Miracle-dz/UniFAR-FTUs huggingface dataset:
Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct in vivo evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein‐mediated assembly of newly engineered split‐effectors, allowing selective targeting of dual‐marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co‐expression of bronchiolar and alveolar epithelial genes. We found that BASCs generate the majority of distal lung airway cells after bronchiolar damage but only moderately contribute to cellular turnover under homeostatic conditions. Importantly, DTA‐mediated ablation of BASCs compromised proper regeneration of distal airways. The study defines BASCs as crucial components of the lung repair machinery and provides a paradigmatic example for the detection and manipulation of stem cells that cannot be recognized by a single marker alone.
Modulation of Adipose Tissue Development by Pharmacological Inhibition of PAI-1

Objective—The effect of a novel small molecule plasminogen activator inhibitor (PAI-1) inhibitor on adipose tissue physiology was investigated. Methods and Results—In human preadipocyte cultures, PAI-039 inhibited both basal and glucose-stimulated increases in active PAI-1 antigen, yet had no effect on PAI-1 mRNA, suggesting a direct inactivation of PAI-1. Differentiation of human preadipocytes to adipocytes was associated with leptin synthesis, which was significantly reduced in the presence of PAI-039, together with an atypical adipocyte morphology characterized by a reduction in the size and number of lipid containing vesicles. In a model of diet-induced obesity, pair-fed C57 Bl/6 mice administered PAI-039 in a high-fat diet exhibited a dose-dependent reduction in body weight, epididymal adipose tissue weight, adipocyte volume, and circulating plasma active PAI-1. Plasma glucose, triglycerides, and leptin were also significantly reduced in drug-treated mice, and concentrations of PAI-039 associated with these physiological effects were near the in vitro IC50 for the inhibition of PAI-1. Conclusions—Our results indicate that a small molecule inactivator of PAI-1 can neutralize glucose-stimulated increases in PAI-1in human preadipocyte cultures, reduce adipocyte differentiation, and prevent the development of diet-induced obesity. These data suggest the pharmacological inhibition of PAI-1 could be beneficial in diseases associated with expansion of adipose tissue mass.
Dental Plaque as a Microbial Biofilm

New technologies have provided novel insights into how dental plaque functions as a biofilm. Confocal microscopy has confirmed that plaque has an open architecture similar to other biofilms, with channels and voids. Gradients develop in areas of dense biomass over short distances in key parameters that influence microbial growth and distribution. Bacteria exhibit an altered pattern of gene expression either as a direct result of being on a surface or indirectly as a response to the local environmental heterogeneity within the biofilm. Bacteria communicate via small diffusible signalling molecules (e.g. competence-stimulating peptide, CSP; autoinducer 2); CSP induces both genetic competence and acid tolerance in recipient sessile cells. Thus, rates of gene transfer increase in biofilm communities, and this is one of several mechanisms (others include: diffusion-reaction, neutralization/inactivation, slow growth rates, novel phenotype) that contribute to the increased antimicrobial resistance exhibited by bacteria in biofilms. Oral bacteria in plaque do not exist as independent entities but function as a co-ordinated, spatially organized and fully metabolically integrated microbial community, the properties of which are greater than the sum of the component species. A greater understanding of the significance of dental plaque as a mixed culture biofilm will lead to novel control strategies.
Analyzing the Potential Risk of Climate Change on Lyme Disease in Eastern Ontario, Canada Using Time Series Remotely Sensed Temperature Data and Tick Population Modelling

The number of Lyme disease cases (Lyme borreliosis) in Ontario, Canada has increased over the last decade, and that figure is projected to continue to increase. The northern limit of Lyme disease cases has also been progressing northward from the northeastern United States into southeastern Ontario. Several factors such as climate change, changes in host abundance, host and vector migration, or possibly a combination of these factors likely contribute to the emergence of Lyme disease cases in eastern Ontario. This study first determined areas of warming using time series remotely sensed temperature data within Ontario, then analyzed possible spatial-temporal changes in Lyme disease risk in eastern Ontario from 2000 to 2013 due to climate change using tick population modeling. The outputs of the model were validated by using tick surveillance data from 2002 to 2012. Our results indicated areas in Ontario where Lyme disease risk changed from unsustainable to sustainable for sustaining Ixodes scapularis (black-legged tick) populations. This study provides evidence that climate change has facilitated the northward expansion of black-legged tick populations’ geographic range over the past decade. The results demonstrate that remote sensing data can be used to increase the spatial detail for Lyme disease risk mapping and provide risk maps for better awareness of possible Lyme disease cases. Further studies are required to determine the contribution of host migration and abundance on changes in eastern Ontario’s Lyme disease risk.
Challenges in the better, faster, cheaper era of aeronautical design, engineering and manufacturing

Abstract 'Better, faster, cheaper’ (BFC) emerged in the 1990s as a new paradigm for aerospace products. In this paper, we examine some of the underlying reasons for BFC and offer some thoughts to help frame the thinking and action of aerospace industry professionals in this new era. Examination of literature on industrial innovation indicates that aeronautical products have evolved to a ‘dominant design’ and entered the ‘specific phase’ of their product life cycle. Innovation in this phase centers on: incremental product improvement, especially for productivity and quality; process technology; technological innovations that offer superior substitutes. The first two of these are aligned with BFC objectives. The concepts of ‘value’ and ‘best lifecycle value’ are introduced as conceptual frameworks. Value is offered as a metric for BFC. Risk management is intimately tied to achieving value and needs to be integrated into aeronautical processes. The process technology area is addressed by considering ‘lean’ practices for design, engineering and manufacturing. Illustrative results of process improvements from the seven-year Lean Aerospace Initiative research programme at MIT indicate opportunities to achieve BFC. Concluding remarks offer some challenges to industry, government and academics in aeronautical design, engineering and manufacturing.
Serum Soluble Mesothelin Concentrations in Malignant Pleural Mesothelioma: Relationship to Tumor Volume, Clinical Stage and Changes in Tumor Burden

Purpose: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma. Experimental Design: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival. Results: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20–4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ2 = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001). Conclusion: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma. Clin Cancer Res; 17(5); 1181–9. ©2010 AACR.
Age‐Related Differences of Organism‐Specific Peritonitis Rates: A Single‐Center Experience

Peritonitis remains an important cause of morbidity and mortality in peritoneal dialysis (PD) patients, but its incidence and the distribution of causative organisms vary widely between institutions and age groups. This study was performed to investigate the recent status and risk factors of PD‐related peritonitis and to clarify differences between age groups. We retrospectively reviewed the medical records of 119 PD patients treated at our department between January 2002 and January 2013. We calculated both overall and organism‐specific peritonitis rates and also analyzed risk factors. Sixty‐three episodes of peritonitis occurred during 261.5 patient‐years for an incident rate of 0.24 episodes/patient‐year. Multivariate analysis showed that older age (≥65 years) and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (≥65 years old), the rate of peritonitis due to Gram‐positive and Gram‐negative bacteria was 0.17 and 0.08 episodes/patient‐year, respectively, and Gram‐positive peritonitis was markedly more frequent than in younger patients (<65 years old). In particular, there was a high frequency of Staphylococcus aureus peritonitis in elderly patients (0.09 episodes/patient‐year) and it had a poor outcome. At our department, the risk of peritonitis was increased in older patients and patients with hypoalbuminemia. The distribution of causative organisms was markedly different between age groups and analysis of organism‐specific peritonitis rates helped to identify current problems with our PD program.
Long-term disturbance dynamics and resilience of tropical peat swamp forests

The coastal peat swamp forests of Sarawak, Malaysian Borneo, are undergoing rapid conversion, predominantly into oil palm plantations. This wetland ecosystem is assumed to have experienced insignificant disturbance in the past, persisting under a single ecologically‐stable regime. However, there is limited knowledge of the past disturbance regime, long‐term functioning and fundamentally the resilience of this ecosystem to changing natural and anthropogenic perturbations through time. In this study, long‐term ecological data sets from three degraded peatlands in Sarawak were collected to shed light on peat swamp forest dynamics. Fossil pollen and charcoal were counted in each sedimentary sequence to reconstruct vegetation and investigate responses to past environmental disturbance, both natural and anthropogenic. Results demonstrate that peat swamp forest taxa have dominated these vegetation profiles throughout the last c. 2000‐year period despite the presence of various drivers of disturbance. Evidence for episodes of climatic variability, predominantly linked to ENSO events, and wildfires is present throughout. However, in the last c. 500 years, burning and indicators of human disturbance have elevated beyond past levels at these sites, concurrent with a reduction in peat swamp forest pollen. Two key insights have been gained through this palaeoecological analysis: (i) peat swamp forest vegetation has demonstrated resilience to disturbance caused by burning and climatic variability in Sarawak in the late Holocene, however (ii) coincident with increased fire combined with human impact c. 500 years ago, these communities started to decline. Synthesis. Sarawak's coastal peat swamps have demonstrated resilience to past natural disturbances, with forest vegetation persisting through episodes of fire and climatic variability. However, palaeoecological data presented here suggest that recent, anthropogenic disturbances are of a greater magnitude, causing the observed decline in the peat swamp forest communities in the last c. 500 years and challenging the ecosystem's persistence. This study greatly extends our knowledge of the ecological functioning of these understudied ecosystems, providing baseline information on the past vegetation and its response to disturbance. This understanding is central to developing management strategies that foster resilience in the remaining peat swamp forests and ensure continued provision of services, namely carbon storage, from this globally important ecosystem.
Towards Automatic UAS-Based Snow-Field Monitoring for Microclimate Research

This article presents unmanned aerial system (UAS)-based photogrammetry as an efficient method for the estimation of snow-field parameters, including snow depth, volume, and snow-covered area. Unlike similar studies employing UASs, this method benefits from the rapid development of compact, high-accuracy global navigation satellite system (GNSS) receivers. Our custom-built, multi-sensor system for UAS photogrammetry facilitates attaining centimeter- to decimeter-level object accuracy without deploying ground control points; this technique is generally known as direct georeferencing. The method was demonstrated at Mapa Republiky, a snow field located in the Krkonose, a mountain range in the Czech Republic. The location has attracted the interest of scientists due to its specific characteristics; multiple approaches to snow-field parameter estimation have thus been employed in that area to date. According to the results achieved within this study, the proposed method can be considered the optimum solution since it not only attains superior density and spatial object accuracy (approximately one decimeter) but also significantly reduces the data collection time and, above all, eliminates field work to markedly reduce the health risks associated with avalanches.
Assortative mating without assortative preference

Significance Assortative mating, the tendency of men and women who marry to have similar social characteristics, is a commonly observed phenomenon in human societies. This study shows that assortative mating could result from structural causes independent of human agents’ preference, because unmarried persons who newly enter marriage are systematically different from those who married earlier. Thus, assortative mating could result from selection, not by rational choice, but by the dynamics of social structures. Assortative mating—marriage of a man and a woman with similar social characteristics—is a commonly observed phenomenon. In the existing literature in both sociology and economics, this phenomenon has mainly been attributed to individuals’ conscious preferences for assortative mating. In this paper, we show that patterns of assortative mating may arise from another structural source even if individuals do not have assortative preferences or possess complementary attributes: dynamic processes of marriages in a closed system. For a given cohort of youth in a finite population, as the percentage of married persons increases, unmarried persons who newly enter marriage are systematically different from those who married earlier, giving rise to the phenomenon of assortative mating. We use microsimulation methods to illustrate this dynamic process, using first the conventional deterministic Gale–Shapley model, then a probabilistic Gale–Shapley model, and then two versions of the encounter mating model.
Adverse-Effect Profile of Kava

ABSTRACT The use of alternative therapies has increased substantially over the last decade, particularly for more chronic conditions such as anxiety. Among the most widely used treatments are medicinal herbs, or phytomedicines, such as kava (Piper methysticum), which has demonstrated anxiolytic activity in both animal models and clinical samples. Kava has several advantages over conventional pharmacologic treatments for anxiety—in clinical settings it has been associated with better tolerability and lack of physiologic dependence and withdrawal. However, phytomedicines are not rigorously regulated in the United States and systematically collected safety data are very limited. These issues are a leading concern regarding the safety of medicinal herbs such as kava. In this report, the safety profile for kava is provided, including findings from a study of its use in generalized anxiety disorder. Safety parameters assessed include occurrence of adverse events, withdrawal symptoms, effect on heart rate, blood pressure, laboratory assessments, and sexual function. No differences were found between kava and placebo on any of the parameters evaluated. The data support the safety of kava in treating anxiety at 280 mg kava lactones/day for 4 weeks.
Workflow for analysis of high mass accuracy salivary data set using MaxQuant and ProteinPilot search algorithm

LTQ Orbitrap data analyzed with ProteinPilot can be further improved by MaxQuant raw data processing, which utilizes precursor‐level high mass accuracy data for peak processing and MGF creation. In particular, ProteinPilot results from MaxQuant‐processed peaklists for Orbitrap data sets resulted in improved spectral utilization due to an improved peaklist quality with higher precision and high precursor mass accuracy (HPMA). The output and postsearch analysis tools of both workflows were utilized for previously unexplored features of a three‐dimensional fractionated and hexapeptide library (ProteoMiner) treated whole saliva data set comprising 200 fractions. ProteinPilot's ability to simultaneously predict multiple modifications showed an advantage from ProteoMiner treatment for modified peptide identification. We demonstrate that complementary approaches in the analysis pipeline provide comprehensive results for the whole saliva data set acquired on an LTQ Orbitrap. Overall our results establish a workflow for improved protein identification from high mass accuracy data.
Profile of Cytokine mRNA Expression in Chronic Adult Periodontitis

Chronic inflammation induced by bacteria often leads to host-mediated destruction of tissues adjacent to the sites of microbial insult. The chronic inflammatory process of adult periodontitis results in the destruction of supporting osseous and connective tissues of the teeth. We hypothesized that virulence factors of periodontal pathogens such as lipopolysaccharide stimulate inflammatory cytokine expression by mononuclear cells of the host which contribute to disease development. In this study, to elucidate the role of these cytokines in chronic adult periodontitis, we tested whether the prevalence of mRNA for inflammatory cytokines generally associated with mononuclear phagocytes was higher in diseased than in healthy gingival tissue. Gingival mononuclear cells or whole gingival biopsies from 32 adult periodontitis patients and five healthy individuals used as controls were evaluated for inflammatory cytokine mRNA expression by reverse-transcription polymerase chain-reaction (RT-PCR) procedures. The cytokines assessed included IL-1α, IL-1β, IL-lra, IL-6, IL-8, IL-12, IL-13, TNF-a, TGF-β, and IFN-γ. The monocyte/macrophage lipopolysaccharide (LPS) receptor CD14 was also assessed. Results showed that TNF-α mRNA was present significantly more frequently in diseased than in healthy biopsies, whereas IL-la, IL-1β, and IL-lra mRNA were found in most (from 80 to 100%) healthy tissues. Message for CD14 was present in both healthy and diseased tissue samples (100%). This study provides evidence for a major role of TNF-a in chronic adult periodontitis. Moreover, our results suggest that the mononuclear cells derived from periodontal tissues have the capacity to respond to components of periodontal pathogens and express both pro- and anti-inflammatory cytokines in these tissues.
Harvesting Multiple Sources for User Profile Learning: a Big Data Study

User profile learning, such as mobility and demographic profile learning, is of great importance to various applications. Meanwhile, the rapid growth of multiple social platforms makes it possible to perform a comprehensive user profile learning from different views. However, the research efforts on user profile learning from multiple data sources are still relatively sparse, and there is no large-scale dataset released towards user profile learning. In our study, we contribute such benchmark and perform an initial study on user mobility and demographic profile learning. First, we constructed and released a large-scale multi-source multi-modal dataset from three geographical areas. We then applied our proposed ensemble model on this dataset to learn user profile. Based on our experimental results, we observed that multiple data sources mutually complement each other and their appropriate fusion boosts the user profiling performance.
The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

Objective Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Methods Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. Results In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e−16) and a significant increase in MTR (p-value < 1e−6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics—and not changes in lesions or brain volume—were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.