Structure and Dynamics of Biological Systems: Integration of Neutron Scattering with Computer Simulation

The combination of molecular dynamics simulation and neutron scattering techniques has emerged as a highly synergistic approach to elucidate the atomistic details of the structure, dynamics and functions of biological systems. Simulation models can be tested by calculating neutron scattering structure factors and comparing the results directly with experiments. If the scattering profiles agree the simulations can be used to provide a detailed decomposition and interpretation of the experiments, and if not, the models can be rationally adjusted. Comparison with neutron experiment can be made at the level of the scattering functions or, less directly, of structural and dynamical quantities derived from them. Here, we examine the combination of simulation and experiment in the interpretation of SANS and inelastic scattering experiments on the structure and dynamics of proteins and other biopolymers

Temperature dependence of protein dynamics simulated with three different water models

The effect of variation of the water model on the temperature dependence of protein and hydration water dynamics is examined by performing molecular dynamics simulations of myoglobin with the TIP3P, TIP4P, and TIP5P water models and the CHARMM protein force field at temperatures between 20 and 300 K. The atomic mean-square displacements, solvent reorientational relaxation times, pair angular correlations between surface water molecules, and time-averaged structures of the protein are all found to be similar, and the protein dynamical transition is described almost indistinguishably for the three water potentials. The results provide evidence that for some purposes changing the water model in protein simulations without a loss of accuracy may be possible

Flexibility to support the future power systems

Power system flexibility relates to the ability of the power system to manage changes. Solutions providing advances in flexibility are of utmost importance for the future power system. Development and deployment of innovative technologies, communication and monitoring possibilities, as well as increased interaction and information exchange, are enablers to provide holistic flexibility solutions. Furthermore, development of new methods for market design and analysis, as well as methods and procedures related to system planning and operation, will be required to utilise available flexibility to provide most value to society. However, flexibility is not a unified term and is lacking a commonly accepted definition. The flexibility term is used as an umbrella covering various needs and aspects in the power system. This situation makes it highly complex to discuss flexibility in the power system and craves for differentiation to enhance clarity. In this report, the solution has been to differentiate the flexibility term on needs, and to categorise flexibility needs in four categories: Flexibility for Power, Flexibility for Energy, Flexibility for Transfer Capacity, and Flexibility for Voltage. Here, flexibility needs are considered from over-all system perspectives (stability, frequency and energy supply) and from more local perspectives (transfer capacities, voltage and power quality). With flexibility support considered for both operation and planning of the power system, it is required in a timescale from fractions of a second (e.g. stability and frequency support) to minutes and hours (e.g. thermal loadings and generation dispatch) to months and years (e.g. planning for seasonal adequacy and planning of new investments). The categorisation presented in this report supports an increased understanding of the flexibility needs, to be able to identify and select the most suitable flexibility solutions

Restrictions on the use of valproate in female patients of reproductive age: the updated recommendations based on recent clinical data

For more than half a century, valproic acid (VA) has been a first-line drug to control seizures in various forms of epilepsy and status epilepticus; VA is also used in bipolar disorders. However, the accumulated clinical evidence indicates negative outcomes of pregnancies in women receiving valproate. Thus, babies born to mothers receiving VA for their epilepsy or bipolar disorder had an increased risk of serious congenital malformations. In addition, VA was found to affect the development of the CNS in a fetus that may result in attention-deficit hyperactivity syndrome (ADHD), autism spectrum disorder (ASD), childhood autism, and other diseases. The data on teratogenic effects of VA have led the regulatory authorities and the manufacturer to adopt restrictive recommendations regarding the use of VA in female patients of reproductive age. The Russian League Against Epilepsy (RLAE) presents this article to inform the medical community about the consequences of using valproic acid in pregnancy and also recommends a number of preventive measures. The article elaborates on the evidence of teratogenic risks associated with VA and reviews documents from the regulatory authorities (EMA, MHRA, Roszdravnadzor of the Russian Federation), which specify the measures needed to prevent the adverse effects of VA during pregnancy. According to these documents, medications containing VA should no longer be used in female patients of childbearing potential, except in cases where other treatments for epilepsy are ineffective or contraindicated. The changes made by the manufacturer in the official instructions for using the reference drug, and the unified instructions of the RF regulatory bodies on the reproduced (generic) drugs containing VA are also presented. The Pregnancy Prevention Program is proposed to minimize individual risks for women using VA. The article also addresses the international clinical practice on the prevention of VA-associated adverse effects during pregnancy and the recommendations of RLAE on alternative anti-epileptic therapy using minimally teratogenic drugs: lamotrigine, levetiracetam, and oxcarbazepine