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A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53 ) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC , KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma—high-grade adenomas—in situ carcinoma: APC gene 42.9–56.0–54.5%; KRAS gene 32.7–32.0–45.5%; TP53 gene 8.2–20.0–18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC , TP53 and KRAS .

The first step in the development of human colorectal cancer is aberrant activation of the Wnt signaling pathway. Wnt signaling hyperactivation is predominantly caused by loss-of-function mutations in the adenomatous polyposis coli ( APC ) gene that encodes the pathway negative regulator. In order to identify genes affected by the Apc loss, we performed expression profiling of intestinal epithelium isolated from mice harboring a conditional Apc allele. The gene encoding transcriptional factor msh homeobox 1 ( Msx 1) displayed robust upregulation upon Apc inactivation. Histological analysis of the Apc-deficient epithelium revealed that in the small intestine, the Msx1 protein was localized exclusively in ectopic crypts, i.e., in pockets of proliferating cells abnormally positioned on the villi. Ablation of the Msx1 gene leads to the disappearance of ectopic crypts and loss of differentiated cells. Moreover, tumors arising from Msx1-deficient cells display altered morphology reminiscent of villous adenomas. In human tumor specimens, MSX1 displayed significantly increased expression in colonic neoplasia with a descending tendency during the lesion progression towards colorectal carcinoma. In summary, the results indicate that Msx1 represents a novel marker of intestinal tumorigenesis. In addition, we described the previously unknown relationship between the Msx1-dependent formation of ectopic crypts and cell differentiation.

Radiation and chemotherapy represent standard‐of‐care cancer treatments. However, most patients eventually experience tumour recurrence, treatment failure and metastatic dissemination with fatal consequences. To elucidate the molecular mechanisms of resistance to radio‐ and chemotherapy, we exposed human cancer cell lines (HeLa, MCF‐7 and DU145) to clinically relevant doses of 5‐azacytidine or ionizing radiation and compared the transcript profiles of all surviving cell subpopulations, including low‐adherent stem‐like cells. Stress‐mobilized low‐adherent cell fractions differed from other survivors in terms of deregulation of hundreds of genes, including those involved in interferon response. Exposure of cancer cells to interferon‐gamma but not interferon‐beta resulted in the development of a heterogeneous, low‐adherent fraction comprising not only apoptotic/necrotic cells but also live cells exhibiting active Notch signalling and expressing stem‐cell markers. Chemical inhibition of mitogen‐activated protein kinase/ERK kinase (MEK) or siRNA‐mediated knockdown of extracellular signal‐regulated kinase 1/2 (Erk1/2) and interferon responsible factor 1 (IRF1) prevented mobilization of the surviving low‐adherent population, indicating that interferon‐gamma‐mediated loss of adhesion and anoikis resistance required an active Erk pathway interlinked with interferon signalling by transcription factor IRF1. Notably, a skin‐specific protein suprabasin (SBSN), a recently identified oncoprotein, was among the top scoring genes upregulated in surviving low‐adherent cancer cells induced by 5‐azacytidine or irradiation. SBSN expression required the activity of the MEK/Erk pathway, and siRNA‐mediated knockdown of SBSN suppressed the low‐adherent fraction in irradiated, interferon‐gamma‐ and 5‐azacytidine‐treated cells, respectively, implicating SBSN in genotoxic stress‐induced phenotypic plasticity and stress resistance. Importantly, SBSN expression was observed in human clinical specimens of colon and ovarian carcinomas, as well as in circulating tumour cells and metastases of the 4T1 mouse model. The association of SBSN expression with progressive stages of cancer development indicates its role in cancer evolution and therapy resistance. Most cancer patients experience tumour recurrence and metastatic dissemination even after radio‐ or chemotherapy. Transcriptome profiling of cancer cells surviving radiation or chemotherapy revealed that, in low‐adherent stem‐like cells, an interferon‐ and mitogen‐activated protein kinase/ERK‐driven transcription program mediated expression of a novel oncoprotein suprabasin that is functionally involved in the survival of low‐adherent cells.

Biochar is a versatile carbon-rich organic material originating from pyrolyzed biomass residues that possess the potential to stabilize organic carbon in the soil, improve soil fertility and water retention, and enhance plant growth. For the utilization of biochar as a soil conditioner, the mutual interconnection of the physicochemical properties of biochar with the production conditions used during the pyrolysis (temperature, heating rate, residence time) and the role of the origin of used biomass seem to be crucial. The aim of the research was focused on a comparison of the properties of biochar samples (originated from oat brans, mixed woodcut, corn residues and commercial compost) produced at different temperatures (400–700 °C) and different residence times (10 and 60 min). The results indicated similar structural features of produced biochar samples; nevertheless, the original biomass showed differences in physicochemical properties. The morphological and structural analysis showed well-developed aromatic porous structures for biochar samples originated from oat brans, mixed woodcut and corn residues. The higher pyrolysis temperature resulted in lower yields; however, it provided products with higher content of organic carbon and a more developed surface area. The lignocellulose biomass with higher contents of lignin is an attractive feedstock material for the production of biochar with potential agricultural applications.

Calcium aluminate phases have a particular effect on the early heat release during setting initiation and have a substantial influence on the further workability of ordinary Portland cement. The nature of the calcium aluminate hydration products and its kinetics strongly depends on sulfate content and humidity. The effect of mineralisers on melt formation and viscosity is well described for calcium silicate systems, but information is still lacking for calcium aluminates. Therefore, the synergistic effect on the crystal structure and hydration mechanism of the tricalcium aluminate phase of the addition of mineralizers, i.e. Li.sub.2O, CuO, SO.sub.3 to the raw meal is here investigated. Co-doped calcium aluminate structures were formed during high-temperature treatment. Thermal analysis (TG-DTA and heating microscopy) was used to describe the ongoing high-temperature reaction. Resulting phase composition was dependent on the concentration of the mineralizer. While phase pure system was prepared with low mineralizer concentrations, with increasing mineralizer content the secondary phases were formed. Raman spectroscopy and XPS analysis were used to investigate the cation substitution and to help describe the cations bonding in co-doped calcium aluminate system. Prepared powders have been hydrated in a controlled manner at different temperatures (288, 298, 308 K). The resulting calorimetric data have been used to investigate the hydration kinetics and determine the rate constant of hydration reaction. First-order reaction (FOR) model was here applied for the activation energy and frequency factor calculations. The metastable and stable calcium aluminate hydrates were formed according to initial phase composition. In phase pure systems with low S content, the formation of stable and metastable hydrates was depended on the reaction temperature. Conversely, in systems with secondary phases and higher S content, the hydration mechanism resembled that which appears in calcium sulfoaluminates.

Calcium aluminate phases have a particular effect on the early heat release during setting initiation and have a substantial influence on the further workability of ordinary Portland cement. The nature of the calcium aluminate hydration products and its kinetics strongly depends on sulfate content and humidity. The effect of mineralisers on melt formation and viscosity is well described for calcium silicate systems, but information is still lacking for calcium aluminates. Therefore, the synergistic effect on the crystal structure and hydration mechanism of the tricalcium aluminate phase of the addition of mineralizers, i.e. Li 2 O, CuO, SO 3 to the raw meal is here investigated. Co-doped calcium aluminate structures were formed during high-temperature treatment. Thermal analysis (TG–DTA and heating microscopy) was used to describe the ongoing high-temperature reaction. Resulting phase composition was dependent on the concentration of the mineralizer. While phase pure system was prepared with low mineralizer concentrations, with increasing mineralizer content the secondary phases were formed. Raman spectroscopy and XPS analysis were used to investigate the cation substitution and to help describe the cations bonding in co-doped calcium aluminate system. Prepared powders have been hydrated in a controlled manner at different temperatures (288, 298, 308 K). The resulting calorimetric data have been used to investigate the hydration kinetics and determine the rate constant of hydration reaction. First-order reaction (FOR) model was here applied for the activation energy and frequency factor calculations. The metastable and stable calcium aluminate hydrates were formed according to initial phase composition. In phase pure systems with low S content, the formation of stable and metastable hydrates was depended on the reaction temperature. Conversely, in systems with secondary phases and higher S content, the hydration mechanism resembled that which appears in calcium sulfoaluminates.

Economically insignificant tick sizes encourage undercutting behavior, thus harming market quality. Theoretical work shows that increasing tick sizes in unconstrained markets reduces undercutting and improves market quality. Equity market pricing grids are generally too coarse to test this prediction. We examine a cryptocurrency market with infinitesimal tick sizes where undercutting limit orders acquire price priority without meaningful economic cost. We show that increasing tick sizes reduces undercutting behavior, increases liquidity provision and quoted depth, and reduces transaction costs for institutional and retail-sized trades while decreasing short-term volatility. Tiny tick sizes are suboptimal, supporting increased minimum trading increments in tick-unconstrained markets.

The contamination of cement binders with zinc represents a significant problem due to the negative effects on cement hydration. Zinc compounds cause a drastic increase in setting time due to prolonging the induction period. The currently accepted mechanism behind this effect is the formation of Ca(Zn(OH) 3 ) 2 ·2 H 2 O hydrates on the surface of cement grains that deplete Ca 2+ ions from the pore solution and creates a diffusion barrier. Hydration accelerators are commonly employed in the concrete industry to counter long setting time caused by low temperature and contamination by heavy metals. These compounds influence both hydration kinetics and composition of hydration products. The influence of various compounds on the mechanism of cement hydration can be studied using calorimetric methods such as isoperibolic and isothermal calorimetry. The hydration of the material was stopped, and the properties of hydrated cement pastes were studied using differential thermal analysis, X-ray diffraction and scanning electron microscopy. Some setting accelerators have been found to significantly decrease setting time of zinc-contaminated cement. Out of the most used compounds in commercial accelerators, the efficiency of thiocyanates is yet to be determined. The results show that thiocyanates induce a visible change in hydration mechanism of cement to various degrees depending on concentration and on the presence of the specific cation. Alkali thiocyanates drastically retard the hydration of zinc-contaminated OPC. With further retarded hydration of cement, the mechanical properties were negatively impacted. Calcium thiocyanate on the other hand effectively accelerates setting and positively impacts compressive strength at low doses. Main difference between the influence of alkali and calcium thiocyanates on setting is the change in ettringite content. Alkali salt promotes AFm phases at the expense of ettringite content while calcium salt promotes formation of ettringite at early stages of cement hydration.