A parallel three stranded α-helical bundle at the nucleation site of collagen triple-helix formation

AbstractA short stretch of 35 amino acids is identified as the structural motif responsible for the tight parallel association and trimerization of the three identical polypeptide chains of lung surfactant protein D, which contains both collagen regions and C-type lectin domains. This ‘neck-region’ is located at the nucleation site at which the collagenous sequences fold into a staggered triple-helix and is shown, by CD, NMR, and cross-linking of recombinant peptides, to consist of a triple-stranded parallel α-helical bundle in a non-staggered, and extremely strong, non-covalent association. This type of association between three polypeptide chains may represent a common structural feature immediately following the C-terminal end of the triple-helical region of collagenous proteins

Notes on Recent Cases

Notes on recent cases by J. P. Guadnola, Kenneth Konop, William H. Konop, A. J. Barlow, J. H. Tuberty, Francis G. Fedder, and William Lee O\u27Malley

Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

UnlabelledMigalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.Trial registrationClinicalTrials.gov NCT01196871

Portfolio Vol. II N 2

Browne, Phil. Beaver ad Sawyer at Night . Picture. 2. Varney, Chester. To Dream Beyond . Prose. 3. West, Bill C. Admonition Poem. 6. West, Bill C. Insomnia Poem. 6. Barlow, Don. Heart Determines . Prose. 7. Gordon, Robert. From an Unknown Innocent to... Poem, 11. Black, James. Playing Around . Prose. 13. Parsons, Edith. The Turtle Baby . Picture. 14. Deeds, Ed. Raymond Scott - - Classic Swing . Prose. 15. Schrechkengost, Viktor. Black Sheep-The Creature God Forgot . Picture. 14. Smith, Bob. Review of New Recordings . Prose. 15. Saunders, Paul. Book Reviews and Comments . Prose. 16. Browne, Phil. to Patsy . Picture. 17. Sandor, Joseph. Meditation . Picture. 18. Maxwell, Kenneth. Unnamed. Poem. 18. Sweitzer, Harry J. Social Life at Denison . Prose. 19. Flory Doris. The Student Rationalizes . Poem. 20. Flory Doris. On Noisess . Poem. 20. Bethune, Don. Senior\u27s Lament . Poem. 20. Flory, Doris. Lines on Lines . Poem. 20. Beckham, Adela. My Man . Poem. 20

Investigation of Vapor-Phase Lubrication in a Gas Turbine Engine,"

ABSTRACT The liquid oil lubrication system of current aircraft jet engines accounts for approximately 10-15% of the total weight of the engine. It has long been a koal of the aircraft gas turbine industry to reduce this weight. Vapor-Phase Lubrication (VPL) is a promising technology to eliminate liquid oil lubrication. The current investigation resulted in the first gas turbine to operate in the absence of conventional liquid lubrication. A phosphate ester, commercially known as DURAD 6208, was chosen for the test. Extensive research at Wright Laboratory demonstrated that this lubricant could reliably lubricate rolling element bearings in the gas turbine engine environment. The Allison T63 engine was selected as the test vehicle because of its small size and bearing configuration. Specifically, VPL was evaluated in the number eight bearing because it is located in a relatively hot environment, in line with the combustor discharge, and it can be isolated from the other bearings and the liquid lubrication system. The bearing was fully instrumented and its performance with standard oil lubrication was documented. Results of this baseline study were used to develop a thermodynamic model to predict the bearing temperature with VPL. The engine was then operated at a ground idle condition with VPL with the lubricant misted into the #8 bearing at 13 ml/hr. The bearing temperature stabilized at 283°C within 10 minutes. Engine operation was continued successfully for a total of one hour. No abnormal wear of the rolling contact surfaces was found when the bearing was later examined. Bearing temperatures after engine shutdown indicated the bearing had reached thermodynamic equilibrium with its surroundings during the test. After shutdown bearing temperatures steadily decreased without the soakback effect seen after shutdown in standard lubricated bearings. In contrast, the oil lubricated bearing ran at a considerably lower operating temperature (83°C) and was significantly heated by its surroundings after engine shutdown. In the baseline tests, the final bearing temperatures never reached that of the operating VPL system. NOMENCLATUR

OMG Do Not Say LOL: Obese Adolescents' Perspectives on the Content of Text Messages to Enhance Weight Loss Efforts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93769/1/oby.2011.266.pd

Exploring Gusev Crater with spirit: Review of science objectives and testable hypotheses

Gusev Crater was selected as the landing site for the Mars Exploration Rover (MER) Spirit mission. Located at the outlet of Ma'adim Vallis and 250 km south of the volcano Apollinaris Patera, Gusev is an outstanding site to achieve the goals of the MER mission. The crater could have collected sediments from a variety of sources during its 3.9 Ga history, including fluvial, lacustrine, volcanic, glacial, impact, regional and local aeolian, and global air falls. It is a unique site to investigate the past history of water on Mars, climate and geological changes, and the potential habitability of the planet, which are central science objectives of the MER mission. Because of its complex history and potential diversity, Gusev will allow the testing of a large spectrum of hypotheses with the complete suite of MER instruments. Evidence consistent with long-lived lake episodes exist in the landing ellipse area. They might offer a unique opportunity to study, for the first time, Martian aqueous sediments and minerals formed in situ in their geological context. We review the geological history and diversity of the landing site, the science hypotheses that can be tested during the MER mission, and the relevance of Gusev to the MER mission objectives and payload

N plus 3 Advanced Concept Studies for Supersonic Commercial Transport Aircraft Entering Service in the 2030-2035 Period

Boeing, with Pratt & Whitney, General Electric, Rolls-Royce, M4 Engineering, Wyle Laboratories and Georgia Institute of Technology, conducted a study of supersonic commercial aircraft concepts and enabling technologies for the year 2030-2035 timeframe. The work defined the market and environmental/regulatory conditions that could evolve by the 2030/35 time period, from which vehicle performance goals were derived. Relevant vehicle concepts and technologies are identified that are anticipated to meet these performance and environmental goals. A series of multidisciplinary analyses trade studies considering vehicle sizing, mission performance and environmental conformity determined the appropriate concepts. Combinations of enabling technologies and the required technology performance levels needed to meet the desired goals were identified. Several high priority technologies are described in detail, including roadmaps with risk assessments that outline objectives, key technology challenges, detailed tasks and schedules and demonstrations that need to be performed. A representative configuration is provided for reference purposes, along with associated performance estimates based on these key technologies

Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.