The Boudouard reaction, which is the reaction of carbon and carbon dioxide to produce carbon monoxide, represents a simple and straightforward method for the remediation of carbon dioxide in the ...environment through reduction: CO2(g) + C(s) ⇌ 2CO. However, due to the large positive enthalpy, typically reported to be 172 kJ/mol under standard conditions at 298 K, the equilibrium does not favor CO production until temperatures >700 °C, when the entropic term, −TΔS, begins to dominate and the free energy becomes negative. We have found that, under microwave irradiation to selectively heat the carbon, dramatically different thermodynamics for the reaction are observed. During kinetic studies of the reaction under conditions of flowing CO2, the apparent activation energy dropped from 118.4 kJ/mol under conventional convective heating to 38.5 kJ/mol under microwave irradiation. From measurement of the equilibrium constants as a function of temperature, the enthalpy of the reaction dropped from 183.3 kJ/mol at ∼1100 K to 33.4 kJ/mol at the same temperature under microwave irradiation. This changes the position of the equilibrium so that the temperature at which CO becomes the major product drops from 643 °C in the conventional thermal reaction to 213 °C in the microwave. The observed reduction in the apparent enthalpy of the microwave driven reaction, compared to what is determined for the thermal reaction from standard heats of formation, can be thought of as arising from additional energy being put into the carbon by the microwaves, effectively increasing its apparent standard enthalpy. Mechanistically, it is hypothesized that the enhanced reactivity arises from the interaction of CO2 with the steady-state concentration of electron–hole pairs that are present at the surface of the carbon due to the space-charge mechanism, by which microwaves are known to heat carbon. Such a mechanism is unique to microwave-induced heating and, given the effect it has on the thermodynamics of the Boudouard reaction, suggests that its use may yield energy savings in driving the general class of gas–carbon reactions.
Abstract
Claudin-low breast cancers are aggressive tumors defined by the low expression of key components of cellular junctions, associated with mesenchymal and stemness features. Although they are ...generally considered as the most primitive breast malignancies, their histogenesis remains elusive. Here we show that this molecular subtype of breast cancers exhibits a significant diversity, comprising three main subgroups that emerge from unique evolutionary processes. Genetic, gene methylation and gene expression analyses reveal that two of the subgroups relate, respectively, to luminal breast cancers and basal-like breast cancers through the activation of an EMT process over the course of tumor progression. The third subgroup is closely related to normal human mammary stem cells. This unique subgroup of breast cancers shows a paucity of genomic aberrations and a low frequency of
TP53
mutations, supporting the emerging notion that the intrinsic properties of the cell-of-origin constitute a major determinant of the genetic history of tumorigenesis.
HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated ...with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism.
The steam–carbon reaction, which is the essential reaction of the gasification processes of carbon-based feed stocks (e.g., coal and biomass), produces synthesis gas (H2 + CO), a synthetically ...flexible, environmentally benign energy source. The reaction is very endothermic, which mandates high temperatures and a large expenditure of energy to drive the reaction. We have found that using microwave irradiation to selectively heat the carbon leads to dramatically different observed thermodynamics for the reaction. From measurement of the equilibrium constants as a function of temperature, the enthalpy of the reaction under microwave radiation was found to become significantly more exothermic, dropping from 144.2 kJ/mol at the median reaction temperature of 880 K to 15.2 kJ/mol under microwave irradiation. The reaction conditions under which the steam–carbon reaction was run, and under which the equilibrium measurements were determined, consisted of three other reactions that came to equilibrium. These reactions were the Boudouard reaction, which is the reaction of CO2 with carbon to form CO; the water–gas shift reaction, where CO and water react to form H2 and CO2; and the carbon–hydrogen reaction, which generates methane from the reaction of H2 with carbon. We determined the equilibrium constants and thermodynamic parameters for all of these reactions. The Boudouard reaction, which is also strongly endothermic, was found to be more exothermic under microwave radiation (180.2 kJ/mol (thermal) and 27.0 kJ/mol (MW)). The water–gas shift reaction became more endothermic (−36.0 kJ/mol (thermal) and −11.4 kJ/mol (MW)). The carbon–hydrogen reaction also underwent an endothermic shift, from −79.7 to −9.1 kJ/mol. From the associated equilibrium expressions and the equilibrium constants for the steam–carbon reaction system, the mole fractions of the system components under thermal and microwave conditions were estimated. The effect of the microwave radiation was to change the position of the equilibrium so that the temperature at which H2 was at a maximum dropped from 643 °C in the conventional thermal reaction to 213 °C in the microwave. Notwithstanding the predicted temperature shift, there was an observable threshold below which microwaves could not produce products. In our system, the minimum energy at which H2 appeared was 373 °C (30 W), while the temperature at which equilibrium could be established in a reasonable period of time (100 min) was 491 °C (100 W).
Thermally promoted Friedel–Crafts benzylation of arene solvents has been examined under both conventional convective heating with an oil bath and heating using microwave (MW) energy. Bulk solution ...temperaturesas measured by internal and external temperature probes and as defined by solvent refluxwere comparable in both sets of experiments. MW-specific rate enhancements were documented under certain conditions and not others. The observed rate enhancements at a given temperature are proposed to arise from selective MW heating of polar solutes, perturbing thermal equilibrium between the solute and bulk solution. Central to MW-specific thermal phenomena is the difference between heat and temperature. Temperature is a measure of the ensemble average kinetic molecular energy of all solution components, but temperature does not provide information about solute-specific energy differences that may arise as a consequence of selective MW heating. Enhanced chemical reactivity of the MW-absorbing solute can be described as a MW-specific “extra-temperature thermal effect”, because the measurable solution temperature only captures a portion of the solute kinetic molecular energy. Experimental factors that favor MW-specific rate enhancements are discussed with an eye toward future development of MW-actuated organic reactions, in which the observed thermal reactivity exceeds what is predicted from temperature-based Arrhenius calculations.
Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to ...megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. We comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of DNA methylation variation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). Repression effects on tumor suppressor genes are negligible as they are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin and may represent tissue-specific silent regions which tolerate instability at the epigenetic, transcriptomic and genetic level.
Abstract PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for ...which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8 + PD-1 + T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2 + endothelial cells, could overcome immune resistance of ovarian cancers.
Temporary superheating and sustained nucleation-limited "superboiling" of unstirred liquids above the normal atmospheric boiling point have been documented during microwave heating. These phenomena ...are reliably observed under prescribed conditions, although the duration (of superheating) and magnitude (of superheating and superboiling) vary according to system parameters such as volume of the liquid and the size and shape of the vessel. Both phenomena are mitigated by rapid stirring with an appropriate stir bar and/or with the addition of boiling chips, which provide nucleation sites to support the phase-change from liquid to gas. With proper experimental design and especially proper stirring, the measured temperature of typical organic reaction mixtures heated at reflux will be close to the normal boiling point temperature of the solvent, whether heated using microwave radiation or conventional convective heat transfer. These observations are important to take into consideration when comparing reaction rates under conventional and microwave heating.
CD8
T cells are critical mediators of pathogen clearance and anti-tumor immunity. Although signaling pathways leading to the activation of NF-κB transcription factors have crucial functions in the ...regulation of immune responses, the CD8
T cell-autonomous roles of the different NF-κB subunits, are still unresolved. Here, we investigated the function of the ubiquitously expressed transcription factor RelA in CD8
T-cell biology using a novel mouse model and gene-edited human cells. We found that CD8
T cell-specific ablation of RelA markedly altered the transcriptome of
stimulated cells, but maintained the proliferative capacity of both mouse and human cells. In contrast,
experiments showed that RelA deficiency did not affect the CD8
T-cell response to acute viral infection or transplanted tumors. Our data suggest that in CD8
T cells, RelA is dispensable for their protective activity in pathological contexts.
A series of heterogeneous catalyst materials possessing good microwave absorption properties were investigated for their activity as oxidation catalysts under microwave irradiation. These catalysts, ...a series of nanoscale magnetic spinel oxides of the composition MCr2O4 (M = Cu, Co, Fe), were irradiated in aqueous methanol solution (1:1 MeOH:H2O v:v). This resulted in rapid conversion of methanol to formaldehyde, directly generating aqueous formalin solutions. The catalytic reaction occurred under relatively mild conditions (1 atm O2, 60 °C), with irradiation times of 80 min converting 24.5%, 17.7%, and 13.2% of the available methanol to formaldehyde by the Cu, Fe, and Co chromite spinel catalysts, respectively. Importantly, reactions run under identical conditions of concentration, time, and temperature using traditional convective heating yielded dramatically lower amounts of conversions; specifically, 1.0% and 0.21% conversions were observed with Cu and Co spinels, and no observable thermal products were obtained from the Fe spinels. This work provides a clear demonstration that microwave-driven catalysis can yield enhanced reactivity and can afford new catalytic pathways.
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