An extensible density-biasing approach for molecular simulations of multicomponent block copolymers.

A node-density biased Monte Carlo methodology is proposed for the molecular structure generation of complex block copolymers. Within this methodology, the block copolymer is represented as bead-spring model. Using self-consistent field theory, a density field for all monomer species within the system is calculated. Block copolymers are generated by random walk configuration biased by the density fields. The proposed algorithm then modifies the generation process by taking the global structure of the polymer into account. It is then demonstrated that these global considerations can be built into the sampling procedure, specifically through functions that assign a permissible difference in density field value between relevant monomer species to each step of the random walk. In this way, the random walk may be naturally controlled to provide the most appropriate conformations. The overall viability of this approach has been demonstrated by using the resulting configurations in molecular dynamics simulations. This new methodology is demonstrated to be powerful enough to generate molecular configurations for a much wider variety of materials than the original approach. Two key examples of the new capabilities of the method are viable configurations for ABABA pentablock copolymers and ABC triblock terpolymers.

Enhancement of island size by dynamic substrate disorder in simulations of graphene growth.

We demonstrate a new mechanism in the early stages of sub-monolayer epitaxial island growth, using Monte Carlo simulations motivated by experimental observations on the growth of graphene on copper foil. In our model, the substrate is "dynamically rough", by which we mean (i) the interaction strength between Cu and C varies randomly from site to site, and (ii) these variable strengths themselves migrate from site to site. The dynamic roughness provides a simple representation of the near-molten state of the Cu substrate in the case of real graphene growth. Counterintuitively, the graphene island size increases when dynamic roughness is included, compared to a static and smooth substrate. We attribute this effect to destabilisation of small graphene islands by fluctuations in the substrate, allowing them to break up and join larger islands which are more stable against roughness. In the case of static roughness, when process (ii) is switched off, island growth is strongly inhibited and the scale-free behaviour of island size distributions, present in the smooth-static and rough-dynamic cases, is destroyed. The effects of the dynamic substrate roughness cannot be mimicked by parameter changes in the static cases.

Probing Potential Energy Surface Exploration Strategies for Complex Systems.

The efficiency of minimum-energy configuration searching algorithms is closely linked to the energy landscape structure of complex systems, yet these algorithms often include a number of steps of which the effect is not always clear. Decoupling these steps and their impacts can allow us to better understand both their role and the nature of complex energy landscape. Here, we consider a family of minimum-energy algorithms based, directly or indirectly, on the well-known Bell-Evans-Polanyi (BEP) principle. Comparing trajectories generated with BEP-based algorithms to kinetically correct off-lattice kinetic Monte Carlo schemes allow us to confirm that the BEP principle does not hold for complex systems since forward and reverse energy barriers are completely uncorrelated. As would be expected, following the lowest available energy barrier leads to rapid trapping. This is why BEP-based methods require also a direct handling of visited basins or barriers. Comparing the efficiency of these methods with a thermodynamical handling of low-energy barriers, we show that most of the efficiency of the BEP-like methods lie first and foremost in the basin management rather than in the BEP-like step.

Automated effective band structures for defective and mismatched supercells.

In plane-wave density functional theory codes, defects and incommensurate structures are usually represented in supercells. However, interpretation of E versus k band structures is most effective within the primitive cell, where comparison to ideal structures and spectroscopy experiments are most natural. Popescu and Zunger recently described a method to derive effective band structures (EBS) from supercell calculations in the context of random alloys. In this paper, we present bs_sc2pc, an implementation of this method in the CASTEP code, which generates an EBS using the structural data of the supercell and the underlying primitive cell with symmetry considerations handled automatically. We demonstrate the functionality of our implementation in three test cases illustrating the efficacy of this scheme for capturing the effect of vacancies, substitutions and lattice mismatch on effective primitive cell band structures.

Replenish and relax: explaining logarithmic annealing in ion-implanted c-Si.

We study ion-damaged crystalline silicon by combining nanocalorimetric experiments with an off-lattice kinetic Monte Carlo simulation to identify the atomistic mechanisms responsible for the structural relaxation over long time scales. We relate the logarithmic relaxation, observed in a number of disordered systems, with heat-release measurements. The microscopic mechanism associated with this logarithmic relaxation can be described as a two-step replenish and relax process. As the system relaxes, it reaches deeper energy states with logarithmically growing barriers that need to be unlocked to replenish the heat-releasing events leading to lower-energy configurations.

Influence of polarizability on metal oxide properties studied by molecular dynamics simulations.

We have studied the dependence of metal oxide properties in molecular dynamics (MD) simulations on the polarizability of oxygen ions. We present studies of both liquid and crystalline structures of silica (SiO(2)), magnesia (MgO) and alumina (Al(2)O(3)). For each of the three oxides, two separately optimized sets of force fields were used: (i) long-range Coulomb interactions between oxide and metal ions combined with a short-range pair potential; (ii) extension of force field (i) by adding polarizability to the oxygen ions. We show that while an effective potential of type (i) without polarizable oxygen ions can describe radial distributions and lattice constants reasonably well, potentials of type (ii) are required to obtain correct values for bond angles and the equation of state. The importance of polarizability for metal oxide properties decreases with increasing temperature.

Ab initio based polarizable force field generation and application to liquid silica and magnesia.

We extend the program potfit, which generates effective atomic interaction potentials from ab initio data, to electrostatic interactions and induced dipoles. The potential parametrization algorithm uses the Wolf direct, pairwise summation method with spherical truncation. The polarizability of oxygen atoms is modeled with the Tangney-Scandolo interatomic force field approach. Due to the Wolf summation, the computational effort in simulation scales linearly in the number of particles, despite the presence of electrostatic interactions. Thus, this model allows to perform large-scale molecular dynamics simulations of metal oxides with realistic potentials. Details of the implementation are given, and the generation of potentials for SiO(2) and MgO is demonstrated. The approach is validated by simulations of microstructural, thermodynamic, and vibrational properties of liquid silica and magnesia.

Kinetic activation-relaxation technique.

We present a detailed description of the kinetic activation-relaxation technique (k-ART), an off-lattice, self-learning kinetic Monte Carlo (KMC) algorithm with on-the-fly event search. Combining a topological classification for local environments and event generation with ART nouveau, an efficient unbiased sampling method for finding transition states, k-ART can be applied to complex materials with atoms in off-lattice positions or with elastic deformations that cannot be handled with standard KMC approaches. In addition to presenting the various elements of the algorithm, we demonstrate the general character of k-ART by applying the algorithm to three challenging systems: self-defect annihilation in c-Si (crystalline silicon), self-interstitial diffusion in Fe, and structural relaxation in a-Si (amorphous silicon).

Direct Wolf summation of a polarizable force field for silica.

We extend the Wolf direct, pairwise r(-1) summation method with spherical truncation to dipolar interactions in silica. The Tangney-Scandolo interatomic force field for silica takes regard of polarizable oxygen atoms whose dipole moments are determined by iteration to a self-consistent solution. With Wolf summation, the computational effort scales linearly in the system size and can easily be distributed among many processors, thus making large-scale simulations of dipoles possible. The details of the implementation are explained. The approach is validated by estimations of the error term and simulations of microstructural and thermodynamic properties of silica.

Olmesartan medoxomil plus amlodipine increases efficacy in patients with moderate-to-severe hypertension after monotherapy: a randomized, double-blind, parallel-group, multicentre study.

BACKGROUND AND OBJECTIVE: Hypertension remains a major global health problem, and evidence suggests that the majority of patients will require two or more antihypertensive agents in order to reach specified BP targets. Combining two drugs from different classes has the potential to target different aspects of hypertension, which may result in additional BP decreases compared with either agent used alone. This randomized, double-blind, parallel-group, multicentre trial in patients with moderate-to-severe hypertension (systolic BP [SBP]/diastolic BP [DBP] > or =160/100 mmHg) investigated the additional efficacy in BP reduction and BP goal rates (<140/90 mmHg for patients without diabetes mellitus, <130/80 mmHg for patients with diabetes) achieved by adding amlodipine 5 or 10 mg/day to olmesartan medoxomil (hereafter olmesartan) 20 mg/day in patients not adequately controlled on olmesartan monotherapy. METHODS: After 8 weeks' open-label olmesartan 20 mg monotherapy, 538 patients with SBP/DBP > or =140/90 mmHg were randomized to 8 weeks' double-blind therapy with olmesartan/placebo, olmesartan/amlodipine 20 mg/5 mg or olmesartan/amlodipine 20 mg/10 mg. This trial is registered on the www.clinicaltrials.gov website (NCT00220220). RESULTS: After 8 weeks (with last observation carried forward), the adjusted mean change in seated DBP (SeDBP) from baseline was -7.6 mmHg for olmesartan/placebo, -10.4 mmHg for olmesartan/amlodipine 20 mg/5 mg (p = 0.0006 vs olmesartan/placebo) and -10.9 mmHg for olmesartan/amlodipine 20 mg/10 mg (p < 0.0001 vs olmesartan/placebo). Mean changes in SeSBP from baseline with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg were -16.1 and -16.7 mmHg, respectively (p < 0.0001 for both dose regimens vs olmesartan/placebo). BP goal rates were significantly higher with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg (44.5% and 45.8%, respectively; p = 0.0011 and p = 0.0004, respectively) versus olmesartan/placebo (28.5%). Combination therapy was well tolerated, and the incidence of drug-related adverse events was 8.9% for olmesartan/placebo, 7.7% for olmesartan/amlodipine 20 mg/5 mg, and 11.3% for olmesartan/amlodipine 20 mg/10 mg (p = 0.490). Most adverse events were mild in severity and were well known drug-class issues. CONCLUSIONS: Combining olmesartan and amlodipine resulted in significantly greater BP lowering in patients not achieving adequate BP control with olmesartan monotherapy, thus allowing a significantly greater proportion of patients to achieve BP goal.

Efficacy and tolerability of olmesartan medoxomil combined with amlodipine in patients with moderate to severe hypertension after amlodipine monotherapy: a randomized, double-blind, parallel-group, multicentre study.

BACKGROUND AND OBJECTIVES: Cerebrovascular and cardiac adverse events can be significantly reduced by effective antihypertensive therapy; however, BP control rates remain poor. The objective of this randomized, double-blind, parallel-group, multicentre study was to determine the efficacy and safety of olmesartan medoxomil/amlodipine combination therapy in patients with moderate to severe hypertension who had failed to respond to treatment with 8 weeks of open-label amlodipine. METHODS: A total of 1017 patients entered the open-label amlodipine monotherapy stage; mean BP at week 0 was 164/102 mmHg. After 8 weeks of amlodipine monotherapy (5 mg/day), non-responding patients (n = 755) were randomized to receive placebo plus amlodipine 5 mg or a combination of olmesartan medoxomil (10-40 mg) with amlodipine 5 mg for 8 weeks. At week 16, patients who had achieved diastolic BP (DBP) <90 mmHg and/or systolic BP (SBP) <140 mmHg continued on randomized treatment for a further 8 weeks. Patients in whom both SBP and DBP were >or=140/90 mmHg at week 16 had their medication uptitrated to olmesartan medoxomil/amlodipine 20/5 mg, olmesartan medoxomil/amlodipine 40/5 mg or olmesartan medoxomil/amlodipine 40/10 mg. RESULTS: Combination of olmesartan medoxomil (10-40 mg) with amlodipine 5 mg for 8 weeks (double-blind) reduced mean SBP/DBP by up to 16.8 mmHg and 9.6 mmHg, respectively. The additional adjusted mean change in seated DBP (SeDBP) [primary endpoint] with last observation carried forward (LOCF) compared with placebo/amlodipine 5 mg was -2.0 mmHg (p = 0.0207), -3.7 mmHg (p < 0.0001) and -3.8 mmHg (p < 0.0001) for olmesartan medoxomil/amlodipine 10/5 mg, 20/5 mg and 40/5 mg, respectively. The corresponding additional adjusted mean change in SeSBP compared with placebo/amlodipine 5 mg was -3.5 mmHg (p = 0.0103), -5.8 mmHg (p < 0.0001) and -7.1 mmHg (p < 0.0001) for the olmesartan medoxomil/amlodipine 10/5 mg, 20/5 mg and 40/5 mg groups, respectively. Uptitration was associated with further mean reductions of up to 12.6 mmHg (SeSBP) and 8.2 mmHg (SeDBP), and allowed additional patients to achieve goal BP. Target BP was defined using both SBP and DBP criteria (patients without diabetes <140/90 mmHg; patients with diabetes <130/80 mmHg). More than 70% of patients on active combination therapy achieved their BP goal by week 24. All combination regimens were well tolerated. CONCLUSION: These results suggest that olmesartan medoxomil combined with amlodipine is effective and well tolerated in reducing BP in patients with moderate to severe hypertension.