Using ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells

Three artificial proteins that bind the gadolinium ion (Gd³⁺) with tumour-specific ligands were de novo engineered and tested as candidate drugs for binary radiotherapy (BRT) and contrast agents for magnetic resonance imaging (MRI). Gd³⁺-binding modules were derived from calmodulin. They were joined with elastin-like polypeptide (ELP) repeats from human elastin to form the four-centre Gd³⁺-binding domain (4MBS-domain) that further was combined with F3 peptide (a ligand of nucleolin, a tumour marker) to form the F3-W4 block. The F3-W4 block was taken alone (E2-13W4 protein), as two repeats (E1-W8) and as three repeats (E1-W12). Each protein was supplemented with three copies of the RGD motif (a ligand of integrin αvβ3) and green fluorescent protein (GFP). In contrast to Magnevist (a Gd-containing contrast agent), the proteins exhibited three to four times higher accumulation in U87MG glioma and A375 melanoma cell lines than in normal fibroblasts. The proteins remained for >24 h in tumours induced by Ca755 adenocarcinoma in C57BL/6 mice. They exhibited stability towards blood proteases and only accumulated in the liver and kidney. The technological advantages of using the engineered proteins as a basis for developing efficient and non-toxic agents for early diagnosis of tumours by MRI as well as part of BRT were demonstrated.     

Immature Vascular Smooth Muscle Cells in Healthy Murine Arteries and Atherosclerotic Plaques: Localization and Activity

The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis.     

330-750 kV 变电所变压器绝缘性能的在线监测方法比较分析

分析了330-750 kV 电压下工作的电流互感器绝缘性能的在线监测方法及每种方法的有效性和可用性。总结了每种方法的主要特性和优缺点及其对应的标准。     

Multi-length scale modeling of martensitic transformations in stainless steels

In the present work a multi-length scale model is developed to study both the athermal and stress-assisted martensitic transformations in a single crystal of 301 type stainless steel. The microstructure evolution is simulated using elastoplastic phase-field simulations in three dimensions. The input data for the simulations is acquired from a combination of computational techniques and experimental works. The driving force for the transformation is calculated by using the CALPHAD technique and the elastic constants of the body-centered cubic phase are calculated by using ab initio method. The other input data is acquired from experimental works. The simulated microstructures resemble a lath-type martensitic microstructure, which is in good agreement with the experimental results obtained for a stainless steel of similar composition. The martensite habit plane predicted by the model is in accordance with experimental results. The Magee effect, i.e. formation of favorable martensite variants depending on the loading conditions, is observed in the simulations. The results also indicate that anisotropic loading conditions give rise to a significant anisotropy in the martensitic microstructure.     

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.     

A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice

Development of differential and early (preclinical) diagnostics of Parkinson’s disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms (72%, p = 0.049), a decreased level of adrenaline on both sides (ipsilateral—53%, p = 0.004; contralateral—42%, p = 0.02), and an increased α-2-macroglobulin activity on both sides (ipsilateral—53%, p = 0.03; contralateral—56%, p = 0.037) compared to controls. These changes are considered as potential biomarkers for differential diagnosis. Similar changes in the TF were found in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice when modeling clinical and preclinical stages of PD. These data show the adequacy of models to the pathogenesis of PD along the selected metabolic pathways, and also suggest that the found TF changes can be considered as potential biomarkers for preclinical diagnosis of PD. In Parkinsonian mice, the level of catecholamines also changes in the lacrimal glands, which makes it possible to consider them as one of the sources of catecholamines in the TF.     

Neural networks catching up with finite differences in solving partial differential equations in higher dimensions

Neural Computing and Applications - Solving partial differential equations using neural networks is mostly a proof of concept approach. In the case of direct function approximation, a single neural...     

Effect of different organic additives on the shape,size and scintillation properties of Bi4Ge3O12 powders synthesized by the microwave-hydrothermal method

A route for production of fine Bi₄Ge₃O₁₂ (BGO) powder is sought after to lower the cost of scintillation devices and make their shapes more versatile. A systematic study of highly dispersed BGO crystallization under the hydrothermal-microwave (HTMW) conditions was carried out in the present work. Anionic, cationic and non-ionic surfactants, chelating agents and polyols were used to modify the synthesis and their respective effects on phase composition and morphology were determined. It was shown that chelating agents or other additives that are capable of forming complexes with the bismuth ions allow the production of smaller, non-aggregated particles and have the procedure be scaleable. BGO powders of various morphology were synthesized and study of the optical properties of the product discovered their advantages over traditional single-crystal material. The BGO powders obtained in optimal HTMW conditions are characterized by the presence of a single intense fast scintillation component with a flash time of about 11 ns which is by an order of magnitude less than that observed in single-crystal BGO (327 ns). This suggests the suitability of these powders for the production of scintillation materials with improved properties. This material is promising for creating highly sensitive composite detectors with a high rate of counting events.