Adsorption and dissociation of ammonia borane outside and inside single-walled carbon nanotubes : A density functional theory study

Amonia borane (AB) has been identified as a potential candidate highcapacity hydrogen storage material. This work probes the adsorption and dissociation of AB inside and outside single-walled carbon nanotubes (SWCNTs) within the framework of density functional theory. The dissociation barriers of AB have been calculated and compared with that of the isolated AB molecule. On the basis of the present calculations, no notable improvement results from SWCNT confinement; on the contrary, the dissociation barrier slightly increases with respect to isolated AB.

A density functional theory study on CO2 capture and activation by graphene-like boron nitride with boron vacancy

First principle calculations for a hexagonal (graphene-like) boron nitride (g-BN) monolayer sheet in the presence of a boron-atom vacancy show promising properties for capture and activation of carbon dioxide. CO2 is found to decompose to produce an oxygen molecule via an intermediate chemisorption state on the defect g-BN sheet. The three stationary states and two transition states in the reaction pathway are confirmed by minimum energy pathway search and frequency analysis. The values computed for the two energy barriers involved in this catalytic reaction after enthalpy correction indicate that the catalytic reaction should proceed readily at room temperature.

The effect of Fe doping on adsorption of CO2/N2within carbon nanotubes : a density functional theory study with dispersion corrections

An ab initio density functional theory (DFT) study with correction for dispersive interactions was performed to study the adsorption of N2 and CO2 inside an (8, 8) single-walled carbon nanotube. We find that the approach of combining DFT and van der Waals correction is very effective for describing the long-range interaction between N2/CO2 and the carbon nanotube (CNT). Surprisingly, exohedral doping of an Fe atom onto the CNT surface will only affect the adsorption energy of the quadrupolar CO2 molecule inside the CNT (20–30%), and not that of molecular N2. Our results suggest the feasibility of enhancement of CO2/N2 separation in CNT-based membranes by using exohedral doping of metal atoms.

First-principle study of adsorption of hydrogen on ti-doped Mg(0001) surface

Ab initio density functional theory (DFT) calculations are performed to study the adsorption of H2 molecules on a Ti-doped Mg(0001) surface. We find that two hydrogen molecules are able to dissociate on top of the Ti atom with very small activation barriers (0.103 and 0.145 eV for the first and second H2 molecules, respectively). Additionally, a molecular adsorption state of H2 above the Ti atom is observed for the first time and is attributed to the polarization of the H2 molecule by the Ti cation. Our results parallel recent findings for H2 adsorption on Ti-doped carbon nanotubes or fullerenes. They provide new insight into the preliminary stages of hydrogen adsorption onto Ti-incorporated Mg surfaces.

The role of Ti as a catalyst for the dissociation of hydrogen on a Mg(0001) surface

In this paper, the dissociative chemisorption of hydrogen on both pure and Ti-incorporated Mg(0001) surfaces are studied by ab initio density functional theory (DFT) calculations. The calculated dissociation barrier of hydrogen molecule on a pure Mg(0001) surface (1.05 eV) is in good agreement with comparable theoretical studies. For the Ti-incorporated Mg(0001) surface, the activated barrier decreases to 0.103 eV due to the strong interaction between the molecular orbital of hydrogen and the d metal state of Ti. This could explain the experimentally observed improvement in absorption kinetics of hydrogen when transition metals have been introduced into the magnesium materials.

Deposition of hydrocarbon molecules on diamond (001) surfaces : atomic scale modeling

The impact induced chemisorption of hydrocarbon molecules (CH3 and CH2) on H-terminated diamond (001)-(2x1) surface was investigated by molecular dynamics simulation using the many-body Brenner potential. The deposition dynamics of the CH3 radical at impact energies of 0.1-50 eV per molecule was studied and the energy threshold for chemisorption was calculated. The impact-induced decomposition of hydrogen atoms and the dimer opening mechanism on the surface was investigated. Furthermore, the probability for dimer opening event induced by chemisorption of CH, was simulated by randomly varying the impact position as well as the orientation of the molecule relative to the surface. Finally, the energetic hydrocarbons were modeled, slowing down one after the other to simulate the initial fabrication of diamond-like carbon (DLC) films. The structure characteristic in synthesized films with different hydrogen flux was studied. Our results indicate that CH3, CH2 and H are highly reactive and important species in diamond growth. Especially, the fraction of C-atoms in the film having sp(3) hybridization will be enhanced in the presence of H atoms, which is in good agreement with experimental observations. (C) 2002 Elsevier Science B.V. All rights reserved.

Nuclear instruments and methods in physics research section B : beam interactions with materials and atoms

The impact-induced deposition of Al13 clusters with icosahedral structure on Ni(0 0 1) surface was studied by molecular dynamics (MD) simulation using Finnis–Sinclair potentials. The incident kinetic energy (Ein) ranged from 0.01 to 30 eV per atom. The structural and dynamical properties of Al clusters on Ni surfaces were found to be strongly dependent on the impact energy. At much lower energy, the Al cluster deposited on the surface as a bulk molecule. However, the original icosahedral structure was transformed to the fcc-like one due to the interaction and the structure mismatch between the Al cluster and Ni surface. With increasing the impinging energy, the cluster was deformed severely when it contacted the substrate, and then broken up due to dense collision cascade. The cluster atoms spread on the surface at last. When the impact energy was higher than 11 eV, the defects, such as Al substitutions and Ni ejections, were observed. The simulation indicated that there exists an optimum energy range, which is suitable for Al epitaxial growth in layer by layer. In addition, at higher impinging energy, the atomic exchange between Al and Ni atoms will be favourable to surface alloying.

Energy dependence of methyl-radical adsorption on diamond (001)-(2×1) surface

The deposition of hyperthermal CH3 on diamond (001)-(2×1) surface at room temperature has been studied by means of molecular dynamics simulation using the many-body hydrocarbon potential. The energy threshold effect has been observed. That is, with fixed collision geometry, chemisorption can occur only when the incident energy of CH3 is above a critical value (Eth). Increasing the incident energy, dissociation of hydrogen atoms from the incident molecule was observed. The chemisorption probability of CH3 as a function of its incident energy was calculated and compared with that of C2H2. We found that below 10 eV, the chemisorption probability of C2H2 is much lower than that of CH3 on the same surface. The interesting thing is that it is even lower than that of CH3 on a hydrogen covered surface at the same impact energy. It indicates that the reactive CH3 molecule is the more important species than C2H2 in diamond synthesis at low energy, which is in good agreement with the experimental observation.

trans-Polyacetylene on sodium and cesium mordenites: a resonance Raman spectroscopic study

Sodium and cesium mordenite (denoted NaM and CsM, respectively) were investigated as potential catalysts for the synthesis of polyacetylene ((CH) x). Both were successful in initiating polymerization of purified gaseous acetylene at room temperature as evidenced by Raman spectroscopic studies. The polyacetylene synthesised in this way exhibited resonance enhancement of the polyene skeletal vibrations. trans-Polyacetylene, but no cis-(CH) x, was detected. As no apparent coloration of the NaM and CsM substrates accompanied the formation of trans-(CH) x it was concluded that only small quantities of the polymer were present. The number of conjugated double bonds was estimated from the frequencies of the Raman active C-C and C=C stretching vibrations, and it was shown that the trans-(CH) x formed on CsM has a distribution of conjugation lengths ranging from less than 6 to at least 30 double bonds. The polyacetylene formed on NaM was significantly shorter and was produced in lower yields than that synthesized on CsM. "Sliced" resonance excitation profiles of polyacetylene formed on CsM were obtained using nearly 40 different excitation wavelengths and these confirmed that the adsorbed trans-(CH) x was composed of segments having a distribution of conjugated lengths. The architecture of the mordenite pore system permitted only a single polymer molecule per channel, thereby preventing cross-linking. Raman spectroscopic studies of the effects of exposure to air revealed that progressive oxidative degradation occurred with a reduction in the number of conjugated double bond

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.

Vibrational spectroscopic study of the uranyl selenite mineral derriksite Cu4UO2(SeO3)2(OH)6⋅H2O

Raman spectrum of the mineral derriksite Cu4UO2(SeO3)2(OH)6⋅H2O was studied and complemented by the infrared spectrum of this mineral. Both spectra were interpreted and partly compared with the spectra of demesmaekerite, marthozite, larisaite, haynesite and piretite. Observed Raman and infrared bands were attributed to the (UO2)2+, (SeO3)2−, (OH)− and H2O vibrations. The presence of symmetrically distinct hydrogen bonded molecule of water of crystallization and hydrogen bonded symmetrically distinct hydroxyl ions was inferred from the spectra in the derriksite unit cell. Approximate U–O bond lengths in uranyl and O–H⋯O hydrogen bond lengths were calculated from the Raman and infrared spectra of derriksite.

Interferon-free therapy for hepatitis C, how prepared is Australia for biosimilars?

The Hepatitis C virus (HCV) affects some 150 million people worldwide. However, unlike hepatitis A and B there is no vaccination for HCV and approximately 75% of people exposed to HCV develop chronic hepatitis. In Australia, around 226,700 people live with chronic HCV infection costing the government approximately $252 million per year. Historically, the standard approved/licenced treatment for HCV is pegylated interferon with ribavirin. There are major drawbacks with interferon-based therapy including side effects, long duration of therapy, limited access and affordability. Our previous survey of an at-risk population reported HCV treatment coverage of only 5%. Since April 2013, a new class of interferon-free treatments for chronic HCV is subsidised under the Pharmaceutical Benefits Scheme: boceprevir and telaprevir - estimated to cost the Australian Government in excess of $220 million over five years. Other biologic interferon-free therapeutic agents are scheduled to enter the Australian market. Use of small molecule generic pharmaceuticals has been advocated as a means of public cost savings. However, with the new biologic agents, generics (biosimilars) may not be feasible or straightforward, due to long patent life; marketing exclusivity; and regulatory complexity for these newer products.

Investigation of an inducible nitric oxide synthase gene (NOS2A) polymorphism in a multiple sclerosis population

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. Nitric oxide (NO) is a biological signaling and effector molecule and is especially important during inflammation. Inducible nitric oxide synthase (iNOS) is one of the three enzymes responsible for generating NO. It has been reported that there is an excessive production of NO in MS concordant with an increased expression of iNOS in MS lesions. This study investigated the role of a bi-allelic tetranucleotide polymorphism located in the promoter region of the human iNOS (NOS2A) gene in MS susceptibility. A group of MS patients (n = 101) were genotyped and compared to an age- and sex-matched group of healthy controls (n = 101). The MS group was subdivided into three subtypes, namely relapsing-remitting MS (RR-MS), secondary-progressive MS (SP-MS) and primary-progressive MS (PP-MS). Results of a chi-squared analysis and a Fisher's exact test revealed that allele and genotype distributions between cases and controls were not significantly different for the total population (chi(2) = 3.4, P(genotype) = 0.15; chi(2) = 3.4, P(allele) = 0.082) and for each subtype of MS (P > 0.05). This suggests that there is no direct association of this iNOS gene variant with MS susceptibility.

Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.