Evidence Of Saturation Research Articles

The Potential Health Benefits of Urban Tree Planting Suggested through Immersive Environments

Disruptive change in urban landscapes, such as large-scale tree planting, is complicated by the different priorities of the wide range of urban stakeholders. Here, we demonstrate an approach to the planning of urban green spaces using virtual reality simulations. We evaluate the health benefits (restorative benefits) and safety concerns of participants using virtual reconstructions of 10 urban parks in Bradford, UK, to simulate changes in woodland cover. Participants experienced each of the 10 parks as immersive environments with each of three scenarios: (i) no trees, (ii) real tree distribution, and (iii) doubling of tree numbers. Participants answered a short questionnaire while in each virtual park to quantify their feelings of safety and the restorative benefit that they thought they would experience. The results show that our VR approach produces reported restorative benefits that are not significantly different from those reported in the physical parks during visits by participants. We then demonstrate that increased tree cover is associated with significant increases in perceived restorative benefit, with some evidence of saturation at higher tree densities. Reductions in tree cover lead to a reduction in reported restorative benefit. We suggest that immersive technologies present a useful tool for the consultation and co-design of urban landscapes.

Enhanced backscatter and unsaturated blue wavelength shifts in F-doped fused silica optical fibers exposed to extreme neutron radiation damage

Amorphous fused silica (a-SiO2) optical fibers, with and without inscribed Bragg gratings, were interrogated using infrared (∼1550 nm) optical backscatter reflectometry during ∼25 days of intense neutron irradiation to a fast (energy > 0.1 MeV) neutron fluence of ∼1021 n/cm2, or ∼1.5 atomic displacements per atom. The reflected light amplitudes in Ge-doped core telecommunications fiber dropped below detection limits (>15 dB attenuation) within 3 days of irradiation (∼1020 fast n/cm2). Amplitudes from a pure silica core, F-doped silica cladding fiber reached equilibrium levels ∼1.5–2 dB higher than pre-irradiation values, whereas Bragg gratings inscribed in the same fiber using a femtosecond laser (point-by-point method) suffered > 45 dB attenuation. Blue wavelength shifts were initially consistent with previous radiation-induced compaction models but increased linearly with increasing neutron fluence (no evidence of saturation) beyond 1020 n/cm2 and exceeded 0.6%, which corresponds to >1,000 °C drift if used to measure temperature changes.

Forest Insect Biosecurity: Processes, Patterns, Predictions, Pitfalls.

The economic and environmental threats posed by non-native forest insects are ever increasing with the continuing globalization of trade and travel; thus, the need for mitigation through effective biosecurity is greater than ever. However, despite decades of research and implementation of preborder, border, and postborder preventative measures, insect invasions continue to occur, with no evidence of saturation, and are even predicted to accelerate. In this article, we review biosecurity measures used to mitigate the arrival, establishment, spread, and impacts of non-native forest insects and possible impediments to the successful implementation of these measures. Biosecurity successes are likely under-recognized because they are difficult to detect and quantify, whereas failures are more evident in the continued establishment of additional non-native species. There are limitations in existing biosecurity systems at global and country scales (for example, inspecting all imports is impossible, no phytosanitary measures are perfect, knownunknowns cannot be regulated against, and noncompliance is an ongoing problem). Biosecurity should be a shared responsibility across countries, governments, stakeholders, and individuals.

Bath-induced delocalization in interacting disordered spin chains

Over a decade of work has culminated in the consensus that one-dimensional systems, subject to sufficiently large disorder, fail to thermalize and possess an extensive set of local integrals of motion. In this Letter, I will provide numerical evidence for the contrary. In particular, this work studies the dynamics of disordered spin chains which are weakly coupled to a Markovian bath. Within this approach, the critical disorder for stability to quantum avalanches exceeds ${W}^{*}\ensuremath{\gtrsim}20$ in the random field Heisenberg chain. In stark contrast to the Anderson insulator, the avalanche threshold drifts considerably with system size, with no evidence of saturation in the studied regime.

Tocopherol more bioavailable than tocopheryl-acetate as a source of vitamin E for broilers.

Vitamin E is typically supplied in the form of tocopheryl-acetate (T-Ac) since tocopherol (T) has stability issues. Tocopheryl-acetate, however, must be hydrolyzed in the intestines before it can be absorbed, a step that is purportedly rate-limiting for its bioavailability. The objective of this study was to compare the efficiency of absorption of T-Ac and T in broilers. In addition, two test procedures were evaluated in which animals received the test substances for either 2 or 4 days only. Animals were adapted to diets without supplemental vitamin E (feedstuffs contributed 14±1 ppm natural vitamin E (RRR-tocopherol)) till the age of 25 d (individual housing) or 28 d (group housing). Subsequently, they were fed T-Ac at 80, 53, 36, 24, or 16 ppm or T at 80, 40, 20, 10, or 5 ppm for a period of 4 d (4-di) or 2 d (2-dg), after which serum and liver were collected for analysis of vitamin E. Measured feed vitamin E levels were used for the data analysis; the recovery of T-Ac was 85%, and that of T was 39%. Both test procedures (2 or 4 days) yielded good quality data. Based on linear regression analysis, the relative efficiency with which T-Ac raised tissue levels as compared to T was 0.24 (2-dg) to 0.37 (4-di), with liver and serum yielding similar results. Analysis using more complex dose response models imply that the hydrolysis of T-Ac was strongly dose-dependent and that it could be saturated at doses above approximately 50 ppm in animals only briefly fed T-Ac; for T there was no evidence of saturation. These data imply that T, provided that stable forms can be developed, has the potential to be much more efficient at providing vitamin E to the animal, and on top, can yield much higher tissue levels, than T-Ac.

Development of the Multiple Myeloma Symptom and Impact Questionnaire: A New Patient-Reported Outcome Instrument to Assess Symptom and Impacts in Patients With Multiple Myeloma

ObjectivesThis study aimed to develop and assess the content validity of a patient-reported outcomes (PROs) instrument to measure symptoms and impacts experienced by patients with active multiple myeloma (MM). MethodsThe PRO instrument was developed using an iterative, mixed-methods approach. The list of concepts was generated based on a review of existing evidence (qualitative studies and literature) and post hoc psychometric evaluations of 2 PRO instruments in 3 clinical trials. A total of 30 adult patients with MM from the United States participated in hybrid concept elicitation/cognitive debriefing interviews to validate the content validity of the newly developed PRO instrument. Translatability assessment was completed in 8 languages. ResultsThe item generation process resulted in 17 symptom and 9 impact concepts for evaluation. The concept elicitation interviews and analysis were based on the first 25 participants; evidence of saturation was observed. The cognitive debriefing interviews and analysis were based on the last 23 participants across 4 waves of interviews. On the basis patient feedback, 10 items were removed, and 1 item was added to the PRO instrument. The translatability assessment resulted in 1 minor revision. The multiple myeloma symptom and impact questionnaire (MySIm-Q) includes 11 symptom and 6 impact concepts, organized within 8 hypothesized subdomains, with each concept measured using a 5-point verbal rating scale and a 7-day recall period. ConclusionsThe MySIm-Q instrument was developed using rigorous and mixed methodology and with direct input from patients who received a diagnosis of MM. The MySIm-Q has good content validity and is culturally relevant for use in global clinical trials.

Sequencing effort dictates gene discovery in marine microbial metagenomes.

SummaryMassive metagenomic sequencing combined with gene prediction methods were previously used to compile the gene catalogue of the ocean and host‐associated microbes. Global expeditions conducted over the past 15 years have sampled the ocean to build a catalogue of genes from pelagic microbes. Here we undertook a large sequencing effort of a perturbed Red Sea plankton community to uncover that the rate of gene discovery increases continuously with sequencing effort, with no indication that the retrieved 2.83 million non‐redundant (complete) genes predicted from the experiment represented a nearly complete inventory of the genes present in the sampled community (i.e., no evidence of saturation). The underlying reason is the Pareto‐like distribution of the abundance of genes in the plankton community, resulting in a very long tail of millions of genes present at remarkably low abundances, which can only be retrieved through massive sequencing. Microbial metagenomic projects retrieve a variable number of unique genes per Tera base‐pair (Tbp), with a median value of 14.7 million unique genes per Tbp sequenced across projects. The increase in the rate of gene discovery in microbial metagenomes with sequencing effort implies that there is ample room for new gene discovery in further ocean and holobiont sequencing studies.

Saturable Absorption and Bistable Switching of Single Mode Fiber Core‐Guided Light by a 6 nm‐thick, Few Layers Graphene Coating on the Cladding Surface

AbstractThe coupling of less than 80 µW of in‐plane polarized near‐infrared light in a 6 nm‐thick graphene layer deposited on an optical fiber produces important permittivity changes leading to bistability and self‐starting 50% modulation of over 1 W of continuous wave light in the core. These features arise from resonant coupling of core‐guided light into the cladding by a 12‐degree tilted, 1 cm long fiber Bragg grating via narrowband, polarization‐dependent resonances that allow the selection of cladding modes with electric fields polarized in the plane of the graphene. The pulse repetition rate of the modulation increases from 10 to 269 Hz for input powers ranging from 0.3 to 1.33 W in the core, with no evidence of saturation. Investigations into the origin of these effects through physical modelling and different experimental conditions point to photo‐induced Joule heating in the graphene layer giving rise to temperature increases of the order of 60 °C and corresponding permittivity changes in the graphene and underlying silica fiber. Those changes lead to shifts in the resonance positions which result in the equivalent of saturable absorption for light guided in the core without direct contact with the absorbing graphene layer.

Enhancement of emission by surfactant-induced aggregation in poly(phenylenevinylene)-based lipochromophores

A study has been carried out on the surfactochromicity of four new highly lipophilic poly(phenylenevinylene) (PPV) chromophores. Micellar encapsulation by a detergent such as cetyltrimethylammonium bromide (CTAB) imparts solubility to these compounds in aqueous solution. Before the critical micelle concentration (CMC) was reached the emission intensity of the chromophores increased significantly with the concentration of CTAB. After reaching the CMC, the quantum yield tended to stabilize. Concentrations of PPV up to 100 μM could be encapsulated without any evidence of saturation or modification of the CMC value of the surfactant. Transmission electron microscopy (TEM) experiments demonstrated that aggregation of the molecules occurred and this led to a highly efficient Förster resonance energy transfer (FRET) when different chromophores were encapsulated within the micelle. This situation was not observed in organic solutions at similar concentrations in the absence of CTAB. The detergent shielding also prevented protonation of amine derivatives 3 and 4 in acidic media. These mixed surfactant/fluorophore systems not only maintained but also improved the already good emission properties of PPVs 1–4 in the solid state. This behavior makes these systems suitable for applications such as 3D printing due to their compatibility with alcoholic and/or aqueous solvents.

Multigluon Correlations and Evidence of Saturation from Dijet Measurements at an Electron-Ion Collider.

We study inclusive and diffractive dijet production in electron-proton and electron-nucleus collisions within the color glass condensate effective field theory. We compute dijet cross sections differentially in both mean dijet transverse momentum P and recoil momentum Δ, as well as the anisotropy in the relative angle between P and Δ. Our results cover a much larger kinematic range than accessible in previous computations performed in the correlation limit approximation, where it is assumed that |P|≫|Δ|. We validate this approximation in its range of applicability and quantify its failure for |P|≲|Δ|. We also predict significant target-dependent deviations from the correlation limit approximation for |P|>|Δ| and |P|≲Q_{s}, which offers a straightforward test of gluon saturation and access to multigluon distributions at a future Electron-Ion Collider.

Multiple pathways of C and N incorporation by consumers across an experimental gradient of salmon carcasses

AbstractNumerous studies link resource subsidies to consumers, yet manipulations of subsidy gradients are rare, limiting our ability to predict their effects. We measured natural abundance levels of the stable isotopes of carbon (δ13C) and nitrogen (δ15N) in consumers representing two taxonomic (invertebrates, fish) and multiple trophic groups (primary, secondary, and tertiary consumers) exposed to a gradient of Pacific salmon carcasses (0–4 kg/m2, eight treatment levels) in 16 experimental streams from September to December. We hypothesized (1) that consumer δ13C and δ15N values would increase with carcass loading and (2) that these relationships would vary among consumers and trophic levels. Within taxonomic groups, both δ13C and δ15N values increased with carcass loading indicating direct consumption of salmon organic matter (δ13C increase) and indirectly by consumption of salmon‐enriched prey (δ15N increase). The relative importance of these two pathways for invertebrates primary consumers varied with carcass loading, with an abrupt increase in direct consumption above ~0.5 kg/m2 salmon carcass wet mass. Both the rates of δ13C and δ15N increase and the shape of the response to the carcass gradient varied among invertebrates. The only fish that responded positively to carcasses was a small benthic, secondary consumer, and only for δ13C. Overall, benthic invertebrate primary consumers were the dominant pathway by which salmon organic matter entered the trophic system, followed by benthic secondary consumers, and then tertiary consumers (juvenile coho salmon and cutthroat trout) that occupy the water column. The attenuating response to subsidies at higher trophic levels was possibly due to a combination of low decomposition and metabolic rates during fall and winter, composition of the subsidy, and habitat use. Our results demonstrate that decomposing salmon carcasses provide variable but potentially important sources of C (range: ~0–60%) and N (range: ~0–35%) supporting benthic consumers during fall and winter, when environmental conditions constrain primary productivity, with some evidence of saturation at carcass loadings >0.1–0.6 kg/m2. Furthermore, stable isotope analysis showed that consumers exploited salmon organic matter in different ways, potentially alleviating competition and allowing for a more efficient processing of this resource subsidy.

Deflexifol (a novel formulation of 5FU): Pharmacokinetics in a phase 1 trial in comparison to 5FU.

2530 Background: Simultaneous administration of 5-fluorouracil (5FU) and leucovorin (LV) is generally not feasible as 5FU and LV are chemically incompatible (CaPO4 crystals), so the maximum possible interaction for benefit is not achieved. Deflexifol, an all in one formulation of 5FU/LV with cyclodextrin (HP-β-CD 100mg/ml, 5-FU 15mg/ml & LV 1mg/ml) at pH 7, was developed to overcome this problem. Methods: Limited sampling PK was done with dose 1 and 6 in a standard 3+3 phase I trial of Deflexifol given in two schedules (46-h infusion Q2W or bolus weekly x6) with no intrapatient dose escalation, at doses shown in Table. Sample times were infusion: 0, 2, 46h; bolus: 0, 0.2, 0.4, 1, 24h. 5FU and dihydroFU were measured as per Ackland et al, Anal Biochem 1997. 5FU AUC, clearance (CLR) and t1/2 were estimated for each patient to assess PK variability and adequacy of dosing compared to previous reports. Results: 40 patients were treated (21 infusion, 19 bolus, median age 67, 19 M, 21 F). The MTD(bolus) was 575 mg/m2, with no DLT in infusion schedule to 3600 mg/m2. PK showed substantial inter-patient variability – CLR(bolus) 21-900 L/h, t1/2 0.11-0.52 h, with intra-patient dose 6 CLR = 54-117% of dose 1, and a trend to increased AUC (mg/L.h) with dose (Table). Infusion CLR and AUC estimates were highly variable (CLR range 2-1200), with many cases with insufficient data. Compared to historical data with 5FU alone, AUC was likely subtherapeutic until 475mg/m2 bolus and for many patients with infusion <3000mg/m2. Conclusions: 5FU PK with Deflexifol is similar to 5FU alone. No evidence of saturation of kinetics over this dose range was seen, or induction of metabolism with repeated dosing. In each schedule AUC data supports the clinical impression of reduced toxicity at the same dose of 5FU. Accurate estimation of infusion PK requires more than 2 timepoints. PK in a phase II study is planned. Clinical trial information: 044867. [Table: see text]

Rates of nitrogen uptake by cyanobacterially-dominated assemblages in Lake Taihu, China, during late summer

Lake Taihu has suffered an increasing number of cyanobacteria harmful algal blooms (CyanoHABs) over the past three decades, bringing about formidable ecological and economical losses. Efforts to control phosphate (P) and/or nitrogen (N) have been applied to mitigate these blooms, but there has been much less attention paid to N and its different forms on the ecology of the blooms. Therefore, kinetic and nutrient enrichment experiments were conducted to assess N uptake rates under differing conditions, and to examine effects of changes in N forms (NH4+, NO3− and urea) and P availability on phytoplankton community physiology. In 2014 these experiments involved mesocosm enrichments; in 2015 these experiments were conducted over a diurnal period. Both involved measurements of short-term N uptake. The kinetic results showed that the utilization of NH4+, NO3− and urea by Microcystis-dominated communities was not efficient at low ambient substrate concentrations. Maximum uptake rates by these phytoplankton was achieved on NH4+ and these rates were significantly higher than those on NO3− or urea with or without nutrient pretreatment. Moreover in the presence of PO43− enrichment, the maximal uptake velocity of NH4+ substantially increased without evidence of saturation. High amounts of NH4+ may have inhibited or repressed the uptake of NO3− at certain times in these studies. In the diurnal study, dissolved inorganic carbon and pH changed substantially throughout the day. The resulting high pH altered N and P in ways that may help to sustain nutrient cycling for the blooms.

Long-term nitrogen deposition increases heathland carbon sequestration

The large increases in reactive nitrogen (N) deposition in developed countries since the Industrial Revolution have had a marked impact on ecosystem functioning, including declining species richness, shifts in species composition, and increased N leaching. A potential mitigation of these harmful effects is the action of N as a fertiliser, which, through increasing primary productivity (and subsequently, organic matter production), has the potential to increase ecosystem carbon (C) storage. Here we report the response of an upland heath to 10years of experimental N addition. We find large increases in plant and soil C and N pools, with N-driven C sequestration rates in the range of 13–138kgCkg−1. These rates are higher than those previously found in forest and lowland heath, mainly due to higher C sequestration in the litter layer. C sequestration is highest at lower N treatments (10, 20, and 40kgNha−1yr−1 above ambient), with evidence of saturation at the highest N treatment, reflecting a physiologically aged Calluna vulgaris (Calluna) canopy. To maintain these rates of sequestration, the Calluna canopy should be managed to maximise it's time in the building phase. Scaling our results across UK heathlands, this equates to an additional 0.77Mt CO2e per annum extra C sequestered into plant litter and the top 15cm of heathland soil as a result of N deposition. The bulk of this is found in the litter and organic soil horizons that hold an average of 23% and 54% of soil C, respectively. This additional C represents around 0.44% of UK annual anthropogenic GHG emissions. When considered in the context of falling biodiversity and altered species composition in heathland, policy focus should remain on reducing N emissions.

Global C‐Band Envisat, RADARSAT‐2 and Sentinel‐1 SAR measurements in copolarization and cross‐polarization

AbstractUsing colocated ASCAT and ECMWF winds, a careful global analysis of ENVISAT and Sentinel‐1 synthetic aperture radar (SAR) measurements helps to refine, at medium resolution (tens of kilometers) and especially for HH configuration, a C‐band geophysical model function (GMF, i.e., C‐SARMOD) to analyze wind sensitivity for different incidence and azimuth angles. Results unify major findings from previous global and case studies for polarization ratio (PR, VV/HH), polarization difference (PD, VV‐HH), and cross‐polarization (CP). At lower level than standard two‐scale predictions, PR increases with increasing incidence angle and decreases with increasing wind speed. PR further exhibits a strong azimuthal modulation, with maximum values in downwind configurations. The PD azimuth modulation is found more pronounced for VV than HH (VV being larger than HH), reaching maximum values for wind speed about 10 m/s. CP signals decrease with incidence angle but increase with wind speed, especially beyond 10 m/s, with no evidence of saturation. Remarkably, this also applies to HH crosswind measurements. This comparable high wind sensitivity for both CP and HH crosswind signals, with a clear departure from PD ones, can be related to the onset of vigorous breaking events, large enough to impact in‐plane and out‐of‐plane local tilts. Considering that VV polarization best maximizes the polarized resonant contribution, combined CP and VV wide swath SAR observations can thus have the potential to efficiently map and contrast local directional aspects.

Constraining FeLoBAL outflows from absorption line variability

FeLoBALs are a rare class of quasar outflows with low-ionization broad absorption lines (BALs), large column densities, and potentially large kinetic energies that might be important for `feedback' to galaxy evolution. In order to probe the physical properties of these outflows, we conducted a multiple-epoch, absorption line variability study of 12 FeLoBAL quasars spanning a redshift range between 0.7 and 1.9 over rest frame time-scales of approximately 10 d to 7.6 yr. We detect absorption line variability with greater than 8 sigma confidence in 3 out of the 12 sources in our sample over time-scales of 0.6 to 7.6 yr. Variable wavelength intervals are associated with ground and excited state Fe II multiplets, the Mg II 2796, 2803 doublet, Mg I 2852, and excited state Ni II multiplets. The observed variability along with evidence of saturation in the absorption lines favors transverse motions of gas across the line of sight (LOS) as the preferred scenario, and allows us to constrain the outflow distance from the supermassive black hole (SMBH) to be less than 69, 7, and 60 pc for our three variable sources. In combination with other studies, these results suggest that the outflowing gas in FeLoBAL quasars resides on a range of scales and includes matter within tens of parsecs of the central source.

Vertical Wavenumber Spectra of Gravity Waves in the Venus Atmosphere Obtained from Venus Express Radio Occultation Data: Evidence for Saturation

Abstract By using the vertical temperature profiles obtained by the radio occultation measurements on the European Space Agency (ESA)’s Venus Express, the vertical wavenumber spectra of small-scale temperature fluctuations that are thought to be manifestations of gravity waves are studied. Wavenumber spectra covering wavelengths of 1.4–7.5 km were obtained for two altitude regions (65–80 and 75–90 km) and seven latitude bands. The spectra show a power-law dependence on the high-wavenumber side with the logarithmic spectral slope ranging from −3 to −4, which is similar to the features seen in Earth’s and Martian atmospheres. The power-law portion of the spectrum tends to follow the semiempirical spectrum of saturated gravity waves, suggesting that the gravity waves are dissipated by saturation as well as radiative damping. The spectral power is larger at 75–90 km than at 65–80 km at low wavenumbers, suggesting amplitude growth with height of unsaturated waves. It was also found that the wave amplitude is larger at higher latitudes and that the amplitude is maximized in the northern high latitudes. On the assumption that gravity waves are saturated in the Venusian atmosphere, the turbulent diffusion coefficient was estimated. The diffusion coefficient in the Venusian atmosphere is larger than those in Earth’s atmosphere because of the longer characteristic vertical wavelength of the saturated waves.

Impact of user-generated and professional critics reviews on Bollywood movie success

User generated (e.g., peer-to-peer or word-of-mouth) reviews and professional experts' reviews are important sources of external information that consumers use in making consumption decisions, but studies of their simultaneous effects is scarce. We develop a conceptual model for hypothesizing the simultaneous effects of the volume and valence of user and expert reviews on sales (i.e., box-office) revenue in the consumption of entertainment products (i.e., movies). We gather and analyze the User Generated Reviews (UGRs) using a text processing algorithm and evaluate resulting semantic networks to validate our approach. Combining these data with other relevant data from multiple sources for all Bollywood movies released over a six month period, we test the hypotheses proposed in the model. We find that, after controlling for effect of expert reviews, both volume and valence of user generated reviews have significant positive association with box-office revenue; however, valence evidences a curvilinear (saturation) effect such that positivity effect shows decreasing returns at high positivity levels. We also find that expert reviews positively affect box office revenue with little evidence of saturation or amplifying effects.

Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development.