Explaining Black-Box Models through Counterfactuals

We present CounterfactualExplanations.jl: a package for generating Counterfactual Explanations (CE) and Algorithmic Recourse (AR) for black-box models in Julia. CE explain how inputs into a model need to change to yield specific model predictions. Explanations that involve realistic and actionable changes can be used to provide AR: a set of proposed actions for individuals to change an undesirable outcome for the better. In this article, we discuss the usefulness of CE for Explainable Artificial Intelligence and demonstrate the functionality of our package. The package is straightforward to use and designed with a focus on customization and extensibility. We envision it to one day be the go-to place for explaining arbitrary predictive models in Julia through a diverse suite of counterfactual generators.Comment: 13 pages, 9 figures, originally published in The Proceedings of the JuliaCon Conferences (JCON

Determination of Tissue Iron and Ferritin in Liver Pathology. Comparison of Histochemical and Biochemical Results

Peer Reviewe

ras Oncogene Activation Does Not Induce Sensitivity to Natural Killer Cell—Mediated Lysis in Human Melanoma

An important phenomenon in tumor immunology that has come under recent attention is the impact of oncogene activation in tumor cells on the sensitivity to lysis by immune effector cells. Several studies suggested that transfer of an activated ras oncogene into cultured rodent fibroblasts induces susceptibility to natural killer cell (NK)-mediated lysis. Experiments using human tumor cells, however, have produced conflicting data on the effect of ras activation in this respect. In studying the activation of the oncogene c-myc, which is often overexpressed in human melanoma, we have found that in cell lines expressing high levels of Myc protein, the sensitivity to lysis by NK cells was dramatically increased due to reduced expression of Human Leukocyte Antigen B locus products. Since the N-ras oncogene was found to be activated in 15% of human melanomas, we examined the possibility that in melanoma, in analogy to the murine systems, the mutated ras oncogene may influence NK susceptibility of human melanoma cells. Two N-ras genes harboring frequently found mutations were cloned into an expression vector. Transfection of the IGR39D melanoma cell line with wildtype and mutant N-ras constructs yielded several ras-expressing clones that were tested for NK sensitivity. Neither high expression of the wildtype N-ras protein, nor expression of two mutant proteins (N61-arg, N61-lys) was shown to result in enhanced NK-mediated lysis. We conclude that activation of ras oncogenes does not lead to the induction of an NK-sensitive phenotype in human melanoma cells. J Invest Dermatol 103:117S–121S, 199

Endogenous Macrodynamics in Algorithmic Recourse

Existing work on Counterfactual Explanations (CE) and Algorithmic Recourse (AR) has largely focused on single individuals in a static environment: given some estimated model, the goal is to find valid counterfactuals for an individual instance that fulfill various desiderata. The ability of such counterfactuals to handle dynamics like data and model drift remains a largely unexplored research challenge. There has also been surprisingly little work on the related question of how the actual implementation of recourse by one individual may affect other individuals. Through this work, we aim to close that gap. We first show that many of the existing methodologies can be collectively described by a generalized framework. We then argue that the existing framework does not account for a hidden external cost of recourse, that only reveals itself when studying the endogenous dynamics of recourse at the group level. Through simulation experiments involving various state-of the-art counterfactual generators and several benchmark datasets, we generate large numbers of counterfactuals and study the resulting domain and model shifts. We find that the induced shifts are substantial enough to likely impede the applicability of Algorithmic Recourse in some situations. Fortunately, we find various strategies to mitigate these concerns. Our simulation framework for studying recourse dynamics is fast and opensourced.Comment: 12 pages, 11 figures. Originally published at the 2023 IEEE Conference on Secure and Trustworthy Machine Learning (SaTML). IEEE holds the copyrigh

Senescent cells in the development of cardiometabolic disease

Purpose of review Senescent cells have recently been identified as key players in the development of metabolic dysfunction. In this review, we will highlight recent developments in this field and discuss the concept of targeting these cells to prevent or treat cardiometabolic diseases. Recent findings Evidence is accumulating that cellular senescence contributes to adipose tissue dysfunction, presumably through induction of low-grade inflammation and inhibition of adipogenic differentiation leading to insulin resistance and dyslipidaemia. Senescent cells modulate their surroundings through their bioactive secretome and only a relatively small number of senescent cells is sufficient to cause persistent physical dysfunction even in young mice. Proof-of-principle studies showed that selective elimination of senescent cells can prevent or delay the development of cardiometabolic diseases in mice. Summary The metabolic consequences of senescent cell accumulation in various tissues are now unravelling and point to new therapeutic opportunities for the treatment of cardiometabolic diseases

Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate

Arhivske vijesti o pučkoj drami u srednjoj Dalmaciji

© 2017 Association for Computing Machinery. Context: The research literature on software development projects usually assumes that effort is a good proxy for cost. Practice, however, suggests that there are circumstances in which costs and effort should be distinguished. Objectives: We determine similarities and differences between size, effort, cost, duration, and number of defects of software projects. Method: We compare two established repositories (ISBSG and EBSPM) comprising almost 700 projects from industry. Results: We demonstrate a (log)-linear relation between cost on the one hand, and size, duration and number of defects on the other. This justifies conducting linear regression for cost. We establish that ISBSG is substantially different from EBSPM, in terms of cost (cheaper) and duration (faster), and the relation between cost and effort. We show that while in ISBSG effort is the most important cost factor, this is not the case in other repositories, such as EBSPM in which size is the dominant factor. Conclusion: Practitioners and researchers alike should be cautious when drawing conclusions from a single repository

Review of harm-benefit analysis in the use of animals in research

This is the final version of the report. Available from the Home Office via the link in this recordReport of our review of the processes of harm-benefit analysis (HBA) carried out under the UK Animals (Scientific Procedures) Act 1986 (A(SP)A).Report of the Animals in Science Committee Harm-Benefit Analysis Sub-Group chaired by Professor Gail Davies. The Animals in Science Committee Harm-Benefit Analysis subgroup, chaired by Professor Gail Davies, has produced a review of the harm-benefit analysis (HBA). This review is an analysis of the underpinnings and implementation of the HBA which remains a crucial step in the justification of the use of animals in science. It is published in response to a ministerial commission.Animals in Science Committe