Miracle-dz/UniFAR-FTUs huggingface dataset:
Chasing Theory with Technology: A Quest to Understand Understanding

ABSTRACT An overarching motivation driving my research has been to further our theoretical understanding of how readers successfully comprehend challenging text. This article describes the theoretical origins of this research program and my quest to understand comprehension processes through the use of technology. Coh-Metrix was developed to measure, and in turn facilitate, manipulations of text cohesion and text ease. iSTART was developed to provide students with instruction and practice on how to explain text and more effectively make use of limited prior knowledge. In addition, we have developed technologies to measure and change writing quality, relations between ideas, and emerging text comprehension. More recently, our attention has turned to comprehension of multiple documents. Understanding relations between documents and how comprehension emerges when reading multiple sources is important educationally and socially, where the internet provides a continuous stream of reliable and unreliable sources. Across these topics, my collaborators and I have conducted numerous experimental studies, but a central theme to my work has been the use of technology. This article describes these technologies, including natural language processing, game-based tutoring systems, and computational simulations; how they were informed by theory; and how they have informed my theoretical and practical understandings of language, comprehension, social interactions, and cognition as multilayered and multidimensional within what I refer to as the M&M Framework.
fHow ATP and dATP act as molecular switches to regulate enzymatic activity in the prototypic bacterial class Ia ribonucleotide reductase

Class Ia ribonucleotide reductases (RNRs) are subject to allosteric regulation to maintain the appropriate deoxyribonucleotide levels for accurate DNA biosynthesis and repair. RNR activity requires a precise alignment of its α2 and β2 subunits such that a catalytically-essential radical species is transferred from β2 to α2. In E. coli, when too many deoxyribonucleotides are produced, dATP binding to RNR generates an inactive α4β4 state in which β2 and α2 are separated, preventing radical transfer. ATP binding breaks the α−β interface, freeing β2 and restoring activity. Here we investigate the molecular basis for allosteric activity regulation in the prototypic E. coli class Ia RNR. Through the determination of six crystal structures we are able to establish how dATP binding creates a binding pocket for β on α that traps β2 in the inactive α4β4 state. These structural snapshots also reveal the numerous ATP-induced conformational rearrangements that are responsible for freeing β2. We further discover, and validate through binding and mutagenesis studies, a previously unknown nucleotide binding site on the α subunit that is crucial for the ability of ATP to dismantle the inactive α4β4 state. These findings have implications for the design of allosteric inhibitors for bacterial RNRs.
Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning

A major challenge to the characterization of intrinsically disordered regions (IDRs), which are widespread in the proteome, but relatively poorly understood, is the identification of molecular features that mediate functions of these regions, such as short motifs, amino acid repeats and physicochemical properties. Here, we introduce a proteome-scale feature discovery approach for IDRs. Our approach, which we call “reverse homology”, exploits the principle that important functional features are conserved over evolution. We use this as a contrastive learning signal for deep learning: given a set of homologous IDRs, the neural network has to correctly choose a held-out homologue from another set of IDRs sampled randomly from the proteome. We pair reverse homology with a simple architecture and standard interpretation techniques, and show that the network learns conserved features of IDRs that can be interpreted as motifs, repeats, or bulk features like charge or amino acid propensities. We also show that our model can be used to produce visualizations of what residues and regions are most important to IDR function, generating hypotheses for uncharacterized IDRs. Our results suggest that feature discovery using unsupervised neural networks is a promising avenue to gain systematic insight into poorly understood protein sequences.
Refugee Mental Health, Global Health Policy, and the Syrian Crisis

The most recent global refugee figures are staggering, with over 82.4 million people forcibly displaced and 26.4 million registered refugees. The ongoing conflict in Syria is a major contributor. After a decade of violence and destabilization, over 13.4 million Syrians have been displaced, including 6.7 million internally displaced persons and 6.7 million refugees registered in other countries. Beyond the immediate political and economic challenges, an essential component of any response to this humanitarian crisis must be health-related, including policies and interventions specific to mental health. This policy and practice review addresses refugee mental health in the context of the Syrian crisis, providing an update and overview of the current situation while exploring new initiatives in mental health research and global health policy that can help strengthen and expand services. Relevant global health policy frameworks are first briefly introduced, followed by a short summary of recent research on refugee mental health. We then provide an update on the current status of research, service provision, and health policy in the leading destinations for Syrians who have been forcibly displaced. This starts within Syria and then turns to Turkey, Lebanon, Jordan, and Germany. Finally, several general recommendations are discussed, including the pressing need for more data at each phase of migration, the expansion of integrated mental health services, and the explicit inclusion and prioritization of refugee mental health in national and global health policy.
Identification of Photoperiod-Induced LncRNAs and mRNAs in Pituitary Pars Tuberalis of Sheep

The pituitary pars tuberalis (PT) is the regulating center of seasonal reproduction, which can sense the melatonin signal and eventually cause downstream changes of GnRH secretion through TSHβ. Recently, lncRNAs have been identified in animal reproductive-related tissues, and they play important roles in reproductive regulation. Therefore, in this study, we expect to identify photoperiod-induced lncRNAs and genes in pituitary PT of sheep by comparison of expression profiles between short photoperiod (SP) and long photoperiod (LP). Through RNA-Seq, a total of 55,472 lncRNAs were identified in pituitary PT of Sunite ewes. The number of differentially expressed (DE) genes and lncRNAs between SP and LP increased gradually with the extension of LP (from LP7 to LP42). The notable LP-induced candidate genes included EYA3, TSHB, SIX1, DCT, VMO1, AREG, SUV39H2, and EZH2, and SP-induced genes involved ENSOARG00000012585, CHGA, FOS, SOCS3, and TH. In enriched pathways for DE genes and lncRNA target genes between SP and LP, the reproduction- and circadian-related pathways were highlighted. In addition, the interactome analysis of lncRNAs and their targets implied that MSTRG.209166 and its trans-target TSHB, MSTRG.288068 and its cis-target SIX1, and ENSOARG00000026131 and its cis-target TH might participate in regulation of seasonal reproduction. Together, these results will help to determine important photoperiod-induced lncRNAs and genes and give us some new insights into the epigenetic regulation of seasonal reproduction in sheep.
Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Background: Category Fluency Test (CFT) is a common measure of semantic memory (SM). Test performance, however, is also influenced by other cognitive functions. We here propose a scoring procedure that quantifies the correlation between the serial recall order (SRO) of words retrieved during the CFT and a number of linguistic features, to obtain purer SM measures. To put this methodology to the test, we addressed a proof-of-concept hypothesis whereby, in alignment with the literature, older adults would show better SM. Methods: Ninety participants (45 aged 18–21 years; 45 aged 70–81 years) with normal neurological and cognitive functioning completed a 1-min CFT. SRO was scored as an ordinal variable incrementing by one unit for each valid entry. Each word was also scored for 16 additional linguistic features. Participant-specific normalised correlation coefficients were calculated between SRO and each feature and were analysed with group comparisons and graph theory. Results: Younger adults showed more negative correlations between SRO and “valence” (a feature of words pleasantness). This was driven by the first five words generated. When analysed with graph theory, SRO had significantly higher degree and lower betweenness centrality among older adults. Conclusion: In older adults, SM relies significantly less on pleasantness of entries typically retrieved without semantic control. Moreover, graph-theory metrics indicated better optimised links between SRO and linguistic features in this group. These findings are aligned with the principle whereby SM processes tend to solidify with ageing. Although additional work is needed in support of an SRO-based item-level scoring procedure of CFT performance, these initial findings suggest that this methodology could be of help in characterising SM in a purer form.
Der p 1 Disrupts the Epithelial Barrier and Induces IL-6 Production in Patients With House Dust Mite Allergic Rhinitis

Background: Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). However, the effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear. Methods: Air–liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects (non-AR) (n = 9) and HDM-AR patients (n = 9) were treated with Der P 1 and Der P 2, followed by testing the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextrans and immunofluorescence of claudin-1 and ZO-1. Interleukin-6 (IL-6) production was evaluated by ELISA. Results: Der p 1 reduced TEER significantly in a transient and dose-dependent manner in HNEC-ALI cultures from HDM-AR and non-AR patients, whilst the paracellular permeability was not affected. TEER was significantly reduced by Der p 1 at the 10-min time point in HDM-AR patients compared to non-AR patients (p = 0.0259). Compared to no-treatment control, in HNECs derived from HDM-AR patients, Der p 1 significantly cleaved claudin-1 after 30 min exposure (72.7 ± 9.5 % in non-AR group, 39.9 ± 7.1 % in HDM-AR group, p = 0.0286) and induced IL-6 secretion (p = 0.0271). Conclusions: Our results suggest that patients with HDM-AR are more sensitive to Der p 1 than non-AR patients with increased effects of Der p1 on the mucosal barrier and induction of inflammation, indicating an important role for Der p1 in sensitization and HDM-AR development.
Edinburgh Research Explorer Understanding Intra-Species and Inter-Species Prion Conversion and Zoonotic Potential Using Protein Misfolding Cyclic Amplification

Prion diseases are fatal neurodegenerative disorders that affect humans and animals, and can also be transmitted from animals to humans. A fundamental event in prion disease pathogenesis is the conversion of normal host prion protein (PrP C ) to a disease-associated misfolded form (PrP Sc ). Whether or not an animal prion disease can infect humans cannot be determined a priori . There is a consensus that classical bovine spongiform encephalopathy (C-type BSE) in cattle transmits to humans
Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study

Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy. Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders. Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8–12 and 30–80 Hz, especially 8–12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80–250 Hz. Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80–250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.
Herbivory on the Invasive Alga Caulerpa cylindracea: The Role of Omnivorous Fishes

Herbivory has long been considered an important component of biotic resistance against macroalgae invasions in marine habitats. However, most of the studies on herbivory of invasive algae refer only to consumption by strictly herbivorous organisms, whereas consumption by omnivorous species has been largely ignored and rarely quantified. In this study, we assess whether the commonest omnivorous sparid species in the Mediterranean Sea are consuming the highly invasive alga, Caulerpa cylindracea, and determine both, its importance in their diet and their electivity toward it as a source of food. Our results confirm that three of the four fish species studied regularly consume C. cylindracea, but in most cases, the importance of C. cylindracea in the diet is low. Indeed, the low electivity values indicate that all species avoid feeding on the invasive alga and that it is probably consumed accidentally. However, despite animals and detritus being the main food for these sparid species, several individual specimens were found to have consumed high amounts of C. cylindracea. This suggests a potential role that these fish species, being really abundant in shallow rocky bottoms, may play in controlling, to some extent, the abundance of the invader.
Microbial-Assisted Wheat Iron Biofortification Using Endophytic Bacillus altitudinis WR10

Microbial-assisted biofortification attracted much attention recently due to its sustainable and eco-friendly nature for improving nutrient content in wheat. An endophytic strain Bacillus altitudinis WR10, which showed sophistical regulation of iron (Fe) homeostasis in wheat seedlings, inspired us to test its potential for enhancing Fe biofortification in wheat grain. In this study, assays in vitro indicated that WR10 has versatile plant growth-promoting (PGP) traits and bioinformatic analysis predicted its non-pathogenicity. Two inoculation methods, namely, seed soaking and soil spraying, with 107 cfu/ml WR10 cells were applied once before sowing of wheat (Triticum aestivum L. cv. Zhoumai 36) in the field. After wheat maturation, evaluation of yield and nutrients showed a significant increase in the mean number of kernels per spike (KPS) and the content of total nitrogen (N), potassium (K), and Fe in grains. At the grain filling stage, the abundance of Bacillus spp. and the content of N, K, and Fe in the root, the stem, and the leaf were also increased in nearly all tissues, except Fe in the stem and the leaf. Further correlation analysis revealed a positive relationship between the total abundance of Bacillus spp. and the content of N, K, and Fe in grains. Seed staining confirmed the enhanced accumulation of Fe, especially in the embryo and the endosperm. Finally, using a hydroponic coculture model, qPCR quantification indicated effective colonization, internalization, translocation, and replication of strain WR10 in wheat within 48 h. Collectively, strain WR10 assisted successful Fe biofortification in wheat in the field, laying a foundation for further large-scale investigation of its applicability and effectiveness.
Multi-Racial Normative Data for Lobar and Subcortical Brain Volumes in Old Age: Korean and Caucasian Norms May Be Incompatible With Each Other†

Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59–89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|β| > 0.20, p < 0.001) and subcortical regions (|β| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.
Lockdown Learning: Changes in Online Foreign-Language Study Activity and Performance of Dutch Secondary School Students During the COVID-19 Pandemic

The COVID-19 pandemic caused lockdowns and sudden school closures around the world in spring 2020, significantly impacting the education of students. Here, we investigate how the switch to distance learning affected study activity and performance in an online retrieval practice tool used for language learning in Dutch secondary education. We report insights from a rich data set consisting of over 115 million retrieval practice trials completed by more than 133 thousand students over the course of two consecutive school years. Our findings show that usage of the tool increased substantially at the start of lockdown, with the bulk of study activity occurring on weekday mornings. In general, students’ progress through the material was largely unaffected by lockdown, although students from the highest educational track were somewhat more likely to be on or ahead of schedule than students from lower tracks, compared to the previous year. Performance on individual study trials was generally stable, but accuracy and response time on open answer questions went up, perhaps as a result of students being more focused at home. These encouraging findings contribute to a growing literature on the educational ramifications of distance learning during lockdown.
On the Cost-Effective Design of Agglomeration Bonus Schemes for the Conservation of Multiple Competing Species

An important mechanism of species co-existence in spatially structured landscapes is the competition-colonisation trade-off which states that co-existence of competing species is possible if, all other things equal, the better competitor is the worse coloniser. The effectiveness of this trade-off for the facilitation of co-existence, however, is likely to depend on the spatial arrangement of the habitat, because too strong agglomeration of the habitat may overly benefit the strong competitor (being the poor disperser), implying extinction of the inferiour competitor, while too much dispersion of the habitat may drive the superiour competitor (being the inferiour coloniser) to extinction. In working landscapes, biodiversity conservation is often induced through conservation payments that offset the forgone profits incurred by the conservation measure. To control the spatial arrangement of conservation measures and habitats in a conservation payment scheme, the agglomeration bonus has been proposed to provide financial incentives for allocating conservation measures in the vicinity of other sites with conservation measures. This paper presents a generic spatially explicit ecological-economic simulation model to explore the ability of the agglomeration bonus to cost-effectively conserve multiple competing species that differ by their competition strengths, their colonisation rates and their dispersal ranges. The interacting effects of the agglomeration bonus and different species traits and their trade-offs on the species richness in the model landscape are analysed. Recommendations for the biodiversity-maximising design of agglomeration bonus schemes are derived.
Positive Information of COVID-19 and Anxiety: A Moderated Mediation Model of Risk Perception and Intolerance of Uncertainty

Although COVID-19 information has been shown to play an important role in anxiety, little is known about the mediating and moderating mechanisms underlying this relationship. In the present study, we examined whether risk perception mediated the relationship between positive information of COVID-19 and anxiety and whether this mediating process was moderated by intolerance of uncertainty. A sample of 3,341 college students participated in this study and completed questionnaires regarding positive information of COVID-19, risk perception, intolerance of uncertainty, and anxiety. The results indicated that positive information of COVID-19 was significantly and negatively associated with anxiety and that risk perception partially mediated this relationship. Intolerance of uncertainty further moderated the relationship between positive information of COVID-19 and risk perception. Specifically, the relationship between positive information of COVID-19 and risk perception was significant for college students with low intolerance of uncertainty, while it became weaker for those with high intolerance of uncertainty.