Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures.Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk.Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20-22). Cases were isolated on average 4•6 days (95% CI 4•1-5•0) after developing symptoms; contact tracing reduced this by 1•9 days (95% CI 1•1-2•7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6•27 [95% CI 1•49-26•33] for household contacts and 7•06 [1•43-34•91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11•2% (95% CI 9•1-13•8), and children were as likely to be infected as adults (infection rate 7•4% in children <10 years vs population average of 6•6%). The observed reproductive number (R) was 0•4 (95% CI 0•3-0•5), with a mean serial interval of 6•3 days (95% CI 5•2-7•6).Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control.

Axin2/Conductin/Axil and its ortholog Axin are negative regulators of the Wnt signaling pathway, which promote the phosphorylation and degradation of ␤-catenin. While Axin is expressed ubiquitously, Axin2 mRNA was seen in a restricted pattern during mouse embryogenesis and organogenesis. Because many sites of Axin2 expression overlapped with those of several Wnt genes, we tested whether Axin2 was induced by Wnt signaling. Endogenous Axin2 mRNA and protein expression could be rapidly induced by activation of the Wnt pathway, and Axin2 reporter constructs, containing a 5.6-kb DNA fragment including the promoter and first intron, were also induced. This genomic region contains eight Tcf/LEF consensus binding sites, five of which are located within longer, highly conserved noncoding sequences. The mutation or deletion of these Tcf/LEF sites greatly diminished induction by ␤-catenin, and mutation of the Tcf/LEF site T2 abolished protein binding in an electrophoretic mobility shift assay. These results strongly suggest that Axin2 is a direct target of the Wnt pathway, mediated through Tcf/LEF factors. The 5.6-kb genomic sequence was sufficient to direct the tissue-specific expression of d2EGFP in transgenic embryos, consistent with a role for the Tcf/LEF sites and surrounding conserved sequences in the in vivo expression pattern of Axin2. Our results suggest that Axin2 participates in a negative feedback loop, which could serve to limit the duration or intensity of a Wnt-initiated signal.

Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.

The record superconducting transition temperature (T(c)) for the iron-based high-temperature superconductors (Fe-HTS) has long been 56 K. Recently, in single-layer FeSe films grown on SrTiO3 substrates, indications of a new record of 65 K have been reported. Using in situ photoemission measurements, we substantiate the presence of spin density waves (SDWs) in FeSe films--a key ingredient of Fe-HTS that was missed in FeSe before--and we find that this weakens with increased thickness or reduced strain. We demonstrate that the superconductivity occurs when the electrons transferred from the oxygen-vacant substrate suppress the otherwise pronounced SDWs in single-layer FeSe. Beyond providing a comprehensive understanding of FeSe films and directions to further enhance its T(c), we map out the phase diagram of FeSe as a function of lattice constant, which contains all the essential physics of Fe-HTS. With the simplest structure, cleanest composition and single tuning parameter, monolayer FeSe is an ideal system for testing theories of Fe-HTS.

We consider the problem of minimizing the sum of two convex functions: one is the average of a large number of smooth component functions, and the other is a general convex function that admits a simple proximal mapping. We assume the whole objective function is strongly convex. Such problems often arise in machine learning, known as regularized empirical risk minimization. We propose and analyze a new proximal stochastic gradient method, which uses a multi-stage scheme to progressively reduce the variance of the stochastic gradient. While each iteration of this algorithm has similar cost as the classical stochastic gradient method (or incremental gradient method), we show that the expected objective value converges to the optimum at a geometric rate. The overall complexity of this method is much lower than both the proximal full gradient method and the standard proximal stochastic gradient method.

Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.

Poly(ADP-ribose) (PAR) and the PAR polymerases (PARPs) that catalyze its synthesis from donor nicotinamide adenine dinucleotide (NAD + ) molecules have received considerable attention in the recent literature. Poly(ADP-ribosyl)ation (PARylation) plays diverse roles in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, cell death pathways, insulator function, and mitotic apparatus function. These processes are critical for many physiological and pathophysiological outcomes, including genome maintenance, carcinogenesis, aging, inflammation, and neuronal function. This review highlights recent work on the biochemistry, molecular biology, physiology, and pathophysiology of PARylation, focusing on the activity of PARP-1, the most abundantly expressed member of a family of PARP proteins. In addition, connections between nuclear NAD + metabolism and nuclear signaling through PARP-1 are discussed.Structural and functional domains of PARP-1, the founding member of the PARP family PARP-1 is the founding member of the PARP family, which contains as many as 18 distinct proteins in humans (Amé et al. 2004). PARPs catalyze the polymerization of ADP-ribose units from donor NAD + molecules on target proteins, resulting in the attachment of linear or branched polymers (Fig.

Animals require rapid, long-range molecular signaling networks to integrate sensing and response throughout their bodies. The amino acid glutamate acts as an excitatory neurotransmitter in the vertebrate central nervous system, facilitating long-range information exchange via activation of glutamate receptor channels. Similarly, plants sense local signals, such as herbivore attack, and transmit this information throughout the plant body to rapidly activate defense responses in undamaged parts. Here we show that glutamate is a wound signal in plants. Ion channels of the family act as sensors that convert this signal into an increase in intracellular calcium ion concentration that propagates to distant organs, where defense responses are then induced.