For diagnosis of coronavirus disease 2019 (COVID-19), a SARS-CoV-2 virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test is routinely used. However, this test can take up to 2 d to complete, serial testing may be required to rule out the possibility of false negative results and there is currently a shortage of RT-PCR test kits, underscoring the urgent need for alternative methods for rapid and accurate diagnosis of patients with COVID-19. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value for ruling out SARS-CoV-2 infection, as some patients may have normal radiological findings at early stages of the disease. In this study, we used artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history and laboratory testing to rapidly diagnose patients who are positive for COVID-19. Among a total of 905 patients tested by real-time RT-PCR assay and next-generation sequencing RT-PCR, 419 (46.3%) tested positive for SARS-CoV-2. In a test set of 279 patients, the AI system achieved an area under the curve of 0.92 and had equal sensitivity as compared to a senior thoracic radiologist. The AI system also improved the detection of patients who were positive for COVID-19 via RT-PCR who presented with normal CT scans, correctly identifying 17 of 25 (68%) patients, whereas radiologists classified all of these patients as COVID-19 negative. When CT scans and associated clinical history are available, the proposed AI system can help to rapidly diagnose COVID-19 patients. The COVID-19 pandemic has rapidly propagated due to widespread person-to-person transmission 1-6. Laboratory confirmation of SARS-CoV-2 is performed with a virus-specific RT-PCR, but the test can take up to 2 d to complete. Chest CT is a valuable component of evaluation and diagnosis in symptomatic patients with

Using single-molecule DNA nanomanipulation, we show that abortive initiation involves DNA "scrunching"--in which RNA polymerase (RNAP) remains stationary and unwinds and pulls into itself downstream DNA--that scrunching requires RNA synthesis, and that scrunching depends on RNA length. We show further that promoter escape involves scrunching, and that scrunching occurs in most or all instances of promoter escape. Our results support existence of an obligatory stressed intermediate, with ~1 turn of additional DNA unwinding, in escape and are consistent with the proposal that stress in this intermediate provides the driving force to break RNAP-promoter and RNAP-initiation-factor interactions in escape.Transcription initiation involves a series of reactions (1-3). RNA polymerase (RNAP) binds to promoter DNA to yield an RNAP-promoter closed complex (RP c ). RNAP then unwinds ~1 turn of DNA surrounding the transcription start site to yield an RNAP-promoter open complex (RP o ). RNAP then enters into abortive cycles of synthesis and release of short RNA products as an RNAP-promoter initial transcribing complex (RP itc ) and, upon synthesis of an RNA product ~9-11 nt in length, escapes the promoter and enters into productive synthesis of RNA as an RNAP-DNA elongation complex (RD e ).The mechanism by which the RNAP active-center translocates in abortive initiation and promoter escape has remained problematic. The problem has been posed by two seemingly contradictory observations: First, RNA products up to ~8-10 nt in length are synthesized in abortive initiation (4-6); thus the RNAP active center translocates relative to DNA in abortive initiation. Second, DNA-footprinting results indicate that there upstream boundary of the DNA 1A;4,7,9-12; see also proposals for structurally unrelated single-subunit RNAP derivatives in 13-19).In previous work, we have developed a single-molecule-DNA-nanomanipulation approach that detects RNAP-dependent DNA unwinding with ~1 bp resolution and ~1 s temporal resolution, and we have applied this approach to detect and characterize RNAP-dependent promoter unwinding upon formation of RP o (Figs. 1B, S1,(20)(21)(22). In this work, we have applied this approach to test the scrunching model for RNAP-active-center translocation in abortive initiation and promoter escape (Fig. 1A;4,7,11,12). The scrunching model--and only the scrunching model--postulates changes in RNAP-dependent DNA unwinding during abortive initiation and promoter escape. Specifically, the scrunching model postulates that RNAP pulls into itself downstream DNA; for each base pair that RNAP pulls into itself, a base pair must be broken and must be maintained broken, and, correspondingly there must be one base pair of additional DNA unwinding.Our first set of experiments addressed abortive initiation occurring in complexes engaged in iterative abortive initiation [complexes prepared using subsets of nucleoside triphosphates (NTPs) insufficient to permit promoter escape and productive initiation]. Our primary experimental...