Development of electron-beam equipment and technology of layer welding of the wire in the conditions of additive technologies

Immunotoxins are powerful tools to specifically eliminate deviated cells. Due to the side effects of the original immunotoxins, they were only considered for the treatment of cancer as in these cases, the potential favourable effect outweighed the unwanted toxic side effects. Over time, many improvements in the construction of immunotoxins have been implemented that circumvent, or at least strongly diminish, the side effects. In consequence this opens the way to employ these immunotoxins for the treatment of non-life threatening diseases. One such category of disease could be the many chronic inflammatory disorders in which an uncontrolled interaction between inflammatory cells leads to chronicity. In several of these chronic conditions, activated macrophages, which are characterised by an increased expression of CD64, are known to play a key role. In this review we discus the data presently available on elimination of activated macrophages through CD64 immunotoxins in several animal models for chronic disease. A chemically linked complete antibody with the plant toxin Ricin-A, proved very effective and provided proof of concept. Subsequently, the development towards genetically engineered, fully human, multivalent single chain based immunotoxins that have diminished immunogenicity, is discussed. The data show that the specific elimination of activated macrophages through CD64 is indeed beneficial for the course of disease. As opposed to other methods used to inactivate or eliminate macrophages, with the CD64 based immunotoxins only the activated population is killed. This may open the way to apply these immunotoxins as therapeutics in chronic inflammatory disease

Evaluation of the ESBL-coding plasmids transmissibility in E. coli isolated from ambulatory patient's urina

Representatives of the Enterobacteriaceae family are the main causative agents of urinary tract infections. Escherichia coli can exhibit resistance to [beta] -lactam antibiotics by synthesizing ESBL (extended spectrum [beta]-lactamases). CTX-M [beta] -lactamases are the dominant group of ESBL. In this paper, we investigated the ability of E. coli urinary isolates to transmit resistance genes within the plasmid. An analysis of the effectiveness of conjugation has shown that E. coli strains producing ESBL are capable of transferring resistance genes to a recipient bacterium at a high frequency

Cellulose hydrolysis-hydrogenolysis to ethyleneglycol and propyleneglycol over Ru and heteropolyacid catalysts

Еthylene and propylene glycols (EG and PG) are widely used in industry to produce cooling systems and other valuable chemical products. But PG is non-toxic, therefore it is used in industries where EG can not be used: pharmaceutical, food, etc. This polyols produced by "one-pot" method, which is one of the promising and effective methods for producing alcohols from cellulose under harsh conditions. The purpose of this study was to determine the optimal composition of the solid bifunctional catalyst and the conditions of its preparation for the hydrolysis-hydrogenolysis of cellulose. Catalists are Ru-HPA/ZrO[2], RuHPA/Nb[2]O[5] and Ru/CsHPK. As a result of the study, the most promising catalyst system is 1%Ru/Cs[3.5]H[0.5]SiW[12]O[40]. In the presence of 1%Ru/CsHPA, the yield of 25% EG and 11% PG was detected (EG and PG selectivity is 60 and 27%). The activity of the catalysts was studied in the presence of Ca(OH)[2]

Influence of spark plasma pre-sintering on denitrification of Y-TZP ceramics

In this work, samples of commercial TZ-3YSB-E powder, sintered by a two-stage method, have been investigated. SPS was carried out at 950, 1000 °C for 1 min. Subsequent sintering was carried out at 1400 ° C for 0, 2, and 6 h. The best compaction results were achieved at a temperature of 1000 ° C, with isothermal holding for compaction up to 99% in 2 hours, which is 7 times faster than for one-stage sample

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Selection of scFv phages on intact cells under low pH conditions leads to a significant loss of insert-free phages

Display of functional antibody fragments on the surface of filamentous bacteriophages allows fast selection of specific phage antibodies against a variety of target antigens. However, enrichment of single chain variable fragment (scFv)-displaying phages is often hampered by the abundance of bacteriophages lacking antibody fragments. Moderate adhesive binding activities and production advantages of these “empty” phages results in their subsequent enrichment during selection on target cells. To date, very limited effort has been made to develop strategies removing nonspecific binding phages during the selection processes. To efficiently reduce insert-free phages when panning on intact cells, we increased the washing stringency by lowering the pH of the buffer with citric acid. Under standard washing procedures (pH 7.4), only approximately 73% of recovered phages were insert-free after three rounds of selection. Using stringent washing procedures (pH 5.0), approximately 12% of recovered phages contained no scFv. Using this protocol, we have cloned an antibody fragment from a mouse/human hybridoma cell line directed against the disialoganglioside GD2. This study confirms that selection of phage antibodies on cells is efficiently enhanced by assays augmenting the stringency to remove nonspecific binding phages

За кадры. 1978. № 35 (2106)

К новым рубежам пятилетки. Соревнованию вузов Урала и Сибири - крепнуть! / Л. ИгнатенкоПоздравляем!Передовые люди институтаПомогая друг другу / Т. Макарова, Д. Хамитова, В. ФроловаУчиться сверяясь по Ленину / Л. БакинаПартийный стаж - полвека / С. ХабибулинСмотр печати и радио / М. Иванова...А воз и ныне там. От главного корреспондента / Н. БедаревНа службе прогресса / Л. М. АнаньевВ Союз наш творческийВ большую поэзиюВозвращение / А. И. КазанцевЛедоход / Ю. ФедоровЗагорался в оконных рамах... / С. БоргуноваСтарушка, зимушка, хоть тресни… / В. ГолиненкоЯ еду в веселом трамвае... / В. ГолиненкоГород дышит предутренней мглою... / В. УшаковВзголубела пьянящая даль... / И. КиселеваКогда бежишь - захватывает дух... / Л. ЩербининаВ эти праздничные дниВесенние картинки / Е. КутолинаЛыжники в марте / В. Ушако

Targeted killing of rhabdomyosarcoma cells by a MAP-based human cytolytic fusion protein

The treatment of rhabdomyosarcoma (RMS) is challenging, and the prognosis remains especially poor for high-grade RMS with metastasis. The conventional treatment of RMS is based on multi-agent chemotherapy combined with resection and radiotherapy, which are often marked by low success rate. Alternative therapeutic options include the combination of standard treatments with immunotherapy. We generated a microtubule-associated protein (MAP)-based fully human cytolytic fusion protein (hCFP) targeting the fetal acetylcholine receptor, which is expressed on RMS cells. We were able to express and purify functional scFv35-MAP from Escherichia coli cells. Moreover, we found that scFv35-MAP is rapidly internalized by target cells after binding its receptor, and exhibits specific cytotoxicity toward FL-OH1 and RD cells in vitro. We also confirmed that scFv35-MAP induces apoptosis in FL-OH1 and RD cells. The in vivo potential of scFv35-MAP will need to be considered in further studies