Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D1-R/D2-R/5-HT2A -R/H3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs

Hardness Properties of AA2014-SiC MMCs

In this study, microstructure and hardness effects of cryogenic and ageing heat treatments applied to AA2014-SiC composites containing vol. 0.5, 1, 2 and 4% SiC reinforcing ratio have been investigated. SEM, EDS, XRD and MAP analyses have been used in the determination of microstructural properties. Macro hardness measurements have been implemented for the investigation of hardness effects. Through the dissolution and cryogenic processes applied, alloying elements such as Cu, which has a direct effect on the formation of secondary phase in the structure, can be homogeneously dispersed in the microstructure. It has been also found that there is a significant increase in the hardness level due to the applied cryogenic treatment. A significant homogenous distribution of alloys is obtained in the MAP analysis after the cryogenic process. This is the reason why the cryogenic cooling process can be working dynamically, especially in ageing applicable alloys.[GRAPHICS]

Reconceptualised family resemblance approach to nature of science in pre-service science teacher education

A recent framework on nature of science (NOS) is the Family Resemblance Approach (FRA). FRA presents NOS as a cognitive-epistemic and social-institutional system with a set of categories: aims and values, scientific methods, scientific practices, scientific knowledge and social-institutional aspects of science. Although FRA has been problematised philosophically and its implications for science education have been considered by science educators, its empirical adaptations in science education are limited. In order to illustrate the educational adaptations of FRA, we refer to Reconceptualised Family Resemblance Approach to Nature of Science or RFN. We present a study based on a funded pre-service science teacher education project whose aim was to design, implement and evaluate the impact of RFN strategies. Fifteen pre-service teachers participated in a 14-week teacher education intervention that infused RFN. A 70-item questionnaire was designed to investigate the outcomes of the teacher education intervention. Individual interviews with pre-service teachers were also conducted. Quantitative and qualitative data analysis suggest that the teacher education intervention had an overall significant impact on pre-service teachers’ views of NOS. The paper contributes to the understanding of how NOS can be incorporated in science teacher education using a new orientation to NOS based on FRA

NiTi SMA Parts Production with Different Porosity Ratios

NiTi SMA has widespread use in commercial and scientific fields with its recycling effect. Today, NiTi SMA alloys, which have different usage areas, are expected to have different properties. At the beginning of these properties, it is necessary to produce of the porosity structures (implant technology) and compact structure (high density material). For this reason, NiTi SMAs were produced with porous and compact structures in this study. Obtained theoretical densities were achieved from 57\% to 90\% in parts production

Reconceptualised family resemblance approach to nature of science in pre-service science teacher education

A recent framework on nature of science (NOS) is the Family Resemblance Approach (FRA). FRA presents NOS as a cognitive-epistemic and social-institutional system with a set of categories: aims and values, scientific methods, scientific practices, scientific knowledge and social-institutional aspects of science. Although FRA has been problematised philosophically and its implications for science education have been considered by science educators, its empirical adaptations in science education are limited. In order to illustrate the educational adaptations of FRA, we refer to Reconceptualised Family Resemblance Approach to Nature of Science or RFN. We present a study based on a funded pre-service science teacher education project whose aim was to design, implement and evaluate the impact of RFN strategies. Fifteen pre-service teachers participated in a 14-week teacher education intervention that infused RFN. A 70-item questionnaire was designed to investigate the outcomes of the teacher education intervention. Individual interviews with pre-service teachers were also conducted. Quantitative and qualitative data analysis suggest that the teacher education intervention had an overall significant impact on pre-service teachers’ views of NOS. The paper contributes to the understanding of how NOS can be incorporated in science teacher education using a new orientation to NOS based on FRA

Perceptions of nature of science emerging in group discussions: A comparative account of pre-service teachers from Turkey and England

The paper presents a study about pre-service science teachers’ perceptions of the Nature of Science (NOS). Although there is a substantial amount of research on NOS in science teacher education, international comparative accounts particularly of in-depth qualitative data emerging from group discussions are fairly minimal. The primary aim of the research was to determine the changes of pre-service science teachers’ NOS perceptions following group discussions in two different national contexts: Turkey and England. Two groups of pre-service teachers from Turkey were contrasted with two groups of pre-service teachers from England. The group discussions were structured with a set of steps. In the first step, the participants were asked to reflect about NOS and record their key ideas on sticky notes. Subsequently, they were presented with a visual framework of NOS, and they were asked to situate their own ideas from the sticky notes in this image. Verbal data from group discussions were investigated by qualitative methodology using thematic analysis. The findings suggest that both groups of pre-service teachers initially focused on epistemic-cognitive aspects of NOS but their ideas became more nuanced in providing some examples about social and institutional dimensions of NOS following the introduction of the NOS image. The study contributes to the understanding of how pre-service teachers view NOS and illustrates how NOS can potentially be incorporated into group discussions in science teacher education

Solid-liquid interfacial energy of solid succinonitrile in equilibrium with succinonitrile-1,4-diiodobenzene eutectic liquid

The grain boundary groove shapes for equilibrated solid SCN in equilibrium with the SCN-0.5 mol% DIB eutectic liquid have been directly observed by using a horizontal linear temperature gradient apparatus. The ratio of thermal conductivity of equilibrated liquid to thermal conductivity of solid SCN has also been determined to be 0.90. From the observed grain boundary groove shapes and measured thermal conductivity ratio, the Gibbs-Thomson coefficient (D") of solid SCN has been determined to be (5.46 +/- A 0.55) x 10(-8) K m. The solid-liquid interfacial energy (sigma (SL)) and the grain boundary energy of solid SCN have also been determined to be (8.25 +/- A 1.24) x 10(-3) J m(-2) and (15.84 +/- A 2.53) x 10(-3) J m(-2), respectively

Solid-liquid interfacial energy of solid succinonitrile solution in equilibrium with succinonitrile-neopentylglycol eutectic liquid

The grain boundary groove shapes for solid succinonitrile solution (SCN-5 mole% NPG) in equilibrium with the succinonitrile (SCN)-neopentylglycol (NPG) eutectic liquid (SCN-9.55 mole% NPG) have been directly observed by using a horizontal linear temperature gradient apparatus at 317.1 K equilibrium temperature. From the observed grain boundary groove shapes, the Gibbs-Thomson coefficient (Gamma) and solid-liquid interfacial energy (sigma(SL)) of solid SCN solution have been determined to be (5.43 +/- 0.50) x 10(-8) K m and (8.09 +/- 1.21) x 10(-3) J m(-2), respectively. The grain boundary energy of solid SCN solution has been determined to be (14.22 +/- 2.28) x 10(-3) J m(-2) from the observed grain boundary groove shapes. The thermal conductivity for SCN-9.55 mole% NPG eutectic solid phase and the thermal conductivity ratio of eutectic liquid phase to eutectic solid phase at the melting temperature have also been measured with a radial heat flow apparatus and Bridgman type growth apparatus, respectively. (C) 2013 Elsevier B.V. All rights reserved