Atomistic Wear Mechanisms in Diamond: Effects of Surface Orientation, Stress, and Interaction with Adsorbed Molecules.

Despite its unrivaled hardness, diamond can be severely worn during the interaction with others, even softer materials. In this work, we calculate from first-principles the energy and forces necessary to induce the atomistic wear of diamond and compare them for different surface orientations and passivation by oxygen, hydrogen, and water fragments. The primary mechanism of wear is identified as the detachment of the carbon chains. This is particularly true for oxidized diamond and diamonds interacting with silica. A very interesting result concerns the role of stress, which reveals that compressive stresses can highly favor wear, making it even energetically favorable.

Adsorption and Dissociation of Ni(acac)2 on Iron by Ab Initio Calculations.

Among metal ß-diketonates, nickel acetylacetonate (Ni(acac)2) has been widely employed as a precursor for many chemical structures, due to its catalytic properties. Here, we investigate, by means of density functional theory (DFT) calculations, the adsorption and dissociation of this complex: after an evaluation of the structural and electronic properties of Ni(acac)2, a comparison between different dissociation patterns reveals that the most favorable pattern for the complex adsorbed on iron is different from the one suggested by considering the strength of the bonds in the isolated complex and an attempt to generalize this dissociation model is made in this work. Moreover, the most favorable adsorption configurations turned out to be a long bridge positioning of the nickel atom along with an on top positioning of the oxygen atoms of Ni(acac)2, while a short bridge positioning is the most favorable for the central metallic unit alone.

Characterization of Molybdenum Dithiocarbamates by First-Principles Calculations.

Molybdenum dithiocarbamate (MoDTC) is a well-known lubricant additive, which, in tribological conditions, is capable of forming layers of MoS2 with excellent friction reduction properties. Despite being widely employed in commercial engine oils, a comprehensive theoretical description of the properties of MoDTC is still lacking. In this work, we employ density functional theory to study the structural, electronic, and vibrational properties of MoDTC. We investigate the relative stability of different isomers, different hydrocarbon terminations, and oxidized complexes. Oxidation was found to be energetically favorable for a wide range of conditions, and the most favorable position for oxygen atoms in MoDTC turned out to be the ligand position. These results, along with the calculated reaction energies for different dissociation paths, can be useful to better identify the elementary steps of the decomposition process of MoDTC.

Interfacial Charge Density and Its Connection to Adhesion and Frictional Forces.

We derive a connection between the intrinsic tribological properties and the electronic properties of a solid interface. In particular, we show that the adhesion and frictional forces are dictated by the electronic charge redistribution occurring due to the relative displacements of the two surfaces in contact. We define a figure of merit to quantify such a charge redistribution and show that simple functional relations hold for a wide series of interactions including metallic, covalent, and physical bonds. This suggests unconventional ways of measuring friction by recording the evolution of the interfacial electronic charge during sliding. Finally, we explain that the key mechanism to reduce adhesive friction is to inhibit the charge flow at the interface and provide examples of this mechanism in common lubricant additives.

Load-induced confinement activates diamond lubrication by water.

Tribochemical reactions are chemical processes, usually involving lubricant or environment molecules, activated at the interface between two solids in relative motion. They are difficult to be monitored in situ, which leaves a gap in the atomistic understanding required for their control. Here we report the real-time atomistic description of the tribochemical reactions occurring at the interface between two diamond films in relative motion, by means of large scale ab initio molecular dynamics. We show that the load-induced confinement is able to catalyze diamond passivation by water dissociative adsorption. Such passivation decreases the energy of the contacting surfaces and increases their electronic repulsion. At sufficiently high coverages, the latter prevents surface sealing, thus lowering friction. Our findings elucidate effects of the nanoscale confinement on reaction kinetics and surface thermodynamics, which are important for the design of new lubricants.

TribChem: A Software for the First-Principles, High-Throughput Study of Solid Interfaces and Their Tribological Properties.

High-throughput first-principles calculations, based on solving the quantum mechanical many-body problem for hundreds of materials in parallel, have been successfully applied to advance many materials-based technologies, from batteries to hydrogen storage. However, this approach has not yet been adopted to systematically study solid-solid interfaces and their tribological properties. To this aim, we developed TribChem, an advanced software program based on the FireWorks platform, which is here presented and released. TribChem is constructed in a modular way, allowing for the separate calculation of bulk, surface, and interface properties. At present, the calculated interfacial properties include adhesion, shear strength, and charge redistribution. Further properties can be easily added due to the general structure of the main workflow. TribChem contains a high-level interface class to store/retrieve results from its own database and connect to public databases.

High-Throughput First-Principles Prediction of Interfacial Adhesion Energies in Metal-on-Metal Contacts.

Adhesion energy, a measure of the strength by which two surfaces bind together, ultimately dictates the mechanical behavior and failure of interfaces. As natural and artificial solid interfaces are ubiquitous, adhesion energy represents a key quantity in a variety of fields ranging from geology to nanotechnology. Because of intrinsic difficulties in the simulation of systems where two different lattices are matched, and despite their importance, no systematic, accurate first-principles determination of heterostructure adhesion energy is available. We have developed robust, automatic high-throughput workflow able to fill this gap by systematically searching for the optimal interface geometry and accurately determining adhesion energies. We apply it here for the first time to perform the screening of around a hundred metallic heterostructures relevant for technological applications. This allows us to populate a database of accurate values, which can be used as input parameters for macroscopic models. Moreover, it allows us to benchmark commonly used, empirical relations that link adhesion energies to the surface energies of its constituent and to improve their predictivity employing only quantities that are easily measurable or computable.

Attractive curves: the role of deformations in adhesion and friction on graphene.

Friction force microscopy measurements reveal a dramatic difference of a factor 3 between the friction forces experienced on single-monolayer graphene on top of oxidized and unoxidized copper substrates. We associate this difference with the strong and weak adhesion that the graphene experiences on these two substrates, respectively, but argue that it is too large to be ascribed either to a difference in contact area or to a difference in contact commensurability or even to a combination of these two effects. We use density functional theory to show a significant increase in the chemical reactivity of graphene when it is curved.

Ab initio calculation of the adhesion and ideal shear strength of planar diamond interfaces with different atomic structure and hydrogen coverage.

We propose a method to calculate the ideal shear strength τ of two surfaces in contact by ab initio calculations. This quantity and the work of adhesion γ are the interfacial parameters usually derived from tip-based friction force measurements. We consider diamond interfaces and quantitatively evaluate the effects of surface orientation and passivation. We find that in the case of fully passivated interfaces, γ is not affected by the orientation and the alignment of the surfaces in contact. On the contrary, τ does show a dependence on the atomic-scale roughness of the interface. The surface termination has a major impact on the tribological properties of diamond. The presence of dangling bonds, even at concentrations low enough to prevent the formation of interfacial C-C bonds, causes an increase in the resistance to sliding by 2 orders of magnitude with respect to the fully hydrogenated case. We discuss our findings in relation to experimental observations.

Development of glyburide fast-dissolving tablets based on the combined use of cyclodextrins and polymers.

Commercial tablets of glyburide exhibit unsatisfactory dissolution profiles and, consequently, problems of bioinequivalence and poor bioavailability. The aim of this work was to develop glyburide fast-dissolving tablets by exploiting the solubilizing effect of different cyclodextrins (CDs), alone or in combination with hydrophilic polymers. Drug-CD and drug-CD-polymer systems, prepared by different techniques, were characterized by differential scanning calorimetry (DSC), X-ray diffractometry, and Fourier transform infra-red (FT-IR) spectroscopy. Tablets containing binary and ternary systems were prepared by direct compression and evaluated for technological properties and dissolution behavior in comparison with a reference formulation containing the plain drug. A significant improvement of the drug dissolution profile was achieved from tablets containing drug-CD systems (coevaporated products doubled drug dissolution efficiency [DE]), but 100% drug dissolution was never reached. Better results were obtained with ternary systems. In particular, polyvinylpyrrolidone (PVP) emerged as the most effective polymer, and tablets with drug-PVP-hydroxypropyl-betaCD coevaporated products showed the best dissolution profiles, reaching 100% dissolved drug within only 15 min.

High-throughput screening of the static friction and ideal cleavage strength of solid interfaces.

We present a comprehensive ab initio, high-throughput study of the frictional and cleavage strengths of interfaces of elemental crystals with different orientations. It is based on the detailed analysis of the adhesion energy as a function of lateral, γ(x, y), and perpendicular displacements, γ(z), with respect to the considered interface plane. We use the large amount of computed data to derive fundamental insight into the relation of the ideal strength of an interface plane with its adhesion. Moreover, the ratio between the frictional and cleavage strengths is provided as good indicator for the material failure mode - dislocation propagation versus crack nucleation. All raw and curated data are made available to be used as input parameters for continuum mechanic models, benchmarks, or further analysis.

Blocking the NGF-TrkA interaction rescues the developmental loss of LTP in the rat visual cortex: role of the cholinergic system.

Although nerve growth factor (NGF) is a crucial factor in the activity-dependent development and plasticity of visual cortex, its role in synaptic efficacy changes is largely undefined. We demonstrate that the maintenance phase of long-term potentiation (LTP) is blocked by local application of exogenous NGF in rat visual cortex at an early stage of postnatal development. Long-term depression (LTD) and bidirectional plasticity are unaffected. At later postnatal ages, blockade of either endogenous NGF by immunoadhesin (TrkA-IgG) or TrkA receptors by monoclonal antibody rescues LTP. Muscarinic receptor activation/inhibition suggests that LTP dependence on NGF is mediated by the cholinergic system. These results indicate that NGF regulates synaptic strength in well-characterized cortical circuitries.

Fascicular nerve stimulation and recording using a novel double-aisle regenerative electrode.

OBJECTIVE: As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. By contrast to extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interfaces with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause impairment to the nerve regeneration. APPROACH: Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically isolated aisles. MAIN RESULTS: We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allow regeneration in nerve gaps of several millimeters without impairment. SIGNIFICANCE: This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses, for the restoration of hand function after amputation or severe nerve injuries.

Activation of the M-CSF gene in mouse macrophages immortalized by retroviruses carrying a v-myc oncogene.

We have recently immortalized murine brain macrophages (microglial cells) with a complex of retroviruses (3RV) transducing separately the myc and mil oncogenes. Surprisingly, the immortalized cells harboured an exogenous v-myc oncogene, but no v-mil sequences. The transformed macrophage cell lines grew in vitro without the addition of exogenous growth factors and were also able to grow in vivo in nude mice. In addition, they released oncogenic retroviruses able to immortalize mouse macrophages from primary splenic or thymic cultures. Molecular cloning of the provirus (VN-11) harboured in a microglial clone demonstrated that no cell-derived sequences apart from an avian v-myc gene were transduced by the recombinant retrovirus. When cells were tested for production of myeloid growth factors, they were found to transcribe and synthesize the Macrophage-Colony Stimulating Factor (M-CSF). The correlation between viral infection and activation of the M-CSF gene was tested using a M-CSF dependent cell line from which growth factor independent clones could be readily obtained after infection. The synthesis of M-CSF was detected only in cells expressing the avian v-myc protein. These data support the hypothesis that, in our conditions, macrophages can be immortalized by the expression of v-myc and the concomitant establishment of an autocrine loop triggered by viral infection.

Generation of new oncogenic murine retroviruses by cotransfection of cloned AKR and MH2 proviruses.

We have obtained a set of oncogenic recombinant retroviruses, the 3RV complex, by cotransfecting murine fibroblasts (SC-1 cells) with plasmids containing the cloned genomes of the avian MH2 and murine AKR viruses. The transfected culture (TAM-2) was shown to release murine transforming viruses by means of reverse transcription and focus formation assays. Analysis of TAM-2 intracellular RNA revealed new transcripts hybridizing with the oncogenes myc and mil and cross-hybridizing with an AKR probe. The biological activity of the 3RV complex was tested for the induction of murine macrophage proliferation in the absence of exogenous growth factors, a property described as the result of mil and myc cooperativity. Cell-free supernatants from 3RV transformed fibroblasts were indeed able to induce the proliferation of macrophage-like cells from murine bone marrow and spleen primary cultures. Such cultures were capable of continuous growth and showed independence from exogenous myeloid growth factors. The cells expressed antigenic markers and functional properties specific of the monocytic-macrophage lineage. These results suggest that transfection-induced recombination could be a novel way to generate biologically active recombinant retroviruses.

Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway.

This study aims to understand the mechanisms of dendritic targeting of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) mRNAs. We show that brief depolarizations are sufficient to induce accumulation of BDNF and TrkB mRNAs in dendrites of hippocampal neurons. Endogenous BDNF, secreted during the KCl stimulation, contributes significantly to the dendritic accumulation of BDNF-TrkB mRNAs. In the absence of depolarization, 1 min pulses of exogenous BDNF are sufficient to induce dendritic accumulation of BDNF-TrkB mRNAs. After binding to TrkB, BDNF exerts this action by activating a PI-3 kinase-dependent pathway. The accumulation of dendritic mRNA by BDNF is not mediated by BDNF-induced neurotransmitter release. Because most hippocampal neurons coexpress BDNF and TrkB receptors, these results show that the subcellular distribution of BDNF-TrkB mRNAs is under the control of an autocrine-paracrine BDNF-TrkB-dependent loop.

Functional blockade of tyrosine kinase A in the rat basal forebrain by a novel antagonistic anti-receptor monoclonal antibody.

We have exploited a new monoclonal antibody against the tyrosine kinase A (TrkA) nerve growth factor (NGF) receptor to block the NGF-TrkA interaction in the rat basal forebrain. The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of NGF to TrkA in a variety of systems. This antibody was used to study the maintenance of the cholinergic phenotype in the rat basal forebrain in vivo, by the implant of antibody-secreting cells. Basal forebrain cholinergic neurons (BFCNs) are greatly affected by the antibody treatment, both in terms of cell number and of cell soma size. When antibody-secreting cells are implanted at postnatal day 2 (P2), the effects observed at P8 are as severe as those obtained with anti-NGF antibodies and, interestingly, are observed also if anti-TrkA cells are implanted at P8, when anti-NGF antibodies, delivered by the same route, are no longer effective (). The effects induced by anti-TrkA, as those induced by anti-NGF, are reversible, but the time required for recovery and the critical period in the sensitivity of BFCNs to the functional inactivation of TrkA is twice as long than that observed when NGF is intercepted. These results demonstrate that BFCNs are more sensitive to the block of TrkA activation than they are to the block of NGF. The cloning of MNAC13 variable regions and their assembly into a functional polypeptide of reduced size (single chain Fv fragment) will allow its use in gene transfer applications.

Extending filamentous phage host range by the grafting of a heterologous receptor binding domain.

fd and IKe are two similar filamentous phage which infect their hosts by means of pili found on the host membrane: fd infects bacteria bearing F pili, whereas IKe infects bacteria bearing N or I pili. Infection is mediated by the gene 3 protein (g3p), which of the nine proteins found in both phage is the most diverse. Previous attempts to incorporate g3p from one phage into the other by complementation have been unsuccessful [Bross et al. (1988) J. Gen. Microbiol. 134, 461-471]. Here we have grafted different parts of IKe g3p to the end of fd g3p and so augmented the host range of fd phage. We show that phage bearing such chimeric g3p are able to infect bacteria bearing both N and F pili providing they contain at least the receptor domain of IKe g3p, the infection of N bearing bacteria occurring at a level 70,000 times greater than background. This level of infection can be increased tenfold by including the glycine-rich domain as well. Addition of the penetration domain does not improve the level of infection above that of the receptor domain alone, indicating that the fd penetration domain is functional in the infection of bacteria bearing either N or F pili. Similarly derived fd phagemid also show increased infection of bacteria bearing N pili, albeit at much lower levels, suggesting that efficient infection requires more than one functional g3p on the surface of the phage.

Targeting vectors for intracellular immunisation.

We define intracellular immunization as the inhibition or inactivation of the function of a molecule by the ectopic intracellular expression of antibody binding domains which recognise the molecule. Such recombinant antibodies can be directed to different compartments of eukaryotic cells by means of previously defined targeting signals, thus permiting the study of any molecule in any cellular compartment for which an antibody is available. For this purpose, we have created a set of vectors based on the VHExpress vector described [Persic, L., Roberts, A., Wilton, J., Cattaneo, A., Bradbury, A. and Hoogenboom, H.R. (1997) An integrated vector system for the eukaryotic expression of antibodies or their fragments after selection from phage display libraries. Gene 187, 000-000], which has been modified to express scFvs (single chain fragments) linked to specific targeting signals. These permit the localisation of scFvs to different intracellular compartments: the endoplasmic reticulum (scFvE-er), the nucleus (scFvE-nuclear), the mitochondria (scFvE-mit), the cytoplasm (scFvE-cyto), and as secreted proteins (scFvE-sec). The function of these vectors has been assessed by the immunofluorescence of COS cells transiently transfected with constructs containing the alphaD11 scFv.

Response to STI571 in chronic myelomonocytic leukemia with platelet derived growth factor beta receptor involvement: a new case report.

Based on its ability to inhibit the tyrosine kinase activity of ABL, as well as the c-kit and the Platelet Derived Growth Factor Receptor tyrosine kinases, the spectrum of diseases that may respond to STI571 is increasing. A recently recognized subgroup of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS) has a t(5;12)(q33;p13) with the activation of the gene for PDGFBR which encodes a receptor tyrosine kinase. Here, we present the case of a patient, with MPD/MDS, and eosinophilia, carrying a translocation t(5;12)(q33;p13) who achieved a complete remission following treatment with STI571, 400 mg daily. At the time of writing he still remains in complete remission with an excellent performance status. There is clearly a need for further studies of STI 571in MPD/MDS with chromosomal translocations involving PDGFBR to confirm this promising initial result.