Despite Antiplatelet therapy (APT), cardiovascular patients undergoing revascularisation remain at high risk for thrombotic events. Individual response to APT varies substantially, resulting in ...insufficient protection from thrombotic events due to high on-treatment platelet reactivity (HTPR) in less than or equal to40% of patients. Individual variation in platelet response impairs APT guidance on a single patient level. Unfortunately, little is known about individual platelet response to APT over time, timing for accurate residual platelet reactivity measurement, or the optimal test to monitor residual platelet reactivity. To investigate residual platelet reactivity variability over time in individual patients undergoing carotid endarterectomy (CEA) treated with clopidogrel. Platelet reactivity was determined in patients undergoing CEA in a prospective, single-centre, observational study using the VerifyNow (change in turbidity from ADP-induced binding to fibrinogen-coated beads), the VASP assay (quantification of phosphorylation of vasodilator-stimulated phosphoprotein), and a flow-cytometry-based assay (PACT) at four perioperative time points. Genotyping identified slow (CYP2C19*2 and CYP2C19*3) and fast (CYP2C19*17) metabolisers. Between December 2017 and November 2019, 50 patients undergoing CEA were included. Platelet reactivity measured with the VerifyNow (p = < .001) and VASP (p = .029) changed over time, while the PACT did not. The VerifyNow identified patients changing HTRP status after surgery. The VASP identified patients changing HTPR status after eight weeks (p = .018). CYP2C19 genotyping identified 13 slow metabolisers. In patients undergoing CEA, perioperative platelet reactivity measurements fluctuate over time with little agreement between platelet reactivity assays. Consequently, HTPR status of individual patients measured with the VerifyNow and VASP assay changed over time. Therefore, generally used perioperative platelet reactivity measurements seem unreliable for adjusting perioperative APT strategy.
An aerobic granular sludge (AGS) reactor was run for 280 days to study the competition between Phosphate and Glycogen Accumulating Organisms (PAOs and GAOs) at high temperatures. Numerous researches ...have proven that in suspended sludge systems PAOs are outcompeted by GAOs at higher temperatures. In the following study a reactor was operated at 30 °C in which the P-removal efficiency declined from 79% to 32% after 69 days of operation when biomass removal for sludge retention time (SRT) control was established by effluent withdrawal. In a second attempt at 24 °C, efficiency of P-removal remained on average at 71 ± 5% for 76 days. Samples taken from different depths of the sludge bed analysed using
Fluorescent in situ hybridization (FISH) microscopy techniques revealed a distinctive microbial community structure: bottom granules contained considerably more
Accumulibacter (PAOs) compared to top granules that were dominated by
Competibacter (GAOs). In a third phase the SRT was controlled by discharging biomass exclusively from the top of the sludge bed. The application of this method increased the P-removal efficiency up to 100% for 88 days at 30 °C. Granules selected near the bottom of the sludge bed increased in volume, density and overall ash content; resulting in significantly higher settling velocities. With the removal of exclusively bottom biomass in phase four, P-removal efficiency decreased to 36% within 3 weeks. This study shows that biomass segregation in aerobic granular sludge systems offers an extra possibility to influence microbial competition in order to obtain a desired population.
► Segregation of granular biomass occurred along the settled sludge bed. ► PAOs were prevalent at the bottom, whereas GAOs dominated at the top of the sludge bed. ► Removal of GAO dominated sludge resulted in 100% P-removal efficiencies at 30 °C. ► Selective sludge withdrawal can be used to engineer the microbial population in the reactor.
The activity of sulfate reducing bacteria (SRB) in domestic wastewater treatment plants (WWTP) is often considered as a problem due to H₂S formation and potential related odour and corrosion of ...materials. However, when controlled well, these bacteria can be effectively used in a positive manner for the treatment of wastewater. The main advantages of using SRB in wastewater treatment are: (1) minimal sludge production, (2) reduction of potential pathogens presence, (3) removal of heavy metals and (4) as pre-treatment of anaerobic digestion. These advantages are accessory to efficient and stable COD removal by SRB. Though only a few studies have been conducted on SRB treatment of domestic wastewater, the many studies performed on industrial wastewater provide information on the potential of SRB in domestic wastewater treatment. A key-parameter analyses literature study comprising pH, organic substrates, sulfate, salt, temperature and oxygen revealed that the conditions are well suited for the application of SRB in domestic wastewater treatment. Since the application of SRB in WWTP has environmental benefits its application is worth considering for wastewater treatment, when sulfate is present in the influent.
We evaluated the potential of feeding high-oil rapeseed cake or natural additives as rumen modifiers on enteric methane (CH4) emissions, nutrient utilization, performance, and milk fatty acid (FA) ...profile of dairy cows. Eight Nordic Red dairy cows averaging (mean ± SD) 81 ± 21 d in milk and 41.0 ± 1.9 kg of milk yield at the beginning of the study were randomly assigned to a replicated 4 × 4 Latin square design with 21-d periods. Treatments comprised grass silage-based diets (45:55 forage to concentrate ratio on dry matter basis) including (1) control containing 19.3% rapeseed meal (CON), (2) CON with full replacement of rapeseed meal with rapeseed cake (RSC), (3) supplementation of CON with 50 g/d of yeast hydrolysate product plus coniferous resin acid-based compound (YHR), and (4) supplementation of CON with 20 g/d of combination of garlic-citrus extract and essential oils in a pellet (GCE). Apparent total-tract digestibility was measured using total collection of feces, and CH4 emissions were measured in respiratory chambers on 4 consecutive days. Data collected during d 17 and 21 in each period were used for ANOVA analysis using a mixed model. Treatments did not affect dry matter intake (DMI), whereas feeding RSC increased crude protein and ether extract digestibility compared with the other diets. Emissions of CH4 per day, per kilogram of DMI, and per kilogram of energy-corrected milk, and gross energy intake were lower for RSC compared with other diets. We found no effect of YHR on daily CH4 emissions, whereas CH4 yield (g of CH4/kg of DMI or as percentage of gross energy intake) decreased with GCE compared with CON. Treatments did not influence energy balance. Further, RSC reduced the proportion of N intake excreted in feces, and YHR improved N balance compared with CON diet. Feeding RSC resulted in greatest yields of milk and energy-corrected milk, and feed efficiency. Relative to the CON diet, RSC decreased saturated FA by 10% in milk fat by increasing cis-monounsaturated FA but also increased the proportion of trans FA. Proportion of odd- and branched-chain FA increased with GCE and YHR compared with CON. We conclude that replacing rapeseed meal by rapeseed cake decreased CH4 emissions, whereas YHR or GCE had no effect on CH4 emissions in this study.
Seawater toilet flushing, seawater intrusion in the sewerage, and discharge of sulfate-rich industrial effluents elevates sulfate content in wastewater. The application of sulfate-reducing bacteria ...(SRB) in wastewater treatment is very beneficial; as for example, it improves the pathogen removal and reduces the volume of waste sludge, energy requirement and costs. This paper evaluates the potential to apply biological sulfate reduction using acetate and propionate to saline sewage treatment in moderate climates. Long-term biological sulfate reduction experiments at 10 and 20 °C were conducted in a sequencing batch reactor with synthetic saline domestic wastewater. Subsequently, acetate and propionate (soluble organic carbon) conversion rate were determined in both reactors, in the presence of either or both fatty acids. Both acetate and propionate consumption rates by SRB were 1.9 times lower at 10 °C than at 20 °C. At 10 °C, propionate was incompletely oxidized to acetate. At 10 °C, complete removal of soluble organic carbon requires a significantly increased hydraulic retention time as compared to 20 °C. The results of the study showed that biological sulfate reduction can be a feasible and promising process for saline wastewater treatment in moderate climate.
The Bohemian Forest Ecosystem encompasses various wildlife management systems. Two large, contiguous national parks (one in Germany and one in the Czech Republic) form the centre of the area, are ...surrounded by private hunting grounds, and hunting regulations in each country differ. Here we aimed at unravelling the influence of management-related and environmental factors on the distribution of red deer (Cervus elaphus) and roe deer (Capreolus capreolus) in this ecosystem. We used the standing crop method based on counts of pellet groups, with point counts every 100 m along 218 randomly distributed transects. Our analysis, which accounted for overdispersion as well as zero inflation and spatial autocorrelation, corroborated the view that both human management and the physical and biological environment drive ungulate distribution in mountainous areas in Central Europe. In contrast to our expectations, protection by national parks was the least important variable for red deer and the third important out of four variables for roe deer; protection negatively influenced roe deer distribution in both parks and positively influenced red deer distribution in Germany. Country was the most influential variable for both red and roe deer, with higher counts of pellet groups in the Czech Republic than in Germany. Elevation, which indicates increasing environmental harshness, was the second most important variable for both species. Forest cover was the least important variable for roe deer and the third important variable for red deer; the relationship for roe deer was positive and linear, and optimal forest cover for red deer was about 70% within a 500 m radius. Our results have direct implications for the future conservation management of deer in protected areas in Central Europe and show in particular that large non-intervention zones may not cause agglomerations of deer that could lead to conflicts along the border of protected, mountainous areas.
In the sewage or wastewater treatment plant, biological sulphate reduction can occur spontaneously or be applied beneficially for its treatment. The results of this study can be applied to control ...SRB in the sewage and WWTP. Therefore, population diversity analyses of SRB for nine activated sludge wastewater treatment plants (WWTP) in the Netherlands and the effect of long-term (months) oxygen exposures on the SRB activity were carried out. T-RFLP and clone sequencing analyses of winter and summer samples revealed that (1) all WWTP have a similar SRB population, (2) there is no seasonal impact (10–20 °C) on the SRB population present in the WWTP and (3) Desulfobacter postgatei, Desulfovibrio desulfuricans and Desulfovibrio intestinalis were the most common and dominant SRB species observed in these samples, and origin from the sewage. Short term activity tests demonstrated that SRB were not active in the aerobic WWTP, but while flushed with N₂-gas SRB became slightly active after 3 h. In a laboratory reactor at a dissolved oxygen concentration of <2 %, sulphate reduction occurred and 89 % COD removal was achieved. SRB grew in granules, in order to protect themselves for oxygen exposures. SRB are naturally present in aerobic WWTP, which is due to the formation of granules.
AIMS: Sulphate‐reducing bacteria (SRB) activity is generally considered as inconvenience in domestic wastewater treatment plants (WWTP), but could also be applied beneficially. The competition ...between SRB and methanogens is a point of concern for stable process design. As limited attention was given to the effect of varying acetate and propionate concentrations on SRB activity, this study focused specially on these substrates. METHODS AND RESULTS: The research was performed in sequencing batch reactors operated at 20°C and an SRT of 15 days. In the acetate‐fed reactor, methanogens became dominant, while in the propionate reactor, SRB were the dominant population. In the mixed‐substrate‐fed reactor, both substrates were converted by SRB. The dominant SRB population in the mixed‐substrate‐fed reactor was different from the propionate‐fed reactor, but all operational characteristics such as the substrate consumption rate, yield and growth rate were similar. The sludge adapted to propionate could easily switch to an acetate feed procedure. CONCLUSIONS: These results indicate that under wastewater temperature of 20°C, the SRB are likely to outcompete methanogens more easily as inferred from pure substrate studies on acetate solely. SIGNIFICANCE AND IMPACT OF THE STUDY: The present results show that the natural presence of propionate in wastewater allows stable sulphate reduction, which decreases the biogas production, but provides an opportunity for using SRB beneficially in wastewater treatment.
The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR antibody that has been approved for use in oncology. Previously we ...investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226. We demonstrated that cetuximab-resistant clones (Ctx(R)) had increased nuclear localization of the EGFR. This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab. To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member(s) controlled this process as well as the EGFR tyrosine residues that are involved. Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all Ctx(R) clones. Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in Ctx(R) clones, but not in cetuximab-sensitive (Ctx(S)) parental cells. Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus. Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing Ctx(S) parental cells led to increased nuclear EGFR. Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS. Further, all Ctx(R) clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels. siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses. SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR. Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance.
A direct diode laser was built with > 800 W output power at 940 nm to 980 nm. The radiation is coupled into a 100 µm fiber and the NA ex fiber is 0.17. The laser system is based on pump modules that ...are wavelength stabilized by VBGs. Dense and coarse wavelength multiplexing are realized with commercially available ultra-steep dielectric filters. The electro-optical efficiency is above 30%. Based on a detailed analysis of losses, an improved e-o-efficiency in the range of 40% to 45% is expected in the near future. System performance and reliability were demonstrated with sheet metal cutting tests on stainless steel with a thickness of 4.2 mm.
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