Promotive effects of hyperthermia on the сytostatic activity to ehrlich ascites tumor cells by diverse delta-alkyllactones

To evaluate promotive effects of hyperthermia on antitumor activity of new delta-alkyllactones (DALs) of low molecular weight (184–254 Da), chemically synthesized, which are different from natural macrocyclic lactones of high molecular weight (348–439 Da), such as camptothecin and sultriecin. Methods: A suspension of Ehrlich ascites tumor (EAT) cells was mixed with a DAL in a glass tube, heated at 37 or 42 °C for 30 min in a water bath, and cultured at 37 °C for 20 or 72 h. Cell viability was measured by the mitochondrial dehydrogenase- based WST-1 assay. DALs incorporated into EAT cells was extracted and measured by gas-liquid chromatography. Results: The reduction of cell viability by DALs was markedly enhanced upon the treatment at 42 °C compared to that at 37 oC. At 37 oC, delta-hexadecalactone (DH16 : 0) and delta-tetradecalactone (DTe14 : 0) displayed cytostatic activity (at 100 µM survival level: 20.7%, 66.1%; at 50 µM — 41.2%, 82.4%, respectively). Their activity was more marked at 42 °C (at 100 µM 10.6%, 27.6%; at 50 µM 30.6, 37.5 %, ibid). The other DALs, delta-undecalactone (DU11 : 0), delta-dodecalactone (DD12 : 0), and delta-tridecanolactone (DTr13 : 0) were almost ineffective. Evaluation of survival rate in the cells treated for 30 min by DALs with the next culturing of EAT cells for 72 h resulted in the enhanced carcinostatic activity of DH16:0 and DTe14:0 even at concentrations as low as 25 µM at either 37 °C (18.5%, 78.5%, ibid) or 42 °C (5.0%, 42.0%, ibid), but the others exhibited slight activity or none. DH16 : 0 was effective at either 37 °C (36.0%) or 42 °C (23.0%) even at a lower dose of 10 µM. At the same time only the most cytostatic DH16 : 0 was incorporated into EAT cells and the rate of incorporation was more at 42 °C than at 37 °C. Conclusion: Delta-hexadecanolactone (DH16 : 0) exhibited the most cytostatic effect that was significantly enhanced by hyperthermia. It allows to consider it as a potent antitumor agent, especially in combination with hyperthermia.Цель: оценить промоторный эффект гипертермии на противоопухолевую активность новых низкомолекулярных (184–254 Да) дельта-алкиллактонов (DALs), химически синтезированных из разных макроциклических высокомолекулярных (348–439Да) лактонов естественного происхождения, таких как камптотецин и салтриецин. Методы: суспензию клеток асцитной опухоли Эрлиха (EAT) смешивали с DAL в стеклянной пробирке, нагревали до 37 °C или 42 °C в течение 30 мин на водяной бане и далее культивировали при 37 °C в течение 20 или 72 ч. Оценку жизнеспособности клеток проводили с помощью WST-1 анализа, основанного на определении митохондриальной дегидрогеназы. Инкорпорированные в EAT-клетки DALs экстрагировали, их уровень измеряли с помощью газо-жидкостной хроматографии. Результаты: DALs значительно снижали жизнеспособность клеток после предварительной обработки при 42 °C по сравнению с 37 °C. При 37 °C были эффективными дельта-гексадекалактон (DH16 : 0) и дельта-тетрадекалактон (DTe14 : 0) (при 100 μM уровень выживаемости: 20,7; 66,1%; при 50 μM — 41,2; 82,4% соответственно). Этот эффект был более выраженным при 42 °C (при 100 μM 10,6; 27,6%; при 50μM 30,6; 37,5% соответственно). Другие DALs, а именно дельта-ундекалактон (DU11 : 0), дельта-додекалактон (DD12 : 0) и дельта-тридекалактон (DTr13 : 0) были практически не эффективны. Оценка уровня выживаемости EAT-клеток, 30 мин обработанных DALs с последующим культивированием в течение 72 ч, показала повышенную канцеростатичсекую активность DH16 : 0 и DTe14 :0 даже при 25 μM концентрации, как при 37 °C (18,5; 78,5% соответсвенно), так и при 42 °C (5,0; 42,0% соответственно). Для других DALs данный эффект был незначительный либо отсутствовал. DH16 : 0 оставался эффективным как при 37 °C (36,0%), так и при 42 °C (23,0%) в 10 μM концентрации. В то же время только наиболее эффективный DAL — DH16 : 0 инкорпорировался в клетки EAT, и уровень инкорпорирования был выше при 42 °C, чем при 37 °C. Выводы: дельта-гексадеканолактон (DH16 : 0) показал наибольшую цитостатическую активность, которая значительно усиливалась в комбинации с гипертермией. Этот DAL можно рассматривать как потенциальный цитостатик, действие которого усиливается при гипертермии

Multi-Cell ECM compaction is predictable via superposition of nonlinear cell dynamics linearized in augmented state space

Cells interacting through an extracellular matrix (ECM) exhibit emergent behaviors resulting from collective intercellular interaction. In wound healing and tissue development, characteristic compaction of ECM gel is induced by multiple cells that generate tensions in the ECM fibers and coordinate their actions with other cells. Computational prediction of collective cell-ECM interaction based on first principles is highly complex especially as the number of cells increase. Here, we introduce a computationally-efficient method for predicting nonlinear behaviors of multiple cells interacting mechanically through a 3-D ECM fiber network. The key enabling technique is superposition of single cell computational models to predict multicellular behaviors. While cell-ECM interactions are highly nonlinear, they can be linearized accurately with a unique method, termed Dual-Faceted Linearization. This method recasts the original nonlinear dynamics in an augmented space where the system behaves more linearly. The independent state variables are augmented by combining auxiliary variables that inform nonlinear elements involved in the system. This computational method involves a) expressing the original nonlinear state equations with two sets of linear dynamic equations b) reducing the order of the augmented linear system via principal component analysis and c) superposing individual single cell-ECM dynamics to predict collective behaviors of multiple cells. The method is computationally efficient compared to original nonlinear dynamic simulation and accurate compared to traditional Taylor expansion linearization. Furthermore, we reproduce reported experimental results of multi-cell induced ECM compaction

Dynamic ordering of driven vortex matter in the peak effect regime of amorphous MoGe films and 2H-NbSe2 crystals

Dynamic ordering of driven vortex matter has been investigated in the peak effect regime of both amorphous MoGe films and 2H-NbSe2 crystals by mode locking (ML) and dc transport measurements. ML features allow us to trace how the shear rigidity of driven vortices evolves with the average velocity. Determining the onset of ML resonance in different magnetic fields and/or temperatures, we find that the dynamic ordering frequency (velocity) exhibits a striking divergence in the higher part of the peak effect regime. Interestingly, this phenomenon is accompanied by a pronounced peak of dynamic critical current. Mapping out field-temperature phase diagrams, we find that divergent points follow well the thermodynamic melting curve of the ideal vortex lattice over wide field and/or temperature ranges. These findings provide a link between the dynamic and static melting phenomena which can be distinguished from the disorder induced peak effect.Comment: 9 pages, 6 figure

The Chang-Refsdal Lens Revisited

This paper provides a complete theoretical treatment of the point-mass lens perturbed by constant external shear, often called the Chang-Refsdal lens. We show that simple invariants exist for the products of the (complex) positions of the four images, as well as moment sums of their signed magnifications. The image topographies and equations of the caustics and critical curves are also studied. We derive the fully analytic expressions for precaustics, which are the loci of non-critical points that map to the caustics under the lens mapping. They constitute boundaries of the region in the image domain that maps onto the interior of the caustics. The areas under the critical curves, caustics and precaustics are all evaluated, which enables us to calculate the mean magnification of the source within the caustics. Additionally, the exact analytic expression for the magnification distribution for the source in the triangular caustics is derived, as well as a useful approximate expression. Finally, we find that the Chang-Refsdal lens with the convergence greater than unity can exhibit third-order critical behaviour, if the reduced shear is exactly equal to \sqrt{3}/2, and that the number of images for N-point masses with non-zero constant shear cannot be greater than 5N-1.Comment: to appear in MNRAS (including 6 figures, 3 appendices; v2 - minor update with corrected typos etc.

Design of a General-Purpose MIMO Predictor with Neural Networks

A new multi-step predictor for multiple-input, multiple-output (MIMO) systems is proposed. The output prediction of such a system is represented as a mapping from its historical data and future inputs to future outputs. A neural network is designed to learn the mapping without re quiring a priori knowledge of the parameters and structure of the system. The major problem in de veloping such a predictor is how to train the neural network. In case of the back propagation algorithm, the network is trained by using the network's output error which is not known due to the unknown predicted future system outputs. To overcome this problem, the concept of updating, in stead of training, a neural network is introduced and verified with simulations. The predictor then uses only the system's historical data to update the configuration of the neural network and always works in a closed loop. If each node can only handle scalar operations, emulation of an MIMO mapping requires the neural network to be excessively large, and it is difficult to specify some known coupling effects of the predicted system. So, we propose a vector-structured, multilayer perceptron for the predictor design. MIMO linear, nonlinear, time-invariant, and time-varying systems are tested via simulation, and all showed very promising performances.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68861/2/10.1177_1045389X9400500206.pd

The Anderson Transition in Two-Dimensional Systems with Spin-Orbit Coupling

We report a numerical investigation of the Anderson transition in two-dimensional systems with spin-orbit coupling. An accurate estimate of the critical exponent $\nu$ for the divergence of the localization length in this universality class has to our knowledge not been reported in the literature. Here we analyse the SU(2) model. We find that for this model corrections to scaling due to irrelevant scaling variables may be neglected permitting an accurate estimate of the exponent $\nu=2.73 \pm 0.02$

Photon trains and lasing : The periodically pumped quantum dot

We propose to pump semiconductor quantum dots with surface acoustic waves which deliver an alternating periodic sequence of electrons and holes. In combination with a good optical cavity such regular pumping could entail anti-bunching and sub-Poissonian photon statistics. In the bad-cavity limit a train of equally spaced photons would arise.Comment: RevTex, 5 pages, 1 figur

The ALMA Discovery of the Rotating Disk and Fast Outflow of Cold Molecular Gas in NGC 1275

We present ALMA Band 6 observations of the CO(2-1), HCN(3-2), and HCO$^{+}$(3-2) lines in the nearby radio galaxy / brightest cluster galaxy (BCG) of NGC 1275 with the spatial resolution of $\sim20$ pc. In the previous observations, CO(2-1) emission was detected as radial filaments lying in the east-west direction. We resolved the inner filament and found that the filament cannot be represented by a simple infalling stream both morphologically and kinematically. The observed complex nature of the filament resembles the cold gas structure predicted by recent numerical simulations of cold chaotic accretion. A crude estimate suggests that the accretion rate of the cold gas can be higher than that of hot gas. Within the central 100 pc, we detected a rotational disk of the molecular gas whose mass is \sim10^{8} M_{\sun}. This is the first evidence of the presence of massive cold gas disk on this spatial scale for BCGs. The disk rotation axis is approximately consistent with the axis of the radio jet on subpc scales. This probably suggests that the cold gas disk is physically connected to the innermost accretion disk which is responsible for jet launching. We also detected absorption features in the HCN(3-2) and HCO$^{+}$(3-2) spectra against the radio continuum emission mostly radiated by $\sim1.2$-pc size jet. The absorption features are blue-shifted from the systemic velocity by $\sim$300-600~km~s$^{-1}$, which suggests the presence of outflowing gas from the active galactic nucleus (AGN). We discuss the relation of the AGN feeding with cold accretion, the origin of blue-shifted absorption, and estimate of black hole mass using the molecular gas dynamics.Comment: Version 2 (accepted version). 18 pages, 16 figures. Accepted for publication in Ap

Accurate screened exchange band structures for transition metal monoxides MnO, FeO, CoO and NiO

We report calculations of the band structures and density of states of the four transition metal monoxides MnO, FeO, CoO and NiO using the hybrid density functional sX-LDA. Late transition metal oxides are prototypical examples of strongly correlated materials, which pose challenges for electronic structure methods. We compare our results with available experimental data and show that our calculations yield accurate predictions for the fundamental band gaps and valence bands of FeO, CoO and NiO. For MnO, the band gaps are underestimated, suggesting additional many-body effects that are not captured by our screened hybrid functional approach.Comment: 9 pages, 3 figures, 3 table