Pragmatic Punitiveness: The Institutionalization of Criminal Domestic Violence Protection Orders

This paper analyzes the implementation of a domestic violence law in Minnesota that, in 2006, made the violation of a Domestic Abuse No-Contact Order a felony-level offense. Since this legal change, the rate of conviction for Domestic Abuse No-Contact Order felonies skyrocketed with stark racial disparities among Black and Native American residents, relative to Whites. Analysis of case files reveals that Domestic Abuse No-Contact Order convictions result from a range of behaviors, from seemingly mutual contact between the defendant and protected party to serious physical violence. We argue that the Domestic Abuse No-Contact Order law facilitates pragmatic punitiveness for legal actors. It is easier for prosecutors to demonstrate contact occurred than to prove domestic assault. Yet, the penalty for a Domestic Abuse No-Contact Order is as severe as the penalties for other domestic abuse-related crimes in Minnesota. Thus, the Domestic Abuse No-Contact Order law enables prosecutors to respond forcefully to domestic violence while avoiding additional burdens on their time and resources.

Error analysis of forced discrete mechanical systems

<p style='text-indent:20px;'>The purpose of this paper is to perform an error analysis of the variational integrators of mechanical systems subject to external forcing. Essentially, we prove that when a discretization of contact order <inline-formula><tex-math id="M1">\begin{document}$ r $\end{document}</tex-math></inline-formula> of the Lagrangian and force are used, the integrator has the same contact order. Our analysis is performed first for discrete forced mechanical systems defined over <inline-formula><tex-math id="M2">\begin{document}$ TQ $\end{document}</tex-math></inline-formula>, where we study the existence of flows, the construction and properties of discrete exact systems and the contact order of the flows (variational integrators) in terms of the contact order of the original systems. Then we use those results to derive the corresponding analysis for the analogous forced systems defined over <inline-formula><tex-math id="M3">\begin{document}$ Q\times Q $\end{document}</tex-math></inline-formula>.</p>

Structural asymmetry along protein sequences and co-translational folding

Proteins are translated from the N- to the C-terminal, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the protein data bank (PDB). We find remarkable enrichment of α-helices at the C terminal and β-sheets at the N terminal. Furthermore, this α-β asymmetry correlates with sequence length and contact order, both determinants of folding rate, hinting at possible links to co-translational folding (CTF). Hence, we propose the ‘slowest-first’ scheme, whereby protein sequences evolved structural asymmetry to accelerate CTF: the slowest-folding elements (e.g. β-sheets) are positioned near the N terminal so they have more time to fold during translation. Our model predicts that CTF can be accelerated, up to double the rate, when folding time is commensurate with translation time; analysis of the PDB reveals that structural asymmetry is indeed maximal in this regime. This correspondence is greater in prokaryotes, which generally require faster protein production. Altogether, this indicates that accelerating CTF is a substantial evolutionary force whose interplay with stability and functionality is encoded in sequence asymmetry.

Effect of protein structure on evolution of cotranslational folding

Cotranslational folding is expected to occur when the folding speed of the nascent chain is faster than the translation speed of the ribosome, but it is difficult to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how native structure influences evolution of cotranslational folding. We developed a model that connects protein folding during and after translation to cellular fitness. Model proteins evolved improved folding speed and stability, with proteins adopting one of two strategies for folding quickly. Low contact order proteins evolve to fold cotranslationally. Such proteins adopt native conformations early on during the translation process, with each subsequently translated residue establishing additional native contacts. On the other hand, high contact order proteins tend not to be stable in their native conformations until the full chain is nearly extruded. We also simulated evolution of slowly translating codons, finding that slowing translation at certain positions enhances cotranslational folding. Finally, we investigated real protein structures using a previously published dataset that identified evolutionarily conserved rare codons in E. coli genes and associated such codons with cotranslational folding intermediates. We found that protein substructures preceding conserved rare codons tend to have lower contact orders, in line with our finding that lower contact order proteins are more likely to fold cotranslationally. Our work shows how evolutionary selection pressure can cause proteins with local contact topologies to evolve cotranslational folding.Statement of significanceSubstantial evidence exists for proteins folding as they are translated by the ribosome. Here we developed a biologically intuitive evolutionary model to show that avoiding premature protein degradation can be a sufficient evolutionary force to drive evolution of cotranslational folding. Furthermore, we find that whether a protein’s native fold consists of more local or more nonlocal contacts affects whether cotranslational folding evolves. Proteins with local contact topologies are more likely to evolve cotranslational folding through nonsynonymous mutations that strengthen native contacts as well as through synonymous mutations that provide sufficient time for cotranslational folding intermediates to form.

How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

The correlations between the logarithm of the unfolding rate of 108 proteins and their structural parameters were calculated. We showed that there is a good correlation between the logarithm of folding rates (in native conditions) and unfolding rates (in denaturing conditions) (0.79) and protein stability and unfolding rate (0.79). Thus, the faster the protein folds, the faster it unfolds. Folding and unfolding rates are higher for the proteins with two-state kinetics, in comparison with the proteins with multi-state kinetics. At the same time, two-state bacterial proteins folds and unfolds two orders of magnitude faster than two-state eukaryotic proteins, and multi-state bacterial proteins folds and unfolds slower than multi-state eukaryotic proteins. Despite the fact that the folding rates of thermophilic and mesophilic proteins are close, the unfolding rates of thermophilic proteins is about two orders of magnitude lower than for mesophilic proteins. The correlation between unfolding rate and stability of thermophilic proteins is high (0.90). We also found that the unfolding rate correlates with such structural parameters as: size of the protein, radius of the cross-section, logarithm of absolute contact order, and radius of gyration. This information will be useful for engineering and designing new proteins with desired properties.

Pluperfect Auxiliaries in the Russian Language of the 14th – 16th Centuries

This paper discusses the syntax of the past tense auxiliaries in the vernacular Old Russian plusperfect construction of the type дал был, дал есми был. I prove that the past tense auxiliaries behaved as enclitics both with the order дал есми был and with the order дал был есми. The order of the pluperfect auxiliaries reflects different types of a clitic template characteristic of late Old Russian dialects. In the 15 th century, the order <дал> есми был was characteristic for the official style of the Moscow charters, while Polotsk charters from the same period generalized the reversed order <дал> был есми. In the 16 th century, the order <дал> был есми has established in the Moscow official tradition as well. The pluperfect auxiliaries were excluded from the clause-initial position and other non-enclitic positions, sentences of the type *#был есмь дал ~ #был дал есмь are not attested. In the clause-internal position, both groups of the Old Russian dialects grammaticalized the fixed contact order of the auxiliaries #...был есми... дал ~ #дал был есми irrespective of the position of the verb. This distribution proves that the pluperfect auxiliaries in the Old Russian texts from the 14 th –16 th centuries have the features typical of the clustering enclitics in the world's languages with Wackernagel's law.

Learning structural bioinformatics and evolution with a snake puzzle

We propose here a working unit for teaching basic concepts of structural bioinformatics and evolution through the example of a wooden snake puzzle, strikingly similar to toy models widely used in the literature of protein folding. In our experience, developed at a Master’s course at the Universidad Autónoma de Madrid (Spain), the concreteness of this example helps to overcome difficulties caused by the interdisciplinary nature of this field and its high level of abstraction, in particular for students coming from traditional disciplines. The puzzle will allow us discussing a simple algorithm for finding folded solutions, through which we will introduce the concept of the configuration space and the contact matrix representation. This is a central tool for comparing protein structures, for studying simple models of protein energetics, and even for a qualitative discussion of folding kinetics, through the concept of the Contact Order. It also allows a simple representation of misfolded conformations and their free energy. These concepts will motivate evolutionary questions, which we will address by simulating a structurally constrained model of protein evolution, again modelled on the snake puzzle. In this way, we can discuss the analogy between evolutionary concepts and statistical mechanics that facilitates the understanding of both concepts. The proposed examples and literature are accessible, and we provide supplementary material (see ‘Data Availability’) to reproduce the numerical experiments. We also suggest possible directions to expand the unit. We hope that this work will further stimulate the adoption of games in teaching practice.