The tumor necrosis factor alpha (TNF-␣) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-␣ gene expression. In LPS-stimulated macrophages, the ERK substrates Ets and Elk-1 bind to the TNF-␣ promoter in vivo. Strikingly, Ets and Elk-1 bind to two TNF-␣ nuclear factor of activated T cells (NFAT)-binding sites, which are required for calcineurin and NFAT-dependent TNF-␣ gene expression in lymphocytes. The transcription factors ATF-2, c-jun, Egr-1, and Sp1 are also inducibly recruited to the TNF-␣ promoter in vivo, and the binding sites for each of these activators are required for LPSstimulated TNF-␣ gene expression. Furthermore, assembly of the LPS-stimulated TNF-␣ enhancer complex is dependent upon the coactivator proteins CREB binding protein and p300. The finding that a distinct set of transcription factors associates with a fixed set of binding sites on the TNF-␣ promoter in response to LPS stimulation lends new insights into the mechanisms by which complex patterns of gene regulation are achieved.Tumor necrosis factor alpha (TNF-␣) is a proinflammatory cytokine that activates multiple-signal transduction pathways and influences a broad range of immunological processes. Multiple extracellular stimuli induce the synthesis of TNF-␣ in a wide variety of cell types, including T and B cells, monocytes and macrophages, mast cells, and fibroblasts (reviewed in reference 1). We have shown that induction of TNF-␣ gene transcription by T or B cell receptor engagement, virus infection, and treatment with a calcium ionophore depends upon the activity of the phosphatase calcineurin (15,18,20). Calcineurin targets the nuclear factor of activated T cells (NFAT) family of proteins (reviewed in references 11 and 38), which are critical for TNF-␣ gene expression by calcineurin-dependent signal transduction pathways (15,48,49).Production of TNF-␣ in response to lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is of particular clinical importance because TNF-␣ is a mediator of septic shock (reviewed in reference 1). Exposure of monocytes and macrophages to LPS results in activation of the mitogen-activated protein kinase (MAPK) pathway, including the extracellular signal-related kinase (ERK), c-jun NH 2 -terminal kinase (JNK), and p38 cascades (reviewed in reference 12).Here, we show that ERK, but not calcineurin or p38, is required for full transcriptional induction of TNF-␣ gene expression by LPS. We identify TNF-␣ promoter elements critical for LPS induction of the gene and demonstrate that two Sp1 binding sites and three Ets binding sites, in addition to a cyclic AMP response element (CRE)-like site and an Egr site, are critical for LPS induction of the TNF-␣ gene. Consistent with this functional analysis of the TNF-␣ promoter, using chromatin immunoprecipitation and formaldehyde crosslinking (ChIP) assays, we directly detect LPS-induc...

Homogeneous charge compression ignition has the potential to significantly reduce NO x emissions, while maintaining a high fuel efficiency. Homogeneous charge compression ignition is characterized by compression-induced autoignition of a lean homogeneous air–fuel mixture. Combustion timing is highly dependent on the in-cylinder state including pressure, temperature and trapped mass. To control homogeneous charge compression ignition combustion, it is necessary to have an accurate representation of the gas exchange process. Currently, microprocessor-based engine control units require that the gas exchange process is linearized around a desired operating point to simplify the model for real-time implementation. This reduces the models’ ability to handle disturbances and limits the flexibility of the model. However, using a field programmable gate array, a detailed simulation of the physical gas exchange process can be implemented in real time. This paper outlines the process of converting physical governing equations to an offline zero-dimensional gas exchange model. The process used to convert this model to a field programmable gate array capable model is described. This model is experimentally validated using a single cylinder research engine with electromagnetic valves to record real-time field programmable gate array gas exchange results and comparing to the offline zero-dimensional physical model. The field programmable gate array model is able to accurately calculate the cylinder temperature and cylinder mass at 0.1 °CA intervals during the gas exchange process for a range of negative valve overlaps, boost conditions and engine speeds making the model useful for future real-time control applications.

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Homogeneous charge compression ignition is a part-load combustion method, which can significantly reduce oxides of nitrogen (NO x) emissions compared to current lean-burn spark ignition engines. The challenge with homogeneous charge compression ignition combustion is the high cyclic variation due to the lack of direct ignition control. A fully variable electromagnetic valve train provides the internal exhaust gas recirculation through negative valve overlap which is required to obtain the necessary thermal energy to enable homogeneous charge compression ignition. This also increases the cyclic coupling as residual gas and unburnt fuel is transferred between cycles through exhaust gas recirculation. To improve combustion stability, an experimentally validated feed-forward water injection controller is presented. Utilizing the low latency and rapid calculation rate of a field programmable gate array, a real-time calculation of residual fuel mass is implemented on a prototyping engine controller. Using this field programmable gate array–based calculation, it is possible to calculate the amount of fuel and the required control interaction during an engine cycle. This controller prevents early rapid combustion following a late combustion cycle using direct water injection to cool the cylinder charge and counter the additional thermal energy from any residual fuel that is transferred between cycles. By cooling the trapped cylinder mass, the upcoming combustion phasing can be delayed to the desired setpoint. The controller was tested at several operating points and showed an improvement in the combustion stability as shown by a reduction in the standard deviation of combustion phasing and indicated mean effective pressure.

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When compared to traditional engines, homogeneous charge compression ignition has the potential to significantly reduce NO x raw emissions, while maintaining a high fuel efficiency. Homogeneous charge compression ignition is characterized by compression-induced autoignition of a lean homogeneous air–fuel mixture. Since homogeneous charge compression ignition does not utilize direct ignition control, it is strongly dependent on the state of the cylinder charge and can suffer from high cyclic variability. With spark-assisted compression ignition, it has been demonstrated that misfires can be reduced, while preserving the high thermal efficiency of homogeneous charge compression ignition as a result of the more favorable physical mixture properties due to dilution. However, spark-assisted compression ignition reduces the NO x benefits of homogeneous charge compression ignition, as it increases the local combustion temperatures. To merge the advantages of the homogeneous charge compression ignition and the spark-assisted compression ignition combustion processes, a field-programmable gate array for detailed simulation of the physical gas exchange is combined with a rapid spark system. The low latency and computational speed of the field-programmable gate array allows the simulation process to be implemented in real time. When combined with the rapid reaction time of the high-frequency current-based rapid ignition system, a feedforward controller based on the cylinder pressure or heat release is realized. The developed model-based controller determines if a spark is required to assist the homogeneous charge compression ignition combustion process. The use of the field-programmable gate array and rapid ignition system allows for the calculation of combustion properties and controller output within 0.1 °CA. This article presents the development and experimental validation of the developed controller on a single-cylinder research engine. The combustion stability has been significantly improved as reflected in an improved standard deviation of the indicated mean effective pressure and a reduction of the combustion phasing variations. Furthermore, compared to a traditional homogeneous charge compression ignition system, the hydrocarbon emissions can be reduced, while maintaining low NO x emissions.

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