Miracle-dz/UniFAR-FTUs huggingface dataset:
Coupling of Electrification and Discharge Processes with WRF Model and Its Preliminary Verification

The processes of cloud electrification and lightning parameterization are introduced into the Weather Research and Forecasting(WRF) model,in which the supercell and squall line are simulated.The numerical formulation of the electrical processes includes the noninductive graupel-ice,hail-ice,hail-snow and inductive graupel-cloud,hail-cloud charge separation mechanisms coupled with the Milbrandt two-moment microphysical scheme.In the mean time,a bulk lightning parameterization is considered in the model.On the one hand,the simulation of supercell produces a normal tripolar charge structure,consisting of a main negative charge region(-10°C to-30°C) with an upper main positive charge region(-40°C to-60°C) and a lower positive charge region(near 0°C). The maximum total charge density is approximately 2 nC/m3.The simulated vertical profile of charge structure is in accordance with the previous classical structure observed in the severe convective weather.On the other hand,the simulation of the squall line shows the inverted dipolar charge structure in some cells and the maximum total charge density is smaller than that of the supercell.Moreover,the simulated distribution of lightning density is similar to the observed cloud-to-ground(CG)lightning density in the mature stage of the squall line.
"Look at Our Smart Shoe" - a Scalable Online Concept for Introducing Design as Part of Computational Thinking in Grades 1-6

While programming is a process covering many stages, many of the tasks K-12 students meet at school are small with little need for, e.g., analysis or design. These earlier phases are, however, important to let children meet open-ended problems, brainstorm solutions and ideate their own creative designs. In this paper we present a model for an online, scalable and scaffolded design workshop for covering such aspects at K-12 level. Through a case study with 1200 students and 60 teachers on IoT and smart things, we describe the workshop and the resulting designs. While the students managed to design their own artifacts, more time had been needed for covering ethical aspects related to technology design. The results suggest creating separate workshops for different grade levels, and also for design and ethical aspects respectively. Moreover, additional resources could support teachers in continuing the discussion with the students after the workshop.
Micro Partitioning: Friendly to the Hardware and the Developer

Modern hardware’s complexity has made studying hardware-conscious algorithms a relevant topic for many years. Partitioning algorithms, for instance, break data into bits that fit into fast CPU caches. Unfortunately, they are often challenging to design, develop, and maintain. While hardware-oblivious algorithms are easier to build, they may perform poorly when hardware or data deviate from expectations. In this paper, we introduce micro partitioning, which enhances the partitioning problem in a way that outperforms state-of-the-art solutions while being hardware-agnostic. By storing tuples in a tight address space, micro partitioning creates an access pattern that is friendly to both caches and translation lookaside buffers. We also show how micro partitioning interacts with task-based execution strategies in a symbiotic way, making micro partitioning intuitive to express for developers.
Interactive environments for training children’s curiosity through the practice of metacognitive skills : a pilot study

Curiosity-driven learning has shown significant positive effects on students’ learning experiences and outcomes. But despite this importance, reports show that children lack this skill, especially in formal educational settings. To address this challenge, we propose an 8-session workshop that aims to enhance children’s curiosity through training a set of specific metacognitive skills we hypothesize are involved in its process. Our workshop contains animated videos presenting declarative knowledge about curiosity and the said metacognitive skills as well as practice sessions to apply these skills during a reading-comprehension task, using a web platform designed for this study (e.g. expressing uncertainty, formulating questions, etc). We conduct a pilot study with 15 primary school students, aged between 8 and 10. Our first results show a positive impact on children’s metacognitive efficiency and their ability to express their curiosity through question-asking behaviors.
Hybrid Pitch Extractor for Speech Utterances

Abstract This paper presents a new pitch detection algorithm similar to the Semiautomatic Pitch Detector (SAPD) [1] in the sense that it initially calculates the pitch period with a time-domain principle cycle extractor. However, it differs from SAPD in that the pitch periods are not only calculated on time-domain, but are assured with an error detector. If there is any ambiguity, the pitch period will be re-calculated with the CEP algorithm. A 'pitch selection logic' is used to select the pitch period from the two estimates. Experimental results show that the algorithm exhibits good performance in the five measurements proposed in [2]. The new algorithm runs at half the speed of the Data Reduction Method (DARD) [3], but faster than the Modified Autocorrelation Method (AUTOC) [4] and the Cepstrum Method [5] in the order of four and eight times, respectively.
Fundamental role for the creatine kinase pathway in protection from murine colitis

Inflammatory diseases of the digestive tract, including inflammatory bowel disease (IBD), cause metabolic stress within mucosal tissue. Creatine is a key energetic regulator. We previously reported a loss of creatine kinases (CKs) and the creatine transporter expression in IBD patient intestinal biopsy samples and that creatine supplementation was protective in a dextran sulfate sodium (DSS) colitis mouse model. In the present studies, we evaluated the role of CK loss in active inflammation using the DSS colitis model. Mice lacking expression of CKB/CKMit (CKdKO) showed increased susceptibility to DSS colitis (weight loss, disease activity, permeability, colon length and histology). In a broad cytokine profiling, CKdKO mice expressed near absent IFN-γ levels. We identified losses in IFN-γ production from CD4+ and CD8+ T cells isolated from CKdKO mice. Addback of IFN-γ during DSS treatment resulted in partial protection for CKdKO mice. We identified basal stabilization of the transcription factor hypoxia-inducible factor (HIF) in CKdKO splenocytes and pharmacological stabilization of HIF resulted in reduced IFN-γ production by control splenocytes. Thus, the loss of IFN-γ production by CD4+ and CD8+ T cells in CKdKO mice resulted in increased colitis susceptibility and indicates that CK is protective in active mucosal inflammation.
Dopamine activation modulates oscillatory synchrony in the hippocampal-prefrontal cortex circuitry

Interaction between brain networks forms the functional unit that sustains cognition and behavior. It has been proposed that oscillatory activity can synchronize distant neuronal populations. One crucial aspect to elucidate brain function and its emergent properties is to understand how functional connectivity is modulated in different time scales according to environmental or physiological demand. Modulatory neurotransmitters such as dopamine have been implicated in changes in membrane excitability, modulation of oscillatory power, and coherence in crucial circuits for cognition, such as the hippocampus-prefrontal cortex (HPC-PFC) pathway. However, it is not known how dopaminergic release modulates specifically the phase synchrony of HPC-PFC or which specific dopaminergic receptors are responsible for the effects. In this context, our objective was to investigate the influence of dopaminergic activity on HPC-PFC synchrony and to assess whether the observed effects are receptor-specific. Our results show that dopamine induces HPC-PFC theta synchrony dose-dependently. This effect is not reproduced by apomorphine unspecific agonism or by SKF and quinpirole agonists, which act respectively on D1- and D2-like receptors. Additionally, we observed a late effect with peak activity between 30 and 40 minutes after dopamine 100 nmol, apomorphine 0.75 mg/kg, or quinpirole administration in which the HPC-PFC delta synchrony increased. Together, these results evidence the participation of dopaminergic neurotransmission in regulating HPC-PFC oscillatory dynamics, Influencing the synchronization in slow frequency oscillation and long-distant brain communication.
METABOLIC MODELLING AS A POWERFUL TOOL TO IDENTIFY CRITICAL COMPONENTS OF THE PNEUMOCYSTIS GROWTH MEDIUM

Establishing suitable in vitro culture conditions for microorganisms is crucial for dissecting their biology and potential applications. However, a significant number of bacterial and fungal species, including Pneumocystis jirovecii, remain unculturable, hampering research efforts. Pneumocystis is a deadly pathogen of humans that causes life-threatening pneumonia in immunocompromised individuals and transplant patients. Despite its major impact on human health, we remain ignorant about the pathobiology of this fungus, largely because its experimental dissection is constrained by the inability to culture Pneumocystis in vitro. In this study, we present a comprehensive in silico genome-scale metabolic model of Pneumocystis growth and metabolism, aiming to identify metabolic requirements and imbalances that hinder its growth in vitro. We utilise recently published genome data, available information in the literature as well as bioinformatics and software tools to develop and validate the model. We also employ Flux Balance Analysis and Machine Learning approaches to make important predictions regarding metabolic flux to predict critical components of the Pneumocystis growth medium. Our findings offer insights into the biology of Pneumocystis and provide a novel strategy to overcome the longstanding challenge of culturing this pathogen in vitro.
Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis

Breast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis results in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA-sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations. Statement of significance The PyMT mouse model of breast cancer, which recapitulates clinical characteristics, exhibits differences in molecular and functional responses of skeletal muscle that are sex-dependent.
Blueprinting expandable nanomaterials with standardized protein building blocks

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies in comparison has been much more complex, largely due to the irregular shapes of protein structures1. Here we describe extendable linear, curved, and angled protein building blocks, as well as inter-block interactions that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight “train track” assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not been previously possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank 3D canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to “back of an envelope” architectural blueprints.
A 3D in vitro cortical tissue model based on dense collagen to study the effects of gamma radiation on neuronal function

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, we have developed a physiologically relevant 3D collagen-based cortical tissue model (CTM) for studying the functional response of human iPSC derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). We quantified cytotoxicity, DNA damage, morphology, and extracellular electrophysiology. We reported that 5 Gy exposure significantly increased cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreased neurite length and neuronal network activity. Additionally, we found that clinically deployed radioprotectant amifostine ameliorated the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which GR affects human cortical tissue and to screen prospective radioprotectant compounds.
Allelic chromatin structure primes imprinted expression of Kcnk9 during neurogenesis

Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brain from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we show that on the maternal allele enhancer-promoter contacts formed early in development prime the brain-specific potassium leak channel Kcnk9 for maternal expression prior to neurogenesis. In contrast, these enhancer-promoter contacts are blocked by CTCF on the paternal allele, preventing paternal Kcnk9 activation. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.
Identification of dialects and individuals of globally threatened Yellow Cardinals using neural networks

Audio-based analysis of bird songs has proven to be a valuable practice for the growth of knowledge in the fields of ethology and ecology. In recent years, machine learning techniques applied to audio field recordings of bird calls have yielded successful results in studying population distributions and identification of individuals for their monitoring in a variety of bird species. This offers promising possibilities in the study of social behavior, biodiversity, and conservation strategies for birds. In this work, we trained deep learning models, directly from the sonograms of audio field recordings, to investigate the statistical properties of vocalizations in the endangered Yellow Cardinal. To our knowledge, this is the first time that this approach has been applied to this threatened species. Our results indicate the presence of vocal signatures that reflect similarities in songs of individuals that inhabit the same region, determining dialects, but which also show differences between individuals. These differences can be exploited by a deep learning classifier to discriminate the bird identities through their songs. Models trained with data labeled by regions showed a good performance in the recognition of dialects with a mean accuracy of (0.84 +/-0.04) significantly higher than accuracy obtained by chance. Precision and recall values also reflected the classifier’s ability to find alike vocal patterns in the songs of neighboring individuals. Models trained with data labeled by individuals showed an accuracy of (0.63 +/-0.03) significantly higher than that obtained by chance. However, the individual discrimination model showed greater confusion with neighboring individuals. This reflects a hierarchical structure in the characteristics of the Yellow Cardinal’s vocalization, where the intra-individual variability is lower than the inter-individual variability, but it is even lower than the variability obtained when individuals inhabit different regions, providing evidence of the existence of dialects. This reinforces the results of previous works but also offers an automated method for characterizing cultural units within the species. Along with genetic data, this method could help better define management units, thereby benefiting the success of reintroduction programmes of recovered individuals of Yellow Cardinal. Moreover, the novelty of individual discrimination using neural networks for the Yellow Cardinal, which has limited data availability, shows promise for non-invasive acoustic monitoring strategies with potentially relevant implications for its conservation.
otpb functions in a Lef1-dependent transcriptional network required for expression of the stress response inhibitor crhbp in the zebrafish hypothalamus

The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish lef1, which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is otpb, which encodes a transcription factor with known roles in hypothalamic development. Here we show that otpb expression in the posterior hypothalamus is Lef1-dependent, and that like lef1, its function is required for the generation of crhbp+ neurons in this region. Transgenic reporter analysis of a crhbp conserved noncoding element suggests that otpb participates in a transcriptional regulatory network with other Lef1 targets. Finally, consistent with a role for crhbp in inhibiting the stress response, zebrafish otpb mutants exhibit decreased exploration in a novel tank diving assay. Together our findings suggest a potential evolutionarily-conserved mechanism for the regulation of innate stress response behaviors through Lef1-mediated hypothalamic neurogenesis.
Daily Activity Profiles over the Lifespan of Female Medflies as Biomarkers of Aging and Longevity

The relationship between the early age activity of Mediterranean fruit flies or other fruit flies and their lifespan has not been much studied, in contrast to the connections between lifespan and diet, sexual signaling and reproduction. The objective of this study is to assess intraday and day-to-day activity profiles of female Mediterranean fruit flies and their role as biomarker of longevity as well as to explore the relationships between these activity profiles, diet and age-at-death throughout the lifespan. Three distinct patterns of activity variations in early age activity profiles can be distinguished. A low-caloric diet is associated with a delayed activity peak, while a high-caloric diet is linked with an earlier activity peak. We find that age-at-death of individual medflies is connected to their activity profiles in early life. An increased risk of mortality is associated with increased activity in early age, as well as with a higher contrast between daytime and nighttime activity. Conversely, medflies are more likely to have a longer lifespan when they are fed a medium caloric diet and when their daily activity is more evenly distributed across the early age span and between daytime and nighttime. The before-death activity profile of medflies displays two characteristic before-death patterns, where one pattern is characterized by slowly declining daily activity and the other by a sudden decline in activity that is followed by death.
Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain

Chronic pain often alternates between transient remission and relapse of severe pain. While most research on chronic pain has focused on mechanisms maintaining pain, there is a critical unmet need to understand what prevents pain from re-emerging in those who recover from acute pain. We found that interleukin (IL)-10, a pain resolving cytokine, is persistently produced by resident macrophages in the spinal meninges during remission from pain. IL-10 upregulated expression and analgesic activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of IL-10 signaling or δOR triggered relapse to pain in both sexes. These data challenge the widespread assumption that remission of pain is simply a return to the naïve state before pain was induced. Instead, our findings strongly suggest a novel concept that: remission is a state of lasting pain vulnerability that results from a long-lasting neuroimmune interactions in the nociceptive system.