A parallel algorithm to produce long polymer chains in molecular dynamics.

Generating initial configurations of polymer melts above the entanglement molecular weight is a challenge in molecular dynamics and Monte Carlo simulations. In this work, we adapt an algorithm mimicking a chemical polymerization to all-atom force fields. The principle of this algorithm is to start from a bath of monomers between which bonds are created and relaxed sequentially. Our implementation is parallel and efficient. The parallelization is that of a classical molecular dynamics code and enables the user to generate large systems, up to 7 × 106 atoms. The efficiency of the algorithm comes from the linear scaling between the simulation time and the chain length in the limit of very long chains. The implementation is able to produce long polymer chains, up to ∼2000 carbon atoms, with thermodynamic and local structural properties in good agreement with their experimental and numerical counterparts. Moreover, the chain conformations are close to being equilibrated right after the end of the polymerization process, corresponding to only a few hundred of picoseconds of simulation, despite a systematical drift from Gaussian-like behavior when the density of reactively available monomers decreases. Finally, the algorithm proposed in this work is versatile in nature because the bond creation can be easily modified to create copolymers, block copolymers, and mixtures of polymer melts with other material.

Anisotropic surface stresses of a solid/fluid interface: Molecular dynamics calculations for the copper/methane interface.

The full tensorial surface stress of an interface between a face-centered cubic crystal (copper) and an isotropic liquid (methane) is computed for two crystal orientations {100} and {110} using molecular dynamics simulations. The bulk crystal orientation {100} is symmetric, whereas the {110} orientation is not. Finite size effects, which can be important in the case of an interface between an isotropic solid and a liquid, are studied in detail for the two crystal orientations. We first show that the symmetry of the surface stress tensor is that of the bulk crystal orientation. In the case of the asymmetric crystal orientation {110}, the relative difference between the components of the surface stress is substantial (∼50%). Finally, we show that finite size effects persist to much larger sizes in the case of the {100} orientation compared to the case of the {110} interface, for instance, through an artificial breakdown of the symmetry of the surface stress tensor.

Granularity impact on hotspot formation and local chemistry in shocked nanostructured RDX.

The nanostructuration of energetic materials results in interesting properties. In particular, the detonation of carbon-rich explosives leads to the formation of nanodiamonds, the size of which is linked to the initial size of the explosive nanograins. This correlation could come from the role played by the granularity in the shock properties, especially the local temperature, which could be enhanced when the shock front crosses the various interfaces and nanoporosities of the material. More generally, the granularity-dependent reactivity also concerns some aspects of the sensitivity of energetic materials and subsequent inhibition or safety issues. In order to investigate this hypothesis, we perform classical and reactive molecular dynamics shock-simulations on cyclotrimethylene trinitramine (RDX), a common high-explosive. We design various nanogranular structures using the body-centered-cubic stacking of nanoparticles shaped as Kelvin cells (truncated octahedra) with slightly-bumped faces. The nanograin size and the bump radius allow to independently control the porosity value and its nanostructure. We show that the global shock properties, especially the temperature, are sensitive to the porosity value but not to the nanograin size. The porosity nanostructure has a local impact, enhancing the temperature heterogeneities between the inter- and intra-grain regions by a few hundred degrees and slowing down the thermal homogenization. For a given porosity, the larger the nanograins, the larger and the hotter the hotspots. In such hotspots, the local chemistry is significantly modified, resulting in a larger reactivity with a quicker formation of some final products. We suggest that the quicker consumption of heteroatoms (namely, H, O, and N) along with higher local temperatures is likely to impact the formation process of solid carbonaceous phases.

Dynamic formation of nanodiamond precursors from the decomposition of carbon suboxide (C3O2) under extreme conditions-A ReaxFF study.

We use molecular dynamics simulations with the ReaxFF-lg potential to model the high pressure pyrolysis of carbon suboxide (C3O2) in mixture with argon as a pressure bath. We show that the reactive simulations catch the experimental behavior of the low-pressure detonation of C3O2 (around 10 bars in shock tube experiments) and allow extrapolations to the high-pressure range of solid-state explosive detonation (up to 60 GPa). While at low pressure carbonaceous nanostructures are formed through the aggregation of species such as carbon dimers C2, it appears that the high pressure deeply modifies the process, with the aggregation of growing CxOy heterostructures, in which the oxygen amount is driven by the pressure and the temperature. Pressures in the order of 60 GPa lead to high oxygen ratios, which prevent carbon atoms to get four carbon neighbors (the first condition to get a diamond structure). But a pressure lowering leads to a substantial carbon enrichment through CO2/CO release and facilitates the formation of pure sp3-carbon phases where diamond precursors can form. These results give new insights on the conditions leading to nanodiamonds during the detonation of carbon-rich high explosives.

Impact of surface energy on the shock properties of granular explosives.

This paper presents the first part of a two-fold molecular dynamics study of the impact of the granularity on the shock properties of high explosives. Recent experimental studies show that the granularity can have a substantial impact on the properties of detonation products {i.e., variations in the size distributions of detonation nanodiamonds [V. Pichot et al., Sci. Rep. 3, 2159 (2013)]}. These variations can have two origins: the surface energy, which is a priori enhanced from micro- to nano-scale, and the porosity induced by the granular structure. In this first report, we study the impact of the surface-energy contribution on the inert shock compression of TATB, TNT, α-RDX, and ß-HMX nano-grains (triaminotrinitrobenzene, trinitrotoluene, hexogen and octogen, respectively). We compute the radius-dependent surface energy and combine it with an ab initio-based equation of state in order to obtain the resulting shock properties through the Rankine-Hugoniot relations. We find that the enhancement of the surface energy results in a moderate overheating under shock compression. This contribution is minor with respect to porosity, when compared to a simple macroscopic model. This result motivates further atomistic studies on the impact of nanoporosity networks on the shock properties.

Calculation of a solid/liquid surface tension: A methodological study.

The surface tension of a model solid/liquid interface constituted of a graphene sheet surrounded by liquid methane has been computed using molecular dynamics in the Kirkwood-Buff formalism. We show that contrary to the fluid/fluid case, the solid/liquid case can lead to different structurations of the first fluid layer, leading to significantly different values of surface tension. Therefore we present a statistical approach that consists in running a series of molecular simulations of similar systems with different initial conditions, leading to a distribution of surface tensions from which an average value and uncertainty can be extracted. Our results suggest that these distributions converge as the system size increases. Besides we show that surface tension is not particularly sensitive to the choice of the potential energy cutoff and that long-range corrections can be neglected contrary to what we observed in the liquid/vapour interfaces. We have not observed the previously reported commensurability effect.

Variety enhances food intake in humans: role of sensory-specific satiety.

Twenty-one subjects were studied to evaluate the effect of renewal of sensory stimulations of previously eaten foods on sensory-specific satiety and intake. The subjects ate French fries then brownie cakes ad libitum in three situations: "monotonous" - fries then brownies were consumed alone; "simultaneous" - condiments (ketchup and mayonnaise for the fries, vanilla cream and whipped cream for the brownies) were added during intakes; "successive" - after intake of fries alone, ketchup then mayonnaise were available with fries and, after intake of brownies alone, vanilla cream then whipped cream were offered with brownies. The quantities eaten in the "simultaneous" and "successive" situations were higher (p<0.001) than those in the "monotonous" one (1485+/-582 and 1682+/-777 kcal vs 1195+/-552 kcal, respectively). In the "successive" situation, hedonic ratings for fries diminished during intake but increased after the introduction of ketchup, leading to additional intake of fries. Similarly, hedonic ratings for brownies diminished during intake and increased after the introduction of vanilla cream leading to additional brownie intake (mayonnaise and whipped cream had no significant effect). Food variety, obtained by adding condiments can increase food intake in the short term. The mechanism by which food consumption is increased after the addition of condiments is introduced is at least partly related to the attenuation of sensory-satiety for a given food.

Theoretical study of the nucleation/growth process of carbon clusters under pressure.

We used molecular dynamics and the empirical potential for carbon LCBOPII to simulate the nucleation/growth process of carbon clusters both in vacuum and under pressure. In vacuum, our results show that the growth process is homogeneous and yields mainly sp(2) structures such as fullerenes. We used an argon gas and Lennard-Jones potentials to mimic the high pressures and temperatures reached during the detonation of carbon-rich explosives. We found that these extreme thermodynamic conditions do not affect substantially the topologies of the clusters formed in the process. However, our estimation of the growth rates under pressure are in much better agreement with the values estimated experimentally than our vacuum simulations. The formation of sp(3) carbon was negligible both in vacuum and under pressure which suggests that larger simulation times and cluster sizes are needed to allow the nucleation of nanodiamonds.

Selective sensing of isoprene by Ti-doped ZnO for breath diagnostics.

Exhaled isoprene could enable non-invasive monitoring of cholesterol-lowering therapies. Here, we report an isoprene-selective sensor at high relative humidity (RH) for the first time (to our knowledge). It is made of nanostructured, chemo-resistive Ti-doped ZnO particles (10-20 nm crystal size) produced by flame spray pyrolysis (FSP) and directly deposited in one step onto compact sensor substrates forming highly porous films. The constituent particles consist of stable Ti-doped ZnO solid solutions for Ti levels up to 10 mol% apparently by substitutional incorporation of Ti4+ into the ZnO wurtzite lattice and dominant presence at the particle surface. These Ti4+ point defects strongly enhance the isoprene sensitivity (>15 times higher than pure ZnO) and turn ZnO isoprene-selective, while also improving its thermal stability. In situ infrared spectroscopy confirms that Ti4+ intensifies the surface interaction of Ti-doped ZnO with isoprene by providing additional sites for chemisorbed hydroxyl species. In fact, at an optimal Ti content of 2.5 mol%, this sensor shows superior isoprene responses compared to acetone, NH3 and ethanol at 90% RH. Most notably, breath-relevant isoprene concentrations can be detected accurately down to 5 ppb with high (>10) signal-to-noise ratio. As a result, an inexpensive isoprene detector has been developed that could be easily incorporated into a portable breath analyzer for non-invasive monitoring of metabolic disorders (e.g. cholesterol).

Structural and functional similarities of breadfruit seed lectin and jacalin.

Aquous extracts from seeds of Artocarpus altilis (breadfruit) and Artocarpus heterophyllus (jackfruit) were compared by polyacrylamide gel electrophoresis. Two bands of the same size (12 and 15 kD) as the jacalin subunits were the major components in breadfruit seed extract. They strongly reacted with anti-jacalin antibodies by western blotting. The breadfruit lectin displayed the same IgAl and IgD precipitation specificity as jacalin in gel double diffusion experiments. It also stimulated in vitro proliferation of human peripheral blood mononuclear cells. These results suggest that lectins from both species of Artocarpus are very similar.

Stimulation of peripheral blood lymphocytes of HIV-infected patients by jacalin, a lectin mitogenic for human CD4+ lymphocytes.

The proliferative response of peripheral blood mononuclear cells stimulated by jacalin was investigated in 157 samples from 104 HIV-infected patients at various clinical stages of disease. Jacalin proliferative response correlated with the absolute numbers and percentages of CD4+ lymphocytes and with the percentages of Leu 8 lymphocytes. It correlated negatively with the percentages of CD8+ and CD38+ lymphocytes. It was depressed during acute HIV infection and at advanced stages. The response in Centers for Disease Control groups II and III was heterogeneous and similar; in both, some patients showed a very low response. Further follow-up of the present patients should indicate whether jacalin responsiveness has a prognostic value.

Jacalin, the human IgA1 and IgD precipitating lectin, also binds IgA2 of both allotypes.

The lectin jacalin from jackfruit seeds shows a human IgA-subclass specificity by gel precipitation and Western blotting. However, its reactivity with IgA2 is a matter of controversy. We further studied the immunoglobulin isotype specificity of jacalin by affinity chromatography with myeloma sera and by inhibition of jacalin binding to solid-phase IgA1 by purified monoclonal immunoglobulins. The lectin proved to bind IgA2 of both allotypes with a lower apparent affinity than for IgA1 and IgD.

The polypeptide PHI discriminates a GTP-insensitive form of VIP receptor in liver membranes.

In early reports on 125I-VIP binding experiments in liver membranes, it has been proposed that, the VIP binding sites were partially sensitive to GTP. Here we confirm that the VIP binding sites of chicken liver membranes consisted mainly in bivalent VIP/PACAP receptors and that about 50% of the 125I-VIP binding capacity was not affected by the GTP analogue GppNHp. Part of these bivalent receptors also appeared to represent PHI binding sites. In GppNHp-treated membranes, the GTP-insensitive VIP binding sites displayed a 17-fold higher relative affinity than in control membranes for the VIP analogue PHI. Such data suggested that GTP-insensitive VIP receptors may correspond to a subclass of high-affinity PHI receptors. Cross-linking of 125 I-VIP or 125 I-PHI to their receptors, revealed 2 components of 48 and 60 kDa. The radiolabelling of the 60 kDa component was strongly affected by increasing concentrations of the GTP analogue but was modestly abolished by an excess of PHI. Conversely, the radiolabelling of the 48 kDa molecular form was not affected by the GTP analogue but was efficiently abolished by increasing concentrations of PHI. Taken together, the data suggest that the 48 kDa component expressed in chicken liver membranes display the properties of a GTP-insensitive VIP/PHI receptor that can be pharmacologically discriminated from the GTP-sensitive 60 kDa form, through its much higher affinity for PHI.

The small G-proteins Rap 1 as potential targets of vasoactive intestinal peptide effects in the human clonic cancer cells HT29.

We recently reported that the vasoactive intestinal peptide (VIP) potently inhibited proliferation and induced in parallel a strong cAMP rise, in the human colonic cancer cell line HT29. In this study, we investigated whether Rap 1 proteins could be potential targets of VIP effects in HT29 cells. These Ras-related proteins in which activity was demonstrated to be regulated by PKA phosphorylation, are considered as potential modulators of the Ras / Raf / MAP kinases cascade that governs cell growth control. Our data revealed that the Rap 1a isoform is highly expressed in HT29 cells and mainly localized in a late endosomal compartment. In these cells, VIP induces Rap 1 phosphorylation and a yet unidentified modification that leads to their acidification. This latter Rap 1 acidification seems to be, at least partially, cAMP-dependent. It is concluded that in HT29 cells, Rap 1 proteins may be part of a VIP-induced signaling cascade.

Pentylenetetrazol seizures induce cell suffering but not death in the immature rat brain.

To investigate whether long-term functional consequences of status epilepticus (SE) induced by pentylenetetrazol in 10-day-old rats correlated with cell injury and/or death, acid fuchsin and TUNEL staining were performed between 4 to 144 h after SE. Acid fuchsin stained hippocampus, amygdala and cerebral cortex at 24 h but not at 72 and 144 h. No DNA fragmentation was apparent at any time. Thus, immature neurons subjected to sustained seizures suffer transiently but survive probably by activating repair processes.

PD135158, a CCK-B antagonist, reduces "state," but not "trait" anxiety in mice.

It has recently been proposed that Balb/c neophobic responses in a free exploratory paradigm are related to "trait" anxiety, while the behavior of mice in the light/dark choice test paradigm is related to "state" anxiety. The purpose of this study was to assess the action of the CCK-B receptor antagonist PD135158 in both models. Results show that PD135158 was effective in the light/dark choice test but not on the Balb/c neophobic reactions in the free exploratory situation. It is suggested that PD135158 is specially effective in state anxiety induced by fear provoking situations.

Local lymph node assay: study of the in vitro proliferation and control of the specificity of the response by FACScan analysis.

The murine local lymph node assay (LLNA) has been proposed as a screening procedure to identify contact allergens (Kimber, Hilton and Weisenberger, Contact Dermatitis 1989, 21, 215; Kimber and Weisenberger, Archives of Toxicology 1989, 63, 274). In some cases irritants have given rise to proliferative responses and it is of interest to investigate whether these responses differ in the type of cells involved. We have studied the proliferative response in vitro to topically applied sodium lauryl sulphate (SLS) and 2,4-dinitrochlorobenzene (DNCB). The test chemical or vehicle alone was applied for 3 consecutive days to the dorsum of both ears of Balb/c strain mice at three different concentrations, the highest concentration being the maximum non-irritating concentration (MNIC). Cell cultures were made 72 hr after the final exposure: draining auricular lymph nodes were excised and a suspension of lymph node cells (LNC) was prepared. Cellularity (total number of LNC/animal) and proliferative activity were assessed; proliferation was measured by culture of LNC for 24 hr with [(3)H]thymidine. LNC were also studied by FACScan analysis: cells were incubated with fluorescein isothiocyanate (FITC)-labelled monoclonal antibodies against the T-cell marker CD3 and the activated T-cell marker CD25 (IL2 receptor). In the case of DNCB dose-response curves were obtained for both cellularity and proliferative response in comparison with the controls: there was a strong increase in both parameters for the MNIC.SLS, a non-sensitizing skin irritant, induced a much lower response, slightly increased at the MNIC in comparison with the controls. By FACScan analysis we measured the rates of CD3- and CD25-positive cells in the LNC. No significant difference was obtained for SLS in comparison with the controls. In the case of DNCB, there was a significant increase in CD3-positive cells and a large increase in CD25-positive cells in comparison with the controls and SLS. These parameters could be of great interest to help distinguish between contact sensitizers and irritants. We are presently investigating other irritants and sensitizers.

Activation of tongue-expressed GPR40 and GPR120 by non caloric agonists is not sufficient to drive preference in mice.

There is mounting evidence that, in addition to texture and olfaction, taste plays a role in the detection of long chain fatty acids. Triglycerides, the main components of oils and dietary fat, are hydrolyzed in the mouth by a lingual lipase secreted from the von Ebner gland and the released free fatty acids are detected by the taste system. GPR40 and GPR120, two fatty acid responsive G-protein-coupled receptors (GPCRs), are expressed in taste bud cells, and knockout mice lacking either of those receptors have blunted taste nerve responses to and reduced preference for fatty acids. Here we investigated whether activation of those GPCRs is sufficient to elicit fat taste and preference. Five non-fatty acid agonists of GPR40 and two non-fatty acid agonists of GPR120 activated the glossopharyngeal nerve of wild-type mice but not of knockout mice lacking the cognate receptor. In human subjects, two-alternative forced choice (2-AFC) tests, triangle tests and sensory profiling showed that non fatty acid agonists of GPR40 dissolved in water are detected in sip and spit tests and elicit a taste similar to that of linoleic acid, whereas 2-AFC tests showed that two agonists of GPR120 in water are not perceived fattier than water alone. Wild-type mice did not show any preference for five agonists of GPR40, two agonists of GPR120 and mixtures of both agonists over water in two-bottle preference tests. Together these data indicate that GPR40 mediated taste perception is not sufficient to generate preference.

Impact of crema on the aroma release and the in-mouth sensory perception of espresso coffee.

A set of six espresso coffees with different foam characteristics and similar above cup and in-mouth flavour sensory profiles was produced by combination of two varying parameters, the extraction pressure and the filtration of the coffee beverage. The coffees were subsequently evaluated in a comparative manner by a set of analytical (headspace, nose-space) and sensory (Temporal Dominance of Sensations) techniques. The presence of espresso crema in its standard quantity was demonstrated to be associated with the optimum release of pleasant high volatiles, both in the above cup headspace and in-mouth. On the other hand, the TDS study demonstrated that increasing amount of crema was associated with increasing roasted dominance along coffee consumption. Furthermore, a parallel was established between the roasted sensory dominance and the dominant release of 2-methylfuran in the nose-space. This was, however, an indirect link as 2-methylfuran was indeed a chemical marker of roasting but does not contribute to the roasted aroma. Lowering the standard amount of crema by filtration clearly decreased the release of pleasant high volatiles and the in-mouth roasted sensory dominance. On the other hand, increasing the usual crema volume by increasing the extraction pressure did not bring any added value concerning the above cup and in-mouth release of pleasant high volatiles.

Physical and related sensory properties of a swallowable bolus.

Rheology and water content properties of cereal boluses collected just before swallowing were investigated. No specific physical markers for swallowing were found between subjects. Each subject had his own mastication strategy leading to food boluses with different rheological and water content properties. However, for most of the subjects, similar physical properties were found for food boluses obtained from consumption of different cereals. Results showed that the food boluses from different cereals exhibited gel-like properties being in a range from 14.1 kPa to 21.2 kPa (G'(1 Hz, 0.4%)), when swallowed. The food boluses had a static yield stress varying from 1.3 kPa to 4.3 kPa. Another interesting finding was that the water content of food boluses might be an important marker for swallowing since it was similar for different cereal food boluses (around 50%). This physical property might drive the fluid sensory perception, which could also be a sensory swallowing threshold.