Разработка плана по локализации и ликвидации аварии в зале нагнетателей компрессорного цеха Юргинского ЛПУМГ ООО «Газпром трансгаз Томск»»

Цель выпускной квалификационной работы: разработка порядка действий производственного персонала Юргинского ЛПУМГ в случае аварии на опасном производственном объекте по сценарию аварии "Разгерметизация технологического оборудования в компрессорном цехе с заполнением помещения природным газом и последующим взрывом". В работе выполнен обзор литературы, выполнен расчет критериев взрывопожарной и пожарной опасности в помещении зала нагнетателей компрессорного цеха, разработан порядок действий производственного персонала при аварии по данному сценарию, рассчитан полный ущерб от аварии.The purpose of the final qualification work: development of the procedure for the actions of the production personnel of the Yurginsky LPGMG in the event of an accident at a hazardous production facility under the accident scenario "Depressurization of the process equipment in the compressor shop with the filling of the room with natural gas and subsequent explosion". The work reviews the literature, calculates the fire and explosion hazard criteria in the room of the compressor room of the compressor room, developed the procedure for operating personnel in the event of an accident in this scenario, and calculates the total damage from the accident

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci.We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)).We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.National Heart, Lung and Blood Institute R01-HL095393 R01-HL097163 P01-HL092870 RC2-HL101715 U01-HL089897 U01-HL089856 U01-HL108642 P50-HL089493

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC., After recovery from acute SARS-CoV-2 infection, mice exhibit chronic lung disease similar to some humans, allowing for testing of therapeutics

Fibroblast Foci Are Not Discrete Sites of Lung Injury or Repair: The Fibroblast Reticulum

Background: Usual interstitial pneumonia (UIP), the pathologic correlate of idiopathic pulmonary fibrosis, contains characteristic discrete areas of fibroblasts, myofibroblasts, and newly formed collagen, termed “fibroblast foci.” These lesions are argued to represent isolated sites of recurrent acute lung injury and suggested to be the mechanism of disease progression. We hypothesized that, rather than isolated, these lesions are part of an organized neoplasm

Serum Amyloid A Regulates Granulomatous Inflammation in Sarcoidosis through Toll-like Receptor-2

Rationale: The critical innate immune mechanisms that regulate granulomatous inflammation in sarcoidosis are unknown. Because the granuloma-inducing component of sarcoidosis tissues has physicochemical properties similar to those of amyloid fibrils, we hypothesized that host proteins capable of forming poorly soluble aggregates or amyloid regulate inflammation in sarcoidosis

The Idiopathic Pulmonary Fibrosis Honeycomb Cyst Contains A Mucocilary Pseudostratified Epithelium

<div><p>Background</p><p>We previously identified a <i>MUC5B</i> gene promoter-variant that is a risk allele for sporadic and familial Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP). This allele was strongly associated with increased MUC5B gene expression in lung tissue from unaffected subjects. Despite the strong association of this airway epithelial marker with disease, little is known of mucin expressing structures or of airway involvement in IPF/UIP.</p> <p>Methods</p><p>Immunofluorescence was used to subtype mucus cells according to MUC5B and MUC5AC expression and to identify ciliated, basal, and alveolar type II (ATII) cells in tissue sections from control and IPF/UIP subjects. Staining patterns were quantified for distal airways (Control and IPF/UIP) and in honeycomb cysts (HC).</p> <p>Results</p><p>MUC5B-expressing cells (EC) were detected in the majority of control distal airways. MUC5AC-EC were identified in half of these airways and only in airways that contained MUC5B-EC. The frequency of MUC5B+ and MUC5AC+ distal airways was increased in IPF/UIP subjects. MUC5B-EC were the dominant mucus cell type in the HC epithelium. The distal airway epithelium from control and IPF/UIP subjects and HC was populated by basal and ciliated cells. Most honeycombing regions were distinct from ATII hyperplasic regions. ATII cells were undetectable in the overwhelming majority of HC.</p> <p>Conclusions</p><p>The distal airway contains a pseudostratified mucocilary epithelium that is defined by basal epithelial cells and mucus cells that express MUC5B predominantly. These data suggest that the HC is derived from the distal airway.</p> </div

MUC5B is the dominant gel-forming mucin in the normal distal airway epithelium.

<p>A–D: Hematoxylin and eosin (H&E) staining of the normal conducting airway. A. Proximal airway; B–D. Distal airways. L, lumen; Arrow: cartilage; Arrowheads: black -submucosal gland, yellow - airway epithelium, blue - smooth muscle bands. Final magnification: 10× E–L: DIF analysis of MUC5B (red), MUC5AC (green) and nuclei (blue). E. Proximal airway. L: lumen; arrow: submucosal gland. F–H. Distal airways. Panels A & E; B & F; C & G; and D & H are adjacent sections. Representative images of airways expressing both MUC5B and MUC5AC (B, F); only MUC5B (C, G); neither MUC5B nor MUC5AC (D, H). Values in each panel indicate the frequency with which the pattern was detected. Final magnification, 10× I–L Single color images of the region indicated in panel F. Final magnification, 20×. M: Pie chart indicating the frequency of distal airways expressing MUC5B and/or MUC5AC. N: Frequency distribution of MUC5B (red) and MUC5AC (green) in distal airways. Asterisks represent significant p value (<0.05) obtained for test of proportions of that category.</p

Modern Age Pathology of Pulmonary Arterial Hypertension

Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH

Demographic Characteristics of Study Participants.

*<p>Smoking history was not available for 5 IPF/UIP cases.</p