Influence of activator type on reaction kinetics, setting time, and compressive strength of alkali-activated mineral wools

Alkali activation is a promising utilisation route for mineral wool wastes, due to suitable chemical composition, high reactivity, and surface area. One key factor in the development of alkali-activated binders is the selection of the suitable alkali activator. Here, the effect of sodium hydroxide, sodium silicate, sodium aluminate, and sodium carbonate solution on the alkali-activation kinetics of two main types of mineral wools, stone wool and glass wool, is investigated. Setting time and compressive strength development results are presented, which are explained and discussed in the context of isothermal calorimeter data obtained at temperature of 40 °C. Sodium hydroxide and sodium silicate solutions provided fast reaction with both mineral wools, evidenced by high heat release, high early strength, and fast setting. The reaction with sodium aluminate solution took several days to initiate, but it produced high compressive strength after 28 days of curing with both mineral wools. Glass wool reacted and hardened rapidly with sodium carbonate solution, but stone wool reacted slowly with sodium carbonate and exhibited a low extent of reaction, likely due to lower extent of reaction of stone wool under less alkaline conditions. These results show that mineral wool alkali activation kinetics and binder gel formation are controlled by the activator type and highlight the importance of choosing the most appropriate activator for each desired application

Nanostructural evolution of alkali-activated mineral wools

Mineral wools are the most widely used building insulation material worldwide. Annually, 2.5 million tonnes of mineral wool waste are generated in the EU alone, and this is a largely unutilised material that is landfilled or incinerated. However, mineral wool wastes are promising precursors for production of alkali-activated cementitious binders due to their favourable chemical and mineralogical composition and high surface area. Alkali-activation is therefore a valuable route for valorisation of large quantities of mineral wool waste. This study resolves the phase assemblage and nanostructure of reaction products formed upon alkali activation of stone wool and glass wool by sodium hydroxide and sodium silicate solutions with X-ray diffraction, electron microscopy and solid state nuclear magnetic resonance spectroscopy experiments probing ^27Al and ^29Si. The stone wool-based alkali-activated binder comprises an amorphous sodium- and aluminium-substituted calcium silicate hydrate (C-(N-)A-S-H) gel, an amorphous sodium aluminosilicate hydrate (N-A-S-H) gel and small amounts of the layered double hydroxide phase quintinite and zeolite F. The glass wool-based alkali-activated binder comprises an amorphous Ca- and Al-substituted sodium silicate (N-(C-)(A-)S–H) gel. Gel chemical composition and reaction kinetics of alkali-activated mineral wools are shown to be dependent on the activating solution chemistry, with reaction rate and extent promoted by inclusion of a source of soluble Si in the reaction mixture. This work provides the most advanced description of the chemistry and structure of alkali-activated mineral wools to date, yielding new insight that is essential in developing valorisation pathways for mineral wools by alkali activation and providing significant impetus for development of sustainable construction materials

Finite element simulation of three-dimensional free-surface flow problems

An adaptive finite element algorithm is described for the stable solution of three-dimensional free-surface-flow problems based primarily on the use of node movement. The algorithm also includes a discrete remeshing procedure which enhances its accuracy and robustness. The spatial discretisation allows an isoparametric piecewise-quadratic approximation of the domain geometry for accurate resolution of the curved free surface. The technique is illustrated through an implementation for surface-tension-dominated viscous flows modelled in terms of the Stokes equations with suitable boundary conditions on the deforming free surface. Two three-dimensional test problems are used to demonstrate the performance of the method: a liquid bridge problem and the formation of a fluid droplet

Atypical multisensory integration in Niemann-Pick type C disease – towards potential biomarkers

Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the respective sensory cortices (e.g. the auditory and visual systems). Methods: A simple way to test integrity of the multisensory system is to ask whether individuals respond faster to the occurrence of a bisensory event than they do to the occurrence of either of the unisensory constituents alone. Here, we presented simple auditory, visual, and audio-visual stimuli in random sequence. Participants responded as fast as possible with a button push. One 11-year-old and two 14-year-old boys with NPC participated in the experiment and their results were compared to those of 35 age-matched neurotypical boys. Results: Reaction times (RTs) to the stimuli when presented simultaneously were significantly faster than when they were presented alone in the neurotypical children, a facilitation that could not be accounted for by probability summation, as evidenced by violation of the so-called ‘race’ model. In stark contrast, the NPC boys showed no such speeding, despite the fact that their unisensory RTs fell within the distribution of RTs observed in the neurotypicals. Conclusions: These results uncover a previously undescribed deficit in multisensory integrative abilities in NPC, with implications for ongoing treatment of the clinical symptoms of these children. They also suggest that multisensory processes may represent a good candidate biomarker against which to test the efficacy of therapeutic interventions

Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation

Current strategies to target RNA splicing mutant myeloid cancers proposes targeting the remaining splicing apparatus. This approach has only been modestly sensitizing and is also toxic to non-mutant-bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of missplicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (acute myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia) was performed to identify conserved missplicing events. From this analysis, we identified that the cell-cycle and DNA repair pathways were overrepresented within the conserved misspliced transcript sets. In parallel, to functionally define pathways essential for survival and proliferation of Srsf2P95H/+ cells, we performed a genome-wide Clustered regularly interspaced short palindromic repeat loss-of-function screen using Hoxb8 immortalized R26-CreERki/+Srsf2P95H/+ and R26-CreERki/+Srsf2+/+ cell lines. We assessed loss of single guide RNA representation at 3 timepoints: immediately after Srsf2P95H/+ activation, and at 1 week and 2 weeks after Srsf2P95H/+ mutation. Pathway analysis demonstrated that the cell-cycle and DNA damage response pathways were among the top synthetic lethal pathways with Srsf2P95H/+ mutation. Based on the loss of guide RNAs targeting Cdk6, we identified that palbociclib, a CDK6 inhibitor, showed preferential sensitivity in Srsf2P95H/+ cell lines and in primary nonimmortalized lin−cKIT+Sca-1+ cells compared with wild-type controls. Our data strongly suggest that the cell-cycle and DNA damage response pathways are required for Srsf2P95H/+ cell survival, and that palbociclib could be an alternative therapeutic option for targeting SRSF2 mutant cancers

RARγ is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation

Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when activated, promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)γ is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RARγ knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RARα is widely expressed in hematopoietic cells, but RARα knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RARα differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RARγ exhibit a much more undifferentiated phenotype. Furthermore, loss of RARγ abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RARγ ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RARγ is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation

HIF-1α is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1α

Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile transcription factor HIF-1α is essential for HSC mobilization in response to G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1α with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G-CSF plus Plerixafor, currently the most potent mobilizing combination used in the clinic

A Study of Preconditioned Jacobian-Free Newton-Krylov Discontinuous Galerkin Method for Compressible Flows on 3D Hexahedral Grids

Storage requirement and computational efficiency have always been challenges for the efficient implementation of discontinuous Galerkin (DG)methods for real life applications. In this paper, a fully implicit Jacobian-Free Newton-Krylov (JFNK) method is developed in the context of DG discretizations for the three-dimensional compressible Euler and Navier-Stokes equations. Compared with the Jacobian-based methods, the Jacobian-Free approach saves the storage for the Jacobian matrix which can be of great importance for DG methods. Three types of preconditioners are investigated in which the block diagonal preconditioner requires the least storage, while the block LU-SGS and ILU0 preconditioners require more storage but are more computationally efficient. An implicit time-stepping strategy is adopted for the stability of the current solver,which is based upon a hexahedral spatialmesh and the nonlinear solver package Kinsol is used to improve the computational efficiency and robustness. Numerical results demonstrate that the preconditioned JFNK-DG solver can substantially reduce the storage requirement compared with the Jacobian based method without significantly compromising accuracy or efficiency. Furthermore, as a good compromise between efficiency and storage requirement, the ILU0 preconditioner shows the best choice of the preconditioners presented

New Structural Model of Hydrous Sodium Aluminosilicate Gels and the Role of Charge-Balancing Extra-Framework Al

A new structural model of hydrous alkali aluminosilicate gel (N-A-S-H) frameworks is proposed, in which charge-balancing extra-framework Al species are observed in N-A-S-H gels for the first time. This model describes the key nanostructural features of these gels, which are identified through the application of 17O, 23Na, and 27Al triple quantum magic angle spinning solid-state nuclear magnetic resonance spectroscopy to synthetic 17O-enriched gels of differing Si/Al ratios. The alkali aluminosilicate gel predominantly comprises Q4(4Al), Q4(3Al), Q4(2Al), and Q4(1Al) Si units charge-balanced by Na+ ions that are coordinated by either 3 or 4 framework oxygen atoms. A significant proportion of Al3+ in tetrahedral coordination exist in sites of lower symmetry, where some of the charge-balancing capacity is provided by extra-framework Al species which have not previously been observed in these materials. The mean SiIV–O–AlIV bond angles for each type of AlIV environments are highly consistent, with compositional changes dictating the relative proportions of individual AlIV species but not altering the local structure of each individual AlIV site. This model provides a more advanced description of the chemistry and structure of alkali aluminosilicate gels and is crucial in understanding and controlling the molecular interactions governing gel formation, mechanical properties, and durability