No abstract

We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.

To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 × 10 −17 ) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.Lung cancer is frequently cited as a malignancy attributable solely to environmental exposures -primarily cigarette smoke. However, evidence that genetic factors influence lung cancer © 2008 Nature Publishing Group Correspondence should be addressed to C.I.A. (E-mail: camos@mdanderson.org). 6 These authors contributed equally to this work. AUTHOR CONTRIBUTIONS Texas: C.I.A. and M.R.S. conceived of this study. M.R.S. established the Texas lung cancer study. C.I.A. supervised and performed the analyses. G.M. provided oversight in manuscript development and in the conduct of genetic studies. I.P.G., Q.D., Q.Z., W.V.C. and X.G. performed statistical analyses. S.S. developed and implemented statistical procedures for joint analysis. X.W. and J. Direct evidence for a genetic predisposition to lung cancer is provided by the increased risk associated with constitutional TP53 (tumor protein p53) 4 and RB1 (retinoblastoma) 5,6 gene mutations, rare mendelian cancer syndromes such as Bloom's 7 and Werner's syndromes 8 , and strongly familial lung cancer 9 . The genetic basis of inherited susceptibility to lung cancer outside the context of these disorders is at present undefined, but a model in which high-risk alleles account for all of the excess familial risk seems unlikely. Alternatively, part of the inherited genetic risk may be caused by low-penetrance alleles. This hypothesis implies that testing for allelic association should be a powerful strategy for identifying alleles that predispose to lung cancer.We conducted a genome-wide association study (GWAS) of histologically confirmed nonsmall cell lung cancer (NSCLC) to identify common low-penetrance alleles influencing lung cancer risk. To minimize confounding effects from cigarette smoking and increase the power to detect genetic effects, we frequency matched controls to cases according to smoking behavior. We also matched controls to cases by age (within 5 year categories) and sex, and we further matched former smokers by year...

The Wide Field Planetary Camera 2 of the Hubble Space T elescope has been used to obtain highresolution images of NGC 4038/4039 that go roughly 3 mag deeper in V than previous observations made during cycle 2. These new images allow us to measure the luminosity functions (LFs) of clusters and stars over a range of 8 mag To Ðrst order, the LF is a power law, with expo-. nent a \ [2.12^0.04. However, using a variety of di †erent techniques to decouple the cluster and stellar LFs, which overlap in the range we Ðnd an apparent bend in the young cluster 9^0.1, and is dominated by young red and blue supergiants. The star clusters of the Antennae appear slightly resolved, with median e †ective radii of 4^1 pc, similar to or perhaps slightly larger than those of globular clusters in our Galaxy. However, the radial extents of some of the very young clusters (ages less than 10 Myr) are much larger than those of old globular clusters (e.g., the outer radius of knot S exceeds 450 pc). This may indicate that the tidal forces from the galaxies have not had time to remove some of the outer stars from the young clusters. A combination of the UBV I colors, Ha morphology, and Goddard High Resolution Spectrograph (GHRS) spectra enables us to age date the clusters in different regions of the Antennae. Star clusters around the edge of the dust overlap region appear to be the youngest, with ages Myr, while clusters in the western loop appear to be 5È10 Myr old. Many star [5 clusters in the northeastern star formation region appear to be D100 Myr old, with an LF in V that has shifted faintward by D1.0 mag relative to the younger (0È20 Myr) clusters that dominate over most of the rest of the galaxy. A third cluster population consists of intermediate-age clusters (D500 Myr) that probably formed during the initial encounter responsible for ejecting the tails. A handful of old globular clusters from the progenitor galaxies are also identiÐed. Most of these lie around NGC 4039, where the lower background facilitates their detection. Age estimates derived from GHRS spectroscopy yield 3^1 Myr for knot K (just south of the nucleus of NGC 4038) and 7^1 Myr for knot S in the western loop, in good agreement with ages derived from the UBV I colors. E †ective gas outÑow velocities from knots S and K are estimated to be about 25È30 km s~1, based on the above cluster ages and the sizes of the surrounding Ha bubbles. However, the measured widths of the interstellar absorption lines suggest dispersion velocities of D400 km s~1 along the lines of sight to knots S and K.

bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems.

Phase control plays an important role in the precise synthesis of inorganic materials, as the phase structure has a profound influence on properties such as conductivity and chemical stability. Phase-controlled preparation has been challenging for the metallic-phase group-VI transition metal dichalcogenides (the transition metals are Mo and W, and the chalcogens are S, Se and Te), which show better performance in electrocatalysis than their semiconducting counterparts. Here, we report the large-scale preparation of micrometre-sized metallic-phase 1T'-MoX (X = S, Se)-layered bulk crystals in high purity. We reveal that 1T'-MoS crystals feature a distorted octahedral coordination structure and are convertible to 2H-MoS following thermal annealing or laser irradiation. Electrochemical measurements show that the basal plane of 1T'-MoS is much more active than that of 2H-MoS for the electrocatalytic hydrogen evolution reaction in an acidic medium.

We present a series of simple, largely analytical models to compute the effects of disruption on the mass function of star clusters. Our calculations include evaporation by two-body relaxation and gravitational shocks and mass loss by stellar evolution. We find that, for a wide variety of initial conditions, the mass function develops a turnover or peak and that, after 12 Gyr, this is remarkably close to the observed peak for globular clusters, at M_p = 2 10^5 solar masses. Below the peak, the evolution is dominated by two-body relaxation, and the mass function always develops a tail of the form psi(M) = const, reflecting that the masses of tidally limited clusters decrease linearly with time just before they are destroyed. This also agrees well with the empirical mass function of globular clusters in the Milky Way. Above the peak, the evolution is dominated by stellar evolution at early times and gravitational shocks at late times. These processes shift the mass function to lower masses while nearly preserving its shape. The radial variation of the mass function within a galaxy depends on the initial position-velocity distribution of the clusters. We find that some radial anisotropy in the initial velocity distribution, especially when this increases outward, is needed to account for the observed near-uniformity of the mass functions of globular clusters. This may be consistent with the observed near-isotropy of the present velocity distributions because clusters on elongated orbits are preferentially destroyed. These results are based on models with static, spherical galactic potentials. We point out that there would be even more radial mixing of the orbits and hence more uniformity of the mass function if the galactic potentials were time-dependent and/or non-spherical.Comment: 39 pages including 13 figures; scheduled for publication in the Astrophysical Journal (issue of 10 Nov 2001); Minor revisions to improve clarity; no changes to equations, figures, or conclusion

As an interesting layered material, molybdenum disulfi de (MoS 2 ) has been extensively studied in recent years due to its exciting properties. However, the applications of MoS 2 in optoelectronic devices are impeded by the lack of high-quality p-n junction, low light absorption for mono-/multilayers, and the diffi culty for large-scale monolayer growth. Here, it is demonstrated that MoS 2 fi lms with vertically standing layered structure can be deposited on silicon substrate with a scalable sputtering method, forming the heterojunctiontype photodetectors. Molecular layers of the MoS 2 fi lms are perpendicular to the substrate, offering high-speed paths for the separation and transportation of photo-generated carriers. Owing to the strong light absorption of the relatively thick MoS 2 fi lm and the unique vertically standing layered structure,