Star Formation Feedback and Metal Enrichment History Of The Intergalactic Medium

Using hydrodynamic simulations we compute the metal enrichment history of the intergalactic medium (IGM). We show that galactic superwind (GSW) feedback can transport metals to the IGM and that the properties of simulated metal absorbers match observations. The distance of influence of GSW is typically limited to >0.5Mpc and within regions of overdensity >10. Most CIV and OVI absorbers are located within shocked regions of elevated temperature (T>2x10^4K), overdensity (>10), and metallicity ([-2.5,-0.5]). OVI absorbers have typically higher metallicity, lower density and higher temperature than CIV absorbers. For OVI absorbers collisional ionization dominates over the entire redshift range z=0-6, whereas for CIV absorbers the transition occurs at moderate redshift z~3 from collisionally dominated to photoionization dominated. We find that the observed column density distributions for CIV and OVI in the range log N cm^2=12-15 are reasonably reproduced by the simulations. The evolution of mass densities contained in CIV and OVI lines, Omega_CIV and Omega_OVI, is also in good agreement with observations, which shows a near constancy at low redshifts and an exponential drop beyond redshift z=3-4. For both CIV and OVI, most absorbers are transient and the amount of metals probed by CIV and OVI lines of column log N cm^2=12-15 is only ~2% of total metal density at any epoch. While gravitational shocks from large-scale structure formation dominate the energy budget (80-90%) for turning about 50% of IGM to the warm-hot intergalactic medium (WHIM) by z=0, GSW feedback shocks are energetically dominant over gravitational shocks at z > 1-2. Most of the so-called "missing metals" at z=2-3 are hidden in a warm-hot (T=10^{4.5-7}K) gaseous phase, heated up by GSW feedback shocks. Their mass distribution is broadly peaked at $\delta=1-10$ in the IGM, outside virialized halos.Comment: 52 pages, 26 figures, published in the Astrophysical Journal, 2011, ApJ, 731, 1

Autophosphorylation on S614 inhibits the activity and the transforming potential of BRAF

International audienceThe BRAF proto-oncogene serine/threonine-protein kinase, known as BRAF, belongs to the RAF kinase family. It regulates the MAPK/ERK signalling pathway affecting several cellular processes such as growth, survival, differentiation, and cellular transformation. BRAF is mutated in ~8% of all human cancers with the V600E mutation constituting ~90% of mutations. Here, we have used quantitative mass spectrometry to map and compare phosphorylation site patterns between BRAF and BRAF V600E. We identified sites that are shared as well as several quantitative differences in phosphorylation abundance. The highest difference is phosphorylation of S614 in the activation loop which is ~5fold enhanced in BRAF V600E. Mutation of S614 increases the kinase activity of both BRAF and BRAF V600E and the transforming ability of BRAF V600E. The phosphorylation of S614 is mitogen inducible and the result of autophosphorylation. These data suggest that phosphorylation at this site is inhibitory, and part of the physiological shut-down mechanism of BRAF signalling

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Characteristics of the diffuse astrophysical electron and tau neutrino flux with six years of IceCube high energy cascade data

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010 -- 2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated ($\sim 90 \%$) by electron and tau flavors. The flux, observed in the sensitive energy range from $16\,\mathrm{TeV}$ to $2.6\,\mathrm{PeV}$, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be $\gamma=2.53\pm0.07$ and a flux normalization for each neutrino flavor of $\phi_{astro} = 1.66^{+0.25}_{-0.27}$ at $E_{0} = 100\, \mathrm{TeV}$, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices $\gamma\leq2.28$ at $\ge3\sigma$ significance level. Due to high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below $\sim100\,{\rm{TeV}}$ compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p-value $\ge 0.06$). The sizable and smooth flux measured below $\sim 100\,{\rm{TeV}}$ remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi-LAT, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma-rays.Comment: 4 figures, 4 tables, includes supplementary materia

IceCube Search for Neutrinos Coincident with Compact Binary Mergers from LIGO-Virgo's First Gravitational-Wave Transient Catalog

Using the IceCube Neutrino Observatory, we search for high-energy neutrino emission coincident with compact binary mergers observed by the LIGO and Virgo gravitational wave (GW) detectors during their first and second observing runs. We present results from two searches targeting emission coincident with the sky localization of each gravitational wave event within a 1000 second time window centered around the reported merger time. One search uses a model-independent unbinned maximum likelihood analysis, which uses neutrino data from IceCube to search for point-like neutrino sources consistent with the sky localization of GW events. The other uses the Low-Latency Algorithm for Multi-messenger Astrophysics, which incorporates astrophysical priors through a Bayesian framework and includes LIGO-Virgo detector characteristics to determine the association between the GW source and the neutrinos. No significant neutrino coincidence is seen by either search during the first two observing runs of the LIGO-Virgo detectors. We set upper limits on the time-integrated neutrino emission within the 1000 second window for each of the 11 GW events. These limits range from 0.02-0.7 $\mathrm{GeV~cm^{-2}}$. We also set limits on the total isotropic equivalent energy, $E_{\mathrm{iso}}$, emitted in high-energy neutrinos by each GW event. These limits range from 1.7 $\times$ 10$^{51}$ - 1.8 $\times$ 10$^{55}$ erg. We conclude with an outlook for LIGO-Virgo observing run O3, during which both analyses are running in real time

Multimessenger Gamma-Ray and Neutrino Coincidence Alerts using HAWC and IceCube sub-threshold Data

The High Altitude Water Cherenkov (HAWC) and IceCube observatories, through the Astrophysical Multimessenger Observatory Network (AMON) framework, have developed a multimessenger joint search for extragalactic astrophysical sources. This analysis looks for sources that emit both cosmic neutrinos and gamma rays that are produced in photo-hadronic or hadronic interactions. The AMON system is running continuously, receiving sub-threshold data (i.e. data that is not suited on its own to do astrophysical searches) from HAWC and IceCube, and combining them in real-time. We present here the analysis algorithm, as well as results from archival data collected between June 2015 and August 2018, with a total live-time of 3.0 years. During this period we found two coincident events that have a false alarm rate (FAR) of $<1$ coincidence per year, consistent with the background expectations. The real-time implementation of the analysis in the AMON system began on November 20th, 2019, and issues alerts to the community through the Gamma-ray Coordinates Network with a FAR threshold of $<4$ coincidences per year.Comment: 14 pages, 5 figures, 3 table

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements