I drop your photograph in the sea

But I am the sailor submerged in your endless blue -

plum rains (梅雨)

Tissue paper petals wilt under the weigh

Customized Porosity in Ceramic Composites via Freeze Casting

Freeze casting is a facile pore-forming technique for ceramics as it affords great tunability in pore structure including size, morphology, wall thickness, tortuosity, and alignment. Nevertheless, similar to any other pore-forming techniques, it has limitations in terms of the range of accessible properties. For example, a porous lamellar structure is highly permeable but easily fractures, while the dendritic structure is the opposite. This research seeks to provide strategies used with freeze casting to achieve a combination of properties that go beyond the current limitations and create optimized pore structures with a specific focus on three properties: strength, permeability, and surface area. Such strategies utilize two composite material principles. First, particle reinforcement was implemented to optimize the mechanical and transport properties. Second, surface area was increased with hierarchical design for enhanced capture or catalysis applications. To optimize the mechanical and transport properties, we reinforced high-permeability lamellar structures with reinforcement fillers of silicon carbide (SiC) whiskers and carbon nanotubes (CNTs). The two fillers afford two different mechanisms of reinforcement: structural and material reinforcement. Additions of 30 vol.% SiC whiskers increased the compressive strength by 325% at a small expense in permeability. Shear failure, common in lamellar structures, was prevented by the interwall bridges produced via particle engulfment during freezing. These bridges were demonstrated by the change in microstructure, stress-strain behavior, and fracture surfaces. A 2D in-situ solidification experiment was conducted to observe solidification and particle engulfment directly. We proposed a modified engulfment model to account for the complexity stemming from high-aspect ratio particles and non-planar freezing fronts. Reasonable agreement was found between the model, the simulation based on the model, and the experimental values from the freeze-casting and 2D-solidification experiments. Freeze-casting with CNTs was explored as an alternative reinforcement strategy, but one which maintains the original pore structure. CNTs were pushed aside by the freezing front to pore walls due to their small diameters for low CNT concentration composites (&lt;4.5 wt.%) such that the original pore structures remained. The compressive strength increased, albeit by smaller percentages (118% for 4.3 wt.%) than those with SiC whiskers. The increase was attributed to the toughening of pore walls with no diminishing effect on permeability. In addition, CNTs changed the electrical conductivity by ten orders of magnitude with the addition of 8.2 wt.% of the reinforcement. Finally, conformal coatings via self-assembly of block copolymers (BCP) were produced by infiltration into a freeze-cast lamellar structure and significantly increased the surface area of the underlying scaffold. A bimodal pore size distribution with nanometer-size pores from the BCP self-assembly and micron-size pores from freeze casting was observed. An increase in compressive strengths was achieved with the introduction of pore hierarchy while retaining permeability of the macroporous structure due to enlarged lamellar spacings from the infiltration process.</p

Duplicate dmbx1 genes regulate progenitor cell cycle and differentiation during zebrafish midbrain and retinal development

Abstract Background The Dmbx1 gene is important for the development of the midbrain and hindbrain, and mouse gene targeting experiments reveal that this gene is required for mediating postnatal and adult feeding behaviours. A single Dmbx1 gene exists in terrestrial vertebrate genomes, while teleost genomes have at least two paralogs. We compared the loss of function of the zebrafish dmbx1a and dmbx1b genes in order to gain insight into the molecular mechanism by which dmbx1 regulates neurogenesis, and to begin to understand why these duplicate genes have been retained in the zebrafish genome. Results Using gene knockdown experiments we examined the function of the dmbx1 gene paralogs in zebrafish, dmbx1a and dmbx1b in regulating neurogenesis in the developing retina and midbrain. Dose-dependent loss of dmbx1a and dmbx1b function causes a significant reduction in growth of the midbrain and retina that is evident between 48-72 hpf. We show that this phenotype is not due to patterning defects or persistent cell death, but rather a deficit in progenitor cell cycle exit and differentiation. Analyses of the morphant retina or anterior hindbrain indicate that paralogous function is partially diverged since loss of dmbx1a is more severe than loss of dmbx1b. Molecular evolutionary analyses of the Dmbx1 genes suggest that while this gene family is conservative in its evolution, there was a dramatic change in selective constraint after the duplication event that gave rise to the dmbx1a and dmbx1b gene families in teleost fish, suggestive of positive selection. Interestingly, in contrast to zebrafish dmbx1a, over expression of the mouse Dmbx1 gene does not functionally compensate for the zebrafish dmbx1a knockdown phenotype, while over expression of the dmbx1b gene only partially compensates for the dmbx1a knockdown phenotype. Conclusion Our data suggest that both zebrafish dmbx1a and dmbx1b genes are retained in the fish genome due to their requirement during midbrain and retinal neurogenesis, although their function is partially diverged. At the cellular level, Dmbx1 regulates cell cycle exit and differentiation of progenitor cells. The unexpected observation of putative post-duplication positive selection of teleost Dmbx1 genes, especially dmbx1a, and the differences in functionality between the mouse and zebrafish genes suggests that the teleost Dmbx1 genes may have evolved a diverged function in the regulation of neurogenesis

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

Improved hippocampal dose with reduced margin radiotherapy for glioblastoma multiforme

BACKGROUND: To dosimetrically evaluate the effect of reduced margin radiotherapy on hippocampal dose for glioblastoma multiforme (GBM) patients. METHODS: GBM patients enrolled on the Radiation Therapy Oncology Group (RTOG) 0825 trial at our institution were identified. Standard RTOG 0825 expansions were 2 cm + 3-5 mm from the gross tumor volume (GTV) to the clinical tumor volume (CTV) and from the CTV to the planning tumor volume (PTV), respectively. These same patients also had reduced margin tumor volumes generated with 8 mm (GTV to CTV) + 3 mm (CTV to PTV) expansions. Individual plans were created for both standard and reduced margin structures. The dose-volume histograms were statistically compared with a paired, two-tailed Student’s t-test with a significance level of p < 0.05. RESULTS: A total of 16 patients were enrolled on RTOG 0825. The reduced margins resulted in statistically significant reductions in hippocampal dose at all evaluated endpoints. The hippocampal D(max) was reduced from a mean of 61.4 Gy to 56.1 Gy (8.7%), D(40%) was reduced from 49.9 Gy to 36.5 Gy (26.9%), D(60%) was reduced from 32.7 Gy to 18.7 Gy (42.9%) and the D(80%) was reduced from 27.3 Gy to 15.3 Gy (44%). CONCLUSIONS: The use of reduced margin PTV expansions in the treatment of GBM patients results in significant reductions in hippocampal dose. Though the exact clinical benefit of this reduction is currently unclear, this study does provide support for a future prospective trial evaluating the neurocognitive benefits of reduced margin tumor volumes in the treatment of GBM patients

Gut microbial diversity is associated with lower arterial stiffness in women

© The Author(s)2018 All rights reserved. Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness.Methods We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and and results gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 10 -4 ) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing—two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3–12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing

Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy

Abstract Tubulointerstitial fibrosis represents the major underlying pathology of diabetic nephropathy where loss of cell-to-cell adhesion is a critical step. To date, research has predominantly focussed on the loss of cell surface molecular binding events that include altered protein ligation. In the current study, atomic force microscopy single cell force spectroscopy (AFM- SCFS) was used to quantify changes in cellular stiffness and cell adhesion in TGF-β1 treated kidney cells of the human proximal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the Elastic modulus (stiffness) compared to control. Fluorescence microscopy confirmed that increased cell stiffness is accompanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrangement, affected the work of detachment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively demonstrate a correlation between cellular elasticity, adhesion and early morphologic/phenotypic changes associated with tubular injury

Reversible spin-optical interface in luminescent organic radicals

Molecules present a versatile platform for quantum information science, and are candidates for sensing and computation applications. Robust spin-optical interfaces are key to harnessing the quantum resources of materials. To date, carbon-based candidates have been non-luminescent, which prevents optical read-out. Here we report the first organic molecules displaying both efficient luminescence and near-unity generation yield of high-spin multiplicity excited states. This is achieved by designing an energy resonance between emissive doublet and triplet levels, here on covalently coupled tris(2,4,6-trichlorophenyl) methyl-carbazole radicals (TTM-1Cz) and anthracene. We observe the doublet photoexcitation delocalise onto the linked acene within a few picoseconds and subsequently evolve to a pure high spin state (quartet for monoradicals, quintet for biradical) of mixed radical-triplet character near 1.8 eV. These high-spin states are coherently addressable with microwaves even at 295 K, with optical read-out enabled by intersystem crossing to emissive states. Furthermore, for the biradical, on return to the ground state the previously uncorrelated radical spins either side of the anthracene show strong spin correlation. Our approach simultaneously supports a high efficiency of initialisation, spin manipulations and light-based read-out at room temperature. The integration of luminescence and high-spin states creates an organic materials platform for emerging quantum technologies

Quantitative investigation of calcimimetic R568 on beta-cell adhesion and mechanics using AFM single-cell force spectroscopy

In this study we use a novel approach to quantitatively investigate mechanical and interfacial properties of clonal b-cells using AFM-Single Cell Force Spectroscopy (SCFS). MIN6 cells were incubated for 48 h with 0.5 mMCa2+ ± the calcimimetic R568 (1 lM). AFM-SCFS adhesion and indentation experiments were performed by using modified tipless cantilevers. Hertz contact model was applied to analyse force–displacement (F–d) curves for determining elastic or Young’s modulus (E). Our results show CaSR-evoked increases in cell-to-cell adhesion parameters and E modulus of single cells, demonstrating that cytomechanics have profound effects on cell adhesion characterization