Overcoming Microenvironment-Mediated Chemoprotection through Stromal Galectin-3 Inhibition in Acute Lymphoblastic Leukemia

Environmentally-mediated drug resistance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) significantly contributes to relapse. Stromal cells in the bone marrow environment protect leukemia cells by secretion of chemokines as cues for BCP-ALL migration towards, and adhesion to, stroma. Stromal cells and BCP-ALL cells communicate through stromal galectin-3. Here, we investigated the significance of stromal galectin-3 to BCP-ALL cells. We used CRISPR/Cas9 genome editing to ablate galectin-3 in stromal cells and found that galectin-3 is dispensable for steady-state BCP-ALL proliferation and viability. However, efficient leukemia migration and adhesion to stromal cells are significantly dependent on stromal galectin-3. Importantly, the loss of stromal galectin-3 production sensitized BCP-ALL cells to conventional chemotherapy. We therefore tested novel carbohydrate-based small molecule compounds (Cpd14 and Cpd17) with high specificity for galectin-3. Consistent with results obtained using galectin-3-knockout stromal cells, treatment of stromal-BCP-ALL co-cultures inhibited BCP-ALL migration and adhesion. Moreover, these compounds induced anti-leukemic responses in BCP-ALL cells, including a dose-dependent reduction of viability and proliferation, the induction of apoptosis and, importantly, the inhibition of drug resistance. Collectively, these findings indicate galectin-3 regulates BCP-ALL cell responses to chemotherapy through the interactions between leukemia cells and the stroma, and show that a combination of galectin-3 inhibition with conventional drugs can sensitize the leukemia cells to chemotherapy.     

Effect of pH and zeta potential of Pickering stabilizing magnetite nanoparticles on the features of magnetized polystyrene microspheres

Styrene as a monomer was emulsified in water using several magnetite nanoparticles concentration and pH values. Emulsified styrene drops were used as templates for polymerization, in presence of water soluble free radical initiator, and formation of composite particles. Styrene template drops stabilization was verified by light as well as scanning electron microscopy imaging, which ensured the participation of the particles in building up a mechanical barrier to stop oil drops coalescence. Furthermore, the produced polystyrene composites were strongly attracted to an external magnet. The difference in particles size as a function of pH was elucidated using zeta potential measurements, which indicated dominance of pH on the hydrophilicity of the particles and consequently the extent of emulsification, which in turn affected the size of the obtained microspheres. Under some circumstances, capsules were formed instead of particles. Thereby, it can be concluded that the magnetic microspheres are optimally formed at pH 2.3 independently of the magnetite content used.     

Synergistic toughening and electrical functionalization of an epoxy using MWCNTs and silane- /plasma-activated basalt fibers

This work studied the effects of adding short basalt fibers (BFs) and multi-walled carbon nanotubes (MWCNTs), both separately and in combination, on the mechanical properties, fracture toughness, and electrical conductivity of an epoxy polymer. The surfaces of the short BFs were either treated using a silane coupling agent or further functionalized by atmospheric plasma to enhance the adhesion between the BFs and the epoxy. The results of a single fiber fragmentation test demonstrated a significantly improved BF/epoxy adhesion upon applying the plasma treatment to the BFs. This resulted in better mechanical properties and fracture toughness of the composites containing the plasma-activated BFs. The improved BF/epoxy adhesion also affected the hybrid toughening performance of the BFs and MWCNTs. In particular, synergistic toughening effects were observed when the plasma-activated BFs/MWCNTs hybrid modifiers were used, while only additive toughening effects occurred for the silane-sized BFs/MWCNTs hybrid modifiers. This work demonstrated a potential to develop strong, tough, and electrically conductive epoxy composites by adding hybrid BF/MWCNT modifiers.     

Application of artificial neural networks for modeling of biohydrogen production

In this study, an artificial neural network (ANN) model was developed to estimate the hydrogen production profile with time in batch studies. A back propagation artificial neural network ANN configuration of 5–6–4–1 layers was developed. The ANN inputs were the initial pH, initial substrate and biomass concentrations, temperature, and time. The model training was done using 313 data points from 26 published experiments. The correlation coefficient between the experimental and estimated hydrogen production was 0.989 for training, validating, and testing the model. Results showed that the trained ANN successfully predicted the hydrogen production profile with time for new data with a correlation coefficient of 0.976.     

Measuring the errors of form of industrial surfaces: prediction and optimization

To acquire maximum information on the geometrical errors of industrially made surfaces at a minimum cost, a method for estimating conditional probabilities of a random signal (Bayesian prediction) is applied to three-dimensional metrology. First, a surface is interpolated between data acquired on a coordinate measuring machine (CMM). Then, for a given probability, limit surfaces are computed that bind a region of space containing the known data and the most probable interpolation of the missing data of the surface. These bounds can be treated as the surface; their points can be considered as if they were actual CMM data when fitting a tolerance zone or a datum feature to the data. For Bayesian prediction, the basic hypotheses on the signal are stationarity, ergodicity, and gaussian density. Deviations from these hypotheses and their consequences on the prediction are taken into account and corrections are proposed.     

Urban water demand,climatic variation,and irrigation-water insecurity: interactive stressors and lessons for water governance from the Angat River basin (Philippines)

Climatic variation and intersectoral water competition increasingly challenge the effective provision of irrigation services. This article explores their combined effects on irrigation allocation from the Angat Reservoir (Philippines), where domestic water use in Metro Manila has overtaken regional irrigation as the dominant right-holder. Rules protecting Metro Manila’s large right to water ‘interact’ with dry spells to affect irrigation security in wet and dry seasons. Historically, irrigators were uncompensated because re-allocation’s cause was contested as (1) an unforeseeable climatic event (releasing domestic utilities of liability), or (2) produced by urban demand (requiring compensation). Trade-off rules must be prepared to navigate combinatory effects.     

Use of low CaO unprocessed steel slag in concrete as fine aggregate

Steel slag, which is produced locally in great amounts, has a negative impact on the environment when disposed. Local steel slag has a low CaO content and has no pozzolanic activity.In this research, local unprocessed steel slag is introduced in concrete mixes. Various mixes with compressive strength ranging from 25 to 45 MPa are studied. The slag is used as fine aggregate replacing the sand in the mixes, partly or totally. Ratios of 0%, 15%, 30%, 50% and 100% are used.Depending on the grade of concrete, the compressive strength is improved when steel slag is used for low sand replacement ratios (up to 30%).When optimum values are used, the 28-day tensile strength of concrete is improved by 1.4–2.4 times and the compressive strength is improved by 1.1–1.3 times depending on the replacement ratio and the grade of concrete. The best results are obtained for replacement ratios of 30–50% for tensile strength and 15–30% for compressive strength.Therefore, the use of steel slag in concrete would enhance the strength of concrete, especially tensile strength, provided the correct ratio is used.     

Stearoyl-CoA desaturase activity in adipose tissue and liver of the cardiomyopathic hamster

Stearoyl-CoA desaturase activity and the fatty acid composition of lipids of adipose tissue and liver were determined in 35- and 180-day-old cardiomyopathic hamsters and age-matched normal controls. Enzyme activity was unchanged in the adipose tissue of 35-day-old animals but was significantly depressed in the 180-day-old cardiomyopathic hamsters. In the liver, stearoyl-CoA desaturase activity was significantly lower in the 35-day-old disease animals but was unchanged in the 180-day-old animals. The analysis of the fatty acid composition of the lipids isolated from adipose tissue showed an increase in the relative percentage of saturated fatty acids accompanied by a decrease in the relative percentage of unsaturated fatty acids in both age groups of the cardiomyopathic hamsters. However, linoleic acid content was increased in the diseased animals. Similar changes in fatty acid composition of lipids from the livers of 35-day-old cardiomyopathic hamsters were observed, but no significant differences in the fatty acid composition between 180-day-old cardiomyopathic hamsters and normal controls were observed. The changes in the fatty acid composition appear to be related to the observed changes in desaturase activity. In is concluded that such changes in desaturase activity and fatty acid composition could affect the normal structure and functions of membranes and membrane-related processes.     

A study of A2/O process in El-Berka WWTP by replacing the anaerobic selector with UASB and adopting a hybrid system in the oxic zone

ABSTRACT

A multistage system comprising an upflow anaerobic sludge blanket (UASB) followed by anoxic unit and then oxic activated sludge (AS) with biofilm is studied in El-Berka WWTP, Egypt. Different organic loading wastewaters of chemical oxygen demand (COD) less than 500 mg/L till 3000 mg/L are tested during the study. The hydraulic retention time (HRT) varies for each loading from 7.5 to 10 to 15 h. The UASB reactor accomplishes the removal efficiency of 50%–70% of influent COD. The overall system performs the removal efficiency of 95% of influent COD and NH₄-N. Also, the results are verified by a modified mathematical model.     

Fe2O3/TUD-1: an efficient catalysts for Friedel–Crafts alkylation of aromatics

Three-dimensional mesoporous (Fe-TUD-1) catalysts with different Si/Fe ratios (100, 50, 20 and 10) are prepared using triethanolamine as template. Physicochemical and textural measurements by XRD, elemental analysis, N₂ adsorption, UV–Vis spectroscopy and HR-TEM imaging indicate the formation of pure solid mesoporous materials and the presence of Fe₂O₃ nanoparticles in the prepared Fe-TUD-1 samples. The catalytic performance of Fe-TUD-1 catalysts is tested in Friedel–Crafts alkylations of single-ring aromatic compounds [e.g. toluene (T), ethyl benzene (EB) and cumene (C)] by benzyl alcohol (BnOH). Dispersion of Fe(III) in the mesoporous matrix of TUD-1 enhanced the catalytic activity of Fe-TUD-1 in the alkylation of aromatic compounds compared to pure Fe₂O₃ and TUD-1 catalysts. The catalytic activity further increases by the decreasing of Si/Fe ratio. Sample loaded with Si/Fe ratio = 10 (Fe-10) showed almost complete conversion of BnOH in a relatively very short reaction time (<30 min) with 95 % selectivity. The catalytic performance of Fe-TUD-1 was superior to other metal-containing TUD-1 (e.g. Ga, Sn, and Ti) catalysts, or other Fe-containing catalysts (e.g. Fe-MCM-41, ZSM-5 and Fe-HMS). Alkylation of C is the fastest among the three aromatic substrates investigated (at temperatures very close to their boiling points) due to the largest inductive effect by the isopropyl group compared to the methyl group of T and the ethyl group in EB. Dibenzyl ether is formed as a byproduct only in the early times of the reaction and proved to act as alkylating agent after being hydrolyzed backwards to reform BnOH. Leaching experiments show the Fe-TUD-1 materials are very stable and can be reused as alkylation catalyst.