Diisopropylamide and TMP turbo-grignard reagents : a structural rationale for their contrasting reactivities

A neutral dimeric molecule in crystal form, the diisopropylamido turbo-Grignard reagent "(iPr2N)MgCl⋅LiCl" (see structure; blue N, red O, green Mg, yellow Cl, black C) separates into several charged ate species in dynamic exchange with each other in THF solution as determined by a combination of EXSY and DOSY NMR studies

Lamellar Structures of MUC2-Rich Mucin: A Potential Role in Governing the Barrier and Lubricating Functions of Intestinal Mucus

Mucus is a ubiquitous feature of mammalian wet epithelial surfaces, where it lubricates and forms a selective barrier that excludes a range of particulates, including pathogens, while hosting a diverse commensal microflora. The major polymeric component of mucus is mucin, a large glycoprotein formed by several MUC gene products, with MUC2 expression dominating intestinal mucus. A satisfactory answer to the question of how these molecules build a dynamic structure capable of playing such a complex role has yet to be found, as recent reports of distinct layers of chemically identical mucin in the colon and anomalously rapid transport of nanoparticles through mucus have emphasized. Here we use atomic force microscopy (AFM) to image a MUC2-rich mucus fraction isolated from pig jejunum. In the freshly isolated mucin fraction, we find direct evidence for trigonally linked structures, and their assembly into lamellar networks with a distribution of pore sizes from 20 to 200 nm. The networks are two-dimensional, with little interaction between lamellae. The existence of persistent cross-links between individual mucin polypeptides is consistent with a non-self-interacting lamellar model for intestinal mucus structure, rather than a physically entangled polymer network. We only observe collapsed entangled structures in purified mucin that has been stored in nonphysiological conditions

Chemical abundances in bright giants of the globular cluster M62 (NGC 6266)

With the exception of Terzan 5, all the Galactic globular clusters that possess significant metallicity spreads, such as omega Cen and M22, are preferentially the more luminous clusters with extended horizontal branches. Here we present radial velocities and chemical abundances for seven bright giants in the globular cluster M62, a previously little-studied cluster. With M_V = -9.18, M62 is the ninth most luminous Galactic globular cluster and has an extended horizontal branch. Within our sample, we find (i) no evidence for a dispersion in metallicity, [Fe/H], beyond the measurement uncertainties, (ii) star-to-star abundance variations for C, O, Na and Al with the usual correlations between these elements as seen in other globular clusters, and (iii) a global enrichment for the elements Zr, Ba and La at the level [X/Fe] = +0.4 dex. For elements heavier than La, the abundance ratios are consistent with the scaled-solar $r$-process distribution. Below La, the abundances are anomalous when compared to the scaled-solar s-process or r-process distributions. For these elements, the abundance signature in M62 is in agreement with predictions of the s-process from fast-rotating massive stars, although the high [Rb/Y] ratio we measure may be a challenge to this scenario.Comment: Accepted for publication in MNRA

Heavy Lift Launch Capability with a New Hydrocarbon Engine

The Advanced Concepts Office at NASA's George C. Marshall Space Flight Center was tasked to define the thrust requirement of a new liquid oxygen rich staged combustion cycle hydrocarbon engine that could be utilized in a launch vehicle to meet NASA s future heavy lift needs. Launch vehicle concepts were sized using this engine for different heavy lift payload classes. Engine out capabilities for one of the heavy lift configurations were also analyzed for increased reliability that may be desired for high value payloads or crewed missions. The applicability for this engine in vehicle concepts to meet military and commercial class payloads comparable to current ELV capability was also evaluated

NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent "go-to" group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA's design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer's needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces between the three disciplines used in the design process: weights and sizing, trajectory, and structural analysis. The tools used to perform such analysis are INtegrated Rocket Sizing (INTROS), Program to Optimize Simulated Trajectories (POST), and Launch Vehicle Analysis (LVA) respectively. The methods each discipline uses to streamline their particular part of the design process will also be discussed

NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent go-to group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA s design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer s needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces between the three disciplines used in the design process: weights and sizing, trajectory, and structural analysis. The tools used to perform such analysis are INtegrated Rocket Sizing (INTROS), Program to Optimize Simulated Trajectories (POST), and Launch Vehicle Analysis (LVA) respectively. The methods each discipline uses to streamline their particular part of the design process will also be discussed

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network

BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy \u3c9 \u3emonths\u27 duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% wereold, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups

Transcriptomic Analysis of Shiga-Toxigenic Bacteriophage Carriage Reveals a Profound Regulatory Effect on Acid Resistance in Escherichia coli

Shiga-toxigenic bacteriophages are converting lambdoid phages that impart the ability to produce Shiga toxin to their hosts. Little is known about the function of most of the genes carried by these phages or the impact that lysogeny has on the Escherichia coli host. Here we use next-generation sequencing to compare the transcriptomes of E. coli strains infected with an Stx phage, before and after triggering of the bacterial SOS response that initiates the lytic cycle of the phage. We were able to discriminate between bacteriophage genes expressed in the lysogenic and lytic cycles, and we describe transcriptional changes that occur in the bacterial host as a consequence of Stx phage carriage. Having identified upregulation of the glutamic acid decarboxylase (GAD) operon, confirmed by reverse transcription-quantitative PCR (RT-qPCR), we used phenotypic assays to establish the ability of the Stx prophage to confer a greater acid resistance phenotype on the E. coli host. Known phage regulators were overexpressed in E. coli, and the acid resistance of the recombinant strains was tested. The phage-encoded transcriptional regulator CII was identified as the controller of the acid response in the lysogen. Infection of an E. coli O157 strain, from which integrated Stx prophages were previously removed, showed increased acid resistance following infection with a nontoxigenic phage, ϕ24B. In addition to demonstrating this link between Stx phage carriage and E. coli acid resistance, with its implications for survival postingestion, the data set provides a number of other potential insights into the impact of lambdoid phage carriage on the biology of E. coli