Non-neutral processes drive the nucleotide composition of non-coding sequences in Drosophila

The nature of the forces affecting base composition is a key question in genome evolution. There is uncertainty as to whether differences in the GC contents of non-coding sequences reflect differences in mutational bias, or in the intensity of selection or biased gene conversion. We have used a polymorphism dataset for non-coding sequences on the X chromosome of Drosophila simulans to examine this question. The proportion of GC→AT versus AT→GC polymorphic mutations in a locus is correlated with its GC content. This implies the action of forces that favour GC over AT base pairs, which are apparently strongest in GC-rich sequences

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

Standard and generalized McDonald–Kreitman test: a website to detect selection by comparing different classes of DNA sites

The McDonald and Kreitman test (MKT) is one of the most powerful and extensively used tests to detect the signature of natural selection at the molecular level. Here, we present the standard and generalized MKT website, a novel website that allows performing MKTs not only for synonymous and nonsynonymous changes, as the test was initially described, but also for other classes of regions and/or several loci. The website has three different interfaces: (i) the standard MKT, where users can analyze several types of sites in a coding region, (ii) the advanced MKT, where users can compare two closely linked regions in the genome that can be either coding or noncoding, and (iii) the multi-locus MKT, where users can analyze many separate loci in a single multi-locus test. The website has already been used to show that selection efficiency is positively correlated with effective population size in the Drosophila genus and it has been applied to include estimates of selection in DPDB. This website is a timely resource, which will presumably be widely used by researchers in the field and will contribute to enlarge the catalogue of cases of adaptive evolution. It is available at http://mkt.uab.es

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

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

A Comprehensive Framework for Human Resources for Health System Development in Fragile and Post-Conflict States

Noriko Fujita and colleagues offer a comprehensive framework for human resource system development, based upon experiences in three fragile and post-conflict health systems: Afghanistan, the Democratic Republic of Congo, and Cambodia

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

Continuous Energy Management of the HVAC&R System in an Office Building System Operation and Energy Consumption for the Eight Years after Building Completion

The authors continuously studied the energy consumption of a heating, ventilating, air- conditioning and refrigerating (HVAC&R) system in an office for the operation of the system in terms of its expected performance. A fault in the system control setting was detected, and the system performance improved significantly as a result of correcting the fault. Recently, however, problematic issues, such as the malfunction of chillers and deteriorated performance of the heat exchangers, have emerged, resulting in the degradation of overall system performance. This paper describes (a) changes in the energy consumption of the building over a period of eight years during which the HVAC&R system was operated, and (b) problematic issues that arose during system operation in order to identify the energy-saving effects of the system found when energy management of the building is continuously practiced. In this HVAC&R system, about 25% of electric power consumption for wintertime could be saved by checking the system operation during the first two years. After that, the electric power consumption gradually increased due to the system deterioration until 2004, but it decreased again by properly dealing with the problems