Evolution of a designless nanoparticle network into reconfigurable Boolean logic.

Natural computers exploit the emergent properties and massive parallelism of interconnected networks of locally active components. Evolution has resulted in systems that compute quickly and that use energy efficiently, utilizing whatever physical properties are exploitable. Man-made computers, on the other hand, are based on circuits of functional units that follow given design rules. Hence, potentially exploitable physical processes, such as capacitive crosstalk, to solve a problem are left out. Until now, designless nanoscale networks of inanimate matter that exhibit robust computational functionality had not been realized. Here we artificially evolve the electrical properties of a disordered nanomaterials system (by optimizing the values of control voltages using a genetic algorithm) to perform computational tasks reconfigurably. We exploit the rich behaviour that emerges from interconnected metal nanoparticles, which act as strongly nonlinear single-electron transistors, and find that this nanoscale architecture can be configured in situ into any Boolean logic gate. This universal, reconfigurable gate would require about ten transistors in a conventional circuit. Our system meets the criteria for the physical realization of (cellular) neural networks: universality (arbitrary Boolean functions), compactness, robustness and evolvability, which implies scalability to perform more advanced tasks. Our evolutionary approach works around device-to-device variations and the accompanying uncertainties in performance. Moreover, it bears a great potential for more energy-efficient computation, and for solving problems that are very hard to tackle in conventional architectures.

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties.

The caspase inhibitors, benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) and benzyloxycarbonyl (Cbz)-Ile-Glu (OMe)-Thr-Asp (OMe)-FMK (z-IETD-FMK) at non-toxic doses were found to be immunosuppressive and inhibit human T cell proliferation induced by mitogens and IL-2 in vitro. Both caspase inhibitors were shown to block NF-κB in activated primary T cells, but have little inhibitory effect on the secretion of IL-2 and IFN-γ during T cell activation. However, the expression of IL-2 receptor α-chain (CD25) in activated T cells was inhibited by both z-VAD-FMK and z-IETD-FMK, whereas the expression of the early activated T cell marker, CD69 was unaffected. During primary T cell activation via the antigen receptor, both caspase-8 and caspase-3 were activated and processed to their respective subunits, but neither caspase inhibitors had any effect on the processing of these two caspases. In sharp contrast both caspase inhibitors readily blocked apoptosis and the activation of caspases during FasL-induced apoptosis in activated primary T cells and Jurkat T cells. Collectively, the results demonstrate that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3.

Hydrogen bond lifetimes and clustering of methanol in carbon tetrachloride solutions.

NMR experiments and ab initio calculations suggest that methanol forms small cyclic hydrogen bond clusters (4-6 molecules) in the condensed phase. In contrast, molecular dynamics simulations have indicated that methanol will form large branched chains that extend to include hundreds of molecules. In this paper, we performed a series of simulations examining the structure and dynamics of methanol/carbon tetrachloride mixtures. We show that two simulation models are capable of reproducing the trends in the experimental NMR data despite the fact that they indicate that the structure of the liquid is dominated by large branched chains. We hypothesize that the experimental results can be described by variations in the hydrogen bond lifetime with methanol concentration.

Molecular dynamics simulations of water transport through butanol films.

It is well-known that well-formed monolayers of long-chain alcohols on water dramatically reduce the rate of water evaporation. Recent experiments, however, have shown that the short-chain surfactant butanol has a negligible effect on the rate of water evaporation from a solution of supercooled sulfuric acid. We used molecular dynamics simulations to examine the condensation of water through a layer of butanol coating water. From those simulations, we observed a reduction in the rate of water condensation by a factor of 3 which would imply a similar reduction in the rate of evaporation. It was observed that a vapor molecule would condense only if it formed a long-lived hydrogen bond with another molecule and that there was no dependence on the initial velocity of the vapor molecule. The ability of the surfactant to participate in hydrogen bonding was found to facilitate the condensation of water into the bulk.

Vibrational spectral diffusion of azide in water.

Vibrational spectral diffusion denotes the time-dependent fluctuations of a solute's vibrational frequencies due to local environmental dynamics. Vibrational line shapes are weakly sensitive to spectral diffusion, whereas three-pulse vibrational echoes are much more sensitive. We report here on theoretical studies of spectral diffusion of the asymmetric stretch of the azide anion in heavy water. We run a classical molecular dynamics simulation of rigid azide in rigid water, and at every time step we calculate the azide's anharmonic asymmetric stretch frequency using an optimized quantum mechanics/molecular mechanics method developed earlier. This generates a frequency trajectory, which we use to calculate the absorption line shape and integrated three-pulse echo intensity. Our results for both the line width and the integrated echo intensity are in excellent agreement with experiment. Our calculated frequency time-correlation function is in excellent agreement with experiment for long times (greater than 250 fs) but differs considerably from experiment at short times; our theoretical correlation function has a very pronounced oscillation, presumably due to intermolecular azide-water hydrogen-bond stretching dynamics.

Approaches for the calculation of vibrational frequencies in liquids: comparison to benchmarks for azide/water clusters.

Ultrafast vibrational spectroscopy experiments, together with molecular-level theoretical interpretation, can provide important information about the structure and dynamics of complex condensed phase systems, including liquids. The theoretical challenge is to calculate the instantaneous vibrational frequencies of a molecule in contact with a molecular environment, accurately and quickly, and to this end a number of different methods have been developed. In this paper we critically analyze these different methods by comparing their results to accurate benchmark calculations on azide/water clusters. We also propose an optimized quantum mechanics/molecular mechanics method, which for this problem is superior to the other methods.

FADD deficiency sensitises Jurkat T cells to TNF-alpha-dependent necrosis during activation-induced cell death.

Activation-induced cell death (AICD) in activated T lymphocytes is largely mediated by Fas/Fas ligand (FasL) interaction. The cytoplasmic adaptor molecule Fas-associated death domain protein (FADD) plays an essential role in the apoptotic signalling of the Fas death pathway. In the present study, we observed that FADD deficient (FADD(-/-)) Jurkat T cells undergo AICD to a similar extent as wild-type cells. AICD in wild-type Jurkat T cells is via apoptosis, whereas it is non-apoptotic in FADD(-/-) cells. The latter took up propidium iodide, exhibit a loss in mitochondrial membrane potential and have no detectable cleavage products of caspase-8 or -3 activation, suggesting that these cells die by necrosis. Wild-type Jurkat T cells undergo apoptosis when incubated with recombinant FasL and Trail but not with TNF-alpha. In contrast, FADD(-/-) Jurkat T cells are resistant to FasL and Trail but die of necrosis when incubated with TNF-alpha. We showed that neutralising anti-TNF-alpha blocked AICD as well as TNF-alpha-induced necrosis in FADD(-/-) Jurkat T cells. Furthermore, down regulating the receptor interacting protein, RIP, with geldanamycin treatment, which is essential for TNF-alpha signalling, markedly inhibited AICD in FADD(-/-) Jurkat T cells. In addition, caspase-8-deficient Jurkat T cells are resistant to Fas- and TNF-alpha-induced cell death. Taken together, our results suggest that a deficiency in FADD and not caspase-8 or the inhibition of the Fas signalling pathway sensitises Jurkat T cells to TNF-alpha-dependent necrosis during AICD.

Quantum corrections in vibrational and electronic condensed phase spectroscopy: line shapes and echoes.

Various linear and nonlinear vibrational and electronic spectroscopy experiments in liquids are usually analyzed within the second-cumulant approximation, and therefore the fundamental quantity of interest is the equilibrium time-correlation function of the fluctuating transition frequency. In the usual approach the "bath" variables responsible for the fluctuating frequency are treated classically, leading to a classical time-correlation function. Alternatively, sometimes a quantum correction appropriate for relatively high temperatures is included, which adds an imaginary part to the classical time-correlation function. This approach, although appealing, does not satisfy detailed balance. One can consider a similar correction, but where detailed balance is satisfied, by using the harmonic quantum correction factor. In this article, we compare these approaches for a model system and two realistic examples. Our conclusion is that for linear spectroscopy the classical result is usually adequate, whereas for nonlinear spectroscopy it can be more important to include quantum corrections.

A mode-coupling theory of vibrational line broadening in near-critical fluids.

We present a fully microscopic mode-coupling theory of near-critical line broadening. All the structural and dynamical input required by the theory is calculated directly from intermolecular potentials. We compute vibrational frequency time-correlation functions and line shapes as the critical point is approached along both the critical isochore and the liquid-gas coexistence curve. Theory is shown to be in good agreement with simulation.

Dynamics of water probed with vibrational echo correlation spectroscopy.

Vibrational echo correlation spectroscopy experiments on the OD stretch of dilute HOD in H(2)O are used to probe the structural dynamics of water. A method is demonstrated for combining correlation spectra taken with different infrared pulse bandwidths (pulse durations), making it possible to use data collected from many experiments in which the laser pulse properties are not identical. Accurate measurements of the OD stretch anharmonicity (162 cm(-1)) are presented and used in the data analysis. In addition, the recent accurate determination of the OD vibrational lifetime (1.45 ps) and the time scale for the production of vibrational relaxation induced broken hydrogen bond "photoproducts" ( approximately 2 ps) aid in the data analysis. The data are analyzed using time dependent diagrammatic perturbation theory to obtain the frequency time correlation function (FTCF). The results are an improved FTCF compared to that obtained previously with vibrational echo correlation spectroscopy. The experimental data and the experimentally determined FTCF are compared to calculations that employ a polarizable water model (SPC-FQ) to calculate the FTCF. The SPC-FQ derived FTCF is much closer to the experimental results than previously tested nonpolarizable water models which are also presented for comparison.

Spectral diffusion in a fluctuating charge model of water.

We apply the combined electronic structure/molecular dynamics approach of Corcelli, Lawrence, and Skinner [J. Chem. Phys. 120, 8107 (2004)] to the fluctuating charge (SPC-FQ) model of liquid water developed by Rick, Stuart, and Berne [J. Chem. Phys. 101, 6141 (1994)]. For HOD in H(2)O the time scale for the long-time decay of the OD stretch frequency time-correlation function, which corresponds to the time scale for hydrogen-bond rearrangement in the liquid, is about 1.5 ps. This result is significantly longer than the 0.9 ps decay previously calculated for the nonpolarizable SPC/E water model. Our results for the SPC-FQ model are in better agreement with recent vibrational echo experiments.

Combined electronic structure/molecular dynamics approach for ultrafast infrared spectroscopy of dilute HOD in liquid H2O and D2O.

We present a new approach that combines electronic structure methods and molecular dynamics simulations to investigate the infrared spectroscopy of condensed phase systems. This approach is applied to the OH stretch band of dilute HOD in liquid D2O and the OD stretch band of dilute HOD in liquid H2O for two commonly employed models of water, TIP4P and SPC/E. Ab initio OH and OD anharmonic transition frequencies are calculated for 100 HOD x (D2O)n and HOD x(H2O)n (n = 4-9) clusters randomly selected from liquid water simulations. A linear empirical relationship between the ab initio frequencies and the component of the electric field from the solvent along the bond of interest is developed. This relationship is used in a molecular dynamics simulation to compute frequency fluctuation time-correlation functions and infrared absorption line shapes. The normalized frequency fluctuation time-correlation functions are in good agreement with the results of previous theoretical approaches. Their long-time decay times are 0.5 ps for the TIP4P model and 0.9 ps for the SPC/E model, both of which appear to be somewhat too fast compared to recent experiments. The calculated line shapes are in good agreement with experiment, and improve upon the results of previous theoretical approaches. The methods presented are simple, and transferable to more complicated systems.

On the mode-coupling theory of vibrational line broadening in near-critical fluids.

Molecular-dynamics simulations of a neat atomic fluid, coupled with a simple model for vibrational frequency perturbations, are used to investigate vibrational line broadening near the liquid-gas critical point. All features of our simulations are in qualitative agreement with recent Raman experiments on nitrogen. We also use our simulation results to assess the validity of the mode-coupling theories that have been used to analyze experiment. We find that the theoretical results are not in good agreement with simulation, both for the temperature dependence of the linewidth, and for the frequency time-correlation functions. However, the mode-coupling prediction that critical line broadening is due to the diverging correlation time of the frequency fluctuations is shown to be correct.

Quantum dynamics in simple fluids.

We use quantum-correction factors to calculate approximately the quantum velocity time-correlation function (TCF) of supercritical Lennard-Jones argon from the classical TCF. We find that for this quite classical system, several different quantum-correction schemes yield essentially identical results for the real and imaginary parts of the quantum TCF, and also agree well with the recent forward-backward semiclassical dynamics (FBSD) results of Wright and Makri [J. Chem. Phys. 119, 1634 (2003)]. We also consider a more quantum-mechanical fluid of lighter atoms (neon) at a lower temperature. In this case different quantum-correction schemes give different results. FBSD calculations show that the harmonic quantum correction factor works the best for this system