87 research outputs found
The Large Hadron Collider project
The Large Hadron Collider (LHC) will enable proton-proton collisions at an energy of more than fourteen thousand times the proton mass. This allows the discovery of new elementary particles with very large masses, in particular of the Higgs boson. The Higgs boson is crucial for understanding the mechanism that Nature chose to give mass to particles. The Higgs boson has turned out to be very hard to find but the LHC should allow a decisive step into new territory, unveiling one or even more Higgs bosons. The new energy domain of the LHC also inspires speculations about discoveries relevant for understanding dark matter and about the discovery of new space dimensions, so far hidden to us. In the talk an overview of the physics at LHC and a report on the status of the project, accelerator and experiments, will be presented
Alcohol consumption and common carotid intima-media thickness: the USE-IMT study
Aims: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. Methods: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. Results: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (10 g per day, after adjusting for a range of confounding factors. Conclusion: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT
The Atacama Cosmology Telescope: Mitigating the impact of extragalactic foregrounds for the DR6 CMB lensing analysis
We investigate the impact and mitigation of extragalactic foregrounds for the
CMB lensing power spectrum analysis of Atacama Cosmology Telescope (ACT) data
release 6 (DR6) data. Two independent microwave sky simulations are used to
test a range of mitigation strategies. We demonstrate that finding and then
subtracting point sources, finding and then subtracting models of clusters, and
using a profile bias-hardened lensing estimator, together reduce the fractional
biases to well below statistical uncertainties, with the inferred lensing
amplitude, , biased by less than . We also show
that another method where a model for the cosmic infrared background (CIB)
contribution is deprojected and high frequency data from Planck is included has
similar performance. Other frequency-cleaned options do not perform as well,
incurring either a large noise cost, or resulting in biased recovery of the
lensing spectrum. In addition to these simulation-based tests, we also present
null tests performed on the ACT DR6 data which test for sensitivity of our
lensing spectrum estimation to differences in foreground levels between the two
ACT frequencies used, while nulling the CMB lensing signal. These tests pass
whether the nulling is performed at the map or bandpower level. The
CIB-deprojected measurement performed on the DR6 data is consistent with our
baseline measurement, implying contamination from the CIB is unlikely to
significantly bias the DR6 lensing spectrum. This collection of tests gives
confidence that the ACT DR6 lensing measurements and cosmological constraints
presented in companion papers to this work are robust to extragalactic
foregrounds.Comment: Companion paper to Qu et al and Madhavacheril et a
The Atacama Cosmology Telescope: CMB Polarization at
We report on measurements of the cosmic microwave background (CMB) and
celestial polarization at 146 GHz made with the Atacama Cosmology Telescope
Polarimeter (ACTPol) in its first three months of observing. Four regions of
sky covering a total of 270 square degrees were mapped with an angular
resolution of . The map noise levels in the four regions are between 11
and 17 K-arcmin. We present TT, TE, EE, TB, EB, and BB power spectra from
three of these regions. The observed E-mode polarization power spectrum,
displaying six acoustic peaks in the range , is an excellent fit
to the prediction of the best-fit cosmological models from WMAP9+ACT and Planck
data. The polarization power spectrum, which mainly reflects primordial plasma
velocity perturbations, provides an independent determination of cosmological
parameters consistent with those based on the temperature power spectrum, which
results mostly from primordial density perturbations. We find that without
masking any point sources in the EE data at , the Poisson tail of
the EE power spectrum due to polarized point sources has an amplitude less than
K at at 95\% confidence. Finally, we report that
the Crab Nebula, an important polarization calibration source at microwave
frequencies, has 8.7\% polarization with an angle of when smoothed with a Gaussian beam.Comment: 16 pages, 15 figures, 5 table
Genome-scale bacterial transcriptional regulatory networks: reconstruction and integrated analysis with metabolic models
Advances in sequencing technology are resulting in the rapid emergence of large numbers of complete genome sequences. High throughput annotation and metabolic modeling of these genomes is now a reality. The high throughput reconstruction and analysis of genome-scale transcriptional regulatory networks represents the next frontier in microbial bioinformatics. The fruition of this next frontier will depend upon the integration of numerous data sources relating to mechanisms, components, and behavior of the transcriptional regulatory machinery, as well as the integration of the regulatory machinery into genome-scale cellular models. Here we review existing repositories for different types of transcriptional regulatory data, including expression data, transcription factor data, and binding site locations, and we explore how these data are being used for the reconstruction of new regulatory networks. From template network based methods to de novo reverse engineering from expression data, we discuss how regulatory networks can be reconstructed and integrated with metabolic models to improve model predictions and performance. Finally, we explore the impact these integrated models can have in simulating phenotypes, optimizing the production of compounds of interest or paving the way to a whole-cell model.J.P.F. acknowledges funding from [SFRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) PhD program. The work was supported in part by the ERDF—European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness), National Funds through the FCT within projects [FCOMP-01-0124-FEDER015079] (ToMEGIM—Computational Tools for Metabolic Engineering using Genome-scale Integrated Models) and FCOMP-01-0124-FEDER009707 (HeliSysBio—molecular Systems Biology in Helicobacter pylori), the U.S. Department of Energy under contract [DE-ACO2-06CH11357] and the National Science Foundation under [0850546]
SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State
SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors
Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression:Identification of a modifier of breast cancer risk at locus 11q22.3
Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of similar to 320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance.We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.</p
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe
The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth
We present new measurements of cosmic microwave background (CMB) lensing over
sq. deg. of the sky. These lensing measurements are derived from the
Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which
consists of five seasons of ACT CMB temperature and polarization observations.
We determine the amplitude of the CMB lensing power spectrum at
precision ( significance) using a novel pipeline that minimizes
sensitivity to foregrounds and to noise properties. To ensure our results are
robust, we analyze an extensive set of null tests, consistency tests, and
systematic error estimates and employ a blinded analysis framework. The
baseline spectrum is well fit by a lensing amplitude of
relative to the Planck 2018 CMB power spectra
best-fit CDM model and relative to
the best-fit model. From our lensing power
spectrum measurement, we derive constraints on the parameter combination
of
from ACT DR6 CMB lensing alone and
when combining ACT DR6 and Planck NPIPE
CMB lensing power spectra. These results are in excellent agreement with
CDM model constraints from Planck or
CMB power spectrum measurements. Our lensing measurements from redshifts
-- are thus fully consistent with CDM structure growth
predictions based on CMB anisotropies probing primarily . We find no
evidence for a suppression of the amplitude of cosmic structure at low
redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see
companion papers Madhavacheril et al and MacCrann et a
The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky
Observations of the millimeter sky contain valuable information on a number
of signals, including the blackbody cosmic microwave background (CMB), Galactic
emissions, and the Compton- distortion due to the thermal Sunyaev-Zel'dovich
(tSZ) effect. Extracting new insight into cosmological and astrophysical
questions often requires combining multi-wavelength observations to spectrally
isolate one component. In this work, we present a new arcminute-resolution
Compton- map, which traces out the line-of-sight-integrated electron
pressure, as well as maps of the CMB in intensity and E-mode polarization,
across a third of the sky (around 13,000 sq.~deg.). We produce these through a
joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release
4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from
the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We
present detailed verification of an internal linear combination pipeline
implemented in a needlet frame that allows us to efficiently suppress Galactic
contamination and account for spatial variations in the ACT instrument noise.
These maps provide a significant advance, in noise levels and resolution, over
the existing \textit{Planck} component-separated maps and will enable a host of
science goals including studies of cluster and galaxy astrophysics, inferences
of the cosmic velocity field, primordial non-Gaussianity searches, and
gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly
available upon publication of the paper. The CMB T and E mode maps will be
made available when the DR6 maps are made publi
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