Voltage-gating and assembly of split Kv10.1 channels

Voltage-gated ion channels allow ions to pass cell membrane upon changes of transmembrane electrical potential. Conformational changes in the voltage-sensing domain of the channel (VSD) are assumed to be transmitted to the pore domain (PD) through an alpha-helical linker between them (S4-S5 linker). We have previously shown that expression of VSD and PD as separate fragments results in functional Kv10.1 channels that retain voltage-dependence. Here we used such ‘split’ channels to investigate functional interactions between VSD and PD. We found that their electrophysiological properties greatly depend on where the S4-S5 linker is interrupted. Remarkably, wild-type-like channel behavior could be fully or largely restored by mutations of crucial linker amino acids, indicating that precise functional interactions between VSD and PD remain when they are not covalently bound. Voltage-Clamp Fluorometry measurements revealed that VSD motion is alerted in specific split channels, but these changes were subtler. Finally, the increased separation between VSD activation and channel opening in the split channel carrying a large deletion in the S4-S5 linker, as well as the failure of the PD expressed alone to give currents, suggest that the role of the VSD in the is to open the channel pore and prevent it from closing

De Novo Drug Design with Joint Transformers

De novo drug design requires simultaneously generating novel molecules outside of training data and predicting their target properties, making it a hard task for generative models. To address this, we propose Joint Transformer that combines a Transformer decoder, Transformer encoder, and a predictor in a joint generative model with shared weights. We formulate a probabilistic black-box optimization algorithm that employs Joint Transformer to generate novel molecules with improved target properties and outperforms other SMILES-based optimization methods in de novo drug design.Comment: Accepted to NeurIPS 2023 Generative AI and Biology Worksho

A Census of Mid-Infrared Selected Active Galactic Nuclei in Massive Galaxy Clusters at 0 < z < 1.3

We conduct a deep mid-infrared census of nine massive galaxy clusters at (0 = 3 sigma level, we identify 12 that host mid-infrared selected active galactic nuclei (IR-AGN). To compare the IR-AGN across our redshift range, we define two complete samples of cluster galaxies: (1) optically-selected members with rest-frame VAB magnitude 0.5 Mpc) and are hosted by highly morphologically disturbed members. Although our sample is limited, our results suggest that f_IR-AGN in massive galaxy clusters is not strongly correlated with star formation at z < 1, and that IR-AGN have a more prominent role at z &gt; 1

Tracking Galaxy Growth During the Past 11 Billion Years with Deep Near Infrared Surveys

Using observations from the FourStar Galaxy Evolution Survey (ZFOURGE), we obtain the deepest measurements to date of the galaxy stellar mass function (SMF) at z < 3. With these data, we find evidence for a steepening of the slope at the low-mass end of the SMF at z ≤ 2, a feature that had only been identified at z ≤ 1. These measurements also allow us for the first time to observe a rapid buildup of low-mass quiescent galaxies and help to constrain the growth rates of galaxies. We next explore star-formation histories (SFHs) of galaxies based on the evolution of the correlation between the star-formation rate and stellar mass of galaxies (SFR−M∗) and compare to the buildup of stellar mass predicted from the evolution of the SMF. By integrating along the SFR−M∗ sequence we generate differential SFHs and estimate stellar mass-growth histories. We find that these integrated SFHs are in broad qualitative agreement with the SMF, but that they do disagree in detail. At early times the SFHs suggest mass-growth rates that are as much as 0.5 dex higher than inferred from the stellar mass function. Lastly, we look into the prevalence of a possible source of feedback preventing star-formation using mid-IR data from the Spitzer Space Telescope with established color selection criteria to identify galaxies hosting active galactic nuclei (AGN). Of the 949 cluster galaxies in our IR-detected sample we identify 12 that are consistent with hosting AGN. We thus measure the fraction of cluster galaxies that host an IR-AGN for a magnitude-limited subsample (fIR−AGN) to be ≈ 0.6% with a strong upper limit of 3.4% at the 99% confidence level at z 1

Z-FIRE: ISM properties of the z = 2.095 COSMOS Cluster

We investigate the ISM properties of 13 star-forming galaxies within the z~2 COSMOS cluster. We show that the cluster members have [NII]/Ha and [OIII]/Hb emission-line ratios similar to z~2 field galaxies, yet systematically different emission-line ratios (by ~0.17 dex) from the majority of local star-forming galaxies. We find no statistically significant difference in the [NII]/Ha and [OIII]/Hb line ratios or ISM pressures among the z~2 cluster galaxies and field galaxies at the same redshift. We show that our cluster galaxies have significantly larger ionization parameters (by up to an order of magnitude) than local star-forming galaxies. We hypothesize that these high ionization parameters may be associated with large specific star formation rates (i.e. a large star formation rate per unit stellar mass). If this hypothesis is correct, then this relationship would have important implications for the geometry and/or the mass of stars contained within individual star clusters as a function of redshift.Comment: 11 pages, 5 figures, accepted for publication in Ap

ZFIRE: Using Hα\alpha equivalent widths to investigate the in situ initial mass function at z~2

We use the ZFIRE survey (http://zfire.swinburne.edu.au) to investigate the high mass slope of the initial mass function (IMF) for a mass-complete (log10(M$_*$/M$_\odot$)~9.3) sample of 102 star-forming galaxies at z~2 using their H$\alpha$ equivalent widths (H$\alpha$-EW) and rest-frame optical colours. We compare dust-corrected H$\alpha$-EW distributions with predictions of star-formation histories (SFH) from PEGASE.2 and Starburst99 synthetic stellar population models. We find an excess of high H$\alpha$-EW galaxies that are up to 0.3--0.5 dex above the model-predicted Salpeter IMF locus and the H$\alpha$-EW distribution is much broader (10--500 \AA) than can easily be explained by a simple monotonic SFH with a standard Salpeter-slope IMF. Though this discrepancy is somewhat alleviated when it is assumed that there is no relative attenuation difference between stars and nebular lines, the result is robust against observational biases, and no single IMF (i.e. non-Salpeter slope) can reproduce the data. We show using both spectral stacking and Monte Carlo simulations that starbursts cannot explain the EW distribution. We investigate other physical mechanisms including models with variations in stellar rotation, binary star evolution, metallicity, and the IMF upper-mass cutoff. IMF variations and/or highly rotating extreme metal poor stars (Z~0.1Z$_\odot$) with binary interactions are the most plausible explanations for our data. If the IMF varies, then the highest H$\alpha$-EWs would require very shallow slopes ($\Gamma$>-1.0) with no one slope able to reproduce the data. Thus, the IMF would have to vary stochastically. We conclude that the stellar populations at z~2 show distinct differences from local populations and there is no simple physical model to explain the large variation in H$\alpha$-EWs at z~2.Comment: Accepted to MNRAS. 43 pages, 27 Figures. Survey website: http://zfire.swinburne.edu.au

The Properties of Radio Galaxies and the Effect of Environment in Large Scale Structures at z∼1z\sim1

In this study we investigate 89 radio galaxies that are spectroscopically-confirmed to be members of five large scale structures in the redshift range of $0.65 \le z \le 0.96$. Based on a two-stage classification scheme, the radio galaxies are classified into three sub-classes: active galactic nucleus (AGN), hybrid, and star-forming galaxy (SFG). We study the properties of the three radio sub-classes and their global and local environmental preferences. We find AGN hosts are the most massive population and exhibit quiescence in their star-formation activity. The SFG population has a comparable stellar mass to those hosting a radio AGN but are unequivocally powered by star formation. Hybrids, though selected as an intermediate population in our classification scheme, were found in almost all analyses to be a unique type of radio galaxies rather than a mixture of AGN and SFGs. They are dominated by a high-excitation radio galaxy (HERG) population. We discuss environmental effects and scenarios for each sub-class. AGN tend to be preferentially located in locally dense environments and in the cores of clusters/groups, with these preferences persisting when comparing to galaxies of similar colour and stellar mass, suggesting that their activity may be ignited in the cluster/group virialized core regions. Conversely, SFGs exhibit a strong preference for intermediate-density global environments, suggesting that dusty starbursting activity in LSSs is largely driven by galaxy-galaxy interactions and merging.Comment: 28 pages, 10 figures, accepted to MNRA

ZFIRE: A KECK/MOSFIRE Spectroscopic Survey of Galaxies in Rich Environments at z~2

We present an overview and the first data release of ZFIRE, a spectroscopic redshift survey of star-forming galaxies that utilizes the MOSFIRE instrument on Keck-I to study galaxy properties in rich environments at $1.5<z<2.5$. ZFIRE measures accurate spectroscopic redshifts and basic galaxy properties derived from multiple emission lines. The galaxies are selected from a stellar mass limited sample based on deep near infra-red imaging ($\mathrm{K_{AB}<25}$) and precise photometric redshifts from the ZFOURGE and UKIDSS surveys as well as grism redshifts from 3DHST. Between 2013--2015 ZFIRE has observed the COSMOS and UDS legacy fields over 13 nights and has obtained 211 galaxy redshifts over $1.57<z<2.66$ from a combination of nebular emission lines (such as \Halpha, \NII, \Hbeta, \OII, \OIII, \SII) observed at 1--2\micron. Based on our medium-band NIR photometry, we are able to spectrophotometrically flux calibrate our spectra to \around10\% accuracy. ZFIRE reaches $5\sigma$ emission line flux limits of \around$\mathrm{3\times10^{-18}~erg/s/cm^2}$ with a resolving power of $R=3500$ and reaches masses down to \around10$^{9}$\msol. We confirm that the primary input survey, ZFOURGE, has produced photometric redshifts for star-forming galaxies (including highly attenuated ones) accurate to $\Delta z/(1+z\mathrm{_{spec})}=0.015$ with $0.7\%$ outliers. We measure a slight redshift bias of $<0.001$, and we note that the redshift bias tends to be larger at higher masses. We also examine the role of redshift on the derivation of rest-frame colours and stellar population parameters from SED fitting techniques. The ZFIRE survey extends spectroscopically-confirmed $z\sim 2$ samples across a richer range of environments, here we make available the first public release of the data for use by the community.\footnote{\url{http://zfire.swinburne.edu.au}}Comment: Published in ApJ. Data available at http://zfire.swinburne.edu.au, Code for figures at https://github.com/themiyan/zfire_survey, 31 pages, 24 figure

Treatment of severe mitral regurgitation with MitraClip system — a single-centre study

Introduction. MitraClip (MC) is a catheter-based device to treat mitral regurgitation (MR). This method uses a transseptal approach and is based on the creation of a double orifice mitral valve by suturing of the middle scallops of the mitral valve’s leaflets. Aim. The aim of the study was to assess the effectiveness of MC method in treating patients with severe MR. We analysed MR severity, patient’s clinical condition evaluated by New York Heart Association (NYHA) functional class, and the function of the left ventricle evaluated by Left Ventricle Ejection Fraction (LVEF). Methods. A retrospective single-centre study with patients hospitalised at the Department of Cardiology and Internal Medicine in Bydgoszcz. All diagnosed with severe MR and treated by performing MC procedure in the time period from August 2010 to December 2014. The following data from medical history (NYHA class) and echocardiography examinations (MR severity and LVEF) were analysed in three time points: before, right after the procedure, and after the follow-up period (four weeks since discharge). Results. The studied group consisted of 11 patients — 8 male, 3 female, aged 64.4 ( ± 10.2) years, treated with MC. All of the three analysed parameters improved relevantly as a result of the evaluated procedure. The percentage of patients classified as NYHA class III/IV presents as follows: 90% before the procedure, 55% after MC implantation (ns), and 44% after the follow-up period (p = 0.01). All patients suffered from severe-to-moderate (3+) and severe (4+) MR before the procedure. After implantation only 9% (ns) were still classified with 3+/4+ MR, and after the follow-up this percentage reached 18% (p = 0.0005). We observed relevant changes of LVEF. The average LVEF at baseline was 27.9 ± 2%, which increased to 29.6 ± 2% (ns) after the MC implantation and 34 ± 7% (p = 0.02) after the follow-up. Conclusion. MC therapy is effective in patients with severe symptomatic MR with congestive heart failure and decreased LVEF. It reduces MR severity both acutely and after the follow-up period and improves NYHA class and LVEF.