Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

Corrosion behavior of T24, T92, VM12, and AISI 304 steels exposed to KCl–NaCl–K2SO4–Na2SO4 salt mixtures

The corrosion mechanisms of T24, T92, VM12, and AISI 304 steels are studied under the influence of NaCl–KCl, NaCl–Na₂SO₄, and KCl–K₂SO₄ salt mixtures in a dry air atmosphere at 650°C for 15 days. NaCl–KCl was the most aggressive deposit and AISI 304 stainless steel exhibited the highest corrosion resistance. There was no relation between the Cr content of the ferritic steels and their corrosion resistance in NaCl–KCl. In contrast, the resistance of high-Cr steels was better when exposed to NaCl–Na₂SO₄ and KCl–K₂SO₄. The high-Cr and the low-Cr steels were more susceptible to NaCl–Na₂SO₄ and to KCl–K₂SO₄, respectively.     

Manganese oxides treated with organic compounds as catalysts for water oxidation reaction

Manganese oxides of different crystalline structures: α-MnO₂, δ-MnO₂, α,γ-MnO₂ and Mn₂O₃; were treated with the organic compounds picolinic acid, ethylenediamine and pyridine; and were applied as catalysts in the chemical water oxidation reaction using Ce(IV) ammonium nitrate as sacrificial oxidant. The treatment led to modifications in the oxides properties, such as reduction of the particle size, increase of surface area and partial reduction of Mn⁴⁺ to Mn³⁺ for the Mn(IV) oxides, or of Mn³⁺ to Mn²⁺ for Mn₂O₃, because of favored interactions of the organic molecules with the lattice planes with higher d spacing. Oxygen evolution reaction (OER) tests showed the superior catalytic activity of the treated Mn(IV) oxides, for instance α,γ-MnO₂-en presented TOF five times higher than pure α,γ-MnO₂. The increase in surface area as well as the higher Mn³⁺ content caused by the treatment of the Mn(IV) oxides were correlated with the improvement in the OER catalytic activity.     

The link between countries’ economic and scientific wealth has a complex dependence on technological activity and research policy

Scientometrics - We studied the research performance of 69 countries by considering two different types of new knowledge: incremental (normal) and fundamental (radical). In principle, these two...     

Activated sludge deflocculation under temperature upshifts from 30 to 45 degrees C

Twelve independent batch experiments (<9h) with fresh municipal activated sludge were conducted to assess the occurrence and the mechanisms of deflocculation under a temperature shift from 30 to 45 degrees C. In each experiment, a transient reactor (2 L) was subjected to the temperature shift and a control reactor was operated at a constant temperature of 30 degrees C. The occurrence of deflocculation was demonstrated by the increase in turbidity and in the concentrations of biopolymers in the sludge supernatant from the transient reactor. The maximum levels of proteins in the supernatants ranged from 53 to 81 mg/L, for DNA from 34 to 36 mg/L, for humic compounds from 20 to 40 mg/L, and for carbohydrates from 21 to 31 mg/L. All the biopolymer concentrations in the control reactor remained below 5-10 mg/L. The release of biopolymers was accompanied by an increase in sludge supernatant conductivity (16-32% increase, up to 1.20 mS/cm), soluble chemical oxygen demand (from 129 to 440 mg/L), total suspended solids (>25 mg/L up to 128 mg/L), and a decrease in the mixed liquor volatile suspended solids (up to 11%). The temperature shift was also found to inhibit microbial metabolism by reducing the sludge biomass substrate removal capacity, as measured by oxygen-uptake rates. The temperature shift had a marginal effect causing sludge lysis (as an increase in beta-galactosidase activity) and had no significant impact on sludge viability (live/dead ratio of bacterial cells). It was concluded that sludge deflocculation under a temperature shift from 30 to 45 degrees C involves the solubilisation of extracellular polymeric substances from the flocs and likely also floc fragmentation. In addition, sludge deflocculation and the inhibition of microbial metabolism explain the poor treatment performance observed in previous continuous reactors under similar temperature shifts.     

A Method to Assess the Accuracy of Pseudo-Random Number Sampling Methods from Evacuation Datasets

We propose a method for assessing the accuracy of pseudo-random number sampling methods for evacuation modelling purposes. It consists of a systematic comparison between experimental and generated distributions. The calculated weighted relative error (E _{w_rel} ) is based on the statistical parameters as central moments (mean, standard deviation, skewness and kurtosis) to shape the distribution. The case study involves the Box–Muller transform, the Kernel-Epanechnikov, the Kernel-Gaussian and the Piecewise linear generating samples from eight evacuation datasets fitted against normal, lognormal and uniform distributions. Keeping in mind that the Bos Muller method has two potential sources of error (i.e. distribution fitting and sampling), this method produces plausible results when generating samples from the three types of distributions (E _{w_rel}  < 0.30 for normal, lognormal and uniform distributions). We also fund that the Kernel Gaussian and the Kernel Epanechnikov methods are well accurate in generating samples from normal distributions (E _{w_rel}  < 0.1) but potentially inaccurate when generating samples from uniform and lognormal distributions (E _{w_rel}  > 0.80). Results suggest that the Piecewise linear is the most accurate method (E _{w_rel}  = 0.01 normal; E _{w_rel}  = 0.04 lognormal; E _{w_rel}  = 0.009 uniform). This method has the advantage of sampling directly from empirical datasets i.e. no previous distribution fitting is needed. While the proposed method is used here for evacuation modelling, it can be extended to other fire safety engineering applications.     

Trace metals in the marine bivalve Macoma balthica in the westerschelde estuary, The Nertherlands. Part 3: Variability of the role of cytosol in metal uptake by the clams

Tellinid clams Macoma balthica were sampled every 2 months for 2.5 years at two locations from the Westerschelde estuary (The Netherlands) and submitted to in vitro short-term exposure to Cd, Cu and Zn. Total and heat-stable cytosolic metal concentrations have been measured before and after exposure to study the effects of the sampling season on metal uptake by the bivalve. We observed much higher uptakes of Cd and, to a lesser extent, Cu in winter than in summer, while Zn appears to be constantly regulated. These phenomena are amplified in the cytosol, especially for Cd, a non-essential element, for which the concentrations after exposure can reach 35–45 μg·g⁻¹ (dry wt.) in winter, but only a maximum of 0.5 μg·g⁻¹ in summer, all natural values being between 0.01 and 0.1 μg·g⁻¹ on average. The contents (μg) of the various elements, either at the total or at the cytosolic level, are not constant, hence showing that the seasonal body weight fluctuation of the clams (dilution or concentration effect) is not the only parameter responsible for the metal uptake variability. Furthermore, we have shown that the proportion of cytosolic metal is not constant, but increases with the absolute cytosolic concentration up to 35–40. Therefore, the cytosolic phase of the cells plays a growing role in Cd, Cu and Zn storage as long as their total concentration increases.     

Aflatoxin and PAH exposure biomarkers in a U.S. population with a high incidence of hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) is significantly elevated in a Hispanic community in Bexar County, Texas. Chronic exposure to dietary aflatoxins (AFs) is a major risk factor for HCC; increased risk has been linked to polycyclic aromatic hydrocarbon (PAH) co-exposure and hepatitis virus infection. The aims of this study were to assess AF and PAH exposures, investigate dietary factors that may contribute to increased AF exposure, and determine the prevalence of hepatitis virus infection in Bexar Co. Blood and urine samples were collected from 184 volunteers for biomarker analyses and hepatitis screening. Serum AFB₁-lysine adduct, urinary AFM₁ and 1-hydroxypyrene (1-OHP) levels were measured using high-performance liquid chromatography. The average AFB₁-lysine adduct level detected in 20.6% of serums was 3.84 ± 3.11 pg/mg albumin (range 1.01-16.57 pg/mg). AFM₁ was detected in 11.7% of urines, averaging 223.85 ± 250.56 pg/mg creatinine (range 1.89-935.49 pg/mg). AFM₁ detection was associated with increased consumption of corn tortillas (p = 0.009), nuts (p = 0.033) and rice (p = 0.037). A significant difference was observed between mean 1-OHP values of non-smokers (0.07 ± 0.13) and smokers (0.80 ± 0.68) μmol/mol creatinine (p < 0.01). A high hepatitis C virus positivity rate (7.1%) was observed. Findings suggest that the incidence and level of AF and PAH exposure were less than those observed in a high-risk population; however, participants consuming higher amounts of foods prone to AF contamination may be more vulnerable to exposure and interactions with other environmental/biological factors (i.e., HCV).