The Concept of the "Field" in Early Soviet Ethnography : A Northern Perspective

Peer reviewedPublisher PD

Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological applications, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 μm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip. The capsule penetration was examined by scanning with fluorescence microscopy followed by quantitative image analysis. The results show that capsules with a size of 0.3 μm passed more easily to the tumor spheroid and penetrated inside. We hope that the device will represent a reliable alternative to in vivo early secondary tumor models and decrease the amount of in vivo experiments in the frame of preclinical study

Comparative evaluation of modern dosimetry techniques near low- and high-density heterogeneities

The purpose of this study is to compare performance of several dosimetric methods in heterogeneous phantoms irradiated by 6 and 18 MV beams. Monte Carlo (MC) calculations were used, along with two versions of Acuros XB, anisotropic analytical algorithm (AAA), EBT2 film, and MOSkin dosimeters. Percent depth doses (PDD) were calculated and measured in three heterogeneous phantoms. The first two phantoms were a 30 x 30 x 30 cm3 solid-water slab that had an air-gap of 20x 2.5 x 2.35 cm3. The third phantom consisted of 30 x 30 x 5 cm3 solid water slabs, two 30 x 30 x 5 cm3 slabs of lung, and one 30 x 30 x 1 cm3 solid water slab. Acuros XB, AAA, and MC calculations were within 1% in the regions with particle equilibrium. At media interfaces and buildup regions, differences between Acuros XB and MC were in the range of +4.4% to −12.8%. MOSkin and EBT2 measurements agreed to MC calculations within ~ 2.5%, except for the first centimeter of buildup where differences of 4.5% were observed. AAA did not predict the backscatter dose from the high-density heterogeneity. For the third, multilayer lung phantom, 6 MV beam PDDs calculated by all TPS algorithms were within 2% of MC. 18 MV PDDs calculated by two versions of Acuros XB and AAA differed from MC by up to 2.8%, 3.2%, and 6.8%, respectively. MOSkin and EBT2 each differed from MC by up to 2.9% and 2.5% for the 6 MV, and by −3.1% and ~2% for the 18 MV beams. All dosimetric techniques, except AAA, agreed within 3% in the regions with particle equilibrium. Differences between the dosimetric techniques were larger for the 18 MV than the 6 MV beam. MOSkin and EBT2 measurements were in a better agreement with MC than Acuros XB calculations at the interfaces, and they were in a better agreement to each other than to MC. The latter is due to their thinner detection layers compared to MC voxel sizes

X-ray crystal structure of MENT: evidence for functional loop–sheet polymers in chromatin condensation

Most serpins are associated with protease inhibition, and their ability to form loop–sheet polymers is linked to conformational disease and the human serpinopathies. Here we describe the structural and functional dissection of how a unique serpin, the non-histone architectural protein, MENT (Myeloid and Erythroid Nuclear Termination stage-specific protein), participates in DNA and chromatin condensation. Our data suggest that MENT contains at least two distinct DNA-binding sites, consistent with its simultaneous binding to the two closely juxtaposed linker DNA segments on a nucleosome. Remarkably, our studies suggest that the reactive centre loop, a region of the MENT molecule essential for chromatin bridging in vivo and in vitro, is able to mediate formation of a loop–sheet oligomer. These data provide mechanistic insight into chromatin compaction by a non-histone architectural protein and suggest how the structural plasticity of serpins has adapted to mediate physiological, rather than pathogenic, loop–sheet linkages