Graphene/tri-block copolymer composites prepared via RAFT polymerizations for dual controlled drug delivery via pH stimulation and biodegradation

A novel tri-block copolymer poly(oxopentanoate ethyl methacrylate)-block-poly(pyridyl disulfide ethyl acrylate)-block-poly(ethylene glycol acrylate) [poly(OEMA-b-PDEA-b-PEGA)], retaining active keto groups and pyridyl disulfide (PDS) side functionalities, was synthesized as a drug delivery vehicle using reversible addition-fragmentation chain transfer (RAFT) polymerization method. One mimic drug pyridine-2-thione (PT) was introduced into the monomer, PDEA for copolymerization. The other mimic drug O-benzylhydroxylamine (BHA) was conjugated with tri-block copolymer via efficient oxime coupling chemistry, followed by the attachment onto graphene via π-π stacking interaction to obtain a graphene/tri-block copolymer composite. 1H NMR, UV-vis absorption spectroscopy, fluorescence spectroscopy, gel permeation chromatography (GPC), atomic force microscope (AFM) and transmission electron microscope (TEM) were used to verify the successful step-wise preparation of the tri-block copolymer and drug loaded composite. In vitro release behaviors of BHA and PT from graphene/tri-block copolymer composite via dual drug release mechanisms were investigated. BHA can be released under acid environment, while PT will be released in the presence of reducing agents, such as dithiothreitol (DTT) or glutathione (GSH). It can be envisioned that this novel composite could be exploited as a novel intracellular drug delivery system via dual release mechanisms.

pH-detachable polymer brushes formed using titanium−diol coordination chemistry and living radical polymerization (RAFT)

pH-detachable poly(styrene) brushes formed on indium−tin oxide (ITO) glass substrates using metal complex chemistry and reversible addition−fragmentation chain transfer (RAFT) polymerization was described. These pH-detachable polymeric brushes were generated using both “graft-from” and “graft-to” methodologies. The methodologies involved either the surface self-assembly of catechol-functional RAFT agents (graft-from) or catechol-terminal polymer chains (graft-to) onto the ITO substrate via titanium−diol coordination. The stepwise functionalization of the ITO glass surfaces was characterized successfully using X-ray photoelectron spectroscopy (XPS) and contact angle measurement. Poly(styrene) brushes generated using the “graft-from” method were denser than those generated using the “graft-to” method, as exemplified by atom force microscopy (AFM) and quantified using cyclic voltammetry. Poly(styrene) brushes assembled using both methods could be detached easily by manipulating the pH of the brush environment. Cyclic voltammetry was utilized to calculate precisely the surface coverage of the RAFT functionality and polymeric brush density.

Synthesis, characterization, and multilayer assembly of pH sensitive graphene−polymer nanocomposites

pH sensitive graphene−polymer composites have been prepared by the modification of graphene basal planes with pyrene-terminated poly(2-N,N′-(dimethyl amino ethyl acrylate) (PDMAEA) and poly(acrylic acid) (PAA) via π−π stacking. The pyrene-terminal PDMAEA and PAA were synthesized using reversible addition−fragmentation chain transfer (RAFT) polymerization with a pyrene-functional RAFT agent. The graphene−polymer composites were found to demonstrate phase transfer behavior between aqueous and organic media at different pH values. Atomic force microscopy (AFM) analysis revealed that the thicknesses of the graphene−polymer sheets were approximately 3.0 nm when prepared using PDMAEA (M_n: 6800 and PDI: 1.12). The surface coverage of polymer chains on the graphene basal plane was calculated to be 5.3 × 10⁻¹¹ mol cm⁻² for PDMAEA and 1.3 × 10⁻¹⁰ mol cm⁻² for PAA. The graphene−polymer composites were successfully characterized using X-ray photoelectron spectroscopy (XPS), attenuated total reflection infrared (ATR-IR) spectroscopy, and thermogravimetric analysis (TGA). Self-assembly of the two oppositely charged graphene−polymer composites afforded layer-by-layer (LbL) structures as evidenced by high-resolution scanning electron microscopy (SEM) and quartz crystal microbalance (QCM) measurements.

RAFT controlled synthesis of graphene/polymer hydrogel with enhanced mechanical property for pH-controlled drug release

A pH-sensitive, mechanically strong and thermally stable graphene/poly (acrylic acid) (graphene/PAA) hydrogel was prepared via reversible addition fragmentation transfer (RAFT) polymerizations in the presence of a cross-linking agent. The RAFT agent was covalently coupled onto graphene basal planes via an esterification reaction, with benzoic acid functionalities pre-attached on graphene with its aryl diazonium salt precursor. AFM and SEM analysis revealed the successful preparation of single layered graphene sheets and graphene/polymer hydrogels with pH controlled porous structures. Attenuated total reflection infrared (ATR-IR) and thermogravimetric analyzer (TGA) verified the successful stepwise preparation of graphene/PAA hydrogel. This graphene/PAA hydrogel was pH-sensitive and more mechanically elastic than the PAA hydrogel prepared without graphene. The pH sensitivity of the hydrogel was further utilized for controlled drug release. Doxorubicin was chosen as a model drug and loaded into the hydrogels. The drug loading and release experiment indicated that this hydrogel can be used to efficiently control drug release in the intestine environment (pH = 7.4), better than release in a more acidic environment.© 2013 Elsevier Ltd. All rights reserved.

Properties of HIV-1 associated cholesterol in addition to raft formation are important for virus infection

The overall HIV-1 membrane lipid contents resemble lipid rafts, and we have previously demonstrated that raft-promoting properties of virus-associated cholesterol (with modifications in either the 3β-OH group or AB rings) are important for HIV-1 infectivity. As cholesterol is present in both rafts and non-rafts domains of HIV-1 membrane, we question whether the interpretation of rafts property of virus-associated cholesterol being an absolute requirement for HIV-1 function is too simplistic. The carbon side chain of cholesterol is the third component of cholesterol that can affect the fluidity of membrane depending on its context within the lipid membrane bilayers. In this work, we have used synthetic cholesterol analogues that have different lengths of carbon side chain for our investigation. In contrast to our previous report, we have found that cholesterol side chain analogues that lack in vitro defined raft promoting-property is able to support HIV-1 replication. More specifically, cholesterol analogues with side chains of intermediate length have greater capacity to support HIV-1 infection, suggesting HIV-1 is able to maintain function using cholesterol variants that promote a range of non-rafts- to rafts-properties. Our data demonstrate cholesterol properties other than raft-promoting function also contribute to the infectivity of HIV-1.

Trophic cul-de-sac, Pyrazus ebeninus, limits trophic transfer through an estuarine detritus-based food web

The importance to food-webs of trophic cul-de-sacs, species that channel energy flow away from higher trophic levels, is seldom considered outside of the pelagic systems in which they were first identified. On intertidal mudflats, inputs of detritus from saltmarshes, macroalgae or microphytobenthos are generally regarded as a major structuring force underpinning food-webs and there has been no consideration of trophic cul-de-sacs to date. A fully orthogonal three-factor experiment manipulating the density of the abundant gastropod, Pyrazus ebeninus, detritus and macrobenthic predators on a Sydney mudflat revealed large deleterious effects of the gastropod, irrespective of detrital loading or the presence of predators. Two months after experimental manipulation, the standing-stock of microphytobenthos in plots with high (44 per m²) densities of P. ebeninus was 20% less than in plots with low (4 per m²) densities. Increasing densities of P. ebeninus from low to high halved the abundance of macroinvertebrates and the average number of species. In contrast, the addition of detritus had differing effects on microphytobenthos (positively affected) and macroinvertebrates (negatively affected). Over the two-months of our experiment, no predatory mortality of P. ebeninus was observed and high densities of P. ebeninus decreased impacts of predators on macroinvertebrate abundances. Given that the dynamics of southeast Australian mudflats are driven more by disturbance than seasonality in predators and their interactions with prey, it is likely that Pyrazus would be similarly resistant to predation and have negative effects on benthic assemblages at other times of the year, outside of our study period. Thus, in reducing microphytobenthos and the abundance and species richness of macrofauna, high abundances of the detritivore P. ebeninus may severely limit the flow of energy up the food chain to commercially-important species. This study therefore suggests that trophic cul-de-sacs are not limited to the eutrophied pelagic systems in which they were first identified, but may exist in other systems as well.

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized.

An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched.

Generation of mutant leukaemia inhibitory factor (LIF)-IgG heavy chain fusion proteins as bivalent antagonists of LIF

Two leukaemia inhibitory factor (LIF) mutants, designated MH35-BD and LIF05, have been shown to have a capacity to inhibit the biological activities of not only human LIF (hLIF) but also other interleukin-6 (IL-6) subfamily cytokines such as human oncostatin M (hOSM). These cytokines share the same receptor complex in which the glycoprotein 130 (gp130) subunit is a common constituent. However, at low concentrations and in their monomeric forms, such molecules have a relatively short plasma half-life due to rapid clearance from the kidneys. Here, to prolong their serum half-lives, we have used a multi-step polymerase chain reaction (PCR) to fuse each of the LIF05 and MH35-BD cDNA fragments to a sequence encoding the Fc portion, and the hinge region, of the human immunoglobulin G (hIgG) heavy chain. The linking was achieved through an oligomer encoding a thrombin-sensitive peptide linker thus generating MH35-BD:Fc and LIF05:Fc, respectively. Both Fc fusion constructs were expressed in insect cell Sf21 and the proteins were purified by two successive affinity chromatography steps using nickel–nitrilotriacetic acid (Ni–NTA) agarose and protein A beads. The Ba/F3 cell-based proliferation assay was used to confirm that the proteins were biologically active. In addition, preliminary pharmacokinetics indicates that the Fc fusion constructs have a longer serum half-life compared to their non-fusion counterparts.

Integrated supply chain construction ecosystem management

Agenda 21 may be considered the most significant programme of action influencing environmental policy for the Australian development and construction industry. The industry has remained one of the most rapidly expanding sectors; yet, we have seen the gradual process of exhausting natural resources and irreversible environmental degradation. Even with the introduction of numerous new environmental policies, it remains questionable as to whether real improvements have occurred across the industry. Legislative mechanisms to direct on-site environmental management appear deficient; information flows between participants along the supply chain appear to impact upon environmental management performance; and industry fragmentation remains compounded by ill-defined external, non-contractual supply chain influences that directly impact on contractual systems. Limited research has considered construction supply chain theory and environmental management particularly in reference to policy. The literature highlighted a need to develop a supply chain model which seeks to integrate chain actors and government regulators through holistic information management. The model assumes that fundamental to industry change is statutory control to mandate construction environmental management plans. However, industry change and subsequent environmental management rely upon effective information dissemination. The next stage involves model refinement, investigating barriers and enablers to widespread diffusion of such an innovative integrated environmental management system.

α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.

Habitat fragmentation disrupts the demography of a widespread native mammal

Fragmentation theory predicts that population persistence should be positively correlated with the size of habitat fragments. The patterns of occurrence of many species are consistent with this prediction, but the demographic processes that determine how species respond to fragmentation are poorly understood. In addition, habitat quality may interact with fragment size as an influence on demographic performance. We investigated these predictions for the native bush rat Rattus fuscipes by testing the following hypotheses: 1) population performance (i.e. viability as determined by various demographic parameters) is positively correlated with fragment size; and 2) population performance is positively correlated with habitat quality. Populations of R. fuscipes were censused in two large (>49 ha) and eight small (<2.5 ha) forest fragments in an agricultural region of southeastern Australia. Fragments with high and low quality habitat were included in each size category. Fragment size influenced multiple aspects of population demography; populations in large fragments had higher densities, older age structures, received more potential immigrants, and were more likely to recruit adults than those in small fragments. Reproductive patterns were more predictable in large fragments. Habitat quality per se had less marked effects; adult females were heavier and subadults more prevalent in fragments with high quality habitat. However, high quality habitat enhanced population performance in small fragments more so than in large ones. Despite being widespread in the study area, R. fuscipes populations are profoundly impacted by habitat fragmentation, with population performance declining with fragment size. Studies based on patterns of species occurrence should be interpreted with caution as they may mask critical processes occurring at the population level. For a thorough understanding of the effects of habitat fragmentation, population-level studies are required.

Effect of Ag addition on the corrosion properties of Sn-based solder alloys

Corrosion properties of three different Sn-Ag lead free solder alloys have been investigated in 0.3 wt% Na₂SO₄ solution as corrosive environment. As cast solder alloy was analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Volume fractions of the Ag₃Sn in the solders were determined by image analysis technique. Pitting potential and corrosion potential for the alloys were determined by potentiodynamic tests. Electrochemical impedance spectroscopy (EIS) was carried out to measure the film and charge transfer resistance. Alloys with lower Ag content have been found as better corrosion resistance material.

Mentoring and the transfer of organizational memory within the context of an aging workforce : cultural implications for competitive advantage

Organizational memory, the knowledge gained from organizational experience, has significant potential for competitive advantage. Many authors in the knowledge management and human resource management literatures consider mentoring to be a particularly effective method of transferring organizational memory. In addition, older workers are often considered ideal mentors in organizations because of their experience and alleged willingness to pass on their knowledge to less experienced employees. There is an associated assumption that these workers also anticipate and experience positive outcomes when mentoring others. This chapter considers whether these assumptions hold up in the workplaces of the 21st century, particularly within Western countries. Individualistic cultural norms and some discriminatory practices towards older workers, along with a changing career contract that no longer guarantees employment in one organization for life, may discourage knowledge sharing in organizations. This chapter discusses the constraints and motivations that may operate when older experienced workers consider mentoring others. It considers relevant global and organizational cultural characteristics that may influence mentoring to transfer knowledge, and accordingly suggests strategies for those eager to capitalise on the knowledge experienced employees possess.