Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender Differences in Murine Airway Responsiveness and Lipopolysaccharide-Induced Inflammation1

The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-α content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens.
Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine

We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA‐Seq data from ‘BrainSpan’ was obtained across 16 brain regions from nine control adults. We also generated RNA‐Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up‐regulated in both alcoholics and cocaine addicts (FDR corrected P = 0.008). Alcoholics showed up‐regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up‐regulated in alcoholics and down‐regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up‐regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit.
A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease

We studied the outcome of 436 patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) who underwent orthotopic liver transplant (OLT) at three major liver transplant centers. Univariate predictors of outcome included age, Karnofsky score, Child's class, Mayo risk score, United Network for Organ Sharing (UNOS) status, nutritional status, serum albumin, serum bilirubin, international normalized ratio, and the presence of ascites, encephalopathy, renal failure (serum creatinine > 2 mg/dL), and edema refractory to diuretics. Using these predictors, we developed a four variable mathematical prognostic model to help the liver transplant physician predict the following: (1) the amount of intraoperative blood loss; (2) the number of days in the intensive care unit (ICU); and (3) severe complications after surgery. The model uses age, renal failure, Child's class, and United Network for Organ Sharing status. This study is the first to model the outcome of liver transplant in patients with a specific etiology of chronic liver disease (PBC or PSC). The model may be used to help select patients for OLT and to plan the timing of their transplantation.
Parental Dietary Fat Intake Alters Offspring Microbiome and Immunity

Mechanisms underlying modern increases in prevalence of human inflammatory diseases remain unclear. The hygiene hypothesis postulates that decreased microbial exposure has, in part, driven this immune dysregulation. However, dietary fatty acids also influence immunity, partially through modulation of responses to microbes. Prior reports have described the direct effects of high-fat diets on the gut microbiome and inflammation, and some have additionally shown metabolic consequences for offspring. Our study sought to expand on these previous observations to identify the effects of parental diet on offspring immunity using mouse models to provide insights into challenging aspects of human health. To test the hypothesis that parental dietary fat consumption during gestation and lactation influences offspring immunity, we compared pups of mice fed either a Western diet (WD) fatty acid profile or a standard low-fat diet. All pups were weaned onto the control diet to specifically test the effects of early developmental fat exposure on immune development. Pups from WD breeders were not obese or diabetic, but still had worse outcomes in models of infection, autoimmunity, and allergic sensitization. They had heightened colonic inflammatory responses, with increased circulating bacterial LPS and muted systemic LPS responsiveness. These deleterious impacts of the WD were associated with alterations of the offspring gut microbiome. These results indicate that parental fat consumption can leave a “lard legacy” impacting offspring immunity and suggest inheritable microbiota may contribute to the modern patterns of human health and disease.
Tag contrast in breath‐hold CINE cardiac MRI

Contrast between tagged and nontagged myocardium was investigated using rapid gradient echo segmented k‐space CINE MRI. The transient behavior of magnetization was measured in stationary and moving phantoms using gradient recalled acquisition in steady‐state GRASS and spoiled GRASS (SPGR) sequences with TR ≈ 7 ms and TE ≈ 2.5 ms. Bloch equation simulations were used to compute theoretical results. Understanding the transient behavior of magnetization is important because tags only persist in the myocardium during the nonequilibrium transition to steady state. The transition to steady state for both SPGR and GRASS is reproducible after one heartbeat, and including unprocessed data from the first heartbeat leads to image artifacts. In a moving phantom, simulations and experimental results showed that GRASS and SPGR are essentially equivalent. Tag‐tissue contrast in SPGR was very sensitive to imaging tip angle. The optimum tip angle for the scanning parameters used in this study was 11°.
Improved Identification of von Hippel-Lindau Gene Alterations in Clear Cell Renal Tumors

Purpose: To provide a comprehensive, thorough analysis of somatic mutation and promoter hypermethylation of the von Hippel-Lindau (VHL) gene in the cancer genome, unique to clear cell renal cancer (ccRCC). Identify relationships between the prevalence of VHL gene alterations and alteration subtypes with patient and tumor characteristics. Experimental Design: As part of a large kidney cancer case-control study conducted in Central Europe, we analyzed VHL mutations and promoter methylation in 205 well-characterized, histologically confirmed patient tumor biopsies using a combination of sensitive, high-throughput methods (endonuclease scanning and Sanger sequencing) and analysis of 11 CpG sites in the VHL promoter. Results: We identified mutations in 82.4% of cases, the highest VHL gene mutation prevalence reported to date. Analysis of 11 VHL promoter CpG sites revealed that 8.3% of tumors were hypermethylated and all were mutation negative. In total, 91% of ccRCCs exhibited alteration of the gene through genetic or epigenetic mechanisms. Analysis of patient and tumor characteristics revealed that certain mutation subtypes were significantly associated with Fuhrman nuclear grade, metastasis, node positivity, and self-reported family history of RCC. Conclusion: Detection of VHL gene alterations using these accurate, sensitive, and practical methods provides evidence that the vast majority of histologically confirmed ccRCC tumors possess genetic or epigenetic alteration of the VHL gene and support the hypothesis that VHL alteration is an early event in ccRCC carcinogenesis. These findings also indicate that VHL molecular subtypes can provide a sensitive marker of tumor heterogeneity among histologically similar ccRCC cases for etiologic, prognostic, and translational studies.
Travel Itinerary Recommendations with Must-see Points-of-Interest

Travelling and touring are popular leisure activities enjoyed by millions of tourists around the world. However, the task of travel itinerary recommendation and planning is tedious and challenging for tourists, who are often unfamiliar with the various Points-of-Interest (POIs) in a city. Apart from identifying popular POIs, the tourist needs to construct a travel itinerary comprising a subset of these POIs, and to order these POIs as a sequence of visits that can be completed within his/her available touring time. For a more realistic itinerary, the tourist also has to account for travelling time between POIs and visiting times at individual POIs. Furthermore, this itinerary should incorporate tourist preferences such as desired starting and ending POIs (e.g., POIs that are near the tourist's hotel) and a subset of must-see POIs (e.g., popular POIs that a tourist must visit). We term this the TourMustSee problem, which is based on a variant of the Orienteering problem. Following which, we propose the LP+M algorithm for solving the TourMustSee problem as an Integer Linear Program (ILP). Using a Flickr dataset of POI visits in seven touristic cities, we compare LP+M against various ILP-based baselines, and the results show that LP+M recommends better travel itineraries in terms of POI popularity, total POIs visited, total touring time utilized and must-visit POI(s) inclusion.
Java Applet Awareness Impacting User Web Browsing Behavior

The purpose of this study is to investigate the web browsing behaviors of computer users and how awareness about threats impacts their behaviors. This research focused on how users behave towards web browser alerts which prompt users to install Java Applets. Applets have become common tools for enhancing user experience. However, installing these features overrides security mechanisms inherent in browsers and provides complete access to users’ computing resources. A survey was administered to two separate groups of students from the University of Massachusetts Boston to collect data. The first group took the survey after being given a few details about the study. The same survey was then given to a second set of students after they watched a video. The video educated participants on the dangers of installing Java Applets. Results showed that after watching the video participants had increased Java Applet Security Awareness and Information Security Awareness. This study can inform management on effective training procedures to improve compliance with security.
The mucosal barrier and immune activation in HIV pathogenesis

Purpose of review Significant gastrointestinal pathology occurs in progressive HIV and simian immunodeficiency virus (SIV) infections. This review will examine the relationship between the detrimental events to the gastrointestinal tract during the acute phase of infection and disease progression through the chronic phase and, ultimately, AIDS. Recent findings Gastrointestinal tract CD4 T cells are dramatically depleted in acutely HIV-infected humans and SIV-infected rhesus macaques, sooty mangabeys, and African green monkeys. In addition HIV infection of humans and SIV-infection of rhesus macaques are characterized by enteropathy and increased intestinal permeability. While SIV-infected rhesus macaques and HIV-infected humans manifest chronic and systemic immune activation and microbial translocation, and progress to chronic infection and AIDS, however, SIV-infected sooty mangabeys and African green monkeys do not. Summary Recent studies have increased our understanding of the mechanisms relating structural and immunological damage to the gastrointestinal tract during the acute phase of HIV/SIV infection to immune activation and disease progression in the chronic phase.
Sequential Signaling Crosstalk Regulates Endomesoderm Segregation in Sea Urchin Embryos

Lineage Identity Segregation of endoderm and mesoderm lineages is a fundamental event in early embryogenesis. Using sea urchin embryos, Sethi et al. (p. 590) found that Notch and canonical Wnt pathways crosstalk progressively partitions the endomesoderm to discrete endoderm and mesoderm fates. This three-step signaling exchange demonstrates how the timing of signaling crosstalk is regulated in vivo through temporally and spatially staggered genetic circuits that intersect only at specific developmental stages. Separation of deuterostome endoderm and mesoderm occurs through sequential interactions between Notch and Wnt signaling. The segregation of embryonic endomesoderm into separate endoderm and mesoderm fates is not well understood in deuterostomes. Using sea urchin embryos, we showed that Notch signaling initiates segregation of the endomesoderm precursor field by inhibiting expression of a key endoderm transcription factor in presumptive mesoderm. The regulatory circuit activated by this transcription factor subsequently maintains transcription of a canonical Wnt (cWnt) ligand only in endoderm precursors. This cWnt ligand reinforces the endoderm state, amplifying the distinction between emerging endoderm and mesoderm. Before gastrulation, Notch-dependent nuclear export of an essential β-catenin transcriptional coactivator from mesoderm renders it refractory to cWnt signals, insulating it against an endoderm fate. Thus, we report that endomesoderm segregation is a progressive process, requiring a succession of regulatory interactions between cWnt and Notch signaling.
The protective effect of melatonin in lungs of newborn rats exposed to maternal nicotine

Abstract We investigated possible healing effects of melatonin (MEL) on biochemical and histological changes in the lungs of rat offspring caused by exposure to nicotine (NT) in utero. Pregnant rats were divided randomly into five groups. The SP group was treated with physiological saline. The EA group was treated with ethyl alcohol. The MEL group was treated with MEL. The NT group was treated with NT. The NT + MEL group was treated with NT and MEL. At the end of the study, the biochemistry and histopathology of lung tissue of the offspring were examined. Reduced alveolar development and increased numbers of alveolar macrophages and mast cells were observed in the NT group compared to the SP, EA and MEL groups. We also found increased malondialdehyde (MDA) levels and decreased total glutathione (GSH) levels in the NT group. Application of MEL ameliorated the histological and biochemical damage caused by NT. The number of alveoli was greater in the NT + MEL group than in the NT group. Also, the increased numbers of alveolar macrophages and mast cells resulting from exposure to NT were decreased following MEL treatment. We found that MEL caused a significant decrease in the level of MDA. Maternal exposure to NT caused significant structural and biochemical changes in the lungs of the offspring and administration of MEL ameliorated the changes.
Edinburgh Research Explorer Susceptibility and immunity to helminth parasites

Parasitic helminth infection remains a global health problem, whilst the ability of worms to manipulate and dampen the host immune system is attracting interest in the ﬁelds of allergy and autoimmunity. Much progress has been made in the last two years in determining the cells and cytokines involved in induction of Type 2 immunity, which is generally protective against helminth infection. Innate cells respond to ‘alarmin’ cytokines (IL-25, IL-33, TSLP) by producing IL-4, IL-5 and IL-13, and this sets the stage for a more potent subsequent adaptive Th2 response. CD4 + Th2 cells then drive a suite of type 2 anti-parasite mechanisms, including class-switched antibodies, activated leukocytes and innate defence molecules; the concerted effects of these multiple pathways disable, degrade and dislodge parasites, leading to their destruction or expulsion.
Floquet Fulde-Ferrell-Larkin-Ovchinnikov superfluids and Majorana fermions in a shaken fermionic optical lattice

Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superfluids, Cooper pairings with finite momentum, and Majorana fermions (MFs), quasiparticles with non-Abelian exchange statistics, are two topics under intensive investigation in the past several decades, but unambiguous experimental evidences for them have not been found yet in any physical system. Here we show that the recent experimentally realized cold atom shaken optical lattice provides a new pathway to realize FFLO superfluids and MFs. By tuning shaken lattice parameters (shaking frequency and amplitude), various coupling between the s- and p-orbitals of the lattice (denoted as the pseudo-spins) can be generated. We show that the combination of the inverted s- and p-band dispersions, the engineered pseudo-spin coupling, and the attractive on-site atom interaction, naturally allows the observation of FFLO superfluids as well as MFs in different parameter regions. While without interaction the system is a topological insulator (TI) with edge states, the MFs in the superfluid may be found to be in the conduction or valence band, distinguished from previous TI-based schemes that utilize edge states inside the band gap.
Evolutionary dynamics of olfactory receptor genes in Drosophila species

Olfactory receptor (OR) genes are of vital importance for animals to find food, identify mates, and avoid dangers. In mammals, the number of OR genes is large and varies extensively among different orders, whereas, in insects, the extent of interspecific variation appears to be small, although only a few species have been studied. To understand the evolutionary changes of OR genes, we identified all OR genes from 12 Drosophila species, of which the evolutionary time is roughly equivalent to that of eutherian mammals. The results showed that all species examined have similar numbers (≈60) of functional OR genes. Phylogenetic analysis indicated that the ancestral species also had similar numbers of genes, but there were frequent gains and losses of genes that occurred in each evolutionary lineage. It appears that tandem duplication and random inactivation of duplicate genes are the major factors of gene number change. However, chromosomal rearrangements have contributed to the establishment of genome-wide distribution of OR genes. These results suggest that the repertoire of OR genes in Drosophila has been quite stable compared with the mammalian genes. The difference in evolutionary pattern between Drosophila and mammals can be explained partly by the differences of gene expression mechanisms and partly by the environmental and behavioral differences.
Writing supports for older students with significant disabilities: examining two students' journeys towards becoming writers

This study describes the changes in linguistic and social communicative competencies that occurred when two older students with significant disabilities where provided with writing opportunities, instruction, and supports over a semester of the academic year. The goals of the study were to identify themes and patterns in the skills associated with linguistic and social communicative competence as evidenced in writing over time. A second aim of this study was to identify instruction methods and assistive technology supports being used in the classroom and describes the themes and patterns that emerged in the students’ writing given the presence of these curriculum components. Video and writing samples from the two students were collected and analyzed using a checklist of selected linguistic and social skills from the formal assessment, Augmentative and Alternative Communication Profiles. The checklist was determined to be not sensitive to the subtle changes in linguistic and social communication competence skills that were seen over time frame of this study. Themes of engagement with the writing process and access methods became evident and were explored. Instruction and opportunities in the areas of revision and writing for different audiences and purposes were identified as critical components of the writing process that were not addressed consistently for the two participants studied. Overall, the two students in this study demonstrated improvements in linguistic and social communication skills with the addition of writing instruction and support. WRITING SUPPORTS FOR OLDER STUDENTS’ WITH SIGNIFICANT DISABILITIES: EXAMINING TWO STUDENTS JOURNEYS TOWARDS BECOMING WRITERS A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree Master of Arts Emily Helen Freeman University of Northern Iowa December 2013
Micro-CT Evaluation of Gutta-Percha Removal by Two Retreatment Systems

Introduction: The aim of the present ex vivo research was to compare the remaining filling material and the volumes of dentine removed after retreatment of curved canals with two rotary systems naming ProTaper Universal Retreatment and Mani NRT-GPR using micro-computed tomography (micro-CT). Methods and Material: Forty mandibular molars containing two completely separated canals, with curvature angle of 25-35° and a curvature radius <10 mm were prepared to the Mtwo instrument 35/0.04 and filled with warm gutta-percha and AH-Plus sealer. The teeth were randomly divided into 2 groups (n=20), according to the retreatment system evaluated: ProTaper Universal Retreatment (PR group) or Mani NRT-GPR (MR group). Retreatment was considered complete when the working length was reached and when smooth dentinal walls were observed, with no evidence of filling material adhered to instruments or in the irrigating solution. Preoperative and postoperative micro-CT images were obtained with an isotropic voxel size of 11.88 µm to observe the volume of residual filling material in the canals and dentine removed after retreatment. Statistical analysis was performed by Student’s t-test (P<0.05). Results: The mean percentage of remaining filling material was 12.96% for PR group and 24.26% for MR group (P=0.0056). The percentage of dentin removal was greater in the PR group (5.02%) than MR group (1.36%) (P=0.0028). Both systems failed to completely remove the filling material from the canals. Conclusion: ProTaper Universal Retreatment system was more effective than Mani NRT-GPR system regarding removal of root filling material and also removed significantly more dentine after retreatment of curved mesial root canals of mandibular molars.