Разработка технологии, проектирование оснастки и участка сборки-сварки основания секции механизированной крепи МКЮ.4У.58.100000

Разработка технологического процесса основания механизированной крепи, проектирование участка сборки-сварки. Выбор составных деталей изделия, определение марки стали, выбор метода сварки, определение режимов сварки и сварочных материалов, нормирование операций, составление технологического процесса, расчет необходимого количество оборудования, численность рабочих и разработка сборочно- сварочного приспособления.Development of the technological process of the foundation of the mechanized support, design of the assembly-welding section. Selection of component parts of the product, determination of the steel grade, selection of the welding method, determination of welding modes and welding materials, rationing of operations, preparation of the technological process, calculation of the required amount of equipment, the number of workers and development of assembly and welding equipment

Production of β‑ionone by combined expression of carotenogenic and plant CCD1 genes in Saccharomyces cerevisiae

Background Apocarotenoids, like the C13-norisoprenoids, are natural compounds that contribute to the flavor and/or aroma of flowers and foods. They are produced in aromatic plantslike raspberries and rosesby the enzymatic cleavage of carotenes. Due to their pleasant aroma and flavour, apocarotenoids have high commercial value for the cosmetic and food industry, but currently their production is mainly assured by chemical synthesis. In the present study, a Saccharomyces cerevisiae strain that synthesizes the apocarotenoid -ionone was constructed by combining integrative vectors and high copy number episomal vectors, in an engineered strain that accumulates FPP. Results Integration of an extra copy of the geranylgeranyl diphosphate synthase gene (BTS1), together with the carotenogenic genes crtYB and crtI from the ascomycete Xanthophyllomyces dendrorhous, resulted in carotenoid producing cells. The additional integration of the carotenoid cleavage dioxygenase gene from the plant Petunia hybrida (PhCCD1) let to the production of low amounts of -ionone (0.073 ± 0.01 mg/g DCW) and changed the color of the strain from orange to yellow. The expression of the crtYB gene from a high copy number plasmid in this former strain increased -ionone concentration fivefold (0.34 ± 0.06 mg/g DCW). Additionally, the episomal expression of crtYB together with the PhCCD1 gene in the same vector resulted in a final 8.5-fold increase of -ionone concentration (0.63 ± 0.02 mg/g DCW). Batch fermentations with this strain resulted in a final specific concentration of 1 mg/g DCW at 50 h, which represents a 15-fold increase. Conclusions An efficient -ionone producing yeast platform was constructed by combining integrative and episomal constructs. By combined expression of the genes BTS1, the carotenogenic crtYB, crtI genes and the plant PhCCD1 genethe highest -ionone concentration reported to date by a cell factory was achieved. This microbial cell factory represents a starting point for flavor production by a sustainable and efficient process that could replace current methods.This work was funded by grants COPEC-UC 6C-063 and FONDECYT No 1130822, and the Novo Nordisk Foundation

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study.

BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake

Kelten bei dem Laienforscher Christian Keferstein (1784 –1866)

Vor und während der Institutionalisierungsphase altertums- und sprachwissenschaftlicher Forschungen im 19. Jh. wurde der Keltenbegriff sowohl von ausgebildeten Sprach- und Altertumswissenschaftlern als auch von sogenannten Keltomanen benutzt. Christian Keferstein gehörte zu den Letztgenannten. Aus wohlhabenden Verhältnissen stammend, jedoch ohne fachwissenschaftliche Ausbildung, beschäftigte er sich zunächst mit Geologie und Geognostik und widmete sich später eingehend den Kelten, die er als das Urvolk Europas ansah. Neben kleineren Artikeln veröffentlichte er zwischen 1846 und 1851 sein mehrbändiges Hauptwerk „Ansichten ueber die keltischen Alterthümer, die Kelten überhaupt und besonders in Teutschland, so wie den keltischen Ursprung der Stadt Halle“. Der vorliegende Beitrag möchte das vergessene Werk Christian Kefersteins vorstellen und einige Aspekte der möglichen Motivation für seine Keltomanie analysieren.85924

Zelluläre Transport- und Endozytosemechanismen des Zytokins MIF und seiner Rezeptoren

First studies on the endocytosis of the cytokine MIF in the context of experiments showing MIF´s interaction with the COP9 signalosome (CSN) component JAB1/CSN5 indicated a receptor-independent mechanism. Afterwards, it was thought about a receptor-mediated endocytosis pathway for MIF because of its rapid cellular uptake in physiological concentrations. Which one of the possible endocytic pathways existing in mammalians are taken by MIF, has remained unknown. In the present thesis, endocytosis of MIF was studied in fibroblasts, T cells and other cell lines. The endocytosis pathway of MIF was successively explored by both conventional and laser-scanning microscopy using endosomal markers in colocalization studies with fluorescently labeled MIF and by using different pharmacological inhibitors. The involvement of the known MIF receptors CD74 and CXCR4 was additionally analysed in blockade and overexpression approaches. Pretreatment with the inhibitors monodansylcadaverine (MDC), chlorpromazine (CPZ) and dynasore in different colocalization studies showed that the MIF endocytosis pathway is dynamin- and clathrin-dependent. MIF is transported to late endosomes within a few minutes (10-20 min) but also colocalizes with early endosomes and lysosomes. Clathrin-independent, caveolin-dependent endocytic pathways were not involved because nystatin and filipin did not significantly effect MIF uptake and MIF did not colocalize with choleratoxin B. By applying the inhibitors bafilomycin and nocodazole, it was demonstrated that the mechanism of endocytosis requires a sufficient acidification of endosomal compartments and the integrity of the microtubule system. An analogy of the MIF endocytosis pathway to that of acetylated LDL was illustrated in colocalization studies with representatives. During early endocytotic passage, the endocytotic pathway of MIF also resembles that of transferrin. When studying the involvement of the known MIF receptors in MIF endocytosis, in the presence of CD74 an accelerated MIF uptake was recognized within the first 10 min. The CD74-deficient cell lines, HEK293 and HeLa, internalized MIF as well. Thus CD74 is not essential but supporting MIF endocytosis. The MIF receptor CXCR4 which is expressed in those cells turned out to be the second important receptor for MIF internalization. Blocking CXCR4 by applying the CXCR4-specific inhibitor AMD3100 showed a prominent inhibition of MIF endocytosis in HEK293 cells. According to that in absence of CD74 MIF uptake seems to be regulated by CXCR4. The involvement of both receptors in the endocytotic mechanism of MIF could be confirmed by the fact that both colocalized with each other and with MIF at the plasma membrane and in intracellular endosomal compartments. MIF and its receptors were shown to colocalize with lysosomes which also approved that MIF endocytosis is clathrin-associated. Similar to CXCR2, CXCR4 can form functional receptor complexes with CD74 which are involved in MIF-triggered activation of the PI3K/AKT signaling pathway which was demonstrated by an inhibition of protein kinase B´s (AKT) phosphorylation after addition of anti-CD74 or anti-CXCR4 antibodies or AMD3100. However, inhibition of CXCL12-triggered AKT activation could be exclusively achieved by anti-CXCR4 antibodies. Therefore, only MIF-triggered activation of the signaling pathway was mediated by both receptors. Chemokine-induced activation of signaling cascades can occur from the plasma membrane or upon endocytosis (‘endosomal signaling’). Corresponding studies to investigate endosomal MIF-induced AKT signaling in T cells, HeLa cells and in human dermal fibroblasts showed a cell type-dependent partially significant inhibition of the AKT activation due to the addition of endocytosis inhibitors which indicated that AKT activation is at least in part caused by endosomal signaling. Moreover, the inhibitory effect of the endocytosis inhibitors on AKT activation could be confirmed by an in vitro kinase assay in T cells. Thus, MIF-induced activation of the PI3K/AKT signaling pathway seems to be triggered, at least in part by an endosomal signaling mechanism

Zelluläre Transport- und Endozytosemechanismen des Zytokins MIF und seiner Rezeptoren

First studies on the endocytosis of the cytokine MIF in the context of experiments showing MIF´s interaction with the COP9 signalosome (CSN) component JAB1/CSN5 indicated a receptor-independent mechanism. Afterwards, it was thought about a receptor-mediated endocytosis pathway for MIF because of its rapid cellular uptake in physiological concentrations. Which one of the possible endocytic pathways existing in mammalians are taken by MIF, has remained unknown. In the present thesis, endocytosis of MIF was studied in fibroblasts, T cells and other cell lines. The endocytosis pathway of MIF was successively explored by both conventional and laser-scanning microscopy using endosomal markers in colocalization studies with fluorescently labeled MIF and by using different pharmacological inhibitors. The involvement of the known MIF receptors CD74 and CXCR4 was additionally analysed in blockade and overexpression approaches. Pretreatment with the inhibitors monodansylcadaverine (MDC), chlorpromazine (CPZ) and dynasore in different colocalization studies showed that the MIF endocytosis pathway is dynamin- and clathrin-dependent. MIF is transported to late endosomes within a few minutes (10-20 min) but also colocalizes with early endosomes and lysosomes. Clathrin-independent, caveolin-dependent endocytic pathways were not involved because nystatin and filipin did not significantly effect MIF uptake and MIF did not colocalize with choleratoxin B. By applying the inhibitors bafilomycin and nocodazole, it was demonstrated that the mechanism of endocytosis requires a sufficient acidification of endosomal compartments and the integrity of the microtubule system. An analogy of the MIF endocytosis pathway to that of acetylated LDL was illustrated in colocalization studies with representatives. During early endocytotic passage, the endocytotic pathway of MIF also resembles that of transferrin. When studying the involvement of the known MIF receptors in MIF endocytosis, in the presence of CD74 an accelerated MIF uptake was recognized within the first 10 min. The CD74-deficient cell lines, HEK293 and HeLa, internalized MIF as well. Thus CD74 is not essential but supporting MIF endocytosis. The MIF receptor CXCR4 which is expressed in those cells turned out to be the second important receptor for MIF internalization. Blocking CXCR4 by applying the CXCR4-specific inhibitor AMD3100 showed a prominent inhibition of MIF endocytosis in HEK293 cells. According to that in absence of CD74 MIF uptake seems to be regulated by CXCR4. The involvement of both receptors in the endocytotic mechanism of MIF could be confirmed by the fact that both colocalized with each other and with MIF at the plasma membrane and in intracellular endosomal compartments. MIF and its receptors were shown to colocalize with lysosomes which also approved that MIF endocytosis is clathrin-associated. Similar to CXCR2, CXCR4 can form functional receptor complexes with CD74 which are involved in MIF-triggered activation of the PI3K/AKT signaling pathway which was demonstrated by an inhibition of protein kinase B´s (AKT) phosphorylation after addition of anti-CD74 or anti-CXCR4 antibodies or AMD3100. However, inhibition of CXCL12-triggered AKT activation could be exclusively achieved by anti-CXCR4 antibodies. Therefore, only MIF-triggered activation of the signaling pathway was mediated by both receptors. Chemokine-induced activation of signaling cascades can occur from the plasma membrane or upon endocytosis (‘endosomal signaling’). Corresponding studies to investigate endosomal MIF-induced AKT signaling in T cells, HeLa cells and in human dermal fibroblasts showed a cell type-dependent partially significant inhibition of the AKT activation due to the addition of endocytosis inhibitors which indicated that AKT activation is at least in part caused by endosomal signaling. Moreover, the inhibitory effect of the endocytosis inhibitors on AKT activation could be confirmed by an in vitro kinase assay in T cells. Thus, MIF-induced activation of the PI3K/AKT signaling pathway seems to be triggered, at least in part by an endosomal signaling mechanism

Biochemical characterization of Artemia ras p21

The biochemical properties of Artemia ras proteins (p21) have been studied after immunoprecipitation with the monoclonal antibody Y13-259. The ras products bind GTP and GDP, and have GTPase activity. Artemia p21 was unable to hydrolyze Gp4G, although this dinucleotide exhibits high affinity for the protein. Our results demonstrate that the protein(s) recognized by the Y13- 259 antibody in this crustacean behave as typical mammalian ras p21s.This work was supported by grants of the CAICYT (BT/18) and FISSS (86/715).Peer Reviewe

Mapping Dominant Boreal Tree Species Groups by Combining Area-Based and Individual Tree Crown LiDAR Metrics with Sentinel-2 Data

Airborne light detection and ranging (LiDAR) data are increasingly used to inform sustainable forest management practices. Information about species composition is needed for a range of applications; however, commonly used area-based summaries of LiDAR data are limited to accurately differentiate tree species. The objective of this study was to map dominant species groups across a large (>580,000 ha) boreal forest by combining area-based and individual tree metrics derived from single photon LiDAR data with multispectral information derived from Sentinel-2 imagery. Classification of the forest into jack pine (Pinus banksiana), black spruce (Picea mariana), mixed conifer, mixedwood, and hardwood species groups resulted in an overall accuracy of 67.8% compared with field data. A more generalized classification into softwood, hardwood, and mixedwood had an overall accuracy of 83.2%. The reflectance in the red edge region of the electromagnetic spectrum (λ = 740 nm), the area and volume of tree crowns, and the cumulative distribution of LiDAR returns in the canopy were particularly important variables to discriminate between species groups. Wall-to-wall predictions of species groups based on remotely sensed data—as derived herein—could provide a spatially-detailed alternative to stand-level species composition information traditionally derived from photo-interpreted aerial imagery