Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.     

Versatile post-functionalisation strategy for the formation of modular organic–inorganic polyoxometalate hybrids

Hybrid structures incorporating different organic and inorganic constituents are emerging as a very promising class of materials since they synergistically combine the complementary and diverse properties of the individual components. Hybrid materials based on polyoxometalate clusters (POMs) are particularly interesting due to their versatile catalytic, redox, electronic, and magnetic properties, yet the controlled incorporation of different clusters into a hybrid structure is challenging and has been scarcely reported. Herein we propose a novel and general strategy for combining multiple types of metal-oxo clusters in a single hybrid molecule. Two novel hybrid POM structures (HPOMs) bis-functionalised with dipentaerythritol (R–POM₁–R; R = (OCH₂)₃CCH₂OCH₂C(CH₂OH)) were synthesised as building-blocks for the formation of heterometallic hybrid triads (POM₂–R–POM₁–R–POM₂). Such a modular approach resulted in the formation of four novel heterometallic hybrids combing the Lindqvist {V₆}, Anderson–Evans {XMo₆} (X = Cr or Al) and trisubstituted Wells–Dawson {P₂V₃W₁₅} POM structures. Their formation was confirmed by multinuclear Nuclear Magnetic Resonance (NMR), infrared (IR) and UV-Vis spectroscopy, as well as Mass Spectrometry, Diffusion Ordered Spectroscopy (DOSY) and elemental analysis. The thermal stability of the hybrids was also examined by Thermogravimetric Analysis (TGA), which showed that the HPOM triads exhibit higher thermal stability than comparable hybrid structures containing only one type of POM. The one-pot synthesis of these novel compounds was achieved in high yields in aqueous and organic media under simple reflux conditions, without the need of any additives, and could be translated to create other hybrid materials based on a variety of metal-oxo cluster building-blocks.

A versatile modular approach has been developed for incorporating different metal-oxo nanoclusters with characteristic structures into a single hybrid molecule by covalently linking them with polyol ligands.     

Maximum confidence quantum measurements

We consider the problem of discriminating between states of a specified set with maximum confidence. For a set of linearly independent states unambiguous discrimination is possible if we allow for the possibility of an inconclusive result. For linearly dependent sets an analogous measurement is one which allows us to be as confident as possible that when a given state is identified on the basis of the measurement result, it is indeed the correct state.     

Exploring the state of science stereotypes: Systematic review and meta-analysis of the Draw-A-Scientist Checklist

This systematic review and meta-analysis examined recent articles that have used the 1995 Draw-A-Scientist Checklist (DAST-C). This study was focused on the current state of students' stereotypes of scientists and the appropriateness of the DAST-C as a tool to assess these perceptions. Articles included in the review were published between 2003 and 2018, resulting in n = 30 studies. Mean results across studies are presented to describe current stereotypes of scientists, and the current format of the DAST-C is evaluated. Findings suggest that students' perceptions of scientists have largely remained consistent across time: scientists are still perceived as Caucasian, middle-aged or elderly males who wear lab coats and work indoors. However, while the DAST-C is a generally appropriate measure to assess students' perceptions of scientists, recommended revisions to the DAST-C could assist in capturing more modern scientist stereotypes and culturally bound perceptions of scientists.     

An interpretation of structural sorting diagrams for AB type compounds using molecular orbital ideas

The factors governing the structure adopted by a particular AB compound are investigated by deriving two parameters reflecting aspects of the interaction between A and B, using simple molecular orbital ideas, which can be quantified by use of atomic parameters derived from pseudopotential theory. A plot of the values of these two parameters, for a large database of compounds, produces a remarkable topological clustering of AB compounds with the same structure. This structural sorting can also be effected for nonoctet AB compounds if the number of electrons is taken into account. These parameters are related to other indices, R_σ, R_π, previously used by Bloch, Zunger, Phillips et al. to construct structural sorting diagrams. Hence we find a justification for the success of such displays, and shed light on the reasons underpinning structural preference, in terms of the number of valence electrons, and the relative positions of the energy levels of the constituent atoms. There appear to be strong similarities between the electronic reasons behind atomic site preferences in molecules and this site preference or coordination number problem in solids.     

Organization in lipid membranes containing cholesterol

A fundamental attribute of raft formation in cell membranes is lateral separation of lipids into coexisting liquid phases. Using fluorescence microscopy, we observe spontaneous lateral separation in free-floating giant unilamellar vesicles. We record coexisting liquid domains over a range of composition and temperature significantly wider than previously reported. Furthermore, we establish correlations between miscibility in bilayers and in monolayers. For example, the same lipid mixtures that produce liquid domains in bilayer membranes produce two upper miscibility critical points in the phase diagrams of monolayers.     

Load balancing via random local search in closed and open systems

In this paper, we analyze the performance of random load resampling and migration strategies in parallel server systems. Clients initially attach themselves to an arbitrary server, but may switch servers independently at random instants of time in an attempt to improve their service rate. This approach to load balancing contrasts with traditional approaches where clients make smart server selections upon arrival (e.g., Join-the-Shortest-Queue policy and variants thereof). Load resampling is particularly relevant in scenarios where clients cannot predict the load of a server before being actually attached to it. An important example is in wireless spectrum sharing where clients try to share a set of frequency bands in a distributed manner. We first analyze the natural Random Local Search (RLS) strategy. Under this strategy, after sampling a new server randomly, clients only switch to it if their service rate is improved. In closed systems, where the client population is fixed, we derive tight estimates of the time it takes under RLS strategy to balance the load across servers. We then study open systems where clients arrive according to a random process and leave the system upon service completion. In this scenario, we analyze how client migrations within the system interact with the system dynamics induced by client arrivals and departures. We compare the load-aware RLS strategy to a load-oblivious strategy in which clients just randomly switch server without accounting for the server loads. Surprisingly, we show that both load-oblivious and load-aware strategies stabilize the system whenever this is at all possible. We use large-system asymptotics to characterize system performance, and augment this with simulations, which suggest that the average client sojourn time under the load-oblivious strategy is not considerably reduced when clients apply smarter load-aware strategies.     

Temperley-Lieb planar algebra modules arising from the ADE planar algebras

A Hilbert module over a planar algebra P is essentially a Hilbert module over a canonically defined algebra spanned by the annular tangles in P. It follows that any planar algebra Q containing P is a module over P, and in particular, any subfactor planar algebra is a module over the Temperley-Lieb planar algebra with the same modulus. We describe a positivity result that allows us to describe irreducible Temperley-Lieb planar algebra modules, and apply the result to decompose the planar algebras determined by the Coxeter graphs A_n (n?3), D_n (n?4), E₆, E₇, and E₈.     

Uniform-in-Bandwidth Functional Limit Laws

We provide uniform-in-bandwidth functional limit laws for the increments of the empirical and quantile processes. Our theorems, established in the framework of convergence in probability, imply new sharp uniform-in-bandwidth limit laws for functional estimators. In particular, they yield the explicit value of the asymptotic limiting constant for the uniform-in-bandwidth sup-norm of the random error of kernel density estimators. We allow the bandwidth to vary within the complete range for which the estimators are consistent.     

Elliptical magnetic resonance spectroscopic imaging with GRAPPA for imaging brain tumors at 3 T

Magnetic Resonance Spectroscopic Imaging (MRSI) is a technique for imaging spatial variation of metabolites and has been very useful in characterizing biochemical changes associated with disease as well as response to therapy in malignant pathologies. This work presents a self-calibrated undersampling to accelerate 3D elliptical MRSI and an extrapolation-reconstruction algorithm based on the GRAPPA method. The accelerated MRSI technique was tested in three volunteers and five brain tumor patients. Acceleration allowed larger spatial coverage and consequently, less lipid contamination in spectra, compared to fully sampled acquisition within the same scantime. Metabolite concentrations measured from the accelerated acquisitions were in good agreement with measurements obtained from fully sampled MRSI scans.