Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids : A Historical Cohort Study

This work was supported by the Respiratory Effectiveness Group. Acknowledgments We thank the Respiratory Effectiveness Group for funding this work, Annie Burden for assistance with statistics, and Simon Van Rysewyk and Lisa Law for assistance with medical writing.Peer reviewedPostprin

Power-law distributions for the areas of the basins of attraction on a potential energy landscape

Energy landscape approaches have become increasingly popular for analysing a wide variety of chemical physics phenomena. Basic to many of these applications has been the inherent structure mapping, which divides up the potential energy landscape into basins of attraction surrounding the minima. Here, we probe the nature of this division by introducing a method to compute the basin area distribution and applying it to some archetypal supercooled liquids. We find that this probability distribution is a power law over a large number of decades with the lower-energy minima having larger basins of attraction. Interestingly, the exponent for this power law is approximately the same as that for a high-dimensional Apollonian packing, providing further support for the suggestion that there is a strong analogy between the way the energy landscape is divided into basins, and the way that space is packed in self-similar, space-filling hypersphere packings, such as the Apollonian packing. These results suggest that the basins of attraction provide a fractal-like tiling of the energy landscape, and that a scale-free pattern of connections between the minima is a general property of energy landscapes.Comment: 4 pages, 3 figure

Southwest Research Institute assistance to NASA in biomedical areas of the technology utilization program Final report, 1 Nov. 1967 - 30 Nov. 1968

Southwest Research Institute activities in technology utilization program in biomedical areas, Nov. 1967 - Nov. 196

Lymphoid Hyperplasia and Lymphoma in Transgenic Mice Expressing the Small Non-Coding RNA, EBER1 of Epstein-Barr Virus

Non-coding RNAs have critical functions in diverse biological processes, particularly in gene regulation. Viruses, like their host cells, employ such functional RNAs and the human cancer associated Epstein-Barr virus (EBV) is no exception. Nearly all EBV associated tumours express the EBV small, non-coding RNAs (EBERs) 1 and 2, however their role in viral pathogenesis remains largely obscure.To investigate the action of EBER1 in vivo, we produced ten transgenic mouse lines expressing EBER1 in the lymphoid compartment using the mouse immunoglobulin heavy chain intronic enhancer Emicro. Mice of several of these EmicroEBER1 lines developed lymphoid hyperplasia which in some cases proceeded to B cell malignancy. The hallmark of the transgenic phenotype is enlargement of the spleen and mesenteric lymph nodes and in some cases enlargement of the thymus, liver and peripheral lymph nodes. The tumours were found to be of B cell origin and showed clonal IgH rearrangements. In order to explore if EBER1 would cooperate with c-Myc (deregulated in Burkitt's lymphoma) to accelerate lymphomagenesis, a cross-breeding study was undertaken with EmicroEBER1 and EmicroMyc mice. While no significant reduction in latency to lymphoma onset was observed in bi-transgenic mice, c-Myc induction was detected in some EmuEBER1 single transgenic tumours, indicative of a functional cooperation.This study is the first to describe the in vivo expression of a polymerase III, non-coding viral gene and demonstrate its oncogenic potential. The data suggest that EBER1 plays an oncogenic role in EBV associated malignant disease

Applying UK real world primary care data to predict asthma attacks in 3776 well-characterised children : a retrospective cohort study

FUNDING This analysis was funded by Respiratory Effectiveness Group DATA AVAILABILITY STATEMENT Data are available from Clinical Practice Research Datalink (https://www.cprd.com/home/) and Optimum Patient Care (http://optimumpatientcare.org/about-us/).Peer reviewedPublisher PD

Role of the C-terminal domain in the structure and function of tetrameric sodium channels

Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil

Multi-technique equation of state for Fe_(2)SiO_4 melt and the density of Fe-bearing silicate melts from 0 to 161 GPa

We have conducted new equation of state measurements on liquid Fe_(2)SiO_4 in a collaborative, multi-technique study. The liquid density (ρ), the bulk modulus (K), and its pressure derivative (K′) were measured from 1 atm to 161 GPa using 1-atm double-bob Archimedean, multi-anvil sink/float, and shock wave techniques. Shock compression results on initially molten Fe_(2)SiO_4 (1573 K) fitted with previous work and the ultrasonically measured bulk sound speed (C_o) in shock velocity (U_S)-particle velocity (u_p) space yields the Hugoniot: U_S = 1.58(0.03) u_p + 2.438(0.005) km/s. Sink/float results are in agreement with shock wave and ultrasonic data, consistent with an isothermal K_T = 19.4 GPa and K′ = 5.33 at 1500°C. Shock melting of initially solid Fe_(2)SiO_4 (300 K) confirms that the Grüneisen parameter (γ) of this liquid increases upon compression where γ = γ_o(ρ_(o)/ρ)^q yields a q value of –1.45. Constraints on the liquid fayalite EOS permit the calculation of isentropes for silicate liquids of general composition in the multicomponent system CaO-MgO-Al_(2)O_3-SiO_2-FeO at elevated temperatures and pressures. In our model a whole mantle magma ocean would first crystallize in the mid-lower mantle or at the base of the mantle were it composed of either peridotite or simplified “chondrite” liquid, respectively. In regards to the partial melt hypothesis to explain the occurrence and characteristics of ultra-low velocity zones, neither of these candidate liquids would be dense enough to remain at the core mantle boundary on geologic timescales, but our model defines a compositional range of liquids that would be gravitationally stable

Multi‐technique equation of state for Fe 2 SiO 4 melt and the density of Fe‐bearing silicate melts from 0 to 161 GPa

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95366/1/jgrb17308.pd