High-temperature Superconductivity in Layered Nitrides \beta-Lix_xMNCl (M = Ti, Zr, Hf): Insights from Density-functional Theory for Superconductors

We present an ab initio analysis with density functional theory for superconductors (SCDFT) to understand the superconducting mechanism of doped layered nitrides \beta-Li$_x$MNCl (M=Ti, Zr, and Hf). The current version of SCDFT is based on the Migdal-Eliashberg theory and has been shown to reproduce accurately experimental superconducting-transition temperatures Tc of a wide range of phonon-mediated superconductors. In the present case, however, our calculated Tc$\leq$4.3 K (M=Zr) and $\leq$10.5 K (M=Hf) are found to be less than a half of the experimental Tc. In addition, Tc obtained in the present calculation increases with the doping concentration x, opposite to that observed in the experiment. Our results indicate that we need to consider some elements missing in the present SCDFT based on the Migdal-Eliashberg theory.Comment: 18 pages, 13 figures, submitted to Physical Review

Current state of knowledge on Takotsubo Syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed

CREB is a critical regulator of normal hematopoiesis and leukemogenesis

The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

Universality of weak selection

Weak selection, which means a phenotype is slightly advantageous over another, is an important limiting case in evolutionary biology. Recently it has been introduced into evolutionary game theory. In evolutionary game dynamics, the probability to be imitated or to reproduce depends on the performance in a game. The influence of the game on the stochastic dynamics in finite populations is governed by the intensity of selection. In many models of both unstructured and structured populations, a key assumption allowing analytical calculations is weak selection, which means that all individuals perform approximately equally well. In the weak selection limit many different microscopic evolutionary models have the same or similar properties. How universal is weak selection for those microscopic evolutionary processes? We answer this question by investigating the fixation probability and the average fixation time not only up to linear, but also up to higher orders in selection intensity. We find universal higher order expansions, which allow a rescaling of the selection intensity. With this, we can identify specific models which violate (linear) weak selection results, such as the one--third rule of coordination games in finite but large populations.Comment: 12 pages, 3 figures, accepted for publication in Physical Review

Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites

Autoantibodies to insulin are a harbinger of autoimmunity in type 1 diabetes in humans and in non-obese diabetic mice. To understand the genesis of these autoantibodies, we investigated the interactions of insulin-specific T and B lymphocytes using T cell and B cell receptor transgenic mice. We found spontaneous anti-insulin germinal center (GC) formation throughout lymphoid tissues with GC B cells binding insulin. Moreover, because of the nature of the insulin epitope recognized by the T cells, it was evident that GC B cells presented a broader repertoire of insulin epitopes. Such broader recognition was reproduced by activating naive B cells ex vivo with a combination of CD40 ligand and interleukin 4. Thus, insulin immunoreactivity extends beyond the pancreatic lymph node–islets of Langerhans axis and indicates that circulating insulin, despite its very low levels, can have an influence on diabetogenesis

Spiralling out of control: 3D hydrodynamical modelling of the colliding winds in η \eta\thinspaceCarinae

Three dimensional (3D) adaptive-mesh refinement (AMR) hydrodynamical simulations of the wind-wind collision between the enigmatic super-massive star \etacar and its mysterious companion star are presented which include radiative driving of the stellar winds, gravity, optically-thin radiative cooling, and orbital motion. Simulations with static stars with a periastron passage separation reveal that the preshock companion star's wind speed is sufficiently reduced that radiative cooling in the postshock gas becomes important, permitting the runaway growth of non-linear thin shell (NTSI) instabilities which massively distort the WCR. However, large-scale simulations which include the orbital motion of the stars, show that orbital motion reduces the impact of radiative inhibition, and thus increases the acquired preshock velocities. As such, the postshock gas temperature and cooling time see a commensurate increase, and sufficient gas pressure is preserved to stabilize the WCR against catastrophic instability growth. We then compute synthetic X-ray spectra and lightcurves and find that, compared to previous models, the X-ray spectra agree much better with {\it XMM-Newton} observations just prior to periastron. The narrow width of the 2009 X-ray minimum can also be reproduced. However, the models fail to reproduce the extended X-ray mimimum from previous cycles. We conclude that the key to explaining the extended X-ray minimum is the rate of cooling of the companion star's postshock wind. If cooling is rapid then powerful NTSIs will heavily disrupt the WCR. Radiative inhibition of the companion star's preshock wind, albeit with a stronger radiation-wind coupling than explored in this work, could be an effective trigger.Comment: 25 pages, 20 figures, accepted for publication in Ap

Amplified biochemical oscillations in cellular systems

We describe a mechanism for pronounced biochemical oscillations, relevant to microscopic systems, such as the intracellular environment. This mechanism operates for reaction schemes which, when modeled using deterministic rate equations, fail to exhibit oscillations for any values of rate constants. The mechanism relies on amplification of the underlying stochasticity of reaction kinetics within a narrow window of frequencies. This amplification allows fluctuations to beat the central limit theorem, having a dominant effect even though the number of molecules in the system is relatively large. The mechanism is quantitatively studied within simple models of self-regulatory gene expression, and glycolytic oscillations.Comment: 35 pages, 6 figure