On Meritocracy in Optimal Set Selection

We consider the problem of selecting a set of individuals from a candidate population in order to maximise utility. When the utility function is defined over sets, this raises the question of how to define meritocracy. We define and analyse an appropriate notion of meritocracy derived from the utility function. We introduce the notion of expected marginal contributions of individuals and analyse its links to the underlying optimisation problem, our notion of meritocracy, and other notions of fairness such as the Shapley value. We also experimentally analyse the effect of different policy structures on the utility and meritocracy in a simulated college admission setting including constraints on statistical parity

Hydrophobically Modified let-7b miRNA Enhances Biodistribution to NSCLC and Downregulates HMGA2 In Vivo

MicroRNAs (miRNAs) have increasingly been shown to be involved in human cancer, and interest has grown about the potential use of miRNAs for cancer therapy. miRNA levels are known to be altered in cancer cells, including in non-small cell lung cancer (NSCLC), a subtype of lung cancer that is the most prevalent form of cancer worldwide and that lacks effective therapies. The let-7 miRNA is involved in the regulation of oncogene expression in cells and directly represses cancer growth in the lung. let-7 is therefore a potential molecular target for tumor therapy. However, applications of RNA interference for cancer research have been limited by a lack of simple and efficient methods to deliver oligonucleotides (ONs) to cancer cells. In this study, we have used in vitro and in vivo approaches to show that HCC827 cells internalize hydrophobically modified let-7b miRNAs (hmiRNAs) added directly to the culture medium without the need for lipid formulation. We identified functional let-7b hmiRNAs targeting the HMGA2 mRNA, one of the let-7 target genes upregulated in NSCLC, and show that direct uptake in HCC827 cells induced potent and specific gene silencing in vitro and in vivo. Thus, hmiRNAs constitute a novel class of ONs that enable functional studies of genes involved in cancer biology and are potentially therapeutic molecules

Philosophy of Hope

The philosophy of hope centers on two interlocking sets of questions. The first concerns the nature of hope. Specific questions here include how to analyze hope, how hope motivates us, and whether there is only one type of hope. The second set concerns the value of hope. Key questions here include whether and when it is good to hope and whether there is a virtue of hope. Philosophers of hope tend to proceed from the first set of questions to the second. This is a natural approach, for one might expect that you must develop a basic understanding of what hope is before you can determine its value. The structure of this chapter thus follows this approach. But readers should not be misled: there is in fact a good deal of feedback between the two sets of questions. A theory of hope is more plausible to the extent that it fits well with plausible ideas about the value of hope. So the movement from hope’s nature to its value is one of emphasis rather than a strict, step-wise process

Hope, Powerlessness, and Agency

Hope is hard to characterise because of the exceptional diversity of its applications, to the point that one may wonder whether there is continuity between ordinary cases of hope and what is often called 'hope against hope'. In this paper, I shall follow the relatively small but growing literature on hope and examine propositional hopes, i.e. hopes of the form 'hoping that p', with a particular focus on recent work by Philip Pettit and Adrienne Martin. I shall do this first by identifying a significant difficulty encountered by what has become known as the 'orthodox definition' (Martin 2014, henceforth 'OD'). The OD defines hope by means of two necessary and sufficient conditions: A hopes that p if and only if (1) A desires that p and (2) A assigns to p a degree of probability between (and excluding) 0 and 1. On this definition, to hope is to desire an outcome we deem neither certain nor impossible. Note that the relevant probability assignment is subjective: the OD allows, for example, that children can hope for Father Christmas to visit them on Christmas Eve

On Meritocracy in Optimal Set Selection

We consider the problem of selecting a set of individuals from a candidate population in order to maximise utility. When the utility function is defined over sets, this raises the question of how to define meritocracy. We define and analyse an appropriate notion of meritocracy derived from the utility function. We introduce the notion of expected marginal contributions of individuals and analyse its links to the underlying optimisation problem, our notion of meritocracy, and other notions of fairness such as the Shapley value. We also experimentally analyse the effect of different policy structures on the utility and meritocracy in a simulated college admission setting including constraints on statistical parity

On Meritocracy in Optimal Set Selection

International audienceTypically, merit is defined with respect to some intrinsic measure of worth. We instead consider a setting where an individual’s worth is relative: when a decision maker (DM) selects a set of individuals from a population to maximise expected utility, it is natural to consider the expected marginal contribution (EMC) of each person to the utility. We show that this notion satisfies an axiomatic definition of fairness for this setting. We also show that for certain policy structures, this notion of fairness is aligned with maximising expected utility, while for linear utility functions it is identical to the Shapley value. However, for certain natural policies, such as those that select individuals with a specific set of attributes (e.g. high enough test scores for college admissions), there is a trade-off between meritocracy and utility maximisation. We analyse the effect of constraints on the policy on both utility and fairness in an extensive experiments based on college admissions and outcomes in Norwegian universities

Detection of mRNA of the Cyclin D1 Breast Cancer Marker by a Novel Duplex-DNA Probe

Previously, we have described 5-((4-methoxy-phenyl)-<i>trans</i>-vinyl)-2′-deoxy-uridine, <b>6</b>, as a fluorescent uridine analogue exhibiting a 3000-fold higher quantum yield (Φ 0.12) and maximum emission (478 nm) which is 170 nm red-shifted as compared to uridine. Here, we utilized <b>6</b> for preparation of labeled oligodeoxynucleotide (ODN) probes based on MS2 and cyclin D1 (a known breast cancer mRNA marker) sequences. Cyclin D1-derived labeled-ssODN showed a 9.5-fold decrease of quantum yield upon duplex formation. On the basis of this finding, we developed the ds-NIF (nucleoside with intrinsic fluorescence)-probe methodology for detection of cyclin D1 mRNA, by which the fluorescent probe is released upon recognition of target mRNA by the relatively dark NIF-duplex-probe. Indeed, we successfully detected, a ss-deoxynucleic acid (DNA) variant of cyclin D1 mRNA using a dark NIF-labeled duplex-probe, and monitoring the recognition process by fluorescence spectroscopy and gel electrophoresis. Furthermore, we successfully detected cyclin D1 mRNA in RNA extracted from cancerous human cells, using ds-NIF methodology