Flow rate control in a plug-flow reactor for liquid organic hydrogen carriers dehydrogenation

Liquid organic hydrogen carriers can store hydrogen for later release through dehydrogenation reactions. The kinetic rate depends on the temperature, pressure, and hydrogen concentration itself, so it varies throughout the discharge. As such, control systems are needed to meet the end-user power demand. An innovative plug flow reactor coupled with two vessels is introduced and accurately sized. Multiple strategies are implemented in a Matlab/Simulink model to test the efficacy of control methods based on pressure, temperature, and mass flow rate. The results obtained with the simulations highlight a dramatic drop in performance (utilisation factor lower than 80 %) associated with relatively high power demands (higher than 70 % in the case of temperature control), whereas low demands are met with satisfactory degrees of utilisation under both pressure and temperature control. Control over the mass flow rate of external fluid leads to lackluster results and should only be chosen as an auxiliary controlled variable. Lastly, Ragone diagrams for pressure and temperature control are presented and used to identify the optimal system sizing range: effective discharge duration should be in the range 10–40 h with pressure control or 5–40 h with temperature control to achieve a utilisation factor of at least 80 %

Ragone plots of material-based hydrogen storage systems

This paper presents an analytical assessment of the energy–power relationship for different material-based hydrogen storage systems, namely Metal Hydrides (MHs) and Liquid Organic Hydrogen Carriers (LOHCs). Storage systems are subjected to continuous flow discharge processes through suitable control systems to meet constant specific power demands of end users. By means of reasonable assumptions, analytical expressions of the time-dependent degree of hydrogenation (representing the state of charge) are obtained to find the amount of hydrogen discharged (delivered energy) as a function of flow rate (required power). The results are first presented in the form of dimensionless Ragone plots to highlight the dependence of the amount of discharged hydrogen on the required mass flow rate. Numerical examples are presented for a couple of illustrative systems. Moreover, these analytical expressions are shown to produce very similar results to those obtained with the solution of a dynamic model, including, beyond the kinetic equation, mass and energy conservation applied to the reactor. The results show a significant impact of power demand on the released hydrogen for most systems, similar to that of capacitors, due to the dependence of the rate of reaction on the degree of hydrogenation: as a consequence, the amount of energy that can be delivered to an end user decreases substantially with an increase in the required power, resulting in a poor utilisation factor. Based on these results, MHs exhibit almost first-order kinetics and can sustain efficient discharge with theoretical specific power up to 2 kW/kg (rate of chemical energy delivered per unit mass of active substance), corresponding to a discharge duration of the order of 0.25 h; some LOHCs are limited by second-order kinetics and the specific power should be lower than 1 kW/kg, with discharge durations that must be above 2 hour, to ensure effective utilisation of stored hydrogen

Feasibility study of LOHC-SOFC systems under dynamic behavior for cargo ships compared to ammonia alternatives

Maritime propulsion is recognized as a hard-to-abate sector and its decarbonization will therefore require transversal efforts, including the introduction of alternative fuels to reduce CO2 emissions. Both ammonia and hydrogen could provide clean power; however, forecasts hint that ammonia will be especially useful for longer routes, while hydrogen suffers from low volumetric energy density. This paper evaluates the feasibility of a cargo ship with a SOFC powertrain equipped with LOHC-based hydrogen storage and compares the sizing and heat management requirements of four LOHC systems, namely N-ethylcarbazole (NEC), dibenzyltoluene (DBT), methylcyclohexane (MCH), decaline (DEC), with an ammonia-based one. The size of the 8.4 MW SOFC system is similar for the five carriers as expected. The dynamic performance of the LOHC system shows that the hydrogen flow rate can be effectively controlled by acting on the LOHC flow rate, reactor temperature, and pressure. However, LOHC systems are heavier (by a factor of 1.6 to 2.1) and larger (by 1.6 to 2.3 times) than ammonia systems. The decalin system results in the lowest mass and volume, while NEC is the heavier, and MCH is the least dense of the evaluated LOHCs. Similarly, the utilization of SOFC waste heat to cover dehydrogenation heat ranges from 45.6 % (NEC) to 27.9 % (ammonia). Overall, even considering the lower reaction temperature, LOHCs do not appear to be competitive with ammonia as hydrogen storage systems in the maritime sector

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types