Integrating Logic Rules with Everything Else, Seamlessly

This paper presents a language, Alda, that supports all of logic rules, sets, functions, updates, and objects as seamlessly integrated built-ins. The key idea is to support predicates in rules as set-valued variables that can be used and updated in any scope, and support queries using rules as either explicit or implicit automatic calls to an inference function. We have defined a formal semantics of the language, implemented a prototype compiler that builds on an object-oriented language that supports concurrent and distributed programming and on an efficient logic rule system, and successfully used the language and implementation on benchmarks and problems from a wide variety of application domains. We describe the compilation method and results of experimental evaluation.Comment: To be published in Theory and Practice of Logic Programming, Special issue for selected papers from 39nd International Conference on Logic Programming. arXiv admin note: substantial text overlap with arXiv:2205.1520

Tissue-specific transcriptome analysis reveals candidate genes for terpenoid and phenylpropanoid metabolism in the medicinal plant ferula assafoetida

© 2019 ABRF. Methionine oxidation plays a critical role in many processes of biologic and biomedical importance, including cellular redox responses and stability of protein pharmaceuticals. Bottom-up methods for analysis of methionine oxidation can suffer from incomplete sequence coverage, as well as an inability to readily detect correlated oxidation between 2 or more methionines. However, the methodology for quantifying protein oxidation in top-down analyses is lacking. Previous work has shown that electron transfer dissociation (ETD)–based tandem mass spectrometry (MS/MS) fragmentation offers accurate and precise quantification of amino acid oxidation in peptides, even in complex samples. However, the ability of ETD-based MS/MS fragmentation to accurately quantify amino acid oxidation of proteins in a top-down manner has not been reported. Using apomyoglobin and calmodulin as model proteins, we partially converted methionines into methionine sulfoxide by incubation in H2O2. Using top-down ETD-based fragmentation, we quantified the amount of oxidation of various ETD product ions and compared the quantified values with those from traditional bottom-up analysis. We find that overall quantification of methionine oxidation by top-down MS/MS ranges from good agreement with traditional bottom-up methods to vast differences between the 2 techniques, including missing oxidized product ions and large differences in measured oxidation quantities. Care must be taken in transitioning ETD-based quantitation of oxidation from the peptide level to the intact protein level

The Mediating Effects of Stigma on Depressive Symptoms in Patients With Tuberculosis: A Structural Equation Modeling Approach

Objectives: To date, the complex interrelationships between family function, doctor-patient communication, knowledge about tuberculosis (TB), stigma, and depressive symptoms among patients with TB are insufficiently understood. We explored the interrelationships between family function, doctor-patient communication, knowledge about TB, TB-related stigma, and depressive symptoms and examined whether TB-related stigma played a mediating role.Methods: A cross-sectional survey was conducted between October 1, 2013 and March 31, 2014 in Hubei province, central China. Data were collected from 1,309 patients with TB using a structured questionnaire that measured family function, doctor-patient communication, knowledge about TB, stigma, and depressive symptoms. Structural equation modeling was used to examine the interrelationships among the study variables based on the hypothesized model.Results: The proposed model provided a good fit to the obtained data. There were indirect effects between family function, doctor-patient communication, knowledge about TB, and depressive symptoms through stigma (β = −0.048, P = 0.002; β = −0.028, P = 0.001; β = −0.021, P = 0.009, respectively). Stigma partially mediated the effect of family function and knowledge about TB on depressive symptoms and fully mediated the effect of doctor-patient communication on depressive symptoms.Conclusions: This study elucidated the pathways linking family function, doctor-patient communication, and knowledge about TB to depressive symptoms and confirmed that the effect of those variables on depressive symptoms can be mediated by stigma. Those findings provide direction and information for depression interventions among patients with TB

Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells. They are of clinical interest because they can be easily isolated from bone marrow aspirates and expanded in vitro with minimal donor site morbidity. The BMSCs are also capable of altering disease pathophysiology by secreting modulating factors in a paracrine manner. Thus, engineering such cells to maximize therapeutic potential has been the focus of cell/gene therapy to date. Here, we discuss the path towards the development of clinical trials utilizing BMSCs for orthopaedic applications. Specifically, we will review the use of BMSCs in repairing critical-sized defects, fracture nonunions, cartilage and tendon injuries, as well as in metabolic bone diseases and osteonecrosis. A review of www.ClinicalTrials.gov of the United States National Institute of Health was performed, and ongoing clinical trials will be discussed in addition to the sentinel preclinical studies that paved the way for human investigations

Defective Osteogenic Differentiation in the Development of Osteosarcoma

Osteosarcoma (OS) is associated with poor prognosis due to its high incidence of metastasis and chemoresistance. It often arises in areas of rapid bone growth in long bones during the adolescent growth spurt. Although certain genetic conditions and alterations increase the risk of developing OS, the molecular pathogenesis is poorly understood. Recently, defects in differentiation have been linked to cancers, as they are associated with high cell proliferation. Treatments overcoming these defects enable terminal differentiation and subsequent tumor inhibition. OS development may be associated with defects in osteogenic differentiation. While early regulators of osteogenesis are unable to bypass these defects, late osteogenic regulators, including Runx2 and Osterix, are able to overcome some of the defects and inhibit tumor propagation through promoting osteogenic differentiation. Further understanding of the relationship between defects in osteogenic differentiation and tumor development holds tremendous potential in treating OS

Conditionally Immortalized Mouse Embryonic Fibroblasts Retain Proliferative Activity without Compromising Multipotent Differentiation Potential

Mesenchymal stem cells (MSCs) are multipotent cells which reside in many tissues and can give rise to multiple lineages including bone, cartilage and adipose. Although MSCs have attracted significant attention for basic and translational research, primary MSCs have limited life span in culture which hampers MSCs' broader applications. Here, we investigate if mouse mesenchymal progenitors can be conditionally immortalized with SV40 large T antigen and maintain long-term cell proliferation without compromising their multipotency. Using the system which expresses SV40 large T antigen flanked with Cre/loxP sites, we demonstrate that mouse embryonic fibroblasts (MEFs) can be efficiently immortalized by SV40 large T antigen. The conditionally immortalized MEFs (iMEFs) exhibit an enhanced proliferative activity and maintain long-term cell proliferation, which can be reversed by Cre recombinase. The iMEFs express most MSC markers and retain multipotency as they can differentiate into osteogenic, chondrogenic and adipogenic lineages under appropriate differentiation conditions in vitro and in vivo. The removal of SV40 large T reduces the differentiation potential of iMEFs possibly due to the decreased progenitor expansion. Furthermore, the iMEFs are apparently not tumorigenic when they are subcutaneously injected into athymic nude mice. Thus, the conditionally immortalized iMEFs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages. Our results suggest that the reversible immortalization strategy using SV40 large T antigen may be an efficient and safe approach to establishing long-term cell culture of primary mesenchymal progenitors for basic and translational research, as well as for potential clinical applications

Degradation of organophosphorus pesticide induced by oxygen plasma: Effects of operating parameters and reaction mechanisms

The degradation effectiveness and degradation mechanism of representative organophosphorus (OP) pesticide during oxygen plasma treatment have been studied. The identification and quantitative determination of OP pesticide, the degradation mechanisms for OP pesticide destruction, its destruction intermediates, and by-products were performed using gas chromatography/mass spectrometry (GC/MS) Plausible mechanisms of the degradation are discussed. Experimental results indicate that oxygen plasma treatment has noticeable effects on OP pesticide with satisfactory degradation efficiency, which mainly depends on related operating parameters including plasma treatment time, discharge power, distance from the center of the induction coil, and concentrations of OP pesticide It was found that OP pesticide was degraded into less-toxic compounds, and free radical reaction and addition reaction were to be the dominated the degradation mechanisms for OP pesticides treated by oxygen plasma. Therefore, our results suggest that oxygen plasma is suitable for degradation of OP pesticide (C) 2010 Elsevier Ltd All rights reservedShaanxi Provincial Center of Disease Control and Prevention ; National Natural Science Foundation of China [30571636, 20877062]; "13115" Key-project of Innovative Science and Technology of Shaanxi Province [2008ZDKG-78]; Key Scientific Technique Project of Shuzhou City [SG0842