Air handling unit performance assessment rules (APAR) is a fault detection tool that uses a set of expert rules derived from mass and energy balances to detect faults in air handling units (AHUs). ...Control signals are used to determine the mode of operation of the AHU. A subset of the expert rules which correspond to that mode of operation are then evaluated to determine whether a fault exists. APAR is computationally simple enough that it can be embedded in commercial building automation and control systems and relies only upon the sensor data and control signals that are commonly available in these systems. APAR was tested using data sets collected from a “hardware-in-the-loop” emulator and from several field sites. APAR was also embedded in commercial AHU controllers and tested in the emulator.
Abstract
Studies of anticancer therapies in traditional cell culture models can demonstrate efficacy of direct-acting compounds but lack the 3-dimensional arrangement of the tumor cells and their ...tissue-specific microenvironments, both of which are important modulators of treatment effects in vivo. Bone cells reside in complex environments that regulate their fate and function. A bioengineered human bone-tumor model has been shown to provide a microphysiological niche for studies of cancer cell behavior. Here, we demonstrate successful transfer between 2 laboratories and utility of this model in efficacy studies using well-established chemotherapeutic agents. The bioengineered human bone-tumor model consisted of Ewing sarcoma (RD-ES) cancer cell aggregates infused into tissue-engineered bone that was grown from human mesenchymal stem cell-derived differentiated into osteoblasts within mineralized bone scaffolds. The tumor model was maintained in culture for over 5 weeks and subjected to clinically relevant doses of linsitinib, doxorubicin, cisplatin, methotrexate, vincristine, dexamethasone, or MAP (methotrexate, doxorubicin, and cisplatin combination). Drug administration cycles were designed to mimic clinical treatment regimens. The bioengineered tumors were evaluated days to weeks after the cessation of treatment to monitor the potential for relapse, using bioengineered bone and ES cell monolayers as controls. Drug binding to the scaffolds and media proteins and gene expression were also evaluated. We show that a bioengineered human bone tumor can be used as a microphysiological model for preclinical studies of anticancer drugs. We found that anticancer efficacy was achieved at concentrations approximating the human Cmax, in contrast to traditional ES cell monolayers. These studies show that the bone-tumor model can be successfully transferred between laboratories and has predictive power in preclinical studies. The effects of drugs on the bone tumors and healthy bone were studied in parallel, in support of the utility of this model for identification of new therapeutic targets.
Streptococcus agalactiae is a well-characterized bovine mastitis pathogen that is known to be highly contagious and capable of spreading rapidly in affected dairy herds. Loop-mediated isothermal ...amplification (LAMP) is a novel molecular diagnostic method that has the capability to provide rapid, cost-effective screening for pathogens to support on-farm disease control and eradication programs. In the current study, a LAMP test was developed to detect S. agalactiae in milk. The assay was validated on a bank of existing clinical mastitis milk samples that had previously been identified as S. agalactiae positive via traditional microbiological culture techniques and PCR. The LAMP assay was conducted on bacterial colonies and DNA extracted from milk in tube- and plate-based formats using multiple detection platforms. The 1-h assay conducted at 64°C exhibited repeatability (coefficient of variation) of 2.07% (tube) and 8.3% (plate), sensitivity to ~20 pg of extracted DNA/reaction, and specificity against a panel of known bacterial mastitis pathogens. Of the 109 known S. agalactiae isolates assessed by LAMP directly from bacterial cells in culture, 108 were identified as positive, in accordance with PCR analysis. The LAMP analysis from the corresponding milk samples indicated that 104 of these milks exhibited a positive amplification curve. Although exhibiting some limitations, this assay provides an opportunity for rapid screening of milk samples to facilitate on-farm management of this pathogen.
Extremum seeking control (ESC) is a model-free control solution for real-time optimization of system operation where model acquisition is difficult and/or cost prohibitive. For many HVAC and ...refrigeration systems, there can be a large number of candidate inputs for ESC design; however, some inputs affect the performance measure to a greater degree than others. This article presents an online input selection method for multivariable ESC, which uses a singular value decomposition (SVD) analysis coupled with a dither-demodulation-based online Hessian estimate for the underlying static map. A subset of physical inputs or a new set of inputs via linear combination of the physical inputs can be determined using the proposed approach. We present an analysis for quantifying the loss bound of achievable optimum output with the underlying input selection. Further, the Hessian estimation error bound is quantified with perturbation analysis. The proposed method is evaluated with Modelica simulation models of chilled-water plants, one with a single chiller and the other with two parallel chillers. The simulation results validate the effectiveness of the proposed method of input selection.
The skin is the first line of defense to cutaneous microbes and viruses, and epidermal keratinocytes play a critical role in preventing infection by viruses and pathogens through activation of the ...type I interferon (IFN) response. Using RNAseq analysis, here we report that the conditional deletion of C/EBPβ transcription factor in mouse epidermis (CKOβ mice) resulted in the upregulation of IFNβ and numerous keratinocyte interferon-stimulated genes (ISGs). The expression of cytosolic pattern recognition receptors (cPRRs), that recognize viral RNA and DNA, were significantly increased, and enriched in the RNAseq data set. cPRRs stimulate a type I IFN response that can trigger cell death to eliminate infected cells. To determine if the observed increases in cPRRs had functional consequences, we transfected CKOβ primary keratinocytes with the pathogen and viral mimics poly(I:C) (dsRNA) or poly(dA:dT) (synthetic B-DNA) that directly activate PRRs. Transfected CKOβ primary keratinocytes displayed an amplified type I IFN response which was accompanied by increased activation of IRF3, enhanced ISG expression, enhanced activation of caspase-8, caspase-3 and increased apoptosis. Our results identify C/EBPβ as a critical repressor of the keratinocyte type I IFN response, and demonstrates that the loss of C/EBPβ primes keratinocytes to the activation of cytosolic PRRs by pathogen RNA and DNA to induce cell death mediated by caspase-8 and caspase-3.
Improvement in Survival Following Successful Percutaneous Coronary Intervention of Coronary Chronic Total Occlusions: Variability by Target Vessel David M. Safley, John A. House, Steven P. Marso, J. ...Aaron Grantham, Barry D. Rutherford This study compared the survival benefits of successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) of the left anterior descending (LAD), left circumflex, or right coronary artery. Eligible patients underwent single vessel PCI. The primary end point was 5-year survival, compared across target vessel groups stratified by procedural success. Of 2,608 patients, the LAD was the target in 936 (36%), the left circumflex in 682 (26%), and the right coronary artery in 990 (38%). In multivariable analysis, CTO PCI success of the LAD was associated with decreased mortality (HR: 0.61, 95% CI: 0.42 to 0.89). This information may assist in selecting patients for CTO PCI.
Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression ...profiling for
toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation. Analyses of high-throughput toxicogenomics data require renewed attention to read-calling algorithms and simplified dose-response modeling for datasets with relatively few samples. Using data from induced pluripotent stem cell-derived cardiomyocytes treated with chemicals at varying concentrations, we describe here and make available a pipeline for handling expression data generated by TempO-Seq to align reads, clean and normalize raw count data, identify differentially expressed genes, and calculate transcriptomic concentration-response points of departure. The methods are extensible to other forms of concentration-response gene-expression data, and we discuss the utility of the methods for assessing variation in susceptibility and the diseased cellular state.
Bleeding in patients undergoing percutaneous coronary intervention (PCI) is associated with increased morbidity, mortality, length of hospitalization, and cost. We identified baseline clinical ...characteristics associated with bleeding complications after PCI and developed a simplified, clinically useful algorithm to predict patient risk.
Data were analyzed from 302 152 PCI procedures performed at 440 US centers participating in the National Cardiovascular Data Registry. As defined by the National Cardiovascular Data Registry, bleeding required transfusion, prolonged hospital stay, and/or a drop in hemoglobin >3.0 g/dL from any location, including percutaneous entry site, retroperitoneal, gastrointestinal, genitourinary, and other/unknown location. Bleeding complications occurred in 2.4% of patients. From the best-fitting model consisting of 15 clinical elements associated with post-PCI bleeding in a random 80% training cohort, we developed a parsimonious risk algorithm. Predictors of bleeding included age, gender, previous heart failure, glomerular filtration rate, peripheral vascular disease, no previous PCI, New York Heart Association/Canadian Cardiovascular Society Functional Classification class IV heart failure, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and cardiogenic shock. The parsimonious model was validated in the remaining 20% of the population (c-statistic, 0.72) and in clinically relevant subgroups of patients. This simplified model was used to derive a clinical risk algorithm, with larger numbers corresponding with greater risk. In 3 categories, bleeding rates were greater in patients with higher estimates (<or=7, 0.7%; 8 to 17, 1.8%; >or=18, 5.1%).
This report identifies baseline clinical factors associated with bleeding and proposes a clinically useful algorithm to estimate bleeding risk. This model is potentially actionable in altering therapeutic decision making and improving outcomes in patients undergoing PCI.
Epidemiological studies show that individuals with underlying diabetes and diet-associated ailments are more susceptible than healthy individuals to adverse health effects of air pollution. Exposure ...to air pollutants can induce metabolic stress and increase cardiometabolic disease risk. Using male Wistar and Wistar-derived Goto-Kakizaki (GK) rats, which exhibit a non-obese type-2 diabetes phenotype, we investigated whether two key metabolic stressors, type-2 diabetes and a high-cholesterol atherogenic diet, exacerbate ozone-induced metabolic effects. Rats were fed a normal control diet (ND) or high-cholesterol diet (HCD) for 12 weeks and then exposed to filtered air or 1.0-ppm ozone (6 h/day) for 1 or 2 days. Metabolic responses were analyzed at the end of each day and after an 18-h recovery period following the 2-day exposure. In GK rats, baseline hyperglycemia and glucose intolerance were exacerbated by HCD vs. ND and by ozone vs. air. HCD also resulted in higher insulin in ozone-exposed GK rats and circulating lipase, aspartate transaminase, and alanine transaminase in all groups (Wistar>GK). Histopathological effects induced by HCD in the liver, which included macrovesicular vacuolation and hepatocellular necrosis, were more severe in Wistar vs. GK rats. Liver gene expression in Wistar and GK rats fed ND showed numerous strain differences, including evidence of increased lipid metabolizing activity and ozone-induced alterations in glucose and lipid transporters, specifically in GK rats. Collectively, these findings indicate that peripheral metabolic alterations induced by diabetes and high-cholesterol diet can enhance susceptibility to the metabolic effects of inhaled pollutants.
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•Diabetic rats are susceptible to HCD-induced obesity, glucose intolerance and adipose atrophy.•Healthy Wistar rats fed HCD had more severe liver pathology when compared to diabetic rats.•Ozone increased insulin only in diabetic rats fed HCD suggesting increased insulin resistance.•Ozone effects on glucose and lipid metabolism are more severe in diabetic than healthy rats.•Ozone inhibited cholesterol synthesis genes in Wistar but increased glucose and fatty acid transport genes in diabetic rats.
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