Methods for control over learning individual trajectory

The article discusses models, methods and algorithms of determining student's optimal individual educational trajectory. A new method of controlling the learning trajectory has been developed as a dynamic model of learning trajectory control, which uses score assessment to construct a sequence of studied subjects

LIFECYCLE MANAGEMENT, MONITORING AND ASSESSMENT FOR SAFE LARGE-SCALE INFRASTRUCTURES: CHALLENGES AND NEEDS

Many European infrastructures dating back to ’50 and ’60 of the last century like bridges and viaducts are approaching the end of their design lifetime. In most European countries costs related to maintenance of infrastructures reach a quite high percentage of the construction budget and additional costs in terms of traffic delay are due to downtime related to the inspection and maintenance interventions. In the last 30 years, the rate of deterioration of these infrastructures has increased due to increased traffic loads, climate change related events and man-made hazards. A sustainable approach to infrastructures management over their lifecycle plays a key role in reducing the impact of mobility on safety (over 50 000 fatalities in EU per year) and the impact of greenhouse gases emission related to fossil fuels. The events related to the recent collapse of the Morandi bridge in Italy tragically highlighted the sheer need to improve resilience of aging transport infrastructures, in order to increase the safety for people and goods and to reduce losses of functionality and the related consequences. In this focus Structural Health Monitoring (SHM) is one of the key strategies with a great potential to provide a new approach to performance assessment and maintenance over the life cycle for an efficient, safe, resilient and sustainable management of the infrastructures. In this paper research efforts, needs and challenges in terms of performance monitoring, assessment and standardization are described and discussed.The networking support of COST Action TU1402 on ‘Quantifying the Value of Structural Health Monitoring’ and of COST Action TU1406 on ‘Quality specifications for roadway bridges, standardization at a European level (BridgeSpec)

Sampling protein motion and solvent effect during ligand binding.

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Formation and Malformation of Cardiac Trabeculae: Biological Basis, Clinical Significance, and Special Yield of Magnetic Resonance Imaging in Assessment

Adult and pediatric cardiologists are familiar with variation in cardiac trabeculation. Abnormal trabeculation is a key feature of left ventricular noncompaction, but it is also common in congenital heart diseases and in cardiomyopathies (dilated and hypertrophied). Trabeculae might be a measurable phenotypic marker that will allow insights into how cardiomyopathy and congenital heart disease arise and develop. This will require the linking together of clinical and preclinical information (such as embryology and genetics), with new analysis methods for trabecular quantitation. In adult cardiology several promising quantitative methods have been developed for echocardiography, computed tomography, and cardiovascular magnetic resonance, and earlier cross-sectional caliper approaches have now been refined to permit more advanced assessment. Adaptation of these methods for use in developmental biology might inform on better ways to measure and track trabecular morphology in model organisms

Perspectives on High-Throughput Ligand/Protein Docking With Martini MD Simulations

Molecular docking is central to rational drug design. Current docking techniques suffer, however, from limitations in protein flexibility and solvation models and by the use of simplified scoring functions. All-atom molecular dynamics simulations, on the other hand, feature a realistic representation of protein flexibility and solvent, but require knowledge of the binding site. Recently we showed that coarse-grained molecular dynamics simulations, based on the most recent version of the Martini force field, can be used to predict protein/ligand binding sites and pathways, without requiring any a priori information, and offer a level of accuracy approaching all-atom simulations. Given the excellent computational efficiency of Martini, this opens the way to high-throughput drug screening based on dynamic docking pipelines. In this opinion article, we sketch the roadmap to achieve this goal

The Free Energy Landscape of GABA Binding to a Pentameric Ligand-Gated Ion Channel and Its Disruption by Mutations.

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop superfamily are important neuroreceptors that mediate fast synaptic transmission. They are activated by the binding of a neurotransmitter, but the details of this process are still not fully understood. As a prototypical pLGIC, here we choose the insect resistance to dieldrin (RDL) receptor involved in resistance to insecticides and investigate the binding of the neurotransmitter GABA to its extracellular domain at the atomistic level. We achieve this by means of μ-sec funnel-metadynamics simulations, which efficiently enhance the sampling of bound and unbound states by using a funnel-shaped restraining potential to limit the exploration in the solvent. We reveal the sequence of events in the binding process from the capture of GABA from the solvent to its pinning between the charged residues Arg111 and Glu204 in the binding pocket. We characterize the associated free energy landscapes in the wild-type RDL receptor and in two mutant forms, where the key residues Arg111 and Glu204 are mutated to Ala. Experimentally these mutations produce nonfunctional channels, which is reflected in the reduced ligand binding affinities due to the loss of essential interactions. We also analyze the dynamical behavior of the crucial loop C, whose opening allows the access of GABA to the binding site and closure locks the ligand into the protein. The RDL receptor shares structural and functional features with other pLGICs; hence, our work outlines a valuable protocol to study the binding of ligands to pLGICs beyond conventional docking and molecular dynamics techniques

The T.O.S.C.A. Project: Research, Education and Care

Despite recent and exponential improvements in diagnostic- therapeutic pathways, an existing “GAP” has been revealed between the “real world care” and the “optimal care” of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF “metabolic pathophysiological model” and to improve the quality of care of HF patients through research and continuing medical education