Low-field magnetotransport in graphene cavity devices

Confinement and edge structures are known to play significant roles in electronic and transport properties of two-dimensional materials. Here, we report on low-temperature magnetotransport measurements of lithographically patterned graphene cavity nanodevices. It is found that the evolution of the low-field magnetoconductance characteristics with varying carrier density exhibits different behaviors in graphene cavity and bulk graphene devices. In the graphene cavity devices, we have observed that intravalley scattering becomes dominant as the Fermi level gets close to the Dirac point. We associate this enhanced intravalley scattering to the effect of charge inhomogeneities and edge disorder in the confined graphene nanostructures. We have also observed that the dephasing rate of carriers in the cavity devices follows a parabolic temperature dependence, indicating that the direct Coulomb interaction scattering mechanism governs the dephasing at low temperatures. Our results demonstrate the importance of confinement in carrier transport in graphene nanostructure devices.Comment: 13 pages, 5 figure

Effect of heteroatom and functionalitysubstitution on the oxidation potential of cyclicnitroxide radicals: role of electrostatics inelectrochemistry†

The oxidation potential of a test set of 21 nitroxide radicals, including a number of novel compounds, has been studied experimentally in acetonitrile and correlated with theoretical calculations. It was found that both Hammett constants (σp) of the substituents on the nitroxide radicals and hyperfine splitting constants of the respective nitrogen atoms (αN) were well correlated to their experimental oxidation potentials. Theoretical calculations, carried out at the G3(MP2,CC)(+)//M06-2X/6-31+G(d,p) level of theory with PCM solvation corrections, were shown to reproduce experiments to within a mean absolute deviation of 33 mV, with a maximum deviation of 64 mV. The oxidation potentials of the nitroxides examined varied over 400 mV, depending on ring size and substitution. This considerable variation can be rationalised by the ability of various substituents to electrostatically stabilize the oxidised oxoammonium cation. Importantly, this can be quantified by a simple predictive relationship involving the distance scaled dipole and quadrupole moments of the analogous cyclohexyl ring. This highlights the often-overlooked role of through-space electrostatic substituent effects, even in formally neutral compounds.Z. J. thanks the financial support from the ARC Future Fellowship and the award of Foundation Research Excellent Award (FREA) from the University of Queensland. M. J. M. acknowledges financial support from the ARC Discovery grant. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano and microfabrication facilities for Australia’s researchers. M. L. C. acknowledges financial support from ARC Centre of Excellence for Electromaterials Science and generous allocations on the National Facility of the Australian National Computational Infrastructure

RAFT-mediated emulsion polymerization of styrene with a thermoresponsive MacroCTA

Heterogeneous RAFT polymerization is an attractive 'living' radical polymerization technique to control not only the molecular weight distribution but also the particles size distribution. Here, we demonstrate the use of a thermoresponsive RAFT macro chain transfer agent (MacroCTA) to form seed particles for the chain extension of styrene to form block copolymer latex particles. By incorporating a few styrene units into the MacroCTA, the polymerizations become faster, producing both narrow particle size and molecular weight distributions. This is due to the 'superswelling effect', in which all the seed particles swell with monomer and nucleated at the same time. The resulting latex particles could then be transformed into a variety of nanostructures by cooling below the lower critical solution temperature of the thermoresponsive block in the presence of a plasticizer for polystyrene. The dominant structure was cylindrical worms with the observation of other structures including jelly fish and the rare disc. Cooling under ultrasound produced either vesicles or cauliflower structures. The work demonstrated that utilizing the 'superswelling effect', control over the rate, and molecular weight and particle size distributions could be obtained, providing design parameters to construct new nanostructures

Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer

Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8(+) cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes. We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge. (C) 2016 Elsevier Ltd. All rights reserved

Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and co-delivery

Novel mesoporous silica nanoparticles (LPMSNs) functionalised with degradable poly(2-dimethylaminoethyl acrylate) (PDMAEA) have been developed (PDMAEA–LPMSNs) as nano-carriers for gene delivery. The unique design of PDMAEA–LPMSNs has endowed this system with multiple functions derived from both the organic and inorganic moieties. The cationic polymer unit binds to genetic molecules and undergoes a self-catalyzed hydrolysis in water to form a non-toxic anionic polymer poly(acrylic acid), allowing controlled release of siRNA in the cells. The nanopores of the LPMSNs provide a reservoir for storage and release of chloroquine to facilitate endosomal escape. The PDMAEA–LPMSN composites were characterized by elemental analysis (EA), X-ray photoelectron spectroscopy (XPS), solid-state 13C magic-angle spinning nuclear magnetic resonance (MAS-NMR), thermogravimetric analysis (TGA), and nitrogen sorption techniques. Their siRNA delivery performance was tested in a KHOS cell line, showing promising potential for co-delivery of genes and drugs

Thermoresponsive worms for expansion and release of human embryonic stem cells

The development of robust suspension cultures of human embryonic stem cells (hESCs) without the use of cell membrane disrupting enzymes or inhibitors is critical for future clinical applications in regenerative medicine. We have achieved this by using long, flexible, and thermoresponsive polymer worms decorated with a recombinant vitronectin subdomain that bridge hESCs, aiding in hESC's natural ability to form embryoid bodies (EBs) and satisfying their inherent requirement for cell-cell and cell-extracellular matrix contact. When the EBs reached an optimal upper size where cytokine and nutrient penetration becomes limiting, these long and flexible polymer worms facilitated EB breakdown via a temperature shift from 37 to 25 C. The thermoresponsive nature of the worms enabled a cyclical dissociation and propagation of the cells. Repeating the process for three cycles (over eighteen days) provided a >30-fold expansion in cell number while maintaining pluripotency, thereby providing a simple, nondestructive process for the 3D expansion of hESC

Self-adjuvanting therapeutic peptide-based vaccine induce CD8+ cytotoxic T lymphocyte responses in a murine human papillomavirus tumor model

Vaccine candidatesfor the treatment of human papillomavirus (HPV)-associated cancers areaimed to activate T-cells and induce development of cytotoxic anti-tumor specific responses. Peptide epitopes derived from HPV-16 E7 oncogenic proteinhave been identified as promising antigens for vaccine development. However, peptide-based antigens alone elicit poor cytotoxic T lymphocyte (CTL) responses and need to be formulated with an adjuvant (immunostimulant) to achieve the desired immune responses. We have reported the ability of polyacrylate 4-arm star-polymer (S4) conjugated with HPV-16 E744-57 (8Qmin) epitope to reduce and eradicate TC-1 tumor in the mouse model. Herein, we have studied the mechanism of induction of immune responses by this polymer-peptide conjugate and found prompt uptake of conjugate by antigen presenting cells, stimulating stronger CD8+ rather than CD4+ or NK cell responses

Investigating the affinity of poly tert-butyl acrylate toward Toll-Like Receptor 2

Despite the high safety profile of peptide-based vaccines over conventional counterparts, the inability of small peptides to produce a strong immune response represents the main obstacle for the development of these types of vaccines. Introducing a self-adjuvanting moiety such as poly tert-butyl acrylate can overcome this problem. However, the mode of action of this polymer to produce the desired humoral and/or cellular immune response is still unknown. An AlphaScreen assay along with the cell-free expression technique were employed to evaluate the affinity of this polymer toward toll-like receptor 2 (TLR2) for stimulation of innate immunity. In this study, B-cell epitope, J14, derived from the M protein of group A streptococcus (GAS) was used in conjugation with the poly tert-butyl acrylate as well as a biotin moiety. Pam2Cys analogue, the potent TLR2 agonist, was synthesized and used as a positive control in this work. The AlphaScreen assay showed the inability of polymer to bind to TLR2, while the Pam2Cys displayed very strong binding to TLR2 as expected. This result indicated that poly tert-butyl acrylate does not express its immunogenic effects through recognition by TLR2 and therefore further studies are required to determine its mode of action

Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway

BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis, cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV infection can sensitize host cells to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis, but the mechanism by which HCV regulates the TRAIL pathway remains unclear. METHODS AND RESULTS: Using a sub-genomic replicon and full length virus, JFH-1, we demonstrate that HCV can sensitize host cells to TRAIL-induced apoptosis by up-regulating two TRAIL receptors, death receptor 4 (DR4) and death receptor 5 (DR5). Furthermore, the HCV replicon enhanced transcription of DR5 via Sp1, and the HCV-mediated up-regulation of DR4 and DR5 required MEK1 activity. HCV infection also stimulated the activity of MEK1, and the inhibition of MEK1 activity or the knockdown of MEK1 increased the replication of HCV. CONCLUSIONS: Our studies demonstrate that HCV replication sensitizes host cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 via a MEK1 dependent pathway. These findings may help to further understand the pathogenesis of HCV infection and provide a therapeutic target