Sterics and Stereoelectronics in Aza-Glycine: Impact of Aza-Glycine Preorganization in Triple Helical Collagen.

We previously demonstrated aza-glycine can serve as a reliable and general replacement of glycine in triple helical collagen. Aza-glycine considerably improves collagen's thermal stability and self-assembly properties without changing collagen's natural triple helix topology. We provided a firm structural basis for this stabilization with an atomic resolution crystal structure of collagen containing aza-glycine which revealed new cross-strand H-bonds within the triple helix interior. Here, using computational analysis, we show the enhanced properties of aza-glycine is a result of noncovalent forces (H-bonding) and backbone preorganization. The interplay of steric repulsion and hyperconjugative interactions in aza-glycine's backbone directly preorganizes the collagen peptide main-chain (φ, ψ) dihedrals for triple helical assembly. The synergy of multiple structural and electronic changes which originate at the residue level in the aza-glycine backbone and culminate at the macromolecular level of the triple helix lead to increased stability and faster refolding of collagen peptides containing aza-glycine.

Domino Fragmentations in Traceless Directing Groups of Radical Cascades: Evidence for the Formation of Alkoxy Radicals via C-O Scission.

Direct evidence for the formation of alkoxy radicals is reported in radical cascades using traceless directing groups. Despite the possibility of hydrogen abstraction in the fragmenting step, followed by loss of R-OH, ß-scission is preferred for the formation of alkoxy radicals. For the first time, the C-O radical was intermolecularly trapped using a silyl enol ether. Various C-X fragmenting groups were explored as possible traceless directing groups for the preparation of extended polyaromatics. Computational evidence shows that a combination of aromatization, steric and stereoelectronic effects assists the fragmentation to alkoxy radicals. Additionally, a new through-space interaction was discovered between O and Sn in the fragmentation as a specific transition state stabilizing effect.

Traceless directing groups in radical cascades: from oligoalkynes to fused helicenes without tethered initiators.

We report the first example of a traceless directing group in a radical cascade. The chemo- and regioselectivity of the initial attack in skipped oligoalkynes is controlled by propargyl OR moiety. Radical translocations lead to the boomerang return of the radical center to the site of initial attack where it assists the elimination of the directing functionality via ß-scission in the last step of the cascade. The Bu3Sn moiety continues further via facile reactions with electrophiles as well as Stille and Suzuki cross-coupling reactions. This selective radical transformation opens a new approach for the controlled transformation of skipped oligoalkynes into polycyclic ribbons of tunable dimensions.

Forecasting West Nile Virus With Graph Neural Networks: Harnessing Spatial Dependence in Irregularly Sampled Geospatial Data.

Machine learning methods have seen increased application to geospatial environmental problems, such as precipitation nowcasting, haze forecasting, and crop yield prediction. However, many of the machine learning methods applied to mosquito population and disease forecasting do not inherently take into account the underlying spatial structure of the given data. In our work, we apply a spatially aware graph neural network model consisting of GraphSAGE layers to forecast the presence of West Nile virus in Illinois, to aid mosquito surveillance and abatement efforts within the state. More generally, we show that graph neural networks applied to irregularly sampled geospatial data can exceed the performance of a range of baseline methods including logistic regression, XGBoost, and fully-connected neural networks.

Asynchronous Changepoint Estimation for Spatially Correlated Functional Time Series.

We propose a new solution under the Bayesian framework to simultaneously estimate mean-based asynchronous changepoints in spatially correlated functional time series. Unlike previous methods that assume a shared changepoint at all spatial locations or ignore spatial correlation, our method treats changepoints as a spatial process. This allows our model to respect spatial heterogeneity and exploit spatial correlations to improve estimation. Our method is derived from the ubiquitous cumulative sum (CUSUM) statistic that dominates changepoint detection in functional time series. However, instead of directly searching for the maximum of the CUSUM-based processes, we build spatially correlated two-piece linear models with appropriate variance structure to locate all changepoints at once. The proposed linear model approach increases the robustness of our method to variability in the CUSUM process, which, combined with our spatial correlation model, improves changepoint estimation near the edges. We demonstrate through extensive simulation studies that our method outperforms existing functional changepoint estimators in terms of both estimation accuracy and uncertainty quantification, under either weak or strong spatial correlation, and weak or strong change signals. Finally, we demonstrate our method using a temperature data set and a coronavirus disease 2019 (COVID-19) study. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00519-w.

Phenology and environmental predictors of Triatoma sanguisuga dispersal in east-central Texas, United States.

Of 11 triatomine species in the United States (US), Triatoma sanguisuga has the widest distribution across a 23-state region encompassing the southeastern US. This species consistently feeds on humans and dogs and has a high infection prevalence with the Chagas parasite Trypanosoma cruzi, with over 30-60% of adults infected. Little is known about the phenology and environmental predictors of dispersal activity of Triatoma sanguisuga. Using manual searches standardized by effort, we sampled kissing bugs in east central Texas, US every other night from June to November 2020 to determine their phenology and environmental predictors of activity. We found 176 triatomines alive, all of which were T. sanguisuga, with peak collections in early August and cessation of activity by late October; the phenology as determined by this active surveillance matched what has been reported using a passive community science approach. Using a negative binomial regression, we found temperature to have a positive correlation with T. sanguisuga dispersal activity, while wind speed had a significant negative correlation. We identified increased collections during sampling sessions with precipitation during the preceding 22 h. Further, wind from the southwest - the direction of most of the sylvatic habitat in the study area - was correlated with an increased dispersal activity, suggesting wind-facilitated dispersal. Given concerns for human and animal Chagas disease within the distribution of T. sanguisuga, vector control strategies can be adapted based on the factors influencing dispersal behavior.

The effect of co-location on human communication networks.

The ability to rewire ties in communication networks is vital for large-scale human cooperation and the spread of new ideas. We show that lack of researcher co-location during the COVID-19 lockdown caused the loss of more than 4,800 weak ties-ties between distant parts of the social system that enable the flow of novel information-over 18 months in the email network of a large North American university. Furthermore, we find that the reintroduction of partial co-location through a hybrid work mode led to a partial regeneration of weak ties. We quantify the effect of co-location in forming ties through a model based on physical proximity, which is able to reproduce all empirical observations. Results indicate that employees who are not co-located are less likely to form ties, weakening the spread of information in the workplace. Such findings could contribute to a better understanding of the spatiotemporal dynamics of human communication networks and help organizations that are moving towards the implementation of hybrid work policies to evaluate the minimum amount of in-person interaction necessary for a productive work environment.

Aza-proline effectively mimics l-proline stereochemistry in triple helical collagen.

The prevalence of l-amino acids in biomolecules has been shown to have teleological importance in biomolecular structure and self-assembly. Recently, biophysical studies have demonstrated that natural l-amino acids can be replaced with non-natural achiral aza-amino acids in folded protein structures such as triple helical collagen. However, the structural consequences of achiral aza-amino acid incorporation has not been elucidated in the context of any relevant folded biomolecule. Herein, we use X-ray crystallography to provide the first atomic resolution crystal structure of an achiral aza-amino acid residue embedded within a folded protein structure, definitively illustrating that achiral aza-proline has the capacity to effectively mimic the stereochemistry of natural amino acids within the context of triple helical collagen. We further corroborate this finding with density functional theory computational analysis showing that the natural l-amino acid stereochemistry for aza-proline is energetically favored when arranged in the aza-proline-hydroxyproline-glycine motif. In addition to providing fundamental insight into peptide and protein structure, the incorporation of achiral stereochemical mimics such as aza-amino acids could have far reaching impacts in areas ranging from synthetic materials to drug design.

Fused Catechol Ethers from Gold(I)-Catalyzed Intramolecular Reaction of Propargyl Ethers with Acetals.

Selective gold(I)-catalyzed rearrangement of aromatic methoxypropynyl acetals leads to fused catechol ethers (1,2-dialkoxynapthalenes) in excellent yields. Furthermore, this process extends to the analogous heterocyclic and aliphatic substrates. Alkyne activation triggers nucleophilic addition of the acetal oxygen that leads to an equilibrating mixture of oxonium ions of similar stability. This mixture is "kinetically self-sorted" via a highly exothermic cyclization. Selective formation of 1,2-dialkoxy naphthalenes originates from chemoselective aromatization of the cyclic intermediate via 1,4-elimination of methanol.