3,063 research outputs found
Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors
Background: One of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs (large organized chromatin lysine-modifications) and LADs (lamin-associated domains). Methods: Here we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform. Results: We find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks. Conclusion: Thus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0061-y) contains supplementary material, which is available to authorized users
Reply to Swartz et al.: Challenges and opportunities for identifying forced labor using satellite-based fishing vessel monitoring
We appreciate Swartz et al. (1) for highlighting several key considerations for interpreting our results (2). While we discuss many of these in our paper, we are grateful to further highlight our work’s strengths, limitations, and future opportunities. A major challenge with understanding fisheries labor abuses is a lack of data. Automatic identification system (AIS) is only used by a subset of the global fishing fleet. However, AIS is valuable for monitoring certain types of fishing vessels, especially those that are large (∼52 to 85% carry AIS) (3) and those fishing on the high seas (∼80% carry AIS) (4). Mandating AIS and unique identifiers on fishing vessels and publishing vessel registries would facilitate more inclusive
AIS-based analyses (5)
Large orders in strong-field QED
We address the issue of large-order expansions in strong-field QED. Our
approach is based on the one-loop effective action encoded in the associated
photon polarisation tensor. We concentrate on the simple case of crossed fields
aiming at possible applications of high-power lasers to measure vacuum
birefringence. A simple next-to-leading order derivative expansion reveals that
the indices of refraction increase with frequency. This signals normal
dispersion in the small-frequency regime where the derivative expansion makes
sense. To gain information beyond that regime we determine the factorial growth
of the derivative expansion coefficients evaluating the first 80 orders by
means of computer algebra. From this we can infer a nonperturbative imaginary
part for the indices of refraction indicating absorption (pair production) as
soon as energy and intensity become (super)critical. These results compare
favourably with an analytic evaluation of the polarisation tensor asymptotics.
Kramers-Kronig relations finally allow for a nonperturbative definition of the
real parts as well and show that absorption goes hand in hand with anomalous
dispersion for sufficiently large frequencies and fields.Comment: 26 pages, 6 figure
Treatable Traits in Elderly Asthmatics from the Australasian Severe Asthma Network: A Prospective Cohort Study.
BACKGROUND: Data on treatable traits (TTs) in different populations are limited. OBJECTIVE: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. METHODS: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. RESULTS: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection-induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection-induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. CONCLUSIONS: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma
Evidence for Pervasive Adaptive Protein Evolution in Wild Mice
The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans
Artificial drainage of peatlands: hydrological and hydrochemical process and wetland restoration
Peatlands have been subject to artificial drainage for centuries. This drainage has been in response to agricultural demand, forestry, horticultural and energy properties of peat and alleviation of flood risk. However, the are several environmental problems associated with drainage of peatlands. This paper describes the nature of these problems and examines the evidence for changes in hydrological and hydrochemical processes associated with these changes. Traditional black-box water balance approaches demonstrate little about wetland dynamics and therefore the science of catchment response to peat drainage is poorly understood. It is crucial that a more process-based approach be adopted within peatland ecosystems. The environmental problems associated with peat drainage have led, in part, to a recent reversal in attitudes to peatlands and we have seen a move towards wetland restoration. However, a detailed understanding of hydrological, hydrochemical and ecological process-interactions will be fundamental if we are to adequately restore degraded peatlands, preserve those that are still intact and understand the impacts of such management actions at the catchment scale
Detecting natural selection in RNA virus populations using sequence summary statistics
Tests of model of color reconnection and a search for glueballs using gluon jets with a rapidity gap
Gluon jets with a mean energy of 22 GeV and purity of 95% are selected from
hadronic Z0 decay events produced in e+e- annihilations. A subsample of these
jets is identified which exhibits a large gap in the rapidity distribution of
particles within the jet. After imposing the requirement of a rapidity gap, the
gluon jet purity is 86%. These jets are observed to demonstrate a high degree
of sensitivity to the presence of color reconnection, i.e. higher order QCD
processes affecting the underlying color structure. We use our data to test
three QCD models which include a simulation of color reconnection: one in the
Ariadne Monte Carlo, one in the Herwig Monte Carlo, and the other by Rathsman
in the Pythia Monte Carlo. We find the Rathsman and Ariadne color reconnection
models can describe our gluon jet measurements only if very large values are
used for the cutoff parameters which serve to terminate the parton showers, and
that the description of inclusive Z0 data is significantly degraded in this
case. We conclude that color reconnection as implemented by these two models is
disfavored. The signal from the Herwig color reconnection model is less clear
and we do not obtain a definite conclusion concerning this model. In a separate
study, we follow recent theoretical suggestions and search for glueball-like
objects in the leading part of the gluon jets. No clear evidence is observed
for these objects.Comment: 42 pages, 18 figure
A study of charm production in beauty decays with the OPAL detector at LEP
Using an inclusive method, BR(b -> D\bar{D}X) has been measured in hadronic
Z^0 decays with the OPAL detector at LEP. The impact parameter significance of
tracks opposite tagged b-jets is used to differentiate b -> D\bar{D}X decays
from other decays. Using this result, the average number of charm and
anti-charm quarks produced per beauty quark decay, n_c, is determined.Comment: 20 pages, 4 figure
Search for Yukawa Production of a Light Neutral Higgs Boson at LEP
Within a Two-Higgs-Doublet Model (2HDM) a search for a light Higgs boson in
the mass range of 4-12 GeV has been performed in the Yukawa process e+e- -> b
bbar A/h -> b bbar tau+tau-, using the data collected by the OPAL detector at
LEP between 1992 and 1995 in e+e- collisions at about 91 GeV centre-of-mass
energy. A likelihood selection is applied to separate background and signal.
The number of observed events is in good agreement with the expected
background. Within a CP-conserving 2HDM type II model the cross-section for
Yukawa production depends on xiAd = |tan beta| and xihd = |sin alpha/cos beta|
for the production of the CP-odd A and the CP-even h, respectively, where tan
beta is the ratio of the vacuum expectation values of the Higgs doublets and
alpha is the mixing angle between the neutral CP-even Higgs bosons. From our
data 95% C.L. upper limits are derived for xiAd within the range of 8.5 to 13.6
and for xihd between 8.2 to 13.7, depending on the mass of the Higgs boson,
assuming a branching fraction into tau+tau- of 100%. An interpretation of the
limits within a 2HDM type II model with Standard Model particle content is
given. These results impose constraints on several models that have been
proposed to explain the recent BNL measurement of the muon anomalous magnetic
moment.Comment: 24 pages, 9 figures, Submitted to Euro. Phys. J.
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