADAM10, a member of the ADAM family, is widely expressed in the brain. There are >40 substrates reported for ADAM10, including Notch, Delta-like ligand-1 (Dll1), and N-cadherin. To date, however, its function in the brain has been largely unknown. We used genetic manipulation to delete Adam10 specifically from glial progenitors in developing brains and observed that conditional knockout mice showed locomotor abnormalities. They all died within 4 months with apparent defects in the cerebellum. By comprehensively analyzing data from bulk RNA sequencing, single-cell RNA sequencing, and staining of the cerebellum, we found that ADAM10 promoted astrocyte generation under physiological conditions. Upon the removal of Adam10 in glial progenitors, the production of oligodendrocytes vastly increased, whereas the generation of astrocytes was substantially inhibited. Our results showed that ADAM10 plays a critical role in macroglial cell fate decisions during brain development.
Minimum number of modulated Stokes parameters in Young’s interference experiment

The contrast parameters associated with the generalized Stokes vector in a Young’s interference experiment are analyzed. It is shown that there are two unitary transformations that can be applied to the electric fields so that a partially polarized light can be described with no more than two non-zero generalized Stokes parameters. Furthermore, general conditions are derived which indicate when totally unpolarized light can be described with only one non-zero generalized Stokes parameter after unitary transformations.
Severe neurometabolic phenotype in npc1−/− zebrafish with a C-terminal mutation

Niemann Pick disease type C (NPC) is an autosomal recessive neurodegenerative lysosomal disorder characterized by an accumulation of lipids in different organs. Clinical manifestations can start at any age and include hepatosplenomegaly, intellectual impairment, and cerebellar ataxia. NPC1 is the most common causal gene, with over 460 different mutations with heterogeneous pathological consequences. We generated a zebrafish NPC1 model by CRISPR/Cas9 carrying a homozygous mutation in exon 22, which encodes the end of the cysteine-rich luminal loop of the protein. This is the first zebrafish model with a mutation in this gene region, which is frequently involved in the human disease. We observed a high lethality in npc1 mutants, with all larvae dying before reaching the adult stage. Npc1 mutant larvae were smaller than wild type (wt) and their motor function was impaired. We observed vacuolar aggregations positive to cholesterol and sphingomyelin staining in the liver, intestine, renal tubules and cerebral gray matter of mutant larvae. RNAseq comparison between npc1 mutants and controls showed 249 differentially expressed genes, including genes with functions in neurodevelopment, lipid exchange and metabolism, muscle contraction, cytoskeleton, angiogenesis, and hematopoiesis. Lipidomic analysis revealed significant reduction of cholesteryl esters and increase of sphingomyelin in the mutants. Compared to previously available zebrafish models, our model seems to recapitulate better the early onset forms of the NPC disease. Thus, this new model of NPC will allow future research in the cellular and molecular causes/consequences of the disease and on the search for new treatments.
GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation

Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at-scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targets in vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils’ yield, purity, functionality, and maturity through the deletion of the transcription factor GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, through CRSPR/Cas9 deletion of CYBB we demonstrate that GATA1 KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification

NAT10 is dysregulated and plays an essential role in various types of cancers. However, the exact machenism of how NAT10 regulates cancer progression remains debatable. In this report, we show that NAT10 affects tumorigeneis mainly based on its acetylation function on tRNA. In addition, we found NAT10 regulate the ac4C of tRNA in cancer via interaction with RNPS1, which in turn protect NAT10 from degradation by E3 ubiquitin ligase ZSWIM6. We developed TRMC-seq method to compreshensively profile tRNA ac4C sites and uncovered the presence of ac4C in a broader range of tRNA isoacceptors than previous studies. Multi-omics analysis identified AP-1 signaling pathway as a major downstream mediator of NAT10. Mechanistically, we found NAT10 is responsible for the translation efficiency genes which contain higher ac4C-tRNA codon. Importantly, our genetic mouse model validated our in vitro findings of NAT10 in cancer. Our study highlights a role of NAT10 in mediating tRNA ac4C to regulate the translation and tumorigenesis of cancer.
Simple in-vitro single stranded linear and circular DNA preparation and validation via SELEX using phosphor-derived modifications

Interest in preparation of single stranded circular DNA library has been increasing recently, therefore developing a simple and efficient method for circular DNA generation will be very useful for all procedures and techniques that are dependent on single stranded circular DNA preparation. In this study a new simple method for in vitro preparation of circular single stranded DNA is proposed. We hypothesized that using a phosphorylated-phosphorothioated primer would not affect the efficiency of PCR reactions, but, more importantly, would suppress the activity of Lambda Exonuclease enzyme even if it is phosphorylated. The produced phosphorylated single stranded DNA is ready to be circularized via a ligation reaction using a bridging oligonucleotide. Several optimizations and enhancements have been conducted in the ligation reaction, notably by embedding an extra thymine nucleotide at the ligation site to compensate for the additional adenosine nucleotide added by Taq during the PCR reaction. In addition, the performance of the proposed method has been validated by selecting linear and circular aptamers against MERS-CoV spike protein during 15 successive cycles of SELEX. Because this new method is simple and user-friendly, it has a potential to be automated for high-throughput purposes and may further stir growing interests in preparation of single stranded circular DNA and its applications.
Inflammation induces bitter taste oversensitization via epigenetic changes in Tas2r gene clusters

T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here we show that, in an inflammation model mimicking bacterial infection, the expression of many Tas2rs are significantly up-regulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly cell type specific and inflammation increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.