Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

California Methanol Assessment; Volume II, Technical Report

A joint effort by the Jet Propulsion Laboratory and the California Institute of Technology Division of Chemistry and Chemical Engineering has brought together sponsors from both the public and private sectors for an analysis of the prospects for methanol use as a fuel in California, primarily for the transportation and stationary application sectors. Increasing optimism in 1982 for a slower rise in oil prices and a more realistic understanding of the costs of methanol production have had a negative effect on methanol viability in the near term (before the year 2000). Methanol was determined to have some promise in the transportation sector, but is not forecasted for large-scale use until beyond the year 2000. Similarly, while alternative use of methanol can have a positive effect on air quality (reducing NOx, SOx, and other emissions), a best case estimate is for less than 4% reduction in peak ozone by 2000 at realistic neat methanol vehicle adoption rates. Methanol is not likely to be a viable fuel in the stationary application sector because it cannot compete economically with conventional fuels except in very limited cases. On the production end, it was determined that methanol produced from natural gas will continue to dominate supply options through the year 2000, and the present and planned industry capacity is somewhat in excess of all projected needs. Nonsubsidized coal-based methanol cannot compete with conventional feedstocks using current technology, but coal-based methanol has promise in the long term (after the year 2000), providing that industry is willing to take the technical and market risks and that government agencies will help facilitate the environment for methanol. Given that the prospects for viable major markets (stationary applications and neat fuel in passenger cars) are unlikely in the 1980s and early 1990s, the next steps for methanol are in further experimentation and research of production and utilization technologies, expanded use as an octane enhancer, and selected fleet implementation. In the view of the study, it is not advantageous at this time to establish policies within California that attempt to expand methanol use rapidly as a neat fuel for passenger cars or to induce electric utility use of methanol on a widespread basis

Artificial Intelligence — An Enabler of Naval Tactical Decision Superiority

The article of record as published may be located at https://doi.org/10.1609/aimag.v40i1.2852Artificial intelligence, as a capability enhancer, offers significant improve- ments to our tactical warfighting advantage. AI provides methods for fus- ing and analyzing data to enhance our knowledge of the tactical environment; it provides methods for generating and assessing decision options from multidi- mensional, complex situations; and it provides predictive analytics to identify and examine the effects of tactical courses of action. Machine learning can improve these processes in an evolution- ary manner. Advanced computing tech- niques can handle highly heterogeneous and vast datasets and can synchronize knowledge across distributed warfare assets. This article presents concepts for applying AI to various aspects of tacti- cal battle management and discusses their potential improvements to future warfare

Proceedings of the 2015 Berry Summer Thesis Institute

Thanks to a gift from the Berry Family Foundation and the Berry family, the University Honors Program launched the Berry Summer Thesis Institute in 2012. The institute introduces students in the University Honors Program to intensive research, scholarship opportunities and professional development. Each student pursues a 12-week summer thesis research project under the guidance of a UD faculty mentor. This contains the product of the students\u27 research

Resilience Profile Barcelona

Presentació dels resultats de la recopilació de dades i d’informació sobre el context de resiliència urbana de la ciutat de Barcelona amb la finalitat de mostrar la situació de la ciutat i la informació sectorial més rellevant

Functional correlates of positional and gender-specific renal asymmetry in drosophila

Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC

Persuasive behavior as a moderator of the relationship between strategic behavior and leadership effectiveness

Based on the notion that leader behaviors are mutually facilitative on their effects on leader effectiveness, this study tested the hypothesis that Persuasive behaviors enhance the predictive relationship between Strategic behaviors and Leadership Effectiveness. Persuasive was hypothesized to act as an enhancer based on the notion that the leader\u27s ability to influence others and develop followership can enhance the impact of a leader\u27s ability to set strategy, provide direction, make decisions and plan on perceived effectiveness