Оптимизация затрат нефтегазовой отрасли на примере предприятия АО «Томскнефть» ВНК

В работе были рассмотрены следующие вопросы: сущность затрат, формирование себестоимости продукции, методы учета и калькуляция затрат, особенности учета затрат в нефтегазовой отрасли, пути снижения затрат., краткая характеристика исследуемого объекта, проведен анализ себестоимости продукции.V rabote byli rassmotreny sleduyushchiye voprosy: sushchnost' zatrat, formirovaniye sebestoimosti produktsii, metody ucheta i kal'kulyatsii zatrat, osobennosti ucheta zatrat v neftegazovoy otrasli, puti snizheniya zatrat., Kratkaya kharakteristika issleduyemogo ob"yekta, proveden analiz sebestoimosti produktsii

Extracellular matrix components indicate remodelling activity in different fibrosis stages of human non-alcoholic fatty liver disease

AIMS: The composition of several important extracellular matrix components (ECM) has not yet been elucidated in human non-alcoholic fatty liver disease (NAFLD). We aim to investigate the proportion of hepatic stellate cells (HSCs) and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in human NAFLD liver tissue with respect to severity of inflammation and fibrosis. METHODS AND RESULTS: Histopathological features were quantified by NAFLD activity score and grading assignment. The collagen proportionate area (CPA) was measured. Slides were stained with alpha-smooth muscle actin (alpha-SMA), as a marker of activated HSCs, and alpha-SMA was quantified digitally. Zymography was performed to measure the proteolytic activity of MMP-2 and MMP-9. TIMP-1 and TIMP-2 protein concentration was measured with enzyme-linked immunosorbent assay (ELISA). alpha-SMA was higher in severe fibrosis (6.3%, interquartile range 2.9-13.1) than mild and no fibrosis (median 1.1 and 0.9%, P < 0.001) and correlated strongly with CPA (Rs = 0.870, P < 0.001). ProMMP-2 activity in severe (4.1%, IQR 2.6-16.2) and mild fibrosis (2.7%, IQR 1.9-3.9) was higher than in no fibrosis (1.5%, (IQR 0.95-2.1); P = 0.001 and P = 0.046) and showed a moderate positive correlation with CPA (Rs = 0.495, P = 0.001). TIMP-1 and TIMP-2 were significantly higher in severe fibrosis than mild or no fibrosis. Both showed moderate correlation with CPA (TIMP-1: Rs = 0.471, P = 0.002 and TIMP-2: Rs = 0.325, P = 0.036). MMP-9 correlated as the only ECM component to inflammation severity. CONCLUSIONS: Advanced human NAFLD-fibrosis has a distinct ECM composition with increased HSCs and increased TIMP inhibition, but there is also ongoing remodelling activity of MMP-2

Apoptosis-Inducing Factor Regulates Skeletal Muscle Progenitor Cell Number and Muscle Phenotype

Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in “slow” muscles such as soleus, as well as in “fast” muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation

Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA-B27 transgenic rats

Germ-free HLA-B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen-free (SPF) bacteria induces colitis accompanied by immune activation. To study host-dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA-B27 TG versus nontransgenic (non-TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL-stimulated unseparated T- or B- cell-depleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-γ, IL-12, TNF, IL-10 and TGF-β production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-γ, IL-12 and TNF than did non-TG MLN cells. In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-β. T cell depletion abolished IFN-γ and decreased IL-12 production, but did not affect IL-10 and TGF-β production. Conversely, neither IL-10 nor TGF-β was produced in cultures of B cell-depleted MLN. In addition, CD4+ T cells enriched from MLN of HLA-B27 TG but not from non-TG rats produced IFN-γ when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-β, but not IFN-γ, IL-12 and TNF were produced by MLN cells from germ-free TG rats. These results indicate that the colitis that develops in SPF HLA-B27 TG rats is accompanied by activation of IFN-γ-producing CD4+ T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation

Exploring transparent reporting and data availability in systematic reviews to identify subgroup evidence:imaging for suspected hepatocellular carcinoma in the non-cirrhotic liver

We aim to illustrate the role of complete and transparent reporting coupled with access to data sourced from published systematic reviews, especially assisting in the identification of evidence for subgroups within the context of a rare disease. To accomplish this principle, we provide a real-world example encountered during the revision of the Dutch clinical practice guideline for hepatocellular carcinoma. Specifically, we retrieved insights from two Cochrane reviews to identify direct evidence concerning the diagnostic test accuracy of computed tomography and magnetic resonance imaging for detecting hepatocellular carcinomas in suspected patients without liver cirrhosis. Through reusing the Cochrane review authors’ efforts already undertaken in their exhaustive literature search and selection, we successfully identified relevant direct evidence for this subgroup of suspected patients without cirrhosis and performed an evidence synthesis within the constraints of limited resources for the guideline revision. This approach holds the potential for replication in other subgroups in the context of rare diseases, contingent on the transparent and complete reporting of systematic reviews, as well as the availability and accessibility of their extracted data. Consequently, we underscore the importance of adhering to established reporting guidelines for systematic reviews, while simultaneously advocating for increased availability and accessibility to data. Such practices would not only increase the transparency and reproducibility of systematic reviews but could also increase reusability of their data. In turn, the increased reusability could result in reduced resource utilization in other sectors such as the guideline developing community as we show in our example.</p

Diabetes Causes Bone Marrow Autonomic Neuropathy and Impairs Stem Cell Mobilization via Dysregulated p66Shc and Sirt1

Diabetes compromises the bone marrow (BM) microenvironment and reduces circulating CD34 + cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system (SNS) is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating CD34 + cells. Experimental diabetes (STZ and Ob/Ob ) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired Lin - cKit + Sca1 + (LKS) cell and endothelial progenitor cells (EPC, CD34 + Flk1 + ) mobilization and vascular recovery after ischemia. DAN increased expression of p66Shc and reduced expression of Sirt1 in mice and humans. p66Shc KO in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, while hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1 , diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L . CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the lifespan regulators p66Shc and Sirt1

Разработка и исследование асинхронного электропривода с наблюдателем состояния

Выпускная квалификационная работа 109 с., 35 рис., 18 табл., 47 источников, 5 прил. Объектом исследования является дискретная математическая модель наблюдателя состояния полного порядка асинхронного двигателя. Цель работы – Разработка и исследование асинхронного электропривода с наблюдателем состояния В процессе исследования проводилось имитационное моделирование разработанной дискретной математической модели асинхронного двигателя и разработанной дискретной математической модели наблюдателя состояния полного порядкаFinal qualifying work 109 p., 35 fig., 18 tab., 47 sources, 5 adj. The object of research is a discrete mathematical model of the observer status of full order of the induction motor. Objective - Development and research of the asynchronous electric drive with observer status The study was conducted simulations developed discrete mathematical model of the induction motor and the developed mathematical model of discrete observer of full order stat

A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14 Mutated Lung Cancer

Introduction: Targeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients' outcomes. The development of more potent MET kinase inhibitors could further benefit these patients. The aim of this trial is to determine the safety and recommended phase 2 dose (RP2D) of OMO-1 (an oral dual MET kinase/OCT-2 inhibitor) and to assess preliminary clinical efficacy in METex14-positive NSCLC and other MET-positive solid tumors. Materials and Methods: This was a first-in-patient, open-label, multicenter study of OMO-1 in patients with locally advanced or metastatic solid malignancies. A standard 3 + 3 dose escalation design was utilized starting at a dose level of 100 mg BID continuously. Preliminary efficacy was investigated in patients with METex14-positive NSCLC, and MET amplified NSCLC and other solid tumors (MET basket). Results: In the dose-escalation part, 24 patients were included in 5 dose levels ranging from 100 mg twice daily (BID) to 400 mg BID. Most common adverse events (≥ 20%) were nausea, fatigue, vomiting, increased blood creatinine, and headache. The RP2D was determined at 250 mg BID. In the expansion cohorts, 15 patients were included (10 in METex14-positive NSCLC cohort and 5 in MET basket cohort) and received either 200 or 250 mg BID. Eight out of the 10 patients with METex14 positive NSCLC had stable disease as the best response. Conclusion: OMO-1 was tolerated at the dose of 250 mg BID and shows initial signs of MET inhibition and anti-tumor activity in METex14 mutated NSCLC patients.</p

A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14 Mutated Lung Cancer

Introduction: Targeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients’ outcomes. The development of more potent MET kinase inhibitors could further benefit these patients. The aim of this trial is to determine the safety and recommended phase 2 dose (RP2D) of OMO-1 (an oral dual MET kinase/OCT-2 inhibitor) and to assess preliminary clinical efficacy in METex14-positive NSCLC and other MET-positive solid tumors.// Materials and Methods: This was a first-in-patient, open-label, multicenter study of OMO-1 in patients with locally advanced or metastatic solid malignancies. A standard 3 + 3 dose escalation design was utilized starting at a dose level of 100 mg BID continuously. Preliminary efficacy was investigated in patients with METex14-positive NSCLC, and MET amplified NSCLC and other solid tumors (MET basket).// Results: In the dose-escalation part, 24 patients were included in 5 dose levels ranging from 100 mg twice daily (BID) to 400 mg BID. Most common adverse events (≥ 20%) were nausea, fatigue, vomiting, increased blood creatinine, and headache. The RP2D was determined at 250 mg BID. In the expansion cohorts, 15 patients were included (10 in METex14-positive NSCLC cohort and 5 in MET basket cohort) and received either 200 or 250 mg BID. Eight out of the 10 patients with METex14 positive NSCLC had stable disease as the best response.// Conclusion: OMO-1 was tolerated at the dose of 250 mg BID and shows initial signs of MET inhibition and anti-tumor activity in METex14 mutated NSCLC patients