All cellular proteins are derived from preexisting ones by natural selection. Because of the random nature of this process, many potentially useful protein structures never arose or were discarded during evolution. Here, we used a single round of genetic selection in mouse cells to isolate chemically simple, biologically active transmembrane proteins that do not contain any amino acid sequences from preexisting proteins. We screened a retroviral library expressing hundreds of thousands of proteins consisting of hydrophobic amino acids in random order to isolate four 29-aa proteins that induced focus formation in mouse and human fibroblasts and tumors in mice. These proteins share no amino acid sequences with known cellular or viral proteins, and the simplest of them contains only seven different amino acids. They transformed cells by forming a stable complex with the platelet-derived growth factor β receptor transmembrane domain and causing ligand-independent receptor activation. We term this approach de novo selection and suggest that it can be used to generate structures and activities not observed in nature, create prototypes for novel research reagents and therapeutics, and provide insight into cell biology, transmembrane protein-protein interactions, and possibly virus evolution and the origin of life.synthetic biology | protein engineering | receptor tyrosine kinase | E5 protein | traptamer A ll extant naturally occurring proteins are derived from preexisting ones by the incremental process of natural selection. Cellular proteins are thus the products of a long chain of evolutionary decisions driven by chance mutations and selective pressures, which allowed some profitable lineages to flourish but drove many others to extinction. Indeed, because of the immense diversity that can result from the arrangement of 20 different amino acids into long polymers, the roster of distinct proteins on earth is a miniscule fraction of possible chemical structures (1). Because they are trapped by their evolutionary history, naturally occurring proteins are not necessarily the optimal proteins for accomplishing a given task. Therefore, one of the major goals of synthetic biology is to generate artificial proteins for a variety of practical applications, such as optimizing catalytic activity and even developing entirely new catalytic activities, generating molecules suitable for industrial processes, and fabricating novel biomaterials.Computational methods have been developed to construct artificial proteins based on detailed understanding of the chemistry, energetics, and structure-function relationships of existing proteins (2-4). This process, known as de novo or computational protein design, typically starts from a known protein structure or a conserved motif and iteratively samples numerous parameters such as amino acid substitutions and side-chain rotamers to identify predicted low-energy states. Although this approach requires enormous computational power, it has been used successfully for both globular and transmemb...

Objective To determine if admission-to-delivery times vary between term nulliparous women with prelabor rupture of membranes (PROM) who initially receive oxytocin compared with buccal misoprostol for labor induction. Study Design This is a retrospective cohort of 130 term, nulliparous women with PROM and cervical dilation of ≤2 cm who underwent induction of labor with intravenous oxytocin or buccal misoprostol. The primary outcome was time from admission to delivery. Linear regressions with log transformation were used to estimate the effect of induction agent on time to delivery. Results Women receiving oxytocin had faster admission-to-delivery times than women receiving misoprostol (16.9 vs. 19.9 hours, p = 0.013). There were no significant differences in secondary outcomes between the groups. In the adjusted model, women who received misoprostol had a 22% longer time from admission to delivery (95% CI 5.0–42.0%) compared with women receiving oxytocin. Conclusion In term nulliparous patients with PROM, intravenous oxytocin is associated with faster admission-to-delivery times than buccal misoprostol.

Objective To examine outcomes among women with prelabor rupture of membranes (PROM) who declined induction and chose outpatient expectant management compared with those admitted for induction. Study Design This is a retrospective cohort study of term women with singleton, vertex-presenting fetuses who presented with PROM between July 2016 and June 2017 and were eligible for outpatient expectant management (n = 166). The primary outcomes were time from PROM to delivery and time from admission to delivery. Maternal and neonatal outcomes were also compared between groups. Multivariable linear regressions were used to assess time differences between groups, adjusting for known maternal and pregnancy characteristics. Results Compared with admitted patients, women managed expectantly at home had significantly longer PROM to delivery intervals (median 29.2 vs. 17 hours, p < 0.001), but were more likely to deliver within 24 hours of admission (95.1 vs. 82.9%, p = 0.004). In the adjusted analysis, PROM to delivery was 7 hours longer (95% confidence interval [CI]: 3.9–10.0) and admission to delivery was 5.3 hours shorter (95% CI: 2.8–7.7) in the outpatient expectant management cohort. There were no differences in secondary outcomes. Conclusion Outpatient management of term PROM is associated with longer PROM to delivery intervals, but shorter admission to delivery intervals.

INTRODUCTION: In our institution, women with premature rupture of membranes (PROM) who decline augmentation are offered outpatient expectant management (OEM) for 24 hours. Our objective was to determine if patients who chose OEM had different time-to-delivery intervals than patients who chose admission. METHODS: This is a retrospective cohort of nulliparous, term women with singleton, vertex-presenting fetuses who presented with PROM from July 2016 to June 2017 at a single institution. Women were eligible for OEM if they were Group B Streptococcus negative, afebrile, had clear fluid, and reactive non-stress tests. Primary outcomes included time from PROM-to-delivery and from admission-to-delivery. Secondary outcomes included chorioamnionitis, cesarean delivery, and neonatal intensive care unit admission. Outcomes were compared using chi-squared and Wilcoxon rank-sum tests, and then adjusted for age, race, insurance, gestational age, augmentation, and provider type using multivariable regressions. IRB approval was obtained. RESULTS: Of 127 eligible women, 74 chose admission and 53 chose OEM. OEM patients had significantly longer PROM-to-delivery intervals than admitted patients (median 29.3 vs 19.2 hours, P<.001), but were more likely to deliver within 24 hours of admission (94.3 vs 74.6%, P=.004). In the adjusted analysis, PROM-to-delivery was 8.1 hours longer (95% CI 4.7-11.6) and admission-to-delivery was 4.5 hours shorter (95% CI 1.7-7.4) for OEM patients. There were no differences in secondary outcomes. CONCLUSION: Outpatient management of term PROM shortens the interval from admission-to-delivery, reducing hospital resource utilization among low-risk women. However, given the known increased risk of infection with prolonged PROM, more research is needed to assess the safety of this protocol.