Acidosis of the tumor microenvironment is typical of a malignant phenotype, particularly in hypoxic tumors. All cells express multiple isoforms of carbonic anhydrase (CA), enzymes catalyzing the reversible hydration of carbon dioxide into bicarbonate and protons. Tumor cells express membrane-bound CAIX and CAXII that are controlled via the hypoxia-inducible factor (HIF). Despite the recognition that tumor expression of HIF-1alpha and CAIX correlates with poor patient survival, the role of CAIX and CAXII in tumor growth is not fully resolved. To understand the advantage that tumor cells derive from expression of both CAIX and CAXII, we set up experiments to either force or invalidate the expression of these enzymes. In hypoxic LS174Tr tumor cells expressing either one or both CA isoforms, we show that (a) in response to a "CO(2) load," both CAs contribute to extracellular acidification and (b) both contribute to maintain a more alkaline resting intracellular pH (pH(i)), an action that preserves ATP levels and cell survival in a range of acidic outside pH (6.0-6.8) and low bicarbonate medium. In vivo experiments show that ca9 silencing alone leads to a 40% reduction in xenograft tumor volume with up-regulation of ca12 mRNA levels, whereas invalidation of both CAIX and CAXII gives an impressive 85% reduction. Thus, hypoxia-induced CAIX and CAXII are major tumor prosurvival pH(i)-regulating enzymes, and their combined targeting shows that they hold potential as anticancer targets.
The ‘acid mantle’ of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e.g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e.g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases.
A classical linear oscillator is treated in the small amplitude limit so that it will be approximately relativistic. The oscillator involves a charge particle in a linear potential in classical zero-point radiation. It is found that the ground state is energy balanced with the power lost in radiation emission equal to the average power gained from resonance with the classical zero-point radiation. Also the oscillator is found to have resonant excited states where the energy emitted as dipole radiation is balanced on average by the energy gained from the zero-point radiation when the action variable of the mechanical system is given by J=(n+1/2)(h/2pi).
Efficient calibration is essential for the practical application of option pricing models. The Fractional Stochastic Volatility Jump Diffusion (FVSJ) model proposed by Zhang and Yong [1] can reproduce several stylized features observed in option markets, including the volatility smile, volatility clustering, and long-memory effects. However, its multiple stochastic components make conventional calibration computationally expensive. This paper proposes a two-step calibration framework that combines a neural network with a differential evolution (DE) algorithm. In the first step, we construct a Physics-Informed Kolmogorov-Arnold Network (PCKAN) to approximate the FVSJ pricing map. Specifically, we replace the B-spline basis in KAN with second-kind Chebyshev polynomials and incorporate a Black-Scholes PDE residual as an additional penalty term in the training objective, aiming to improve global approximation and enhance numerical stability and interpretability. In the second step, the trained PCKAN is used as a fast surrogate pricer within the DE algorithm to accelerate parameter estimation. Empirical results show that the proposed method achieves calibration accuracy comparable to direct pricing while substantially reducing computational time.
Rotary dynamics of polarized composite particles as dipole rigid bodies is considered. It is described the Euler equations singularly perturbed by the radiation reaction torque. The Schott term is taken into account, and the reduction procedure lowering higher derivatives is applied. Asymptotic methods of nonlinear mechanics are used to analyze the rotary dynamics of askew-polarized spinning top. Numerical estimates are relevant to the hypothetical DAST-nanocrystals that might possess a huge dipole moment.
Highlights ► High odour emission from food waste compost was correlated to low pH. ► Microbes in high-odour samples included Lactic acid bacteria and Clostridia. ► For odour prevention, try high initial aeration rate and recycled compost as additive.
An application of variational principle to bifurcation of periodic solution in Lagrangian mechanics is shown. A few higher derivatives of the action integral at a periodic solution reveals the behaviour of the action in function space near the solution. Then the variational principle gives a method to find bifurcations from the solution. The second derivative (Hessian) of the action has an important role. At a bifurcation point, an eigenvalue of Hessian tends to zero. Inversely, if an eigenvalue tends to zero, the zero point is a bifurcation point. The third and higher derivatives of the action determine the properties of the bifurcation and bifurcated solution.