Tunable assembly of host-guest colloidal crystals.

Entropy compartmentalization provides new self-assembly routes to colloidal host-guest (HG) structures. Leveraging host particle shape to drive the assembly of HG structures has only recently been proposed and demonstrated. However, the extent to which the guest particles can dictate the structure of the porous network of host particles has not been explored. In this work, by modifying only the guest shape, we show athermal, binary mixtures of star-shaped host particles and convex polygon-shaped guest particles assemble as many as five distinct crystal structures, including rotator and discrete rotator guest crystals, two homoporous host crystals, and one heteroporous host crystal. Edge-to-edge alignment of neighboring stars results in the formation of three distinct pore motifs, whose preferential formation is controlled by the size and shape of the guest particles. Finally, we confirm, via free volume calculations, that assembly is driven by entropy compartmentalization, where the hosts and guests contribute differently to the free energy of the system; free volume calculations also explain differences in assembly based on guest shape. These results provide guest design rules for assembling colloidal HG structures, especially on surfaces and interfaces.

Molecular characterization of adenocarcinomas arising in the urinary bladder following augmentation cystoplasty: a multi-institutional study.

Development of malignancy is a rare complication following augmentation cystoplasty, and the majority of tumors observed in this setting are adenocarcinomas. Here, we sought to genetically profile these tumors by targeted DNA sequencing of a multi-institutional cohort of adenocarcinomas that developed in the urinary bladder following augmentation cystoplasty. Carcinomas arising in the urinary bladder of patients with history of augmentation cystoplasty were obtained from 4 major academic institutions, with cases diagnosed as urothelial carcinoma excluded from the study. The cases were analyzed using a DNA sequencing panel that includes 529 genes and genome-wide copy number assessment. The most frequently altered genes included TP53, KRAS, and MYC, and the vast majority of cases demonstrated mutational profiles consistent with gastrointestinal adenocarcinomas. One case demonstrated an EML4::ALK fusion together with an MSH3 frameshift mutation and hypermutated phenotype, characteristic of a rare but aggressive subtype of colorectal adenocarcinoma that may benefit from targeted ALK inhibition therapy. Importantly, six other tumors in the cohort also had potentially targetable molecular alterations, involving ATM (2 cases), BRCA1 (2 cases), EGFR (1 case), and ERBB2 (1 case). To our knowledge, this study represents the most comprehensive molecular characterization to date of adenocarcinomas arising in the urinary bladder following augmentation cystoplasty. Despite the unique environment of the augmented tissue, the resulting tumors demonstrate a spectrum of driver mutations similar to that of primary gastrointestinal adenocarcinomas. Importantly, molecular alterations potentially amenable to targeted therapy were identified in the majority of cases.

Newtonian Event-Chain Monte Carlo and Collision Prediction with Polyhedral Particles.

Polyhedral nanocrystals are building blocks for nanostructured materials that find applications in catalysis and plasmonics. Synthesis efforts and self-assembly experiments have been assisted by computer simulations that predict phase equilibria. Most current simulations employ Monte Carlo methods, which generate stochastic dynamics. Collective and correlated configuration updates are alternatives that promise higher computational efficiency and generate trajectories with realistic dynamics. One such alternative involves event-chain updates and has recently been proposed for spherical particles. In this contribution, we develop and apply event-chain Monte Carlo for hard convex polyhedra. Our simulation makes use of an improved computational geometry algorithm XenoSweep, which predicts sweep collision in a particularly simple way. We implement Newtonian event chains in the open-source general-purpose particle simulation toolkit HOOMD-blue for serial and parallel simulation. The speedup over state-of-the-art Monte Carlo is between a factor of 10 for nearly spherical polyhedra and a factor of 2 for highly aspherical polyhedra. Finally, we validate the Newtonian event-chain algorithm by applying it to a current research problem, the multistep nucleation of two classes of hard polyhedra.

Shape-driven entropic self-assembly of an open, reconfigurable, binary host-guest colloidal crystal.

Entropically driven self-assembly of hard anisotropic particles, where particle shape gives rise to emergent valencies, provides a useful perspective for the design of nanoparticle and colloidal systems. Hard particles self-assemble into a rich variety of crystal structures, ranging in complexity from simple close-packed structures to structures with 432 particles in the unit cell. Entropic crystallization of open structures, however, is missing from this landscape. Here, we report the self-assembly of a two-dimensional binary mixture of hard particles into an open host-guest structure, where nonconvex, triangular host particles form a honeycomb lattice that encapsulates smaller guest particles. Notably, this open structure forms in the absence of enthalpic interactions by effectively splitting the structure into low- and high-entropy sublattices. This is the first such structure to be reported in a two-dimensional athermal system. We discuss the observed compartmentalization of entropy in this system, and show that the effect of the size of the guest particle on the stability of the structure gives rise to a reentrant phase behavior. This reentrance suggests the possibility for a reconfigurable colloidal material, and we provide a proof-of-concept by showing the assembly behavior while changing the size of the guest particles in situ. Our findings provide a strategy for designing open colloidal crystals, as well as binary systems that exhibit co-crystallization, which have been elusive thus far.

Invasive poorly differentiated adenocarcinoma of the bladder following augmentation cystoplasty: a multi-institutional clinicopathological study.

Augmentation cystoplasty is a surgical procedure used in the management of patients with neurogenic bladder. This procedure involves anastomosis of the bladder with gastrointestinal grafts, including portions of ileum, colon, or stomach. A rare but important complication of augmentation cystoplasty is the development of malignancy. The majority of malignancies arising in this setting have been described in case reports. A search for cases of non-urothelial carcinoma following augmentation cystoplasty was conducted through the urological pathology files of four major academic institutions. Ten cases were identified, including six cystoprostatectomy/cystectomy, two partial cystectomy, and two transurethral resection of bladder tumour specimens. The mean patient age at diagnosis was 47 years (range 27-87 years). The male:female ratio was 4:6. The tumours tended to present at an advanced stage; four cystoprostatectomy/cystectomy cases were categorised as pT3a, one was categorised as pT3b, and one was categorised as pT4a. Lymph node metastases were present in all cases which had lymph node excision (range 1-16 positive nodes per case). The majority of cases (90%) were predominantly characterised by a poorly differentiated adenocarcinoma with signet ring cell features. Other morphological features included mucinous features (30%), plasmacytoid features (20%), enteric/villous architecture (10%), and large cell undifferentiated morphology (10%). This is the largest study to date on the clinicopathological features of invasive non-urothelial carcinoma of the bladder following augmentation cystoplasty. The tumours are typically poorly differentiated adenocarcinoma, with diffuse signet ring cell features, aggressive, and present at high stage. Further molecular characterisation may provide additional insights into the pathogenesis of this entity.

A mean-field approach to simulating anisotropic particles.

We introduce a mean-field theoretical framework for generalizing isotropic pair potentials to anisotropic shapes. This method is suitable for generating pair potentials that can be used in both Monte Carlo and molecular dynamics simulations. We demonstrate the application of this theory by deriving a Lennard-Jones (LJ)-like potential for arbitrary geometries along with a Weeks-Chandler-Anderson-like repulsive variant, showing that the resulting potentials behave very similarly to standard LJ potentials while also providing a nearly conformal mapping of the underlying shape. We then describe an implementation of this potential in the simulation engine HOOMD-blue and discuss the challenges that must be overcome to achieve a sufficiently robust and performant implementation. The resulting potential can be applied to smooth geometries like ellipsoids and to convex polytopes. We contextualize these applications with reference to the existing methods for simulating such particles. The pair potential is validated using standard criteria, and its performance is compared to existing methods for comparable simulations. Finally, we show the results of self-assembly simulations, demonstrating that this method can be used to study the assembly of anisotropic particles into crystal structures.

Symmetries in hard polygon systems determine plastic colloidal crystal mesophases in two dimensions.

Orientational ordering is a necessary step in the crystallization of molecules and anisotropic colloids. Plastic crystals, which are possible mesophases between the fluid and fully ordered crystal, are translationally ordered but exhibit no long range orientational order. Here, we study the two-dimensional phase behavior of hard regular polygons with edge number n = 3-12. This family of particles provides a model system to isolate the effect of shape and symmetry on the existence of plastic crystal phases. We show that the symmetry group of the particle, G, and the symmetry group of the local environment in the crystal, H, together determine plastic colloidal crystal phase behavior in two dimensions. If G contains completely the symmetry elements of H, then a plastic crystal phase is absent. If G and H share some but not all nontrivial symmetry elements, then a plastic crystal phase exists with preferred particle orientations that recover the absent symmetry elements of the crystal; we call this phase the discrete plastic crystal phase. If G and H share no nontrivial symmetry elements, then a plastic crystal phase exists without preferred orientations, which we call an indiscrete plastic crystal.

Shape allophiles improve entropic assembly.

We investigate a class of "shape allophiles" that fit together like puzzle pieces as a method to access and stabilize desired structures by controlling directional entropic forces. Squares are cut into rectangular halves, which are shaped in an allophilic manner with the goal of re-assembling the squares while self-assembling the square lattice. We examine the assembly characteristics of this system via the potential of mean force and torque, and the fraction of particles that entropically bind. We generalize our findings and apply them to self-assemble triangles into a square lattice via allophilic shaping. Through these studies we show how shape allophiles can be useful for assembling and stabilizing desired phases with appropriate allophilic design.

Phase behavior and complex crystal structures of self-assembled tethered nanoparticle telechelics.

Motivated by growing interest in the self-assembly of nanoparticles for applications such as photonics, organic photovoltaics, and DNA-assisted designer crystals, we explore the phase behavior of tethered spherical nanoparticles. Here, a polymer tether is used to geometrically constrain a pair of nanoparticles creating a tethered nanoparticle "telechelic". Using simulation, we examine how varying architectural features, such as the size ratio of the two end-group nanospheres and the length of the flexible tether, affects the self-assembled morphologies. We demonstrate not only that this hybrid building block maintains the same phase diversity as linear triblock copolymers, allowing for a variety of nanoparticle materials to replace polymer blocks, but also that new structures not previously reported are accessible. Our findings imply a robust underlying ordering mechanism is common among these systems, thus allowing flexibility in synthesis approaches to achieve a target morphology.

Hard-disk equation of state: first-order liquid-hexatic transition in two dimensions with three simulation methods.

We report large-scale computer simulations of the hard-disk system at high densities in the region of the melting transition. Our simulations reproduce the equation of state, previously obtained using the event-chain Monte Carlo algorithm, with a massively parallel implementation of the local Monte Carlo method and with event-driven molecular dynamics. We analyze the relative performance of these simulation methods to sample configuration space and approach equilibrium. Our results confirm the first-order nature of the melting phase transition in hard disks. Phase coexistence is visualized for individual configurations via the orientational order parameter field. The analysis of positional order confirms the existence of the hexatic phase.

Optimal filling of shapes.

We present filling as a type of spatial subdivision problem similar to covering and packing. Filling addresses the optimal placement of overlapping objects lying entirely inside an arbitrary shape so as to cover the most interior volume. In n-dimensional space, if the objects are polydisperse n-balls, we show that solutions correspond to sets of maximal n-balls. For polygons, we provide a heuristic for finding solutions of maximal disks. We consider the properties of ideal distributions of N disks as N→∞. We note an analogy with energy landscapes.

Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse.

AIMS: To investigate apelin-APJ (angiotensin receptor-like 1) signalling in vascular remodelling, we have examined the pathophysiological response to carotid ligation in apelin knockout mice. METHODS AND RESULTS: Apelin null animals compared with wild-type mice had significantly decreased neointimal lesion area (1.17 +/- 0.17 vs. 3.33 +/- 1.04 x 10(4) microm(2), P < 0.05) and intima/media ratio (0.81 +/- 0.23 vs. 1.49 +/- 0.44, P < 0.05), averaged over four sites 0.5-2 mm from the ligation. Exogenous apelin infusion rescued the apelin-KO phenotype, promoting neointima formation in the null animals. Apelin null animals showed decreased smooth muscle positive area in the neointima (82.3 +/- 2.4 vs. 63.9 +/- 8.4, P < 0.05), and a smaller percentage BrdU positive cells in the neointima and media (11.06 +/- 1.00 vs. 6.53 +/- 0.86, P < 0.05). Apelin mRNA expression increased initially (5.2-fold, P < 0.01) followed by increased apelin receptor expression (10.1-fold, P < 0.05) in the ligated artery. Cytochemistry studies localized apelin expression to luminal endothelial cells and apelin receptor upregulation to smooth muscle cells (SMC) in the media and neointima. In vitro experiments with cultured rat aortic SMC revealed that apelin stimulation increased migration. In contrast to the increased expression of apelin and apelin receptor in carotid remodelling, expression was not upregulated in the apoE high fat model, and correlated with the known disease-inhibitory effect in this model. CONCLUSION: These data suggest that increased apelin receptor expression by SMC provides a paracrine pathway in injured vessels that allows endothelial-derived apelin to stimulate their division and migration into the neointima.

Nanoparticle ordering via functionalized block copolymers in solution.

We consider nanoparticles and functionalized copolymers, block copolymers with attached end groups possessing a specific affinity for nanoparticles, in solution. Using molecular dynamics, we show that nanoparticles are able to direct the self-assembly of the polymer/nanoparticle composite. We perform a detailed study for a wide range of nanoparticle sizes and concentrations. We show that the nanoparticles order in a number of distinct phases: simple cubic, layered hexagonal, hexagonal columnar, gyroid, and a novel square columnar. Our results show that nanoparticles ordered with functionalized block copolymers can provide a simple and efficient tool for assembling novel materials with nanometer scale resolution.