The high rate of glycolysis despite the presence of oxygen in tumor cells (Warburg effect) suggests an important role for this process in cell division. The glycolytic rate is dependent on the cellular concentration of fructose 2,6-bisphosphate (Fru-2,6-P 2 ), which, in turn, is controlled by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2). The ubiquitous PFK-2 isoenzyme (uPFK-2, alternatively named UBI2K5 or ACG) coded by the pfkfb3 gene is induced by different stimuli (serum, progesterone, insulin, hypoxia, etc.) and has the highest kinase/phosphatase activity ratio amongst all PFK-2 isoenzymes discovered to date, which is consistent with its role as a powerful activator of glycolysis. uPFK-2 is expressed in brain, placenta, transformed cells and proliferating cells. In the present work, we analyze the impact of small interfering RNA (siRNA)-induced silencing of uPFK-2 on the inhibition of cell proliferation. HeLa cells treated with uPFK-2 siRNA showed a decrease in uPFK-2 RNA levels measured at 24 h. uPFK-2 protein levels were severely depleted at 48-72 h when compared with cells treated with an unrelated siRNA, correlating with decreased glycolytic activity, Fru-2,6-P 2 , lactate and ATP concentrations. These metabolic changes led to reduced viability, cell-cycle delay and an increase in the population of apoptotic cells. Moreover, uPFK-2 suppression inhibited anchorage-independent growth. The results obtained highlight the importance of uPFK-2 on the regulation of glycolysis, on cell viability and proliferation and also on anchorage-independent growth. These data underscore the potential for uPFK-2 as an effective tumor therapeutic target.

The experimental stress-strain curves from the standardized tests of Tensile, Plane Stress, Compression, Volumetric Compression, and Shear, are normally used to obtain the invariant λi and constants of material Ci that will define the behavior elastomers. Obtaining these experimental curves requires the use of expensive and complex experimental equipment. For years, a direct method called model updating, which is based on the combination of parameterized finite element (FE) models and experimental force-displacement curves, which are simpler and more economical than stress-strain curves, has been used to obtain the Ci constants. Model updating has the disadvantage of requiring a high computational cost when it is used without the support of any known optimization method or when the number of standardized tests and required Ci constants is high. This paper proposes a methodology that combines the model updating method, the mentioned standardized tests and the multi-response surface method (MRS) with desirability functions to automatically determine the most appropriate Ci constants for modeling the behavior of a group of elastomers. For each standardized test, quadratic regression models were generated for modeling the error functions (ER), which represent the distance between the force-displacement curves that were obtained experimentally and those that were obtained by means of the parameterized FE models. The process of adjusting each Ci constant was carried out with desirability functions, considering the same value of importance for all of the standardized tests. As a practical example, the proposed methodology was validated with the following elastomers: nitrile butadiene rubber (NBR), ethylene-vinyl acetate (EVA), styrene butadiene rubber (SBR) and polyurethane (PUR). Mooney–Rivlin, Ogden, Arruda–Boyce and Gent were considered as the hyper-elastic models for modeling the mechanical behavior of the mentioned elastomers. The validation results, after the Ci parameters were adjusted, showed that the Mooney–Rivlin model was the hyper-elastic model that has the least error of all materials studied (MAEnorm = 0.054 for NBR, MAEnorm = 0.127 for NBR, MAEnorm = 0.116 for EVA and MAEnorm = 0.061 for NBR). The small error obtained in the adjustment of the Ci constants, as well as the computational cost of new materials, suggests that the methodology that this paper proposes could be a simpler and more economical alternative to use to obtain the optimal Ci constants of any type of elastomer than other more sophisticated methods.

Growth of urban areas, the corresponding increased demand for utility services and the possibility of new types of utility systems are overcrowding near surface underground space with urban utilities. Available subsurface space will continue to diminish to the point where utilidors (utility tunnels) may become inevitable. Establishing future sustainable strategies in urban underground engineering consists of the ability to lessen the use of traditional trenching. There is an increasing interest in utility tunnels for urban areas as a sustainable technique to avoid congestion of the subsurface. One of the principal advantages of utility tunnels is the substantially lower environmental impact compared with common trenches. Implementing these underground facilities is retarded most by the initial cost and management procedures. The habitual procedure is to meet problems as they arise in current practice. The moral imperative of sustainable strategies fails to confront the economic and political conflicts of interest. Municipal engineers should act as a key enabler in urban underground sustainable development.

To ensure realistic results when modeling welded joints using the finite element method (FEM), it is essential to appropriately characterize the thermo-mechanical behavior of the elastic-plastic Finite Element (FE) models. This task is complex. Any small differences between the actual welded joints and the welded joints based on FEM can be amplified enormously in the presence of nonlinearities. Due to the intense concentration of heat on a small area to create such joints, the regions near the weld line undergo severe thermal cycles. These generate significant angular distortion due mainly to the residual stresses. This paper proposes a method to determine the parameters that are most appropriate for modeling the Butt joint single V-groove welded joint FE models' thermo-mechanical behavior that were created by the one-pass Gas Metal Arc Welding (GMAW). The method is based on experimental data, as well as genetic algorithms (GA) with multi-objective functions. As a practical example, the proposed methodology is validated with three different welded joints specimens that are manufactured by different voltages and currents (26 volts and 140 amps, 28 volts and 210 amps, and 35 volts and 260 amps). The electrode orientation, shielding gas flow rate, distance between nozzle and plate, and welding speed were considered to be constant for all of the specimens that were studied, and their values were 80 • , 20.0 L/min, 4.0 mm, and 6 mm/s, respectively. The base material was EN 235JR low carbon steel, whereas the weld bead was ER70S-6 for the three specimens that were welded. An agreement between the temperature field and the angular distortion that was obtained by the adjusted FE models and those that were obtained experimentally demonstrates that the proposed methodology may be valid for automatically determining the most appropriate parameters.