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•Methane selectivity increases sharply beyond a critical value of Thiele modulus.•Kinetic region extends with increase in pressure or decrease in H2/CO feed ratio.•Methane selectivity ...decreases with increase in conversion and/or decrease in H2/CO.•Multiple steady-state solutions are possible for some values of Thiele modulus.•Hybrid kinetic model was used to predict hydrocarbon product distribution.
In this study we investigate performance characteristics (catalyst effectiveness, CH4 selectivity, and hydrocarbon product distribution) of with a highly active Co/Re/Al2O3 catalyst particle for Fischer-Tropsch synthesis. In numerical simulations we utilize kinetic parameters for CO consumption rate, CH4 formation rate and hydrocarbon formation rates (C2+ hydrocarbons) determined from experiments with this catalyst to study effects of catalyst activity, catalyst particle shape (sphere, slab, solid and hollow cylinder), size (i.e. diffusion length), catalyst distribution (uniform vs. eggshell type distribution for a spherical particle) and process conditions (temperature, pressure, syngas composition and conversion level) on the catalyst performance. With increase in Thiele modulus (i.e. particle size at a fixed set of process conditions) we observe increasing H2/CO ratio profile towards the center of the particle resulting in increase of local and average CH4 selectivity. The goal is to find conditions which allow one to use sufficiently large particles to reduce pressure drop, while avoiding negative influence of diffusional limitations on selectivity and activity. For each catalyst particle shape we determined values of Thiele modulus, i.e. characteristic length of diffusion, corresponding to the upper limit of the kinetic region, and investigated how it changes with operating conditions. We found that simultaneous increase of pressure and the use of syngas with H2/CO feed ratio of 1.4–1.7 is the best strategy for mitigating the negative impact of intraparticle diffusional limitations on CH4 selectivity. For a spherical particle of 1 mm in diameter, one can achieve CH4 selectivity of 5.6% with catalyst effectiveness factor of 1.07 at the reactor inlet by operating at 50 bar, 473 K and H2/CO = 1.4.
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•Forced periodic operations in milli-fixed-bed FTS reactor can be beneficial.•High amplitude modulations are optimal for maximization of C5+ productivity.•Optimal forcing of coolant ...temperature resulted in 30% gain of productivity.•Three inputs forcing resulted in highest C5+ productivity improvement of 52%.•Methane selectivity increased relatively less than C5+ productivity in optimal FPO.
One-dimensional pseudo-homogenous dynamic reactor model, incorporating detailed Fischer-Tropsch kinetics, was applied in a theoretical analysis of forced periodic operations. A milli-scale fixed-bed reactor was analyzed, using design and operation parameters, obtained previously in a steady-state optimization. Dynamic optimization and NLP methods were utilized to obtain optimal values of amplitude(s), frequency and phase shift(s) of sine-wave variation of inputs, around the corresponding optimal steady-state values, which maximize the productivity of C5+ hydrocarbons. Inlet variables that were modulated are: coolant temperature, reactants molar ratio, mass flow rate and pressure. In addition to the single input forcing, simultaneous modulations of multiple inputs were also considered, with combinations of the listed inlet variables. Among the single input cases, periodic variation of the coolant temperature resulted in the highest relative improvement of C5+ productivity by 30%. Multiple inputs forcing showed additional potential for improvement, resulting in relative C5+ productivity increase of 52% for synchronized modulation of the coolant temperature, reactants molar ratio and mass flow rate. However, the increase in C5+ productivity is accompanied with relative increase in methane selectivity of 22–33% (relative to the steady-state value). The results suggest that, in the case of multiple input variations with high amplitudes, modulation of the inlet reactants molar ratio mainly contributes to the increase of CO conversion (e.g. reaction rate), the coolant temperature forcing slightly increases selectivity towards the desirable higher hydrocarbons (C5+), while the variation of the inlet mass flow rate enables better reaction temperature control and prevents a thermal runway.
A two-dimensional pseudo-homogeneous model of wall-cooled fixed bed Fischer-Tropsch synthesis (FTS) reactor with Co/Re/
γ
-Al
2
O
3
catalyst was developed to study the effect of process and design ...parameters on heat generation and removal characteristics. The influence of liquid-phase formation on heat transport was accounted for by using two-phase correlations. The effect of intraparticle diffusion on heat generation was considered. Detailed numerical simulations were performed to analyze the effect of process and design parameters on the reactor performance in terms of heat management. Results show that thermal behavior of FTS fixed bed reactors is very sensitive and any large disturbances can lead to temperature runaway. Large tube diameters are shown to be particularly unfavorable, with d
t
>5 cm resulting in axial and radial gradients greater than 20 K and 13 K, respectively. The importance of detailed reactor modeling when designing and optimizing FTS fixed bed reactors is highlighted.
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•Milli fixed bed Fischer-Tropsch reactors exhibit fast and highly nonlinear dynamics.•Thermal runaway may occur with disturbance of coolant temperature and feed flowrate.•Forced ...periodic operation may enhance Fischer-Tropsch reactor performance.•Temperature control is crucial – advanced control systems are recommended.
Dynamic performance of a milli-scale fixed bed reactor for Fischer-Tropsch synthesis (FTS) was studied using a dynamic pseudo-homogeneous 1D reactor model. The model uses detailed kinetics to describe the rates of FTS product formation. Dynamic responses of the process variables and main performance indicators, including productivity of C5+ hydrocarbons and CH4 selectivity, to input step changes, were analyzed. Total of 7 inlet variables were used in step-change-response analysis, with different magnitudes of change and for two initial steady-state conditions. Reactor simulations show highly nonlinear behavior due to phenomena coupling and fast dynamics due to system small scale and intensified rates within. In addition, reactor model shows instability related to thermal runaway with certain magnitudes of step change of coolant temperature and feed flow rate. The analysis outlines the effects of potential process disturbances on operation of milli-scale fixed bed reactor for FTS and provides general guidelines for control systems.
As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital ...admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin ...(mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.
Abstract Autophagy is a lysosome‐mediated self‐degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and substrates for energy ...metabolism during nutrient or energy deficiency, which are the main stimuli for autophagy induction. However, like most biological processes, autophagy itself requires ATP, and there is an energy threshold for its initiation and execution. We here present the first comprehensive review of this often‐overlooked aspect of autophagy research. The studies in which ATP deficiency suppressed autophagy in vitro and in vivo were classified according to the energy pathway involved (oxidative phosphorylation or glycolysis). A mechanistic insight was provided by pinpointing the critical ATP‐consuming autophagic events, including transcription/translation/interaction of autophagy‐related molecules, autophagosome formation/elongation, autophagosome fusion with the lysosome, and lysosome acidification. The significance of energy‐dependent fine‐tuning of autophagic response for preserving the cell homeostasis, and potential implications for the therapy of cancer, autoimmunity, metabolic disorders, and neurodegeneration are discussed.
We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate ...(PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
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•Phorbol myristate acetate (PMA) activates autophagy in HL-60 leukemia cells.•PMA induces autophagy through PKC-mediated activation of ERK and JNK.•PMA-activated ERK/JNK induces TFEB/FOXO1/3-dependent autophagy gene transcription.•Beclin-1/BCL2 dissociation contributes to PMA-induced ERK/JNK-dependent autophagy.•ERK/JNK-mediated autophagy controls PMA-induced HL-60 macrophage differentiation.
