Bayesian estimation applied to multiple species

Observed data are often contaminated by undiscovered interlopers, leading to biased parameter estimation. Here we present BEAMS (Bayesian estimation applied to multiple species) which significantly improves on the standard maximum likelihood approach in the case where the probability for each data point being “pure” is known. We discuss the application of BEAMS to future type-Ia supernovae (SNIa) surveys, such as LSST, which are projected to deliver over a million supernovae light curves without spectra. The multiband light curves for each candidate will provide a probability of being Ia (pure) but the full sample will be significantly contaminated with other types of supernovae and transients. Given a sample of N supernovae with mean probability, ⟨P⟩, of being Ia, BEAMS delivers parameter constraints equal to N⟨P⟩ spectroscopically confirmed SNIa. In addition BEAMS can be simultaneously used to tease apart different families of data and to recover properties of the underlying distributions of those families (e.g. the type-Ibc and II distributions). Hence BEAMS provides a unified classification and parameter estimation methodology which may be useful in a diverse range of problems such as photometric redshift estimation or, indeed, any parameter estimation problem where contamination is an issue

Alkali and Alkaline Earth Metal Compounds: Core-Valence Basis Sets and Importance of Subvalence Correlation

Core-valence basis sets for the alkali and alkaline earth metals Li, Be, Na, Mg, K, and Ca are proposed. The basis sets are validated by calculating spectroscopic constants of a variety of diatomic molecules involving these elements. Neglect of $(3s,3p)$ correlation in K and Ca compounds will lead to erratic results at best, and chemically nonsensical ones if chalcogens or halogens are present. The addition of low-exponent $p$ functions to the K and Ca basis sets is essential for smooth convergence of molecular properties. Inclusion of inner-shell correlation is important for accurate spectroscopic constants and binding energies of all the compounds. In basis set extrapolation/convergence calculations, the explicit inclusion of alkali and alkaline earth metal subvalence correlation at all steps is essential for K and Ca, strongly recommended for Na, and optional for Li and Mg, while in Be compounds, an additive treatment in a separate `core correlation' step is probably sufficient. Consideration of $(1s)$ inner-shell correlation energy in first-row elements requires inclusion of $(2s,2p)$ `deep core' correlation energy in K and Ca for consistency. The latter requires special CCV$n$Z `deep core correlation' basis sets. For compounds involving Ca bound to electronegative elements, additional $d$ functions in the basis set are strongly recommended. For optimal basis set convergence in such cases, we suggest the sequence CV(D+3d)Z, CV(T+2d)Z, CV(Q+$d$)Z, and CV5Z on calcium.Comment: Molecular Physics, in press (W. G. Richards issue); supplementary material (basis sets in G98 and MOLPRO formats) available at http://theochem.weizmann.ac.il/web/papers/group12.htm

Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans

<p>Abstract</p> <p>Background</p> <p>Invasion of host tissue by the human fungal pathogen <it>Candida albicans </it>is an important step during the development of candidosis. However, not all <it>C. albicans </it>strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the <it>in vitro </it>phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.</p> <p>Results</p> <p>In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion <it>in vitro</it>. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an <it>in vitro </it>invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, <it>in vitro </it>transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal <it>in vitro </it>growth conditions.</p> <p>Conclusion</p> <p>Our data suggest that the reason for differential virulence of <it>C. albicans </it>strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.</p

Universal fluctuations in subdiffusive transport

Subdiffusive transport in tilted washboard potentials is studied within the fractional Fokker-Planck equation approach, using the associated continuous time random walk (CTRW) framework. The scaled subvelocity is shown to obey a universal law, assuming the form of a stationary Levy-stable distribution. The latter is defined by the index of subdiffusion alpha and the mean subvelocity only, but interestingly depends neither on the bias strength nor on the specific form of the potential. These scaled, universal subvelocity fluctuations emerge due to the weak ergodicity breaking and are vanishing in the limit of normal diffusion. The results of the analytical heuristic theory are corroborated by Monte Carlo simulations of the underlying CTRW

New Relations and Constraints on Quark Spin-flavor Contents in Symmetry-breaking Chiral Quark Model

New relations between the quark spin-flavor contents of the nucleon and axial weak coupling constants are obtained in the chiral quark model with both SU(3) and U(1)-breaking effects. Using the nonsinglet spin combinations, $\Delta_3$ and $\Delta_8$, all spin-flavor observables are functions of only one parameter $a$ $-$ probability for the chiral pionic fluctuation. The upper and lower bounds of these observables are given. The optimal range of $a$, determined by NMC data $\bar d-\bar u$, gives a constraint to the cutoff of the chiral quark field theory. The model predictions are in good agreement with the existing data in this range of $a$. The roles of kaon, $\eta$ and $\eta'$ are also discussed.Comment: 20 pages, Revtex, 3 tables, 4 figure

The Flavor Asymmetry of the Nucleon Sea

We re-examine the effects of anti-symmetry on the anti-quarks in the nucleon sea arising from gluon exchange and pion exchange between confined quarks. While the effect is primarily to suppress anti-down relative to anti-up quarks, this is numerically insignificant for the pion terms.Comment: To appear in Phys. Rev.

The Candida albicans-Specific Gene EED1 Encodes a Key Regulator of Hyphal Extension

The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues

Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00063.Multiple sclerosis represents the world’s most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act non-specifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving conjugation of disease causing auto-antigen, PLP139–151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugate to SJL mice induced with experimental autoimmune encephalomyelitis protected the mice from symptom onset throughout the 25-day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of auto-antigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases.National Institutes of Health Graduate Training Program in Dynamic Aspects of Chemical Biology Grant (T32 GM008545)Howard Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of KansasNational Institutes of Health Biotechnology Training Grant (NIH0073415)NIH Shared Instrumentation Grant # S10RR024664NSF Major Research Instrumentation Award # 162592

Pion Content of the Nucleon as seen in the NA51 Drell-Yan experiment

In a recent CERN Drell-Yan experiment the NA51 group found a strong asymmetry of $\bar u$ and $\bar d$ densities in the proton at $x\simeq0.18$. We interpret this result as a decisive confirmation of the pion-induced sea in the nucleon.Comment: 10 pages + 3 figures, Preprint KFA-IKP(TH)-1994-14 .tex file. After \enddocument a uu-encodeded Postscript file comprising the figures is appende

The Mars Science Laboratory record of optical depth measurements via solar imaging

The Mars Science Laboratory Curiosity rover has monitored the Martian environment in Gale crater since landing in 2012. This study reports the record of optical depth derived from visible and near-infrared images of the Sun. Aerosol optical depth, which is mostly due to dust but also includes ice, dominates the record, with gas optical depth too small to measure. The optical depth record includes the effects of regional dust storms and one planet-encircling dust event, showing the expected peaks during southern spring and summer and relatively lower and more stable optical depth in fall and winter. The measurements show that there is a seasonally varying diurnal change in dust load, with the optical depth peaking in the morning during southern spring and summer, correlated with thermotidal pressure changes. However, there was no systematic diurnal change during autumn and winter, except after one regional storm. There were indications that the dust was relatively enhanced at high altitudes during high-optical-depth periods and that high-altitude ice was significant during winter. The observations did not provide much information about particle size or composition, but they were consistent with a smaller particle size after aphelion (in southern winter). No scattering halos were seen in associated sky images, even when there was visual evidence of ice hazes or clouds, which suggests small or amorphous ice particles. Unexpectedly, the measurement campaign revealed that the cameras collected saltating sand in their sunshades 1.97 m above the surface. As a result, the measurement strategy had to be adjusted to avoid high-elevation imaging to avoid sand covering the optics