ENDER: a statistical framework for boosting decision rules

Induction of decision rules plays an important role in machine learning. The main advantage of decision rules is their simplicity and human-interpretable form. Moreover, they are capable of modeling complex interactions between attributes. In this paper, we thoroughly analyze a learning algorithm, called ENDER, which constructs an ensemble of decision rules. This algorithm is tailored for regression and binary classification problems. It uses the boosting approach for learning, which can be treated as generalization of sequential covering. Each new rule is fitted by focusing on examples which were the hardest to classify correctly by the rules already present in the ensemble. We consider different loss functions and minimization techniques often encountered in the boosting framework. The minimization techniques are used to derive impurity measures which control construction of single decision rules. Properties of four different impurity measures are analyzed with respect to the trade-off between misclassification (discrimination) and coverage (completeness) of the rule. Moreover, we consider regularization consisting of shrinking and sampling. Finally, we compare the ENDER algorithm with other well-known decision rule learners such as SLIPPER, LRI and RuleFit.     

Modeling of the degradation kinetics of biodegradable scaffolds: The effects of the environmental conditions

The rate of hydrolytic degradation of tissue‐engineered scaffolds made from bioresorbable polyesters is dependent on several factors. Some are related to the properties of the degrading polymeric material, but others are related to the geometry of the porous structure and the operating environment. It is well known that the rate of hydrolytic degradation of a given object, porous or nonporous, is lower when it is exposed to dynamic conditions, a flowing medium, than when it operates in static conditions. The most likely reason is the more efficient removal of the acidic degradation products from the vicinity of the polymeric material when it is operating in a flowing medium. In this article, we present a new phenomenological reaction–diffusion model of aliphatic polymer degradation. The model can be used to predict the significance of various factors in in vitro degradation tests, with particular reference to the flow of the degradation medium, and the frequency of medium replacement in the case of static conditions. The developed model was used to simulate the degradation of poly(dl ‐lactide‐co‐glycolide) scaffolds with different porosities subjected to static and dynamic testing conditions. The results confirm that the porosity of the scaffold had a significant influence on the degradation rate. It was shown that the combination of dynamic conditions and high porosity effectively reduced the mass loss and molecular weight loss of the degrading polymer. However, the effect of changes in the velocity of the flowing medium had a negligible effect on the rate of degradation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40280.     

Sensitivity Analysis as a Tool for Estimating Numerical Modeling Results

Modeling of real physical processes by numerical methods is highly time-consuming and requires significant computational capacity. In some cases, tens or even hundreds of hours of high-power computing are needed to virtually model a real process that lasts one second. Processes that take many hours, such as drying, pose an even greater challenge. This problem can be solved in two ways: by using faster computers (such as computing clusters) or by significantly simplifying the modeled process (its geometry, physical phenomena, or the impact of individual factors). For this reason, all methods which speed up or minimize the number of simulations required to achieve the research objective should be analyzed. This article focuses on the latter approach, and it proposes a simple method for predicting the responses of a numerical model (values of any output parameter) to changes in input values (values of any input parameter). This method requires a base model, such as a numerical model which is qualitatively and quantitatively consistent with experimental observations, and a sensitivity analysis. This article discusses the mathematical and logical premises for the discussed model, and it proposes two methods for predicting numerical simulation results. Those methods are illustrated with examples which analyze the behavior of the Eulerian Multiphase Model and describe phase interactions based on Gidaspow's approach. The discussed example relies on data from a series of articles published by the authors in Drying Technology. This article was inspired by the observations made during a time-consuming process of modeling a spouted bed grain dryer, which was described in the above publications. The objective of this study was to discuss the advantages and possibilities created by sensitivity analyses of numerical models and to encourage their practical application.     

Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.     

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.     

The Mutation in wbaP cps Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of Klebsiella pneumoniae

Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting K. pneumoniae against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on K. pneumoniae virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from Klebsiella siphovirus KP36 was used as the selective agent during the treatment of K. pneumoniae 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the wbaP gene located within the cps gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response.     

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.     

Microwave-assisted synthesis and characterization of bioactive chitosan scaffolds doped with Au nanoparticles for mesenchymal stem cells culture

In this work we present a novel strategy for chitosan-based scaffolds. Chitosan is a versatile biopolymer obtained from waste biomass known of its favorable biological properties. Thus it can replace other polymers in the preparation of bioactive scaffolds. To increase its durability chitosan can be crosslinked into form of the hydrogel yet application of toxic crosslinkers may lead to loss of biocompability. Mesenchymal stem cells can be used in cell therapy for advanced wound treatment. However their culture requires special biomaterials application. In this article a novel microwave-assisted synthesis method for bioactive chitosan scaffolds is presented.