Resource Recovery from Wastewater Treatment Sludge Containing Gypsum

The disposal of wastewater treatment sludge generated at the Radford Army Ammunition Plant (RAAP) is a serious problem. The sludge is produced by neutralizing spent acid contained in the wastewater with lime, and consists principally of very finely divided wet gypsum (calcium sulfate dihydrate). Although the sludge is presently being disposed of in a landfill, the sludge is difficult to handle and convert into a load-bearing material. Therefore an alternative method of disposal is being developed and evaluated. The alternative method involves drying and granulating the sludge, followed by high temperature calcination in a fluidized bed reactor to recover usable sulfur dioxide and lime. If the method is adopted, these products would be used within the plant with considerable cost savings. The sulfur dioxide would be added to the feed stream of an oleum manufacturing facility and the lime would be reused in wastewater treatment

Utilizing a biology-driven approach to map the exposome in health and disease:An essential investment to drive the next generation of environmental discovery

BACKGROUND: Recent developments in technologies have offered opportunities to measure the exposome with unprecedented accuracy and scale. However, because most investigations have targeted only a few exposures at a time, it is hypothesized that the majority of the environmental determinants of chronic diseases remain unknown. OBJECTIVES: We describe a functional exposome concept and explain how it can leverage existing bioassays and high-resolution mass spectrometry for exploratory study. We discuss how such an approach can address well-known barriers to interpret exposures and present a vision of next-generation exposomics. DISCUSSION: The exposome is vast. Instead of trying to capture all exposures, we can reduce the complexity by measuring the functional exposome— the totality of the biologically active exposures relevant to disease development—through coupling biochemical receptor-binding assays with affinity purification–mass spectrometry. We claim the idea of capturing exposures with functional biomolecules opens new opportunities to solve critical problems in exposomics, including low-dose detection, unknown annotations, and complex mixtures of exposures. Although novel, biology-based measurement can make use of the existing data processing and bioinformatics pipelines. The functional exposome concept also complements conven-tional targeted and untargeted approaches for understanding exposure-disease relationships. CONCLUSIONS: Although measurement technology has advanced, critical technological, analytical, and inferential barriers impede the detection of many environmental exposures relevant to chronic-disease etiology. Through biology-driven exposomics, it is possible to simultaneously scale up discovery of these causal environmental factors. https://doi.org/10.1289/EHP8327

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

Resource Recovery from Wastewater Treatment Sludge Containing Gypsum

The disposal of wastewater treatment sludge generated at the Radford Army Ammunition Plant (RAAP) is a serious problem. The sludge is produced by neutralizing spent acid contained in the wastewater with lime, and consists principally of very finely divided wet gypsum (calcium sulfate dihydrate). Although the sludge is presently being disposed of in a landfill, the sludge is difficult to handle and convert into a load-bearing material. Therefore an alternative method of disposal is being developed and evaluated. The alternative method involves drying and granulating the sludge, followed by high temperature calcination in a fluidized bed reactor to recover usable sulfur dioxide and lime. If the method is adopted, these products would be used within the plant with considerable cost savings. The sulfur dioxide would be added to the feed stream of an oleum manufacturing facility and the lime would be reused in wastewater treatment.This is a conference proceeding from Proceedings of the 1984 National Waste Processing Conference (1984): 441. Posted with permission.</p

Building Multivariate Systems Biology Models

Vascular Surger

Different Lipid Regulation in Ovarian Cancer: Inhibition of the Immune System

Contains fulltext : 190940.pdf (publisher's version ) (Open Access)Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality. Therefore, we analyzed 109 lipid mediators and found differentially regulated lipids in suppressive ascitic fluid compared to normal abdominal fluid. Our study indicates the presence of lipid intermediates in ascites of ovarian cancer patients, which coincidences with T cell dysfunctionality. Since the immune system in the abdominal cavity is compromised, this may explain the high seeding efficiency of disseminated tumor cells. Further research is needed to fully understand the correlation between the various lipids and T cell proliferation, which could lead to new treatment options

Systems biology approaches and pathway tools for investigating cardiovascular disease

Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine how they evolve with temporal and environmental changes. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies, such as inflammatory-related diseases, herein exemplified by atherosclerosis. In this paper, the initial studies in this discipline are reviewed and examined within the context of the development of the field. In addition, several different software tools are briefly described and a novel application for the KEGG database suite called KegArray is presented. This tool is designed for mapping the results of high-throughput omics studies, including transcriptomics, proteomics and metabolomics data, onto interactive KEGG metabolic pathways. The utility of KegArray is demonstrated using a combined transcriptomics and lipidomics dataset from a published study designed to examine the potential of cholesterol in the diet to influence the inflammatory component in the development of atherosclerosis. These data were mapped onto the KEGG PATHWAY database, with a low cholesterol diet affecting 60 distinct biochemical pathways and a high cholesterol exposure affecting 76 biochemical pathways. A total of 77 pathways were differentially affected between low and high cholesterol diets. The KEGG pathways "Biosynthesis of unsaturated fatty acids" and "Sphingolipid metabolism" evidenced multiple changes in gene/lipid levels between low and high cholesterol treatment, and are discussed in detail. Taken together, this paper provides a brief introduction to systems biology and the applications of pathway mapping to the study of cardiovascular disease, as well as a summary of available tools. Current limitations and future visions of this emerging field are discussed, with the conclusion that combining knowledge from biological pathways and high-throughput omics data will move clinical medicine one step further to individualize medical diagnosis and treatment. © The Royal Society of Chemistry 2009

Temporal Fluctuation of Systemic Markers in Urine During a Nasal Rhinovirus Challenge in Healthy and Asthmatic Subjects

International audienceBiological processes are dynamic as reflected by temporal fluctuations of biomarkers. These dynamics underline the adaptive capacity of physiological systems to respond to external perturbations. We have captured differences in the pattern of fluctuations in biomarkers sampled locally at the sites of respiratory infection between healthy individuals and asthma patients, before and after perturbation by rhinovirus exposure [Sinha et al, eLife]. The detection of fluctuating biomarker signals in a systemic matrix, e.g. urine could aid in the development of better prognostic, non-invasive markers for monitoring disease progression especially during loss-of-control/exacerbation events due to viral exposures in asthma. Aims:Probe and compare temporal fluctuations of metabolomic signatures in the systemic circulation (urine) after a rhinovirus (RV-16) challenge in healthy and asthmatic subjects. Methods: In this prospective follow-up study, urine from 12 healthy individuals and 12 asthma patients was sampled thrice weekly for 3 months. After two months (stable phase) individuals were exposed to a 100 TCID50 Rhinovirus 16 and followed for another month (unstable phase). Non-targeted metabolomics data were acquiredwith liquid chromatography-mass spectrometry (LC-MS) using HILIC chromatography in positive ionization mode. Urine specific gravity (SG) was measured to normalize urine concentration and to reduce matrix effects. Data was processed independently using MZmine, MS-DIAL and Profinder software packages.A modified robust regression analysis technique, LASSO (least absolute shrinkage and selection operator) was applied on the mass spectrometric fragments to compare healthy and asthma groups both before and after rhinovirus challenge interventions. The machine learning pipeline was applied to the non-targeted metabolomics dataset and selected features were identified using an in-house chemical library. Results: We have identified a total of 164 metabolites in urine, several of which were found differentially regulated in healthy and asthmatic volunteers before and after the challenge (See Figure 1). Interestingly carnitine species decreased during the Rhinovirus challenge. Decreases in urinary carnitines have been previously observed in relationto asthma severity levels which confirm and substantiate our findings. Derivates of GABA (γ-aminobutyric acid) were also found to be differentially regulated. Conclusions: Our studyreports for the first time the fluctuating signals of metabolites in systemic signals in response to an exogenous trigger in the local nasal compartment in healthy and asthmaticsubjects. Carnitine compounds could prove to be useful markers of viral infection. The differential regulation of urinary metabolites could be useful to monitor patient prognosis andspot viral infections

MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma.

In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of β-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN-amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies