Miracle-dz/UniFAR-FTUs huggingface dataset:
AC6 is the major adenylate cyclase forming a diarrheagenic protein complex with cystic fibrosis transmembrane conductance regulator in cholera

The World Health Organization(WHO) has reported a worldwide surge in cases of cholera caused by the intestinal pathogen Vibrio cholerae, and, combined, such surges have claimed several million lives, mostly in early childhood. Elevated cAMP production in intestinal epithelial cells challenged with cholera toxin (CTX) results in diarrhea due to chloride transport by a cAMP-activated channel, the cystic fibrosis transmembrane conductance regulator (CFTR). However, the identity of the main cAMP-producing proteins that regulate CFTR in the intestine and may be relevant for secretory diarrhea is unclear. Here, using RNA-Seq to identify the predominant AC isoform in mouse and human cells and extensive biochemical analyses for further characterization, we found that the cAMP-generating enzyme adenylate cyclase 6 (AC6) physically and functionally associates with CFTR at the apical surface of intestinal epithelial cells. We generated epithelium-specific AC6 knockout mice and demonstrated that CFTR-dependent fluid secretion is nearly abolished in AC6 knockout mice upon CTX challenge in ligated ileal loops. Furthermore, loss of AC6 function dramatically impaired CTX-induced CFTR activation in human and mouse intestinal spheroids. Our finding that the CFTR–AC6 protein complex is the key mediator of CTX-associated diarrhea may facilitate development of antidiarrheal agents to manage cholera symptoms and improve outcomes.
TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2‐1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase‐3, Bax and Bcl‐2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl‐2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase‐3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC.
Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator

Many disease-causing mutations impair protein stability. Here, we explore a thermodynamic strategy to correct the disease-causing F508del mutation in the human cystic fibrosis transmembrane conductance regulator (hCFTR). F508del destabilizes nucleotide-binding domain 1 (hNBD1) in hCFTR relative to an aggregation-prone intermediate. We developed a fluorescence self-quenching assay for compounds that prevent aggregation of hNBD1 by stabilizing its native conformation. Unexpectedly, we found that dTTP and nucleotide analogs with exocyclic methyl groups bind to hNBD1 more strongly than ATP and preserve electrophysiological function of full-length F508del-hCFTR channels at temperatures up to 37 °C. Furthermore, nucleotides that increase open-channel probability, which reflects stabilization of an interdomain interface to hNBD1, thermally protect full-length F508del-hCFTR even when they do not stabilize isolated hNBD1. Therefore, stabilization of hNBD1 itself or of one of its interdomain interfaces by a small molecule indirectly offsets the destabilizing effect of the F508del mutation on full-length hCFTR. These results indicate that high-affinity binding of a small molecule to a remote site can correct a disease-causing mutation. We propose that the strategies described here should be applicable to identifying small molecules to help manage other human diseases caused by mutations that destabilize native protein conformation.
Leakage Flux Modeling of Medium-Voltage Phase-Shift Transformers for System-Level Simulations

Cascaded H-Bridge converters in medium-voltage (MV) applications have all the dc link capacitors supplied from external source through a multiwinding phase-shift transformer. This type of transformers has a complex winding geometry, which leads to unbalanced leakage flux paths. The unbalance affects the dynamic behavior of the converters. This work proposes a modeling approach, which realistically captures the unbalance in the leakage flux path of phase-shift transformers, using permeance magnetic circuit. The model can be seamlessly integrated into system-level simulation of power electronic circuits. Taking advantage of the repetitive structure of the windings, the model requires very limited number of parameters, which can be easily obtained from the geometry data together with only a few experimental tests. The fidelity of the model is experimentally confirmed on a phase-shift transformer from a commercial MV drive system.
Global impact of accelerated plant breeding: Evidence from a meta-analysis on rice breeding

Rice breeders in Asia and elsewhere in the world have long overlooked trying to shorten the time it takes to develop new varieties. Plant breeders have proposed a technique called Rapid Generation Advance (RGA) as a way to accelerate the results of public rice breeding programs. However, little is known about RGA’s potential impact. Here, we present the first results of a global impact study of RGA. More specifically, we calculated the multiplicator effects of RGA on the research benefits generated by conventional rice breeding programs and applied them to a meta-analysis of selected impact studies in the literature. These insights are a first crucial step in developing a targeted approach for disseminating RGA technology among rice breeders to accelerate the impact of their public rice breeding programs around the world. We show that the additional benefits due to time savings are considerable and offer some insights into the economics of breeding. Our results confirm that the adoption of accelerated breeding would lead to substantial advantages to rice breeding programs and the earlier variety release leads to significant economic benefits to society. This can be important to policy makers when reshaping their public breeding methods and optimising their return on research investments in breeding.
Keys Under the Welcome Mat 6 . 857 Final Project Report

The inspiration for this project was a description of a security flaw in Snapchat, published on the internet. [1] The idea behind the Snapchat application is that pictures sent to and from users will disappear within ten seconds of being opened. However, rather than being erased from the device, images are actually stored permanently in device memory unless manually deleted. Snapchat uses two methods to prevent users from viewing these images. First, its UI does not allow them to open these images. Second, if a user tries to manually open the image from their disk, they will discover that Snapchat has encrypted it. Unfortunately, Snapchat encrypts these images using the encryption key ”M02cnQ51Ji97vwT4,” which has been hard-coded into the application. Once this key is found and known, any user can use it to decrypt these images, accessing images they’re not meant to be able to see. We were easily able to find this key ourselves in the source code, and thus the idea for our project was born. With the rapid iteration and agile development style of current software development, new versions of apps get rolled out week to week. With such a fast paced environment, it makes sense that some security may be overlooked and things like hard-coded encryption keys may happen. The purpose of this project was to perform a broad security survey of Android applications as well as a more in-depth look at security vulnerabilities in Snapchat. We would begin by looking for similarly hard-coded encryption strings but expand to look for other security flaws such as the use of depricated algorithms.
Pre-Service Teachers’ Perspectives on How the Use of TOON Comic Books during Guided Reading Influenced Learning by Struggling Readers

Samantha McGeorge Daughtrey Elementary School, mcgeorges@manateeschools.net Follow this and additional works at: https://digitalcommons.unl. edu/sane Part of the American Literature Commons, American Popular Culture Commons, Art Education Commons, Comparative Literature Commons, Creative Writing Commons, Curriculum and Instruction Commons, Educational Assessment, Evaluation, and Research Commons, Educational Methods Commons, Educational Psychology Commons, Feminist, Gender, and Sexuality Studies Commons, Higher Education Commons, Illustration Commons, Interdisciplinary Arts and Media Commons, Other Teacher Education and Professional Development Commons, Rhetoric and Composition Commons, and the Visual Studies Commons
Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis

Osteoarthritis (OA) significantly influences the quality life of people around the world. It is urgent to find an effective way to understand the genetic etiology of OA. We used weighted gene coexpression network analysis (WGCNA) to explore the key genes involved in the subchondral bone pathological process of OA. Fifty gene expression profiles of GSE51588 were downloaded from the Gene Expression Omnibus database. The OA‐associated genes and gene ontologies were acquired from JuniorDoc. Weighted gene coexpression network analysis was used to find disease‐related networks based on 21756 gene expression correlation coefficients, hub‐genes with the highest connectivity in each module were selected, and the correlation between module eigengene and clinical traits was calculated. The genes in the traits‐related gene coexpression modules were subject to functional annotation and pathway enrichment analysis using ClusterProfiler. A total of 73 gene modules were identified, of which, 12 modules were found with high connectivity with clinical traits. Five modules were found with enriched OA‐associated genes. Moreover, 310 OA‐associated genes were found, and 34 of them were among hub‐genes in each module. Consequently, enrichment results indicated some key metabolic pathways, such as extracellular matrix (ECM)‐receptor interaction (hsa04512), focal adhesion (hsa04510), the phosphatidylinositol 3'‐kinase (PI3K)‐Akt signaling pathway (PI3K‐AKT) (hsa04151), transforming growth factor beta pathway, and Wnt pathway. We intended to identify some core genes, collagen (COL)6A3, COL6A1, ITGA11, BAMBI, and HCK, which could influence downstream signaling pathways once they were activated. In this study, we identified important genes within key coexpression modules, which associate with a pathological process of subchondral bone in OA. Functional analysis results could provide important information to understand the mechanism of OA.
Female Futsal Players’ Profile and Biochemical Alterations through Intermittent High-Intensity Exercise Training

The aim of the study was to determine the physical, physiological and nutritionalcharacteristics of female futsal players and selected markers of oxidative stress after their exercise training (Loughborough Intermittent Shuttle Test). Eight health female futsal players (age 21.3 ± 3.2 years, body mass 64.5 ± 5.6 kg, height 169.5 ± 6.5 cm, body mass index 22.45 ± 2.25 kg/m2; mean ± SD) participated in this study. Blood samples were collected before, during and immediately after the exercise for glucose, lactate, ascorbic acid, total plasma antioxidant potential, lipid hydroperoxides, malondialdehyde and creatine kinase concentrations. Female futsal players appeared to meet caloric needs but failed to meet minimum carbohydrate and vitamin A, C and E recommendations. Immediately after the exercise there were an increase in lipid hydroperoxides (ranging from 9.32 ± 1.86 μmol? L–1 to 13.02 ± 1.62 μmol? L–1, p –11 to 3.29 ± 0.62 nmol? L–1, p –1 to 185.59 ± 6.96 U.I.L–1, p < 0.05). In parallel, ascorbic acid and total plasma antioxidant potential had a slight decrease during and after exercise. Considering that alterations in oxidative stress parameters associated with inadequate ingestion of nutrients can affect health and performance of game players, further studies are needed to evalu- ate the inclusion of an nutritional education program and extent of biochemical changes through athlete’s recovery pe- riod.
Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used “survival” model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed.
Disentangling nonradiative recombination processes in Ge micro-crystals on Si substrates

We address nonradiative recombination pathways by leveraging surface passivation and dislocation management in μm-scale arrays of Ge crystals grown on deeply patterned Si substrates. The time decay photoluminescence (PL) at cryogenic temperatures discloses carrier lifetimes approaching 45 ns in band-gap engineered Ge micro-crystals. This investigation provides compelling information about the competitive interplay between the radiative band-edge transitions and the trapping of carriers by dislocations and free surfaces. Furthermore, an in-depth analysis of the temperature dependence of the PL, combined with capacitance data and finite difference time domain modeling, demonstrates the effectiveness of GeO2 in passivating the surface of Ge and thus in enhancing the room temperature PL emission.
Critical Event Intervals in Determining Candidacy for Intravenous Thrombolysis in Acute Stroke

Background The aim of the study was to determine the optimal set point for the critical event benchmarks described in stroke guidelines and validate the ability of these goals to predict successful administration of intravenous thrombolysis within 60 min of hospital arrival. Methods This was a retrospective cohort analysis of patients with acute ischemic stroke who received intravenous thrombolysis following presentation to the emergency department. The national benchmarks for time intervals associated with the completion of critical events required to determine candidacy for thrombolysis were evaluated for the ability to predict successful administration of thrombolysis within 60 min of hospital arrival. Optimal time interval cut points were then estimated using regression and receiver-operator characteristic curve analysis and compared to guidelines. Results Of the 523 patients included in the analysis, 229 (43.8%) received intravenous thrombolysis within 60 min of hospital arrival. Of the patients who met the critical event interval goals described in guidelines, only 51.6% received thrombolysis within 60 min. The optimized cut points suggested by the regression analysis aligned with the guideline benchmarks with the only substantial difference being a shortened goal of arrival to neuroimaging start time of 19 min. This difference did not impact the overall predictive value. Conclusion The critical event benchmarks proposed in this study by logistic regression closely correlate with the critical event benchmarks described in the AHA/ASA acute stroke guidelines.
Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice

Bifurcation of axons from dorsal root ganglion (DRG) and cranial sensory ganglion (CSG) neurons is mediated by a cGMP-dependent signaling pathway composed of the ligand C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2 and the cGMP-dependent protein kinase I (cGKI). Here, we demonstrate that mesencephalic trigeminal neurons (MTN) which are the only somatosensory neurons whose cell bodies are located within the CNS co-express Npr2 and cGKI. Afferents of MTNs form Y-shaped branches in rhombomere 2 where the ligand CNP is expressed. Analyzing mouse mutants deficient for CNP or Npr2 we found that in the absence of CNP-induced cGMP signaling MTN afferents no longer bifurcate and instead extend either into the trigeminal root or caudally in the hindbrain. Since MTNs provide sensory information from jaw closing muscles and periodontal ligaments we measured the bite force of conditional mouse mutants of Npr2 (Npr2flox/flox;Engr1Cre) that lack bifurcation of MTN whereas the bifurcation of trigeminal afferents is normal. Our study revealed that the maximal biting force of both sexes is reduced in Npr2flox/flox;Engr1Cre mice as compared to their Npr2flox/flox littermate controls. In conclusion sensory feedback mechanisms from jaw closing muscles or periodontal ligaments might be impaired in the absence of MTN axon bifurcation.
Use of the WHO’s Perceived Well-Being Index (WHO-5) as an Efficient and Potentially Valid Screen for Depression in a Low Income Country

Introduction: Depression is associated with negative social, economic, and family outcomes and the majority of individuals with depression in low and middle income countries (LMICs) are untreated. A critical first step in bridging the treatment gap is accurate, feasible, and culturally appropriate screening to identify those who need treatment. The WHO’s Perceived Well-Being Index (WHO-5) well-being instrument can potentially meet the screening needs of LMICs in primary care and community-based settings. This study tested the feasibility and validity of this tool to identify depression among adult parents of young children in Addis Ababa, Ethiopia. Successful identification and treatment of depression in parents extends benefits to children and families. Method: The WHO-5 was translated to Amharic and administered to 849 adults and compared with simultaneous administration of the well-established PHQ-9 instrument. Feasibility was assessed and analyses evaluated frequency of positive screens for depression, internal consistency, sensitivity and specificity of the WHO-5, and sociodemographic correlates of depression. Results: The prevalence of probable depression was similar as assessed by the PHQ-9 (17.3%) and the WHO-5 (18.5%). The internal consistency of the WHO-5 was strong (Cronbach’s alpha = .83). WHO-5 agreement with the PHQ-9 was moderate; sensitivity and specificity were strong. Correlates of depression included unemployment and financial status. Discussion: The study provides promising evidence to support use of the WHO-5 to identify depression in Ethiopia. Feasibility was good, and it was culturally and linguistically acceptable. The results suggest that minimally trained community health and education workers in countries like Ethiopia could use the WHO-5 effectively in primary health and education settings.
Imaging Investigation of Thyroid Eye Disease.

INTRODUCTION Thyroid eye disease (TED), is a term referring to the extrathyroidal manifestation of Grave's disease, a disorder which is currently the most common cause of hyperthyroidism and is characterised by underlying autoimmunity.The pathogenic course of the disease can be broadly classified into two stages, an early inflammatory and a late fibrotic stage. These stages are reflected in clinical severity and activity classifications, such as Clinical Activity Score and Class 0: No signs or symptoms, 1: Only signs, no symptoms (e. g. lid retraction), 2: Soft tissue involvement, 3: Proptosis, 4: Extraocular muscle involvement, 5: Corneal involvement, 6: Sight loss (NOSPECS). Classifications based on the latter, have important implications in treatment decisions since patients in the early active stage of the disease are more likely to respond to anti-inflammatory and immunosuppressive therapies, whereas patients in the late fibrotic stage require different therapeutic approaches, including rehabilitative surgery. METHODS We reviewed cases of TED investigated with CT and Magnetic Resonance Imaging (MRI) in our department. We assessed the findings of imaging studies and their role in the clinical investigation of patients with TED as well as in the differential diagnosis from other disorders. RESULTS Imaging has a significant role in the investigation of TED, however a consensus on the use of different imaging modalities in the course of disease has yet to be reached. Nevertheless, imaging and specifically CT and MRI can have a vital role in the initial diagnosis of clinically atypical presentation of TED, in surgical planning, as well as in the differential diagnosis from other orbital disorders. CONCLUSION In this review, we attempt to present current trends in imaging investigation of TED. Rather than focusing on the findings of each imaging modality separately, we present the two main imaging modalities focusing on CT and MRI, in the context of pathogenic stages of the disease.