A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

A question of scale: Human migrations writ large and small

Several recent papers illustrate the importance of migration and gene flow in molding the patterns of genetic variation observed in humans today. We place the varied demographic processes covered by these terms into a more general framework, and discuss some of the challenges facing attempts to reconstruct past human mobility and determine its influence on our genetic heritage

A cross-national study on the antecedents of work–life balance from the fit and balance perspective

Drawing on the perceived work–family fit and balance perspective, this study investigates demands and resources as antecedents of work–life balance (WLB) across four countries (New Zealand, France, Italy and Spain), so as to provide empirical cross-national evidence. Using structural equation modelling analysis on a sample of 870 full time employees, we found that work demands, hours worked and family demands were negatively related to WLB, while job autonomy and supervisor support were positively related to WLB. We also found evidence that resources (job autonomy and supervisor support) moderated the relationships between demands and work–life balance, with high resources consistently buffering any detrimental influence of demands on WLB. Furthermore, our study identified additional predictors of WLB that were unique to some national contexts. For example, in France and Italy, overtime hours worked were negatively associated with WLB, while parental status was positively associated with WLB. Overall, the implications for theory and practice are discussed.Peer ReviewedPostprint (author's final draft

Predicting mental imagery based BCI performance from personality, cognitive profile and neurophysiological patterns

Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy— EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants’ BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants’ performance with a mean error of less than 3 points. This study determined how users’ profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user

Toward a Unification of Star Formation Rate Determinations in the Milky Way and Other Galaxies

The star formation rate (SFR) of the Milky Way remains poorly known, with often-quoted values ranging from 1 to 10 solar masses per year. This situation persists despite the potential for the Milky Way to serve as the ultimate SFR calibrator for external galaxies. We show that various estimates for the Galactic SFR are consistent with one another once they have been normalized to the same initial mass function (IMF) and massive star models, converging to 1.9 +/- 0.4 M_sun/yr. However, standard SFR diagnostics are vulnerable to systematics founded in the use of indirect observational tracers sensitive only to high-mass stars. We find that absolute SFRs measured using resolved low/intermediate-mass stellar populations in Galactic H II regions are systematically higher by factors of ~2-3 as compared with calibrations for SFRs measured from mid-IR and radio emission. We discuss some potential explanations for this discrepancy and conclude that it could be allayed if (1) the power-law slope of the IMF for intermediate-mass (1.5 M_sun < m < 5 M_sun) stars were steeper than the Salpeter slope, or (2) a correction factor was applied to the extragalactic 24 micron SFR calibrations to account for the duration of star formation in individual mid-IR-bright H II regions relative to the lifetimes of O stars. Finally, we present some approaches for testing if a Galactic SFR of ~2 M_sun/yr is consistent with what we would measure if we could view the Milky Way as external observers. Using luminous radio supernova remnants and X-ray point sources, we find that the Milky Way deviates from expectations at the 1-3 sigma level, hinting that perhaps the Galactic SFR is overestimated or extragalactic SFRs need to be revised upwards.Comment: Accepted for publication in A

DustPedia: Multiwavelength photometry and imagery of 875 nearby galaxies in 42 ultraviolet-microwave bands

Aims. The DustPedia project is capitalising on the legacy of the Herschel Space Observatory, using cutting-edge modelling techniques to study dust in the 875 DustPedia galaxies – representing the vast majority of extended galaxies within 3000 km s-1 that were observed by Herschel. This work requires a database of multiwavelength imagery and photometry that greatly exceeds the scope (in terms of wavelength coverage and number of galaxies) of any previous local-Universe survey. Methods. We constructed a database containing our own custom Herschel reductions, along with standardised archival observations from GALEX, SDSS, DSS, 2MASS, WISE, Spitzer, and Planck. Using these data, we performed consistent aperture-matched photometry, which we combined with external supplementary photometry from IRAS and Planck. Results. We present our multiwavelength imagery and photometry across 42 UV-microwave bands for the 875 DustPedia galaxies. Our aperture-matched photometry, combined with the external supplementary photometry, represents a total of 21 857 photometric measurements. A typical DustPedia galaxy has multiwavelength photometry spanning 25 bands. We also present the Comprehensive & Adaptable Aperture Photometry Routine (CAAPR), the pipeline we developed to carry out our aperture-matched photometry. CAAPR is designed to produce consistent photometry for the enormous range of galaxy and observation types in our data. In particular, CAAPR is able to determine robust cross-compatible uncertainties, thanks to a novel method for reliably extrapolating the aperture noise for observations that cover a very limited amount of background. Our rich database of imagery and photometry is being made available to the community

Efimov effect in quantum magnets

Physics is said to be universal when it emerges regardless of the underlying microscopic details. A prominent example is the Efimov effect, which predicts the emergence of an infinite tower of three-body bound states obeying discrete scale invariance when the particles interact resonantly. Because of its universality and peculiarity, the Efimov effect has been the subject of extensive research in chemical, atomic, nuclear and particle physics for decades. Here we employ an anisotropic Heisenberg model to show that collective excitations in quantum magnets (magnons) also exhibit the Efimov effect. We locate anisotropy-induced two-magnon resonances, compute binding energies of three magnons and find that they fit into the universal scaling law. We propose several approaches to experimentally realize the Efimov effect in quantum magnets, where the emergent Efimov states of magnons can be observed with commonly used spectroscopic measurements. Our study thus opens up new avenues for universal few-body physics in condensed matter systems.Comment: 7 pages, 5 figures; published versio

Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis

Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN) induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGESeq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified numerous genes with altered expression to date not associated with role in chronic inflammation, underlying the relevance of our in vitro model for further characterization of IFNprimed iDCs

Post-starburst galaxies: more than just an interesting curiosity

From the VIMOS VLT DEEP Survey (VVDS) we select a sample of 16 galaxies with spectra which identify them as having recently undergone a strong starburst and subsequent fast quenching of star formation. These post-starburst galaxies lie in the redshift range 0.510^9.75Msun. They have a number density of 1x10^-4 per Mpc^3, almost two orders of magnitude sparser than the full galaxy population with the same mass limit. We compare with simulations to show that the galaxies are consistent with being the descendants of gas rich major mergers. Starburst mass fractions must be larger than ~5-10% and decay times shorter than ~10^8 years for post-starburst spectral signatures to be observed in the simulations. We find that the presence of black hole feedback does not greatly affect the evolution of the simulated merger remnants through the post-starburst phase. The multiwavelength spectral energy distributions of the post-starburst galaxies show that 5/16 have completely ceased the formation of new stars. These 5 galaxies correspond to a mass flux entering the red-sequence of rhodot(A->Q, PSB) = 0.0038Msun/Mpc^3/yr, assuming the defining spectroscopic features are detectable for 0.35Gyr. If the galaxies subsequently remain on the red sequence, this accounts for 38(+4/-11)% of the growth rate of the red sequence. Finally, we compare our high redshift results with a sample of galaxies with 0.05<z<0.1 observed in the SDSS and UKIDSS surveys. We find a very strong redshift evolution: the mass density of strong post-starburst galaxies is 230 times lower at z~0.07 than at z~0.7.Comment: 18 pages, 12 figures, to match version accepted to MNRAS. Minor reordering of text in places and Sec 2.2 on SPH simulation comparisons expande

Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences

(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited