Ontology-based model abstraction

In recent years, there has been a growth in the use of reference conceptual models to capture information about complex and critical domains. However, as the complexity of domain increases, so does the size and complexity of the models that represent them. Over the years, different techniques for complexity management in large conceptual models have been developed. In particular, several authors have proposed different techniques for model abstraction. In this paper, we leverage on the ontologically well-founded semantics of the modeling language OntoUML to propose a novel approach for model abstraction in conceptual models. We provide a precise definition for a set of Graph-Rewriting rules that can automatically produce much-reduced versions of OntoUML models that concentrate the models’ information content around the ontologically essential types in that domain, i.e., the so-called Kinds. The approach has been implemented using a model-based editor and tested over a repository of OntoUML models

Image Schemas and Conceptual Dependency Primitives: A Comparison

A major challenge in natural language understanding research in artificial intelligence (AI) has been and still is the grounding of symbols in a representation that allows for rich semantic interpretation, inference, and deduction. Across cognitive linguistics and other disciplines, a number of principled methods for meaning representation of natural language have been proposed that aim to emulate capacities of human cognition. However, little cross-fertilization among those methods has taken place. A joint effort of human-level meaning representation from AI research and from cognitive linguistics holds the potential of contributing new insights to this profound challenge. To this end, this paper presents a first comparison of image schemas to an AI meaning representation system called Conceptual Dependency (CD). Restricting our study to the domain of physical and spatial conceptual primitives, we find connections and mappings from a set of action primitives in CD to a remarkably similar set of image schemas. We also discuss important implications of this connection, from formalizing image schemas to improving meaning representation systems in AI

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation

Heme oxygenase-1 derived carbon monoxide permits maturation of myeloid cells

Critical functions of the immune system are maintained by the ability of myeloid progenitors to differentiate and mature into macrophages. We hypothesized that the cytoprotective gas molecule carbon monoxide (CO), generated endogenously by heme oxygenases (HO), promotes differentiation of progenitors into functional macrophages. Deletion of HO-1, specifically in the myeloid lineage (Lyz-Cre:Hmox1flfl), attenuated the ability of myeloid progenitors to differentiate toward macrophages and decreased the expression of macrophage markers, CD14 and macrophage colony-stimulating factor receptor (MCSFR). We showed that HO-1 and CO induced CD14 expression and efficiently increased expansion and differentiation of myeloid cells into macrophages. Further, CO sensitized myeloid cells to treatment with MCSF at low doses by increasing MCSFR expression, mediated partially through a PI3K-Akt-dependent mechanism. Exposure of mice to CO in a model of marginal bone marrow transplantation significantly improved donor myeloid cell engraftment efficiency, expansion and differentiation, which corresponded to increased serum levels of GM-CSF, IL-1α and MCP-1. Collectively, we conclude that HO-1 and CO in part are critical for myeloid cell differentiation. CO may prove to be a novel therapeutic agent to improve functional recovery of bone marrow cells in patients undergoing irradiation, chemotherapy and/or bone marrow transplantation

Cyclin A1 and P450 aromatase promote metastatic homing and growth of stem-like prostate cancer cells in the bone marrow

Bone metastasis is a leading cause of morbidity and mortality in prostate cancer (PCa). While cancer stem-like cells have been implicated as a cell of origin for PCa metastases, the pathways which enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in PCa metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDHhigh subpopulation of PC3M cells, one model of PCa, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colony forming assays. In the bone marrow, Cyclin A1 and aromatase enhanced local bone marrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted hte metastatic growth of PCa cells. Moreover, ALDHhigh tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired a growth advantage in the presence of host bone marrow cells. Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDHhigh PCa cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases

Limit Cycle Instability of Proton Beams Generated by Nonlinear Electron-Cooling Force

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Landscape and soundscape quality promote stress recovery in nearby urban nature: A multisensory field experiment

Cities have different benefits and risks, but are often stressful environments to live in. Everyday contact with nearby nature can be a crucial way to alleviate stress and increase the well-being of citizens. However, there is still limited evidence on how nature-health benefits vary according to the type and quality of natural environments. This study integrated multiple landscape and soundscape objective and perceived assessments to examine stress recovery in different types of neighbourhood nature. We used a field randomised experiment (n=45) to analyse effects of various random and fixed factors on restoration including: environmental conditions (e.g. temperature, wind, air quality), personal characteristics (e.g. age, gender, perceived health, nature connectedness), presence of other people and environmental quality (e.g. Perceived Environmental Aesthetic Qualities Scale and Perceived Sound Affective Quality scale). We found that physiological and psychological restoration is significantly greater in sites with higher visual (% visual natural elements) and acoustic (Normalized Difference Soundscape Index (NDSI)) naturalness i.e. the beach and forest, compared to the urban park (control site). Perceived landscape and soundscape quality were strongly associated with stress recovery, and these results were more pronounced for the soundscape. This highlights that soundscape quality assessments deserve more systematic attention in urban green infrastructure research and planning. Finally, we found important early evidence of reduction in Electrodermal activity (EDA) only within 3 minutes of nature exposure especially in the forest

The Beam Transfer Function Experiments: CE-37

This research was sponsored by the National Science Foundation Grant NSF PHY-931478