Goodness-of-Fit Tests to study the Gaussianity of the MAXIMA data

Goodness-of-Fit tests, including Smooth ones, are introduced and applied to detect non-Gaussianity in Cosmic Microwave Background simulations. We study the power of three different tests: the Shapiro-Francia test (1972), the uncategorised smooth test developed by Rayner and Best(1990) and the Neyman's Smooth Goodness-of-fit test for composite hypotheses (Thomas and Pierce 1979). The Smooth Goodness-of-Fit tests are designed to be sensitive to the presence of ``smooth'' deviations from a given distribution. We study the power of these tests based on the discrimination between Gaussian and non-Gaussian simulations. Non-Gaussian cases are simulated using the Edgeworth expansion and assuming pixel-to-pixel independence. Results show these tests behave similarly and are more powerful than tests directly based on cumulants of order 3, 4, 5 and 6. We have applied these tests to the released MAXIMA data. The applied tests are built to be powerful against detecting deviations from univariate Gaussianity. The Cholesky matrix corresponding to signal (based on an assumed cosmological model) plus noise is used to decorrelate the observations previous to the analysis. Results indicate that the MAXIMA data are compatible with Gaussianity.Comment: MNRAS, in pres

Comparative demography and diversity of small mammals in precordilleran temperate rainforests of Southern Chile

Small mammals were studied in two southern Chilean temperate rainforests in the precordillean Andes during 2 low-rainfall years following the 1982 El Niño event. Forests had somewhat different levels of canopy, shrub, and herbaceous cover, and species richness of trees but most of the same plants. Most captures were of four sigmodontine rodents, Akodon olivaceus, Abrothrix longipilis, Abrothrix sanborni, and Oligoryzomys longicaudatus; five other species and a putative hybrid were recorded. Maximum numbers were in January-July (late summer to winter) and lower numbers in August-December (late winter to early summer). All species had seasonal reproduction in September-April (spring to autumn). A. olivaceus and A. longipilis generally were long-lived, whereas survival rates were low for O. longicaudatus. Responses after the 1982 El Niño were small, and some populations increased during 1984. Populations of A. olivaceus fluctuated more than those of A. longipilis; those of A. sanborni were low and O. longicaudatus was sporadic and irruptive. Lower-elevational Chilean and precordilleran Argentine forests have similar species composition, but differences in demography and dominance of the former by more widespread, omnivorous A. olivaceus, animalivorous-fungivorous Abrothrix, and granivorous O. longicaudatus. Opportunities for immigration may explain greater homogeneity of populations of small mammals in Chilean rainforests relative to Argentine ones. Although responses to El Niño and subsequent droughts were weak, flowering episodes of bamboo (Chusquea) can have strong effects due to increased availability of food

Cell and animal models of SARS-CoV-2 pathogenesis and immunity

The spread of the novel virus SARS coronavirus 2 (SARS-CoV-2) was explosive, with cases first identified in December 2019, and >22 million people infected and >775,000 deaths as of August 2020. SARS-CoV-2 can cause severe respiratory disease in humans leading to coronavirus disease 2019 (COVID-19). The development of effective clinical interventions, such as antivirals and vaccines that can limit or even prevent the burden and spread of SARS-CoV-2, is a global health priority. Testing of leading antivirals, monoclonal antibody therapies and vaccines against SARS-CoV-2 will require robust animal and cell models of viral pathogenesis. In this Special Article, we discuss the cell-based and animal models of SARS-CoV-2 infection and pathogenesis that have been described as of August 2020. We also outline the outstanding questions for which researchers can leverage animal and cell-based models to improve our understanding of SARS-CoV-2 pathogenesis and protective immunity. Taken together, the refinement of models of SARS-CoV-2 infection will be critical to guide the development of therapeutics and vaccines against SARS-CoV-2 to end the COVID-19 pandemic

Dengue Vaccines: The Promise and Pitfalls of Antibody-Mediated Protection

More than 390 million human dengue virus (DENV) infections occur each year, worldwide. Dengvaxia, a live-virus tetravalent vaccine from Sanofi Pasteur, was recently approved for human clinical use, although vaccine performance against the four DENV serotypes is highly variable. Other dengue vaccines in advanced clinical testing also demonstrate variability in efficacy. In this review, we outline the benefits and challenges of developing a safe, effective, and balanced DENV vaccine that can provide uniform protection against all four serotypes. Even though T cell biology plays an important role in establishing protective immunity, this review focuses on B cell responses. We discuss the leading dengue vaccine candidates and review the specificity of antibody responses and the known immune correlates of protection against DENV infection. A better understanding of immune correlates of protection against DENV infection will inform the development of a vaccine that can provide long-term, uniform protection. © 2020; Dengue virus remains one of the most significant vector-borne viruses with a heavy public health burden. Despite recent approvals of vaccine candidates, full antibody-mediated protection remains a challenge. In this review, Martinez, Metz, and Baric summarize these challenges and outline directions for developing a safe vaccine with uniform protection

Lethal Surface Ozone Concentrations Are Possible on Habitable Zone Exoplanets

Ozone (O3) is important for the survival of life on Earth because it shields the surface from ionizing ultraviolet radiation. However, the existence of O3 in Earth's atmosphere is not always beneficial. Resulting from anthropogenic activity, O3 exists as a biologically harmful pollutant at the surface when it forms in the presence of sunlight and other pollutants. As a strong oxidizer, O3 can be lethal to several different organisms; thus, when assessing the potential habitability of an exoplanet, a key part is determining whether toxic gases could be present at its surface. Using the Whole Atmosphere Community Climate Model version 6 (WACCM6; a three-dimensional chemistry-climate model), 12 atmospheric simulations of the terrestrial exoplanet TRAPPIST-1 e are performed with a variety of O2 concentrations and assuming two different stellar spectra proposed in the literature. Four atmospheric simulations of the exoplanet Proxima Centauri b are also included. Some scenarios for both exoplanets exhibit time-averaged surface O3 mixing ratios exceeding harmful levels of 40 ppbv, with 2120 ppbv the maximum concentration found in the cases simulated. These concentrations are toxic and can be fatal to most life on Earth. In other scenarios O3 remains under harmful limits over a significant fraction of the surface, despite there being present regions that may prove inhospitable. In the case in which O3 is detected in a terrestrial exoplanet's atmosphere, determining the surface concentration is an important step when evaluating a planet's habitability

A nano-luciferase expressing human coronavirus OC43 for countermeasure development

The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against novel emerging viruses. Antivirals with broad-spectrum activity overcome this limitation by targeting highly conserved regions or catalytic domains within viral proteins that are essential for replication. For rapid identification of small molecules with broad antiviral activity, assays with viruses representing family-wide genetic diversity are needed. Viruses engineered to express a reporter gene (i.e. luminescence, fluorescence, etc.) can increase the efficiency, sensitivity or precision of drug screening over classical measures of replication like observation of cytopathic effect or measurement of infectious titers. We have previously developed reporter virus systems for multiple other endemic, pandemic, epidemic and enzootic CoV. Human CoV OC43 (HCoV-OC43) is a human endemic CoV that causes respiratory infection with age-related exacerbations of pathogenesis. Here, we describe the development of a novel recombinant HCoV-OC43 reporter virus that expresses nano-luciferase (HCoV-OC43 nLuc), and its potential application for screening of antivirals against CoV

Manifestation of ageing in the low temperature conductance of disordered insulators

We are interested in the out of equilibrium phenomena observed in the electrical conductance of disordered insulators at low temperature, which may be signatures of the electron coulomb glass state. The present work is devoted to the occurrence of ageing, a benchmark phenomenon for the glassy state. It is the fact that the dynamical properties of a glass depend on its age, i.e. on the time elapsed since it was quench-cooled. We first critically analyse previous studies on disordered insulators and question their interpretation in terms of ageing. We then present new measurements on insulating granular aluminium thin films which demonstrate that the dynamics is indeed age dependent. We also show that the results of different relaxation protocols are related by a superposition principle. The implications of our findings for the mechanism of the conductance slow relaxations are then discussed

Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees

Martinez et al. demonstrate that dengue virus serotype 2 (DENV2) genetic variation modulates neutralizing antibody activity from infection and vaccination. This observation underlines that genotypic variation impacts dengue virus 2 evasion from humoral immunity, suggesting that intraserotype genotypic variation should be considered in designing dengue vaccines. © 2020 The Author(s); Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) proteins of DENV2 on vaccine performance. We generated a recombinant DENV2 genotype variant panel with contemporary prM and E isolates that are representative of global genetic diversity. The DENV2 genotype variants differ in growth kinetics, morphology, and virion stability. Importantly, the DENV2 genotypic variants are differentially neutralized by monoclonal antibodies, polyclonal serum neutralizing antibodies from DENV2-infected human subjects, and vaccine-elicited antibody responses from the TV003 NIH DENV2 monovalent and DENV tetravalent vaccines. We conclude that DENV2 prM and E genetic diversity significantly modulates antibody neutralization activity. These findings have important implications for dengue vaccines, which are being developed under the assumption that intraserotype variation has minimal impact on neutralizing antibodies

The kinetics of the gas-phase reactions of selected monoterpenes and cyclo-alkenes with ozone and the NO3 radical

The relative rate method has been used to measure the room-temperature rate constants for the gasphase reactions of ozone and NO3 with selected monoterpenes and cyclo-alkenes with structural similarities to monoterpenes. Measurements were carried out at 298 ! 2 K and 760 ! 10 Torr. The following rate constants (in units of 10"18 cm3 molecule"1 s"1) were obtained for the reaction with ozone: methyl cyclohexene (132 ! 17), terpinolene (1290 ! 360), ethylidene cyclohexane (223 ! 57), norbornene (860 ! 240), t-butyl isopropylidene cyclohexane (1500 ! 460), cyclopentene (543 ! 94), cyclohexene (81 ! 18), cyclooctene (451 ! 66), dicyclopentadiene (1460 ! 170) and a-pinene (107 ! 13). For the reaction with NO3 the rate constants obtained (in units of 10"12 cm3 molecule"1 s"1) were: methyl cyclohexene (7.92 ! 0.95), terpinolene (47.9 ! 4.0), ethylidene cyclohexane (4.30 ! 0.24), norbornene (0.266 ! 0.029), cyclohexene (0.540 ! 0.017), cyclooctene (0.513 ! 0.029), dicyclopentadiene (1.20 ! 0.10) and a-pinene (5.17 ! 0.62). Errors are quoted as the root mean square of the statistical error (95% con!dence) and the quoted error in the rate constant for the reference compound. Combining these results with previous studies, new recommendations for the rate constants are presented. Molecular orbital energies were calculated for each alkene and the kinetic data are discussed in terms of the deviation from the structureeactivity relationship obtained from the rate constants for a series of simple alkenes. Lifetimes with respect to key initiators of atmospheric oxidation have been calculated suggesting that the studied reactions play dominant roles in the night-time removal of these compounds from the atmosphere