1,069 research outputs found
Bench-to-bedside review: Future novel diagnostics for sepsis - a systems biology approach
The early, accurate diagnosis and risk stratification of sepsis remains an important challenge in the critically ill. Since traditional biomarker strategies have not yielded a gold standard marker for sepsis, focus is shifting towards novel strategies that improve assessment capabilities. The combination of technological advancements and information generated through the human genome project positions systems biology at the forefront of biomarker discovery. While previously available, developments in the technologies focusing on DNA, gene expression, gene regulatory mechanisms, protein and metabolite discovery have made these tools more feasible to implement and less costly, and they have taken on an enhanced capacity such that they are ripe for utilization as tools to advance our knowledge and clinical research. Medicine is in a genome-level era that can leverage the assessment of thousands of molecular signals beyond simply measuring selected circulating proteins. Genomics is the study of the entire complement of genetic material of an individual. Epigenetics is the regulation of gene activity by reversible modifications of the DNA. Transcriptomics is the quantification of the relative levels of messenger RNA for a large number of genes in specific cells or tissues to measure differences in the expression levels of different genes, and the utilization of patterns of differential gene expression to characterize different biological states of a tissue. Proteomics is the large-scale study of proteins. Metabolomics is the study of the small molecule profiles that are the terminal downstream products of the genome and consists of the total complement of all low-molecular-weight molecules that cellular processes leave behind. Taken together, these individual fields of study may be linked during a systems biology approach. There remains a valuable opportunity to deploy these technologies further in human research. The techniques described in this paper not only have the potential to increase the spectrum of diagnostic and prognostic biomarkers in sepsis, but they may also enable the discovery of new disease pathways. This may in turn lead us to improved therapeutic targets. The objective of this paper is to provide an overview and basic framework for clinicians and clinical researchers to better understand the 'omics technologies' to enhance further use of these valuable tools
The X-ray luminosity function of Active Galactic Nuclei in the redshift interval z=3-5
We combine deep X-ray survey data from the Chandra observatory and the
wide-area/shallow XMM-XXL field to estimate the AGN X-ray luminosity function
in the redshift range z=3-5. The sample consists of nearly 340 sources with
either photometric (212) or spectroscopic (128) redshift in the above range.
The combination of deep and shallow survey fields provides a luminosity
baseline of three orders of magnitude, Lx(2-10keV)~1e43-1e46erg/s at z>3. We
follow a Bayesian approach to determine the binned AGN space density and
explore their evolution in a model-independent way. Our methodology accounts
for Poisson errors in the determination of X-ray fluxes and uncertainties in
photometric redshift estimates. We demonstrate that the latter is essential for
unbiased measurement of space densities. We find that the AGN X-ray luminosity
function evolves strongly between the redshift intervals z=3-4 and z=4-5. There
is also suggestive evidence that the amplitude of this evolution is luminosity
dependent. The space density of AGN with Lx<1e45erg/s drops by a factor of 5
between the redshift intervals above, while the evolution of brighter AGN
appears to be milder. Comparison of our X-ray luminosity function with that of
UV/optical selected QSOs at similar redshifts shows broad agreement at bright
luminosities, Lx>1e45erg/s. The faint-end slope of UV/optical luminosity
functions however, is steeper than for X-ray selected AGN. This implies that
the type-I AGN fraction increases with decreasing luminosity at z>3, opposite
to trends established at lower redshift. We also assess the significance of AGN
in keeping the hydrogen ionised at high redshift. Our X-ray luminosity function
yields ionising photon rate densities that are insufficient to keep the
Universe ionised at redshift z>4. A source of uncertainty in this calculation
is the escape fraction of UV photons for X-ray selected AGN.Comment: MNRAS accepte
The X-ray luminosity function of AGN at z~3
We combine Lyman-break colour selection with ultradeep (> 200 ks) Chandra
X-ray imaging over a survey area of ~0.35 deg^2 to select high redshift AGN.
Applying careful corrections for both the optical and X-ray selection
functions, the data allow us to make the most accurate determination to date of
the faint end of the X-ray luminosity function (XLF) at z~3. Our methodology
recovers a number density of X-ray sources at this redshift which is at least
as high as previous surveys, demonstrating that it is an effective way of
selecting high z AGN. Comparing to results at z=1, we find no evidence that the
faint slope of the XLF flattens at high z, but we do find significant (factor
~3.6) negative evolution of the space density of low luminosity AGN. Combining
with bright end data from very wide surveys we also see marginal evidence for
continued positive evolution of the characteristic break luminosity L*. Our
data therefore support models of luminosity-dependent density evolution between
z=1 and z=3. A sharp upturn in the the XLF is seen at the very lowest
luminosities (Lx < 10^42.5 erg s^-1), most likely due to the contribution of
pure X-ray starburst galaxies at very faint fluxes.Comment: 16 pages, 9 figures, accepted for publication in MNRA
The incidence of AGN in galaxies with different stellar population ages
It has been argued that recycled gas from stellar mass loss in galaxies might
serve as an important fuelling source for black holes (BHs) in their centers.
Utilizing spectroscopic samples of galaxies from the Sloan Digital Sky Survey
(SDSS) at and the Large Early Galaxy Astrophysics Census (LEGA-C)
survey at that have X-ray coverage from XMM-Newton or Chandra, we
test this stellar mass loss fuelling scenario by investigating how AGN activity
and BH growth vary with the break strength at 4000 ,
(which is closely related to the age of stellar populations), as younger
galaxies are considered to have higher stellar mass loss rates. We found that
when controlling for host-galaxy properties, the fraction of log / > 32 (which roughly corresponds to Eddington ratios %)
AGN and sample-averaged black hole accretion rate ()
decrease with among 1.9 galaxies,
suggesting a higher level of AGN activity among younger galaxies, which
supports the stellar mass loss fuelling scenario. For the oldest and most
massive galaxies at , this decreasing trend is not present anymore.
We found that, among these most massive galaxies at low redshift, the fraction
of low specific-accretion-rate (31 log / 32) AGNs
increases with , which may be associated with additional
fuelling from hot halo gas and/or enhanced accretion capability.Comment: 24 pages, 28 figures. Accepted for publication in MNRA
Investigating evidence for different black hole accretion modes since redshift z~1
Chandra data in the COSMOS, AEGIS-XD and 4Ms CDFS are combined with
optical/near-IR photometry to determine the rest-frame U-V vs V-J colours of
X-ray AGN hosts at mean redshifts 0.40 and 0.85. This combination of colours
(UVJ) provides an efficient means of separating quiescent from star-forming,
including dust reddened, galaxies. Morphological information emphasises
differences between AGN split by their UVJ colours. AGN in quiescent galaxies
are dominated by spheroids, while star-forming hosts are split between bulges
and disks. The UVJ diagram of AGN hosts is then used to set limits on the
accretion density associated with evolved and star-forming systems. Most of the
black hole growth since z~1 is associated with star-forming hosts.
Nevertheless, ~15-20% of the X-ray luminosity density since z~1, is taking
place in the quiescent region of the UVJ diagram. For the z~0.40 subsample,
there is tentative evidence (2sigma significance), that AGN split by their UVJ
colours differ in Eddington ratio. AGN in star-forming hosts dominate at high
Eddington ratios, while AGN in quiescent hosts become increasingly important as
a fraction of the total population toward low Eddington ratios. At higher
redshift, z~0.8, such differences are significant at the 2sigma level only at
Eddington ratios >1e-3. These findings are consistent with scenarios in which
diverse accretion modes are responsible for the build-up of SMBHs at the
centres of galaxies. We compare our results with the GALFORM semi-analytic
model, which postulates two black hole fuelling modes, the first linked to
star-formation and the second occuring in passive galaxies. GALFORM predicts a
larger fraction of black hole growth in quiescent galaxies at z<1, compared to
the data. Relaxing the strong assumption of the model that passive AGN hosts
have zero star-formation rate could reconcile this disagreement.Comment: MNRAS accepte
The galaxy’s gas content regulated by the dark matter halo mass results in a superlinear M BH–M ⋆ Relation
Supermassive black holes (SMBHs) are tightly correlated with their hosts, but the origin of such connection remains elusive. To explore the cosmic buildup of this scaling relation, we present an empirically motivated model that tracks galaxy and SMBH growth down to z = 0. Starting from a random mass seed distribution at z = 10, we assume that each galaxy evolves on the star-forming "main sequence" (MS) and each BH follows the recently derived stellar mass (M sstarf) dependent ratio between BH accretion rate and star formation rate, going as . Our simple recipe naturally describes the BH–galaxy buildup in two stages. At first, the SMBH lags behind the host that evolves along the MS. Later, as the galaxy grows in M sstarf, our M sstarf-dependent BHAR/SFR induces a superlinear BH growth, as . According to this formalism, smaller BH seeds increase their relative mass faster and earlier than bigger BH seeds, at fixed M sstarf, thus setting along a gradually tighter M BH–M sstarf locus toward higher M sstarf. Assuming reasonable values of the radiative efficiency epsilon ~ 0.1, our empirical trend agrees with both high-redshift model predictions and intrinsic M BH–M sstarf relations of local BHs. We speculate that the observed nonlinear BH–galaxy buildup is reflected in a twofold behavior with dark matter halo mass (M DM), displaying a clear turnover at M DM ~ 2 × 1012 M ⊙. While supernovae-driven feedback suppresses BH growth in smaller halos (), above the M DM threshold cold gas inflows possibly fuel both BH accretion and star formation in a similar fashion ()
Bone mineral content after renal transplantation
Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased signifiantly (p<0.05) but marginally in placebo-treated patients (n=14) (initial BMC 1.09±0.25 g/cm; final BMC 1.05±0.24). Fourteen patients were prophylactically given 1,25(OH)2vitamin D3 in a dose which avoided hypercalcemia and hypercalciuria (sim0.25 µg/day); under 1,25(OH)2 vitamin D3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94±0.21 g/cm; final BMC 0.95±0.21), but the difference between placebo and 1,25(OH)2 vitamin D3 narrowly missed statistical significance (p=0.066).
It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)2 vitamin D3 to slightly ameliorate forearm (cortical) BMC loss
A new method for determining the sensitivity of X-ray imaging observations and the X-ray number counts
We present a new method for determining the sensitivity of X-ray imaging
observations, which correctly accounts for the observational biases that affect
the probability of detecting a source of a given X-ray flux, without the need
to perform a large number of time consuming simulations. We use this new
technique to estimate the X-ray source counts in different spectral bands
(0.5-2, 0.5-10, 2-10 and 5-10keV) by combining deep pencil-beam and shallow
wide-area Chandra observations. The sample has a total of 6295 unique sources
over an area of and is the largest used to date to determine
the X-ray number counts. We determine, for the first time, the break flux in
the 5-10 keV band, in the case of a double power-law source count distribution.
We also find an upturn in the 0.5-2keV counts at fluxes below about
6e-17erg/s/cm2. We show that this can be explained by the emergence of normal
star-forming galaxies which dominate the X-ray population at faint fluxes. The
fraction of the diffuse X-ray background resolved into point sources at
different spectral bands is also estimated. It is argued that a single
population of Compton thick AGN cannot be responsible for the entire unresolved
X-ray background in the energy range 2-10keV.Comment: Accepted for publication in MNRAS. Data products available at
http://astro.imperial.ac.uk/research/xray
Concentration Dependence of Superconductivity and Order-Disorder Transition in the Hexagonal Rubidium Tungsten Bronze RbxWO3. Interfacial and bulk properties
We revisited the problem of the stability of the superconducting state in
RbxWO3 and identified the main causes of the contradictory data previously
published. We have shown that the ordering of the Rb vacancies in the
nonstoichiometric compounds have a major detrimental effect on the
superconducting temperature Tc.The order-disorder transition is first order
only near x = 0.25, where it cannot be quenched effectively and Tc is reduced
below 1K. We found that the high Tc's which were sometimes deduced from
resistivity measurements, and attributed to compounds with .25 < x < .30, are
to be ascribed to interfacial superconductivity which generates spectacular
non-linear effects. We also clarified the effect of acid etching and set more
precisely the low-rubidium-content boundary of the hexagonal phase.This work
makes clear that Tc would increase continuously (from 2 K to 5.5 K) as we
approach this boundary (x = 0.20), if no ordering would take place - as its is
approximately the case in CsxWO3. This behaviour is reminiscent of the
tetragonal tungsten bronze NaxWO3 and asks the same question : what mechanism
is responsible for this large increase of Tc despite the considerable
associated reduction of the electron density of state ? By reviewing the other
available data on these bronzes we conclude that the theoretical models which
are able to answer this question are probably those where the instability of
the lattice plays a major role and, particularly, the model which call upon
local structural excitations (LSE), associated with the missing alkali atoms.Comment: To be published in Physical Review
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