Broken symmetry and pseudogaps in ropes of carbon nanotubes

We investigate the influence of tube-tube interactions in ropes of (10,10) carbon nanotubes, and find that these effects induce a pseudogap in the density of state (DOS) of the rope of width 0.1 eV at the Fermi level. In an isolated (n,n) carbon nanotube there are two bands that cross in a linear fashion at the Fermi level, making the nanotube metallic with a DOS that is constant in a 1.5 eV wide window around the Fermi energy. The presence of the neighbouring tubes causes these two bands to repel, opening up a band gap that can be as large as 0.3 eV. The small dispersion in the plane perpendicular to the rope smears out this gap for a rope with a large cross-sectional area, and we see a pseudogap at the Fermi energy in the DOS where the DOS falls to one third of its value for the isolated tube. This phenomenon should affect many properties of the behavior of ropes of (n,n) nanotubes, which should display a more semimetallic character than expected in transport and doping experiments, with the existence of both hole and electron carriers leading to qualitatively different thermopower and Hall-effect behaviors from those expected for a normal metal. Band repulsion like this can be expected to occur for any tube perturbed by a sufficiently strong interaction, for example, from contact with a surface or with other tubes.

Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery

This work investigates the polyanion initiated gelation process in fabricating chitosan-TPP (tripolyphosphate) nanoparticles in the size range of 100-250 nm intended to be used as carriers for the delivery of gene or protein macromolecules. It demonstrates that ionic gelation of cationic chitosan molecules offers a flexible and easily controllable process for systematically and predictably manipulating particle size and surface charge which are important properties in determining gene transfection efficacy if the nanoparticles are used as non-viral vectors for gene delivery, or as delivery carriers for protein molecules. Variations in chitosan molecular weight, chitosan concentration, chitosan to TPP weight ratio and solution pH value were examined systematically for their effects on nanoparticle size, intensity of surface charge, and tendency of particle aggregation so as to enable speedy fabrication of chitosan nanoparticles with predetermined properties. The chitosan-TPP nanoparticles exhibited a high positive surface charge across a wide pH range, and the isoelectric point (IEP) of the nanoparticles was found to be at pH 9.0. Detailed imaging analysis of the particle morphology revealed that the nanoparticles possess typical shapes of polyhedrons (e.g., pentagon and hexagon), indicating a similar crystallisation mechanism during the particle formation and growth process. This study demonstrates that systematic design and modulation of the surface charge and particle size of chitosan-TPP nanoparticles can be readily achieved with the right control of critical processing parameters, especially the chitosan to TPP weight ratio. (c) 2005 Elsevier B.V. All rights reserved.

Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen.

Skin-draining LN contain several phenotypically distinguishable DC populations, which may be immature or mature. Mature DC are generally considered to have lost the capacity to acquire and present newly encountered Ag. Using antibody-opsonized liposomes as Ag carriers, we show that mature DC purified from skin explants are able to efficiently capture liposomes, process Ag encapsulated within them and activate Ag-specific CD4(+) T cells. Explant DC from mice with Langerhans cells (LC) expressing the primate diphtheria toxin receptor that were exposed to diphtheria toxin in vivo presented Ag as well as explant DC from wild-type mice, indicating that LC are not required and dermal DC are probably responsible for this presentation. We further show that all DC subtypes from LN that capture opsonized Ag are capable of cross-presenting it to CD8(+) T cells. Induction of additional maturation in vivo by LPS or treatment with double-stranded RNA did not alter the Ag presentation capacity of the skin or LN DC subtypes. These results suggest that mature DC present in skin-draining LN may play an important role in the induction of primary and/or secondary immune responses against Ag delivered to the LN that they take up by receptor-mediated endocytosis.

A new route to synthesize high degree polythiophene in a room temperature melt medium

Conducting polymers suffer from folds and kinks because of random nucleation and solvation of a free radical cation to yield a cross linked/disordered polymer and therefore a solvent free electrochemical polymerization in a room temperature melt medium is adopted to yield a high degree polymer with high electronic conductivity. Electropolymerization of thiophene was performed on platinum/ITO substrates using cyclic voltametry or galvenostatic mode in chloroaluminate room temperature melt medium to obtain a reddish brown free standing film which can be peeled off from the electrode surface after a minimum of 10 cycles. The conductivity was found to be around 102 S/cm. The degree of polymerization was calculated to be around 44 from IR studies. A layered structure supportive for high degree of polymerization was witnessed from potential step technique. From UV spectra the charge carriers were found to be bipolarons. The morphology of the film was found to be crystalline from SEM and XRD studies. Capacitative impedance properties for doped samples were interpreted from impedance spectroscopy.

Chitosan nanoparticle as protein delivery carrier - Systematic examination of fabrication conditions for efficient loading and release

Chitosan nanoparticles fabricated via different preparation protocols have been in recent years widely studied as carriers for therapeutic proteins and genes with varying degree of effectiveness and drawbacks. This work seeks to further explore the polyionic coacervation fabrication process, and associated processing conditions under which protein encapsulation and subsequent release can be systematically and predictably manipulated so as to obtain desired effectiveness. BSA was used as a model protein which was encapsulated by either incorporation or incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan-TPP nanoparticles were characterized for particle size, morphology, zeta potential, BSA encapsulation efficiency, and subsequent release kinetics, which were found predominantly dependent on the factors of chitosan molecular weight, chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio. The BSA loaded nanoparticles prepared under varying conditions were in the size range of 200-580 nm, and exhibit a high positive zeta potential. Detailed sequential time frame TEM imaging of morphological change of the BSA loaded particles showed a swelling and particle degradation process. Initial burst released due to surface protein desorption and diffusion from sublayers did not relate directly to change of particle size and shape, which was eminently apparent only after 6 h. It is also notable that later stage particle degradation and disintegration did not yield a substantial follow-on release, as the remaining protein molecules, with adaptable 3-D conformation, could be tightly bound and entangled with the cationic chitosan chains. In general, this study demonstrated that the polyionic coacervation process for fabricating protein loaded chitosan nanoparticles offers simple preparation conditions and a clear processing window for manipulation of physiochemical properties of the nanoparticles (e.g., size and surface charge), which can be conditioned to exert control over protein encapsulation efficiency and subsequent release profile. The weakness of the chitosan nanoparticle system lies typically with difficulties in controlling initial burst effect in releasing large quantities of protein molecules. (C) 2007 Elsevier B.V. All rights reserved.

Herpes simplex virus type 1 and Alzheimer's disease: the autophagy connection.

The causes of Alzheimer's disease (AD) and of the characteristic pathological features—amyloid plaques and neurofibrillary tangles—of AD brain are unknown, despite the enormous resources provided over the years for their investigation. Indeed, the only generally accepted risk factors are age, Down syndrome, carriage of the type 4 allele of the apolipoprotein E gene (APOE-e 4), and possibly brain injury. Following the authors' previous studies implicating herpes simplex virus type 1 (HSV1) in brain of APOE-e 4 carriers as a major cause of AD, the authors propose here, on the basis of their and others' recent studies, that not only does HSV1 generate the main components of amyloid plaques and neurofibrillary tangles (NFTs)—ß -amyloid (Aß) and abnormally phosphorylated tau but also, by disrupting autophagy, it prevents degradation of these aberrant proteins, leading to their accumulation and deposition, and eventually to AD.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.

AIMS
To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the in?uence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or in?ammatory bowel disease (IBD).
METHODS
Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94?A and IVS2+21A?C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined.
RESULTS
Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients,P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A?C variants among ALL and IBD patients had signi?cantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients,P = 0.047 in IBD patients). The study con?rmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a signi?cant association between inosine triphosphatase IVS2+21A?C variants with thrombocytopenia (P = 0.012).
CONCLUSIONS
Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose
individualization.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

AIMS
The aim of this study was to investigate the in?uence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation.
METHODS
Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular ?ltration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes.
RESULTS
The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls,P = 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%,P = 0.057). Carriers of the G2677->T variant allele also had a signi?cant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P = 0.031). Haplotype analysis showed a signi?cant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P = 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were signi?cantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation.
CONCLUSIONS
These ?ndings suggest that ABCB1 polymorphisms in the native intestine signi?cantly in?uence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the ?rst year posttransplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety

Photosensitiser delivery for photodynamic therapy. Part 2: systemic carrier platforms

Background: The treatment of solid tumours and angiogenic ocular diseases by photodynamic therapy (PDT) requires the injection of a photosensitiser (PS) to destroy target cells through a combination of visible light irradiation and molecular oxygen. There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic PDT. Objective: This article aims to review recent developments in systemic carrier delivery platforms for PDT, with an emphasis on target specificity. Methods: Recent publications, spanning the last five years, concerning delivery carrier platforms for systemic PDT were reviewed, including PS conjugates, dendrimers, micelles, liposomes and nanoparticles. Results/conclusion: PS conjugates and supramolecular delivery platforms can improve PDT selectivity by exploiting cellular and physiological specificities of the targeted tissue. Overexpression of receptors in cancer and angiogenic endothelial cells allows their targeting by affinity-based moieties for the selective uptake of PS conjugates and encapsulating delivery carriers, while the abnormal tumour neovascularisation induces a specific accumulation of heavy weighted PS carriers by enhanced permeability and retention (EPR) effect. in addition, polymeric prodrug delivery platforms triggered by the acidic nature of the tumour environment or the expression of proteases can be designed. Promising results obtained with recent systemic carrier platforms will, in due course, be translated into the clinic for highly efficient and selective PDT protocols.

Newtonian origin of the spin motive force in ferromagnetic atomic wires

We demonstrate numerically the existence of a spin-motive force acting on spin carriers when moving in a time and space dependent internal ?eld. This is the case for electrons in a one-dimensional wire with a precessing domain wall. The effect can be explained solely by adiabatic dynamics and is shown to exist for both classical and quantum systems.

Carrying religion into a secularising Europe: Montserratian migrants' experiences of global processes in British methodism

Migrants to Europe often perceive themselves as entering a secular society that threatens their religious identities and practices. Whilst some sociological models present their responses in terms of cultural defence, ethnographic analysis reveals a more complex picture of interaction with local contexts. This essay draws upon ethnographic research to explore a relatively neglected situation in migration studies, namely the interactions between distinct migration cohorts - in this case, from the Caribbean island of Montserrat, as examined through their experiences in London Methodist churches. It employs the ideas of Weber and Bourdieu to view these migrants as 'religious carriers', as collective and individual embodiments of religious dispositions and of those socio-cultural processes through which their religion is reproduced. Whilst the strategies of the cohort migrating after the Second World War were restricted through their marginalised social status and experience of racism, the recent cohort of evacuees fleeing volcanic eruptions has had greater scope for strategies which combat secularisation and fading Methodist identity.

Efficacy of a standard meticillin-resistant Staphylococcus aureus decolonisation protocol in routine clinical practice

Summary

Decolonisation may reduce the risk of meticillin-resistant Staphylococcus aureus (MRSA) infection in individual carriers and prevent transmission to other patients. The aims of this prospective cohort study were to determine the long-term efficacy of a standardised decolonisation regimen and to identify factors associated with failure. Patients colonised with MRSA underwent decolonisation, which was considered to be successful if there was no growth in three consecutive sets of site-specific screening swabs obtained weekly post treatment. If patients were successfully decolonised, follow-up cultures were performed 6 and 12 months later. Of 137 patients enrolled, 79 (58%) were successfully decolonised. Of these 79, 53 (67%) and 44 (56%) remained decolonised at 6 and 12 months respectively. Therefore only 44/137 (32%) patients who completed decolonisation were MRSA negative 12 months later. Outcome was not associated with a particular strain of MRSA. Successful decolonisation was less likely in patients colonised with a mupirocin-resistant isolate (adjusted odds ratio: 0.08; 95% confidence interval: 0.02–0.30), in patients with throat colonisation (0.22; 0.07–0.68) and in patients aged >80 years (0.30; 0.10–0.93) compared with those aged 60–80 years. These findings suggest that although initially successful in some cases, the protocol used did not result in long-term clearance of MRSA carriage for most patients.

Apolipoprotein epsilon4 and neuropsychological performance in Alzheimer's disease and vascular dementia

The apolipoprotein (APOE) epsilon4 allele is a genetic risk factor for the development of Alzheimer's disease (AD). It has also been associated with vascular dementia (VaD) in some but not all studies. Previous studies have examined the role of APOE in predicting performance on cognitive tests in both demented and non-demented populations. In cognitively intact individuals, statistically significant group differences between APOE epsilon4 carriers and non-carriers have been demonstrated for several cognitive domains. In AD studies of the impact of APOE epsilon4 on cognition have been conflicting while no previous study has assessed cognition and impact of APOE epsilon4 in VaD. In this study we investigated the impact of APOE epsilon4 on performance in neuropsychological tests including information processing speed in patients with mild-moderate AD and VaD. We incorporated both computerized and pen and paper tests to ensure a sensitive method of assessing cognition. 109 patients participated in the study (VaD=41, AD=68). Neurocognitive performance of 44 epsilon4 present AD patients was compared to 24 epsilon4absent patients and performance of 23 epsilon4 present VaD patients was compared to 18 epsilon4 absent patients. There was evidence that APOE epsilon4 conferred a risk of poorer cognitive functioning in both patient groups. In the AD group presence of epsilon4 conferred a negative impact on some measures of speed of information processing and immediate recall while in the VaD group epsilon4 present patients had evidence of poorer accuracy on tasks such as choice reaction time and spatial working memory. In AD and VaD groups epsilon4 present patients showed impairment in selective attention. These findings provide further support of the negative impact of the epsilon4 allele in cognition.

A Population-Based Study of IGF Axis Polymorphisms and the Esophageal Inflammation, Metaplasia, Adenocarcinoma Sequence

BACKGROUND & AIMS: Insulin-like growth factor (IGF) axis plays a key role in cell development, proliferation, and survival and is implicated in the etiology of several cancers. Few studies have examined the relationship between genetic variation of this axis and esophageal adenocarcinoma (EAC) or its precursors. METHODS: In a population-based case-control study, we investigated the association of common polymorphisms of IGF-1, IGF-2, IGF-1 receptor, IGF binding protein -3, growth hormones (GH) 1 and GH2, and GH receptor with reflux esophagitis (RE), Barrett esophagus (BE), and EAC. Two hundred and thirty RE, 224 BE, 227 EAC cases, and 260 controls were studied. Gene polymorphisms were identified using publicly available online resources; 102 IGF axis tag and putatively functional single-nucleotide polymorphisms (SNPs) were analyzed using MassARRAY iPLEX and Taqman assays. Results were analyzed using Haploview.
RESULTS: Three polymorphisms were disease-associated. IGF1 SNP rs6214 was associated with BE (adjusted P = .039). Using GG genotype as reference, odds ratio for BE in AA (wild-type) was 0.43 (95% confidence interval [CI], 0.24-0.75). GH receptor SNP rs6898743 was associated with EAC (adjusted P = .0112). With GG as reference, odds ratio for EAC in CC (wildtype) genotype was 0.42 (95% CI, 0.23-0.76). IGF1 (CA)(17) 185-bp allele was associated with RE (adjusted P = .0116). Using IGF1(non17) as reference, odds ratio for RE in IGF1(17) carriers was 7.29 (95% CI, 1.57-46.7).
CONCLUSIONS: In this study, 3 polymorphisms of IGF genes were associated with EAC or its precursors. These polymorphisms may be markers of disease risk; independent validation of our findings is required. These results suggest the IGF pathway is involved in EAC development.