Aneurysms of the sinuses of Valsalva, when detected before rupture, are repaired electively. When they are small, they are most frequently repaired by direct closure; when they are large, they are repaired with a prosthetic patch. When they are associated with prolapse of the corresponding aortic cusp and aortic insufficiency, valve replacement is usually performed concomitantly. We present the case of a patient in whom both abnormalities were corrected by implantation of a Freestyle® bioprosthesis, the wall of which completely excluded the aneurysm of the sinus of Valsalva. The patient remains asymptomatic 18 months after surgery. (Tex Heart Inst J 2003;30:202–4)

The accelerating expansion of the universe is the most surprising cosmological discovery in many decades. In this short review, we briefly summarize theories for the origin of cosmic acceleration and the observational methods being used to test these theories. We then discuss the current observational state of the field, with constraints from the cosmic microwave background (CMB), baryon acoustic oscillations (BAO), Type Ia supernovae (SN), direct measurements of the Hubble constant ($H_0$), and measurements of galaxy and matter clustering. Assuming a flat universe and dark energy with a constant equation-of-state parameter $w = P/\rho$, the combination of Planck CMB temperature anisotropies, WMAP CMB polarization, the Union2.1 SN compilation, and a compilation of BAO measurements yields $w = -1.10^{+0.08}_{-0.07}$, consistent with a cosmological constant ($w=-1$). However, with these constraints the cosmological constant model predicts a value of $H_0$ that is lower than several of the leading recent estimates, and it predicts a parameter combination $\sigma_8(\Omega_m)^{0.5}$ that is higher than many estimates from weak gravitational lensing, galaxy clusters, and redshift-space distortions. Individually these tensions are only significant at the ~$2\sigma$ level, but they arise in multiple data sets with independent statistics and distinct sources of systematic uncertainty. The tensions are stronger with Planck CMB data than they were with WMAP because of the smaller statistical errors and the higher central value of $\Omega_m.$ With the improved measurements expected from the next generation of data sets, these tensions may diminish, or they may sharpen in a way that points towards a more complete physical understanding of cosmic acceleration.

Ribosomes can stall during translation due to defects in the mRNA template or translation machinery, leading to the production of incomplete proteins. The Ribosome-associated Quality control Complex (RQC) engages stalled ribosomes and targets nascent polypeptides for proteasomal degradation. However, how each RQC component contributes to this process remains unclear. Here we demonstrate that key RQC activities-Ltn1p-dependent ubiquitination and Rqc2p-mediated Carboxy-terminal Alanine and Threonine (CAT) tail elongation-can be recapitulated in vitro with a yeast cell-free system. Using this approach, we determined that CAT tailing is mechanistically distinct from canonical translation, that Ltn1p-mediated ubiquitination depends on the poorly characterized RQC component Rqc1p, and that the process of CAT tailing enables robust ubiquitination of the nascent polypeptide. These findings establish a novel system to study the RQC and provide a framework for understanding how RQC factors coordinate their activities to facilitate clearance of incompletely synthesized proteins.

Changes in the 5' leader of an mRNA can have profound effects on its translational efficiency with little effect on abundance. Sequencing-based methods to accurately map the 5' leader by identifying the first transcribed nucleotide rely on enzymatic removal of the 5' eukaryotic cap structure by tobacco acid pyrophosphatase (TAP). However, commercial TAP production has been problematic and has now been discontinued. RppH, a bacterial enzyme that can also cleave the 5' cap, and Cap-Clip, a plant-derived enzyme, have been marketed as TAP replacements. We have engineered a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme that functions as a superior TAP replacement. It can be purified from E. coli overexpression in high yields using standard biochemical methods. This constitutively active enzyme is four orders of magnitude more catalytically efficient than RppH at 5' cap removal, compares favorably to Cap-Clip, and the 5' monophosphorylated RNA product is suitable for standard RNA cloning methods. This engineered enzyme is a better replacement for TAP treatment than the current marketed use of RppH and can be produced cost-effectively in a general laboratory setting, unlike Cap-Clip.

The cold dark matter (CDM) cosmological model has been remarkably successful in explaining cosmic structure over an enormous span of redshift, but it has faced persistent challenges from observations that probe the innermost regions of dark matter halos and the properties of the Milky Way's dwarf galaxy satellites. We review the current observational and theoretical status of these "small-scale controversies." Cosmological simulations that incorporate only gravity and collisionless CDM predict halos with abundant substructure and central densities that are too high to match constraints from galaxy dynamics. The solution could lie in baryonic physics: Recent numerical simulations and analytical models suggest that gravitational potential fluctuations tied to efficient supernova feedback can flatten the central cusps of halos in massive galaxies, and a combination of feedback and low star formation efficiency could explain why most of the dark matter subhalos orbiting the Milky Way do not host visible galaxies. However, it is not clear that this solution can work in the lowest mass galaxies, where discrepancies are observed. Alternatively, the small-scale conflicts could be evidence of more complex physics in the dark sector itself. For example, elastic scattering from strong dark matter self-interactions can alter predicted halo mass profiles, leading to good agreement with observations across a wide range of galaxy mass. Gravitational lensing and dynamical perturbations of tidal streams in the stellar halo provide evidence for an abundant population of low-mass subhalos in accord with CDM predictions. These observational approaches will get more powerful over the next few years.

Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates.

For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the "alarmin" IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. PAPERCLIP.

We present the measurements and modelling of the projected and redshift-space clustering of CMASS galaxies in the Sloan Digital Sky Survey-III Baryon Oscillation Spectroscopic Survey Data Release 11. For a volume-limited luminous red galaxy sample in the redshift range of 0.48 < z < 0.55, we perform halo occupation distribution modelling of the small- and intermediate-scale (0.1-60 h-1 Mpc) projected and redshift-space two-point correlation functions, with an accurate model built on high-resolution N-body simulations. To interpret the measured redshift-space distortions, the distribution of galaxy velocities must differ from that of the dark matter inside haloes of ~1013-1014 h-1 M⊙, i.e. the data require the existence of galaxy velocity bias. Most notably, central galaxies on average are not at rest with respect to the core of their host haloes, but rather move around it with a 1D velocity dispersion of 0.22-0.04+0.03 times that of the dark matter, implying a spatial offset from the centre at the level of ≲1 per cent of the halo virial radius. The luminous satellite galaxies move more slowly than the dark matter, with velocities 0.86-0.03+0.08 times those of the dark matter, which suggests that the velocity and spatial distributions of these satellites cannot both be unbiased. The constraints mainly arise from the Fingers-of-God effect at non-linear scales and the smoothing to the Kaiser effect in the translinear regime; the robustness of the results is demonstrated by a variety of tests. We discuss the implications of the existence of galaxy velocity bias for investigations of galaxy formation and cosmology.

We measure the two-point clustering of spectroscopically confirmed quasars from the final sample of the Baryon Oscillation Spectroscopic Survey (BOSS) on comoving scales of 4 ≲ s ≲ 22 h-1 Mpc. The sample covers 6950 deg2 [~19 (h-1Gpc)3] and, over the redshift range 2.2 ≲ z ≲ 2.8, contains 55 826 homogeneously selected quasars, which is twice as many as in any similar work. We deduce bQ = 3.54 ± 0.10; the most precise measurement of quasar bias to date at these redshifts. This corresponds to a host halo mass of ~2 × 1012 h-1M⊙ with an implied quasar duty cycle of ~1 per cent. The real-space projected correlation function is well fitted by a power law of index 2 and correlation length r0 = (8.12 ± 0.22) h-1 Mpc over scales of 4 ≲ rp ≲ 25 h-1 Mpc. To better study the evolution of quasar clustering at moderate redshift, we extend the redshift range of our study to z ~ 3.4 and measure the bias and correlation length of three subsamples over 2.2 ≲ z ≲ 3.4. We find no significant evolution of r0 or bias over this range, implying that the host halo mass of quasars decreases somewhat with increasing redshift. We find quasar clustering remains similar over a decade in luminosity, contradicting a scenario in which quasar luminosity is monotonically related to halo mass at z ≈ 2.5. Our results are broadly consistent with previous BOSS measurements, but they yield more precise constraints based upon a larger and more uniform data set.

The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation¹. Mutations in DDX3 are linked to tumorigenesis^2-4 and intellectual disability⁵, and the enzyme is targeted by a range of viruses⁶. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions.