Analysis of growth kinetics and proliferative heterogeneity of Lewis lung carcinoma cells growing as unfed culture

Аim: To analyze the growth kinetics and proliferative heterogeneity of Lewis lung carcinoma (LLC) cells during their growth in monolayer for 5 days without replacement of culture medium (unfed culture). Methods: Cell biology methods, sandwich enzyme-linked immunosorbent assay for vascular endothelial growth factor (VEGF) detection (ELISA), enzymatic glucose-oxidase method for glucose measurements, mathematical modeling. Results: Created mathematical model showed good fit to experimental data; that allowed to determine kinetic (model) parameters of LLC cells and predict the changes in number of proliferating and quiescent cells (proliferative heterogeneity) during their growth. It was shown that growth kinetics of viable LLC cells possesses non-monotonous character — during first three days of growth the number of cells raised exponentially, with following decrease after the maximal level was achieved. At the same time the decrease of number of viable cells/increase of number of dead cells has been observed upon complete depletion of culture medium by glucose content. Glucose dependence of cell transition rate from proliferation to resting state predicted by mathematical model possessed a pronounced two-phase character. At a wide range of relatively high glucose concentrations (> 1.0 mg/ml) the transition rate was close to zero. At concentrations lower than 0.7 mg/ml, the rate of transition swiftly increased resulting in sharp change in cellular composition. At an interval from 70 to 90 h, practically all proliferating cells transited to a resting state. The rate of quiescent cell death was relatively low, and this was in part caused by too low level of glucose consumption compared to proliferating cells. It was shown that during LLC cells growth VEGF production rate decreased monotonously in spite of the fact that the level of VEGF in incubation medium increased monotonously. Observed monotonous decrease of VEGF production rate could not be explained by VEGF degradation in incubation medium (our results displayed the stability of VEGF molecule during investigations). Conclusions: Weak dependence of cell transition rate from proliferating to resting state from glucose level (> 0.7 mg/ml) and low rate of cell death provided slow decrease of the pool of quiescent cells in the population, thus significantly increasing their chance to survive upon nutritional deficiency.Цель: провести анализ кинетики роста и пролиферативной гетерогенности клеток карциномы легкого Льюис (LLC) при их росте в монослое на протяжении 5 сут без замены культуральной среды (unfed culture). Методы: иммуноферментный метод определения уровня продукции VEGF опухолевыми клетками; глюкозооксидазный метод определения уровня глюкозы в среде инкубации; математическое моделирование. Результаты: предложенная математическая модель хорошо описывает экспериментальные данные, что позволяет определить кинетические параметры роста клеток LLC и предсказать изменения количества пролиферирующих и покоящихся клеток (пролиферативная гетерогенность) в процессе их роста. Кинетика роста клеток LLC носит немонотонный характер — в течение первых 3 сут их роста количество клеток экспоненциально увеличивается и далее, по достижении максимальной плотности, снижается. В то же время уменьшение количества живых клеток/увеличение количества мертвых клеток тесно связано с истощением глюкозы в среде инкубации. Зависимость скорости перехода клеток из состояния пролиферации в состояние покоя от содержания глюкозы в среде инкубации имеет выраженный двухфазный характер. В широком диапазоне относительно высоких концентраций глюкозы (> 1,0 мг/ мл) скорость перехода близка к нулю. При концентрациях < 0,7 мг/мл скорость перехода стремительно возрастает, что приводит к резким изменениям клеточного состава клеточной популяции. В интервале от 70 до 90 ч практически все пролиферирующие клетки переходят в состояние покоя. Скорость гибели покоящихся клеток относительно низкая, что, в частности, связано с низким уровнем потребления глюкозы этими клетками по сравнению с таковым пролиферирующими клетками. Установлено, что в процессе роста скорость продукции VEGF клетками LLC монотонно снижается, несмотря на то, что в среде инкубации его уровень монотонно нарастает. Выводы: низкая зависимость скорости перехода клеток LLC из состояния пролиферации в состояние покоя от уровня глюкозы (> 0,7 мг/мл) в среде инкубации, а также низкий уровень их гибели обусловливает медленное снижение пула покоящихся клеток в популяции, что значительно повышает их шансы выжить в условиях дефицита питательных субстратов

Ferroelectric switching in epitaxial GeTe films

In this paper, using a resonance-enhanced piezoresponse force microscopy approach supported by density functional theory computer simulations, we have demonstrated the ferroelectric switching in epitaxial GeTe films. It has been shown that in films with thickness on the order of several nanometers reversible reorientation of polarization occurs due to swapping of the shorter and longer Ge-Te bonds in the interior of the material. It is also hinted that for ultra thin films consisting of just several atomic layers weakly bonded to the substrate, ferroelectric switching may proceed through exchange of Ge and Te planes within individual GeTe layers

Spatial antibunching of photons with parametric down-conversion

The theoretical framework behind a recent experiment by Nogueira et. al. [Phys. Rev. Lett. 86}, 4009 (2001)] of spatial antibunching in a two-photon state generated by collinear type II parametric down-conversion and a birefringent double-slit is presented. The fourth-order quantum correlation function is evaluated and shown to violate the classical Schwarz-type inequality, ensuring that the field does not have a classical analog. We expect these results to be useful in the rapidly growing fields of quantum imaging and quantum information.Comment: 5 pages, 3 figures. Minor changes made, accepted for publication in PR

Non-local model of hollow cathode and glow discharge - theory calculations and experiment comparison

General form of the non-local equation for an ionization source in glow discharge and hollow cathode 3D-simulation is formulated. It is a fundamental equation in a hollow cathode theory, which allows to make up a complete set of field equations for a self-consistent problem in a stationary glow discharge and a hollow cathode. It enables to describe adequately the region of negative glow and the hollow cathode effect. Here you can see first attempts to compare calculation results of electrical dependences (pressure - voltage) and experimental data, - under conditions of gradual appearance of the hollow cathode effect.Comment: 4 pages, 2 figure

Multi-photon, multi-mode polarization entanglement in parametric down-conversion

We study the quantum properties of the polarization of the light produced in type II spontaneous parametric down-conversion in the framework of a multi-mode model valid in any gain regime. We show that the the microscopic polarization entanglement of photon pairs survives in the high gain regime (multi-photon regime), in the form of nonclassical correlation of all the Stokes operators describing polarization degrees of freedom

A toy model of fractal glioma development under RF electric field treatment

A toy model for glioma treatment by a radio frequency electric field is suggested. This low-intensity, intermediate-frequency alternating electric field is known as the tumor-treating-field (TTF). In the framework of this model the efficiency of this TTF is estimated, and the interplay between the TTF and the migration-proliferation dichotomy of cancer cells is considered. The model is based on a modification of a comb model for cancer cells, where the migration-proliferation dichotomy becomes naturally apparent. Considering glioma cancer as a fractal dielectric composite of cancer cells and normal tissue cells, a new effective mechanism of glioma treatment is suggested in the form of a giant enhancement of the TTF. This leads to the irreversible electroporation that may be an effective non-invasive method of treating brain cancer.Comment: Submitted for publication in European Physical Journal

Transition from Townsend to glow discharge: subcritical, mixed or supercritical

The full parameter space of the transition from Townsend to glow discharge is investigated numerically in one space dimension in the classical model: with electrons and positive ions drifting in the local electric field, impact ionization by electrons ($\alpha$ process), secondary electron emission from the cathode ($\gamma$ process) and space charge effects. We also perform a systematic analytical small current expansion about the Townsend limit up to third order in the total current that fits our numerical data very well. Depending on $\gamma$ and system size pd, the transition from Townsend to glow discharge can show the textbook subcritical behavior, but for smaller values of pd, we also find supercritical or some intermediate ``mixed'' behavior. The analysis in particular lays the basis for understanding the complex spatio-temporal patterns in planar barrier discharge systems.Comment: 12 pages, 10 figures, submitted to Phys. Rev.

ЭКСПЕРИМЕНТАЛЬНАЯ ОЦЕНКА КОМПОЗИЦИОННОГО МАТЕРИАЛА НА ОСНОВЕ БЕЛКОВО-МИНЕРАЛЬНЫХ КОМПОНЕНТОВ И РЕКОМБИНАНТНОГО КОСТНОГО МОРФОГЕНЕТИЧЕСКОГО БЕЛКА-2 В КАЧЕСТВЕ ПОКРЫТИЯ ТИТАНОВЫХ ИМПЛАНТАТОВ

The influence of both, the composite material based on the protein-mineral components including the prolonged form of the recombinant human bone morphogenetic protein 2 (rhBMP-2) and the method of the titanium implant’s surface treatment, on the reparative osteogenesis and adhesion strength of the bone tissue – implant’s surface contact was evaluated. Covering of implants with the composite coating promotes significant acceleration of the bone tissue regeneration processes in the site of implants loading. The composition coating with prolonged form of the rhBMP-2 promoted increasing of the neogenic bone tissue’s adhesion with the implants, as compared with the coating without recombinant human bone morphogenetic protein. The implants treated with microarc oxidation demonstrated higher values of the breakout force during the separation of the implants from the bone than the implants treated with sandblasting method.Проведена оценка влияния композиционного материала на основе белково-минеральных компонентов, содержащего пролонгированную форму рекомбинантного костного морфогенетического белка-2 человека (rhВМР-2), и способа обработки поверхности титанового имплантата на репаративный остеогенез и адгезионную прочность контакта костной ткани с поверхностью имплантата. Нанесение на имплантаты композиционного препарата/покрытия способствовало значительному ускорению процессов регенерации костной ткани в месте введения имплантатов. Композиционное покрытие с пролонгированной формой rhBMP-2, способствовало увеличению адгезионных связей новообразованной костной ткани с поверхностью образцов по сравнению с покрытием, не содержащим рекомбинантного костного морфогенетического белка. Имплантаты с поверхностью, обработанной с помощью микродугового оксидирования, демонстрировали более высокие значения величины усилия отрыва имплантата от кости, чем модифицированные пескоструйной обработкой