Characterization of urea SCR using Taguchi technique and computational methods.

Use of biodiesel in diesel engine helps to reduce HC, CO, and smoke emissions due to their enormous oxygen content, whereas NOx emissions formed by Zeldovich mechanism shoot up. Implementation of Bharat Stage (BS) VI by April 2020 in India has created extreme pressure on automobile manufacturers to include after treatment technology in their systems. Selective catalytic reduction (SCR), a NOx control technology, is operated using aqueous urea solution as the reductant. There are several parameters that need to be monitored to enhance the NOx conversion efficiency of SCR retrofit. The uniformity index of ammonia, which determines the conversion efficiency, is greatly influenced by parameters like exhaust gas temperature, injection angle, injector position, mass flow rate, and SCR geometry. This paper considers two types of SCR design, namely SCR with and without mixer design and their impact on NOx reduction. The effect of mass flow rate on urea conversion in SCR design without mixer is 27%, but the impact is reduced greatly in SCR design with mixer with less than 2% variation. The UI resulting from different cases ranges from 0.59 to 0.83. Using Taguchi technique and CFD tool, the impact of parameters on both the SCR designs has been investigated and the optimum SCR design is reported.

Emission profiling of CI engine fueled with neem and wintergreen oil blend with hexanol and octanol manifold injection.

The present work details the effects of injection of higher order alcohols, namely hexanol (Hex) and octanol (Oct) as secondary fuels in a CI engine. The last decade has seen an exponential increase in the carbon emission chief of which have been contributed by fossil fuels. Vegetable oils provide a viable alternative to the current scenario as they can be synthesized easily from nature and can be readily adapted for use in CI engines. Neem oil (NO) is non-edible and widely available and hence taken as a base fuel for this research. The poor properties of neem oil were improved by the addition of novel low viscous biofuel, namely wintergreen oil (WGO). During the course of this research work, a blend containing a mixture of 50% of neat neem oil and 50% of wintergreen oil (NO50-WGO50) was optimized based on trial tests and taken as pilot fuel while Hex and Oct were injected along with intake air as secondary fuels. The alcohols were injected into the engine successively in the 10%, 20%, and 30% (by mass) ratios. Experiments were conducted in a single-cylinder CI engine fabricating 5.2-kW power at a constant speed of 1500 rpm at varying load conditions. It is observed that inferior performance of NO led to more smoke, HC, and CO in comparison to diesel at all the loads and these are improved with NO50-WGO50 blend. Nevertheless, a minor increase in NOx emission was perceived with the blend. Addition of higher order alcohol promoted reduction of both NOx and smoke emission without affecting performance. Among the various combinations, NO50-WGO50 + Hex30 and Oct30 reduced NOx emission by 12% and 9.5% and smoke emission by 13% and 19% respectively. These results are on par with the diesel performance and emission characteristics.

The combined effect of low viscous biofuel and EGR on NO-smoke tradeoff in a biodiesel engine-an experimental study.

The present study aims to study the effect of low viscous biofuel, namely pine oil (PO) and orange oil (O) blending with Jatropha methyl ester (JOME) along with exhaust gas recirculation (EGR) on NO-smoke tradeoff in a single-compression ignition (CI) engine. Two blends of pine oil and orange oil (30% by volume) with JOME were prepared and tested at 10%, 15%, and 20% EGR rates for various load conditions and compared with base fuels. JOME operation increased NO emission by 4% and reduced smoke opacity by 10% in comparison to diesel at maximum load condition. Poor physical properties of JOME, namely high viscosity and inferior volatility leads to reduced brake thermal efficiency with higher HC and CO emissions. Blends of JOME with low viscous biofuel reduces smoke emission with a further increase in NO emission in comparison to JOME as a result of combustion enhancement. Addition of EGR with JOME70 + PO30 and JOME70 + O30 aids in the reduction of NO emission with a slight increase in smoke opacity. Considering the NO-smoke tradeoff, JOME70 + O30 + EGR (10%) is optimum, NO emission is reduced by 14% and 11% in comparison to JOME and diesel and smoke opacity is reduced by 5% and 15% in comparison to JOME and diesel at maximum load, respectively.

Experimental study on NOx reduction in a grapeseed oil biodiesel-fueled CI engine using nanoemulsions and SCR retrofitment.

Stringent emission norms impose challenges to original equipment manufacturer (OEM) in reducing diesel engine emissions. Implementing renewable fuels as alternative energy sources in diesel engines leads to increased emission levels particularly NOx. In this work, performance, combustion, and emission parameters from a diesel engine powered with grapeseed oil biodiesel (GSBD) was investigated. Nano additive emulsions of cerium oxide (CeO2) and zinc oxide (ZnO) at 100 ppm each were added to grapeseed oil biodiesel. To enhance the NOx reduction task further, an advanced technology called selective catalytic reduction (SCR) system was used. With easy availability of aqueous urea, careful injection, and distribution of the reductant solution, a paradigm change was brought about in NOx reduction technology. The experiments were carried out with and without SCR for better understanding and investigation. The percentage reduction of NOx emission by adding cerium oxide and zinc oxide emulsion blends were 4.19% and 13.13%, respectively. The overall reduction in NOx emission were 74.16% and 80.06% with SCR for cerium oxide and zinc oxide emulsion blends. The research conclusions make grapeseed oil biodiesel conceivable as an effective alternate fuel for diesel engines without any engine modifications.

The potential impact of unsaturation degree of the biodiesels obtained from beverage and food processing biomass streams on the performance, combustion and emission characteristics in a single-cylinder CI engine.

The purpose of this study is to experimentally investigate the effect of unsaturation of the biodiesels obtained from grapeseed oil, wheat germ oil and coconut oil (reference fuel) for compression ignition (CI) engine application. Fatty acid profile analysis and physio-chemical properties were determined by standard test procedures. Engine testing was carried out in a 5.2-kW single-cylinder CI engine and the combustion, performance and emission characteristics were analysed. The effect of fuel property variation and the combustion reaction kinetics due to unsaturation difference have been discussed. The maximum brake thermal efficiency at full load for diesel was found to be 32.3% followed by 31.3%, 30.2% and 27.4 %, respectively, for coconut biodiesel (CBD), grapeseed biodiesel (GSBD) and wheat germ biodiesel (WGBD). Maximum heat release rate as observed for diesel, CBD, GSBD and WGBD are 63.2 J/°CA 60.7 J/°CA and 59 J/°CA and 43.4 J/°CA respectively. The brake-specific NO emission at full load is higher for CBD followed by GSBD, WGBD and diesel having values of 9.23 g/kWh, 8.91 g/kWh, 8.21 g/kWh and 7.6 g/kWh respectively. Conversely, the smoke emission is lower for CBD compared to the other tested fuels.

Combined effect of fuel-design and after-treatment system on reduction of local and global emissions from CI engine.

This experimental study aims to mitigate harmful emissions from a CI engine using bio-energy with carbon capture and storage (BECCS) approach. The engine used for this experimental work is a single cylinder CI engine with a rated power of 5.2 kW at a constant speed of 1500 rpm. The BECCS approach is a combination of plant-based biofuels and carbon capture and storage (CCS) system. The whole investigation was done in four phases: (1) Substituting diesel with Karanja oil methyl ester (KOME) (2) Equal volume blending of Orange oil (ORG) with KOME (3) 20% blending of n-butanol (B) with KOME-ORG blend (4) CCS system with zeolite based non-selective catalytic reduction (NSCR) and mono ethanolamine (MEA) based selective non-catalytic reduction (SNCR) system with KOME-ORG + B20 blend. The experimental results show that substitution of diesel with KOME reduces smoke emission, but increases NO and CO2 emission. KOME-ORG blend reduces CO2 and smoke emissions with high NO emission due to combustion improvement. In comparison with the sole combustion of KOME at full load condition, the combination of KOME-ORG + B20 as bio-fuel with zeolite based post-combustion treatment system resulted in a maximum reduction of NO, smoke and CO2 emission by 41%, 19% and 15% respectively.

Effect of lower and higher alcohol fuel synergies in biofuel blends and exhaust treatment system on emissions from CI engine.

The present study deals with performance, emission and combustion studies in a single cylinder CI engine with lower and higher alcohol fuel synergies with biofuel blends and exhaust treatment system. Karanja oil methyl ester (KOME), widely available biofuel in India, and orange oil (ORG), a low carbon biofuel, were taken for this study, and equal volume blend was prepared for testing. Methanol (M) and n-pentanol (P) was taken as lower and higher alcohol and blended 20% by volume with KOME-ORG blend. Activated carbon-based exhaust treatment indigenous system was designed and tested with KOME-ORG + M20 and KOME-ORG + P20 blend. The tests were carried out at various load conditions at a constant speed of 1500 rpm. The study revealed that considering performance, emission and combustion studies, KOME-ORG + M20 + activated carbon are found optimum in reducing NO, smoke and CO2 emission. Compared to KOME, for KOME-ORG + M20 + activated carbon, NO emission is reduced from 10.25 to 7.85 g/kWh, the smoke emission is reduced from 49.4 to 28.9%, and CO2 emission is reduced from 1098.84 to 580.68 g/kWh. However, with exhaust treatment system, an increase in HC and CO emissions and reduced thermal efficiency is observed due to backpressure effects.

Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations.

Purpose: While multikinase inhibitors with RET activity are active in RET-rearranged thyroid and lung cancers, objective response rates are relatively low and toxicity can be substantial. The development of novel RET inhibitors with improved potency and/or reduced toxicity is thus an unmet need. RXDX-105 is a small molecule kinase inhibitor that potently inhibits RET. The purpose of the preclinical and clinical studies was to evaluate the potential of RXDX-105 as an effective therapy for cancers driven by RET alterations.Experimental design: The RET-inhibitory activity of RXDX-105 was assessed by biochemical and cellular assays, followed by in vivo tumor growth inhibition studies in cell line- and patient-derived xenograft models. Antitumor activity in patients was assessed by imaging and Response Evaluation Criteria in Solid Tumors (RECIST).Results: Biochemically, RXDX-105 inhibited wild-type RET, CCDC6-RET, NCOA4-RET, PRKAR1A-RET, and RET M918T with low to subnanomolar activity while sparing VEGFR2/KDR and VEGFR1/FLT. RXDX-105 treatment resulted in dose-dependent inhibition of proliferation of CCDC6-RET-rearranged and RET C634W-mutant cell lines and inhibition of downstream signaling pathways. Significant tumor growth inhibition in CCDC6-RET, NCOA4-RET, and KIF5B-RET-containing xenografts was observed, with the concomitant inhibition of p-ERK, p-AKT, and p-PLCγ. Additionally, a patient with advanced RET-rearranged lung cancer had a rapid and sustained response to RXDX-105 in both intracranial and extracranial disease.Conclusions: These data support the inclusion of patients bearing RET alterations in ongoing and future molecularly enriched clinical trials to explore RXDX-105 efficacy across a variety of tumor types. Clin Cancer Res; 23(12); 2981-90. ©2016 AACR.

Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations.

Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTC) and the rapid degradation of their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SMG7-UPF1 complex and inhibit NMD. Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with minimal toxicity in cell-based assays. As expected, pharmacologic NMD inhibition disrupted SMG7-UPF1 interactions. When used in cells with PTC-mutated p53, pharmacologic NMD inhibition combined with a PTC "read-through" drug led to restoration of full-length p53 protein, upregulation of p53 downstream transcripts, and cell death. These studies serve as proof-of-concept that pharmacologic NMD inhibitors can restore mRNA integrity in the presence of PTC and can be used as part of a strategy to restore full-length protein in a variety of genetic diseases.

Inhibition of nonsense-mediated RNA decay activates autophagy.

Nonsense-mediated RNA decay (NMD) is an mRNA surveillance mechanism which rapidly degrades select cytoplasmic mRNAs. We and others have shown that NMD is a dynamically regulated process inhibited by amino acid deprivation, hypoxia, and other cellular stresses commonly generated by the tumor microenvironment. This inhibition of NMD can result in the accumulation of misfolded, mutated, and aggregated proteins, but how cells adapt to these aberrant proteins is unknown. Here we demonstrate that the inhibition of NMD activates autophagy, an established protein surveillance mechanism, both in vitro and in vivo. Conversely, the hyperactivation of NMD blunts the induction of autophagy in response to a variety of cellular stresses. The regulation of autophagy by NMD is due, in part, to stabilization of the documented NMD target ATF4. NMD inhibition increases intracellular amino acids, a hallmark of autophagy, and the concomitant inhibition of autophagy and NMD, either molecularly or pharmacologically, leads to synergistic cell death. Together these studies indicate that autophagy is an adaptive response to NMD inhibition and uncover a novel relationship between an mRNA surveillance system and a protein surveillance system, with important implications for the treatment of cancer.

Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes tumorigenesis.

While nonsense-mediated RNA decay (NMD) is an established mechanism to rapidly degrade select transcripts, the physiological regulation and biological significance of NMD are not well characterized. We previously demonstrated that NMD is inhibited in hypoxic cells. Here we show that the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) translation initiation factor by a variety of cellular stresses leads to the inhibition of NMD and that eIF2α phosphorylation and NMD inhibition occur in tumors. To explore the significance of this NMD regulation, we used an unbiased approach to identify approximately 750 NMD-targeted mRNAs and found that these mRNAs are overrepresented in stress response and tumor-promoting pathways. Consistent with these findings, the inhibition of NMD promotes cellular resistance to endoplasmic reticulum stress and encourages tumor formation. The transcriptional and translational regulations of gene expression by the microenvironment are established mechanisms by which tumor cells adapt to stress. These data indicate that NMD inhibition by the tumor microenvironment is also an important mechanism to dynamically regulate genes critical for the response to cellular stress and tumorigenesis.

Regulation of the unfolded protein response by eif2Bdelta isoforms.

Cells respond to a variety of stresses, including unfolded proteins in the endoplasmic reticulum (ER), by phosphorylating a subunit of translation initiation factor eIF2, eIF2α. eIF2α phosphorylation inactivates the eIF2B complex. The inactivation of eIF2B not only suppresses the initiation of protein translation but paradoxically up-regulates the translation and expression of transcription factor ATF-4. Both of these processes are important for the cellular response to ER stress, also termed the unfolded protein response. Here we demonstrate that cellular response resulting from eIF2α phosphorylation is attenuated in several cancer cell lines. The deficiency of the unfolded protein response in these cells correlates with the expression of a specific isoform of a regulatory eIF2B subunit, eIF2Bδ variant 1 (V1). Replacement of total eIF2Bδ with V1 renders cells insensitive to eIF2α phosphorylation; specifically, they neither up-regulate ATF-4 and ATF-4 targets nor suppress protein translation. Expression of variant 2 eIF2Bδ in ER stress response-deficient cells restores the stress response. Our data suggest that V1 does not interact with the eIF2 complex, a requisite for eIF2B inhibition by eIF2α phosphorylation. Together, these data delineate a novel physiological mechanism to regulate the ER stress response with a large potential impact on a variety of diseases that result in ER stress.

PD184352 releases the regular hypoxic reversible DNA replication arrest in T24 cells.

The oxygen dependent regulation of DNA replication is an essential property of proliferating mammalian cells. In human T24 bladder cancer cells, several hours of hypoxia leads to reversible DNA replication arrest and re-entry of oxygen induces a burst of replication initiation. This short communication provides strong evidence that PD184352 initiates DNA replication in living hypoxic cells without elevating the oxygen level. PD184352 releases the regular hypoxic replicon arrest, however, at a low intensity compared to the effect of reoxygenation. Moreover, PD184352 shows no effect on normoxically incubated as well as reoxygenated T24 cells.

The replicon initiation burst released by reoxygenation of hypoxic T24 cells is accompanied by changes of MCM2 and Cdc7.

Although MCM2 is obviously important for the initiation of eukaryotic DNA replication, its role in O2 dependent regulation of replicon initiation is poorly understood. In this report, I analysed the changes of MCM2 during the transition from hypoxically suppressed replicon initiation to the burst of initiation triggered by reoxygenation in T24 cells. A high level of chromatin bound and nucleosolic MCM2 was found under the hypoxic replicon arrest. In contrast low cytosolic MCM2 was noticed. Recovery of O2 induced phosphorylation and diminution of chromatin bound MCM2, whereas cytosolic MCM2 increased. The level of chromatin bound Cdc7 did not change significantly upon reoxygenation. However, after reoxygenation, significant phosphorylation of Cdc7 and an increase of coimmunoprecipitation with its substrate (MCM2) were observed. This provides a hint that reoxygenation may promote the kinase activity of Cdc7. These changes might be the critical factors in O2 dependent regulation of replicon initiation. Moreover, phosphorylation of Cdc7 by Cdk2 can be observed in vitro, but seems to fail to regulate the level of chromatin bound Cdc7 as well as the changes of MCM2 in response to reoxygenation of hypoxically suppressed cells.