Molecular Gas in the Host Galaxy of a Quasar at Redshift z=6.42

Observations of the molecular gas phase in quasar host galaxies provide fundamental constraints on galaxy evolution at the highest redshifts. Molecular gas is the material out of which stars form; it can be traced by spectral line emission of carbon--monoxide (CO). To date, CO emission has been detected in more than a dozen quasar host galaxies with redshifts (z) larger 2, the record holder being at z=4.69. At these distances the CO lines are shifted to longer wavelengths, enabling their observation with sensitive radio and millimetre interferometers. Here we present the discovery of CO emission toward the quasar SDSS J114816.64+525150.3 (hereafter J1148+5251) at a redshift of z=6.42, when the universe was only 1/16 of its present age. This is the first detection of molecular gas at the end of cosmic reionization. The presence of large amounts of molecular gas (M(H_2)=2.2e10 M_sun) in an object at this time demonstrates that heavy element enriched molecular gas can be generated rapidly in the earliest galaxies.Comment: 12 pages, 2 figures. To appear in Nature, July, 200

Constraining the nature of two Lyα emitters detected by ALMA at z = 4.7

We report optical VLT FORS2 spectroscopy of the two Ly-alpha emitters (LAEs) companions to the quasi-stellar object (QSO) - sub-millimetre galaxy (SMG) system BRI1202-0725 at z = 4.7, which have recently been detected in the [CII]158um line by the Atacama Large Millimetre/Sub-millimetre Array (ALMA). We detect Ly-alpha emission from both sources and so confirm that these Ly-alpha emitter candidates are physically associated with the BRI1202- 0725 system. We also report the lack of detection of any high ionisation emission lines (N V, Si IV, C IV and He II) and find that these systems are likely not photoionised by the quasar, leaving in situ star formation as the main powering source of these LAEs. We also find that both LAEs have Ly-alpha emission much broader (1300 km/s) than the [CII] emission and broader than most LAEs. In addition, both LAEs have roughly symmetric Ly-alpha profiles implying that both systems are within the HII sphere produced by the quasar. This is the first time that the proximity zone of a quasar is probed by exploiting nearby Ly-alpha emitters. We discuss the observational properties of these galaxies in the context of recent galaxy formation models.This work was co-funded under the Marie Curie Actions of the European Commission (FP7-COFUND).This is the final published version, which originally appeared in MNRAS and is available at http://mnras.oxfordjournals.org/content/439/2/2096

Imaging the cold molecular gas in SDSS J1148 + 5251 at z = 6.4

We present Karl G. Jansky Very Large Array (VLA) observations of the CO ($J = 2 \rightarrow 1$) line emission towards the $z = 6.419$ quasar SDSS J$114816.64+525150.3$ (J$1148+5251$). The molecular gas is found to be marginally resolved with a major axis of $0.9"$ (consistent with previous size measurements of the CO ($J = 7 \rightarrow 6$) emission). We observe tentative evidence for extended line emission towards the south west on a scale of ~$1.4"$, but this is only detected at $3.3\sigma$ significance and should be confirmed. The position of the molecular emission region is in excellent agreement with previous detections of low frequency radio continuum emission as well as [C ii] line and thermal dust continuum emission. These CO ($J = 2 \rightarrow 1$) observations provide an anchor for the low excitation part of the molecular line SED. We find no evidence for extended low excitation component, neither in the spectral line energy distribution nor the image. We fit a single kinetic gas temperature model of 50 K. We revisit the gas and dynamical masses in light of this new detection of a low order transition of CO, and confirm previous findings that there is no extended reservoir of cold molecular gas in J$1148+5251$, and that the source departs substantially from the low $z$ relationship between black hole mass and bulge mass. Hence, the characteristics of J$1148+5251$ at $z = 6.419$ are very similar to $z$~$2$ quasars, in the lack of a diffuse cold gas reservoir and kpc-size compactness of the star forming region.IIS thanks the Science & Technology Facilities Council for a studentship.This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society (c): 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved

Linear approaches to intramolecular Förster Resonance Energy Transfer probe measurements for quantitative modeling

Numerous unimolecular, genetically-encoded Forster Resonance Energy Transfer (FRET) probes for monitoring biochemical activities in live cells have been developed over the past decade. As these probes allow for collection of high frequency, spatially resolved data on signaling events in live cells and tissues, they are an attractive technology for obtaining data to develop quantitative, mathematical models of spatiotemporal signaling dynamics. However, to be useful for such purposes the observed FRET from such probes should be related to a biological quantity of interest through a defined mathematical relationship, which is straightforward when this relationship is linear, and can be difficult otherwise. First, we show that only in rare circumstances is the observed FRET linearly proportional to a biochemical activity. Therefore in most cases FRET measurements should only be compared either to explicitly modeled probes or to concentrations of products of the biochemical activity, but not to activities themselves. Importantly, we find that FRET measured by standard intensity-based, ratiometric methods is inherently non-linear with respect to the fraction of probes undergoing FRET. Alternatively, we find that quantifying FRET either via (1) fluorescence lifetime imaging (FLIM) or (2) ratiometric methods where the donor emission intensity is divided by the directly-excited acceptor emission intensity (denoted R<sub>alt</sub>) is linear with respect to the fraction of probes undergoing FRET. This linearity property allows one to calculate the fraction of active probes based on the FRET measurement. Thus, our results suggest that either FLIM or ratiometric methods based on R<sub>alt</sub> are the preferred techniques for obtaining quantitative data from FRET probe experiments for mathematical modeling purpose

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Probiotic Bacteria Induce a ‘Glow of Health’

Radiant skin and hair are universally recognized as indications of good health. However, this ‘glow of health’ display remains poorly understood. We found that feeding of probiotic bacteria to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals. Eating probiotic yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due to a bacteria-triggered interleukin-10-dependent mechanism. Aged male animals eating probiotics exhibited increased subcuticular folliculogenesis, when compared with matched controls, yielding luxuriant fur only in probiotic-fed subjects. Female animals displayed probiotic-induced hyperacidity coinciding with shinier hair, a feature that also aligns with fertility in human females. Together these data provide insights into mammalian evolution and novel strategies for integumentary health

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses