Constraint methods for determining pathways and free energy of activated processes

Activated processes from chemical reactions up to conformational transitions of large biomolecules are hampered by barriers which are overcome only by the input of some free energy of activation. Hence, the characteristic and rate-determining barrier regions are not sufficiently sampled by usual simulation techniques. Constraints on a reaction coordinate r have turned out to be a suitable means to explore difficult pathways without changing potential function, energy or temperature. For a dense sequence of values of r, the corresponding sequence of simulations provides a pathway for the process. As only one coordinate among thousands is fixed during each simulation, the pathway essentially reflects the system's internal dynamics. From mean forces the free energy profile can be calculated to obtain reaction rates and insight in the reaction mechanism. In the last decade, theoretical tools and computing capacity have been developed to a degree where simulations give impressive qualitative insight in the processes at quantitative agreement with experiments. Here, we give an introduction to reaction pathways and coordinates, and develop the theory of free energy as the potential of mean force. We clarify the connection between mean force and constraint force which is the central quantity evaluated, and discuss the mass metric tensor correction. Well-behaved coordinates without tensor correction are considered. We discuss the theoretical background and practical implementation on the example of the reaction coordinate of targeted molecular dynamics simulation. Finally, we compare applications of constraint methods and other techniques developed for the same purpose, and discuss the limits of the approach

Parametric Assessment of Stress Development and Cracking in Restrained Mortars Containing Internal Curing Under Autogenous and Thermal Loading

A finite element model is used to examine how the properties of cementitious mortar are related to the stress development in the dual ring test. The results of this investigation are used to explain the thermal cracking behavior of mixtures containing prewetted lightweight aggregates (LWA) by quantifying the contribution of several material properties individually. In addition to the beneficial effects of using the LWA as an internal curing agent to reduce the autogenous shrinkage of concrete, the LWA also helps to reduce the potential for thermal cracking due to a lower elastic modulus and increased stress relaxation. The rate of stress development, age of cracking, and magnitude of the temperature drop necessary to induce cracking in a dual ring specimen are dependent on a variety of factors, including the coefficient of thermal expansion of both the cementitious mortar and the restraining rings, elastic modulus of the mortar, creep effect of the mortar, and rate of thermal loading. Depending on the rate of cooling, cracking may or may not occur. The slowest rate of cooling (2.5 C/h) minimizes the effects of creep while cooling rates faster than 8 C/h can produce a thermal gradient through the mortar cross-section that needs to be considered

BATS OF THE WEST INDIAN ISLAND OF DOMINICA: NATURAL HISTORY, AREOGRAPHY, AND TROPHIC STRUCTURE

Because the islands in the Caribbean long have interested students of mammals and zoogeography, considerable information has been published concerning the biology of the Antillean mammalian fauna in the past three decades (Jones and Schwartz, 1967; Schwartz and Jones, 1967; Koopman, 1968, 1989; Jones and Phillips, 1970, 1976; Varona, 1974; Baker and Genoways, 1978; Baker et al., 1978; Swanepoel and Genoways, 1978; Jones and Baker, 1979; Silva Taboada, 1979; Baker et al., 1984; Eshelman and Morgan, 1985; Buden, 1986; Griffiths and Klingener, 1988; Jones, 1989; Masson et al., 1990; Pederson et al., 1996; Genoways et al., 1998). This increasing interest in the systematics and zoogeography of mammals in the region has involved both studies in the field and re-examination of collections made in earlier years. One problem facing investigators who attempt to assess the faunal relationships of the Antilles is the fact that natural conditions on most islands have been altered significantly as a result of early settlement, first by Ameridians, then by Europeans beginning in the 1500s. Changes wrought by agricultural practices have destroyed much of the original environment, and introduction on many islands of the mongoose (Herpestes javanicus) as a supposed means of controlling introduced rats (both Rattus norvegicus and R. rattus) has disturbed natural conditions

The impact of histological annotations for accurate tissue classification using mass spectrometry imaging

Knowing the precise location of analytes in the tissue has the potential to provide information about the organs’ function and predict its behavior. It is especially powerful when used in diagnosis and prognosis prediction of pathologies, such as cancer. Spatial proteomics, in particular mass spectrometry imaging, together with machine learning approaches, has been proven to be a very helpful tool in answering some histopathology conundrums. To gain accurate information about the tissue, there is a need to build robust classification models. We have investigated the impact of histological annotation on the classification accuracy of different tumor tissues. Intrinsic tissue heterogeneity directly impacts the efficacy of the annotations, having a more pronounced effect on more heterogeneous tissues, as pancreatic ductal adenocarcinoma, where the impact is over 20% in accuracy. On the other hand, in more homogeneous samples, such as kidney tumors, histological annotations have a slenderer impact on the classification accuracy

Self-organised criticality in base-pair breathing in DNA with a defect

We analyse base-pair breathing in a DNA sequence of 12 base-pairs with a defective base at its centre. We use both all-atom molecular dynamics (MD) simulations and a system of stochastic differential equations (SDE). In both cases, Fourier analysis of the trajectories reveals self-organised critical behaviour in the breathing of base-pairs. The Fourier Transforms (FT) of the interbase distances show power-law behaviour with gradients close to -1. The scale-invariant behaviour we have found provides evidence for the view that base-pair breathing corresponds to the nucleation stage of large-scale DNA opening (or 'melting') and that this process is a (second-order) phase transition. Although the random forces in our SDE system were introduced as white noise, FTs of the displacements exhibit pink noise, as do the displacements in the AMBER/MD simulations.Comment: 18 pages, 8 figure

Parametric Assessment of Stress Development and Cracking in Internally Cured Restrained Mortars Experiencing Autogenous Deformations and Thermal Loading

A finite element model is used to examine how the properties of cementitious mortar are related to the stress development in the dual ring test. The results of this investigation are used to explain the thermal cracking behavior of mixtures containing prewetted lightweight aggregates (LWA) by quantifying the contribution of several material properties individually. In addition to the beneficial effects of using the LWA as an internal curing agent to reduce the autogenous shrinkage of concrete, the LWA also helps to reduce the potential for thermal cracking due to a lower elastic modulus and increased stress relaxation. The rate of stress development, age of cracking, and magnitude of the temperature drop necessary to induce cracking in a dual ring specimen are dependent on a variety of factors, including the coefficient of thermal expansion of both the cementitious mortar and the restraining rings, elastic modulus of the mortar, creep effect of the mortar, and rate of thermal loading. Depending on the rate of cooling, cracking may or may not occur. The slowest rate of cooling (2.5∘C/h) minimizes the effects of creep while cooling rates faster than 8∘C/h can produce a thermal gradient through the mortar cross-section that needs to be considered

Business game as instrument of staff recruitment

The aim of the article consists in giving the reader some information on recruiting and business game as the instrument of staff recruitment. The article explains the concept of the business game and its role in the recruitment of staff, also the basic rules and forms of the business game.Цель статьи состоит в предоставлении читателю информации о рекрутинге и деловой игре как инструменте подбора персонала. Статья объясняет понятие деловой игры и ее роли в наборе персонала, а также основные правила и формы деловой игры