Recent improvements in the speed, cost and accuracy of next generation sequencing are revolutionizing the discovery of single nucleotide polymorphisms (SNPs). SNPs are increasingly being used as an ...addition to the molecular ecology toolkit in nonmodel organisms, but their efficient use remains challenging. Here, we discuss common issues when employing SNP markers, including the high numbers of markers typically employed, the effects of ascertainment bias and the inclusion of nonneutral loci in a marker panel. We provide a critique of considerations specifically associated with the application and population genetic analysis of SNPs in nonmodel taxa, focusing specifically on some of the most commonly applied methods.
Estimating waves via measured ship responses Nielsen, Ulrik D.; Bingham, Harry B.; Brodtkorb, Astrid H. ...
Scientific reports,
10/2023, Letnik:
13, Številka:
1
Journal Article
Recenzirano
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Abstract
Optimisation of energy efficiency and operational performance as well as assessment of safety levels and emissions of marine operations require detailed information about the acting wave ...system. It is possible—with an analogy to classical wave buoys—to estimate the directional wave spectrum by processing sensor measurements of wave-induced responses (e.g., motions and structural responses) from a ship. Compared to other sources of wave data (e.g., buoys, satellites, third-generation wave models), estimation concepts using the ship itself as a buoy provide the wave spectrum at the exact spatio-temporal point, potentially increasing accuracy and with minimal associated cost. This paper gives an overview of the technology, discusses associated uncertainties, and highlights new developments made for estimating waves via measured ship responses.
•Biocrude compounds from woody biomass can be classified into two groups: cyclopentenones and oxygenated aromatics.•Biocrude quality can be predicted based on the feedstock model compound ...composition.•Elemental composition is almost invariant to feedstock composition.•Reaction scheme from model compound, through intermediates, to biocrude is proposed.•Residual oxygen in the biocrude is mainly positioned in ketones and phenolic alcohols.
Hydrothermal liquefaction is a promising technology for the conversion of a wide range of bio-feedstock into a biocrude; a mixture of chemical compounds that holds the potential for a renewable production of chemicals and fuels. Most research in hydrothermal liquefaction is performed in batch type reactors, although a continuous and energy-efficient operation is paramount for such process to be feasible. In this work an experimental campaign in a continuous bench scale unit is presented. The campaign is based on glycerol-assisted hydrothermal liquefaction of aspen wood carried out with the presence of a homogeneous catalyst at supercritical water conditions, 400°C and 300bar. Furthermore, in the experimental campaign a water phase recirculation step is incorporated to evaluate the technical feasibility of such procedure. In total, four batches of approximately 100kg of feed each were processed successfully at steady state conditions without any observation of system malfunctioning. The biocrude obtained was characterized using several analytical methods to evaluate the feasibility of the process and the quality of the product. Results showed that a high quality biocrude was obtained having a higher heating value of 34.3MJ/kg. The volatile fraction of the biocrude consisted mostly of compounds having number of carbon atoms in the C6–C12 range similar to gasoline. In terms of process feasibility, it was revealed that total organic carbon (TOC) and ash significantly accumulated in the water phase when such is recirculated for the proceeding batch. After four batches the TOC and the ash mass fraction of the water phase were 136.2 g/L and 12.6 %, respectively. Water phase recirculation showed a slight increase in the biocrude quality in terms on an effective hydrogen-to-carbon ratio, but it showed no effects on the product gas composition or the pH of the water phase. The successful operation demonstrated the technical feasibility of a continuous production of high quality biocrude.
Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR β-chains. MAIT ...TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to structural alterations in MR1 that subsequently affected MAIT TCR recognition via conformational changes within the complementarity-determining region (CDR) 3β loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3β hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag-dependent manner, thereby modulating MAIT cell recognition.
Simulations from eleven coupled chemistry‐climate models (CCMs) employing nearly identical forcings have been used to project the evolution of stratospheric ozone throughout the 21st century. The ...model‐to‐model agreement in projected temperature trends is good, and all CCMs predict continued, global mean cooling of the stratosphere over the next 5 decades, increasing from around 0.25 K/decade at 50 hPa to around 1 K/decade at 1 hPa under the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES) A1B scenario. In general, the simulated ozone evolution is mainly determined by decreases in halogen concentrations and continued cooling of the global stratosphere due to increases in greenhouse gases (GHGs). Column ozone is projected to increase as stratospheric halogen concentrations return to 1980s levels. Because of ozone increases in the middle and upper stratosphere due to GHG‐induced cooling, total ozone averaged over midlatitudes, outside the polar regions, and globally, is projected to increase to 1980 values between 2035 and 2050 and before lower‐stratospheric halogen amounts decrease to 1980 values. In the polar regions the CCMs simulate small temperature trends in the first and second half of the 21st century in midwinter. Differences in stratospheric inorganic chlorine (Cly) among the CCMs are key to diagnosing the intermodel differences in simulated ozone recovery, in particular in the Antarctic. It is found that there are substantial quantitative differences in the simulated Cly, with the October mean Antarctic Cly peak value varying from less than 2 ppb to over 3.5 ppb in the CCMs, and the date at which the Cly returns to 1980 values varying from before 2030 to after 2050. There is a similar variation in the timing of recovery of Antarctic springtime column ozone back to 1980 values. As most models underestimate peak Cly near 2000, ozone recovery in the Antarctic could occur even later, between 2060 and 2070. In the Arctic the column ozone increase in spring does not follow halogen decreases as closely as in the Antarctic, reaching 1980 values before Arctic halogen amounts decrease to 1980 values and before the Antarctic. None of the CCMs predict future large decreases in the Arctic column ozone. By 2100, total column ozone is projected to be substantially above 1980 values in all regions except in the tropics.
Transfer functions are often used together with a wave spectrum for analysis of wave–ship interactions, where one application addresses the prediction of wave-induced motions or other types of global ...responses. This paper presents a simple and practical method which can be used to tune the transfer function of such responses to facilitate improved prediction capability. The input to the method consists of a measured response, i.e. time series sequences from a given sensor, the 2D wave spectrum characterising the seaway in which the measurements are taken, and an initial estimate of the transfer function for the response in study. The paper presents results obtained using data from an in-service container ship. The 2D wave spectra are taken from the ERA5 database, while the transfer function is computed by a simple closed-form expression. The paper shows that the application of the tuned transfer function leads to predictions which are significantly improved compared to using the transfer function without tuning.
•Seakeeping analysis using ERA5 2D spectra, response measurements and closed-form RAOs•An algorithm for the spectral analysis accounting for forward speed•Tuning of RAOs to correct theoretical estimates of response spectra•Calculation of a mean tuning coefficient, potentially as a function of sea state•Better prediction capability in seakeeping analyses
The microbial community of a fermented molasses-fed sequencing batch reactor (SBR) operated under feast and famine conditions for production of polyhydroxyalkanoates (PHAs) was identified and ...quantified through a 16 S rRNA gene clone library and fluorescence in situ hybridization (FISH). The microbial enrichment was found to be composed of PHA-storing populations (84% of the microbial community), comprising members of the genera Azoarcus, Thauera and Paracoccus. The dominant PHA-storing populations ensured the high functional stability of the system (characterized by high PHA-storage efficiency, up to 60% PHA content). The fermented molasses contained primarily acetate, propionate, butyrate and valerate. The substrate preferences were determined by microautoradiography-FISH and differences in the substrate-uptake capabilities for the various probe-defined populations were found. The results showed that in the presence of multiple substrates, microbial populations specialized in different substrates were selected, thereby co-existing in the SBR by adapting to different niches. Azoarcus and Thauera, primarily consumed acetate and butyrate, respectively. Paracoccus consumed a broader range of substrates and had a higher cell-specific substrate uptake. The relative species composition and their substrate specialization were reflected in the substrate removal rates of different volatile fatty acids in the SBR reactor.
We studied the flocculation mechanism at the molecular level by determining the atomic structures of N-Flo1p and N-Lg-Flo1p in complex with their ligands. We show that they have similar ligand ...binding mechanisms but distinct carbohydrate specificities and affinities, which are determined by the compactness of the binding site. We characterized the glycans of Flo1p and their role in this binding process and demonstrate that glycan-glycan interactions significantly contribute to the cell-cell adhesion mechanism. Therefore, the extended flocculation mechanism is based on the self-interaction of Flo proteins and this interaction is established in two stages, involving both glycan-glycan and protein-glycan interactions. The crucial role of calcium in both types of interaction was demonstrated: Ca(2+) takes part in the binding of the carbohydrate to the protein, and the glycans aggregate only in the presence of Ca(2+). These results unify the generally accepted lectin hypothesis with the historically first-proposed "Ca(2+)-bridge" hypothesis. Additionally, a new role of cell flocculation is demonstrated; i.e., flocculation is linked to cell conjugation and mating, and survival chances consequently increase significantly by spore formation and by introduction of genetic variability. The role of Flo1p in mating was demonstrated by showing that mating efficiency is increased when cells flocculate and by differential transcriptome analysis of flocculating versus nonflocculating cells in a low-shear environment (microgravity). The results show that a multicellular clump (floc) provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation and mating.
Yeast cells can form multicellular clumps under adverse growth conditions that protect cells from harsh environmental stresses. The floc formation is based on the self-interaction of Flo proteins via an N-terminal PA14 lectin domain. We have focused on the flocculation mechanism and its role. We found that carbohydrate specificity and affinity are determined by the accessibility of the binding site of the Flo proteins where the external loops in the ligand-binding domains are involved in glycan recognition specificity. We demonstrated that, in addition to the Flo lectin-glycan interaction, glycan-glycan interactions also contribute significantly to cell-cell recognition and interaction. Additionally, we show that flocculation provides a uniquely organized multicellular ultrastructure that is suitable to induce and accomplish cell mating. Therefore, flocculation is an important mechanism to enhance long-term yeast survival.
Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing ϵ‐N‐carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been ...linked to potential treatment of several cancers but potent compounds with activity in cells have been lacking. Here we developed mechanism‐based inhibitors that incorporate isosteres of a carboxylic acid residue that is important for high‐affinity binding to the enzyme active site. By masking of the tetrazole moiety of the most potent candidate from our initial SAR study, we achieved potent and cytoselective growth inhibition for the treatment of SIRT5‐dependent leukemic cancer cell lines in culture. Thus, we provide an efficient, cellularly active small molecule that targets SIRT5, which can help elucidate its function and potential as a future drug target. This work shows that masked isosteres of carboxylic acids are viable chemical motifs for the development of inhibitors that target mitochondrial enzymes, which may have applications beyond the sirtuin field.
A SAR study of mechanism‐based inhibitors of the sirtuin 5 (SIRT5) hydrolase, containing isosteres of an essential carboxylic acid moiety, furnished heterocycles with excellent potency and slow, tight‐binding kinetics against the enzyme. Evaluation of selected compounds in cells revealed that transient masking of the heterocycle provided improved inhibitors with a high level of target engagement in cultured cells.
To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA1c after 26 weeks, and compare ...efficacy and safety between groups at W26 + W38.
A 38-week, randomised, open-label, treat-to-target (HbA1c < 7.0%) trial in adults with type 2 diabetes mellitus (on basal insulin ± oral antidiabetic drugs; HbA1c 7.0–10.0%). Randomisation (1:1): IDegAsp or IGlar U100 + IAsp. Intensification to IDegAsp twice daily (BID) was permitted at W26 + W32, or with additional IAsp injections at W26 (maximum IAsp BID) or W32 (maximum IAsp three-times daily).
For W0–W26, mean percentage-change (standard deviation) HbA1c was: IDegAsp, −1.1 (0.9); IGlar U100 + IAsp, −1.1 (0.8); estimated treatment difference: 0.07% (95% confidence interval CI: −0.06; 0.21) confirmed non-inferiority. At W26 and W38, target HbA1c achievement, and mean fasting and postprandial glucose were similar across groups. At W38, more subjects achieved target HbA1c without hypoglycaemia with IDegAsp (22.5%) than with IGlar U100 + IAsp (21.1%), with significantly fewer nocturnal episodes (W0–W38, estimated rate ratio: 0.61 95% CI: 0.40; 0.93). Safety profiles were similar across treatment groups throughout.
IDegAsp OD/BID are effective treatment intensification options versus multiple injection basal–bolus therapies, achieving similar glycaemic control, with significantly less nocturnal hypoglycaemia.
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