Site‐specific encoding of photoactivity in antibodies enables light‐mediated antibody‐antigen binding on live cells

Antibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody‐antigen binding using an external agent remain limited. Here, we have developed photoactive antibody fragments by genetic site‐specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light‐mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells. Presence of photocaged tyrosine reduces 7D12‐EGFR binding affinity by over 20‐fold in two out of three 7D12 mutants studied, and binding is restored upon exposure to 365 nm light. Molecular dynamics simulations explain the difference in effect of photocaging on 7D12‐EGFR interaction among the mutants. Finally, we demonstrate the application of photoactive antibodies in delivering fluorophores to EGFR‐positive live cancer cells in a light‐dependent manner

Submillimetre observations of WISE-selected high-redshift, luminous, dusty galaxies

We present SCUBA-2 850um submillimetre (submm) observations of the fields of 10 dusty, luminous galaxies at z ~ 1.7 - 4.6, detected at 12um and/or 22um by the WISE all-sky survey, but faint or undetected at 3.4um and 4.6um; dubbed hot, dust-obscured galaxies (Hot DOGs). The six detected targets all have total infrared luminosities greater than 10^13 L_sun, with one greater than 10^14 L_sun. Their spectral energy distributions (SEDs) are very blue from mid-infrared to submm wavelengths and not well fitted by standard AGN SED templates, without adding extra dust extinction to fit the WISE 3.4um and 4.6um data. The SCUBA-2 850um observations confirm that the Hot DOGs have less cold and/or more warm dust emission than standard AGN templates, and limit an underlying extended spiral or ULIRG-type galaxy to contribute less than about 2% or 55% of the typical total Hot DOG IR luminosity, respectively. The two most distant and luminous targets have similar observed submm to mid-infrared ratios to the rest, and thus appear to have even hotter SEDs. The number of serendipitous submm galaxies (SMGs) detected in the 1.5-arcmin-radius SCUBA-2 850um maps indicates there is a significant over-density of serendipitous sources around Hot DOGs. These submm observations confirm that the WISE-selected ultra-luminous galaxies have very blue mid-infrared to submm SEDs, suggesting that they contain very powerful AGN, and are apparently located in unusual arcmin-scale overdensities of very luminous dusty galaxies.Comment: 12 pages, 8 figures, 3 tables, accepted for publication in MNRA

Modeling effects of L-type ca(2+) current and na(+)-ca(2+) exchanger on ca(2+) trigger flux in rabbit myocytes with realistic T-tubule geometries.

The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+) current affects intracellular Ca(2+) dynamics. Our model includes a realistic 3D geometry of a single t-tubule and its surrounding half-sarcomeres for rabbit ventricular myocytes. The effects of spatially distributed membrane ion-transporters (LCC, Na(+)/Ca(2+) exchanger, sarcolemmal Ca(2+) pump, and sarcolemmal Ca(2+) leak), and stationary and mobile Ca(2+) buffers (troponin C, ATP, calmodulin, and Fluo-3) are also considered. We used a coupled reaction-diffusion system to describe the spatio-temporal concentration profiles of free and buffered intracellular Ca(2+). We obtained parameters from voltage-clamp protocols of L-type Ca(2+) current and line-scan recordings of Ca(2+) concentration profiles in rabbit cells, in which the sarcoplasmic reticulum is disabled. Our model results agree with experimental measurements of global Ca(2+) transient in myocytes loaded with 50 μM Fluo-3. We found that local Ca(2+) concentrations within the cytosol and sub-sarcolemma, as well as the local trigger fluxes of Ca(2+) crossing the cell membrane, are sensitive to details of t-tubule micro-structure and membrane Ca(2+) flux distribution. The model additionally predicts that local Ca(2+) trigger fluxes are at least threefold to eightfold higher than the whole-cell Ca(2+) trigger flux. We found also that the activation of allosteric Ca(2+)-binding sites on the Na(+)/Ca(2+) exchanger could provide a mechanism for regulating global and local Ca(2+) trigger fluxes in vivo. Our studies indicate that improved structural and functional models could improve our understanding of the contributions of L-type and Na(+)/Ca(2+) exchanger fluxes to intracellular Ca(2+) dynamics

The role of the most luminous, obscured AGN in galaxy assembly at z~2

We present HST WFC3 F160W imaging and infrared spectral energy distributions for twelve extremely luminous, obscured AGN at $1.8<z<2.7$, selected via "Hot, Dust Obscured" mid-infrared colors. Their infrared luminosities span $2-15\times10^{13}$L$_{\odot}$, making them among the most luminous objects in the Universe at $z\sim2$. In all cases the infrared emission is consistent with arising at least in most part from AGN activity. The AGN fractional luminosities are higher than those in either sub-millimeter galaxies, or AGN selected via other mid-infrared criteria. Adopting the $G$, M$_{20}$ and $A$ morphological parameters, together with traditional classification boundaries, infers that three quarters of the sample as mergers. Our sample do not, however, show any correlation between the considered morphological parameters and either infrared luminosity or AGN fractional luminosity. Moreover, their asymmetries and effective radii are distributed identically to those of massive galaxies at $z\sim2$. We conclude that our sample is not preferentially associated with mergers, though a significant merger fraction is still plausible. Instead, we propose that our sample are examples of the massive galaxy population at $z\sim2$ that harbor a briefly luminous, "flickering" AGN, and in which the $G$ and M$_{20}$ values have been perturbed, due to either the AGN, and/or the earliest formation stages of a bulge in an inside-out manner. Furthermore, we find that the mass assembly of the central black holes in our sample leads the mass assembly of any bulge component. Finally, we speculate that our sample represent a small fraction of the immediate antecedents of compact star-forming galaxies at $z\sim2$.Comment: ApJ, accepted. Updated to reflect the accepted versio

Interferometric Follow-Up of WISE Hyper-Luminous Hot, Dust-Obscured Galaxies

WISE has discovered an extraordinary population of hyper-luminous dusty galaxies which are faint in the two bluer passbands ($3.4\, \mu$m and $4.6\, \mu$m) but are bright in the two redder passbands of WISE ($12\, \mu$m and $22\, \mu$m). We report on initial follow-up observations of three of these hot, dust-obscured galaxies, or Hot DOGs, using the CARMA and SMA interferometer arrays at submm/mm wavelengths. We report continuum detections at $\sim$ 1.3 mm of two sources (WISE J014946.17+235014.5 and WISE J223810.20+265319.7, hereafter W0149+2350 and W2238+2653, respectively), and upper limits to CO line emission at 3 mm in the observed frame for two sources (W0149+2350 and WISE J181417.29+341224.8, hereafter W1814+3412). The 1.3 mm continuum images have a resolution of 1-2 arcsec and are consistent with single point sources. We estimate the masses of cold dust are 2.0$\times 10^{8} M_{\odot}$ for W0149+2350 and 3.9$\times 10^{8} M_{\odot}$ for W2238+2653, comparable to cold dust masses of luminous quasars. We obtain 2$\sigma$ upper limits to the molecular gas masses traced by CO, which are 3.3$\times 10^{10} M_{\odot}$ and 2.3$\times 10^{10} M_{\odot}$ for W0149+2350 and W1814+3412, respectively. We also present high-resolution, near-IR imaging with WFC3 on the Hubble Space Telescope for W0149+2653 and with NIRC2 on Keck for W2238+2653. The near-IR images show morphological structure dominated by a single, centrally condensed source with effective radius less than 4 kpc. No signs of gravitational lensing are evident.Comment: 13 pages, 3 figures. ApJ in pres

Gallery of contemporary noted mycologists

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43269/1/11046_2005_Article_BF02155513.pd

The Lyman Alpha Reference Sample. VIII. Characterizing Lyman-Alpha Scattering in Nearby Galaxies

We examine the dust geometry and Ly{\alpha} scattering in the galaxies of the Lyman Alpha Reference Sample (LARS), a set of 14 nearby (0.02 < $z$ < 0.2) Ly{\alpha} emitting and starbursting systems with Hubble Space Telescope Ly{\alpha}, H{\alpha}, and H{\beta} imaging. We find that the global dust properties determined by line ratios are consistent with other studies, with some of the LARS galaxies exhibiting clumpy dust media while others of them show significantly lower Ly{\alpha} emission compared to their Balmer decrement. With the LARS imaging, we present Ly{\alpha}/H{\alpha} and H{\alpha}/H{\beta} maps with spatial resolutions as low as $\sim$ 40 pc, and use these data to show that in most galaxies, the dust geometry is best modeled by three distinct regions: a central core where dust acts as a screen, an annulus where dust is distributed in clumps, and an outer envelope where Ly{\alpha} photons only scatter. We show that the dust that affects the escape of Ly{\alpha} is more restricted to the galaxies' central regions, while the larger Ly{\alpha} halos are generated by scattering at large radii. We present an empirical modeling technique to quantify how much Ly{\alpha} scatters in the halo, and find that this "characteristic" scattering distance correlates with the measured size of the Ly{\alpha} halo. We note that there exists a slight anti-correlation between the scattering distance of Ly{\alpha} and global dust properties.Comment: 32 pages, 51 figures, accepted to Ap