Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM.     

Aluminium content of beers

 The aluminium (Al) concentration in different brands of beers packaged in Al cans and glass bottles was measured at the end of the shelf-life of the beer, by the Zeeman graphite furnace atomic absorption spectrophotometry (ZGFAAS) method. The results show that in all cases a brand of beer packaged in an Al can has a higher Al content than the same brand bottled in glass. The measurements of the Al concentration in some Al-canned beers throughout 12 months of storage show that a relatively small increase of the Al concentration in beers occurs throughout storage. All these results indicate that some Al is taken up by the beer in Al cans, presumably through the slight and slow dissolution of Al from the can wall, due to some defects in the protective lacquer layer. The evaluated daily intake of Al (0.256 mg) possible through the consumption of beer was practically negligible in relation to both the total daily dietary Al intake and the tolerable daily Al intake. Thus, beers are an insignificant source of dietary Al intake and it appears that the Al intake from beers (due to the low content of Al in beers and its low bioavailability) should not be a cause for concern with regard to Al toxicity for the human body. Received: 22 April 1996     

Phenolic compound composition and antioxidant activity of fruits of Rubus and Prunus species from Croatia

Two fraction, one containing flavonols, flavan-3-ols, phenolic acids and the other containing anthocyanins, were isolated from Rubus (red raspberry, blackberry) and Prunus (sweet cherry, sour cherry) fruits to study their phenol content by HPLC and antioxidant activity using the DPPH test. Raspberries and blackberries were characterised by catechins and ellagic acid derivatives; sour and sweet cherries by phenolic acids. All fruits had relatively high anthocyanin content. Anthocyanins contributed more to the antioxidant activity of all fruits (∼90%) than flavonols, flavan-3-ols and phenolic acids (∼10%). A biphasic reaction was observed between DPPH^• radicals and phenols, with 'fast' and 'slow' scavenging rates which might be important in the biological activity of these fruits. Sour cherries and blackberries which stand out with the highest total phenol content (1416 and 1040 mg kg⁻¹) had also the strongest antioxidant activity (EC₅₀ = 807 and 672 g of fruit per gram of DPPH) and can be considered as good source of dietary phenols.     

Moisture loss and oil uptake during deep fat frying of “Kroštula” dough

The mechanism of moisture transfer by diffusion and uptake of frying oil was studied during deep fat frying of Krotula dough with an initial moisture content of 0.4358 kg/kg (db). The experimental data were found to fit well to a first-order exponential model for moisture transfer (with a regression coefficient of 0.99). The effective moisture diffusivity of Krotula dough was determined for two periods of moisture loss (intensive in first 60 s and constant after 60 s of frying). In the frying range 0–60 s at temperatures of 160, 170, 180 and 190±1 °C, the effective moisture diffusivity values were 5.837, 6.607, 8.472 and 9.728×10^–9 m²/s, from which the activation energy (30 kJ/mol) was calculated by using an Arrhenius-type equation. The effective oil diffusivity values of Krotula dough in the frying time range 0–210 s at temperatures of 160, 170, 180 and 190±1 °C were 0.932, 1.135, 1.094 and 1.054×10^–9 m²/s, from which the activation energy (5.5 kJ/mol) was calculated by using an Arrhenius-type equation.     

Determination of thermal conductivity and convective heat transfer coefficient during deep fat frying of “Kroštula” dough

In this study, the influence of oil temperature, water migration and surface temperature of Krotula dough on convective heat transfer coefficient was investigated. The convective heat transfer coefficient during deep fat frying was determined at temperatures 160, 170, 180 and 190±1 °C. Heat transfer coefficient was the highest at the start of deep fat frying process; 579.12±2.46, 583.88±1.81, 597.05±1.10 and 657.91±0.95 W/m² K for 160, 170, 180 and 190 °C of oil temperature, respectively. The smallest heat transfer coefficient was in the case of setting up a uniform period of water migration from sample, which corresponded to surface temperatures slightly higher than 100 °C; 26.53±0.63, 14.42±0.56, 56.78±0.49 and 37.52±0.54 W/m² K for 160, 170, 180 and 190 °C of oil temperature, respectively. Higher oil temperature for deep fat frying increased values of heat transfer coefficient. A steady-state method was used to determine thermal conductivity of Krotula dough in temperature range of 40–70±1 °C. The thermal conductivity first increased with temperature and then after reaching maximum values decreased. The maximum value 0.5985±0.0196 W/(m K) was determined at 47.5 °C. The minimal value 0.4723±0.0192 W/(m K) was determined at 65 °C.     

Efficacy of Rainfall-Runoff Models in Loose Coupling Spacial Decision Support Systems Modelbase

Water Resources Management - The need for a prognosis for water resources management in Brazil means that studies with hydrological models are required, as part of a Spatial Decision Support System...     

Aluminium content of beers

 The aluminium (Al) concentration in different brands of beers packaged in Al cans and glass bottles was measured at the end of the shelf-life of the beer, by the Zeeman graphite furnace atomic absorption spectrophotometry (ZGFAAS) method. The results show that in all cases a brand of beer packaged in an Al can has a higher Al content than the same brand bottled in glass. The measurements of the Al concentration in some Al-canned beers throughout 12 months of storage show that a relatively small increase of the Al concentration in beers occurs throughout storage. All these results indicate that some Al is taken up by the beer in Al cans, presumably through the slight and slow dissolution of Al from the can wall, due to some defects in the protective lacquer layer. The evaluated daily intake of Al (0.256 mg) possible through the consumption of beer was practically negligible in relation to both the total daily dietary Al intake and the tolerable daily Al intake. Thus, beers are an insignificant source of dietary Al intake and it appears that the Al intake from beers (due to the low content of Al in beers and its low bioavailability) should not be a cause for concern with regard to Al toxicity for the human body. Received: 22 April 1996     

Specific Heat and Thermal Conductivity of the Croatian Unleavened Dough

A line heat source probe method was used to determine thermal conductivity of the Croatian unleavened dough in a temperature range of 27–125°C. For estimation of the specific heat of the Croatian unleavened dough, a mixing method was used. The maximum value of 4.0 ± 0.8 kJ/(kg °C) was determined at 57.1°C for the potato dough, and the minimum value of 1.4 ± 0.6 kJ/(kg °C) was determined at 35.3°C for the Kro?tula dough. Thermal conductivity first increased with temperature and then decreased after reaching its maximum value. Minimum value of 0.29 ± 0.04 W/(m °C) was determined at 123.8°C for the Kro?tula dough. Further on, a set of empirical equations was established using regression analysis to correlate the results and to predict the specific heat and thermal conductivity of the Croatian unleavened dough within the studied temperature range and moisture levels.     

Evolutionary Radial Basis Functions for Credit Assessment

Credit analysts generally assess the risk of credit applications based on their previous experience. They frequently employ quantitative methods to this end. Among the methods used, Artificial Neural Networks have been particularly successful and have been incorporated into several computational tools. However, the design of efficient Artificial Neural Networks is largely affected by the definition of adequate values for their free parameters. This article discusses a new approach to the design of a particular Artificial Neural Networks model, RBF networks, through Genetic Algorithms. It presents an overall view of the problems involved and the different approaches employed to optimize Artificial Neural Networks genetically. For such, several methods proposed in the literature for optimizing RBF networks using Genetic Algorithms are discussed. Finally, the model proposed by the authors is described and experimental results using this model for a credit risk assessment problem are presented.