PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small ...biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.
People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found ...evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.
Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin’s effects on food intake are ...mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp−/−;Npy−/− and Mc3r−/−;Mc4r−/− double knockout mice as well as Npy−/− and Agrp−/− single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.
Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other ...psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.
We present a sample of low-resolution 5-38 km Spitzer IRS spectra of the inner few square kiloparsecs of 59 nearby galaxies spanning a large range of star formation properties. A robust method for ...decomposing mid-infrared galaxy spectra is described and used to explore the behavior of PAH emission and the prevalence of silicate dust extinction. Evidence for silicate extinction is found in6 of the sample, at strengths that indicate that most normal galaxies undergo A sub(V) 3 mag averaged over then-centers. The contribution of PAH emission to the total infrared power is found to peak near 10% and extend up to 620% and is suppressed at metallicities Z Z /4, as well as in low-luminosity AGN environments. Strong interband PAH feature strength variations (2-5 times) are observed, with the presence of a weak AGN and, to a lesser degree, increasing metallicity shifting power to the longer wavelength bands. A peculiar PAH emission spectrum with markedly diminished 5-8 km features arises among the sample solely in systems with relatively hard radiation fields harboring low-luminosity AGNs. The AGNs may modify the emitting grain distribution and provide the direct excitation source of the unusual PAH emission, which cautions against using absolute PAH strength to estimate star formation rates in systems harboring active nuclei. Alternatively, the low star formation intensity often associated with weak AGNs may affect the spectrum. The effect of variations in the mid-infrared spectrum on broadband infrared surveys is modeled and points to more than a factor of 2 uncertainty in results that assume a fixed PAH emission spectrum, for redshifts z = 0-2.5.
We report the detection of an ultra-bright fast radio burst (FRB) from a modest, 3.4-day pilot survey with the Australian Square Kilometre Array Pathfinder. The survey was conducted in a wide-field ...fly's-eye configuration using the phased-array-feed technology deployed on the array to instantaneously observe an effective area of 160 deg2, and achieve an exposure totaling 13200 deg2 hr . We constrain the position of FRB 170107 to a region in size (90% containment) and its fluence to be 58 6 Jy ms. The spectrum of the burst shows a sharp cutoff above 1400 MHz, which could be due to either scintillation or an intrinsic feature of the burst. This confirms the existence of an ultra-bright ( Jy ms) population of FRBs.
Optically luminous quasars at
z
> 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio ...sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed
z
> 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 μJy beam
−1
(at 144 MHz) over an area of ∼5720 deg
2
. We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2
σ
significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29
−0.09
+0.10
by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at
z
< 3. We compare the radio loudness of the high-
z
quasar sample to a lower-
z
quasar sample at
z
∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-
z
quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the
z
= 6 quasar radio luminosity function, which is used to derive the expected number of high-
z
sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-
z
quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts.
With the goal of investigating the degree to which the MIR emission traces the SFR, we analyze Spitzer 8 and 24 mu m data of star-forming regions in a sample of 33 nearby galaxies with available HST ...NICMOS images in the Pa alpha (1.8756 mu m) emission line. The galaxies are drawn from the SINGS sample and cover a range of morphologies and a factor similar to 10 in oxygen abundance. Published data on local low-metallicity starburst galaxies and LIRGs are also included in the analysis. Both the stellar continuum-subtracted 8 mu m emission and the 24 mu m emission correlate with the extinction-corrected Pa alpha line emission, although neither relationship is linear. Simple models of stellar populations and dust extinction and emission are able to reproduce the observed nonlinear trend of the 24 mu m emission versus number of ionizing photons, including the modest deficiency of 24 mu m emission in the low-metallicity regions, which results from a combination of decreasing dust opacity and dust temperature at low luminosities. Conversely, the trend of the 8 mu m emission as a function of the number of ionizing photons is not well reproduced by the same models. The 8 mu m emission is contributed, in larger measure than the 24 mu m emission, by dust heated by nonionizing stellar populations, in addition to the ionizing ones, in agreement with previous findings. Two SFR calibrations, one using the 24 mu m emission and the other using a combination of the 24 mu m and H alpha luminosities (Kennicutt and coworkers), are presented. No calibration is presented for the 8 mu m emission because of its significant dependence on both metallicity and environment. The calibrations presented here should be directly applicable to systems dominated by ongoing star formation.
Abstract
We present a study of the low-frequency radio properties of star-forming (SF) galaxies and active galactic nuclei (AGNs) up to redshift z = 2.5. The new spectral window probed by the Low ...Frequency Array (LOFAR) allows us to reconstruct the radio continuum emission from 150 MHz to 1.4 GHz to an unprecedented depth for a radio-selected sample of 1542 galaxies in ∼ 7 deg2 of the LOFAR Boötes field. Using the extensive multiwavelength data set available in Boötes and detailed modelling of the far-infrared to ultraviolet spectral energy distribution (SED), we are able to separate the star formation (N = 758) and the AGN (N = 784) dominated populations. We study the shape of the radio SEDs and their evolution across cosmic time and find significant differences in the spectral curvature between the SF galaxy and AGN populations. While the radio spectra of SF galaxies exhibit a weak but statistically significant flattening, AGN SEDs show a clear trend to become steeper towards lower frequencies. No evolution of the spectral curvature as a function of redshift is found for SF galaxies or AGNs. We investigate the redshift evolution of the infrared–radio correlation for SF galaxies and find that the ratio of total infrared to 1.4-GHz radio luminosities decreases with increasing redshift: q
1.4 GHz = (2.45 ± 0.04) (1 + z)−0.15 ± 0.03. Similarly, q
150 MHz shows a redshift evolution following q
150 GHz = (1.72 ± 0.04) (1 + z)−0.22 ± 0.05. Calibration of the 150 MHz radio luminosity as a star formation rate tracer suggests that a single power-law extrapolation from q
1.4 GHz is not an accurate approximation at all redshifts.
Eutrophication of Chesapeake Bay Kemp, W. M.; Boynton, W. R.; Adolf, J. E. ...
Marine ecology. Progress series,
11/2005, Letnik:
303
Journal Article
Recenzirano
Odprti dostop
This review provides an integrated synthesis with timelines and evaluations of ecological responses to eutrophication in Chesapeake Bay, the largest estuary in the USA. Analyses of dated sediment ...cores reveal initial evidence of organic enrichment in ~200 yr old strata, while signs of increased phytoplankton and decreased water clarity first appeared ~100 yr ago. Severe, recurring deep-water hypoxia and loss of diverse submersed vascular plants were first evident in the 1950s and 1960s, respectively. The degradation of these benthic habitats has contributed to declines in benthic macroinfauna in deep mesohaline regions of the Bay and blue crabs in shallow polyhaline areas. In contrast, copepods, which are heavily consumed in pelagic food chains, are relatively unaffected by nutrient-induced changes in phytoplankton. Intense mortality associated with fisheries and disease have caused a dramatic decline in eastern oyster stocks and associated Bay water filtration, which may have exacerbated eutrophication effects on phytoplankton and water clarity. Extensive tidal marshes, which have served as effective nutrient buffers along the Bay margins, are now being lost with rising sea level. Although the Bay’s overall fisheries production has probably not been affected by eutrophication, decreases in the relative contribution of demersal fish and in the efficiency with which primary production is transferred to harvest suggest fundamental shifts in trophic and habitat structures. Bay ecosystem responses to changes in nutrient loading are complicated by non-linear feedback mechanisms, including particle trapping and binding by benthic plants that increase water clarity, and by oxygen effects on benthic nutrient recycling efficiency. Observations in Bay tributaries undergoing recent reductions in nutrient input indicate relatively rapid recovery of some ecosystem functions but lags in the response of others.
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