Quantum free energy differences from non-equilibrium path integrals: I. Methods and numerical application

The imaginary-time path integral representation of the canonical partition function of a quantum system and non-equilibrium work fluctuation relations are combined to yield methods for computing free energy differences in quantum systems using non-equilibrium processes. The path integral representation is isomorphic to the configurational partition function of a classical field theory, to which a natural but fictitious Hamiltonian dynamics is associated. It is shown that if this system is prepared in an equilibrium state, after which a control parameter in the fictitious Hamiltonian is changed in a finite time, then formally the Jarzynski non-equilibrium work relation and the Crooks fluctuation relation are shown to hold, where work is defined as the change in the energy as given by the fictitious Hamiltonian. Since the energy diverges for the classical field theory in canonical equilibrium, two regularization methods are introduced which limit the number of degrees of freedom to be finite. The numerical applicability of the methods is demonstrated for a quartic double-well potential with varying asymmetry. A general parameter-free smoothing procedure for the work distribution functions is useful in this context.Comment: 20 pages, 4 figures. Added clarifying remarks and fixed typo

Ab initio and finite-temperature molecular dynamics studies of lattice resistance in tantalum

This manuscript explores the apparent discrepancy between experimental data and theoretical calculations of the lattice resistance of bcc tantalum. We present the first results for the temperature dependence of the Peierls stress in this system and the first ab initio calculation of the zero-temperature Peierls stress to employ periodic boundary conditions, which are those best suited to the study of metallic systems at the electron-structure level. Our ab initio value for the Peierls stress is over five times larger than current extrapolations of experimental lattice resistance to zero-temperature. Although we do find that the common techniques for such extrapolation indeed tend to underestimate the zero-temperature limit, the amount of the underestimation which we observe is only 10-20%, leaving open the possibility that mechanisms other than the simple Peierls stress are important in controlling the process of low temperature slip.Comment: 12 pages and 9 figure

Genome Analysis of Minibacterium massiliensis Highlights the Convergent Evolution of Water-Living Bacteria

Filtration usually eliminates water-living bacteria. Here, we report on the complete genome sequence of Minibacterium massiliensis, a β-proteobacteria that was recovered from 0.22-μm filtered water used for patients in the hospital. The unexpectedly large 4,110,251-nucleotide genome sequence of M. massiliensis was determined using the traditional shotgun sequencing approach. Bioinformatic analyses shows that the M. massiliensis genome sequence illustrates characteristic features of water-living bacteria, including overrepresentation of genes encoding transporters and transcription regulators. Phylogenomic analysis based on the gene content of available bacterial genome sequences displays a congruent evolution of water-living bacteria from various taxonomic origins, principally for genes involved in energy production and conversion, cell division, chromosome partitioning, and lipid metabolism. This phylogenomic clustering partially results from lateral gene transfer, which appears to be more frequent in water than in other environments. The M. massiliensis genome analyses strongly suggest that water-living bacteria are a common source for genes involved in heavy-metal resistance, antibiotics resistance, and virulence factors

Factors affecting the measurement variability of SV95C in ambulant patients with Duchenne muscular dystrophy

peer reviewedStride Velocity at the 95th Centile (SV95C) is a novel clinical outcome measure that is captured during normal daily living using wearable technology and represents the maximum ambulatory ability of a patient. SV95C is qualified by the European Medicines agency (EMA) for use as a secondary endpoint in pivotal studies in DMD, and is an important real-world functional endpoint complementary to the traditional in-clinic assessments such as the North Star Ambulatory Assessment scale and the Six Meter Walk Test. The Context of Use of SV95C as defined by EMA states that SV95C should be measured for at least 50h during normal daily living to yield an outcome variability that would render SV95C suitable for regulatory decision-making. Considering the increasing use of SV95C in drug development for DMD, it is critical to understand the most common drivers of endpoint variability. Using data from ActiLiège-NEXT, a prospective natural history study in ambulant patients with DMD designed to longitudinally characterise functional disease progression using multiple outcome measures, we evaluated the impact of the time of day, the day of the week as well as seasonal changes on the measurement variability of SV95C in ambulant patients with DMD. Specifically, SV95C will be computed for morning only (8am-12pm) and afternoon recording periods (2pm-6pm) and compared. A similar sensitivity analysis will be done for SV95C computed on weekdays (Monday-Friday) and weekend (Saturday-Sunday). The seasonal impact on the compliance and SV95C will be conducted on longitudinal data and adjusted by the geographical location of the patients, restricting to countries where the maximal temperature difference over the year exceeds 15° and maximal temperature does not exceed 30°C. This data provides important context to the factors that impact the measurement variability of SV95C and will be useful to inform clinical trial design in DMD, when using SV95C as an outcome measure of efficacy

Analysis of the natural evolution of SV95C in ambulant patients with Duchenne muscular dystrophy

peer reviewedThe progressive nature of functional loss in Duchenne Muscular Dystrophy (DMD) is well established and routinely characterised in clinic using assessments such as the North Star Ambulatory Assessment and the Six Meter Walk Test. The trajectory of functional loss depends on the patient's age and baseline functional ability. There is a need to better characterise the trajectory of disease progression in order to try to predict disease evolution and optimise patient care. Stride Velocity at the 95th Centile (SV95C) is a novel clinical outcome measure that is captured during normal daily living using wearable technology and represents the maximum ambulatory ability of a patient. SV95C is qualified by the European Medicines agency (EMA) for use as a secondary endpoint in pivotal studies in DMD and is an important real-world functional endpoint complementing the traditional in-clinic assessments. SV95C declines by approximately 7% per year in ambulant patients with DMD who are on a stable dose of steroids. In other functional endpoints such as the NSAA and 6MWT the decline is dependent on the patient's age and baseline ambulatory abilities. This study aims to investigate how yearly change of SV95C is also dependent upon age and baseline function. We will analyse how the evolution of SV95C can be predicted by the baseline value of SV95C and age, using non-linear and linear multiparametric regression models. This analysis will be conducted on data from ActiLiège-NEXT, a prospective natural history study in ambulant patients with DMD. This study was designed to characterise longitudinal functional disease progression using multiple outcome measures, including SV95C. It includes patients with DMD between 4 and 20 years old studied over 1 year. SV95C was measured daily using ActiMyo®, a class I CE medical device with two sensors worn on the ankles. These data will advance our understanding of the importance of SV95C as an outcome measure for functional disease progression in DMD

Superionic Conduction in Substoichiometric LiAl Alloy: An Ab Initio Study

Based on the new ab initio molecular dynamics method by Kuhne et al. [Phys. Rev. Lett. 98, 066401 (2007)], we studied the mechanism of superionic conduction in substoichiometric Li-poor Li1xAl alloys by performing simulations at different temperatures for an overall simulation time of about 1 ns. The dynamical simulations revealed the microscopic path for the diffusion of Li vacancies. The calculated activation energy (0.11 eV) and the prefactor (D0=6:9 x 10-4 cm2/s) for Li diffusivity via a vacancy-mediated mechanism are in good agreement with experimental NMR data. The calculation of the formation energies of different defects-Li and Al Frenkel pair and Li antisites- revealed that only Li vacancies and LiAl antisites are present in the stability range of the Zintl phase -0.1 <x<0.2