Order Reconstruction for Nematics on Squares and Regular Polygons: A Landau-de Gennes Study

We construct an order reconstruction (OR)-type Landau-de Gennes critical point on a square domain of edge length $\lambda$, motivated by the well order reconstruction solution numerically reported by Kralj and Majumdar. The OR critical point is distinguished by an uniaxial cross with negative scalar order parameter along the square diagonals. The OR critical point is defined in terms of a saddle-type critical point of an associated scalar variational problem. The OR-type critical point is globally stable for small $\lambda$ and undergoes a supercritical pitchfork bifurcation in the associated scalar variational setting. We consider generalizations of the OR-type critical point to a regular hexagon, accompanied by numerical estimates of stability criteria of such critical points on both a square and a hexagon in terms of material-dependent constants.Comment: 29 pages, 12 figure

Order reconstruction for nematics on squares and hexagons:a Landau-de Gennes study

We construct an order reconstruction (OR-)type Landau-de Gennes critical point on a square domain of edge length 2λ, motivated by the well order reconstruction solution numerically reported in [S. Kralj and A. Majumdar, Proc. R. Soc. Lond. Ser. A Math. Phys. Eng. Sci., 470 (2014), 20140276]. The OR critical point is distinguished by a uniaxial cross with negative scalar order parameter along the square diagonals. The OR critical point is defined in terms of a saddle-type critical point of an associated scalar variational problem. The OR-type critical point is globally stable for small λ and undergoes a supercritical pitchfork bifurcation in the associated scalar variational setting. We consider generalizations of the OR-type critical point to a regular hexagon, accompanied by numerical estimates of stability criteria of such critical points on both a square and a hexagon in terms of material-dependent constants

Front Propagation at the Nematic-Isotropic Transition Temperature

We study the gradient flow model for the Landau--de Gennes energy functional for nematic liquid crystals at the nematic-isotropic transition temperature on prototype geometries. We study the dynamic model on a three-dimensional droplet and on a disc with Dirichlet boundary conditions and different types of initial conditions. In the case of a droplet with radial boundary conditions, a large class of physically relevant initial conditions generate dynamic solutions with a well-defined nematic-isotropic interface which propagates according to mean curvature for small times. On a disc, we make a distinction between “planar” and “nonplanar” initial conditions, and “minimal” and “nonminimal” Dirichlet boundary conditions. Planar initial conditions generate solutions with an isotropic core for all times, whereas nonplanar initial conditions generate solutions which escape into the third dimension. Nonminimal boundary conditions generate solutions with boundary layers, and these solutions can either have a largely ordered interior profile or an almost entirely disordered isotropic interior profile. Our examples suggest that while critical points of the Landau--de Gennes energy typically have highly localized disordered-ordered interfaces, the transient dynamics exhibits observable interfaces of potential experimental relevance

An Electroactive Oligo-EDOT Platform for Neural Tissue Engineering

The unique electrochemical properties of the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties in processing and lack of biodegradability have hindered progress in this field. Here, the functionality of PEDOT:PSS for neural tissue engineering is improved by incorporating 3,4-ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end-capping strategy, into block co-polymers. By exploiting end-functionalized oligoEDOT constructs as macroinitiators for the polymerization of poly(caprolactone), a block co-polymer is produced that is electroactive, processable, and bio-compatible. By combining these properties, electroactive fibrous mats are produced for neuronal culture via solution electrospinning and melt electrospinning writing. Importantly, it is also shown that neurite length and branching of neural stem cells can be enhanced on the materials under electrical stimulation, demonstrating the promise of these scaffolds for neural tissue engineering

Endogenous production of IL-1B by breast cancer cells drives metastasis and colonisation of the bone microenvironment

Background: Breast cancer bone metastases are incurable highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL-1B by tumor cells drives metastasis and growth in bone. Methods: Tumor/stromal IL-B and IL-1R1 expression was assessed in patient samples and effects of the IL-1R antagonist, Anakinra or the IL-1B antibody Canakinumab on tumor growth and spontaneous metastasis were measured in a humanized mouse model of breast cancer bone metastasis. Effects of tumor cell-derived IL-1B on bone colonisation and parameters associated with metastasis were measured in MDA-MB-231, MCF7 and T47D cells transfected with IL-1B/control. Results: In tissue samples from >1300 patients with stage II/III breast cancer, IL-1B in tumor cells correlated with relapse in bone (hazard ratio 1.85; 95% CI 1.05-3.26; P=0.02) and other sites (hazard ratio 2.09; 95% CI 1.26-3.48; P=0.0016). In a humanized model of spontaneous breast cancer metastasis to bone, Anakinra or Canakinumab reduced metastasis and reduced the number of tumor cells shed into the circulation. Production of IL-1B by tumor cells promoted EMT (altered E-Cadherin, N-Cadherin and G-Catenin), invasion, migration and bone colonisation. Contact between tumor and osteoblasts or bone marrow cells increased IL-1B secretion from all three cell types. IL-1B alone did not stimulate tumor cell proliferation. Instead, IL-1B caused expansion of the bone metastatic niche leading to tumor proliferation. Conclusion: Pharmacological inhibition of IL-1B has potential as a novel treatment for breast cancer metastasis

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies