Metrics for Identifying Bias in Datasets

Nowadays automated decision-making systems are pervasively used and more often, they are used for taking important decisions in sensitive areas such as the granting of a bank overdraft, the susceptibility of an individual to a virus infection, or even the likelihood of repeating a crime. The widespread use of these systems raises a growing ethical concern about the risk of a potential discriminatory impact. In particular, machine-learning systems trained on unbalanced data could rise to systematic discriminations in the real world. One of the most important challenges is to determine metrics capable of detecting when an unbalanced training dataset may lead to discriminatory behaviour of the model built on it. In this paper, we propose an approach based on the notion of data completeness using two different metrics: one based on the combinations of the values of the dataset, which will be our benchmark, and the second using frame theory, widely used among others for quality measures of control systems. It is important to remark that the use of metrics cannot be a substitute for a broader design that must take into account the columns that could lead to the presence of bias in the data. The line of research does not end with these activities but aims to continue the path towards a standardised register of measures

Integrating SQuARE data quality model with ISO 31000 risk management to measure and mitigate software bias

In the last decades the exponential growth of available information, together with the availability of systems able to learn the knowledge that is present in the data, has pushed towards the complete automation of many decision- making processes in public and private organizations. This circumstance is posing impelling ethical and legal issues since a large number of studies and journalistic investigations showed that software-based decisions, when based on historical data, perpetuate the same prejudices and bias existing in society, resulting in a systematic and inescapable negative impact for individuals from minorities and disadvantaged groups. The problem is so relevant that the terms data bias and algorithm ethics have become familiar not only to researchers, but also to industry leaders and policy makers. In this context, we believe that the ISO SQuaRE standard, if appropriately integrated with risk management concepts and procedures from ISO 31000, can play an important role in democratizing the innovation of software-generated decisions, by making the development of this type of software systems more socially sustainable and in line with the shared values of our societies. More in details, we identified two additional measure for a quality characteristic already present in the standard (completeness) and another that extends it (balance) with the aim of highlighting information gaps or presence of bias in the training data. Those measures serve as risk level indicators to be checked with common fairness measures that indicate the level of polarization of the software classifications/predictions. The adoption of additional features with respect to the standard broadens its scope of application, while maintaining consistency and conformity. The proposed methodology aims to find correlations between quality deficiencies and algorithm decisions, thus allowing to verify and mitigate their impact

designing digital circuits in multi valued logic

In the last few decades we have witnessed an increase in CPU performance, which has been made possible thanks to the increase in the clock frequency and the increase in the number of transistors in the unit of space. In the last few years, however, we reached the limit for the clock and for the miniaturization of the transistor grid. Beyond this growth new problems arose such as the disposal of the produced heat and the minimum distance to be respected between elements for the electrical signals transfer. So the chip makers, to further increase the processing power of the processors, started to insert more cores on the same chip. The presence of several cores undoubtedly improves performance and improves consumption, but the ability to transfer data between cores and components remains limited by the number of pins of the cores themselves. Furthermore, it is necessary to manage the synchronization between cores during the access to common resources and all those multi-core architectures typical problems. This article provides a different approach to improve the computing capacity of the CPUs that is based on the extension of the binary system in a multi-value coding system or, commonly, called MVL. Although this direction has already been explored, the idea behind the study is in the representation of the generic function in the MVL domain. This representation has a link to the binary system and a surprisingly greater simplicity of the corresponding digital circuits (combinatorial and sequential). A different mathematical approach is thus provided for the realization of the multivalue logic gates. This could enable the use of different data encoding systems no longer linked to the voltage value of a signal but to other physical quantities as it happens at present, for example, in the world of telecommunications

Effectiveness of the histone deacetylase inhibitor (S)-2 against LNCaP and PC3 human prostate cancer cells

Histone deacetylase inhibitors (HDACi) represent a promising class of epigenetic agents with anticancer properties. Here, we report that (S)-2, a novel hydroxamate-based HDACi, shown previously to be effective against acute myeloid leukemia cells, was also a potent inducer of apoptosis/differentiation in human prostate LNCaP and PC3 cancer cells. In LNCaP cells (S)-2 was capable of triggering H3/H4 histone acetylation, H2AX phosphorylation as a marker of DNA damage and producing G(0)/G(1) cell cycle arrest. Consistently, (S)-2 led to enhanced expression of both the protein and mRNA p21 levels in LNCaP cells but, contrary to SAHA, not in normal non-tumorigenic prostate PNT1A cells. Mechanistic studies demonstrated that (S)-2-induced apoptosis in LNCaP cells developed through the cleavage of pro-caspase 9 and 3 and of poly(ADP-ribose)-polymerase accompanied by the dose-dependent loss of mitochondrial membrane potential. Indeed, the addition of the pan-caspase inhibitor Z-VAD-fmk greatly reduced drug-mediated apoptosis while the antioxidant N-acetyl-cysteine was virtually ineffective. Importantly, preliminary data with nude mice xenografted with LNCaP cells showed that (S)-2 prompted a decrease in the tumor volume and an increase in H2AX phosphorylation within the cancer cells. Moreover, the highly metastatic prostate cancer PC3 cells were also sensitive to (S)-2 that: i) induced growth arrest and moderate apoptosis; ii) steered cells towards differentiation and neutral lipid accumulation; iii) reduced cell invasiveness potential by decreasing the amount of MMP-9 activity and up-regulating TIMP-1 expression; and iv) inhibited cell motility and migration through the Matrigel. Overall, (S)-2 has proven to be a powerful HDACi capable of inducing growth arrest, cell death and/or differentiation of LNCaP and PC3 prostate cancer cells and, due to its low toxicity and efficacy in vivo, might also be of clinical interest to support conventional prostate cancer therapy

HDAC1 controls CIP2A transcription in human colorectal cancer cells

This work describes the effectiveness of HDAC-inhibitor (S)-2 towards colorectal cancer (CRC) HCT116 cells in vitro by inducing cell cycle arrest and apoptosis, and in vivo by contrasting tumour growth in mice xenografts. Among the multifaceted drug-induced events described herein, an interesting link has emerged between the oncoprotein histone deacetylase HDAC1 and the oncogenic Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) which is overexpressed in several cancers including CRCs. HDAC1 inhibition by (S)-2 or specific siRNAs downregulates CIP2A transcription in three different CRC cell lines, thus restoring the oncosuppressor phosphatase PP2A activity that is reduced in most cancers. Once re-activated, PP2A dephosphorylates pGSK-3β(ser9) which phosphorylates β-catenin that remains within the cytosol where it undergoes degradation. The decreased amount/activity of β-catenin transcription factor prompts cell growth arrest by diminishing c-Myc and cyclin D1 expression and abrogating the prosurvival Wnt/β-catenin signaling pathway. These results are the first evidence that the inhibition of HDAC1 by (S)-2 downregulates CIP2A transcription and unleashes PP2A activity, thus inducing growth arrest and apoptosis in CRC cells

GROWTH INHIBITION AND DIFFERENTIATION OF HUMAN BREAST CANCER CELLS BY THE PAFR ANTAGONIST WEB-2086

WEB-2086 – an antagonist of platelet-activating factor receptor (PAFR) with known anti-inflammatory, antiangiogenic and antileukaemic properties – also proved to inhibit the proliferation in human solid tumour cell lines of different histology, and with much higher efficacy than in normal fibroblasts. A detailed analysis of WEB-2086 anticancer activity was then performed focusing on breast adenocarcinoma MCF-7 and MDA-MB-231 cells. WEB-2086-treated cells, either expressing (MCF-7) or unexpressing (MDA-MB-231) the oestrogen receptor (ER)α, underwent a dose-dependent growth arrest (IC(50)=0.65±0.09 and 0.41±0.07 mM, respectively) and accumulation in G(0)–G(1) phase. WEB-2086 also induced morphological and functional changes typical of mature mammary phenotype including (i) cell enlargement and massive neutral lipid deposition (best accomplished in MCF-7 cells); (ii) decrease in motility and active cathepsin D levels (mainly observed in highly invasive MDA-MB-231 cells). The expression of ERα was neither increased nor reactivated in treated MCF-7 or MDA-MB-231 cells, respectively. WEB-2086-induced differentiation in breast cancer cells involved the upregulation of PTEN, a key tumour suppressor protein opposing tumorigenesis, and was apparently independent of p53, PAFR, peripheral benzodiazepine receptor and ERα status. Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy

Impacts of air pollution on human and ecosystem health, and implications for the National Emission Ceilings Directive. Insights from Italy

Across the 28 EU member states there were nearly half a million premature deaths in 2015 as a result of exposure to PM2.5, O3 and NO2. To set the target for air quality levels and avoid negative impacts for human and ecosystems health, the National Emission Ceilings Directive (NECD, 2016/2284/EU) sets objectives for emission reduction for SO2, NOx, NMVOCs, NH3 and PM2.5 for each Member State as percentages of reduction to be reached in 2020 and 2030 compared to the emission levels into 2005. One of the innovations of NECD is Article 9, that mentions the issue of “monitoring air pollution impacts” on ecosystems. We provide a clear picture of what is available in term of monitoring network for air pollution impacts on Italian ecosystems, summarizing what has been done to control air pollution and its effects on different ecosystems in Italy. We provide an overview of the impacts of air pollution on health of the Italian population and evaluate opportunities and implementation of Article 9 in the Italian context, as a case study beneficial for all Member States. The results showed that SO42− deposition strongly decreased in all monitoring sites in Italy over the period 1999–2017, while NO3− and NH4+ decreased more slightly. As a consequence, most of the acid-sensitive sites which underwent acidification in the 1980s partially recovered. The O3 concentration at forest sites showed a decreasing trend. Consequently, AOT40 (the metric identified to protect vegetation from ozone pollution) showed a decrease, even if values were still above the limit for forest protection (5000 ppb h−1), while PODy (flux-based metric under discussion as new European legislative standard for forest protection) showed an increase. National scale studies pointed out that PM10 and NO2 induced about 58,000 premature deaths (year 2005), due to cardiovascular and respiratory diseases. The network identified for Italy contains a good number of monitoring sites (6 for terrestrial ecosystem monitoring, 4 for water bodies monitoring and 11 for ozone impact monitoring) distributed over the territory and will produce a high number of monitored parameters for the implementation of the NECD

The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukemia cells

Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++)-chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4– but not (R)-2 – caused G0/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum