Integrative structural and dynamical biology with PLUMED-ISDB

Accurate structural models of biological systems can be obtained by properly combining experimental data with a priori physico-chemical knowledge. Here we present PLUMED-ISDB, an open-source, freely-available module of the popular PLUMED library, which enables the simultaneous determination of structure and dynamics of conformationally heterogeneous systems by integrating experimental data with a priori information. This integration is achieved using metainference, a general Bayesian framework that accounts for both noise in the data and their ensemble-averaged nature. PLUMED-ISDB implements different types of experimental data, such as several NMR observables, FRET, SAXS and cryo-electron microscopy data, and enables modelling structure and dynamics of individual proteins, protein complexes, membrane proteins, RNA and DNA, using a variety of enhanced sampling methods and resolutions of the system

Inversion of electrical conductivity data with Tikhonov regularization approach: some considerations

Electromagnetic induction measurements, which are generally used to determine lateral variations of apparent electrical conductivity, can provide quantitative estimates of the subsurface conductivity at different depths. Quantitative inference about the Earth’s interior from experimental data is, however, an ill-posed problem. Using the generalised McNeill’s theory for the EM38 ground conductivity meter, we generated synthetic apparent conductivity curves (input data vector) simulating measurements at different heights above the soil surface. The electrical conductivity profile (the Earth model) was then estimated solving a least squares problem with Tikhonov regularization optimised with a projected conjugate gradient algorithm. Although the Tikhonov approach improves the conditioning of the resulting linear system, profile reconstruction can be surprisingly far from the desired true one. On the contrary, the projected conjugate gradient provided the best solution without any explicit regularization (a = 0) of the objective function of the least squares problem. Also, if the initial guess belongs to the image of the system matrix, Im(A), we found that it provides a unique solution in the same subspace Im(A)

Effect of Duroc genes proportion on growth performance and on carcass and meat quality characteristics in heavy pigs

By means of the application of covariance models, the linear effects of the proportion of Duroc genes were evaluated with respect to growth (from 6 to 170 kg live weight) and feed/gain ratios, as well as carcass (lean cuts, adipose cuts, linear measures, backfat thickness, loin area and lean percentage) and meat quality (L* a* b* colour, reflectance, electrical conductivity, pH) in 167 heavy pigs (87 castrated males, 80 females) from different crosses of Duroc (D), Large White (LW) and Landrace (L) breeds, from 25 to approximately 300 d of age. The pigs were weighed at 25, 105, 170, 235 d and at the end of the trial (298 ± 6 d of age), and were raised under the same conditions. The proportion of Duroc genes was 0% (LWxL; no. 33), 25% [(LWx(DxL); n. 31 and Lx(DxLW); n. 35)] and 50% [Dx(LWx(LWxL)); n. 68]. The increase in the proportion of Duroc genes negatively affected the live weight at the different ages (P0.10). In fact, during the final phase (from 120 to 170 kg l.w.) the effect of the Duroc breed on daily gain became positive (P=0.08), and the feed/gain ratios were significantly lower (P=0.02). The carcass composition was not significantly influenced by the increase in the proportion of Duroc genes, with the exception of a rise in the weight of neck (P<0.01) and flare fat (P=0.02) and a reduction of ham (P=0.09). Carcass length resulted lower as the proportion of Duroc genes increased (P<0.01); at 24 h from slaughtering, meat colour showed lower values for lightness (P=0.08), redness (P=0.02) and yellowness (P=0.03)

Inversion of electrical conductivity data with Tikhonov regularization approach: some considerations

Electromagnetic induction measurements, which are generally used to determine lateral variations of apparent electrical conductivity, can provide quantitative estimates of the subsurface conductivity at different depths. Quantitative inference about the Earth's interior from experimental data is, however, an ill-posed problem. Using the generalised McNeill's theory for the EM38 ground conductivity meter, we generated synthetic apparent conductivity curves (input data vector) simulating measurements at different heights above the soil surface. The electrical conductivity profile (the Earth model) was then estimated solving a least squares problem with Tikhonov regularization optimised with a projected conjugate gradient algorithm. Although the Tikhonov approach improves the conditioning of the resulting linear system, profile reconstruction can be surprisingly far from the desired true one. On the contrary, the projected conjugate gradient provided the best solution without any explicit regularization ( a= 0) of the objective function of the least squares problem. Also, if the initial guess belongs to the image of the system matrix, Im(A), we found that it provides a unique solution in the same subspace Im(A)

Micropulse Transscleral Cyclophotocoagulation: A Hypothesis for the Ideal Parameters

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis

An application of simulated annealing to the optimum design of reinforced concrete retaining structures

This paper reports on the application of a simulated annealing algorithm to the minimum cost design of reinforced concrete retaining structures. Cantilever retaining walls are investigated, being representative of reinforced concrete retaining structures that are required to resist a combination of earth and hydrostatic loading. To solve such a constrained optimisation problem, a modified simulated annealing algorithm is proposed that avoids the simple rejection of infeasible solutions and improves convergence to a minimum cost. The algorithm was implemented using an object-orientated visual programming language, offering facilities for continual monitoring, assessing and changing of the simulated annealing control parameters. Results show that the simulated annealing can be successfully applied to the minimum cost design of reinforced concrete retaining walls, overcoming the difficulties associated with the practical and realistic assessment of the structural costs and their complex inter-relationship with the imposed constraints on the solution space

Breakdown rates and macroinvertebrate colonisation of alder (Alnus glutinosa) leaves in an acid lake (Lake Orta, N Italy), before, during and after a liming intervention

To test the effectiveness of the liming intervention on Lake Orta, the speed of leaves decay and of colonisation processes by macrobenthonic fauna were studied on alder leaves (Alnus glutinosa) placed on the bottom of the lake and recovered after appropriate time intervals. Experiments were performed at two sites (North and South) and two depths (-3 and –18 m), during three successive winters: 1988-1989 (pre-liming), 1989-1990 (liming), 1990-1991 (post-liming). Two main results emerged: 1) alder leaves, which are known to have a medium to high decaying speed in a number of aquatic environments, behave in Lake Orta as a low speed species. Decaying processes in the three years are significantly different only in station N3, where the mean breakdown rate in 1988- 1989 is more than twice that measured in the two subsequent winters. 2) The species richness of colonising benthic fauna is low: the community is made up almost exclusively of Chironomidae, which form 70 to 100% of the whole population; among them, the genus Phenopsectra is always present, while Tanytarsus was collected only during the first year and in the less deep sampling sites. The mean population abundances were higher before liming

Limits on the low energy antinucleon-nucleus annihilations from the Heisenberg principle

We show that the quantum uncertainty principle puts some limits on the effectiveness of the antinucleon-nucleus annihilation at very low energies. This is caused by the fact that the realization a very effective short-distance reaction process implies information on the relative distance of the reacting particles. Some quantitative predictions are possible on this ground, including the approximate A-independence of antinucleon-nucleus annihilation rates.Comment: 10 pages, no figure