Automation and digitalization of both the entire process and components of technological operations of the terminal are one of the conditions for the balanced development of the port infrastructure of the Russian Federation. Container transshipment in the warehouse area is the most labor-intensive and frequently performed auxiliary operation of the technological process of any container terminal. That is why development of advanced driver assistance systems for mobile reloading equipment based on a digital twin of this operation is in high demand from the point of view of the terminal digitalization. The object of the study is the technological process of containers transshipment in the operating areas of the terminal with formation of auxiliary stacks to speed up the transfer of goods by the different transport means, as well as carrying out other auxiliary operations. The reloader performs the operation of partially dismantling the operational stack with removal from it of a certain number of target containers that make up the logistics flow of cargo moved to the auxiliary stack with the subsequent return of the blocking containers back to their previous stacks of the operational stack. The research method is the modeling of scenarios depending on the sequence of possible states of the simulated technological process. The used mathematical apparatus is automatic programming. The modeling tools are deterministic finite state machine. The main goal of developing the model is to convert the loader control function when performing a selective search operation for containers in an operational stack into a digital code, i. e. mapping the sequence of its possible states into a sequence of characters in the control line of the machine. The result of the study is a digital simulation model of the operation of selective removal of containers from the operational stack with implementation of the work scheme based on the principle of complete disassembly of blocking stacks and removal of containers only from the nearest row, as well as proof of the adequacy of the transition diagram of the finite state machine to the functioning mechanism of the simulated operation. The virtual environment of the automated control system for a mobile loader operating in the rear zone is the place where the digital model of selective removal of containers is used in the architecture of the digital twin of the container terminal. The main advantage of using this version of the finite state machine as an element of the automated control system is that there is no need to urgently interrupt the technological process to adjust operation of the loader at work positions.

A number of molecules expressed on mammalian cells are involved in the formation of autotolerance. These primarily include CTLA-4/B7 and PD1-PD-L1 signaling pathways. Blockers of these signaling pathways, called checkpoint inhibitors (CPIs) of immunity, are used in the clinic for the treatment of various forms of cancer. Antibodies to CTLA-4 cause systemic toxicity and are approved only for some tumors. Antibodies against PD1 or PD-L1 have been successfully used for the treatment of various forms of cancer and are characterized by low toxicity. However, the response to therapy using CPIs is not always observed. The development of more effective approaches to cancer therapy based on PD1/PD-L1 inhibitors requires additional research. The aim of this work was to express the extracellular part of the murine PD-L1 protein (exPD-L1) and obtain antibodies to PD-L1. The mouse exPD-L1 protein was obtained and characterized in the bacterial expression system. exPD-L1 protein was used to immunize mice in order to produce anti-PD-L1 antibodies. Using hybridomic technology, 5 clones expressing antibodies to exPD-L1 were obtained. Antibodies of the B12 clone were developed in the ascitic fluid of BALB/c mice and purified by affinity chromatography. The ELISA method for purified antibodies showed specific binding to the exPD-L1 protein and the commercial protein of the extracellular part of murine PD-L1. Experiments using flow cytometry and confocal microscopy have shown that the antibodies obtained bind the intracellular form of the PD-L1 protein, unlike commercial antibodies binding the membrane form.

Objective: A number of molecules expressed on mammalian cells are involved in the formation of auto-tolerance. These primarily include CTLA-4/B7 and PD1-PD-L1 signaling pathways. Blockers of these signaling pathways, called checkpoint inhibitors (ICTs) of immunity, are used in the clinic for the treatment of various forms of cancer. Antibodies to CTLA-4 cause systemic toxicity and are approved only for the treatment of melanoma. Antibodies against PD1 or PD-L1 have been successfully used for the treatment of various forms of cancer and are characterized by low toxicity. However, the response to therapy using ICT does not exceed 25–30

Due to the new concept of the country transport logistics development “Turning to the East”, it is becoming the more important to increase the processing capacity of container terminals in the Far East. This research work is to study the possibilities of increasing the throughput capacity of container terminal areas by making the technical and technological management decisions. The opportunity of introducing automation elements into the terminal operation through the creation of a technological cyclic automatic machine on the basis of mobile container transporters is investigated as an idea to increase the processing capacity of the terminal equipment. In the context of developing the concept of the loader operation as a technological machine, the “working cycle” term is defined as a sequence of actions during performing the technological operation of picking up the target container from the stack, and then the transition diagram of the machine is an analogue of the technological scheme of this operation. Based on the foregoing, the purpose of the study is defined as the rationale for choosing a unified scheme for the technological operation of dismantling the container stack as part of automating the working cycle of a loader. To achieve this purpose, the following tasks are solved: the technical capabilities of loaders such as a reach stacker and a loader with an upper grip spreader are studied when working with a stack depending on the location of the target container in the latter; technological schemes for the execution of the operation of picking up target containers from a stack, differing in the type of equipment used and the method of disbanding blocking stacks, are considered; the positive and negative aspects of using each of the technological schemes as an analogue of the transition diagram of the technological machine control unit are revealed. The result of the research work is the technological scheme “the use of a reach stacker or a loader with a top grip spreader with complete disassembly of blocking stacks and picking up containers only from the near row”, which is the most preferable in terms of such important indicators for automating the technological process as versatility, “trouble-free” execution technology, insensitivity to stack capacity.

The aim of the research is to provide a comprehensive linguocultural characteristic of a folk tale. The research is based on the material of the Irish Fairy and Folk Tales tale anthology, compiled and edited by W. B. Yeats. The research results allow for a suggestion that linguocultural markers are to be found on both ideologic-compositional and speech levels of a text. Thus, the motives of Christian morality form the basis for reciprocal altruism which is the conceptual entity of Irish folk tales. The tale structure is often linear and consists of a short introduction, the main part and the climax turning into a short sharp denouement. Irish folk tales are often a metaphor for the rite of passage. The didactic function of tales consists in demonstrating the possibilities of sin purge through their recognition and repentance. Tales also set social rules and norms. Culture-specific language units encountered in the texts of Irish folk tales belong to different levels of the English language system. The phonetic level reveals such features as metathesis, final consonant reduction, imitation of aspiration, alliteration, wordplay based on homophony, etc. They imitate a peculiar Irish accent and exert some vernacular effect. The lexical level is represented by culture-bound vocabulary including ethnographical terms, anthroponyms and geographical names, both real and invented, various kinds of borrowings from Irish Gaeilge,quotations etc. Some cultural features are exhibited in grammar and text rhythm, chiefly through the use of specific verb forms of Irish English as well as certain correlations of repetition-based rhythmic devices – polysyndeton, diacope, anaphora, epizeuxis, symploce etc. The study of linguocultural text markers gives a comprehensive idea of intra- and extralinguistic characteristics of the tale.

Background Patient's age at RA onset predefines the course of the disease, rate of progression and severity of erosive-destructive changes in hand and feet joints, mineral bone density (BMD) and deformities of the spine vertebrae. Objectives To compare the changes in axial and peripheral skeleton in pts in relation to the age of RA onset. Methods 164 females with RA aged 20 -65 y. were included. Mean age was 47,9±12,9 y., RA duration - 12,1±9,3 y. Genant semiqiantitative radiographic morphometry of lumbar and thoracic spine was obtained for all patients, erosive and destructive changes assessed using Sharp/van der Heijde scoring system. BMD was measured at lumbar spine level (L1–4), femoral neck (FM) and distal forearm (DF) of a non-dominant arm using Hologic “Discovery A” system. Data analysis was made with Statistica 6.0 software. Results All pts were grouped into 3 arms depending on the age at RA onset: Group 1 – 63 (38,4%) pts, whose age at RA onset was ≥18 ≤30 y., Group 2 – 78 (47,6%) pts, ≥31 ≤50 y. age at RA onset, Group 3 – 23 (14,0%) pts, ≥51 y. age at RA onset. Mean age of pts from Group 1 was 37,8±12,7 y, Group 2 – 51,9±7,8 y., Group 3 – 62,1 ±2,6 y (p<0.05), disease duration - 15,1±12,3 y., 11,0±6,6 y., and 7,1±3,1 y., respectively (p<0.05). Menopause was established in 30% of pts in Group 1, in 60% - in Group 2, in 100% - in Group 3; peripheral fractures in past medical history were documented in 19 (30%), 28 (36%), and 11 (49%) pts from Groups 1, 2, and 3, respectively (p>0.05), 50% of fractures occurred before RA onset. The groups were comparable in terms of the number of RF-positive pts, receiving DMARDs, the duration and cumulative dose of GCs. DAS28 RA activity score, the number of pts with extra-articular RA manifestations and the number of pts taking GCs by the moment of examination were less in Group 1vs Group 2 (p<0.05). Lumbar vertebral deformity scores (VDS), BMD values of L1–4, FN, DF, narrowed joint spaces and total Sharp score were comparable in all groups (p>0,05). Number of erosions in Group 1 was 46,3±59,7 scores, in Group 2 - 30,8±38,5 scores, in Group 3 - 19,3±27,4 scores (Groups 1 and 3 p<0,05). Vertebral deformities were found in 19% pts from Groups 1 and 2, and in 39% pts from Group 3 (Groups 2–3 p<0,05). Thoracic VDS was 0,78±0,08, 0,78±0,07 and 0,73±0,13, respectively (Groups 3 and 1; 3 and 2 p<0,05). Conclusions RA onset during attainment of peak bone mass and long lasting disease produced negative effect on axial and peripheral skeleton. Despite young age and absence of menopause the majority of pts presented with OP, peripheral fractures, BMD in all skeletal sites, and lumbar VDS values that were comparable to those in pts with later onset of the disease. Pts with RA onset after menopause and shorter duration of the disease present with equal to pts with early onset degree of joint space narrowing and total Sharp score, but not with similar number of erosions. Early onset of RA and therefore longer duration of disease is associated with more amount of erosions. Disclosure of Interest None declared

Background Chronic synovitis and RANKL-dependent osteoclastogenesis in rheumatoid arthritis (RA) lead to bone damage, such as local and systemic bone destruction (osteoporosis (OP), erosions and joint space narrowing). RANK-ligand is essential for osteoclast development, activation, and survival. The addition of an anti-RANKL antibody (denosumab) to the traditional scheme of RA treatment is a potentiality to control and prevent joint destruction as well as inhibit systemic osteoporosis. Objectives The aim is to evaluate the effects of continuous treatment with denosumab on bone mineral density and structural damage in patients with RA and OP. Methods 27 postmenopausal women (mean age 58,4±7,4 years) with RA (mean duration of RA 19,5±11,8 years) and OP received subcutaneously denosumab 60 mg every 6 months pro 2 years. According to X-ray 8 (29,6%) patients had the 2nd, 8 (29,6%) – the 3rd and 11 (40,8%) – the 4th stage of RA. 17 patients (62,9%) continued glucocorticoids (GC). The primary end points were the change from baseline in BMD (by dual energy x-ray absorptiometry at three sites: lumbar spine (L1-L4), hip neck (HN) and distal forearm (DF), the change in Sharp/van der Heijde (SVH) score by X-ray of hands and feet and the change in X-ray morphometric analysis of deformations in vertebrae (Genant method). The change of pain severity in spine was assessed using VAS. The Statistica 6.0 was used. Results At L1-L4 the significant increase of BMD was noted both at 12- and 24-month point in comparison with baseline: 0,789±0,079 g/cm2 vs 0,818±0,077 g/cm2 (p<0.001) and 0,789±0,079 g/cm2 vs 0,836±0,078 g/cm2 (p<0.001), respectively. The same was noted at DF – the increase of BMD at 12- and then at 24-month: 0,480±0,102 g/cm2 vs 0,493±0,095 g/cm2 (p=0.01) and 0,480±0,102 g/cm2 vs 0,511±0,104 g/cm2 (p<0.001), respectively. At HN it was noted the stabilization in BMD (statistically nonsignificant improvement) at both points. After separation on groups based on GC intake, this trend was also seen at both points in both groups: increase of BMD at L1-L4 and DF, stabilization of BMD at HN. The erosion and total SVH score were increased at 12- and 24-month (p<0.05), while the narrowing score was not changed significantly at both points. The index of vertebral deformations was not changed after 24-month compared with baseline: 0,79±0,01 for lumbar site and 0,76±0,04 for thoracic site, respectively. At baseline 13 patients had pain in thoracic site of spine, while after the treatment their number significantly decreased (p=0.019) more that 2-fold – 4 (mean VAS 41.1±16.9 and 31.2±8.5 mm, respectively), at lumbar spine pain was also reduced (p=0.09): 15 and 8 patients (44.3± 23.3 and 35.6±14.7 mm, respectively). Conclusions Throughout the 24 months of therapy with denosumab it was shown the continued increase of BMD at L1-L4 and distal part of forearm - the significant increase was observed both at the first and the following year of therapy regardless of GC intake. At HN it was observed the stabilization of BMD. The erosion and total SVH score were increased, but the narrowing score didn9t change after two years of observation. The index of vertebral deformations remained stable. The frequency and severity of pain in spine were decreased. Disclosure of Interest None declared

Background Osteoporosis (OP) is 2–3 times more frequent in rheumatoid arthritis (RA) patients as compared to general population with associated 1,5–2,5 – fold increased risk of fractures. Femoral neck fracture is the most unfavorable prognosis and outcome in these patients, compromising their quality of life. Objectives To identify major risk factors of femoral neck OP in female RA patients. Methods The study included 206 female RA patients (ACR criteria), aged 20–75 years (mean age 56,6±11,2 years). An individual patient9s file contained social and demographic data, anthropometric parameters, case history, clinical examination and lab findings, traditional OP risk factors, patient9s joint status and comorbidities. Hand and distal feet X-ray was taken in each case. Van der Heijde modified Sharp method was used to score the erosions and joint space narrowing in hands and feet. Axial bone mineral density (BMD) was measured using DEXA scan. DEXA T-score was used in post-menopausal women, and Z-score – in menstruating women. Results Femoral neck OP was diagnosed in 68 patients (33%), while in 138 (67%) no OP was found. Patients with and without OP were of comparable age (58,7 ± 12,3 vs 55,5 ± 10,2 years, p=0,06), but differed in disease duration (12 (7; 22) vs 11 (7; 15) years, p=0,04) and total Sharp score (181,5 (92; 267) vs 112 (59; 173), p=0,006). OP patients were taking higher average daily dose of glucocorticosteroids (GC) during the previous year (5 (2,5; 7,5) vs 2,5 (1,3; 5) mg/day, p=0,03) and were prescribed greater number of intra-articular (i/a) GC injections vs patients without OP (8 (3; 18) vs 6 (2; 10), p=0,04, respectively). Analysis of traditional OP risk factors identified lower body weight in OP patients (62,8 ± 11,4 vs 69,6 ± 12,4 kg, p<0,001) and post-menopause status in the majority of them (89,7 vs 74,6%, RR =1,2, 95% CI 1,06–1,36, p=0,007). Higher incidence of femoral neck fractures within the immediate family members was found in OP patients family history (16,4 vs 2,9%, RR =5,57, 95% CI 1,82–17,07, p=0,001). Multifactorial analysis identified the following major femoral neck OP risk factors: total Sharp score, average daily GC dose during the previous year, total number of intra-articular GC injections, and menopause; the contribution of these variables in OP development was assessed (discriminant function coefficients: 0,006; 0,37; 0,07; 2,91, respectively) to suggest a model (with the area under the ROC curve equal to 0,926), allowing prediction of femoral neck OP with high accuracy, equal to 89,7%. Conclusions The degree of erosive joint destruction in hand and feet (based on total Sharp score), average daily GC dose during the previous year, total number of intra-articular GC injections, and menopause are major risk factors of femoral neck OP in female patients with RA. Disclosure of Interest None declared

Objectives Through the Programme of the Russian Association of Rheumatology for the diagnosis, prevention and treatment osteoporosis (OP) in patients with RA we evaluated the ten year probability of major osteoporotic fracture by FRAX for Russia in patients with RA, and identified prevalence osteoporosis treatment in patients with high or low risk of osteoporotic fractures (OF). Methods Trough the Programme of a large amount of patients with RA from 12 clinical centers in Russia 560 patients aged 41 to 89 years were selected and have been evaluated the risk of OF by FRAX. Results 485 (87%) women and 75 (13%) men were involved in our study. Female average age was 60,46 years, male one was 60,1 years. OP was diagnosed in 97 (17%) patients, 74 (13%) had a history of OF, however, of these people OP treatment was approved only 86 (87%) and 36 (49%), respectively. 185 (33%) patients have indications to approve OP treatment, defined using FRAX, only 57 (31%) of these people treatment was imposed. Assignment of treatment didn9t need for 375 (67%) patients, however treatment was approved 48 (13%) from them. 77 (73%) patients were taking prescribed medications, 49 (60%) of them – bisphosphonates plus calcium and/or vitamin D supplementation, 14 (18%) – calcium and vitamin D, 11 (14%) – calcitonin, 3 (4%) - strontium ranelate. Osteoporosis evaluation (DXA) was performed in 421 (75%) patients, including 54 (72%) patients with history of OF and 128 (69%) patients with indications to approve OP treatment, defined using FRAX. Conclusions Osteoporosis management is not quite enough in patients with RA in Russia. There is substantial variation in the quality of risk evaluation of the osteoporotic fractures, osteoporosis evaluation and treatment. Introduction of FRAX for allocation of group of patients with RA with a high risk of fracture will contribute to a personalized approach to approving treatment. Disclosure of Interest None declared

Background Rate of vertebral body fractures and spinal deformities is 2-fold higher in RA patients compared to general population, compromising their quality of life. Objectives To identify major risk factors of lumbar osteoporosis (OP) in RA female patients. Methods The study included 220 RA female patients (ACR criteria), aged 20-75 y. (mean age – 57,1±10,8 y). An individual patient9s file contained anthropometric parameters, social and demographic data, case history, clinical examination and lab findings, traditional OP risk factors, patient9s joint status, info on concurrent diseases, pain intensity evaluation by VAS and evaluation of general health status. Bone mineral density (BMD) was measured using DEXA scan. DEXA T-score was used in post-menopausal women, and Z-score - in menstruating women. Results Patients were grouped in two arms: patients with lumbar spine OP – 74 (33,6%) and without OP in the lumbar spine – 146 (66,4%). OP patients were somewhat older (59,8±10,2 vs 56±11,1 y., p=0,02 respectively), greater extent of functional impairment (HAQ >2) (43,4 vs 29,5%, RR =1,47, 95% CI 0,98–2,21, p=0,05), longer use of glucocorticosteroids (GC) (72 (36–110) vs 50 (12–95) mo, p=0,05), and at higher average daily doses during the previous year (6,3 (2,5–8,75) vs 5 (2,5–7,5) mg/day., p=0,01), as well as higher total GC dose 14,4 (5,4–25,8) vs 9 (2,4–16,5) g, p=0,02). RA activity by DAS28 and current radiographic lesions (Van der Heijde modification of Sharp method) was comparable in both groups. Analysis of traditional OP risk factors identified lower body weight in OP patients (64,4±10,6 vs 69,2±12,9 kg, p=0,01) and post-menopause status in the majority of them (94,6 vs 74%, RR =1,28, 95% CI 1,14–1,42, p=0,0001). Discriminate analysis identified the following major lumbar spine OP risk factors: RA duration, severe functional impairment by HAQ, average GC daily dose in the previous year and menopause. Based on identified factors and their coefficients a model was suggested (with area under the curve – AUC- equal to 0,784), allowing to predict lumbar spine OP with high precision, equal to 74.5%. Conclusions Lumbar spine OP in RA female patients is to great extent predetermined by RA duration, higher degree of functional impairment by HAQ, average daily GS dose in the previous year and the menopause status. Disclosure of Interest None declared

Background RANK-ligand is essential for osteoclast development, activation, and survival. Denosumab (DMB), an antiosteoporotic drug, is a monoclonal antibody that binds RANKL. The addition of antiresorption preparations to the traditional scheme of rheumatoid arthritis (RA) treatment – the perspective direction of prevention and treatment of osteoporosis (OP) and control of erosive and destructive changes (control of local and generalized bone loss). Objectives The aim of our study was to evaluate the dynamics of BMD, structural damage in hands, feet and vertebrae after 12-months of treatment with DMB in patients with RA and OP. Methods 52 postmenopausal women with RA and OP received subcutaneously denosumab 60 mg injections every 6 months for 12 months. The primary end point was the change from baseline in the Sharp/van der Heijde (SVH) score by X-ray of hands and feet, X-ray morphometric analysis of deformations in vertebrae (Genant method) and BMD (by dual energy x-ray absorptiometry (DXA) at three sites: lumbar spine (L1-L4), hip neck (HN) and distal forearm (DF) at 12 months. The change of pain severity in spine (using VAS) also was assessed. The Statistica 6.0 was used. Results The mean age was 58,4±6,4 years, the mean duration of RA 19,0±10,9 years. During the study 30 patients (58%) continued glucocorticoids (GC). According to X-ray 15 (29%) patients had the 2nd, 17 (33%) – the 3rd and 20 (38%) - the 4th stage of RA. Mean BMD (L1-L4) before/after the treatment was 0,814±0,101 g/cm2 and 0,848±0,103 g/cm2 (p<0.001), at HN was 0,629±0,089 g/cm2 and 0,641±0,090 g/cm2 (p=0,02). At DF was 0,497±0,094 g/cm2 and 0,502±0,091 g/cm2 (p>0,05), respectively. The significant increase of BMD (L1-L4) was noted both in groups, receiving GC or not. The index of vertebral deformations at lumbar site of spine did not change after treatment – 0.78±0.04, similar trend was seen at thoracic site: before - 0,77±0,07 and after - 0,76±0,07 (p>0,05). The erosion score, the amount of narrowed cracks and total SVH score were increased after treatment: 47.7 (M 29.0; 9.5–80.5) and 48.4 (M 29.0; 10.5–83.0) (p=0.017), 98.7 (M 109.0; 72.5–132.5) and 99.1 (M 109.0; 72.5–132.5) (p=0.043), 146.5 (M 135.0; 84.0–212.5) and 147.5 (M 135.0; 85.0–216.0) (p=0.017), respectively. Interesting to note, that after separation of groups based on GC intake, the increase of erosion score and total SVH score was only seen in patients taking GC. Patients without GC therapy did not show the negative dynamic. At baseline 18 patients had pain in thoracic site of spine, while after treatment their number decreased more that 2-fold - 6 (mean VAS 42.5±17.9 and 33.3±10.8 mm, respectively), at lumbar spine pain was significantly (p=0.02) reduced: 29 and 22 patients (50.3±21.7 and 36.3±14.0 mm, respectively). Conclusions After 12 months of therapy with denosumab it was shown the significant increase of BMD in L1-L4, HN, and stabilization in the forearm. The erosion score, the amount of narrowed cracks and total SVH score were increased after treatment, the increase of erosion score and total SVH score was only in patients with GC. The index of vertebral deformations remained stable. The frequency and severity of spine pain were decreased. Disclosure of Interest None declared

The process of hardening of the mining equipment by detonation spraying has been considered. The aim of the work is the hardness increase, anti-friction properties and wear resistance of machines parts surfaces, such as bushings, of hydrocylinder joints of boom and the bucket, crowns, etc., which are made from copper-based alloys. The research reveals influence of modification of the samples surface made in the process of detonation spraying of a mixture of powders of PR-BrAЋ9-4-3 and Al 2O 3 on the service properties.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

A highly sensitive test system, based on the immuno-PCR method, was developed for the detection of two staphylococcal toxins: enterotoxin A (SEA) and toxic shock syndrome toxin (TSST). A key element of the developed systems was to obtain supramolecular complexes of bisbiotinylated oligodeoxynucleotides and streptavidin, which were to be used as DNA-tags. Specificity studies showed no cross-reactivity when determining SEA and TSST. The sensitivity of detection of these toxins in the culture supernatants S. aureus was not lower than 10 pg/mL.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)