Highly penetrating cosmic ray muons constantly shower the earth at a rate of about 1 muon per cm² per minute. We have developed a technique which exploits the multiple Coulomb scattering of these particles to perform nondestructive inspection without the use of artificial radiation. In prior work , we have described heuristic methods for processing muon data to create reconstructed images. In this paper, we present a maximum likelihood/expectation maximization tomographic reconstruction algorithm designed for the technique. This algorithm borrows much from techniques used in medical imaging, particularly emission tomography, but the statistics of muon scattering dictates differences. We describe the statistical model for multiple scattering, derive the reconstruction algorithm, and present simulated examples. We also propose methods to improve the robustness of the algorithm to experimental errors and events departing from the statistical model.

In many situations, simulation of complex phenomena requires a large number of inputs and is computationally expensive. Identifying the inputs that most impact the system so that these factors can be further investigated can be a critical step in the scientific endeavor. In computer experiments, it is common to use a Gaussian spatial process to model the output of the simulator. In this article we introduce a new, simple method for identifying active factors in computer screening experiments. The approach is Bayesian and only requires the generation of a new inert variable in the analysis; however, in the spirit of frequentist hypothesis testing, the posterior distribution of the inert factor is used as a reference distribution against which the importance of the experimental factors can be assessed. The methodology is demonstrated on an application in material science, a computer experiment from the literature, and simulated examples.

Neutralizing antibodies (nAbs) are a high priority for vaccines that aim to prevent the acquisition of HIV-1 infection. Vaccine effectiveness will depend on the extent to which induced antibodies neutralize the global diversity of circulating HIV-1 variants. Using large panels of genetically and geographically diverse HIV-1 Env-pseudotyped viruses and chronic infection plasma samples, we unambiguously show that cross-clade nAb responses are commonly induced in response to infection by any virus clade. Nonetheless, neutralization was significantly greater when the plasma clade matched the clade of the virus being tested. This within-clade advantage was diminished in older, more-diverse epidemics in southern Africa, the United States, and Europe compared to more recent epidemics in Asia. It was most pronounced for circulating recombinant form (CRF) 07_BC, which is common in China and is the least-divergent lineage studied; this was followed by the slightly more diverse Asian CRF01_AE. We found no evidence that transmitted/founder viruses are generally more susceptible to neutralization and are therefore easier targets for vaccination than chronic viruses. Features of the gp120 V1V2 loop, in particular, length, net charge, and number of N-linked glycans, were associated with Env susceptibility and plasma neutralization potency in a manner consistent with neutralization escape being a force that drives viral diversification and plasma neutralization breadth. The overall susceptibility of Envs and potencies of plasma samples were highly predictive of the neutralization outcome of any single virus-plasma combination. These findings highlight important considerations for the design and testing of candidate HIV-1 vaccines that aim to elicit effective nAbs.IMPORTANCEAn effective HIV-1 vaccine will need to overcome the extraordinary variability of the virus, which is most pronounced in the envelope glycoproteins (Env), which are the sole targets for neutralizing antibodies (nAbs). Distinct genetic lineages, or clades, of HIV-1 occur in different locales that may require special consideration when designing and testing vaccines candidates. We show that nAb responses to HIV-1 infection are generally active across clades but are most potent within clades. Because effective vaccine-induced nAbs are likely to share these properties, optimal coverage of a particular clade or combination of clades may require clade-matched immunogens. Optimal within-clade coverage might be easier to achieve in regions such as China and Thailand, where the epidemic is more recent and the virus less diverse than in southern Africa, the United States, and Europe. Finally, features of the first and second hypervariable regions of gp120 (V1V2) may be critical for optimal vaccine design.

The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R ₀ , was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R ₀ value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus. One-sentence summary: By collecting and analyzing spatiotemporal data, we estimated the transmission potential for 2019-nCoV.