Industrial methanol production involves a multi component feed containing methanol, water and trace levels of ethanol being refined to produce AA grade methanol at high product recovery. Due to ...practical constraints, the bottoms discharge of the column is primarily water with only trace of methanol impurities. As a result of these constraints, ethanol, which is a non-key middle boiling component gets “trapped” near the side draw of the column forming an ethanol bulge, which in turn results in non-linear, inverse, time and state varying behaviour of the side draw ethanol composition. In this work, we established that the existence of the ethanol bulge creates the complex process behaviour of the side draw ethanol composition and that this bulge needs to be explicitly controlled. This type of explicit composition bulge analysis and subsequent control has not been attempted on methanol distillation columns before. For this purpose a novel, robust and practical side draw control scheme to detect and remedy the excess ethanol bulge movement using override control is presented. The side draw controller, together with other regulatory controllers is shown to maintain on-specification operations of the column. Disturbance rejection tests carried out illustrate that the side draw control scheme will keep the column operating within commercial specification. It is also shown that a traditional DV control structure is unable to achieve this objective.
•The industrial methanol distillation column with a side draw was modelled.•Analysis shows that the ethanol profile creates a bulge near the side draw.•Ethanol bulge found to play a key role in stable collumn operations.•A new algorithm and control structure developed to detect and control the ethanol bulge.•Disturbance rejection tests show new control structure achieves on specification performance.
Operating lignocellulosic fermentation processes to produce fuels and chemicals is challenging due to the inherent complexity and variability of the fermentation media. Real‐time monitoring is ...necessary to compensate for these challenges, but the traditional process monitoring methods fail to deliver actionable information that can be used to implement advanced control strategies. In this study, a hybrid‐modeling approach is presented to monitor cellulose‐to‐ethanol (EtOH) fermentations in real‐time. The hybrid approach uses a continuous‐discrete extended Kalman filter to reconciliate the predictions of a data‐driven model and a kinetic model and to estimate the concentration of glucose (Glu), xylose (Xyl), and EtOH. The data‐driven model is based on partial least squares (PLS) regression and predicts in real‐time the concentration of Glu, Xyl, and EtOH from spectra collected with attenuated total reflectance mid‐infrared spectroscopy. The estimations made by the hybrid approach, the data‐driven models and the internal model were compared in two validation experiments showing that the hybrid model significantly outperformed the PLS and improved the predictions of the internal model. Furthermore, the hybrid model delivered consistent estimates even when disturbances in the measurements occurred, demonstrating the robustness of the method. The consistency of the proposed hybrid model opens the doors towards the implementation of advanced feedback control schemes.
‐Data‐based models allow measuring key process variables in real‐time. However, they lack predictive power to forecast the progress of the fermentation.
‐Mechanistic models use the initial conditions to predict the progress of the fermentation, but they cannot account for process deviations.
‐The hybrid approach uses a continuous‐discrete extended Kalman to incorporate the real‐time measurements obtained with the data‐driven models to the mechanistic models to improve the forecasts.
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•A multi-layered view of chemical and biochemical engineering (C&BE) is given.•Aspects of research, education and practice are highlighted.•Perspectives in terms of current state and ...significance of C&BE are presented.•Perspectives in terms of future scope and significance of C&BE are presented.
The contents of this article are based on the results of discussions the corresponding author has had since 2015 with the co-authors, who are members of academia and industry in Europe, on the scope and significance of chemical and biochemical engineering as a discipline. The result is a multi-layered view of chemical and biochemical engineering where the inner-layer deals with the fundamental principles and their application; the middle-layer deals with consolidation and expansion of the principles through a combination of science and engineering, leading to the development of sustainable technologies; and the outer-layer deals with integration of knowledge and collaboration with other disciplines to achieve a more sustainable society. Through this multi-layered view several important issues with respect to education, research and practice are highlighted together with current and future challenges and opportunities.
ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed ...mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.
Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in pediatric gliomas. These H3.3 point mutations affect many ...chromatin modifications but the exact oncogenic mechanisms are currently unclear. Histone H3.3 is known to localize to nuclear compartments known as promyelocytic leukemia (PML) nuclear bodies, which are frequently mutated and confirmed as oncogenic drivers in acute promyelocytic leukemia.
We find that the pediatric glioma-associated H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to leukemias driven by PML mutations, H3.3-mutated glioma cells are sensitive to drugs that target PML bodies. We also find that point mutations in IDH1/2-which are common events in adult gliomas and myeloid leukemias-also disrupt the formation of PML bodies.
We identify PML as a contributor to oncogenesis in a subset of gliomas and show that targeting PML bodies is effective in treating these H3.3-mutated pediatric gliomas.
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•Economic assessment of a Sargassum biogas plant with hydrothermal pretreatment (HTP).•Sargassum harvesting and HTP increase the overall process operation cost.•Maximum income derived ...from pretreated Sargassum/raw food waste blend (25:75).•Process environmental impact is nearly 10-fold lower than direct landfill disposal.•Local electricity and digestate consumption can promote energy and food security.
Pelagic Sargassum inundation of coastlines across the North Atlantic is an ongoing challenge but presents new opportunities for value-added resource recovery. This study assessed the techno-economic feasibility and environmental impact of utilising these invasive brown seaweed, and food waste as feedstock for energy production and fertiliser recovery in Barbados. The biorefinery concept evaluated was designed with hydrothermal pretreatment (HTP) and anaerobic digestion (AD) technologies. Financial analyses of four varied feedstock and process scenarios (S1-S4) established a linear relationship between profitability and the sale of products (electricity and fertiliser). In all cases, simple sale of power generated to the national grid resulted in a negative cash flow and required the introduction of fertiliser sales to achieve positive cash flows. Moreover, the net loss in the electricity only scenarios exceeded that of the landfill disposal, the present operation employed on the island for Sargassum management. The addition of the solid digestate to the revenue stream increased the profit margin and financial attractiveness of the process. Maximum income generation could be attained through 100% supply of the digestate to international markets. However, this approach provides zero support to local food security. The preferred option involves the 50/50 split utilisation of the solid digestate in local and international agricultural practice. While HTP is energy-intensive technology, the recirculation of waste heat generated by a combined heat and power unit for HTP reduced the input energy demand. It also lowered the potential environmental impact by more than 10-fold, relative to landfill disposal. Recycling of the liquid digestate also reduced the fresh water demand and its associated costs. Despite the promising results, process scale-up and commercialisation remain a main challenge, primarily due to the seasonality and variability of Sargassum seaweed for continuous bioprocessing.
In addition to being a hallmark at active genes, histone variant H3.3 is deposited by ATRX at repressive chromatin regions, including the telomeres. It is unclear how H3.3 promotes heterochromatin ...assembly. We show that H3.3 is targeted for K9 trimethylation to establish a heterochromatic state enriched in trimethylated H3.3K9 at telomeres. In H3f3a(-/-) and H3f3b(-/-) mouse embryonic stem cells (ESCs), H3.3 deficiency results in reduced levels of H3K9me3, H4K20me3 and ATRX at telomeres. The H3f3b(-/-) cells show increased levels of telomeric damage and sister chromatid exchange (t-SCE) activity when telomeres are compromised by treatment with a G-quadruplex (G4) DNA binding ligand or by ASF1 depletion. Overexpression of wild-type H3.3 (but not a H3.3K9 mutant) in H3f3b(-/-) cells increases H3K9 trimethylation level at telomeres and represses t-SCE activity induced by a G4 ligand. This study demonstrates the importance of H3.3K9 trimethylation in heterochromatin formation at telomeres. It provides insights into H3.3 function in maintaining integrity of mammalian constitutive heterochromatin, adding to its role in mediating transcription memory in the genome.
Human ALT cancers show high mutation rates in ATRX and DAXX. Although it is well known that the absence of ATRX/DAXX disrupts H3.3 deposition at heterochromatin, its impact on H3.3 deposition and ...post-translational modification in the global genome remains unclear. Here, we explore the dynamics of phosphorylated H3.3 serine 31 (H3.3S31ph) in human ALT cancer cells. While H3.3S31ph is found only at pericentric satellite DNA repeats during mitosis in most somatic human cells, a high level of H3.3S31ph is detected on the entire chromosome in ALT cells, attributable to an elevated CHK1 activity in these cells. Drug inhibition of CHK1 activity during mitosis and expression of mutant H3.3S31A in these ALT cells result in a decrease in H3.3S31ph levels accompanied with increased levels of phosphorylated H2AX serine 139 on chromosome arms and at the telomeres. Furthermore, the inhibition of CHK1 activity in these cells also reduces cell viability. Our findings suggest a novel role of CHK1 as an H3.3S31 kinase, and that CHK1-mediated H3.3S31ph plays an important role in the maintenance of chromatin integrity and cell survival in ALT cancer cells.
Anaerobic digestion is one of the most sensitive wastewater treatment processes where a major component of organic matter such as carbohydrates, proteins, and lipids are degraded by the syntrophic ...correlation between anaerobic microorganisms. The anaerobic reactors in desiccated coconut processing plants are frequently subjected to lipid inhibition due to the presence of oily compounds consisting of high concentrations of medium-chain and long-chain fatty acids. Improper treatment leads to severe issues such as biomass washout, inefficient treatment, and reactor failures during anaerobic digestion. This review critically analyzes lipid inhibition mechanism and controlling factors to overcome the inhibition during anaerobic digestion. The existing strategies provide positive outcomes to overcome lipid inhibition. However, the effectiveness of these strategies may change due to process variations and different environmental conditions. Therefore, more research should be further conducted to optimize these strategies to improve process stability, treatment efficiency, and economic viability of desiccated coconut wastewater treatment.
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•Lipid inhibition is the major challenge in the anaerobic digestion of DCWW.•The mechanism and effects of lipid inhibition are elaborated.•Existing strategies to overcome lipid inhibition are critically discussed.•Novel strategies to overcome lipid inhibition for DCWW are presented.•The commercially viable novel strategies to avoid lipid inhibition are essential.
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