Comprehensive profiling of social mixing patterns in resource poor countries: a mixed methods research protocol.

Background: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. Methods: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures.We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. Discussion: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.

Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021.

Non-pharmaceutical interventions minimize social contacts, hence the spread of respiratory pathogens such as influenza and SARS-CoV-2. Globally, there is a paucity of social contact data from the workforce. In this study, we quantified two-day contact patterns among USA employees. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic self-kept diaries. Data were collected over 4 rounds from 2020 to 2021 during the COVID-19 pandemic. Mean (standard deviation) contacts reported by 1456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April-June 2020), 2 (November 2020-January 2021), 3 (June-August 2021), and 4 (November-December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2-4. We then modeled SARS-CoV-2 transmission at home, work, and community settings. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained exceptionally low in work settings. To accurately parameterize models of infection transmission and control, we need empirical social contact data that capture human mixing behavior across time.

Molecular system for an exponentially fast growing programmable synthetic polymer.

In this paper, we demonstrate a molecular system for the first active self-assembly linear DNA polymer that exhibits programmable molecular exponential growth in real time, also the first to implement "internal" parallel insertion that does not rely on adding successive layers to "external" edges for growth. Approaches like this can produce enhanced exponential growth behavior that is less limited by volume and external surface interference, for an early step toward efficiently building two and three dimensional shapes in logarithmic time. We experimentally demonstrate the division of these polymers via the addition of a single DNA complex that competes with the insertion mechanism and results in the exponential growth of a population of polymers per unit time. In the supplementary material, we note that an "extension" beyond conventional Turing machine theory is needed to theoretically analyze exponential growth itself in programmable physical systems. Sequential physical Turing Machines that run a roughly constant number of Turing steps per unit time cannot achieve an exponential growth of structure per time. In contrast, the "active" self-assembly model in this paper, computationally equivalent to a Push-Down Automaton, is exponentially fast when implemented in molecules, but is taxonomically less powerful than a Turing machine. In this sense, a physical Push-Down Automaton can be more powerful than a sequential physical Turing Machine, even though the Turing Machine can compute any computable function. A need for an "extended" computational/physical theory arises, described in the supplementary material section S1.

Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021.

Non-pharmaceutical interventions minimize social contacts, hence the spread of SARS-CoV-2. We quantified two-day contact patterns among USA employees from 2020-2021 during the COVID-19 pandemic. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic diaries. Mean (standard deviation) contacts reported by 1,456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April-June 2020), 2 (November 2020-January 2021), 3 (June-August 2021), and 4 (November-December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2-4. We modeled SARS-CoV-2 transmission at home, work, and community. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained very low in work settings. Contact data are important to parameterize models of infection transmission and control. Teaser: Changes in social contact patterns shape disease dynamics at workplaces in the USA.

Deterministic Function Computation with Chemical Reaction Networks.

Chemical reaction networks (CRNs) formally model chemistry in a well-mixed solution. CRNs are widely used to describe information processing occurring in natural cellular regulatory networks, and with upcoming advances in synthetic biology, CRNs are a promising language for the design of artificial molecular control circuitry. Nonetheless, despite the widespread use of CRNs in the natural sciences, the range of computational behaviors exhibited by CRNs is not well understood. CRNs have been shown to be efficiently Turing-universal (i.e., able to simulate arbitrary algorithms) when allowing for a small probability of error. CRNs that are guaranteed to converge on a correct answer, on the other hand, have been shown to decide only the semilinear predicates (a multi-dimensional generalization of "eventually periodic" sets). We introduce the notion of function, rather than predicate, computation by representing the output of a function f : ℕ k → ℕ l by a count of some molecular species, i.e., if the CRN starts with x1, …, xk molecules of some "input" species X1, …, Xk , the CRN is guaranteed to converge to having f(x1, …, xk ) molecules of the "output" species Y1, …, Yl . We show that a function f : ℕ k → ℕ l is deterministically computed by a CRN if and only if its graph {(x, y) ∈ ℕ k × â„• l ∣ f(x) = y} is a semilinear set. Finally, we show that each semilinear function f (a function whose graph is a semilinear set) can be computed by a CRN on input x in expected time O(polylog ∥x∥1).

An O(n(5)) algorithm for MFE prediction of kissing hairpins and 4-chains in nucleic acids.

Efficient methods for prediction of minimum free energy (MFE) nucleic secondary structures are widely used, both to better understand structure and function of biological RNAs and to design novel nano-structures. Here, we present a new algorithm for MFE secondary structure prediction, which significantly expands the class of structures that can be handled in O(n(5)) time. Our algorithm can handle H-type pseudoknotted structures, kissing hairpins, and chains of four overlapping stems, as well as nested substructures of these types.

Reducing facet nucleation during algorithmic self-assembly.

Algorithmic self-assembly, a generalization of crystal growth, has been proposed as a mechanism for bottom-up fabrication of complex nanostructures and autonomous DNA computation. In principle, growth can be programmed by designing a set of molecular tiles with binding interactions that enforce assembly rules. In practice, however, errors during assembly cause undesired products, drastically reducing yields. Here we provide experimental evidence that assembly can be made more robust to errors by adding redundant tiles that "proofread" assembly. We construct DNA tile sets for two methods, uniform and snaked proofreading. While both tile sets are predicted to reduce errors during growth, the snaked proofreading tile set is also designed to reduce nucleation errors on crystal facets. Using atomic force microscopy to image growth of proofreading tiles on ribbon-like crystals presenting long facets, we show that under the physical conditions we studied the rate of facet nucleation is 4-fold smaller for snaked proofreading tile sets than for uniform proofreading tile sets.