Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

Dental pathology of the wild Iberian wolf (Canis lupus signatus): The study of a 20th century Portuguese museum collection

For some wild canids, such as the Iberian wolf, there is a lack of in-depth knowledge about dental pathology. We aimed to evaluate it, in a standardized manner, in specimens from a Portuguese museum collection. Sixty-five deceased specimens of wild Iberian wolves, 61 complete skulls and 4 mandibles, collected in Portugal between 1977 and 1995, were analyzed. Sample comprised 18 females, 24 males and 23 individuals of undetermined sex. Teeth were evaluated by visual observation and dental radiography for tooth wear, periodontitis, fractures and other dental lesions. We have found several causes for teeth absence: artefactual, secondary to periodontitis and agenesia. About 30% of the teeth showed signs of wear. Only a small (<13%) fraction of maxillary and mandibular teeth did not show periodontitis. The tooth 308 showed periodontitis in all males (p = 0.017) and the tooth 104 was significantly affected by this condition in females (p = 0.020). A significant relationship was found between females and tooth wear in three teeth. Periodontitis showed a significant association with tooth wear (p < 0.001) and fractures (p = 0.027). Tooth fractures were more frequent in the maxilla than in the mandible. Seven periapical lesions, seven root fusions and three specimens with malocclusion were identified in the collection. Results are discussed integrating information from diet, habitat, genetic and spatial behavior. Dental radiography is here proposed as an approach for the age estimation in archaeological canids. This research contributes to the knowledge of the dental disease in the largest wolf population in Western Europe, a target subspecies of multiple conservation measures.info:eu-repo/semantics/publishedVersio

Seeded Bayesian Networks: Constructing genetic networks from microarray data

<p>Abstract</p> <p>Background</p> <p>DNA microarrays and other genomics-inspired technologies provide large datasets that often include hidden patterns of correlation between genes reflecting the complex processes that underlie cellular metabolism and physiology. The challenge in analyzing large-scale expression data has been to extract biologically meaningful inferences regarding these processes – often represented as networks – in an environment where the datasets are often imperfect and biological noise can obscure the actual signal. Although many techniques have been developed in an attempt to address these issues, to date their ability to extract meaningful and predictive network relationships has been limited. Here we describe a method that draws on prior information about gene-gene interactions to infer biologically relevant pathways from microarray data. Our approach consists of using preliminary networks derived from the literature and/or protein-protein interaction data as seeds for a Bayesian network analysis of microarray results.</p> <p>Results</p> <p>Through a bootstrap analysis of gene expression data derived from a number of leukemia studies, we demonstrate that seeded Bayesian Networks have the ability to identify high-confidence gene-gene interactions which can then be validated by comparison to other sources of pathway data.</p> <p>Conclusion</p> <p>The use of network seeds greatly improves the ability of Bayesian Network analysis to learn gene interaction networks from gene expression data. We demonstrate that the use of seeds derived from the biomedical literature or high-throughput protein-protein interaction data, or the combination, provides improvement over a standard Bayesian Network analysis, allowing networks involving dynamic processes to be deduced from the static snapshots of biological systems that represent the most common source of microarray data. Software implementing these methods has been included in the widely used TM4 microarray analysis package.</p

Molecular Modeling Study for Inhibition Mechanism of Human Chymase and Its Application in Inhibitor Design

Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I) bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymasecomplexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most activecompound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitorymechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes