Machine Learning Enabled Models to Predict Sulfur Solubility in Nuclear Waste Glasses.

The U.S. Department of Energy is considering implementing the direct feed approach for the vitrification of low-activity waste (LAW) and high-level waste (HLW) at the Hanford site in Washington state. If implemented, the nuclear waste with a higher concentration of alkali/alkaline-earth sulfates (than expected under the previously proposed vitrification scheme) will be sent to the vitrification facility. It will be difficult for the existing empirical models to predict sulfate solubility in these glasses or design glass formulations with enhanced sulfate loadings in such a scenario. Further, the existing models are unable to produce reliable predictions when applied to HLW glasses whose composition falls outside of the range encompassed by the database used to develop/calibrate the models. Accordingly, this study harnesses the power of artificial intelligence (machine learning, ML) with a goal to address the limitations of the existing models. Toward this, three ML models have been trained using a large database; comprising >1000 LAW and HLW glasses and encompassing a wide range of glass compositions and processing variables. Next, the ML model with the best prediction performance has been used to quantitatively assess and rank the influence (i.e., importance) of glasses' compositional/processing variables on the SO3 solubility in the glasses. Finally, on the premise of such understanding of influential and inconsequential variables, two closed-form analytical models─with disparate degrees of complexity (one highly parametrized and one with fewer input variables)─have been developed. Results show that both analytical models produce predictions of SO3 solubility in LAW and HLW glasses with an accuracy analogous to ML models and substantially higher than the analytical models that represent the current state-of-the-art. Overall, this study's outcomes present a roadmap─informed by data and channeled by artificial intelligence─that can be leveraged in the future to design nuclear waste glasses with unprecedented sulfur loadings.

Composition-Structure-Solubility Relationships in Borosilicate Glasses: Toward a Rational Design of Bioactive Glasses with Controlled Dissolution Behavior.

Owing to their fast but tunable degradation kinetics (in comparison to silicates) and excellent bioactivity, the past decade has witnessed an upsurge in the research interest of borate/borosilicate-based bioactive glasses for their potential use in a wide range of soft tissue regeneration applications. Nevertheless, most of these glasses have been developed using trial-and-error approaches wherein SiO2 has been gradually replaced by B2O3. One major reason for using this empirical approach is the complexity of short-to-intermediate range structures of these glasses which greatly complicate the development of a thorough understanding of composition-structure-solubility relationships in these systems. Transitioning beyond the current style of composition design to a style that facilitates the development of bioactive glasses with controlled ion release tailored for specific patients/diseases requires a deeper understanding of the compositional/structural dependence of glass degradation behavior in vitro and in vivo. Accordingly, the present study aims to decipher the structural drivers controlling the dissolution kinetics and ion-release behavior of potentially bioactive glasses designed in the Na2O-B2O3-P2O5-SiO2 system across a broad compositional space in simulated body environments (pH = 7.4). By employing state-of-the-art spectroscopy-based characterization techniques, it has been shown that the degradation kinetics of borosilicate glasses depend on their R (Na2O/B2O3) and K (SiO2/B2O3) ratios, while the release of particular network-forming moieties from the glass into solution is strongly influenced by their role in-and effect on-the short-to-intermediate-range molecular structure. The current study aims to promote a rational design of borosilicate-based bioactive glasses, where a delicate balance between maximizing soft tissue regeneration and minimizing calcification and cytotoxicity can be achieved by tuning the release of ionic dissolution products (of controlled identity and abundance) from bioactive glasses into physiological media.

Dissolution kinetics of a sodium borosilicate glass in Tris buffer solutions: impact of Tris concentration and acid (HCl/HNO3) identity.

Understanding the corrosion behavior of glasses in near-neutral environments is crucial for many technologies including glasses for regenerative medicine and nuclear waste immobilization. To maintain consistent pH values throughout experiments in the pH = 7 to 9 regime, buffer solutions containing tris(hydroxymethyl)aminomethane ("Tris", or sometimes called THAM) are recommended in ISO standards 10993-14 and 23317 for evaluating biomaterial degradation and utilized throughout glass dissolution behavior literature-a key advantage being the absence of dissolved alkali/alkaline earth cations (i.e. Na+ or Ca2+) that can convolute experimental results due to solution feedback effects. Although Tris is effective at maintaining the solution pH, it has presented concerns due to the adverse artificial effects it produces while studying glass corrosion, especially in borosilicate glasses. Therefore, many open questions still remain on the topic of borosilicate glass interaction with Tris-based solutions. We have approached this topic by studying the dissolution behavior of a sodium borosilicate glass in a wide range of Tris-based solutions at 65 °C with varied acid identity (Tris-HCl vs. Tris-HNO3), buffer concentration (0.01 M to 0.5 M), and pH (7-9). The results have been discussed in reference to previous studies on this topic and the following conclusions have been made: (i) acid identity in Tris-based solutions does not exhibit a significant impact on the dissolution behavior of borosilicate glasses, (ii) ∼0.1 M Tris-based solutions are ideal for maintaining solution pH in the absence of obvious undesirable solution chemistry effects, and (iii) Tris-boron complexes can form in solution as a result of glass dissolution processes. The complex formation, however, exhibits a distinct temperature-dependence, and requires further study to uncover the precise mechanisms by which Tris-based solutions impact borosilicate glass dissolution behavior.

Why does B2O3 suppress nepheline (NaAlSiO4) crystallization in sodium aluminosilicate glasses?

The uncontrolled growth of nepheline (NaAlSiO4) crystals during the manufacturing of sodium aluminosilicate glasses via the fusion draw or float techniques and during the vitrification of some of the sodium- and alumina-rich nuclear waste glasses is a well-known problem. The addition of B2O3 to suppress the crystallization in these glasses is well documented in the literature. Another advantage of B2O3 is that it lowers the viscosity of the glass melt and, if incorporated in its trigonal coordination state, will improve the intrinsic damage resistance of the final glass product. Hence, B2O3 has been an integral component of glass compositions for advanced industrial applications and for nuclear waste vitrification. However, one major disadvantage of adding B2O3 to alkali aluminosilicate based glasses is its adverse impact on their chemical durability due to the rapid hydrolysis of B[3,4]-O-B[3,4] bonds in comparison to (Si, Al)-O-(Si, Al) bonds. Therefore, designing a boron-containing alkali aluminosilicate based functional glass with minimal tendency towards crystallization and high chemical durability requires an in-depth fundamental understanding of the mechanism through which B2O3 tends to suppress crystallization in these glasses. There is no current consensus on the fundamental mechanism through which B2O3 tends to suppress nepheline crystallization in these glasses. Based on the mechanisms described and the questions raised in the preceding literature, the present study focuses on addressing the ongoing debate through a detailed structural and thermo-kinetic investigation of glasses designed in the Na2O-Al2O3-B2O3-SiO2 based quaternary system over a broad composition space. Using a combination of Raman and (1D and 2D) nuclear magnetic resonance spectroscopies along with equilibrium and non-equilibrium viscosity, and liquidus temperature measurements, it has been shown that the substitution of Si-O-Al by Si-O-B linkages in the glass structure results in a significant increase in the glass forming ability as well as an increase in the liquidus viscosity (slower diffusivity), thereby suppressing the nepheline crystallization.

Machine learning as a tool to design glasses with controlled dissolution for healthcare applications.

The advancement of glass science has played a pivotal role in enhancing the quality and length of human life. However, with an ever-increasing demand for glasses in a variety of healthcare applications - especially with controlled degradation rates - it is becoming difficult to design new glass compositions using conventional approaches. For example, it is difficult, if not impossible, to design new gene-activation bioactive glasses, with controlled release of functional ions tailored for specific patient states, using trial-and-error based approaches. Notwithstanding, it is possible to design new glasses with controlled release of functional ions by using artificial intelligence-based methods, for example, supervised machine learning (ML). In this paper, we present an ensemble ML model for reliable prediction of time- and composition-dependent dissolution behavior of a wide variety of oxide glasses relevant for various biomedical applications. A comprehensive database, comprising of over 1300 data-records consolidated from original glass dissolution experiments, has been used for training and subsequent testing of prediction performance of the ML model. Results demonstrate that the ensemble ML model can predict chemical degradation behavior of glasses in aqueous solutions over a wide range of pH relevant for their usage in a human body where the environment can be highly acidic (for example, pH = 3), for example, due to secretion of citric acid by osteoclasts, or highly alkaline (pH ≈10) due to the release of alkali cations from bioactive glasses. Outcomes of this study can be leveraged to design glasses with controlled dissolution behavior in various biological environments. STATEMENT OF SIGNIFICANCE: In this paper, we present an ensemble machine learning (ML) model for prediction of dissolution behavior of a wide variety of oxide glasses relevant for various biomedical applications. The results demonstrate that the ML model can predict the chemical degradation behavior of glasses in aqueous solutions over a wide range of pH relevant for their usage in a human body where the environment can be highly acidic (for example, pH = 3), for example, due to secretion of citric acid by osteoclasts, or highly alkaline (pH ≈10) due to the release of alkali cations from bioactive glasses. Outcomes of this study can be leveraged to design new biomedical glasses with controlled (desired) dissolution behavior in various biological environments.

An insight into the corrosion of alkali aluminoborosilicate glasses in acidic environments.

The majority of the literature on glass corrosion focuses on understanding the dissolution kinetics and mechanisms of silicate glass chemistries in the neutral-to-alkaline aqueous regime owing to its relevance in the fields of nuclear waste immobilization and biomaterials. However, understanding the corrosion of silicate-based glass chemistries over a broad composition space in the acidic pH regime is essential for glass packaging and touch screen electronic display industries. A thorough literature review on this topic reveals only a handful of studies that discuss acid corrosion of silicate glasses and their derivatives-these include only a narrow set of silicate-based glass chemistries. Although the current literature successfully explains the dissolution kinetics of glasses based upon classically understood aqueous corrosion mechanisms, more recent advancements in atomic-scale characterization techniques, have enabled a better understanding of reactions taking place directly at the pristine glass-fluid interface which has facilitated the development of a unifying model describing corrosion behavior of silicate glasses. Based on the corrosion mechanisms described and the questions raised in preceding literature, the present study focuses on understanding the corrosion mechanisms governing metaluminous (Na/Al = 1) sodium aluminoborosilicate glasses in acidic environments across a wide composition-space (ranging from SiO2-rich to B2O3-rich compositions), with particular emphasis on understanding the reactions taking place near the glass-fluid interface. Using state-of-the-art characterization techniques including nuclear magnetic resonance (NMR) spectroscopy, Rutherford backscattering, X-ray photoelectron spectroscopy (XPS) and elastic recoil detection analysis (ERDA), it has been shown that stepwise B2O3 substitutions into nepheline (NaAlSiO4) glass, although causing non-linear changes in glass structure network structural features, leads to strikingly linear increases in the forward dissolution rate at pH = 2. While the glasses undergo congruent dissolution in the forward rate regime, the residual rate regime displays evidence of preferential extraction near the glass surface (i.e., enrichment in aluminum content upon corrosion through AlO4→ Al(OH)3 evolution) implying that dissolution-re-precipitation processes may occur at the glass-fluid interface in both B2O3-rich and SiO2-rich glass compositions-albeit with vastly dissimilar reaction kinetics.

Structural and Chemical Approach toward Understanding the Aqueous Corrosion of Sodium Aluminoborate Glasses.

Despite an ongoing strenuous effort to understand the compositional and structural drivers controlling the chemical durability of oxide glasses, there is still no complete consensus on the basic mechanism of glass dissolution that applies to a wide composition space. One major reason for this problem is the structural complexity contained within the multicomponent silicate glasses chosen for glass corrosion studies. The nonsilicate network polyhedra present in these glasses interact with one another, often in unpredictable ways, by forming a variety of structural associations, for example, Al[IV]-B[III] and B[III]-B[IV], resulting in significant influence on both the structure of the glass network and related macroscopic properties. Likewise, the formation of a variety of next-neighbor linkages, as well as increasingly complex interactions involving Si and differently coordinated next-nearest neighbor cations, is very difficult to decipher experimentally. Consideration of these factors motivates instead a different strategy: that is, the study of a sequence of SiO2-free ternary or quaternary glass compositions, whose structures can be unambiguously determined and robustly linked to their corrosion properties. With this aim, the present study is focused on understanding the structural drivers governing the kinetics and mechanism of corrosion of ternary Na2O-Al2O3-B2O3 glasses (in water) over a broad composition space comprising compositions with distinct structural features. It has been shown that the addition of Al2O3 to binary sodium borate glasses decreases their corrosion rate in water and converts their dissolution behavior from congruent to incongruent leading to the formation of six-coordinated alumina, and higher concentration of four-coordinated boron (in comparison to pre-dissolution glasses) in post-dissolution glass samples. The drivers controlling the corrosion kinetics and mechanism in these glasses based on their underlying structure have been elucidated. Some open questions have been proposed which require an extensive analysis of surface chemistry of pre- and post-dissolution samples and will be investigated in our future work.

Adherence to recommended electronic health record safety practices across eight health care organizations.

Objective: The Safety Assurance Factors for EHR Resilience (SAFER) guides were released in 2014 to help health systems conduct proactive risk assessment of electronic health record (EHR)- safety related policies, processes, procedures, and configurations. The extent to which SAFER recommendations are followed is unknown. Methods: We conducted risk assessments of 8 organizations of varying size, complexity, EHR, and EHR adoption maturity. Each organization self-assessed adherence to all 140 unique SAFER recommendations contained within 9 guides (range 10-29 recommendations per guide). In each guide, recommendations were organized into 3 broad domains: "safe health IT" (total 45 recommendations); "using health IT safely" (total 80 recommendations); and "monitoring health IT" (total 15 recommendations). Results: The 8 sites fully implemented 25 of 140 (18%) SAFER recommendations. Mean number of "fully implemented" recommendations per guide ranged from 94% (System Interfaces-18 recommendations) to 63% (Clinical Communication-12 recommendations). Adherence was higher for "safe health IT" domain (82.1%) vs "using health IT safely" (72.5%) and "monitoring health IT" (67.3%). Conclusions: Despite availability of recommendations on how to improve use of EHRs, most recommendations were not fully implemented. New national policy initiatives are needed to stimulate implementation of these best practices.

Compositional Dependence of Solubility/Retention of Molybdenum Oxides in Aluminoborosilicate-Based Model Nuclear Waste Glasses.

Molybdenum oxides are an integral component of the high-level waste streams being generated from the nuclear reactors in several countries. Although borosilicate glass has been chosen as the baseline waste form by most of the countries to immobilize these waste streams, molybdate oxyanions (MoO42-) exhibit very low solubility (∼1 mol %) in these glass matrices. In the past three to four decades, several studies describing the compositional and structural dependence of molybdate anions in borosilicate and aluminoborosilicate glasses have been reported in the literature, providing a basis for our understanding of fundamental science that governs the solubility and retention of these species in the nuclear waste glasses. However, there are still several open questions that need to be answered to gain an in-depth understanding of the mechanisms that control the solubility and retention of these oxyanions in glassy waste forms. This article is focused on finding answers to two such questions: (1) What are the solubility and retention limits of MoO3 in aluminoborosilicate glasses as a function of chemical composition? (2) Why is there a considerable increase in the solubility of MoO3 with incorporation of rare-earth oxides (for example, Nd2O3) in aluminoborosilicate glasses? Accordingly, three different series of aluminoborosilicate glasses (compositional complexity being added in a tiered approach) with varying MoO3 concentrations have been synthesized and characterized for their ability to accommodate molybdate ions in their structure (solubility) and as a glass-ceramic (retention). The contradictory viewpoints (between different research groups) pertaining to the impact of rare-earth cations on the structure of aluminoborosilicate glasses are discussed, and their implications on the solubility of MoO3 in these glasses are evaluated. A novel hypothesis explaining the mechanism governing the solubility of MoO3 in rare-earth containing aluminoborosilicate glasses has been proposed.

Understanding the structural drivers governing glass-water interactions in borosilicate based model bioactive glasses.

The past decade has witnessed a significant upsurge in the development of borate and borosilicate based resorbable bioactive glasses owing to their faster degradation rate in comparison to their silicate counterparts. However, due to our lack of understanding about the fundamental science governing the aqueous corrosion of these glasses, most of the borate/borosilicate based bioactive glasses reported in the literature have been designed by "trial-and-error" approach. With an ever-increasing demand for their application in treating a broad spectrum of non-skeletal health problems, it is becoming increasingly difficult to design advanced glass formulations using the same conventional approach. Therefore, a paradigm shift from the "trial-and-error" approach to "materials-by-design" approach is required to develop new-generations of bioactive glasses with controlled release of functional ions tailored for specific patients and disease states, whereby material functions and properties can be predicted from first principles. Realizing this goal, however, requires a thorough understanding of the complex sequence of reactions that control the dissolution kinetics of bioactive glasses and the structural drivers that govern them. While there is a considerable amount of literature published on chemical dissolution behavior and apatite-forming ability of potentially bioactive glasses, the majority of this literature has been produced on silicate glass chemistries using different experimental and measurement protocols. It follows that inter-comparison of different datasets reveals inconsistencies between experimental groups. There are also some major experimental challenges or choices that need to be carefully navigated to unearth the mechanisms governing the chemical degradation behavior and kinetics of boron-containing bioactive glasses, and to accurately determine the composition-structure-property relationships. In order to address these challenges, a simplified borosilicate based model melt-quenched bioactive glass system has been studied to depict the impact of thermal history on its molecular structure and dissolution behavior in water. It has been shown that the methodology of quenching of the glass melt impacts the dissolution rate of the studied glasses by 1.5×-3× depending on the changes induced in their molecular structure due to variation in thermal history. Further, a recommendation has been made to study dissolution behavior of bioactive glasses using surface area of the sample - to - volume of solution (SA/V) approach instead of the currently followed mass of sample - to - volume of solution approach. The structural and chemical dissolution data obtained from bioactive glasses following the approach presented in this paper can be used to develop the structural descriptors and potential energy functions over a broad range of bioactive glass compositions. STATEMENT OF SIGNIFICANCE: Realizing the goal of designing third generation bioactive glasses requires a thorough understanding of the complex sequence of reactions that control their rate of degradation (in physiological fluids) and the structural drivers that control them. In this article, we have highlighted some major experimental challenges and choices that need to be carefully navigated in order to unearth the mechanisms governing the chemical dissolution behavior of borosilicate based bioactive glasses. The proposed experimental approach allows us to gain a new level of conceptual understanding about the composition-structure-property relationships in these glass systems, which can be applied to attain a significant leap in designing borosilicate based bioactive glasses with controlled dissolution rates tailored for specific patient and disease states.

The in vivo performance of an alkali-free bioactive glass for bone grafting, FastOs® BG, assessed with an ovine model.

Although bioactive glasses are successfully used as bone substitutes, recent studies have revealed that the high alkali content in these glasses leads to fast in vivo degradation rates that may not match the rate of new bone ingrowth. This prompted us to design and develop novel bioactive glasses that are devoid of alkali but still demonstrate high bioactivity in vitro. This article describes the in vivo performance of an alkali-free bioactive glass with the following composition (Wt %): 13.03 MgO-33.98 CaO-13.37 P2 O5 -38.84 SiO2 -0.77 CaF2 (labelled as FastOs® BG). An animal model was used to assess the in vivo performance of FastOs® BG, using 45S5 Bioglass® as control. The evaluation was performed through implantation of FastOs® BG and 45S5 Bioglass® , during one month, in femoral bone defects in sheep. Subcutaneous implantation of both glasses was also performed in order to assess tissue response through a standardized method. Histological and scanning electron microscopy assessment of retrieved subcutaneous and bone samples demonstrated that FastOs® BG is biocompatible, osteoconductive, that it can be osteointegrated, and that it is more slowly resorbed than 45S5 Bioglass® . These features suggest that FastOs® BG is a potential candidate for bone grafting. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 30-38, 2017.

Influence of ZnO/MgO substitution on sintering, crystallisation, and bio-activity of alkali-free glass-ceramics.

The present study reports on the influence of partial replacement of MgO by ZnO on the structure, crystallisation behaviour and bioactivity of alkali-free bioactive glass-ceramics (GCs). A series of glass compositions (mol%): 36.07 CaO-(19.24-x) MgO-x ZnO-5.61 P2O5-38.49 SiO2-0.59 CaF2 (x=2-10) have been synthesised by melt-quench technique. The structural changes were investigated by solid-state magic angle spinning nuclear magnetic resonance (MAS-NMR), X-ray diffraction and differential thermal analysis. The sintering and crystallisation behaviours of glass powders were studied by hot-stage microscopy and differential thermal analysis, respectively. All the glass compositions exhibited good densification ability resulting in well sintered and mechanically strong GCs. The crystallisation and mechanical behaviour were studied under non-isothermal heating conditions at 850 °C for 1h. Diopside was the primary crystalline phase in all the GCs followed by fluorapatite and rankinite as secondary phases. Another phase named petedunnite was identified in GCs with ZnO content >4 mol. The proliferation of mesenchymal stem cells (MSCs) and their alkaline phosphatase activity (ALP) on GCs was revealed to be Zn-dose dependent with the highest performance being observed for 4 mol% ZnO.

Understanding the composition-structure-bioactivity relationships in diopside (CaO·MgO·2SiO2)-tricalcium phosphate (3CaO·P2O5) glass system.

The present work is an amalgamation of computation and experimental approach to gain an insight into composition-structure-bioactivity relationships of alkali-free bioactive glasses in the CaO-MgO-SiO2-P2O5 system. The glasses have been designed in the diopside (CaO·MgO·2SiO2; Di)-tricalcium phosphate (3CaO·P2O5; TCP) binary join by varying the Di/TCP ratio. The melt-quenched glasses have been investigated for their structure by molecular dynamic (MD) simulations as well as by nuclear magnetic resonance spectroscopy (NMR). In all the investigated glasses silicate and phosphate components are dominated by Q(2) (Si) and Q(0) (P) species, respectively. The apatite forming ability of the glasses was investigated using X-ray diffraction (XRD), infrared spectroscopy after immersion of glass powders in simulated body fluid (SBF) for time durations varying between 1 h and 14 days, while their chemical degradation has been studied in Tris-HCl in accordance with ISO 10993-14. All the investigated glasses showed good bioactivity without any substantial variation. A significant statistical increase in metabolic activity of human mesenchymal stem cells (hMSCs) when compared to the control was observed for Di-60 and Di-70 glass compositions under both basal and osteogenic conditions.

Ligand and structure-based approaches for the identification of SIRT1 activators.

SIRT1 is a NAD(+)-dependent deacetylase that involved in various important metabolic pathways. Combined ligand and structure-based approach was utilized for identification of SIRT1 activators. Pharmacophore models were developed using DISCOtech and refined with GASP module of Sybyl X software. Pharmacophore models were composed of two hydrogen bond acceptor (HBA) atoms, two hydrogen bond donor (HBD) sites and one hydrophobic (HY) feature. The pharmacophore models were validated through receiver operating characteristic (ROC) and Güner-Henry (GH) scoring methods. Model-2 was selected as best model among the model 1-3, based on ROC and GH score value, and found reliable in identification of SIRT1 activators. Model-2 (3D search query) was searched against Zinc database. Several compounds with different chemical scaffold were retrieved as hits. Currently, there is no experimental SIRT1 3D structure available, therefore, we modeled SIRT1 protein structure using homology modeling. Compounds with Qfit value of more than 86 were selected for docking study into the SIRT1 homology model to explore the binding mode of retrieved hits in the active allosteric site. Finally, in silico ADMET prediction study was performed with two best docked compounds. Combination of ligand and structure-based modeling methods identified active hits, which may be good lead compounds to develop novel SIRT1 activators.

Structure-solubility relationships in fluoride-containing phosphate based bioactive glasses.

The dissolution of fluoride-containing bioactive glasses critically affects their biomedical applications. Most commercial fluoride-releasing bioactive glasses have been designed in the soda-lime-silica system. However, their relatively slow chemical dissolution and the adverse effect of fluoride on their bioactivity are stimulating the study of alternative biodegradable materials with higher biodegradability, such as biodegradable phosphate-based bioactive glasses, which can be a good candidate for applications where a fast release of active ions is sought. In order to design new biomaterials with controlled degradability and high bioactivity, it is essential to understand the connection between chemical composition, molecular structure, and solubility in physiological fluids. Accordingly, in this work we have combined the strengths of various experimental techniques with Molecular Dynamics (MD) simulations, to elucidate the impact of fluoride ions on the structure and chemical dissolution of bioactive phosphate glasses in the system: 10Na2O-(45 -x)CaO-45P2O5-xCaF2, where x varies between 0-10 mol%. NMR and MD data reveal that the medium-range atomic-scale structure of these glasses is dominated by Q2 phosphate units followed by Q1 units, and the MD simulations further show that fluoride tends to associate with network modifier cations to form alkali/alkaline-earth rich ionic aggregates. The impact of fluoride on chemical dissolution of glasses has been studied in deionized water, acidic (pH = 3.0), neutral (pH = 7.4) and basic (pH = 9.0) buffer solutions, while the bioactivity and cytotoxicity of glasses has been studied in vitro through their apatite-forming ability in simulated body fluid (SBF) and cell culture tests on mesenchymal stem cells (MSCs), respectively. The macroscopic trends observed from various chemical dissolution and bioactivity studies are discussed on the basis of the effect of fluoride on the atomistic structure of glasses, such as F-induced phosphate network re-polymerization, in an attempt to establish composition-structure-property relationships for these biomaterials.

Role of glass structure in defining the chemical dissolution behavior, bioactivity and antioxidant properties of zinc and strontium co-doped alkali-free phosphosilicate glasses.

We investigated the structure-property relationships in a series of alkali-free phosphosilicate glass compositions co-doped with Zn(2+) and Sr(2+). The emphasis was laid on understanding the structural role of Sr(2+) and Zn(2+) co-doping on the chemical dissolution behavior of glasses and its impact on their in vitro bioactivity. The structure of glasses was studied using molecular dynamics simulations in combination with solid state nuclear magnetic resonance spectroscopy. The relevant structural properties are then linked to the observed degradation behavior, in vitro bioactivity, osteoblast proliferation and oxidative stress levels. The apatite-forming ability of glasses has been investigated by X-ray diffraction, infrared spectroscopy and scanning electron microscopy-energy-dispersive spectroscopy after immersion of glass powders/bulk in simulated body fluid (SBF) for time durations varying between 1h and 14 days, while their chemical degradation has been studied in Tris-HCl in accordance with ISO 10993-14. All the glasses exhibit hydroxyapatite formation on their surface within 1-3h of their immersion in SBF. The cellular responses were observed in vitro on bulk glass samples using human osteosarcoma MG63 cell line. The dose-dependent cytoprotective effect of glasses with respect to the concentration of zinc and strontium released from the glasses is also discussed.

Pharmacophore modeling, virtual screening, docking and in silico ADMET analysis of protein kinase B (PKB ß) inhibitors.

Protein kinase B (PKB) is a key mediator of proliferation and survival pathways that are critical for cancer growth. Therefore, inhibitors of PKB are useful agents for the treatment of cancer. Herein, we describe pharmacophore-based virtual screening combined with docking study as a rational strategy for identification of novel hits or leads. Pharmacophore models of PKB ß inhibitors were established using the DISCOtech and refined with GASP from compounds with IC50 values ranging from 2.2 to 246nM. The best pharmacophore model consists of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD) site and two hydrophobic (HY) features. The pharmacophore models were validated through receiver operating characteristic (ROC) and Güner-Henry (GH) scoring methods indicated that the model-3 was statistically valuable and reliable in identifying PKB ß inhibitors. Pharmacophore model as a 3D search query was searched against NCI database. Several compounds with different structures (scaffolds) were retrieved as hits. Molecules with a Qfit value of more than 95 and three other known inhibitors were docked in the active site of PKB to further explore the binding mode of these compounds. Finally in silico pharmacokinetic and toxicities were predicted for active hit molecules. The hits reported here showed good potential to be PKB ß inhibitors.

Structural role of zinc in biodegradation of alkali-free bioactive glasses.

We report on the effect of varying the Zn2+/Mg2+ ratio on the structure and biodegradation of glasses in an alkali-free system designed in the glass forming region of diopside (CaMgSi2O6)-fluorapatite [Ca5(PO4)3F]-TCP (3CaO·P2O5). The zinc-containing glasses designed in the as-mentioned ternary system are potential materials for their application in bone regeneration and tissue engineering. The melt-quenched glasses with compositions (mol%), 36.07CaO - (19.24 -x) MgO -xZnO - 5.61P2O5- 38.49SiO2- 0.59CaF2, where x varies between 0 and 10, have been investigated for their structure by molecular dynamics simulations as well as by nuclear magnetic resonance spectroscopy. In all the investigated glasses silicate and phosphate components are mainly present as Q2 (Si) and Q0 (orthophosphate) species, respectively. Zinc retains structural features similar to magnesium, with predominant five-fold coordination. The apatite-forming ability of glasses has been investigated by X-ray diffraction and infrared spectroscopy after immersion of glass powders in simulated body fluids for time durations varying between 1 h and 7 days, while their chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. The increasing Zn2+/Mg2+ ratio decreases the chemical degradation of glasses as well as reducing their apatite forming ability. The results allowed us to discuss the biodegradation of alkali-free bioactive glasses on the basis of the structural role of zinc and magnesium.

Rhenium solubility in borosilicate nuclear waste glass: implications for the processing and immobilization of technetium-99.

The immobilization of technetium-99 ((99)Tc) in a suitable host matrix has proven to be a challenging task for researchers in the nuclear waste community around the world. In this context, the present work reports on the solubility and retention of rhenium, a nonradioactive surrogate for (99)Tc, in a sodium borosilicate glass. Glasses containing target Re concentrations from 0 to 10,000 ppm [by mass, added as KReO(4) (Re(7+))] were synthesized in vacuum-sealed quartz ampules to minimize the loss of Re from volatilization during melting at 1000 °C. The rhenium was found as Re(7+) in all of the glasses as observed by X-ray absorption near-edge structure. The solubility of Re in borosilicate glasses was determined to be ~3000 ppm (by mass) using inductively coupled plasma optical emission spectroscopy. At higher rhenium concentrations, additional rhenium was retained in the glasses as crystalline inclusions of alkali perrhenates detected with X-ray diffraction. Since (99)Tc concentrations in a glass waste form are predicted to be <10 ppm (by mass), these Re results implied that the solubility should not be a limiting factor in processing radioactive wastes, assuming Tc as Tc(7+) and similarities between Re(7+) and Tc(7+) behavior in this glass system.

Alkali-free bioactive glasses for bone tissue engineering: a preliminary investigation.

An alkali-free series of bioactive glasses has been designed and developed in the glass system CaO-MgO-SiO(2)-P(2)O(5)-CaF(2) along the diopside (CaMgSi(2)O(6))-fluorapatite (Ca(5)(PO(4))(3)F)-tricalcium phosphate (3CaO·P(2)O(5)) join. The silicate network in all the investigated glasses is predominantly coordinated in Q(2) (Si) units, while phosphorus tends to remain in an orthophosphate (Q(0)) environment. The in vitro bioactivity analysis of glasses has been made by immersion of glass powders in simulated body fluid (SBF) while chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Some of the investigated glasses exhibit hydroxyapatite formation on their surface within 1-12 h of their immersion in SBF solution. The sintering and crystallization kinetics of glasses has been investigated by differential thermal analysis and hot-stage microscopy, respectively while the crystalline phase evolution in resultant glass-ceramics has been studied in the temperature range of 800-900°C using powder X-ray diffraction and scanning electron microscopy. The alkaline phosphatase activity and osteogenic differentiation for glasses have been studied in vitro on sintered glass powder compacts using rat bone marrow mesenchymal stem cells. The as-designed glasses are ideal candidates for their potential applications in bone tissue engineering in the form of bioactive glasses as well as glass/glass-ceramic scaffolds.