ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

A Concurrent Tuple Set Architecture for Call Level Interfaces

Call Level Interfaces (CLI) are low level API aimed at providing services to connect two main components in database applications: client applications and relational databases. Among their functionalities, the ability to manage data retrieved from databases is emphasized. The retrieved data is kept in local memory structures that may be permanently connected to the host database. Client applications, beyond the ability to read their contents, may also execute Insert, Update and Delete actions over the local memory structures, following specific protocols. These protocols are row (tuple) oriented and, while being executed, cannot be preempted to start another protocol. This restriction leads to several difficulties when applications need to deal with several tuples at a time. The most paradigmatic case is the impossibility to cope with concurrent environments where several threads need to access to the same local memory structure instance, each one pointing to a different tuple and executing its particular protocol. To overcome the aforementioned fragility, a Concurrent Tuple Set Architecture (CTSA) is proposed to manage local memory structures. A performance assessment of a Java component based on JDBC (CLI) is also carried out and compared with a common approach. The main outcome of this research is the evidence that in concurrent environments, components relying on the CTSA may significantly improve the overall performance when compared with solutions based on standard JDBC API.(undefined

On the Linearization of the First and Second Painleve' Equations

We found Fuchs--Garnier pairs in 3X3 matrices for the first and second Painleve' equations which are linear in the spectral parameter. As an application of our pairs for the second Painleve' equation we use the generalized Laplace transform to derive an invertible integral transformation relating two its Fuchs--Garnier pairs in 2X2 matrices with different singularity structures, namely, the pair due to Jimbo and Miwa and the one found by Harnad, Tracy, and Widom. Together with the certain other transformations it allows us to relate all known 2X2 matrix Fuchs--Garnier pairs for the second Painleve' equation with the original Garnier pair.Comment: 17 pages, 2 figure

Очистка водных сред от микробиологических загрязнений с использованием адсорбентов на основе газобетона

Объект исследования: газобетон (ГОСТ 25485-89), штамм бактерий E. coli ATCC-25922. Цель работы: оценка эффективности использования газобетона для очистки водных сред от микробиологических загрязнений. В процессе исследования проводились оценка гидродинамического сопротивления, определение фильтрующей способности сорбентов в отношении бактерий E. Coli. В результате исследования получены оптимальные фракции сорбента, определены физико-химические характеристики и сорбционные свойства сорбентов. Область применения: водоочистка и водоподготовка в различных отраслях промышленности.Subject of research: aerated concrete (State Standard 25485-89), a strain of the bacteria E. coli ATCC-25922. The main goal of this study was investigation of sorbent on the basis of the aerated concrete for water purification. The study assesses the hydrodynamic resistance, determining the ability of the filter sorbents against the bacteria E. Coli. The research obtained the optimal fraction of the sorbent, determined physico-chemical characteristics and sorption properties of the sorbents. Applications: water purification and water conditioning in various industries

3D Traction Forces in Cancer Cell Invasion

Cell invasion through a dense three-dimensional (3D) matrix is believed to depend on the ability of cells to generate traction forces. To quantify the role of cell tractions during invasion in 3D, we present a technique to measure the elastic strain energy stored in the matrix due to traction-induced deformations. The matrix deformations around a cell were measured by tracking the 3D positions of fluorescent beads tightly embedded in the matrix. The bead positions served as nodes for a finite element tessellation. From the strain in each element and the known matrix elasticity, we computed the local strain energy in the matrix surrounding the cell. We applied the technique to measure the strain energy of highly invasive MDA-MB-231 breast carcinoma and A-125 lung carcinoma cells in collagen gels. The results were compared to the strain energy generated by non-invasive MCF-7 breast and A-549 lung carcinoma cells. In all cases, cells locally contracted the matrix. Invasive breast and lung carcinoma cells showed a significantly higher contractility compared to non-invasive cells. Higher contractility, however, was not universally associated with higher invasiveness. For instance, non-invasive A-431 vulva carcinoma cells were the most contractile cells among all cell lines tested. As a universal feature, however, we found that invasive cells assumed an elongated spindle-like morphology as opposed to a more spherical shape of non-invasive cells. Accordingly, the distribution of strain energy density around invasive cells followed patterns of increased complexity and anisotropy. These results suggest that not so much the magnitude of traction generation but their directionality is important for cancer cell invasion

Mechanical Translation

Contains research objectives and reports on two research objectives.National Science Foundation (Grant GN-244

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand