The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities

Long-term effects of liming on soil physico-chemical properties and micro-arthropod communities in Scotch pine forest

Contains fulltext : 205615.pdf (publisher's version ) (Open Access

Redox potential is a robust indicator for decomposition processes in drained agricultural peat soils:A valuable tool in monitoring peatland wetting efforts

Peat decomposition driven by soil metabolic processes is responsible for approximately 2 % of global annual anthropogenic greenhouse gas emissions. A peat soil's redox potential (Eh) and pH reflect its biogeochemical state and are therefore linked to the rate of peat decomposition and greenhouse gas production. In this study, we aim to establish if continuous Eh measurements are an effective tool to monitor metabolic peat decomposition processes and thus to quantify the effects of peat wetting efforts. We applied continuous in-situ Eh measurements (&gt;150 sensors 2020–2022) as a proxy for metabolic peat decomposition processes, which we validated under field conditions with extensive sampling of porewater chemistry (pH, NO3–, SO42−, Mn(II), Fe(II), S2− and CH4, &gt;2000 samples) for five agricultural, drained, minerotrophic peatland sites in the Netherlands. These 5 sites consisted of plots with and without subsoil irrigation (SSI), where SSI aims to raise groundwater levels and thus wet the peat soil. We found that in-situ continuous Eh measurements closely reflected spatial and temporal heterogeneity in pore water chemistry. Therefore, we concluded that Eh is a robust proxy for peat decomposition processes. Building on this result, we used continuous Eh measurements to study the prevalence of specific metabolic processes from site-to-site in relation with groundwater level changes. We found that, while groundwater levels are an important driver for (an)aerobic conditions, groundwater levels do not explain the full dynamics and extent of (an)aerobic conditions. O2 intrusion was mostly limited to approximately 0.5 m depth at deep (&gt;0.8 m) groundwater levels, likely due to air diffusion limitation. Higher and more constant groundwater levels year-round at SSI plots decreased oxygen intrusion and tended to deplete porewater Fe(II) and SO42−, which led to more reducing Eh and higher porewater CH4 concentrations. The depletion of electron acceptors and occurrence of methanogenesis differed from site to site. In summary, high-frequent Eh monitoring is found to be an effective tool to monitor metabolic peat decomposition processes and quantify the effects of peatlands wetting efforts. Therefore, this methodology is suitable to evaluate and further optimize peatland monitoring and preservation.</p

Biogeochemical Characteristics of the Last Floating Coastal Bog Remnant in Europe, the Sehestedt Bog

Contains fulltext : 203557.pdf (publisher's version ) (Closed access

Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response

Meningococcal outer membrane vesicles (OMVs) have been extensively investigated and successfully implemented as vaccines. They contain pathogen associated molecular patterns including lipopolysaccharide (LPS), capable of triggering innate immunity. However, Neisseria meningitidis contains an extremely potent hexa-acylated LPS, leading to adverse effects when its OMVs are applied as vaccines. To create safe OMV vaccines detergent treatment is generally used to reduce LPS content. While effective, this method also leads to loss of protective antigens such as lipoproteins. Alternatively, genetic modification of LPS can reduce its toxicity. In the present study, we have compared standard OMV isolation methods using detergent or EDTA with genetic modifications of LPS to yield a penta-acylated lipid A (lpxL1 and pagL), on the in vitro induction of innate immune responses. The use of detergent decreased both TLR4 and TLR2 activation by OMVs, while the LPS modifications only reduced TLR4 activation. Mutational removal of PorB or fHbp, two proteins known to trigger TLR2 signaling, had no effect indicating that multiple TLR2 ligands are removed by detergent treatment. Detergent treated OMV and lpxL1 OMV showed similar reduction of cytokine profiles in the human monocytic cell line MM6 and human DCs. OMVs with the alternative penta-acylated LPS structure obtained after PagL-mediated deacylation showed reduced induction of pro-inflammatory cytokines IL-6 and IL-1β but not of IP-10, a typical TRIF dependent chemokine. Taken together, these data show that lipid A modification can be used to obtain OMVs with reduced activation of innate immunity, similar to what is found after detergent treatment

Development and testing of a prototype of a dental extraction trainer with real-time feedback on forces, torques, and angular velocity

The need for a training modality for tooth extraction procedures is increasing, as dental students do not feel properly trained. In this study, a prototype of a training setup is designed, in which extraction procedures can be performed on jaw models and cadaveric jaws. The prototype was designed in a way that it can give real-time feedback on the applied forces in all three dimensions (buccal/lingual, mesial/distal, and apical/coronal), torques, and angular velocity. To evaluate the prototype, a series of experimental extractions on epoxy models, conserved jaws, and fresh frozen jaws were performed. Extraction duration (s), angular velocity (degrees/s), average force (N), average torque (Nm), linear impulse (Ns), and angular impulse (N ms) were shown in real-time to the user and used to evaluate the prototype. In total, 342 (92.9%) successful extractions were performed using the prototype (n= 113 epoxy factory-made, n=187 epoxy re-used, n=17 conserved, n=25 fresh frozen). No significant differences were found between the conserved and the fresh frozen jaws. The fresh frozen extraction duration, linear impulse, and angular impulse differed significantly from the corresponding values obtained for the epoxy models. Extractions were successfully performed, and the applied forces, torques, and angular velocity were recorded and shown as real-time feedback using the prototype of the dental extraction trainer. The feedback of the prototype is considered reliable

Evaluation of the elevated-temperature performance and degradation mechanisms of thread compounds

Thread compounds play an important role in the sealing ability of casing connections in the oil and gas industry. Next to their lubricating role during assembly, most of these thread compounds make use of nonbiodegradable or persistent particle additives to aid in the sealing ability. Replacing these additives for biodegradable and nonpersistent alternatives is, however, a challenge in high-temperature (>150◦C) well environments. This paper presents an investigation of the high-temperature failure mechanisms of thread compounds, with the aim of developing biodegradable high-temperature-resistant thread compounds. To this end, the performance of commercially available, environmentally acceptable thread compounds was investigated using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), high-temperature rheometry, and high-temperature pin-on-disk experiments. The compounds are assessed for their stability, consistency, lubricity, and the resulting wear at high temperature. The results indicated that, without exception, the commercially available thread compounds investigated in this study fail by adhesive and/or abrasive wear at approximately 150◦C because of thermally induced degradation. To remedy this and to validate the found failure mechanisms, a prototype thread compound was developed. The conclusion was that a successful high-temperature-resistant environmentally acceptable thread compound can be developed using the methodology described. The key property of this thread compound is the ability to form a tribofilm during makeup that protects the surface at a later stage when the lubricant has lost its consistency and the base oil is fully evaporated

Evaluation of the elevated temperature performance and degradation mechanisms of thread compounds

Thread compounds play an important role in the sealing ability of casing connections in the oil and gas industry. Next to their lubricating role during assembly, most of these thread compounds make use of nonbiodegradable or persistent particle additives to aid in the sealing ability. Soon, these additives need to be replaced by benign alternatives as agreed in the proceedings of the Oslo-Paris Commission. This is, however, a challenge in high temperature (>150°C) well environments. This paper presents an investigation of the high temperature failure mechanisms of thread compounds with the aim to develop biodegradable high temperature resistant thread compounds. To this end, the performance of commercially available, environmentally acceptable thread compounds was investigated with thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), high temperature rheometry and high temperature pin-on-disc experiments. The compounds are assessed on their stability, consistency, lubricity, and the resulting wear at high temperature. The results indicated that, without exception the commercially available thread compounds investigated in this study fail by adhesive and/or abrasive wear at around 150 degrees Celsius because of thermally induced degradation. To remedy this and to validate the mechanisms, a prototype thread compound was developed which exhibits strong film forming. The conclusion is that a successful high temperature resistant environmentally acceptable thread compound can likely be developed. The key property of this thread compound should be the ability to form a tribofilm during make-up which protects the surface at a later stage when the lubricant has lost its consistency and the base oil is fully evaporated

On the sealability of metal-to-metal seals with application to premium casing and tubing connections

Metal-to-metal seals are used in connections of casing and tubing in oil and gas wells. This paper describes the mechanisms of sealing metal-to-metal seals as investigated using an experimental setup and a stochastic numerical sealing model. Experiments were conducted for a variety of thread compounds and applied pin/box surface coatings. The results were used to validate a stochastic numerical sealing model for sealability. The model couples a contact-mechanics model with a flow model and takes into account the influence of all the surface-topography features by introducing the concept of seal permeability. Once validated, the model was used together with the experimental results to better understand the sealing mechanisms of metal-to-metal seals. The sealing configuration is a face seal with an 80-mm roundoff radius on one face pressing against a flat on the other face. The face-seal specimens were manufactured from P110 tubing to ensure material properties that are representative for casing or tubing. The test setup used is designed for investigating only the metal-to-metal seal of the connection. The setup can perform rotary sliding under constant load to simulate surface changes during makeup and subsequently perform a leakage test. The sealing limit is determined by applying 700-bar fluid pressure and then gradually reducing the normal force until leakage is observed. The data are subsequently used to validate the previously published stochastic numerical sealing model. The results indicate a strong dependence on the type of thread compound used for the onset of leakage. The thread compound affects the amount of wear and thus changes the surface topography of the interacting surfaces. It is shown that the stochastic numerical sealing model is capable of predicting the onset of leakage within the experimental accuracy. The model shows further that certain surface topographical features improve the sealing performance. In particular, a surface manufactured by turning on a lathe that is in contact with, for instance, a smooth shot-blasted surface topography leads to highly localized contact areas, which in turn yield the best sealing performance