Synthesis of novel interlocked architectures in solution and solid phase

Mechanically interlocked molecules, such as catenanes and rotaxanes, are fascinating due to their unique sensing and catalytic properties and their potential to act as molecular motors or switches. Traditionally their synthesis has been laborious and expensive, however this research project endeavoured to overcome this challenge by exploring novel ways of preparing mechanically interlocked molecules both in solution and on surfaces. A series of disulfide-linked macrocycles, [2]catenanes and [2]rotaxanes were synthesised in solution using reversible dynamic covalent chemistry. Subsequently, the interlocked architectures were adapted into solid-tethered systems via attachment to swelling polystyrene resins.

Automotive modal lock-in: The role of path dependence and large socio-economic regimes in market failure

This paper addresses less recognised factors which influence the diffusion of a particular technology. While an innovation’s attributes and performance are paramount, many fail because of external factors which favour an alternative. This paper, with theoretic input from diffusion, lock-in and path-dependency, presents a qualitative study of external factors that influenced the evolution of transportation in USA. This historical account reveals how one technology and its emergent systems become dominant while other choices are overridden by socio-political, economic and technological interests which include not just the manufacturing and service industries associated with the automobile but also government and market stakeholders. Termed here as a large socio-economic regime (LSER),its power in ensuring lock-in and continued path-dependency is shown to pass through three stages, weakening eventually as awareness improves. The study extends to transport trends in China, Korea, Indonesia and Malaysia and they all show the dominant role of an LSER. As transportation policy is increasingly accountable to address both demand and environmental concerns and innovators search for solutions, this paper presents important knowledge for innovators, marketers and policy makers for commercial and societal reasons, especially when negative externalities associated with an incumbent transportation technology may lead to market failure.

Potentiation of ciprofloxacin action against Gram-negative bacterial biofilms by a nitroxide

We previously showed that soluble nitroxides (nitric oxide analogues) mimicked the well-established ability of nitric oxide to cause biofilm dispersal and further showed that these compounds could prevent biofilm formation. Here, we investigated the effect of the nitroxide carboxy-TEMPO in combination with sub μg/ml concentrations of ciprofloxacin on pre-formed flow cell biofilms formed by Gram-negative bacteria. Combination therapy led to substantial eradication of existing biofilms formed by Pseudomonas aeruginosa PA14 (99.3%) and Escherichia coli O157 (93%).

In-situ carbon control in the preparation of precursors to boron carbide by a non-aqueous solution technique

Synthesis of high quality boron carbide (B4C) powders is achieved by carbothermal reduction of boron oxide (B2O3) from a condensed boric acid (H3BO3)/polyvinyl acetate (PVAc) product. Precursor solutions are prepared via free radical polymerisation of vinyl acetate (VA) monomer in methanol in the presence of dissolved H3BO3. A condensed product is then formed by flash evaporation under vacuum. As excess VA monomer is removed at the evaporation step, the polymerisation time is used to manage availability of carbon for reaction. This control of carbon facilitates dispersion of H3BO3 in solution due to the presence of residual VA monomer. B4C powders with very low residual carbon are formed at temperatures as low as 1,250 °C with a 4 hour residence time.

Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer

Background The VEGF pathway has become an important therapeutic target in lung cancer, where VEGF has long been established as a potent pro-angiogenic growth factor expressed by many types of tumors. While Bevacizumab (Avastin) has proven successful in increasing the objective tumor response rate and in prolonging progression and overall survival in patients with NSCLC, the survival benefit is however relatively short and the majority of patients eventually relapse. The current use of tyrosine kinase inhibitors alone and in combination with chemotherapy has been underwhelming, highlighting an urgent need for new targeted therapies. In this study, we examined the mechanisms of VEGF-mediated survival in NSCLC cells and the role of the Neuropilin receptors in this process. Methods NSCLC cells were screened for expression of VEGF and its receptors. The effects of recombinant VEGF and its blockade on lung tumor cell proliferation and cell cycle were examined. Phosphorylation of Akt and Erk1/2 proteins was examined by high content analysis and confocal microscopy. The effects of silencing VEGF on cell proliferation and survival signaling were also assessed. A Neuropilin-1 stable-transfected cell line was generated. Cell growth characteristics in addition to pAkt and pErk1/2 signaling were studied in response to VEGF and its blockade. Tumor growth studies were carried out in nude mice following subcutaneous injection of NP1 over-expressing cells. Results Inhibition of the VEGF pathway with anti-VEGF and anti-VEGFR-2 antibodies or siRNA to VEGF, NP1 and NP2 resulted in growth inhibition of NP1 positive tumor cell lines associated with down-regulation of PI3K and MAPK kinase signaling. Stable transfection of NP1 negative cells with NP1 induced proliferation in vitro, which was further enhanced by exogenous VEGF. In vivo, NP1 over-expressing cells significantly increased tumor growth in xenografts compared to controls. Conclusions Our data demonstrate that VEGF is an autocrine growth factor in NSCLC signaling, at least in part, through NP1. Targeting this VEGF receptor may offer potential as a novel therapeutic approach and also support the evaluation of the role of NP1 as a biomarker predicting sensitivity or resistance to VEGF and VEGFR-targeted therapies in the clinical arena.

Post traumatic success: Positive psychology and solution-focused strategies to help clients survive and thrive

I am an academic who has spent a career using a strengths-based approach in researching ways to promote and maintain mental health in people who have experienced trauma. When I read the title of the book, the notion of “post traumatic success” immediately brought many questions to my mind. What is success anyway? How do we measure success following trauma? Who decides if a person has been successful? However, as I started to read, the intention of the book became clear and my bias regarding the title lessened...

Classic identity negative priming involves accessing semantic representations in the left anterior temporal cortex

Classic identity negative priming (NP) refers to the finding that when an object is ignored, subsequent naming responses to it are slower than when it has not been previously ignored (Tipper, S.P., 1985. The negative priming effect: inhibitory priming by ignored objects. Q. J. Exp. Psychol. 37A, 571-590). It is unclear whether this phenomenon arises due to the involvement of abstract semantic representations that the ignored object accesses automatically. Contemporary connectionist models propose a key role for the anterior temporal cortex in the representation of abstract semantic knowledge (e.g., McClelland, J.L., Rogers, T.T., 2003. The parallel distributed processing approach to semantic cognition. Nat. Rev. Neurosci. 4, 310-322), suggesting that this region should be involved during performance of the classic identity NP task if it involves semantic access. Using high-field (4 T) event-related functional magnetic resonance imaging, we observed increased BOLD responses in the left anterolateral temporal cortex including the temporal pole that was directly related to the magnitude of each individual's NP effect, supporting a semantic locus. Additional signal increases were observed in the supplementary eye fields (SEF) and left inferior parietal lobule (IPL).

Negative priming in naming of categorically related objects: An fMRI study

Ignoring an object slows subsequent naming responses to it, a phenomenon known as negative priming (NP). A central issue in NP research concerns the level of representation at which the effect occurs. As object naming is typically considered to involve access to abstract semantic representations, Tipper 1985 proposed that the NP effect occurred at this level of processing, and other researchers supported this proposal by demonstrating a similar result with categorically related objects (e.g., Allport et al., 1985; Murray, 1995), an effect referred to as semantic NP. However, objects within categories share more physical or structural features than objects from different categories. Consequently, the NP effect observed with categorically related objects might occur at a structural rather than semantic level of representation. We used event related fMRI interleaving overt object naming and image acquisition to demonstrate for the first time that the semantic NP effect activates the left posterior-mid fusiform and insular-opercular cortices. Moreover, both naming latencies and left posterior-mid fusiform cortex responses were influenced by the structural similarity of prime-probe object pairings in the categorically related condition, increasing with the number of shared features. None of the cerebral regions activated in a previous fMRI study of the identity NP effect (de Zubicaray et al., 2006) showed similar activation during semantic NP, including the left anterolateral temporal cortex, a region considered critical for semantic processing. The results suggest that the identity and semantic NP effects differ with respect to their neural mechanisms, and the label "semantic NP" might be a misnomer. We conclude that the effect is most likely the result of competition between structurally similar category exemplars that determines the efficiency of object name retrieval.

Applying HYDRUS to flow in a sodic clay soil with solution composition–dependent hydraulic conductivity

Management of sodic soils under irrigation often requires application of chemical ameliorants to improve permeability combined with leaching of excess salts. Modeling irrigation, soil treatments, and leaching in these sodic soils requires a model that can adequately represent the physical and chemical changes in the soil associated with the amelioration process. While there are a number of models that simulate reactive solute transport, UNSATCHEM and HYDRUS-1D are currently the only models that also include an ability to simulate the impacts of soil chemistry on hydraulic conductivity. Previous researchers have successfully applied these models to simulate amelioration experiments on a sodic loam soil. To further gauge their applicability, we extended the previous work by comparing HYDRUS simulations of sodic soil amelioration with the results from recently published laboratory experiments on a more reactive, repacked sodic clay soil. The general trends observed in the laboratory experiments were able to be simulated using HYDRUS. Differences between measured and simulated results were attributed to the limited flexibility of the function that represents chemistry-dependent hydraulic conductivity in HYDRUS. While improvements in the function could be made, the present work indicates that HYDRUS-UNSATCHEM captures the key changes in soil hydraulic properties that occur during sodic clay soil amelioration and thus extends the findings of previous researchers studying sodic loams.

P-n junction organic photovoltaics fabricated by all solution processing

We have prepared p-n junction organic photovoltaic cells using an all solution processing method with poly(3-hexylthiophene) (P3HT) as the donor and phenyl-C 61-butyric acid methyl ester (PCBM) as the acceptor. Interdigitated donor/acceptor interface morphology was observed in the device processed with the lowest boiling point solvent for PCBM used in this study. The influences of different solvents on donor/acceptor morphology and respective device performance were investigated simultaneously. The best device obtained had characteristically rough interface morphology with a peak to valley value ∼15 nm. The device displayed a power conversion efficiency of 1.78%, an open circuit voltage (V oc) 0.44 V, a short circuit current density (J sc) 9.4 mA/cm 2 and a fill factor 43%.

Solution chemistry impacts on the seawater neutralisation process: Benefits of nanofiltered seawater and reverse osmosis brine

It is well known that the neutralisation of Bayer liquor with seawater causes the precipitation of stable alkaline products and a reduction in pH and dissolved metal concentrations in the effluent. However, there is limited information available on solution chemistry effects on the stability and reaction kinetics of these precipitates. This investigation shows the influence of reactive species (magnesium and calcium) in seawater on precipitate stabilities and volumetric efficiencies during the neutralisation of bauxite refinery residues. Correlations between synthetic seawater solutions and real samples of seawater (filtered seawater, nanofiltered seawater and reverse osmosis brine) have been made. These investigations have been used to confirm that alternative seawater sources can be used to increase the productivity potential of the neutralisation process with minimal implications on the composition and stability of precipitates formed. The volume efficiency of the neutralisation process using synthetic analogues has been shown to be almost directly proportional with the concentration of magnesium. This was further confirmed in the nanofiltered seawater and reverse osmosis brine that showed increases in the efficiency of neutralisation by factors of 3 and 2 compared to seawater, which corresponds with relatively the same increase in the concentration of magnesium in these alternative seawater sources. An assessment of the chemical stability of the precipitates, volumetric efficiency, and discharge water quality have been determined using numerous techniques that include pH, conductivity, inductively coupled plasma optical emission spectroscopy, infrared spectroscopy, thermogravimetric analysis coupled to mass spectrometry and X-ray diffraction. Correlations between synthetic solution compositions and alternative seawater sources have been used to determine if alternative seawater sources are potential substitutes for seawater based on improvements in productivity, implementation costs, savings to operations and environmental benefits.

An Electron-Accepting Chromophore Based on Fluorene and Naphthalenediimide Building Blocks for Solution-Processable Bulk Heterojunction Devices

We have designed, synthesized and utilized a new non-fullerene electron acceptor, 9,9′-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis(2,7-dioctyl-4-(octylamino)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) (B2), for use in solution-processable bulk-heterojunction devices. B2 is based on a central fluorene moiety, which was capped at both ends with an electron-accepting naphthalenediimide functionality. B2 exhibited excellent solubility (>30 mg mL−1 in chloroform), high thermal and photochemical stability, and appropriate energy levels for use with the classical polymer donor regioregular poly(3-hexylthiophene). A power conversion efficiency of 1.16 % was achieved for primitive bulk-heterojunction devices with a high fill factor of approximately 54 %.

Conjoint use of Dibenzosilole and Indan-1,3-dione Functionalities to Prepare an Efficient Non-Fullerene Acceptor for Solution-Processable Bulk-Heterojunction Solar Cells

A solution-processable, non-fullerene electron acceptor, 2,2′-(((5,5-dioctyl-5 H-dibenzo[b,d]silole-3,7-diyl)bis(thiophene-5,2-diyl))bis(methanylylidene))bis(1 H-indene-1,3(2 H)-dione) (called N5) comprised of dibenzosilole and 1,3-indanedione building blocks was designed, synthesized, and fully characterized. N5 is highly soluble in various organic solvents, has high thermal stability, and has energy levels matching those of archetypal donor poly(3-hexylthiophene). Solution-processable, bulk-heterojunction solar cells afforded promising power conversion efficiency of 2.76 % when N5 was used as a non-fullerene electron acceptor along with the conventional donor polymer poly(3-hexylthiophene). As per our knowledge, the material reported herein is the first example in the literature where synchronous use of such building blocks is demonstrated in the design an efficient, non-fullerene acceptor.

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study...