Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigations into Retinal Pathology in the Early Stages of a Mouse Model of Alzheimer’s Disease

There is increasing recognition that visual performance is impaired in early stages of Alzheimer’s disease (AD); however, no consensus exists as to the mechanisms underlying this visual dysfunction, in particular regarding the timing, nature, and extent of retinal versus cortical pathology. If retinal pathology presents sufficiently early, it offers great potential as a source of novel biomarkers for disease diagnosis. The current project utilized an array of immunochemical and molecular tools to perform a characterization of retinal pathology in the early stages of disease progression using a well-validated mouse model of AD (APPSWE/PS1ΔE9). Analytical endpoints included examination of aberrant amyloid and tau in the retina, quantification of any neuronal degeneration, delineation of cellular stress responses of neurons and particularly glial cells, and investigation of oxidative stress. Brain, eyes, and optic nerves were taken from transgenic and wild-type mice of 3 to 12 months of age and processed for immunohistochemistry, qPCR, or western immunoblotting. The results revealed robust expression of the human APP transgene in the retinas of transgenic mice, but a lack of identifiable retinal pathology during the period when amyloid deposits were dramatically escalating in the brain. We were unable to demonstrate the presence of amyloid plaques, dystrophic neurites, neuronal loss, macro- or micro-gliosis, aberrant cell cycle re-entry, oxidative stress, tau hyperphosphorylation, or upregulations of proinflammatory cytokines or stress signaling molecules in the retina. The overall results do not support the hypothesis that detectable retinal pathology occurs concurrently with escalating amyloid deposition in the brains of APPSWE/PS1ΔE9 mice.
Genetic Map Construction and Fiber Quality QTL Mapping Using the CottonSNP80K Array in Upland Cotton

Cotton fiber quality traits are controlled by multiple quantitative trait loci (QTL), and the improvement of these traits requires extensive germplasm. Herein, an Upland cotton cultivar from America, Acala Maxxa, was crossed with a local high fiber quality cultivar, Yumian 1, and 180 recombinant inbred lines (RILs) were obtained. In order to dissect the genetic basis of fiber quality differences between these parents, a genetic map containing 12116 SNP markers was constructed using the CottonSNP80K assay, which covered 3741.81 cM with an average distance of 0.31 cM between markers. Based on the genetic map and growouts in three environments, we detected a total of 104 QTL controlling fiber quality traits. Among these QTL, 25 were detected in all three environments and 35 in two environments. Meanwhile, 19 QTL clusters were also identified, and nine contained at least one stable QTL (detected in three environments for a given trait). These stable QTL or QTL clusters are priorities for fine mapping, identifying candidate genes, elaborating molecular mechanisms of fiber development, and application in cotton breeding programs by marker-assisted selection (MAS).
Morphological investigation of various orthodontic lingual bracket slots using scanning electron microscopy and atomic force microscopy

Various labial and lingual orthodontic appliances with aesthetic materials have been developed due to an increased demand in aesthetic orthodontic treatment. However, there are few reports regarding the morphology of lingual orthodontic appliances. Therefore, this study evaluates the roughness of slot surfaces of various orthodontic lingual brackets using field emission scanning electron microscopy (FE‐SEM) and atomic force microscopy (AFM). Three types of stainless steel lingual brackets (Stealth®, 7th Generation®, and Clippy L®) and one gold lingual bracket (Incognito™) with a slot size of 0.018 inches × 0.025 inches (0.457 × 0.635 mm2) were selected as representative lingual materials. Both FE‐SEM and AFM examinations showed that the Stealth® and Clippy L® brackets had the lowest surface roughness, while the 7th Generation® bracket had the highest surface roughness. There was a significant difference in surface morphology between the types of lingual brackets, even when composed of the same material. The surface roughness of the bracket slot was dependent on the manufacturing process or surface polishing process rather than the fundamental properties of the bracket materials. There was no significant difference in the mean surface roughness of the slot floor between gold and stainless steel lingual brackets. These findings suggest that, although the gold lingual bracket is very expensive, it has great potential for use in patients with nickel allergy.
Expression ratio of histone demethylase KDM3A to protamine‐1 mRNA is predictive of successful testicular sperm extraction in men with obstructive and non‐obstructive azoospermia

To evaluate the predictive value of histone demethylase KDM3A to protamine 1 (PRM1) mRNA expression ratio as a reliable marker of sperm retrieval in men with obstructive and non‐obstructive azoospermia (NOA). Fifty eight azoospermic men, including 44 with NOA and 14 with obstructive azoospermia (OA). Testis tissue samples were collected from azoospermic men who have been referred for testicular sperm extraction (TESE) and micro‐TESE. Relative expression ratio of KDM3A to PRM1 was analyzed after selection of approved reference genes. Histological classification of testis biopsies was performed. Sperm retrieval following TESE and micro‐TESE was evaluated. A sperm retrieval prediction sensitivity of 95% was established when the Cq of PRM1 became smaller than the Cq of both KDM3A and GAPDH genes. However, azoospermic men with down‐regulated KDM3A and decreased expression of PRM1 mRNA showed very low success for sperm retrieval (<25%), even after micro‐TESE surgery. The KDM3A to PRM1 mRNA expression ratio can be used as a reliable marker of successful testicular sperm extraction in men with obstructive and non‐obstructive azoospermia with 95% sensitivity.
The 5′–3′ exoribonuclease pacman is required for epithelial sheet sealing in Drosophila and genetically interacts with the phosphatase puckered

Background information. Ribonucleases have been well studied in yeast and bacteria, but their biological significance to developmental processes in multicellular organisms is not well understood. However, there is increasing evidence that specific timed transcript degradation is critical for regulation of many cellular processes, including translational repression, nonsense‐mediated decay and RNA interference. The Drosophila gene pacman is highly homologous to the major yeast exoribonuclease XRN1 and is the only known cytoplasmic 5′–3′ exoribonuclease in eukaryotes. To determine the effects of this exoribonuclease in development we have constructed a number of mutations in pacman by P‐element excision and characterized the resulting phenotypes.
Gestural Hesitation Reveals Children's Competence on Multimodal Communication: Emergence of Disguised Adaptor

Speakers sometimes modify their gestures during the process of production into adaptors such as hair touching or eye scratching. Such disguised adaptors are evidence that the speaker can monitor their gestures. In this study, we investigated when and how disguised adaptors are first produced by children. Sixty elementary school children participated in this study. There were ten from each school year (from 7 to 12 years of age). They were instructed to remember a cartoon and retell its story to their parents. The results showed that children did not produce disguised adaptors until the age of 8. The disguised adaptors accompany fluent speech until the children are 10 years old and accompany dysfluent speech until they reach 11 or 12 years of age. These results suggest that children start to monitor their gestures when they are 9 or 10 years old. Cultural influences and cognitive changes were considered as factors to influence emergence of disguised adaptors.
Droplet digital PCR is a powerful technique to demonstrate frequent FGFR1 duplication in dysembryoplastic neuroepithelial tumors

Dysembryoplastic neuroepithelial tumors (DNT) share V600E mutation in the BRAF gene with other low grade neuroepithelial tumors (LGNTs). FGFR1 internal tandem duplication of the tyrosine-kinase domain (FGFR1-ITD), another genetic alteration that also leads to MAP kinase pathway alteration, has been previously reported in LGNTs by whole-genome sequencing. In the present study we searched for FGFR1-ITD by droplet digital PCR (DDPCR™) and for FGFR1 point mutations by HRM-sequencing in a series of formalin-fixed paraffin-embedded (FFPE) LGNTs including 12 DNT, 2 oligodendrogliomas lacking IDH mutation and 1p/19q co- deletion (pediatric-type oligodendrogliomas; PTOs), 3 pediatric diffuse astrocytomas (PDAs), 14 gangliogliomas (GGs) and 5 pilocytic astrocytomas (PAs). We showed by DDPCR™ that 5/12 DNT, but none of the other LGNTs, demonstrated FGFR1-ITD. In addition, these cases also accumulated phosphorylated-FGFR1 protein as shown by immunohistochemistry. FGFR1G539R point mutation was only recorded in one DNT that also showed FGFR1-ITD. Interestingly, these FGFR1 alterations were mutually exclusive from BRAFV600E mutation that was recorded in 13 LGNTs (3 DNTs, 1 PTO, 2 PDAs, 5 GGs and 2 PAs). Therefore, FGFR1 alteration mainly represented by FGFR1-ITD is a frequent event in DNT. DDPCR™ is an easy and alternative method than whole-genome sequencing to detect FGFR1-ITD in FFPE brain tumors, in routine practice.
Model predictive controller with fixed switching frequency for a 3L-NPC inverter

This paper introduces a new control scheme based on a Finite Set-Model Predictive Control (FS-MPC) and aims of a fixed switching frequency operation. The proposed scheme allows of obtaining a voltage vector that is responsible of nullifying the cost function's derivative for its optimization. Moreover, a closed-loop space vector modulation (SVM) based on the proposed predictive control scheme is introduced for a three-level grid connected inverter. The proposed algorithm that injects a desired current to the grid is investigated through external perturbations such as change in the line current amplitude as well as DC voltage variation. Discrete-time system model was developed and simulated. Simulation results on MATLAB/Simulink are provided to verify the fast dynamic performance, and good voltage balancing of DC bus capacitors of the NPC inverter.
Evaluating the biogeochemical cycle of selenium in San Francisco Bay through modeling

A biogeochemical model was developed to simulate salinity, total suspended material, phytoplankton biomass, dissolved selenium concentrations (selenite, selenate, and organic selenide), and particulate selenium concentrations (selenite + selenate, elemental selenium, and organic selenide) in the San Francisco Bay estuary. Model‐generated estuarine profiles of total dissolved selenium reproduced observed estuarine profiles at a confidence interval of 91–99% for 8 different years under various environmental conditions. The model accurately reproduced the observed dissolved speciation at confidence intervals of 81–98% for selenite, 72–91% for selenate, and 60–96% for organic selenide. For particulate selenium, model‐simulated estuarine profiles duplicated the observed behavior of total particulate selenium (76–93%), elemental selenium (80–97%), selenite + selenate (77–82%), and organic selenide (70–83%). Discrepancies between model simulations and the observed data provided insights into the estuarine biogeochemical cycle of selenium that were largely unknown (e.g., adsorption/desorption). Forecasting simulations investigated how an increase in the discharge from the San Joaquin River and varying refinery inputs affect total dissolved and particulate selenium within the estuary. These model runs indicate that during high river flows the refinery signal is undetectable, but when river flow is low (70‐ day residence time) total particle‐associated selenium concentrations can increase to >2 µg g−1. Increasing the San Joaquin River discharge could also increase the total particle‐associated selenium concentrations to >1 µg g−1. For both forecasting simulations, particle‐associated selenium was predicted to be higher than current conditions and reached levels where selenium could accumulate in the estuarine food web.
Atomic Layer Deposition of LiF Thin Films from Lithd, Mg(thd)2, and TiF4 Precursors

Lithium fluoride is an interesting material because of its low refractive index and large band gap. Previously LiF thin films have been deposited mostly by physical methods. In this study a new way of depositing thin films of LiF using atomic layer deposition (ALD) is presented. Mg(thd)2, TiF4 and Lithd were used as precursors, and they produced crystalline LiF at a temperature range of 300–350 °C. The films were studied by UV–vis spectrometry, field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), atomic force microscopy (AFM), time-of-flight elastic recoil detection analysis (ToF-ERDA), and energy dispersive X-ray spectroscopy (EDX). In addition, film adhesion was tested by a Scotch tape test. This method results in LiF films with a growth rate of approximately 1.4 A per cycle. According to the ToF-ERDA measurements, the films are pure LiF with very small Mg and Ti impurities, the largest impurity being hydrogen with contents below 1 atom %.
Closing the Loop with Quantitative Cognitive Task Analysis

Many educational data mining studies have explored methods for discovering cognitive models and have emphasized improving prediction accuracy. Too few studies have “closed the loop” by applying discovered models toward improving instruction and testing whether proposed improvements achieve higher student outcomes. We claim that such application is more effective when interpretable, explanatory models are produced. One class of such models involves a matrix mapping hypothesized (and typically human labeled) latent knowledge components (KCs) to the instructional practice tasks that require them. An under-investigated assumption in these models is that both task difficulty and learning transfer are modeled and predicted by the same latent KCs. We provide evidence for this assumption. More specifically, we investigate the data-driven hypothesis that competence with Algebra story problems may be better enhanced not through story problem practice but through, apparently task irrelevant, practice with symbolic expressions. We present new data and analytics that extend a prior close-the-loop study to 711 middle school math students. The results provide evidence that quantitative cognitive task analysis can use data from task difficulty differences to aid discovery of cognitive models that include non-obvious or hidden skills. In turn, student learning and transfer can be improved by closing the loop through instructional design of novel tasks to practice those hidden skills.
Food allergy and gastrointestinal disease Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH 2 subsets

David Chiang, PhD,* Xintong Chen, MD, MPH,* Stacie M. Jones, MD, Robert A. Wood, MD, Scott H. Sicherer, MD, A. Wesley Burks, MD, Donald Y. M. Leung, MD, Charuta Agashe, MSc, Alexander Grishin, PhD, Peter Dawson, PhD, Wendy F. Davidson, PhD, Leah Newman, MS, Robert Sebra, PhD, Miriam Merad, MD, PhD, Hugh A. Sampson, MD, Bojan Losic, PhD,* andM. Cecilia Berin, PhD* New York, NY, Little Rock, Ark, Baltimore and Bethesda, Md, Chapel Hill, NC, and Denver, Colo
A theory of effects and resources: adjunction models and polarised calculi

We consider the Curry-Howard-Lambek correspondence for effectful computation and resource management, specifically proposing polarised calculi together with presheaf-enriched adjunction models as the starting point for a comprehensive semantic theory relating logical systems, typed calculi, and categorical models in this context. Our thesis is that the combination of effects and resources should be considered orthogonally. Model theoretically, this leads to an understanding of our categorical models from two complementary perspectives: (i) as a linearisation of CBPV (Call-by-Push-Value) adjunction models, and (ii) as an extension of linear/non-linear adjunction models with an adjoint resolution of computational effects. When the linear structure is cartesian and the resource structure is trivial we recover Levy’s notion of CBPV adjunction model, while when the effect structure is trivial we have Benton’s linear/non-linear adjunction models. Further instances of our model theory include the dialogue categories with a resource modality of Melliès and Tabareau, and the [E]EC ([Enriched] Effect Calculus) models of Egger, Møgelberg and Simpson. Our development substantiates the approach by providing a lifting theorem of linear models into cartesian ones. To each of our categorical models we systematically associate a typed term calculus, each of which corresponds to a variant of the sequent calculi LJ (Intuitionistic Logic) or ILL (Intuitionistic Linear Logic). The adjoint resolution of effects corresponds to polarisation whereby, syntactically, types locally determine a strict or lazy evaluation order and, semantically, the associativity of cuts is relaxed. In particular, our results show that polarisation provides a computational interpretation of CBPV in direct style. Further, we characterise depolarised models: those where the cut is associative, and where the evaluation order is unimportant. We explain possible advantages of this style of calculi for the operational semantics of effects.
Low‐dose effect of developmental bisphenol A exposure on sperm count and behaviour in rats

Bisphenol A is widely used in food contact materials and other products and is detected in human urine and blood. Bisphenol A may affect reproductive and neurological development; however, opinion of the European Food Safety Authority (EFSA) on bisphenol A (EFSA J, 13, 2015 and 3978) concluded that none of the available studies were robust enough to provide a point of departure for setting a tolerable daily intake for bisphenol A. In the present study, pregnant Wistar rats (n = 17–21) were gavaged from gestation day 7 to pup day 22 with bisphenol A doses of 0, 25 μg, 250 μg, 5 mg or 50 mg/kg bw/day. In the offspring, growth, sexual maturation, weights and histopathology of reproductive organs, oestrus cyclicity and sperm counts were assessed. Neurobehavioural development was investigated using a behavioural testing battery including tests for motor activity, sweet preference, anxiety and spatial learning. Decreased sperm count was found at the lowest bisphenol A dose, that is 25 μg/kg/day, but not at the higher doses. Reproductive organ weight and histology were not affected and no behavioural effects were seen in male offspring. In the female offspring, exposure to 25 μg/kg bw/day bisphenol A dose resulted in increased body weight late in life and altered spatial learning in a Morris water maze, indicating masculinization of the brain. Decreased intake of sweetened water was seen in females from the highest bisphenol A dose group, also a possible sign of masculinization. The other investigated endpoints were not significantly affected. In conclusion, the present study using a robust experimental study design, has shown that developmental exposure to 25 μg/kg bw/day bisphenol A can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead to increased female body weight late in life. These results suggest that the new EFSA temporary tolerable daily intake of 4 μg/kg bw/day is not sufficiently protective with regard to endocrine disrupting effects of bisphenol A in humans.
New approaches for identifying and testing potential new anti-asthma agents

ABSTRACT Introduction: Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.
Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway

Nerve growth factor (NGF)/nerve growth factor receptors (NGFRs) axis and canonical WNT/β-catenin pathway have shown to play crucial roles in tumor initiation, progression and prognosis. But little did we know the relationship between them in modulation of tumor progress. In this report, we found that NGF/NGFRs and β-catenin were coexpression in ovarian cancer cell lines, and NGF can decrease the expression level of β-catenin and affect its activities, which may be related to the NGF-induced down-regulation of B-cell CLL/lymphoma 9-like (BCL9L, BCL9-2). Furthermore, NGF can also increase or decrease the downstream target gene expression levels of WNT/β-catenin depending on the cell types. Especially, we created a novel in vitro cell growth model based on a microfluidic device to intuitively observe the effects of NGF/NGFRs on the motility behaviors of ovarian cancer cells. The results showed that the migration area and maximum distance into three dimensional (3D) matrigel were decreased in CAOV3 and OVCAR3 cells, but increased in SKOV3 cells following the stimulation with NGF. In addition, we found that the cell colony area was down-regulated in CAOV3 cells, however, it was augmented in OVCAR3 cells after treatment with NGF. The inhibitors of NGF/NGFRs, such as Ro 08-2750, K252a and LM11A-31,can all block NGF-stimulated changes of gene expression or migratory behavior on ovarian cancer cells. The different results among ovarian cancer cells illustrated the heterogeneity and complexity of ovarian cancer. Collectively, our results suggested for the first time that NGF is functionally linked to β-catenin in the migration of human ovarian cancer cells, which may be a novel therapeutic perspective to prevent the spread of ovarian carcinomas by studying the interaction between NGF/NGFRs and canonical WNT/β-catenin signaling.