Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1 , JAK3 , STAT3 , and SOCS1 . We also identified mutations in KRAS , TP53 , and TERT . Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes

Constraining the rp-process by measuring 23

The 23Al(p, γ)24Si stellar reaction rate has a significant impact on the light-curve emitted in X-ray bursts. Theoretical calculations show that the reaction rate is mainly determined by the properties of direct capture as well as low-lying 2+ states and a possible 4+ state in 24Si. Currently, there is little experimental information on the properties of these states. In this proceeding we will present a new experimental study to investigate this reaction, using the surrogate reaction 23Al(d,n) at 47 AMeV at the National Superconducting Cyclotron Laboratory (NSCL). We will discuss our new experimental setup which allows us to use full kinematics employing the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to detect the γ-rays following the de-excitation of excited states of the reaction products and the Low Energy Neutron Detector Array (LENDA) to detect the recoiling neutrons. The S800 was used for identification of the 24Si recoils. As a proof of principle to show the feasibility of this concept the Q-value spectrum of 22Mg(d,n)23Al is reconstructed

Searching for stochastic gravitational waves using data from the two colocated LIGO Hanford detectors

Searches for a stochastic gravitational-wave background (SGWB) using terrestrial detectors typically involve cross-correlating data from pairs of detectors. The sensitivity of such cross-correlation analyses depends, among other things, on the separation between the two detectors: the smaller the separation, the better the sensitivity. Hence, a colocated detector pair is more sensitive to a gravitational-wave background than a noncolocated detector pair. However, colocated detectors are also expected to suffer from correlated noise from instrumental and environmental effects that could contaminate the measurement of the background. Hence, methods to identify and mitigate the effects of correlated noise are necessary to achieve the potential increase in sensitivity of colocated detectors. Here we report on the first SGWB analysis using the two LIGO Hanford detectors and address the complications arising from correlated environmental noise. We apply correlated noise identification and mitigation techniques to data taken by the two LIGO Hanford detectors, H1 and H2, during LIGO’s fifth science run. At low frequencies, 40–460 Hz, we are unable to sufficiently mitigate the correlated noise to a level where we may confidently measure or bound the stochastic gravitational-wave signal. However, at high frequencies, 460–1000 Hz, these techniques are sufficient to set a 95% confidence level upper limit on the gravitational-wave energy density of Ω(f) < 7.7 × 10[superscript -4](f/900  Hz)[superscript 3], which improves on the previous upper limit by a factor of ~180. In doing so, we demonstrate techniques that will be useful for future searches using advanced detectors, where correlated noise (e.g., from global magnetic fields) may affect even widely separated detectors.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio

Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models

Although abnormal TGFβ signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, its precise role in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to elucidate the role of TGFβ signaling in three Fbn1 mutant mouse models representing a range of aortic disease from microdissection (without aneurysm) to aneurysm (without rupture) to aneurysm and rupture. Results indicated that reduced TGFβ signaling and increased mast cell proteases were associated with microdissection. In contrast, increased abundance of extracellular matrix proteins, which could be reporters for positive TGFβ signaling, were associated with aneurysm. Marked reductions in collagens and fibrillins, and increased TGFβ signaling, were associated with aortic rupture. Our data indicate that TGFβ signaling performs context-dependent roles in the pathogenesis of thoracic aortic disease

Constraining the rp-process by measuring 23Al(d,n)24Si with GRETINA and LENDA at NSCL

The 23Al(p, γ)24Si stellar reaction rate has a significant impact on the light-curve emitted in X-ray bursts. Theoretical calculations show that the reaction rate is mainly determined by the properties of direct capture as well as low-lying 2+ states and a possible 4+ state in 24Si. Currently, there is little experimental information on the properties of these states. In this proceeding we will present a new experimental study to investigate this reaction, using the surrogate reaction 23Al(d,n) at 47 AMeV at the National Superconducting Cyclotron Laboratory (NSCL). We will discuss our new experimental setup which allows us to use full kinematics employing the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to detect the γ-rays following the de-excitation of excited states of the reaction products and the Low Energy Neutron Detector Array (LENDA) to detect the recoiling neutrons. The S800 was used for identification of the 24Si recoils. As a proof of principle to show the feasibility of this concept the Q-value spectrum of 22Mg(d,n)23Al is reconstructed

Constraining the rp-process by measuring 23Al(d,n)24Si with GRETINA and LENDA at NSCL

The 23Al(p, γ)24Si stellar reaction rate has a significant impact on the light-curve emitted in X-ray bursts. Theoretical calculations show that the reaction rate is mainly determined by the properties of direct capture as well as low-lying 2+ states and a possible 4+ state in 24Si. Currently, there is little experimental information on the properties of these states. In this proceeding we will present a new experimental study to investigate this reaction, using the surrogate reaction 23Al(d,n) at 47 AMeV at the National Superconducting Cyclotron Laboratory (NSCL). We will discuss our new experimental setup which allows us to use full kinematics employing the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to detect the γ-rays following the de-excitation of excited states of the reaction products and the Low Energy Neutron Detector Array (LENDA) to detect the recoiling neutrons. The S800 was used for identification of the 24Si recoils. As a proof of principle to show the feasibility of this concept the Q-value spectrum of 22Mg(d,n)23Al is reconstructed

Constraining the rp-process by measuring

The 23Al(p, γ)24Si stellar reaction rate has a significant impact on the light-curve emitted in X-ray bursts. Theoretical calculations show that the reaction rate is mainly determined by the properties of direct capture as well as low-lying 2+ states and a possible 4+ state in 24Si. Currently, there is little experimental information on the properties of these states. In this proceeding we will present a new experimental study to investigate this reaction, using the surrogate reaction 23Al(d,n) at 47 AMeV at the National Superconducting Cyclotron Laboratory (NSCL). We will discuss our new experimental setup which allows us to use full kinematics employing the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to detect the γ-rays following the de-excitation of excited states of the reaction products and the Low Energy Neutron Detector Array (LENDA) to detect the recoiling neutrons. The S800 was used for identification of the 24Si recoils. As a proof of principle to show the feasibility of this concept the Q-value spectrum of 22Mg(d,n)23Al is reconstructed

X-ray Burst Studies with the JENSA Gas Jet Target

When a neutron star accretes hydrogen and helium from the outer layers of its companion star, thermonuclear burning enables the αp-process as a break out mechanism from the hot CNO cycle. Model calculations predict (α, p) reaction rates significantly affect both the light curves and elemental abundances in the burst ashes. The Jet Experiments in Nuclear Structure and Astrophysics (JENSA) gas jet target enables the direct measurement of previously inaccessible (α,p) reactions with radioactive beams provided by the rare isotope re-accelerator ReA3 at the National Superconducting Cyclotron Laboratory (NSCL), USA. JENSA is going to be the main target for the Recoil Separator for Capture Reactions (SECAR) at the Facility for Rare Isotope Beams (FRIB). Commissioning of JENSA and first experiments at Oak Ridge National Laboratory (ORNL) showed a highly localized, pure gas target with a density of ∼1019 atoms per square centimeter. Preliminary results are presented from the first direct cross section measurement of the 34Ar(α, p)37 K reaction at NSCL