Showing papers by "Andrew B. Holmes published in 2015"

A molecular nematic liquid crystalline material for high-performance organic photovoltaics

Abstract: Solution-processed organic photovoltaic cells (OPVs) hold great promise to enable roll-to-roll printing of environmentally friendly, mechanically flexible and cost-effective photovoltaic devices. Nevertheless, many high-performing systems show best power conversion efficiencies (PCEs) with a thin active layer (thickness is ~100 nm) that is difficult to translate to roll-to-roll processing with high reproducibility. Here we report a new molecular donor, benzodithiophene terthiophene rhodanine (BTR), which exhibits good processability, nematic liquid crystalline behaviour and excellent optoelectronic properties. A maximum PCE of 9.3% is achieved under AM 1.5G solar irradiation, with fill factor reaching 77%, rarely achieved in solution-processed OPVs. Particularly promising is the fact that BTR-based devices with active layer thicknesses up to 400 nm can still afford high fill factor of ~70% and high PCE of ~8%. Together, the results suggest, with better device architectures for longer device lifetime, BTR is an ideal candidate for mass production of OPVs.

Organic solar cells using a high-molecular-weight benzodithiophene-benzothiadiazole copolymer with an efficiency of 9.4%.

Abstract: A high molecular weight donor-acceptor conjugated polymer is synthesized using the Suzuki polycondensation method. Using this polymer, a single-junction bulk-heterojunction solar cell is fabricated giving a power conversion efficiency of 9.4% using a fullerene-modified ZnO interlayer at the cathode contact.

Delayed Inhibition of VEGF Signaling after Stroke Attenuates Blood–Brain Barrier Breakdown and Improves Functional Recovery in a Comorbidity-Dependent Manner

Abstract: Diabetes is a common comorbidity in stroke patients and a strong predictor of poor functional outcome. To provide a more mechanistic understanding of this clinically relevant problem, we focused on how diabetes affects blood–brain barrier (BBB) function after stroke. Because the BBB can be compromised for days after stroke and thus further exacerbate ischemic injury, manipulating its function presents a unique opportunity for enhancing stroke recovery long after the window for thrombolytics has passed. Using a mouse model of Type 1 diabetes, we discovered that ischemic stroke leads to an abnormal and persistent increase in vascular endothelial growth factor receptor 2 (VEGF-R2) expression in peri-infarct vascular networks. Correlating with this, BBB permeability was markedly increased in diabetic mice, which could not be prevented with insulin treatment after stroke. Imaging of capillary ultrastructure revealed that BBB permeability was associated with an increase in endothelial transcytosis rather than a loss of tight junctions. Pharmacological inhibition (initiated 2.5 d after stroke) or vascular-specific knockdown of VEGF-R2 after stroke attenuated BBB permeability, loss of synaptic structure in peri-infarct regions, and improved recovery of forepaw function. However, the beneficial effects of VEGF-R2 inhibition on stroke recovery were restricted to diabetic mice and appeared to worsen BBB permeability in nondiabetic mice. Collectively, these results suggest that aberrant VEGF signaling and BBB dysfunction after stroke plays a crucial role in limiting functional recovery in an experimental model of diabetes. Furthermore, our data highlight the need to develop more personalized stroke treatments for a heterogeneous clinical population.

Electroactive and Photoactive Poly[Isoindigo-alt-EDOT] Synthesized Using Direct (Hetero)Arylation Polymerization in Batch and in Continuous Flow

Abstract: In this work, a combined approach was used to obtain a low-cost material for organic electronics by focusing on inexpensive monomers, short synthetic pathway, high-yielding polymerization method, low waste, and easy scalability. To achieve this, a new material, poly[isoindigo-alt-3,4-ethylenedioxythiophene], was synthesized using direct (hetero)arylation polymerization (DHAP). Only a few synthetic steps are required to obtain this material, and no organometallic intermediates are used. In order to make a bigger step toward a truly inexpensive technology, continuous flow methods were applied for the first time to DHAP. This method helped solving a common problem encountered in conjugated polymers synthesis, namely, batch-to-batch variations. Electronic properties of this polymeric material were evaluated using field effect transistors (μh = 7 × 10–3 cm2·V–1·s–1) and solar cells (η = 3.0%).

Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites

Abstract: Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. To date, however, the basis for directional motility is not known. Whilst myosin is very likely orientated as a result of its anchorage within the parasite, how actin filaments are orientated to facilitate directional force generation remains unexplained. In addition, recent evidence has questioned the linkage between actin filaments and secreted surface antigens leaving the way by which motor force is transmitted to the extracellular milieu unknown. Malaria parasites possess a markedly reduced repertoire of actin regulators, among which few are predicted to interact with filamentous (F)-actin directly. One of these, PF3D7_1251200, shows strong homology to the coronin family of actin-filament binding proteins, herein referred to as PfCoronin. Here the N terminal beta propeller domain of PfCoronin (PfCor-N) was expressed to assess its ability to bind and bundle pre-formed actin filaments by sedimentation assay, total internal reflection fluorescence (TIRF) microscopy and confocal imaging as well as to explore its ability to bind phospholipids. In parallel a tagged PfCoronin line in Plasmodium falciparum was generated to determine the cellular localization of the protein during asexual parasite development and blood-stage merozoite invasion. A combination of biochemical approaches demonstrated that the N-terminal beta-propeller domain of PfCoronin is capable of binding F-actin and facilitating formation of parallel filament bundles. In parasites, PfCoronin is expressed late in the asexual lifecycle and localizes to the pellicle region of invasive merozoites before and during erythrocyte entry. PfCoronin also associates strongly with membranes within the cell, likely mediated by interactions with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at the plasma membrane. These data suggest PfCoronin may fulfil a key role as the critical determinant of actin filament organization in the Plasmodium cell. This raises the possibility that macro-molecular organization of actin mediates directional motility in gliding parasites.

Ultrafast Fabrication of Flexible Dye-Sensitized Solar Cells by Ultrasonic Spray-Coating Technology.

Abstract: This study investigates novel deposition techniques for the preparation of TiO2 electrodes for use in flexible dye-sensitized solar cells. These proposed new methods, namely pre-dye-coating and codeposition ultrasonic spraying, eliminate the conventional need for time-consuming processes such as dye soaking and high-temperature sintering. Power conversion efficiencies of over 4.0% were achieved with electrodes prepared on flexible polymer substrates using this new deposition technology and N719 dye as a sensitizer.

Confining Liquids on Silicon Surfaces to Lubricate MEMS

Abstract: Liquid lubrication may provide a solution to the problem of high friction and wear in micro-electro-mechanical systems. Although the effectiveness of this approach has been demonstrated in laboratory-based friction tests, practical constraints prevent it from being applied in commercial devices. The main problem is how to position the lubricant on a silicon surface in order to limit spreading and evaporation. This paper describes two techniques to address this issue. First, low concentrations of additives are used to promote autophobic behaviour. Tests’ results show that certain concentrations of both multiply alkylated cyclopentane and amine additives are effective in halting the spread of hexadecane on silicon, and, in the latter case, cause the hexadecane drop to subsequently retract. The second approach involves applying a micro-contact printing technique previously used on gold surfaces. Here, silicon surfaces are coated with octadecyltrichlorosilane mono-layers that are then selectively removed, using oxygen plasma, to leave regions of contrasting surface energy. Results from spin tests show that surfaces treated in this way can anchor 1 μl drops of hexadecane and water when forces of up to 22 and 230 μN, respectively, are applied.

Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction

Abstract: The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9-membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins.

Synthesis of a Tethered myo-Inositol (1,3,4,5,6)Pentakisphosphate (IP5) Derivative as a Probe for Biological Studies

Abstract: There is sufficient evidence to suggest that myo-inositol pentakisphosphate is a vital intermediate species in higher inositol phosphate metabolism, however, its biological roles and physiological function in cells remain uncertain. A tethered myo-inositol pentakisphosphate (IP5) derivative with a terminal amine group is synthesised allowing facilitated immobilisation onto M-270 magnetic Dynabeads for pull-down experiments and biosensor chip preparation for surface plasmon resonance studies. The probes are validated by both pull-down and surface plasmon resonance (SPR) studies of the known binding protein GRP-1 (general receptor for phosphoinositides 1), and furthermore by SPR studies of protein kinase B (PKB or AKT) binding.

Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives

Abstract: Phosphatidylinositol phosphates are key regulators of cell signalling pathways and membrane trafficking in eukaryotic cells, and there is a need for new chemical probes to further understand how they interact with lipid-binding proteins. Here, the synthesis of phosphatidylinositol phosphate analogues containing adamantyl carboxylic ester groups, in place of the natural lipid side chains, is described. These derivatives are considerably more soluble in water than analogues containing other lipid side chains and do not form large aggregates such as liposomes or micelles. These adamantyl analogues bind to known phosphoinositide-binding proteins with similar affinities to native ligands and will facilitate future studies on the substrate specificities of these proteins involving cocrystallisation studies with proteins.