Tantalum pentoxide Ta2O5 with the orthorhombic L-Ta2O5 structure has been experimentally studied up to 28.3 GPa (at ambient temperature) using synchrotron angle-dispersive powder X-ray diffraction (XRD). The ambient pressure phase remains stable up to 25 GPa where with increased pressure a crystalline to amorphous phase transition occurs. A detailed equation of state (EOS), including pressure dependent lattice parameters, is reported. The results of this study were compared with a previous high-pressure XRD study by Li et al. A clear discrepancy between the ambient-pressure crystal structures and, consequently, the reported EOSs between the two studies was revealed. The origin of this discrepancy is attributed to two different crystal structures used to index the XRD patterns.

Magnesium chloride (MgCl2) with the rhombohedral layered CdCl2-type structure (α-MgCl2) has been studied experimentally using synchrotron angle-dispersive powder x-ray diffraction and Raman spectroscopy using a diamond-anvil cell up to 100 GPa at room temperature and theoretically using first-principles density functional calculations. The results reveal a pressure-induced second-order structural phase transition to a hexagonal layered CdI2-type structure (β-MgCl2) at 0.7 GPa: the stacking sequence of the Cl anions are altered resulting in a reduction of the c-axis length. Theoretical calculations confirm this phase transition sequence and the calculated transition pressure is in excellent agreement with the experiment. Lattice dynamics calculations also reproduce the experimental Raman spectra measured for the ambient and high-pressure phase. According to our experimental results MgCl2 remains in a 2D layered phase up to 100 GPa and further, the 6-fold coordination of Mg cations is retained. Theoretical calculations of relative enthalpy suggest that this extensive pressure stability is due to a low enthalpy of the layered structure ruling out kinetic barrier effects. This observation is unusual, as it contradicts with the general structural behavior of highly compressed AB2 compounds.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens-bis-acrylic 1 and 2, flowable and bulk-fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control-were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20-30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk-fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.

Recent theoretical studies of 2,6-diamino-3,5-dinitropyrazine-1-oxide (C4H4N6O5 Lawrence Livermore Molecule No. 105, LLM-105) report unreacted high pressure equations of state that include several structural phase transitions, between 8 and 50 GPa, while one published experimental study reports equation of state (EOS) data up to a pressure of 6 GPa with no observed transition. Here we report the results of a synchrotron-based X-ray diffraction study and also ambient temperature isobaric-isothermal atomistic molecular dynamics simulations of LLM-105 up to 20 GPa. We find that the ambient pressure phase remains stable up to 20 GPa; there is no indication of a pressure induced phase transition. We do find a prominent decrease in b-axis compressibility starting at approximately 13 GPa and attribute the stiffening to a critical length where inter-sheet distance becomes similar to the intermolecular distance within individual sheets. The ambient temperature isothermal equation of state was determined through refinements of measured X-ray diffraction patterns. The pressure-volume data were fit using various EOS models to yield bulk moduli with corresponding pressure derivatives. We find very good agreement between the experimental and theoretically derived EOS.

α-Glycine is studied up to 50 GPa using synchrotron angle-dispersive X-ray powder diffraction (XRD), Raman spectroscopy, and quantum chemistry calculations performed at multiples levels of theory. Results from both XRD and Raman experiments reveal an extended pressure stability of the α phase up to 50 GPa and the room temperature (RT) equation of state (EOS) was determined up to this pressure. This extended stability is corroborated by density functional theory (DFT) based calculations using the USPEX evolutionary structural search algorithm. Two calculated EOSs, as determined by DFT at T = 0 K and semiempirical density functional tight-binding (DFTB) at RT, and the calculated Raman modes frequencies show a good agreement with the corresponding experimental results. Our work provides a definitive phase diagram and EOS for α-glycine up to 50 GPa, which informs prebiotic synthesis scenarios that can involve pressures well in excess of 10 GPa.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Most cases are sporadic, but well characterized germline alterations in APC, ELP1, GPR161, PTCH1, SUFU, and TP53 predispose to medulloblastoma. However, knowledge about pathogenic/likely pathogenic (P/LP) variants that predispose to medulloblastoma vary based on genes evaluated, patient demographics, and pathogenicity definitions. METHODS: Germline exome sequencing was conducted on 160 childhood survivors of medulloblastoma. Analyses focused on rare variants in 239 known cancer susceptibility genes (CSGs). P/LP variants were identified using ClinVar and InterVar. Variants of unknown significance in known medulloblastoma predisposing genes (APC, ELP1, GPR161, PTCH1, SUFU, TP53) were further classified for loss of function variants. We compared the frequency of P/LP variants in cases to that in 1,259 cancer-free adult controls. RESULTS: Twenty cases (12.5%) had a P/LP variant in an autosomal dominant CSG versus 5% in controls (p=1.0 x10-3), and 10 (6.3%) of these were P/LP variants in a known medulloblastoma gene, significantly greater than 0.2% observed in controls (p=1.4x10-8). The CSGs with the most P/LP variants in cases, and significantly higher than controls, were ELP1 (p=3.0x10-4) and SUFU (p=1.4x10-3). CONCLUSION: Approximately one in eight pediatric medulloblastoma survivors had an autosomal dominant P/LP CSG variant. We confirm several known associated genes and identify novel genes that may be important in medulloblastoma.

Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α₁-antitrypsin-derived peptide to confer binding specificity to neutrophil elastase on activated neutrophils. Surface decoration with this peptide enabled specific anchorage of nanoparticles to activated neutrophils and platelet-neutrophil aggregates, in vitro and in vivo. Nanoparticle delivery of a model drug, hydroxychloroquine, demonstrated significant reduction of neutrophil activities in vitro and a therapeutic effect on murine venous thrombosis in vivo. This innovative approach of cell-specific and activation-state-specific targeting can be applied to several neutrophil-driven pathologies.