A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

Aim4GDI: Facilitating the Synthesis of GDI Resources through Mapping and Superimpositions of Metadata Summaries

In the world of geospatial data infrastructures, geoportals are developed to facilitate access and use of geospatial resources, including data. The design and implementation of effective and efficient geoportals are becoming crucial. Providing possibilities for users to organize and integrate available resources can arguably enhance the process of data discovery and spatial analysis required, and hence, is the focus of this paper. We argue that the synthesis of summaries of distributed datasets, map and feature services through the geoportal can present a coherent view to support data discovery. For this purpose, the atlas metaphor is used as an indexing server and integration interface of summaries. Thematic maps and a storyteller view are accessible through the atlas metaphor. They can be used to provide a supporting context for data discovery and access purposes.

Simflowny: A general-purpose platform for the management of physical models and simulation problems

Simflowny is a software platform which aims to formalize the main elements of a simulation flow. It allows users to manage (i) formal representations of physical models based on Initial Value Problems (hyperbolic, parabolic and mixed-type partial differential equations), (ii) simulation problems based on such models, and (iii) discretization schemes to translate the problem to a finite mesh. Additionally, Simflowny generates automatically code for general-purpose simulation frameworks. This paper first presents an introductory example of such problems. Then, formal representations are explained. Afterwards, it summarizes the platform’s architecture. Finally, validation results are provided.     

From the times of the first scribes: innovation and technology within graphic design

The authors use their different work and training background as perspectives for discussing the changing world of graphical design. In this digital world, expert knowledge of the technology is essential, but the authors argue that a consequence of prioritising technical expertise in the new interdisciplinary IT- design studies may be a loss of quality in design. To improve the depth in design the authors introduce a psychological framework for design work and on this basis they suggest a systematic method. The method is a 4-step conceptual model: reason, function, emotion and senses, and technology. The model interacts with all phases of the design, and functions as a generating-creating and execution-evaluation system. The authors emphasise that evaluation is embedded throughout the design process. They suggest that a systematic method becomes the guiding tool in interdisciplinary design education, an essential part of the students design qualifications as well as an essential tool in design work.     

Trading properties after the earthquake: the rebuilding of eighteenth‐century Lisbon

This paper introduces the innovative system used in the reconstruction of Lisbon after the 1755 earthquake. Its findings are based on original documents that offer a detailed picture of the principles and methods established to convert the land and properties of the old city into the new and standardized gridded Plan. Implemented in the mid‐eighteenth century, the methodical system outlined was, undoubtedly, an important point of reference for the large‐scale urban improvement and redevelopment operations that would follow in nineteenth‐century Europe.     

ElectroStatic Discharge Fault Localization by Laser Probing

This paper deals with the localization of ElectroStatic Discharge (ESD) failure in digital circuits by thermoelastic laser probing. After ESD simulation on a NAND TTL LS circuit, the device was scanned using an interferometric laser probe. In sine wave regime the surface displacement induced by the leakage current was recorded. The heat source acts as a hot spot inducing a thermal expansion in its neighborhood. This expansion, whose magnitude varies from several hundred to a few picometers (10⁻¹²m), allows the localization of the leakage region corresponding to the ESD failure area.     

Crack propagation in quasi-brittle two-dimensional isotropic lattices

Materials with cellular structure are gaining prominence in recent years due to improvements in production processes, that enable the manufacture of new materials, and biomechanics, that requires mechanical analysis of cellular structures such as bones. The possibility to use the Fracture Mechanics tools developed for the continua to the fracture of cellular materials is analyzed in the present paper. As proposed by Maiti et al. the fracture toughness of cellular solids can be obtained through two procedures: taking into account the stress at crack tip or the fracture toughness of the base material. Both procedures are analyzed and the equivalent R-curve and a cohesive law is obtained in function of the cell size and structure morphology. A critical truss length exists from which crack propagation goes from being governed by the energy dissipated to being governed by the stress field.