Numerical extraction of a macroscopic pde and a lifting operator from a lattice Boltzmann model

Lifting operators play an important role in starting a lattice Boltzmann model from a given initial density. The density, a macroscopic variable, needs to be mapped to the distribution functions, mesoscopic variables, of the lattice Boltzmann model. Several methods proposed as lifting operators have been tested and discussed in the literature. The most famous methods are an analytically found lifting operator, like the Chapman-Enskog expansion, and a numerical method, like the Constrained Runs algorithm, to arrive at an implicit expression for the unknown distribution functions with the help of the density. This paper proposes a lifting operator that alleviates several drawbacks of these existing methods. In particular, we focus on the computational expense and the analytical work that needs to be done. The proposed lifting operator, a numerical Chapman-Enskog expansion, obtains the coefficients of the Chapman-Enskog expansion numerically. Another important feature of the use of lifting operators is found in hybrid models. There the lattice Boltzmann model is spatially coupled with a model based on a more macroscopic description, for example an advection-diffusion-reaction equation. In one part of the domain, the lattice Boltzmann model is used, while in another part, the more macroscopic model. Such a hybrid coupling results in missing data at the interfaces between the different models. A lifting operator is then an important tool since the lattice Boltzmann model is typically described by more variables than a model based on a macroscopic partial differential equation.Comment: submitted to SIAM MM

Разработка станций и проведение на них исследований по облучению микросхем и радиобиологии пучками ионов низких и высоких энергий ускорительного комплекса NICA

The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines-reflecting different stages of the disease-on (18)F-fluorodeoxyglucose (FDG), (11)C-choline and (11)C-acetate uptake. Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of (18)F-FDG, (11)C-choline and (11)C-acetate in PCa cell lines, 10(-8)M R1881, 10(-10)M R1881, the combination of 10(-10)M R1881 plus 10(-6)M Casodex or 10(-6)M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. Compared to BPH-1, a higher (18)F-FDG uptake was observed only in PC346C cells, whereas a higher (11)C-choline and markedly increased (11)C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of (18)F-FDG in LNCaP, PC346C and 22Rv1 cells, and of (11)C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on (11)C-choline and (18)F-FDG uptake was observed in PC-3 and PC346DCC cells. (11)C-Acetate uptake was independent of androgen status in all PCa cell lines studied. (18)F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to (18)F-FDG and (11)C-choline, (11)C-acetate uptake was unaffected by androgens and thus (11)C-acetate seems best for monitoring PCa progression

Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype.

Aggressive cancer cells typically show a high rate of energy-consuming anabolic processes driving the synthesis of lipids, proteins, and DNA. Here, we took advantage of the ability of the cell-permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside to increase the intracellular levels of AICA ribotide, an AMP analogue, mimicking a low energy status of the cell. Treatment of cancer cells with AICA riboside impeded lipogenesis, decreased protein translation, and blocked DNA synthesis. Cells treated with AICA riboside stopped proliferating and lost their invasive properties and their ability to form colonies. When administered in vivo, AICA riboside attenuated the growth of MDA-MB-231 tumors in nude mice. These findings point toward a central tie between energy, anabolism, and cancer and suggest that the cellular energy sensing machinery in cancer cells is an exploitable target for cancer prevention and/or therapy

Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy

Whereas significant anti-tumor responses are observed in most BRAFV600E-mutant melanoma patients exposed to MAPK-targeting agents, resistance almost invariably develops. Here, we show that in therapy-responsive cells BRAF inhibition induces downregulation of the processing of Sterol Regulator Element Binding (SREBP-1) and thereby lipogenesis. Irrespective of the escape mechanism, therapy-resistant cells invariably restore this process to promote lipid saturation and protect melanoma from ROS-induced damage and lipid peroxidation. Importantly, pharmacological SREBP-1 inhibition sensitizes BRAFV600E-mutant therapy-resistant melanoma to BRAFV600E inhibitors both in vitro and in a pre-clinical PDX in vivo model. Together, these data indicate that targeting SREBP-1-induced lipogenesis may offer a new avenue to overcome acquisition of resistance to BRAF-targeted therapy. This work also provides evidence that targeting vulnerabilities downstream of oncogenic signaling offers new possibilities in overcoming resistance to targeted therapies.nrpages: 132status: publishe

Lipidomic profiling of clinical prostate cancer reveals targetable alterations in membrane lipid composition

Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting. Significance: This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.Lisa M. Butler, Chui Yan Mah, Jelle Machiels, Andrew D. Vincent, Swati Irani, Shadrack M. Mutuku, Xander Spotbeen, Muralidhararao Bagadi, David Waltregny, Max Moldovan, Jonas Dehairs, Frank Vanderhoydonc, Katarzyna Bloch, Rajdeep Das, Jurgen Stahl, James G. Kench, Thomas Gevaert, Rita Derua, Etienne Waelkens, Zeyad D. Nassar, Luke A. Selth, Paul J. Trim, Marten F. Snel, David J. Lynn, Wayne D. Tilley, Lisa G. Horvath, Margaret M. Centenera, and Johannes V. Swinne

Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition.

peer reviewedDysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the "lipidome" in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting. SIGNIFICANCE: This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents