Microstructure evolution during high-pressure spark plasma sintering (HPSPS) of transparent alumina

Applying high-pressure during spark plasma sintering (so-called HPSPS) enables rapid densification of a ceramic powder at relatively lower temperatures, limiting grain growth and allowing fabrication of fine-grained highly transparent ceramics. The present work focuses on the fabrication of fine submicron transparent alumina from untreated commercial powder by HPSPS and the microstructure evolution during consolidation under high applied pressure. The sintering was conducted at relatively low temperatures (1000-1100°C) under high pressure varied from 250 to 800 MPa. We review unique sintering phenomena such as stress-enhanced grain growth and de-sintering, which are related to creep taking place during the final stage of pressure-assisted densification. In addition, optical and mechanical properties of obtained samples are discussed. Please click Additional Files below to see the full abstract

Photoluminescence in SPS-processed transparent Ce:YAG ceramics

Ceramic phosphors display great promise for the realization of high-power lighting devices. Cerium-doped yttrium aluminum garnet (Ce:YAG) is commonly used as a phosphor in white light emitting diodes. Therefore, it was chosen as a case study to investigate photoluminescence of transparent ceramic phosphors fabricated by spark plasma sintering (SPS). In the present work, 0.5 at.% Ce:YAG nano-powder was synthesized by a co-precipitation method and subsequently consolidated by SPS into highly transparent ceramic samples. The effect of varying sintering parameters (temperature and pressure) and post-sintering treatments (hot isostatic pressing and air atmosphere thermal treatment) on optical properties was investigated. Correlations between in-line transmittance, photoluminescence (PL) and residual porosity characteristics (pore size and volume fraction) were established. It was also found that PL emission intensity and external quantum efficiency were significantly affected by intentionally created surface roughness. Please click Additional Files below to see the full abstract

Macromolecular sheets direct the morphology and orientation of plate-like biogenic guanine crystals

Animals precisely control the morphology and assembly of guanine crystals to produce diverse optical phenomena in coloration and vision. However, little is known about how organisms regulate crystallization to produce optically useful morphologies which express highly reflective crystal faces. Guanine crystals form inside iridosome vesicles within chromatophore cells called iridophores. By following iridosome formation in developing scallop eyes, we show that pre-assembled, fibrillar sheets provide an interface for nucleation and direct the orientation of the guanine crystals. The macromolecular sheets cap the (100) faces of immature guanine crystals, inhibiting growth along the π-stacking growth direction. Crystal growth then occurs preferentially along the sheets to generate highly reflective plates. Despite their different physical properties, the morphogenesis of iridosomes bears a striking resemblance to melanosome morphogenesis in vertebrates, where amyloid sheets template melanin deposition. The common control mechanisms for melanin and guanine formation inspire new approaches for manipulating the morphologies and properties of molecular materials.publishedVersio

Structure determination of biogenic crystals directly from 3D electron diffraction data

Highly reflective assemblies of purine, pteridine, and flavin crystals are used in the coloration and visual systems of many different animals. However, structure determination of biogenic crystals by single-crystal XRD is challenging due to the submicrometer size and beam sensitivity of the crystals, and powder XRD is inhibited due to the small volumes of powders, crystalline impurity phases, and significant preferred orientation. Consequently, the crystal structures of many biogenic materials remain unknown. Herein, we demonstrate that the 3D electron diffraction (3D ED) technique provides a powerful alternative approach, reporting the successful structure determination of biogenic guanine crystals (from spider integument, fish scales, and scallop eyes) from 3D ED data confirmed by analysis of powder XRD data. The results show that all biogenic guanine crystals studied are the previously known β-polymorph. This study highlights the considerable potential of 3D ED for elucidating the structures of biogenic molecular crystals in the nanometer-to-micrometer size range. This opens up an important opportunity in the development of organic biomineralization, for which structural knowledge is critical for understanding the optical functions of biogenic materials and their possible applications as sustainable, biocompatible optical materials

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

Rationalizing the influence of small-molecule dopants on guanine crystal morphology

Many spectacular optical phenomena in animals are produced by reflective assemblies of guanine crystals. The crystals comprise planar H-bonded layers of π-stacked molecules with a high in-plane refractive index. By preferentially expressing the highly reflective π-stacked (100) crystal face and controlling its cross-sectional shape, organisms generate a diverse array of photonic superstructures. How is this precise control over crystal morphology achieved? Recently, it was found that biogenic guanine crystals are composites, containing high quantities of hypoxanthine and xanthine in a molecular alloy. Here, we crystallized guanine in the presence of these dopants and used computations to rationalize their influence on the crystal morphology and energy. Exceptional quantities of hypoxanthine are incorporated into kinetically favored solid solutions, indicating that fast crystallization kinetics underlies the heterogeneous compositions of biogenic guanine crystals. We find that weakening of H-bonding interactions by additive incorporation elongates guanine crystals along the stacking direction─the opposite morphology of biogenic crystals. However, by modulation of the strength of competing in-plane H-bonding interactions, additive incorporation strongly influences the cross-sectional shape of the crystals. Our results suggest that small-molecule H-bond disrupting additives may be simultaneously employed with π-stack blocking additives to generate reflective platelet crystal morphologies exhibited by organisms

Biogenic guanine crystals are solid solutions of guanine and other purine metabolites

Highly reflective crystals of the nucleotide base guanine are widely distributed in animal coloration and visual systems. Organisms precisely control the morphology and organization of the crystals to optimize different optical effects, but little is known about how this is achieved. Here we examine a fundamental question that has remained unanswered after over 100 years of research on guanine: what are the crystals made of? Using solution-state and solid-state chemical techniques coupled with structural analysis by powder XRD and solid-state NMR, we compare the purine compositions and the structures of seven biogenic guanine crystals with different crystal morphologies, testing the hypothesis that intracrystalline dopants influence the crystal shape. We find that biogenic “guanine” crystals are not pure crystals but molecular alloys (aka solid solutions and mixed crystals) of guanine, hypoxanthine, and sometimes xanthine. Guanine host crystals occlude homogeneous mixtures of other purines, sometimes in remarkably large amounts (up to 20% of hypoxanthine), without significantly altering the crystal structure of the guanine host. We find no correlation between the biogenic crystal morphology and dopant content and conclude that dopants do not dictate the crystal morphology of the guanine host. The ability of guanine crystals to host other molecules enables animals to build physiologically “cheaper” crystals from mixtures of metabolically available purines, without impeding optical functionality. The exceptional levels of doping in biogenic guanine offer inspiration for the design of mixed molecular crystals that incorporate multiple functionalities in a single material

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Pressure-assisted sintering and characterization of Nd:YAG ceramic lasers

Abstract Spark plasma sintering (SPS) is an advanced one-stage, rapid, near-net shape densification technique combining uniaxial pressure with resistive heating. Various transparent ceramics have been successfully fabricated by SPS, despite the existence of inherent carbon contamination and residual pores. Due to the disk-shape of SPS-processed samples, the technique may be suited for producing thin-disk ceramic laser materials. Nevertheless, an in-depth study of these materials has never been reported. With that goal in mind, the major focus of this study was to characterize the laser performance of Nd:YAG ceramics fabricated by one-stage SPS under conventional (60 MPa) and high (300 MPa) applied pressures. In addition to measuring the lasing slope efficiency and threshold, the passive losses associated with each sample were also evaluated. Surprisingly, it was found that in-line transmittance spectra do not provide accurate predictions of laser performance due to the nature of residual porosity. Moreover, homogeneity and beam quality were assessed, and comparisons were drawn between conventional and high-pressure SPS ceramics. This study lays the groundwork for the future of laser materials fabricated by SPS or similar pressure-assisted techniques