7,804 research outputs found

    Effort and Ethics

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    In this paper, I start by describing two categories into which effort can be divided. The first category I call objective effort, which refers to the external factors associated with an action; the second I call subjective effort, which deals with the internal psychological or mental effort required to bring oneself to perform an action. I then track my intuitions about how objective effort and subjective effort are relevant to the moral evaluations of actions and agents, and further develop this descriptive account by explaining these intuitions normatively through the lenses of contractualism and virtue ethics. Having given my account of how effort plays a role in ethics, I show how understanding the role of effort can change the way we look at the distinction between doing harm and allowing harm. I do this by describing how actions and omissions can be understood through effort, giving my account of the distinction between doing harm and allowing harm, and then comparing my account with others’ accounts. Finally, I touch on the distinction between intending harm and foreseeing harm to show that thinking about effort is relevant not only to the particular example of the dialogue surrounding the distinction between doing harm and allowing harm, but also to other discussions as well

    Exact Algorithms via Multivariate Subroutines

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    We consider the family of Phi-Subset problems, where the input consists of an instance I of size N over a universe U_I of size n and the task is to check whether the universe contains a subset with property Phi (e.g., Phi could be the property of being a feedback vertex set for the input graph of size at most k). Our main tool is a simple randomized algorithm which solves Phi-Subset in time (1+b-(1/c))^n N^(O(1)), provided that there is an algorithm for the Phi-Extension problem with running time b^{n-|X|} c^k N^{O(1)}. Here, the input for Phi-Extension is an instance I of size N over a universe U_I of size n, a subset X subseteq U_I, and an integer k, and the task is to check whether there is a set Y with X subseteq Y subseteq U_I and |Y X| <= k with property Phi. We derandomize this algorithm at the cost of increasing the running time by a subexponential factor in n, and we adapt it to the enumeration setting where we need to enumerate all subsets of the universe with property Phi. This generalizes the results of Fomin et al. [STOC 2016] who proved the case where b=1. As case studies, we use these results to design faster deterministic algorithms for: - checking whether a graph has a feedback vertex set of size at most k - enumerating all minimal feedback vertex sets - enumerating all minimal vertex covers of size at most k, and - enumerating all minimal 3-hitting sets. We obtain these results by deriving new b^{n-|X|} c^k N^{O(1)}-time algorithms for the corresponding Phi-Extension problems (or enumeration variant). In some cases, this is done by adapting the analysis of an existing algorithm, or in other cases by designing a new algorithm. Our analyses are based on Measure and Conquer, but the value to minimize, 1+b-(1/c), is unconventional and requires non-convex optimization

    A Small Family of Elements with Long Inverted Repeats is Located Near Sites of Developmentally Regulated DNA Rearrangement in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e

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    Extensive DNA rearrangement occurs during the development of the somatic macronucleus from the germ line micronucleus in ciliated protozoans. The micronuclear junctions and the macronuclear product of a developmentally regulated DNA rearrangement in Tetrahymena thermophila, Tlr1, have been cloned. The intrachromosomal rearrangement joins sequences that are separated by more than 13 kb in the micronucleus with the elimination of moderately repeated micronucleus-specific DNA sequences. There is a long, 825-bp, inverted repeat near the micronuclear junctions. The inverted repeat contains two different 19-bp tandem repeats. The 19-bp repeats are associated with each other and with DNA rearrangements at seven locations in the micronuclear genome. Southern blot analysis is consistent with the occurrence of the 19-bp repeats within pairs of larger repeated sequences. Another family member was isolated. The 19-mers in that clone are also in close proximity to a rearrangement junction. We propose that the 19-mers define a small family of developmentally regulated DNA rearrangements having elements with long inverted repeats near the junction sites. We discuss the possibility that transposable elements evolve by capture of molecular machinery required for essential cellular functions

    Quantifying polarization across political groups on key policy issues using sentiment analysis

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    There is growing concern that over the past decade, industrialized democratic nations are becoming increasingly politically polarized. Indeed, elections in the US, UK, France, and Germany have all seen tightly won races, with notable examples including the 2016 Trump vs. Clinton presidential election and the UK's Brexit referendum. However, while there has been much qualitative discussion of polarization on key issues, there are few examples of formal quantitative assessments examining this topic. Therefore, in this paper, we undertake a statistical evaluation of political polarization for representatives elected to the US congress on key policy issues between 2021-2022. The method is based on applying sentiment analysis to Twitter data and developing quantitative analysis for six political groupings defined based on voting records. Two sets of policy groups are explored, including geopolitical policies (e.g., Ukraine-Russia, China, Taiwan, etc.) and domestic policies (e.g., abortion, climate change, LGBTQ, immigration, etc.). We find that out of the twelve policies explored here, gun control was the most politically polarizing, with significant polarization results found for all groups (four of which were P < 0.001). The next most polarizing issues include immigration and border control, fossil fuels, and Ukraine-Russia. Interestingly, the least polarized policy topics were Taiwan, LGBTQ, and the Chinese Communist Party, potentially demonstrating the highest degree of bipartisanship on these issues. The results can be used to guide future policy making, by helping to identify areas of common ground across political groups.Comment: 31 pages, 7 figure

    Insights Into The Roles of Desolvation and π-Electron Interactions During DNA Polymerization

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    This report describes the use of several isosteric non-natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π-electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high- and low-fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high-fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low-fidelity HIV-1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non-natural nucleotides that are capable of hydrogen-bonding or π-stacking interactions. Surprisingly, hydrophobic analogues that function as efficient substrates for the E. coli Klenow fragment behave as noncompetitive or uncompetitive inhibitors against HIV-1 reverse transcriptase. In these cases, the mode of inhibition depends upon the absence or presence of a templating nucleobase. Molecular modeling studies suggest that these analogues bind to the active site of reverse transcriptase as well as to a nearby hydrophobic binding pocket. Collectively, the studies using these non-natural nucleotides reveal important mechanistic differences between representative high- and low-fidelity DNA polymerases during nucleotide selection and incorporation

    Quantifying the energetic contributions of desolvation and π-electron density during translesion DNA synthesis

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    This report examines the molecular mechanism by which high-fidelity DNA polymerases select nucleotides during the replication of an abasic site, a non-instructional DNA lesion. This was accomplished by synthesizing several unique 5-substituted indolyl 2′-deoxyribose triphosphates and defining their kinetic parameters for incorporation opposite an abasic site to interrogate the contributions of π-electron density and solvation energies. In general, the Kd, app values for hydrophobic non-natural nucleotides are ∼10-fold lower than those measured for isosteric hydrophilic analogs. In addition, kpol values for nucleotides that contain less π-electron densities are slower than isosteric analogs possessing higher degrees of π-electron density. The differences in kinetic parameters were used to quantify the energetic contributions of desolvation and π-electron density on nucleotide binding and polymerization rate constant. We demonstrate that analogs lacking hydrogen-bonding capabilities act as chain terminators of translesion DNA replication while analogs with hydrogen bonding functional groups are extended when paired opposite an abasic site. Collectively, the data indicate that the efficiency of nucleotide incorporation opposite an abasic site is controlled by energies associated with nucleobase desolvation and π-electron stacking interactions whereas elongation beyond the lesion is achieved through a combination of base-stacking and hydrogen-bonding interactions
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