Search

We present measurements of the radial profiles of the mass and galaxy number density around Sunyaev–Zel’dovich (SZ)-selected clusters using both weak lensing and galaxy counts. The clusters are selected from the Atacama Cosmology Telescope Data Release 5 and the galaxies from the Dark Energy Survey Year 3 data set. With signal-to-noise ratio of 62 (45) for galaxy (weak lensing) profiles over scales of about 0.2–20 h-1 Mpc, these are the highest precision measurements for SZ-selected clusters to date. Because SZ selection closely approximates mass selection, these measurements enable several tests of theoretical models of the mass and light distribution around clusters. Our main findings are: (1) The splashback feature is detected at a consistent location in both the mass and galaxy profiles and its location is consistent with predictions of cold dark matter N-body simulations. (2) The full mass profile is also consistent with the simulations. (3) The shapes of the galaxy and lensing profiles are remarkably similar for our sample over the entire range of scales, from well inside the cluster halo to the quasilinear regime. We measure the dependence of the profile shapes on the galaxy sample, redshift, and cluster mass. We extend the Diemer & Kravtsov model for the cluster profiles to the linear regime using perturbation theory and show that it provides a good match to the measured profiles. We also compare the measured profiles to predictions of the standard halo model and simulations that include hydrodynamics. Applications of these results to cluster mass estimation, cosmology, and astrophysics are discussed.

We present the steps taken to produce a reliable and complete input galaxy catalogue for the Dark Energy Spectroscopic Instrument (DESI) Bright Galaxy Survey (BGS) using the photometric Legacy Survey DR8 DECam. We analyse some of the main issues faced in the selection of targets for the DESI BGS, such as star-galaxy separation, contamination by fragmented stars and bright galaxies. Our pipeline utilizes a new way to select BGS galaxies using Gaia photometry and we implement geometrical and photometric masks that reduce the number of spurious objects. The resulting catalogue is cross-matched with the Galaxy And Mass Assembly (GAMA) survey to assess the completeness of the galaxy catalogue and the performance of the target selection. We also validate the clustering of the sources in our BGS catalogue by comparing with mock catalogues and the Sloan Digital Sky Survey (SDSS) data. Finally, the robustness of the BGS selection criteria is assessed by quantifying the dependence of the target galaxy density on imaging and other properties. The largest systematic correlation we find is a 7 per cent suppression of the target density in regions of high stellar density.

We present a measurement of baryon acoustic oscillations (BAO) in the cross-correlation of quasars with the Lyα-forest flux transmission at a mean redshift of z = 2.40. The measurement uses the complete Sloan Digital Sky Survey (SDSS-III) data sample: 168 889 forests and 234 367 quasars from the SDSS data release DR12. In addition to the statistical improvement on our previous study using DR11, we have implemented numerous improvements at the analysis level enabling a more accurate measurement of this cross-correlation. We have also developed the first simulations of the cross-correlation that allow us to test different aspects of our data analysis and to search for potential systematic errors in the determination of the BAO peak position. We measure the two ratios DH(z = 2.40) /rd = 9.01 ± 0.36 and DM(z = 2.40) /rd = 35.7 ± 1.7, where the errors include marginalization over the non-linear velocity of quasars and the cross-correlation of metals and quasars, among other effects. These results are within 1.8σ of the prediction of the flat-ΛCDM model describing the observed cosmic microwave background anisotropies. We combine this study with the Lyα-forest auto-correlation function, yielding DH(z = 2.40) /rd = 8.94 ± 0.22 and DM(z = 2.40) /rd = 36.6 ± 1.2, within 2.3σ of the same flat-ΛCDM model.

We present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. Our combined galaxy sample comprises 1.2 million massive galaxies over an effective area of 9329 deg2 and volume of 18.7 Gpc3, divided into three partially overlapping redshift slices centred at effective redshifts 0.38, 0.51 and 0.61. We measure the angular diameter distance DM and Hubble parameterHfrom the baryon acoustic oscillation (BAO) method, in combinationwith a cosmic microwave background prior on the sound horizon scale, after applying reconstruction to reduce non-linear effects on the BAO feature. Using the anisotropic clustering of the pre-reconstruction density field, we measure the product DMH from the Alcock-Paczynski (AP) effect and the growth of structure, quantified by fσ8(z), from redshift-space distortions (RSD). We combine individual measurements presented in seven companion papers into a set of consensus values and likelihoods, obtaining constraints that are tighter and more robust than those from any one method; in particular, the AP measurement from sub-BAO scales sharpens constraints from post-reconstruction BAOs by breaking degeneracy between DM and H. Combined with Planck 2016 cosmic microwave background measurements, our distance scale measurements simultaneously imply curvature ωK = 0.0003 ± 0.0026 and a dark energy equation-of-state parameter ω =-1.01 ± 0.06, in strong affirmation of the spatially flat cold dark matter (CDM) model with a cosmological constant (ΛCDM). Our RSD measurements of fσ8, at 6 per cent precision, are similarly consistent with this model. When combined with supernova Ia data, we find H0 = 67.3 ± 1.0 kms-1 Mpc-1 even for our most general dark energy model, in tension with some direct measurements. Adding extra relativistic species as a degree of freedom loosens the constraint only slightly, to H0 = 67.8 ± 1.2 kms-1 Mpc-1. Assuming flat ΛCDM, we find ωm = 0.310 ± 0.005 and H0 = 67.6 ± 0.5 kms-1 Mpc-1, and we find a 95 per cent upper limit of 0.16 eV c-2 on the neutrino mass sum.

We have used flux-transmission correlations in Lyα forests to measure the imprint of baryon acoustic oscillations (BAO). The study uses spectra of 157 783 quasars in the redshift range 2:1 ≤ z ≤ 3:5 from the Sloan Digital Sky Survey (SDSS) data release 12 (DR12). Besides the statistical improvements on our previous studies using SDSS DR9 and DR11, we have implemented numerous improvements in the analysis procedure, allowing us to construct a physical model of the correlation function and to investigate potential systematic errors in the determination of the BAO peak position. The Hubble distance, DH = c=H(z), relative to the sound horizon is DH(z = 2:33)=rd = 9:07 ± 0:31. The best-determined combination of comoving angular-diameter distance, DM, and the Hubble distance is found to be D0:7 H D0:3 M =rd = 13:94±0:35. This value is 1:028±0:026 times the prediction of the flat-ΛCDM model consistent with the cosmic microwave background (CMB) anisotropy spectrum. The errors include marginalization over the effects of unidentified high-density absorption systems and fluctuations in ultraviolet ionizing radiation. Independently of the CMB measurements, the combination of our results and other BAO observations determine the open-ΛCDM density parameters to be ΩM = 0:296 ± 0:029, ΩΛ = 0:699 ± 0:100 and Ωk = -0:002 ± 0:119.

We present the Data Release 12 Quasar catalog (DR12Q) from the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey III. This catalog includes all SDSS-III/BOSS objects that were spectroscopically targeted as quasar candidates during the full survey and that are confirmed as quasars via visual inspection of the spectra, have luminosities Mi [z = 2] 2.15 (184 101, of which 167 742 are new discoveries) is about an order of magnitude greater than the number of z > 2.15 quasars known prior to BOSS. Redshifts and FWHMs are provided for the strongest emission lines (C iv, C iii], Mg ii). The catalog identifies 29 580 broad absorption line quasars and lists their characteristics. For each object, the catalog presents five-band (u, g, r, i, z) CCD-based photometry with typical accuracy of 0.03 mag together with some information on the optical morphology and the selection criteria. When available, the catalog also provides information on the optical variability of quasars using SDSS and Palomar Transient Factory multi-epoch photometry. The catalog also contains X-ray, ultraviolet, near-infrared, and radio emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra, covering the wavelength region 3600-10 500 Å at a spectral resolution in the range 1300 < R < 2500, can be retrieved from the SDSS Catalog Archive Server. We also provide a supplemental list of an additional 4841 quasars that have been identified serendipitously outside of the superset defined to derive the main quasar catalog.

We present a tentative detection of the large-scale structure of Ly α emission in the Universe at redshifts z = 2-3.5 by measuring the cross-correlation of Ly α surface brightness with quasars in Sloan Digital Sky Survey/Baryon Oscillation Spectroscopic Survey.We use amillion spectra targeting luminous red galaxies at z < 0.8, after subtracting a best-fitting model galaxy spectrum from each one, as an estimate of the high-redshift Ly α surface brightness. The quasar- Ly α emission cross-correlation is detected on scales 1 ~ 15 h-1 Mpc, with shape consistent with a Λ (CDM model with) Ωm = 0.30+0.10-0.07. The predicted amplitude of this cross-correlation is proportional to the product of the mean Ly α surface brightness, (μα), the amplitude of mass fluctuations and the quasar and Ly α emission bias factors. We infer (μα) (bα/3) = (3.9 ± 0.9) × 10-21 erg s-1 cm-2 Å-1 arcsec-2, where bα is the Ly α emission bias. If star-forming galaxies dominate this emission, we find ρSFR = (0.28 ± 0.07)(3/bα) yr-1 Mpc-3. For bα = 3, this value is~30 times larger than previous estimates from individually detected Ly α emitters, but consistent with the total ρSFR derived from dust-corrected, continuum UV galaxy surveys, if most of the Ly α photons from these galaxies avoid dust absorption and are reemitted after diffusing in large gas haloes. Heating of intergalactic gas by He II photoionization from quasar radiation or jets may alternatively explain the detected correlation, and cooling radiation from gas in galactic haloes may also contribute. We also detect redshift space anisotropy of the quasar-Ly α emission cross-correlation, finding evidence at the 3.0σ level that it is radially elongated, which may be explained by radiative-transfer effects. Our measurements represent the first application of the intensity mapping technique to optical observations.

We derive constraints on cosmological parameters and tests of dark energy models from the combination of baryon acoustic oscillation (BAO) measurements with cosmic microwave background (CMB) data and a recent reanalysis of Type Ia supernova (SN) data. In particular, we take advantage of high-precision BAO measurements from galaxy clustering and the Lyman-α forest (LyaF) in the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS). Treating the BAO scale as an uncalibrated standard ruler, BAO data alone yield a high confidence detection of dark energy; in combination with the CMB angular acoustic scale they further imply a nearly flat universe. Adding the CMB-calibrated physical scale of the sound horizon, the combination of BAO and SN data into an "inverse distance ladder" yields a measurement of H0=67.3±1.1 km s-1 Mpc-1, with 1.7% precision. This measurement assumes standard prerecombination physics but is insensitive to assumptions about dark energy or space curvature, so agreement with CMB-based estimates that assume a flat ΛCDM cosmology is an important corroboration of this minimal cosmological model. For constant dark energy (Λ), our BAO+SN+CMB combination yields matter density Ωm=0.301±0.008 and curvature Ωk=-0.003±0.003. When we allow more general forms of evolving dark energy, the BAO+SN+CMB parameter constraints are always consistent with flat ΛCDM values at ≈1σ. While the overall χ2 of model fits is satisfactory, the LyaF BAO measurements are in moderate (2-2.5σ) tension with model predictions. Models with early dark energy that tracks the dominant energy component at high redshift remain consistent with our expansion history constraints, and they yield a higher H0 and lower matter clustering amplitude, improving agreement with some low redshift observations. Expansion history alone yields an upper limit on the summed mass of neutrino species, mν

We measure the two-point clustering of spectroscopically confirmed quasars from the final sample of the Baryon Oscillation Spectroscopic Survey (BOSS) on comoving scales of 4 ≲ s ≲ 22 h-1 Mpc. The sample covers 6950 deg2 [~19 (h-1Gpc)3] and, over the redshift range 2.2 ≲ z ≲ 2.8, contains 55 826 homogeneously selected quasars, which is twice as many as in any similar work. We deduce bQ = 3.54 ± 0.10; the most precise measurement of quasar bias to date at these redshifts. This corresponds to a host halo mass of ~2 × 1012 h-1M⊙ with an implied quasar duty cycle of ~1 per cent. The real-space projected correlation function is well fitted by a power law of index 2 and correlation length r0 = (8.12 ± 0.22) h-1 Mpc over scales of 4 ≲ rp ≲ 25 h-1 Mpc. To better study the evolution of quasar clustering at moderate redshift, we extend the redshift range of our study to z ~ 3.4 and measure the bias and correlation length of three subsamples over 2.2 ≲ z ≲ 3.4. We find no significant evolution of r0 or bias over this range, implying that the host halo mass of quasars decreases somewhat with increasing redshift. We find quasar clustering remains similar over a decade in luminosity, contradicting a scenario in which quasar luminosity is monotonically related to halo mass at z ≈ 2.5. Our results are broadly consistent with previous BOSS measurements, but they yield more precise constraints based upon a larger and more uniform data set.

We present the measurements and modelling of the projected and redshift-space clustering of CMASS galaxies in the Sloan Digital Sky Survey-III Baryon Oscillation Spectroscopic Survey Data Release 11. For a volume-limited luminous red galaxy sample in the redshift range of 0.48 < z < 0.55, we perform halo occupation distribution modelling of the small- and intermediate-scale (0.1-60 h-1 Mpc) projected and redshift-space two-point correlation functions, with an accurate model built on high-resolution N-body simulations. To interpret the measured redshift-space distortions, the distribution of galaxy velocities must differ from that of the dark matter inside haloes of ~1013-1014 h-1 M⊙, i.e. the data require the existence of galaxy velocity bias. Most notably, central galaxies on average are not at rest with respect to the core of their host haloes, but rather move around it with a 1D velocity dispersion of 0.22-0.04+0.03 times that of the dark matter, implying a spatial offset from the centre at the level of ≲1 per cent of the halo virial radius. The luminous satellite galaxies move more slowly than the dark matter, with velocities 0.86-0.03+0.08 times those of the dark matter, which suggests that the velocity and spatial distributions of these satellites cannot both be unbiased. The constraints mainly arise from the Fingers-of-God effect at non-linear scales and the smoothing to the Kaiser effect in the translinear regime; the robustness of the results is demonstrated by a variety of tests. We discuss the implications of the existence of galaxy velocity bias for investigations of galaxy formation and cosmology.

We present measurements of the angular diameter distance to and Hubble parameter at z = 0.57 from the measurement of the baryon acoustic peak in the correlation of galaxies from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey. Our analysis is based on asample from Data Release 9 of 264 283 galaxies over 3275 square degrees in the redshift range 0.43 < z < 0.70. We use two different methods to provide robust measurement of the acoustic peak position across and along the line of sight in order to measure the cosmological distance scale. We find DA(0.57) = 1408 ± 45 Mpc and H(0.57) = 92.9 ± 7.8 km s-1 Mpc-1 for our fiducial value of the sound horizon. These results from the anisotropic fitting are fully consistent with the analysis of the spherically averaged acoustic peak position presented in Anderson et al. Our distance measurements are a close match to the predictions of the standard cosmological model featuring a cosmological constant and zero spatial curvature. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

present composite spectra constructed from a sample of 242 150 Lyman a (Lyα) forest absorbers at redshifts 2.4 < z < 3.1 identified in quasar spectra from the Baryon Oscillation Spectroscopic Survey (BOSS) as part of Data Release 9 of the Sloan Digital Sky Survey III. We select forest absorbers by their flux in bins 138 km s-1 wide (approximately the size of the BOSS resolution element). We split these absorbers into five samples spanning the range of flux -0.05 ≤ F < 0.45. Tests on a smaller set of high-resolution spectra show that our three strongest absorption samples would probe circumgalactic regions (projected separation

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations (BAO) in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released DR9 and DR10 samples. Assuming a concordance Λ cold dark matter (ΛCDM) cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = (1264 ± 25 Mpc)(rd/rd,fid) at z = 0.32 and DV = (2056 ± 20 Mpc)(rd/rd,fid) at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = (1421 ± 20 Mpc)(rd/rd,fid) and H = (96.8 ± 3.4 kms-1 Mpc-1)(rd,fid/rd). Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

We have developed two independent methods for measuring the one-dimensional power spectrum of the transmitted flux in the Lyman-α forest. The first method is based on a Fourier transform and the second on a maximum-likelihood estimator. The two methods are independent and have different systematic uncertainties. Determination of the noise level in the data spectra was subject to a new treatment, because of its significant impact on the derived power spectrum. We applied the two methods to 13 821 quasar spectra from SDSS-III/BOSS DR9 selected from a larger sample of over 60 000 spectra on the basis of their high quality, high signal-to-noise ratio (S/N), and good spectral resolution. The power spectra measured using either approach are in good agreement over all twelve redshift bins from 〈z〉 = 2.2 to 〈z〉 = 4.4, and scales from 0.001 km s-1 to 0.02 km s-1. We determined the methodological andinstrumental systematic uncertainties of our measurements. We provide a preliminary cosmological interpretation of our measurements using available hydrodynamical simulations. The improvement in precision over previously published results from SDSS is a factor 2-3 for constraints on relevant cosmological parameters. For a ΛCDM model and using a constraint on H0 that encompasses measurements based on the local distance ladder and on CMB anisotropies, we infer σ8 = 0.83 ± 0.03 and ns = 0.97 ± 0.02 based on Hi absorption in the range 2.1 < z < 3.7. © ESO, 2013.

We report a detection of the baryon acoustic oscillation (BAO) feature in the three-dimensional correlation function of the transmitted flux fraction in the Lya forest of high-redshift quasars. The study uses 48 640 quasars in the redshift range 2.1 = z = 3.5 from the Baryon Oscillation Spectroscopic Survey (BOSS) of the third generation of the Sloan Digital Sky Survey (SDSS-III). At a mean redshift z = 2.3, we measure the monopole and quadrupole components of the correlation function for separations in the range 20 h-1 Mpc < r < 200 h-1 Mpc. A peak in the correlation function is seen at a separation equal to (1.01 ± 0.03) times the distance expected for the BAO peak within a concordance .CDM cosmology. This first detection of the BAO peak at high redshift, when the universe was strongly matter dominated, results in constraints on the angular diameter distance DA and the expansion rate H at z = 2.3 that, combined with priors on H0 and the baryon density, require the existence of dark energy. Combined with constraints derived from cosmic microwave background observations, this result implies H(z = 2.3) = (224 ± 8) km s-1 Mpc-1, indicating that the time derivative of the cosmological scale parameter .a = H(z = 2.3)/(1 + z) is significantly greater than that measured with BAO at z ∼ 0.5. This demonstrates that the expansion was decelerating in the range 0.7 < z < 2.3, as expected from the matter domination during this epoch. Combined with measurements of H0, one sees the pattern of deceleration followed by acceleration characteristic of a dark-energy dominated universe. © 2013 ESO.

We report on the small-scale (0.5 < r < 40 h-1 Mpc) clustering of 78 895 massive (M 1011.3M) galaxies at 0.2 < z< 0.4 from the first two years of data from the Baryon Oscillation Spectroscopic Survey (BOSS), to be released as part of Sloan Digital Sky Survey (SDSS) Data Release 9 (DR9). We describe the sample selection, basic properties of the galaxies and caveats for working with the data. We calculate the real- and redshift-space twopoint correlation functions of these galaxies, fit these measurements using halo occupation distribution (HOD) modelling within dark matter cosmological simulations, and estimate the errors using mock catalogues. These galaxies lie in massive haloes, with a mean halo mass of 5.2 1013 h-1M, a large-scale bias of ~2.0 and a satellite fraction of 12 ± 2 per cent. Thus, these galaxies occupy haloes with average masses in between those of the higher redshift BOSS CMASS sample and the original SDSS I/II luminous red galaxy sample © 2012 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society © doi:10.1093/mnras/sts314.

We present the Data Release 10 Quasar (DR10Q) catalog from the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey III. The catalog includes all BOSS objects that were targeted as quasar candidates during the first 2.5 years of the survey and that are confirmed as quasars via visual inspection of the spectra, have luminosities Mi[z = 2] 2.15 (117 668) is ~5 times greater than the number of z > 2.15 quasars known prior to BOSS. Redshifts and FWHMs are provided for the strongest emission lines (C iv, C iii, Mg ii). The catalog identifies 16 461 broad absorption line quasars and gives their characteristics. For each object, the catalog presents five-band (u, g, r, i, z) CCD-based photometry with typical accuracy of 0.03 mag and information on the optical morphology and selection method. The catalog also contains X-ray, ultraviolet, near-infrared, and radio emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3600-10 500 Å at a spectral resolution in the range 1300 < R < 2500; the spectra can be retrieved from the SDSS Catalog Archive Server. We also provide a supplemental list of an additional 2376 quasars that have been identified among the galaxy targets of the SDSS-III/BOSS. © 2014 ESO.

The placenta is vital to the health and development of the fetus, serving to deliver oxygen and nutrients, facilitate the removal of waste products, and provide a barrier to pathogens and other harmful substances present in the maternal circulation. When these processes fail to operate normally, they can lead to complications of pregnancy such as preeclampsia or fetal growth restriction. The development of novel therapeutics for the mother, fetus, or placenta requires a mechanistic understanding of the development and functions of the placenta. For the obstetric clinician, being able to monitor the placenta throughout the pregnancy and to measure the impact of any treatment modality on the mother and the developing fetus are essential for providing the best possible care. The Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health has been a longtime supporter of research on the placenta. In 2014, the Human Placenta Project was initiated to help to drive an understanding of the biology of the human placenta and to facilitate the development of novel tools and approaches to allow for safe, noninvasive, real-time assessment of the placenta across pregnancy. Those efforts, along with others from around the globe, are showing promise. Although not yet ready for clinical application, these advances are moving the field forward and are certain to have a tremendous impact on the development and assessment of therapeutics designed for treating conditions of pregnancy., Competing Interests: Disclosures The author has indicated that he has no conflicts of interest with regard to the content of this article., (Published by Elsevier Inc.)

Purpose of Review: Myasthenia gravis is an autoimmune disease that commonly affects the palpebral and extraocular muscles. Ocular myasthenia gravis (OMG) is a variant of the disease that is confined to the ocular muscles but frequently becomes generalized over time. The diagnosis of OMG is often challenging but both clinical and laboratory findings are helpful in confirming the clinical suspicion. This review provides an update on the diagnostic approach and therapeutic options for OMG., Recent Findings: Antimuscle-specific tyrosine kinase and LDL-related receptor-related protein 4 are newly available serologic testing for myasthenia gravis that can help in increasing the diagnostic sensitivity of OMG. They should be included to the diagnostic algorithm of OMG in appropriate clinical situations., Summary: OMG remains a primarily clinical diagnosis, but recent advances in laboratory testing can improve the diagnostic accuracy and should be used in appropriate clinical settings. The mainstay of treatment for OMG has not significantly changed over the past years, but the increasing availability of steroid-sparing agents improved the disease control while minimizing steroid-induced complications.

We model the luminosity-dependent projected and redshift-space two-point correlation functions (2PCFs) of the Sloan Digital Sky Survey (SDSS) Data Release 7 Main galaxy sample, using the halo occupation distribution (HOD) model and the subhalo abundance matching (SHAM) model and its extension. All the models are built on the same high-resolution N -body simulations. We find that the HOD model generally provides the best performance in reproducing the clustering measurements in both projected and redshift spaces. The SHAM model with the same halo-galaxy relation for central and satellite galaxies (or distinct haloes and subhaloes), when including scatters, has a best-fitting χ 2 /dof around 2-3. We therefore extend the SHAM model to the subhalo clustering and abundance matching (SCAM) by allowing the central and satellite galaxies to have different galaxy-halo relations. We infer the corresponding halo/subhalo parameters by jointly fitting the galaxy 2PCFs and abundances and consider subhaloes selected based on three properties, the mass M acc at the time of accretion, the maximum circular velocity V acc at the time of accretion, and the peak maximum circular velocity V peak over the history of the subhaloes. The three subhalo models work well for luminous galaxy samples (with luminosity above L * ). For low-luminosity samples, the V acc model stands out in reproducing the data, with the V peak model slightly worse, while the M acc model fails to fit the data. We discuss the implications of the modelling results.

The cold dark matter (CDM) cosmological model has been remarkably successful in explaining cosmic structure over an enormous span of redshift, but it has faced persistent challenges from observations that probe the innermost regions of dark matter halos and the properties of the Milky Way's dwarf galaxy satellites. We review the current observational and theoretical status of these "small-scale controversies." Cosmological simulations that incorporate only gravity and collisionless CDM predict halos with abundant substructure and central densities that are too high to match constraints from galaxy dynamics. The solution could lie in baryonic physics: Recent numerical simulations and analytical models suggest that gravitational potential fluctuations tied to efficient supernova feedback can flatten the central cusps of halos in massive galaxies, and a combination of feedback and low star formation efficiency could explain why most of the dark matter subhalos orbiting the Milky Way do not host visible galaxies. However, it is not clear that this solution can work in the lowest mass galaxies, where discrepancies are observed. Alternatively, the small-scale conflicts could be evidence of more complex physics in the dark sector itself. For example, elastic scattering from strong dark matter self-interactions can alter predicted halo mass profiles, leading to good agreement with observations across a wide range of galaxy mass. Gravitational lensing and dynamical perturbations of tidal streams in the stellar halo provide evidence for an abundant population of low-mass subhalos in accord with CDM predictions. These observational approaches will get more powerful over the next few years.

Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.

The circumgalactic medium (CGM) is fed by galaxy outflows and accretion of intergalactic gas, but its mass, heavy element enrichment, and relation to galaxy properties are poorly constrained by observations. In a survey of the outskirts of 42 galaxies with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope, we detected ubiquitous, large (150-kiloparsec) halos of ionized oxygen surrounding star-forming galaxies; we found much less ionized oxygen around galaxies with little or no star formation. This ionized CGM contains a substantial mass of heavy elements and gas, perhaps far exceeding the reservoirs of gas in the galaxies themselves. Our data indicate that it is a basic component of nearly all star-forming galaxies that is removed or transformed during the quenching of star formation and the transition to passive evolution.

We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed., (2010 Elsevier Ltd. All rights reserved.)

Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties., (Copyright 2010 Elsevier Ltd. All rights reserved.)

We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models., (Copyright 2010 Elsevier Ltd. All rights reserved.)

We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models., (2010 Elsevier Ltd. All rights reserved.)

Objective: Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy., Methods: Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing., Results: Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious., Interpretation: Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study.

Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed.

SAR about the piperidine core in a series of MC4R agonists is described. A number of alkyl substituents that furnish compounds with good affinity and functional potency are reported.

Toxic neuropathy represents an important clinical problem in the use of the chemotherapeutic substances Taxol and thalidomide. Sensory neuropathy has a high incidence, lacks an effective treatment and is the dose-limiting factor for these drugs. The pathogenic basis of these neuropathies is unknown. We investigated the hypothesis that the experimental toxic neuropathies from Taxol and thalidomide results from destruction of vasa nervorum and can be reversed by the administration of an angiogenic cytokine. In animal models of Taxol- and thalidomide-induced neuropathy, nerve blood flow has been attenuated and the number of vasa nervorum has been reduced. Intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 administered in parallel with Taxol injections completely inhibited deterioration of nerve function and diminution of the peripheral nerve vasculature. Gene therapy in animals with established Taxol- or thalidomide-induced neuropathies resulted in recovery of vascularity and improved nerve electrophysiology. These findings implicate microvascular damage as the basis for toxic neuropathy and suggest that angiogenic growth factors may constitute a novel treatment for this disorder.

Design and synthesis of potent MC4 selective agonists based on cyclohexylpiperidine derived cyclic urea, oxazolidinones, and sulfonamide based privileged structures are disclosed.

Objective: This study evaluated validity and reliability of automated median and ulnar sensory nerve conduction study (NCS) measurements by the NC-stat., Methods: Median and ulnar distal sensory latencies (DSL) and amplitudes (SNAP) were measured in sixty subjects with the NC-stat and by a neurologist (reference) using traditional instrumentation. The median-ulnar DSL differences (MUD) was calculated. Validity was quantified by the Pearson correlation. Reliability was evaluated by the intraclass correlation coefficient (ICC), Bland-Altman analysis, and inter-rater agreement of MUD abnormalities., Results: As a result of differences in electrode placement, NC-stat and reference mean values had systematic differences. The correlation ranged from 0.70 (ulnar DSL) to 0.91 (median DSL). The ICC ranged from 0.69 (ulnar DSL) to 0.91 (median DSL). In Bland-Altman analysis of DSLs, NC-stat measurements had a bias of 0.56 ms (median) and 0.31 ms (ulnar) and precision of 0.31 and 0.30 ms. Inter-rater agreement for MUD abnormalities was 93.8% (raw) and 0.80 (Kappa)., Conclusions: NC-stat validity and reliability metrics were similar to traditional NCS. Use of the NC-stat would require applicable reference ranges., Significance: NC-stat median and ulnar NCS are valid and reliable. This device may be useful for increasing availability of NCS when clinically appropriate.

The melanocortin subtype-4 receptor (MC4R) has been implicated in the control of feeding behavior and body weight regulation. A series of tetrapeptides, based on Tic-DPhe-Arg-Trp-NH2-a mimic of the putative message sequence "His-Phe-Arg-Trp" and modified at the DPhe position, were prepared and pharmacologically characterized for potency and selectivity. Substitution of His with Tic gave peptides with significant increases in selectivity. The effects of the substitution pattern of DPhe were investigated and it has significant influences on potency and the level of the maximum cAMP accumulation. Intracerebroventricular administration of peptide 10 induced significant inhibition of cumulative overnight food intake and feeding duration in rats.

Optimization of the biological activity of a new class of non-peptidyl, pyridazinone derived human melanocortin subtype-4 receptor agonists is disclosed.

Specific interactions of human melanocortin-4 receptor (hMC4R) with its nonpeptide and peptide agonists were studied using alanine-scanning mutagenesis. The binding affinities and potencies of two synthetic, small-molecule agonists (THIQ, MB243) were strongly affected by substitutions in transmembrane alpha-helices (TM) 2, 3, 6, and 7 (residues Glu(100), Asp(122), Asp(126), Phe(261), His(264), Leu(265), and Leu(288)). In addition, a I129A mutation primarily affected the binding and potency of THIQ, while F262A, W258A, Y268A mutations impaired interactions with MB243. By contrast, binding affinity and potency of the linear peptide agonist NDP-MSH were substantially reduced only in D126A and H264A mutants. Three-dimensional models of receptor-ligand complexes with their agonists were generated by distance-geometry using the experimental, homology-based, and other structural constraints, including interhelical H-bonds and two disulfide bridges (Cys(40)-Cys(279), Cys(271)-Cys(277)) of hMC4R. In the models, all pharmacophore elements of small-molecule agonists are spatially overlapped with the corresponding key residues (His(6), d-Phe(7), Arg(8), and Trp(9)) of the linear peptide: their charged amine groups interact with acidic residues from TM2 and TM3, similar to His(6) and Arg(6) of NDP-MSH; their substituted piperidines mimic Trp(9) of the peptide and interact with TM5 and TM6, while the d-Phe aromatic rings of all three agonists contact with Leu(133), Trp(258), and Phe(261) residues.

A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist, 3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents.

The discovery of 1-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid analogs as potent human melanocortin-4 selective agonists is described.

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations.

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed.