Complex social networks have received increasing attention from researchers. Recent work has focused on mechanisms that produce scale-free networks. We theoretically and empirically characterize the buyer-supplier network of the US economy and find that purely scale-free models have trouble matching key attributes of the network. We construct an alternative model that incorporates realistic features of firms' buyer-supplier relationships and estimate the model's parameters using microdata on firms' self-reported customers. This alternative framework is better able to match the attributes of the actual economic network and aids in further understanding several important economic phenomena.industrial organization | network dynamics F irms' interconnections through buyer-supplier relationships affect economic phenomena ranging from the spread of innovative ideas (1) to the transmission of economic shocks (2) to trade patterns (3). Recognizing this, economists have started to pay explicit attention to firm network structures (refs. 4 and 5 and the studies discussed in ref. 6). However, no one has theoretically or empirically characterized the actual firm network structure in any large economy. Here, we establish basic features of the buyer-supplier network of firms in the United States and develop a model of firm birth, death, and input-output link formation that closely replicates the observed network.Earlier research modeled the formation and structure of complex social networks more broadly. Examples include links on the worldwide web (7), job-search networks (8), and friendships (9); refs. 10 and 11 have recent surveys. Much of this recent work was spurred by seminal work (7) documenting the scalefree nature of many networks. We show, however, that scale-free network models miss important elements of the US economy's firm network. In particular, the fat-tail nature of scale-free networks overstates the connectivity of the economy's most central vertices-that is, the most vertically interconnected firms. At the same time, it overpredicts the number of minimally connected firms.We propose an alternative model of network formation that better matches the connectivity distribution of US firms. Following the model in ref. 12, our model adds processes for vertex (firm) death and reattachment of those edges (buyersupplier relationships) among surviving firms. It also allows new edges to be formed through a mix of the preferential attachment mechanisms emblematic of scale-free network models (where new edges are more likely to be formed with vertices that already have more edges) and random attachment (similar to that in ref. 13). Although these extensions are sparsely parameterized, they considerably extend the ability of network formation models to match observed firm network structures. Importantly, they also embody realistic features of the actual firm network: firms often go out of business, and many suppliers actively prefer to work with less-connected downstream firms because of product specialization and long-...

The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.

Arthrospira platensis (commonly known as spirulina) is a photosynthetic cyanobacterium1. It is a highly nutritious food that has been consumed for decades in the US, and even longer by indigenous cultures2. Its widespread use as a safe food source and proven scalability have driven frequent attempts to convert it into a biomanufacturing platform. But these were repeatedly frustrated by spirulina’s genetic intractability. We report here efficient and versatile genetic engineering methodology for spirulina that allows stable expression of bioactive protein therapeutics at high levels. We further describe large-scale, indoor cultivation and downstream processing methods appropriate for the manufacturing of biopharmaceuticals in spirulina. The potential of the platform is illustrated by pre-clinical development and human testing of an orally delivered antibody therapeutic against campylobacter, a major cause of infant mortality in the developing world and a growing antibiotic resistance threat3,4. This integrated development and manufacturing platform blends the safety of food-based biotechnology with the ease of genetic manipulation, rapid growth rates and high productivity characteristic of microbial platforms. These features combine for exceptionally low-cost production of biopharmaceuticals to address medical needs that are unfeasible with current biotechnology platforms.

Circular tandem repeat proteins (‘cTRPs’) are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubility, a wide range of sizes, and are useful as protein display particles for biotechnology applications. However, cTRPs also demonstrate inefficient self-assembly from smaller subunits. In this study, we describe a new generation of cTRPs, with longer repeats and increased interaction surfaces, which enhanced the self-assembly of two significantly different sizes of homotrimeric constructs. Finally, we demonstrated functionalization of these constructs with (1) a hexameric array of peptide-binding SH2 domains, and (2) a trimeric array of anti-SARS CoV-2 VHH domains. The latter proved capable of sub-nanomolar binding affinities towards the viral receptor binding domain and potent viral neutralization function.

Antibodies against the Plasmodium falciparum circumsporozoite protein (PfCSP) can block hepatocyte infection by sporozoites and protect against malaria. Needle-free vaccination strategies are desirable, yet most PfCSP-targeted vaccines like RTS,S require needle-based administration. Here, we evaluated the edible algae, Arthrospira platensis (commonly called ‘spirulina’) as a malaria vaccine platform. Spirulina were genetically engineered to express virus-like particles (VLPs) consisting of the woodchuck hepatitis B core capsid protein (WHcAg) displaying a (NANP)15 PfCSP antigen on its surface. PfCSP-spirulina administered to mice intranasally followed by oral PfCSP-spirulina boosters resulted in a strong, systemic anti-PfCSP immune response that was protective against subcutaneous challenge with PfCSP-expressing P. yoelii. Unlike male mice, female mice did not require Montanide adjuvant to reach high antibody titers or protection. The successful use of spirulina as a vaccine delivery system warrants further development of spirulina-based vaccines as a useful tool in addressing malaria and other diseases of global health importance.