Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences

Mapping Inhibitor Binding Modes on an Active Cysteine Protease via Nuclear Magnetic Resonance Spectroscopy

Cruzain is a member of the papain/cathepsin L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We report an autoinduction methodology that provides soluble cruzain in high yields (>30 mg/L in minimal medium). These increased yields provide sufficient quantities of active enzyme for use in nuclear magnetic resonance (NMR)-based ligand mapping. Using circular dichroism and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective [(15)N]Cys, [(15)N]His, and [(13)C]Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low-molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verified that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely, covalent, noncovalent, and noninteracting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions to facilitate lead compound identification and subsequent structural studies

Free Economy! On 3628800 Alternatives of and to Capitalism

Even the sharpest problem focus cannot help but sharpen the problem. Thus, the key to our understanding of alternatives to capitalism and alternative forms of capitalism is not in the on-going problematization of the dominance of the economic principle. Rather, the question addressed in the present form-theoretical argument is as to which distinctions we need to draw in order to be at all able to observe capitalism. Answering this question, we show that capitalism is a form that can only be unfolded in the medium of functional differentiation. In resituating the economy as only one out of ten function systems, we demonstrate that both pro- and anti-capitalist concepts of society imply an economy-bias and, consequently, a neglect of the remaining function systems. We therefore suggest that the observation of both alternatives to capitalism and alternative capitalisms calls for a stronger focus on the non-economic function systems. Finally, we present an outlook on a way to more than three million alternatives of and to capitalism