Zeolite-like liquid crystals

Zeolites represent inorganic solid-state materials with porous structures of fascinating complexity. Recently, significant progress was made by reticular synthesis of related organic solid-state materials, such as metal-organic or covalent organic frameworks. Herein we go a step further and report the first example of a fluid honeycomb mimicking a zeolitic framework. In this unique self-assembled liquid crystalline structure, transverse-lying π-conjugated rod-like molecules form pentagonal channels, encircling larger octagonal channels, a structural motif also found in some zeolites. Additional bundles of coaxial molecules penetrate the centres of the larger channels, unreachable by chains attached to the honeycomb framework. This creates a unique fluid hybrid structure combining positive and negative anisotropies, providing the potential for tuning the directionality of anisotropic optical, electrical and magnetic properties. This work also demonstrates a new approach to complex soft-matter self-assembly, by using frustration between space filling and the entropic penalty of chain extension

Shape-tuning the colloidal assemblies in nematic liquid crystals

Colloidal platelets are natural building blocks for the shape-controlled assembly of two-dimensional periodic lattices and can form versatile optical elements. Using three-dimensional (3D) numerical modelling, we demonstrate the self-assembly of triangular, square and pentagonal sub-micrometer sized platelets in a thin layer of nematic liquid crystal. Torques acting on individual platelets are calculated, showing that platelets with quadrupolar symmetry (squares, hexagons, etc) are, orientationally, more strongly bound than platelets with dipolar symmetry (triangles, pentagons) which is important for switching applications. Inter-platelet potentials are shown to depend in a complex way on the orientations of the platelets, exhibiting easy and hard reorientation axes and multiple minima. Linear chains of elastic dipoles form into two-dimensional periodic lattices via interesting rotational and translational shifts, to minimize the distortions in the surrounding nematic medium. © 2012 The Royal Society of Chemistry

A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody, in patients with advanced solid tumors

PURPOSE: The platelet-derived growth factor receptor (PDGFR) has an important role in tumorigenesis and tumor progression. Olaratumab (IMC-3G3) is a fully human monoclonal antibody that selectively binds human PDGFRα and blocks ligand binding. This phase I study assessed the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), pharmacokinetics, and preliminary antitumor activity of olaratumab in patients with advanced solid tumors. METHODS: Patients were enrolled into five dose-escalating cohorts of 3-6 patients each. Olaratumab was administered intravenously weekly at 4, 8, or 16 mg/kg (cohorts 1-3) or once every other week at 15 or 20 mg/kg (cohorts 4-5), with 4 weeks/cycle. RESULTS: Nineteen patients were treated in five cohorts. There were no dose-limiting toxicities; the MTD was not identified with the doses studied. The most common olaratumab-related adverse events (AE) were fatigue and infusion reactions (10.5 % each). With the exception of 1 patient (20 mg/kg) experiencing two grade 3 drug-related AEs after the dose-limiting toxicity assessment period, all drug-related AEs were grade 1 or 2. The trough concentrations (C min) for 16 mg/kg weekly and 20 mg/kg biweekly were higher than 155 μg/mL, and the concentration found to be efficacious in preclinical xenograft models. Twelve patients (63.2 %) had a best response of stable disease [median duration of 3.9 months (95 % CI 2.3-8.7)]. CONCLUSIONS: Olaratumab was well tolerated and showed preliminary antitumor activity. RP2Ds are 16 mg/kg weekly and 20 mg/kg biweekly. Phase II studies of olaratumab as monotherapy and in combination are ongoing in several tumor types.E. Gabriela Chiorean, Christopher Sweeney, Hagop Youssoufian, Amy Qin, Aruna Dontabhaktuni, Nick Loizos, Johannes Nippgen, Robert Amat