Publications

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiome or the host immune phenotype.

Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers.

IFN-γ treatment did not change α or β diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-β in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found.

These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF.

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

Strongly correlated systems exhibit intriguing properties caused by intertwined microscopic interactions that are hard to disentangle in equilibrium. Employing non-equilibrium time-resolved photoemission spectroscopy on the quasi-two-dimensional transition-metal dichalcogenide 1T-TaS2, we identify a spectroscopic signature of double occupied sites (doublons) that are reflects fundamental Mott physics. Doublon-hole recombination is estimated to occur on time scales of one electronic hopping cycle ℏ/J ≈ 14 fs. Despite strong electron-phonon coupling the dynamics can be explained by purely electronic effects captured by the single band Hubbard model, where thermalization is fast in the small-gap regime. Qualitative agreement with the experimental results however requires the assumption of an intrinsic hole-doping. The sensitivity of the doublon dynamics on the doping level provides a way to control ultrafast processes in such strongly correlated materials.

We explore the implications of the observed low spins aligned with the orbital axis in Advanced~LIGO~O1 run on binary black hole (BBH)~merger scenarios in which the merging BBHs have evolved from field binaries. The coalescence time determines the initial orbital separation of BBHs. This, in turn, determines whether the stars are synchronized before collapse and hence determines their projected spins. Short coalescence times imply synchronization and large spins. Among known stellar objects, Wolf-Rayet~(WR) stars seem the only progenitors consistent with the low aligned spins observed in LIGO's~O1 provided that the orbital axis maintains its direction during the collapse. We calculate the spin distribution of BBH mergers in the local Universe and its redshift evolution for WR progenitors. Assuming that the BBH formation rate peaks around a redshift of ∼2--3, we show that BBH mergers in the local Universe are dominated by low spin events. The high spin population starts to dominate at a redshift of ∼0.5--1.5. WR stars are also progenitors of long Gamma-Ray~Bursts~(LGRBs) that take place at a comparable rate to BBH mergers. We discuss the possible connection between the two phenomena. Additionally, we show that hypothetical Population~III star progenitors are also possible. Although WR and Population~III progenitors are consistent with the current data, both models predict a non-vanishing fraction of high aligned spin BBH mergers. If those are not detected within the coming LIGO/Virgo runs, it will be unlikely that the observed BBHs formed via field binaries.

In recent years, semidefinite programs (SDP) have been the subject of interesting research in the field of clustering. In many cases, these convex programs deliver the same answers as non-convex alternatives and come with a guarantee of optimality. Unexpectedly, we find that a popular semidefinite relaxation of K-means (SDP-KM), learns manifolds present in the data, something not possible with the original K-means formulation. To build an intuitive understanding of its manifold learning capabilities, we develop a theoretical analysis of SDP-KM on idealized datasets. Additionally, we show that SDP-KM even segregates linearly non-separable manifolds. SDP-KM is convex and the globally optimal solution can be found by generic SDP solvers with polynomial time complexity. To overcome poor performance of these solvers on large datasets, we explore efficient algorithms based on the explicit Gramian representation of the problem. These features render SDP-KM a versatile and interesting tool for manifold learning while remaining amenable to theoretical analysis.

We study the dynamics of screening in photodoped Mott insulators with long-ranged interactions using a nonequilibrium implementation of the GW plus extended dynamical mean-field theory formalism. Our study demonstrates that the complex interplay of the injected carriers with bosonic degrees of freedom (charge fluctuations) can result in long-lived transient states with properties that are distinctly different from those of thermal equilibrium states. Systems with strong nonlocal interactions are found to exhibit a self-sustained population inversion of the doublons and holes. This population inversion leads to low-energy antiscreening which can be detected in time-resolved electron-energy-loss spectra.

We determine the radio size distribution of a large sample of 152 SMGs in COSMOS that were detected with ALMA at 1.3 mm. For this purpose, we used the observations taken by the VLA-COSMOS 3 GHz Large Project. One hundred and fifteen of the 152 target SMGs were found to have a 3 GHz counterpart. The median value of the major axis FWHM at 3 GHz is derived to be 4.6±0.4 kpc. The radio sizes show no evolutionary trend with redshift, or difference between different galaxy morphologies. We also derived the spectral indices between 1.4 and 3 GHz, and 3 GHz brightness temperatures for the sources, and the median values were found to be α=−0.67 and TB=12.6±2 K. Three of the target SMGs, which are also detected with the VLBA, show clearly higher brightness temperatures than the typical values. Although the observed radio emission appears to be predominantly powered by star formation and supernova activity, our results provide a strong indication of the presence of an AGN in the VLBA and X-ray-detected SMG AzTEC/C61. The median radio-emitting size we have derived is 1.5-3 times larger than the typical FIR dust-emitting sizes of SMGs, but similar to that of the SMGs' molecular gas component traced through mid-J line emission of CO. The physical conditions of SMGs probably render the diffusion of cosmic-ray electrons inefficient, and hence an unlikely process to lead to the observed extended radio sizes. Instead, our results point towards a scenario where SMGs are driven by galaxy interactions and mergers. Besides triggering vigorous starbursts, galaxy collisions can also pull out the magnetised fluids from the interacting disks, and give rise to a taffy-like synchrotron-emitting bridge. This provides an explanation for the spatially extended radio emission of SMGs, and can also cause a deviation from the well-known IR-radio correlation.

We explore theoretically the aerodynamics of a recently fabricated jellyfish-like flying machine (Ristroph & Childress, J. R. Soc. Interface, vol. 11 (92), 2014, 20130992). This experimental device achieves flight and hovering by opening and closing opposing sets of wings. It displays orientational or postural flight stability without additional control surfaces or feedback control. Our model ‘machine’ consists of two mirror-symmetric massless flapping wings connected to a volumeless body with mass and moment of inertia. A vortex sheet shedding and wake model is used for the flow simulation. Use of the fast multipole method allows us to simulate for long times and resolve complex wakes. We use our model to explore the design parameters that maintain body hovering and ascent, and investigate the performance of steady ascent states. We find that ascent speed and efficiency increase as the wings are brought closer, due to a mirror-image ‘ground-effect’ between the wings. Steady ascent is approached exponentially in time, which suggests a linear relationship between the aerodynamic force and ascent speed. We investigate the orientational stability of hovering and ascent states by examining the flyer’s free response to perturbation from a transitory external torque. Our results show that bottom-heavy flyers (centre of mass below the geometric centre) are capable of recovering from large tilts, whereas the orientation of the top-heavy flyers diverges. These results are consistent with the experimental observations in Ristroph & Childress (J. R. Soc. Interface, vol. 11 (92), 2014, 20130992), and shed light upon future designs of flapping-wing micro aerial vehicles that use jet-based mechanisms.

Distances to individual stars in our own Galaxy are critical in order to piece together the nature of its velocity and spatial structure. Core helium burning red clump (RC) stars have similar luminosities, are abundant throughout the Galaxy, and thus constitute good standard candles. We build a hierarchical probabilistic model to quantify the quality of RC stars as standard candles using parallax measurements from the first Gaia data release. A unique aspect of our methodology is to fully account for (and marginalize over) parallax, photometry, and dust corrections uncertainties, which leads to more robust results than standard approaches. We determine the absolute magnitude and intrinsic dispersion of the RC in 2MASS bands J, H, Ks, Gaia G band, and WISE bands W1, W2, W3, and W4. We find that the absolute magnitude of the RC is −1.61± 0.01 (in Ks), +0.44± 0.01 (in G) , −0.93± 0.01 (in J), −1.46± 0.01 (in H), −1.68± 0.02 (in W1), −1.69± 0.02 (in W2), −1.67± 0.02 (in W3), 1.76± 0.01 mag (in W4). The mean intrinsic dispersion is ∼0.17± 0.03 mag across all bands (yielding a typical distance precision of ∼ 8%). Thus RC stars are reliable and precise standard candles. In addition, we have also re-calibrated the zero point of the absolute magnitude of the RC in each band, which provide a benchmark for future studies to estimate distances to RC stars. Finally, the parallax error shrinkage in the hierarchical model outlined in this work can be used to obtain more precise parallaxes than Gaia for the most distant RC stars across the Galaxy.

The absolute number and the density profiles of different types of stars in the solar neighborhood are a fundamental anchor for studies of the initial mass function, stellar evolution, and galactic structure. Using data from the Gaia DR1 Tycho-Gaia Astrometric Solution, we reconstruct Gaia's selection function and we determine Gaia's volume completeness, the local number density, and the vertical profiles of different spectral types along the main sequence from early A stars to late K stars as well as along the giant branch. We clearly detect the expected flattening of the stellar density profile near the mid-plane for all stellar types: All vertical profiles are well represented by sech^2 profiles, with scale heights ranging from ~50 pc for A stars to ~150 pc for G and K dwarfs and giants. We determine the luminosity function along the main sequence for M_V < 7 (M >~ 0.72M⊙) and along the giant branch for M_J >~ -2.5. Converting this to a mass function, we find that the high-mass (M > 1M⊙) present-day mass function along the main sequence is d n / d M = 0.016 (M/M⊙)−4.7 stars/pc^3/M⊙. Extrapolating below M = 0.72M⊙, we find a total mid-plane stellar density of 0.040+/-0.002 M⊙/pc^3. Giants contribute 0.00039+/-0.00001 stars/pc^3 or about 0.00046+/-0.00005 M⊙/pc^3. The star-formation rate surface density is \Sigma(t) = 7+/-1 exp(-t/[7+/-1 Gyr]) M⊙/pc^2/Gyr. Overall, we find that Gaia DR1's selection biases are manageable and allow a detailed new inventory of the solar neighborhood to be made that agrees with and extends previous studies. This bodes well for mapping the Milky Way with the full Gaia data set.