Evolutionary Dynamics of Co-Segregating Gene Clusters Associated with Complex Diseases

BACKGROUND: The distribution of human disease-associated mutations is not random across the human genome. Despite the fact that natural selection continually removes disease-associated mutations, an enrichment of these variants can be observed in regions of low recombination. There are a number of mechanisms by which such a clustering could occur, including genetic perturbations or demographic effects within different populations. Recent genome-wide association studies (GWAS) suggest that single nucleotide polymorphisms (SNPs) associated with complex disease traits are not randomly distributed throughout the genome, but tend to cluster in regions of low recombination. PRINCIPAL FINDINGS: Here we investigated whether deleterious mutations have accumulated in regions of low recombination due to the impact of recent positive selection and genetic hitchhiking. Using publicly available data on common complex diseases and population demography, we observed an enrichment of hitchhiked disease associations in conserved gene clusters subject to selection pressure. Evolutionary analysis revealed that these conserved gene clusters arose by multiple concerted rearrangements events across the vertebrate lineage. We observed distinct clustering of disease-associated SNPs in evolutionary rearranged regions of low recombination and high gene density, which harbor genes involved in immunity, that is, the interleukin cluster on 5q31 or RhoA on 3p21. CONCLUSIONS: Our results suggest that multiple lineage specific rearrangements led to a physical clustering of functionally related and linked genes exhibiting an enrichment of susceptibility loci for complex traits. This implies that besides recent evolutionary adaptations other evolutionary dynamics have played a role in the formation of linked gene clusters associated with complex disease traits

High Temperature Processing of Metallurgical Slags: A Method to Promote Recycling (Hoge temperatuursbewerkingen op metallurgische slakken: een methode om het hergebruik te bevorderen)

In een literatuurstudie wordt aangetoond dat een breed gamma aan slakbehandelingen in de warme fase technologisch uitgevoerd kunnen worden. Ook worden de mogelijke voordelen van een wel uitgedachte behandeling geïllustreerd aan de hand van gevalstudies over slakdesintegratie en chroomloging. Door de chemische samenstelling van de slak te wijzigene aan de hand van kleine toevoegingen op hoge temperatuur, kunnen slakdesintegratie en chroomloging grotendeels voorkomen worden. Ondanks de technologische haalbaarheid en het duidelijke potentieel, zijn gerichte slakbehandelingen in de warme fase zeldzaam. De literatuurstudie wijst erop dat dit wordt veroorzaakt door een beperkte kennis van de relaties tussen proces, microstructuur en eigenschappen.In een tweede deel van dit werk worden deze relaties voor enkele onderwerpen verder ontwikkeld. Eerst wordt de koeling van slakken aan de lucht geanalyseerd om het verband tussen de samenstelling op hoge temperatuur en de mineralogie op omgevingstemperatuur te begrijpen. Het wordt besloten dat de trage stolling van slakken best beschreven wordt als een Scheil stolling in een gesloten systeem. Voor de eerste keer wordt er aangetoond dat er zich metalen kunnen vormen tijdens het koelen van een volledig oxidische slak. Vervolgens worden de mechanismen van de boraatbehandeling van desintegrerende slakken uitgewerkt. Met behulp van EPMA-WDS wordt er aangetoond dat een kleine fractie van de boraten effectief een vaste oplossing vormen met dicalciumsilicaat, het mineraal dat de desintegratie veroorzaakt door een expansieve fasetransformatie. Tevens wordt de vereiste hoeveelheid boraten om stabilisatie te bereiken opgemeten in functie van de slaksamenstelling. Tenslotte worden de mogelijke bronnen van chroomloging uit roestvast staalslakken bepaald. Hoewel het overgrote deel van het chroom in spinelstructuren zit gebonden zoals algemeen aangenomen, blijkt een niet verwaarloosbare fractie gebonden te zijn in silicaatstructuren. Deze laatsten zijn mogelijk dé bron voor chroomloging.1. General introduction p.1 2. The slag recycling p.7 3. Hot stage slag processing p.21 4. Air-cooling of pO2 independent slags p.43 5. Air-cooling of pO2 dependent slags p.63 6. Predicting slag disintegration p.85 7. Borate distribution in stabilized slags p.93 8. Slag composition vs. borate treatment p.109 9. Chromium distribution in stainless steel slags p.117 10. Conclusions p.129status: publishe

Quantitative mineralogical analysis of hydraulic limes by X-ray diffraction

A combined selective dissolution/quantitative X-ray diffraction (QXRD) approach is proposed for the quantitative mineralogical phase analysis of hydraulic limes. The proposed methodology is validated by the analysis of two model mixtures. Afterwards two commercial hydraulic binders and one self-burned hydraulic quicklime were analysed. Chemical, thermal and microprobe analyses were performed to check the results. It is shown that the proposed selective dissolution/QXRD approach yields reliable quantitative mineralogical information for hydraulic limes in spite of their complex phase composition and the presence of amorphous material.status: publishe

Exergy based efficiency analysis of pyrometallurgical processes

Exergy based efficiency analysis provides a powerful tool for optimizing industrial processes. In this paper, the use of this technique for pyrometallurgical applications is explored in four steps. First, the exergy concept is introduced, the outline of exergy calculations is presented and the role of a reference state is discussed. Second, it is shown that an unambiguous exergy calculation for pyrometallurgical streams with a complex, unknown phase composition is not straightforward. Hence, a practical methodology is proposed in which a suitable phase-based stream description is estimated prior to the actual exergy calculation. For this, the equilibrium phase composition is calculated while all known stream properties are incorporated as boundary conditions. Thirdly, the proposed methodology is validated by recalculating literature results. This reveals significant deviations for exergy values of the same pyrometallurgical streams. Our results are probably more accurate due to the incorporation of additional phase related information. And fourthly, a full analysis of a zinc recycling process is presented. In a base case scenario, the total exergetic efficiency turns out to be only 1.2%. Based on this result, different process modifications are suggested and quantitatively evaluated. We find that significant efficiency gains are possible.status: publishe

Quantitative mineralogical analysis of hydraulic limes by X-ray diffraction

A combined selective dissolution/quantitative X-ray diffraction (QXRD) approach is proposed for the quantitative mineralogical phase analysis of hydraulic limes. The proposed methodology is validated by the analysis of two model mixtures. Afterwards two commercial hydraulic binders and one self-burned hydraulic quicklime were analysed. Chemical, thermal and microprobe analyses were performed to check the results. It is shown that the proposed selective dissolution/QXRD approach yields reliable quantitative mineralogical information for hydraulic limes in spite of their complex phase composition and the presence of amorphous material. © 2007 Elsevier Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Exergetic efficiency analysis of a pyrometallurgical zinc recycling process

The exergy content of a process stream is a thermodynamic quantity, indicating the maximum amount of work the stream can perform in a reference environment. It can be calculated for energy streams as well as for mass streams, allowing an unambiguous comparison between the two. Starting from an exergy balance the global efficiency of any thermodynamic process can be quantified by comparing the exergy in the useful output streams to the exergy provided by the input streams. This is an advantage over traditional process analyses based on separate mass and energy balances. From an ecological and economical point of view, exergy analysis thus provides a powerful tool for the evaluation and optimization of industrial processes. In this article the thermodynamic principles behind an exergy analysis are first elaborated. Next, it is illustrated that the outcome of an exergy calculation can be substantially influenced by the choice of a reference state, a thermodynamic database and a description method for the stream. The latter is of particular importance for pyrometallurgical process streams with complex compositions and phase structures. Due to these effects, comparisons between different exergy analyses should be ap-proached with care. However, when the analyses are performed systematically and consistently, they can be very useful for the optimization of process efficiencies. This is shown in the last part of this article, in which a case study on a recently developed zinc recycling process is discussed. For the first time, well adapted solution models are used for an accurate and consistent description of the involved pyrometallurgical process streams. An analysis of a base case scenario shows that the process efficiency is limited by the production of low exergetic zinc oxide and high exergetic waste streams. Based on this outcome, appropriate modifications are suggested to improve the overall process efficiency.status: publishe

Phase relations, solidification and stabilisation studies for reuse of stainless steel slags

Stainless steel slags are more and more being reused in construction applications, where they can be an economically and ecologically viable alternative to natural minerals. To compete with those natural materials, slags need to comply with standards imposed by slag consumers and ever stricter regulations. Certain mechanical properties, particle sizes and environmentally suitable properties are required. In this work, we investigate several thermodynamic aspects having an effect on the eventual slag properties. First, the phase relations at high temperature were studied by equilibration in controlled reducing atmospheres, followed by quenching and EPMA-WDS analysis. The results were compared with commercially available thermodynamic databases. This lead to the detection of discrepancies at lower basicities, which could be tracked down to missing ternary interactions in the system MgO-CrOx-SiO2. A new thermodynamic description of the MgO-CrOx-SiO2 system is pro-posed. Second, the solidification of CrOx containing slags was studied using thermodynamic Scheil modelling. This proved to be a predictive tool for the low temperature mineralogy even after slow air cooling, correctly calculating the presence of Cr metal or 2CaO.SiO2 (C2S). Third, the modification of slag chemistry during cooling to prevent the destructive C2S transformation was studied by experiments and modelling. It was found that 0.3 wt% B2O3 is capable of stabilizing all slags with basicities lower than 2. The amount needed is, however, strongly dependent on the C2S fraction and hence the C/S ratio. To understand the mechanisms behind this, the distribution of boron in the phases present during and after solidification was studied by modelling and EPMA-WDS. The majority of the boron was present in the liquid or CaBxSiyOz phases, which explains the need for a higher boron content than needed for pure C2S.status: accepte

Borate distribution in stabilized stainless-steel slag

Disintegration of stainless-steel slag during cooling is caused by the beta ->gamma transformation of dicalcium silicate (2CaO center dot SiO2 or C2S). It is well established that disintegration can be avoided by borate additions, which are commonly believed to stabilize the high-temperature polymorphs by forming a solid solution with C2S. In this study, the borate distributions in slowly cooled synthetic and industrial slag samples are determined. The slag microstructures are characterized using electron probe microanalysis (EPMA), quantitative X-ray diffraction (QXRD), and wavelength dispersive spectroscopy (WDS). The results show that only a limited fraction of the added borates forms a solid solution with the C2S phase, while the main fraction is found in a calcium borosilicate phase. In combination with literature data, this suggests that slag stabilization involves more than the chemical stabilization of the high-temperature C2S polymorphs.status: publishe

Hot stage processing of metallurgical slags

Slags are an indispensable tool for the pyrometallurgical industry to extract and purify metals at competitive prices. Large volumes are produced annually, leading to important economical and ecological issues regarding their afterlife. To maximise the recycling potential, slag processing has become an integral part of the valorisation chain. However, processing is often directed solely towards the cooled slag. In this article, the authors present an overview of the scientific studies dedicated to the hot stage of slag processing, i.e. from the moment of slag/metal separation to complete cooling at the slag yard. Using in-depth case studies on C2S driven slag disintegration and chromium leaching, it is shown that the functional properties of the cooled slag can be significantly enhanced by small or large scale additions to the high temperature slag and/or variations in the cooling path, even without interfering with the metallurgical process. The technology to implement such hot stage processing steps in an industrial environment is currently available. No innovative technological solutions are required. Rather, advances in hot stage slag processing seem to rely primarily on further unravelling the relationships between process, structure and properties. This knowledge is required to identify the critical process parameters for quality control. Moreover. it could even allow to consciously alter slag compositions and cooling paths to tailor the slag to a certain application.status: publishe

Degradation mechanisms of magnesia-carbon refractories by high-alumina stainless steel slags under vacuum

The corrosion behaviour of a pitch-bonded magnesia-carbon refractory by an Al2O3 rich (similar to 15 wt.%) stainless steelmaking slag was investigated by rotating finger tests in a vacuum induction furnace at high temperature (> 1650 degrees C and low oxygen partial pressure (1.5-4.3 x 10(-10) atm). This study confirms the poor slagline behaviour of MgO-C bricks industrially observed in VOD ladies. Higher temperatures and longer exposure times lead to more severe slag infiltration and direct MgO dissolution. The intrinsic MgO-C reaction is the major decarburisation mechanism, while extrinsic decarburisation by oxygen from the atmosphere and/or reducible slag components (CrOx, FeOx) was limited. Three kinds of metallic particles with different size, shape, location, composition and origin were observed in the refractory specimens. Concurrently, the thermodynamic conditions for the formation of a protective Mg(Al,Cr)(2)O-4 spinel layer at the slag/refractory interface are investigated. The industrial relevance of this spinel layer formation is discussed with respect to the chosen Al2O3 level. Guidelines are proposed to minimise MgO refractory dissolution in VOD slaglines.status: publishe