A third generation of radical fluorinating agents based on N-fluoro-N-arylsulfonamides

Radical fluorination has been known for a long time, but synthetic applications were severely limited by the hazardous nature of the first generation of reagents such as F-2 and the strongly electrophilic nature of the second generation of reagents such as N-fluorobenzenesulfonimide (NFSI) and Selecfluor (R). Here, we report the preparation, use and properties of N-fluoro-N- arylsulfonamides (NFASs), a class of fluorinating reagents suitable for radical fluorination under mild conditions. Their N-F bond dissociation energies (BDE) are 30-45 kJ moI(-1) lower than the N-F BDE of the reagents of the second generation. This favors clean radical fluorination processes over undesired side reactions. The utility of NFASs is demonstrated by a metal-free radical hydrofluorination of alkenes including an efficient remote C-H fluorination via a 1,5-hydrogen atom transfer. NFASs have the potential to become the reagents of choice in many radical fluorination processes

Highly strained, radially π-conjugated porphyrinylene nanohoops

Small π-conjugated nanohoops are difficult to prepare, but offer an excellent platform for studying the interplay between strain and optoelectronic properties, and, increasingly, these shape-persistent macrocycles find uses in host-guest chemistry and self-assembly. We report the synthesis of a new family of radially π-conjugated porphyrinylene/phenylene nanohoops. The strain energy in the smallest nanohoop [2]CPT is approximately 54 kcal mol⁻¹, which results in a narrowed HOMO-LUMO gap and a red shift in the visible part of the absorption spectrum. Because of its high degree of preorganization and a diameter of ca. 13 Å, [2]CPT was found to accommodate C₆₀ with a binding affinity exceeding 10⁸ M⁻¹ despite the fullerene not fully entering the cavity of the host (X-ray crystallography). Moreover, the ?-extended nanohoops [2]CPTN, [3]CPTN, and [3]CPTA (N for 1,4-naphthyl; A for 9,10-anthracenyl) have been prepared using the same strategy, and [2]CPTN has been shown to bind C₇₀ 5 times more strongly than [2]CPT. Our failed synthesis of [2]CPTA highlights a limitation of the experimental approach most commonly used to prepare strained nanohoops, because in this particular case the sum of aromatization energies no longer outweighs the buildup of ring strain in the final reaction step (DFT calculations). These results indicate that forcing ring strain onto organic semiconductors is a viable strategy to fundamentally influence both optoelectronic and supramolecular properties

Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts

We analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts' aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77 % of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging

CoMet—a web server for comparative functional profiling of metagenomes

Analyzing the functional potential of newly sequenced genomes and metagenomes has become a common task in biomedical and biological research. With the advent of high-throughput sequencing technologies comparative metagenomics opens the way to elucidate the genetically determined similarities and differences of complex microbial communities. We developed the web server ‘CoMet’ (http://comet.gobics.de), which provides an easy-to-use comparative metagenomics platform that is well-suitable for the analysis of large collections of metagenomic short read data. CoMet combines the ORF finding and subsequent assignment of protein sequences to Pfam domain families with a comparative statistical analysis. Besides comprehensive tabular data files, the CoMet server also provides visually interpretable output in terms of hierarchical clustering and multi-dimensional scaling plots and thus allows a quick overview of a given set of metagenomic samples

Warm Dust and Spatially Variable PAH Emission in the Dwarf Starburst Galaxy NGC 1705

We present Spitzer observations of the dwarf starburst galaxy NGC 1705 obtained as part of SINGS. The galaxy morphology is very different shortward and longward of ~5 microns: short-wavelength imaging shows an underlying red stellar population, with the central super star cluster (SSC) dominating the luminosity; longer-wavelength data reveals warm dust emission arising from two off-nuclear regions offset by ~250 pc from the SSC. These regions show little extinction at optical wavelengths. The galaxy has a relatively low global dust mass (~2E5 solar masses, implying a global dust-to-gas mass ratio ~2--4 times lower than the Milky Way average). The off-nuclear dust emission appears to be powered by photons from the same stellar population responsible for the excitation of the observed H Alpha emission; these photons are unassociated with the SSC (though a contribution from embedded sources to the IR luminosity of the off-nuclear regions cannot be ruled out). Low-resolution IRS spectroscopy shows moderate-strength PAH emission in the 11.3 micron band in the eastern peak; no PAH emission is detected in the SSC or the western dust emission complex. There is significant diffuse 8 micron emission after scaling and subtracting shorter wavelength data; the spatially variable PAH emission strengths revealed by the IRS data suggest caution in the interpretation of diffuse 8 micron emission as arising from PAH carriers alone. The metallicity of NGC 1705 falls at the transition level of 35% solar found by Engelbracht and collaborators; the fact that a system at this metallicity shows spatially variable PAH emission demonstrates the complexity of interpreting diffuse 8 micron emission. A radio continuum non-detection, NGC 1705 deviates significantly from the canonical far-IR vs. radio correlation. (Abridged)Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

The Nature of Infrared Emission in the Local Group Dwarf Galaxy NGC 6822 As Revealed by Spitzer

We present Spitzer imaging of the metal-deficient (Z ~30% Z_sun) Local Group dwarf galaxy NGC 6822. On spatial scales of ~130 pc, we study the nature of IR, H alpha, HI, and radio continuum emission. Nebular emission strength correlates with IR surface brightness; however, roughly half of the IR emission is associated with diffuse regions not luminous at H alpha (as found in previous studies). The global ratio of dust to HI gas in the ISM, while uncertain at the factor of ~2 level, is ~25 times lower than the global values derived for spiral galaxies using similar modeling techniques; localized ratios of dust to HI gas are about a factor of five higher than the global value in NGC 6822. There are strong variations (factors of ~10) in the relative ratios of H alpha and IR flux throughout the central disk; the low dust content of NGC 6822 is likely responsible for the different H alpha/IR ratios compared to those found in more metal-rich environments. The H alpha and IR emission is associated with high-column density (> ~1E21 cm^-2) neutral gas. Increases in IR surface brightness appear to be affected by both increased radiation field strength and increased local gas density. Individual regions and the galaxy as a whole fall within the observed scatter of recent high-resolution studies of the radio-far IR correlation in nearby spiral galaxies; this is likely the result of depleted radio and far-IR emission strengths in the ISM of this dwarf galaxy.Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

The Pan-STARRS1 z>5.6 quasar survey II: Discovery of 55 Quasars at 5.6<z<6.5

The identification of bright quasars at z>6 enables detailed studies of supermassive black holes, massive galaxies, structure formation, and the state of the intergalactic medium within the first billion years after the Big Bang. We present the spectroscopic confirmation of 55 quasars at redshifts 5.6<z<6.5 and UV magnitudes -24.5<M1450<-28.5 identified in the optical Pan-STARRS1 and near-IR VIKING surveys (48 and 7, respectively). Five of these quasars have been independently discovered in other studies. The quasar sample shows an extensive range of physical properties, including 17 objects with weak emission lines, ten broad absorption line quasars, and five with strong radio emission (radio-loud quasars). There are also a few notable sources in the sample, including a blazar candidate at z=6.23, a likely gravitationally lensed quasar at z=6.41, and a z=5.84 quasar in the outskirts of the nearby (D~3 Mpc) spiral galaxy M81. The blazar candidate remains undetected in NOEMA observations of the [CII] and underlying emission, implying a star-formation rate <30-70 Msun/yr. A significant fraction of the quasars presented here lies at the foundation of the first measurement of the z~6 quasar luminosity function from Pan-STARRS1 (introduced in a companion paper). The quasars presented here will enable further studies of the high-redshift quasar population with current and future facilities.Comment: Version after addressing referee report. See companion paper by Schindler et a

The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease.

Lung disease accounts for every sixth death globally. Profiling the molecular state of all lung cell types in health and disease is currently revolutionizing the identification of disease mechanisms and will aid the design of novel diagnostic and personalized therapeutic regimens. Recent progress in high-throughput techniques for single-cell genomic and transcriptomic analyses has opened up new possibilities to study individual cells within a tissue, classify these into cell types, and characterize variations in their molecular profiles as a function of genetics, environment, cell-cell interactions, developmental processes, aging, or disease. Integration of these cell state definitions with spatial information allows the in-depth molecular description of cellular neighborhoods and tissue microenvironments, including the tissue resident structural and immune cells, the tissue matrix, and the microbiome. The Human Cell Atlas consortium aims to characterize all cells in the healthy human body and has prioritized lung tissue as one of the flagship projects. Here, we present the rationale, the approach, and the expected impact of a Human Lung Cell Atlas.Supported by the Helmholtz Association and the German Center for Lung Research (DZL) (H.B.S.); the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 753039 (L.M.S.); U.K. Medical Research Council grant G0900424 (E.L.R.); National Institutes of Health (NIH) grants ES013995, HL071643, and AG049665, and Veterans Administration grant BX000201 and Department of Defense grant PR141319 (G.R.S.B.); NIH grants HL135124 and AI135964 and Department of Defense grant PR141319 (A.V.M.); NIH grants R01HL141852, R01HL127349, UHHL3123886, U01HL122626, and UG3TR002445, and Department of Defence grant PR151124 (N.K.); and the Netherlands Lung Foundation grants 5.1.14.020 and 4.1.18.226 (M.C.N.)

Mapping dusty galaxy growth at z>5z>5 with FRESCO: Detection of Hα\alpha in submm galaxy HDF850.1 and the surrounding overdense structures

We report the detection of a 13$\sigma$ H$\alpha$ emission line from HDF850.1 at $z=5.188\pm0.001$ using the FRESCO NIRCam F444W grism observations. Detection of H$\alpha$ in HDF850.1 is noteworthy, given its high far-IR luminosity, substantial dust obscuration, and the historical challenges in deriving its redshift. HDF850.1 shows a clear detection in the F444W imaging data, distributed between a northern and southern component, mirroring that seen in [CII] from the Plateau de Bure Interferometer. Modeling the SED of each component separately, we find that the northern component has a higher mass, star formation rate (SFR), and dust extinction than the southern component. The observed H$\alpha$ emission appears to arise entirely from the less-obscured southern component and shows a similar $\Delta$v$\sim$+130 km/s velocity offset to that seen for [CII] relative to the source systemic redshift. Leveraging H$\alpha$-derived redshifts from FRESCO observations, we find that HDF850.1 is forming in one of the richest environments identified to date at $z>5$, with 100 $z=5.17-5.20$ galaxies distributed across 10 structures and a $\sim$(15 cMpc)$^3$ volume. Based on the evolution of analogous structures in cosmological simulations, the $z=5.17-5.20$ structures seem likely to collapse into a single $>$10$^{14}$ $M_{\odot}$ cluster by $z\sim0$. Comparing galaxy properties forming within this overdensity with those outside, we find the masses, SFRs, and $UV$ luminosities inside the overdensity to be clearly higher. The prominence of H$\alpha$ line emission from HDF850.1 and other known highly-obscured $z>5$ galaxies illustrates the potential of NIRCam-grism programs to map both the early build-up of IR-luminous galaxies and overdense structures.Comment: Submitted to MNRAS. 20 pages, 10 figures and 8 tables (including appendices