Better decision support through exploratory discrimination-aware data mining: foundations and empirical evidence

Decision makers in banking, insurance or employment mitigate many of their risks by telling “good” individuals and “bad” individuals apart. Laws codify societal understandings of which factors are legitimate grounds for differential treatment (and when and in which contexts)—or are considered unfair discrimination, including gender, ethnicity or age. Discrimination-aware data mining (DADM) implements the hope that information technology supporting the decision process can also keep it free from unjust grounds. However, constraining data mining to exclude a fixed enumeration of potentially discriminatory features is insufficient. We argue for complementing it with exploratory DADM, where discriminatory patterns are discovered and flagged rather than suppressed. This article discusses the relative merits of constraint-oriented and exploratory DADM from a conceptual viewpoint. In addition, we consider the case of loan applications to empirically assess the fitness of both discrimination-aware data mining approaches for two of their typical usage scenarios: prevention and detection. Using Mechanical Turk, 215 US-based participants were randomly placed in the roles of a bank clerk (discrimination prevention) or a citizen / policy advisor (detection). They were tasked to recommend or predict the approval or denial of a loan, across three experimental conditions: discrimination-unaware data mining, exploratory, and constraint-oriented DADM (eDADM resp. cDADM). The discrimination-aware tool support in the eDADM and cDADM treatments led to significantly higher proportions of correct decisions, which were also motivated more accurately. There is significant evidence that the relative advantage of discrimination-aware techniques depends on their intended usage. For users focussed on making and motivating their decisions in non-discriminatory ways, cDADM resulted in more accurate and less discriminatory results than eDADM. For users focussed on monitoring for preventing discriminatory decisions and motivating these conclusions, eDADM yielded more accurate results than cDADM.     

Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity

12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).     

Theophylline: Old Drug in a New Light,Application in COVID-19 through Computational Studies

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.     

Impact of microarray technology in nutrition and food research

Microarrays have become standard tools for gene expression profiling as the mRNA levels of a large number of genes can be measured in a single assay. Many technical aspects concerning microarray production and laboratory usage have been addressed in great detail, but it remains still crucial to establish this technology in new research fields such as human nutrition and food-related areas. The correlation between diet and inter-individual variation in gene expression is an important and relatively unexplored issue in human nutrition. Therefore, nutritionists changed their research field dramatically from epidemiology and physiology towards the "omics" sciences. Nutrigenomics as a field of research is based on the complete knowledge of the human genome and refers to the entire spectrum of human genes that determine the interactions of nutrition with the organism. Nutrigenetics is based on the inter-individual, genetically determined differences in metabolism. Nutrigenomics and nutrigenetics carry the hope that individualized diet can improve human health and prevent nutrition-related diseases. In this article we give an overview of current DNA and protein microarray techniques (including fabrication, experimental procedure and data analysis), we describe their applications to nutrition and food research and point out the limitations, problems and pitfalls of microarray experiments.     

Groundwater quota versus tiered groundwater pricing: two cases of groundwater management in north-west China

Difficulties in monitoring groundwater extraction cause groundwater regulations to fail worldwide. In two counties in north-west China local water authorities have installed smart card machines to monitor and regulate farmers’ groundwater use. Data from a household survey and in-depth interviews are used to evaluate the effectiveness of the different regulatory institutions implemented with help of the smart card machines. In the given context, groundwater quota is more effective in curbing farmers’ groundwater use than the tiered groundwater pricing. The study shows that the usefulness of smart card machines depends on their embedding in the societal context and related regulatory institutions.     

Crystal Structure Determination and Mutagenesis Analysis of the Ene Reductase NCR

The crystal structure of the “ene” nicotinamide‐dependent cyclohexenone reductase (NCR) from Zymomonas mobilis (PDB ID: 4A3U) has been determined in complex with acetate ion, FMN, and nicotinamide, to a resolution of 1.95 Å. To study the activity and enantioselectivity of this enzyme in the bioreduction of activated α,β‐unsaturated alkenes, the rational design methods site‐ and loop‐directed mutagenesis were applied. Based on a multiple sequence alignment of various members of the Old Yellow Enzyme family, eight single‐residue variants were generated and investigated in asymmetric bioreduction. Furthermore, a structural alignment of various ene reductases predicted four surface loop regions that are located near the entrance of the active site. Four NCR loop variants, derived from loop‐swapping experiments with OYE1 from Saccharomyces pastorianus, were analysed for bioreduction. The three enzyme variants, P245Q, D337Y and F314Y, displayed increased activity compared to wild‐type NCR towards the set of substrates tested. The active‐site mutation Y177A demonstrated a clear influence on the enantioselectivity. The loop‐swapping variants retained reduction efficiency, but demonstrated decreased enzyme activity compared with the wild‐type NCR ene reductase enzyme.     

Algorithmic Aspects of Proportional Symbol Maps

Proportional symbol maps visualize numerical data associated with point locations by placing a scaled symbol—typically an opaque disk or square—at the corresponding point on a map. The area of each symbol is proportional to the numerical value associated with its location. Every visually meaningful proportional symbol map will contain at least some overlapping symbols. These need to be drawn in such a way that the user can still judge their relative sizes accurately.