Development of mainshaft seals for advanced air breathing propulsion systems, phase 1 Final report, 25 Jun. 1965 - 25 Jul. 1967

Comparison of gas film mainshaft seals with rubbing contract seals for high temperature, high speed, and high pressure gas turbine application

Quantum mechanics/molecular mechanics minimum free-energy path for accurate reaction energetics in solution and enzymes: Sequential sampling and optimization on the potential of mean force surface

To accurately determine the reaction path and its energetics for enzymatic and solution-phase reactions, we present a sequential sampling and optimization approach that greatly enhances the efficiency of the ab initio quantum mechanics/molecular mechanics minimum free-energy path (QM/MM-MFEP) method. In the QM/MM-MFEP method, the thermodynamics of a complex reaction system is described by the potential of mean force (PMF) surface of the quantum mechanical (QM) subsystem with a small number of degrees of freedom, somewhat like describing a reaction process in the gas phase. The main computational cost of the QM/MM-MFEP method comes from the statistical sampling of conformations of the molecular mechanical (MM) subsystem required for the calculation of the QM PMF and its gradient. In our new sequential sampling and optimization approach, we aim to reduce the amount of MM sampling while still retaining the accuracy of the results by first carrying out MM phase-space sampling and then optimizing the QM subsystem in the fixed-size ensemble of MM conformations. The resulting QM optimized structures are then used to obtain more accurate sampling of the MM subsystem. This process of sequential MM sampling and QM optimization is iterated until convergence. The use of a fixed-size, finite MM conformational ensemble enables the precise evaluation of the QM potential of mean force and its gradient within the ensemble, thus circumventing the challenges associated with statistical averaging and significantly speeding up the convergence of the optimization process. To further improve the accuracy of the QM/MM-MFEP method, the reaction path potential method developed by Lu and Yang [Z. Lu and W. Yang, J. Chem. Phys. 121, 89 (2004)] is employed to describe the QM/MM electrostatic interactions in an approximate yet accurate way with a computational cost that is comparable to classical MM simulations. The new method was successfully applied to two example reaction processes, the classical SN 2 reaction of Cl- + CH3 Cl in solution and the second proton transfer step of the reaction catalyzed by the enzyme 4-oxalocrotonate tautomerase. The activation free energies calculated with this new sequential sampling and optimization approach to the QM/MM-MFEP method agree well with results from other simulation approaches such as the umbrella sampling technique with direct QM/MM dynamics sampling, demonstrating the accuracy of the iterative QM/MM-MFEP method. © 2008 American Institute of Physics.published_or_final_versio

On the origins of oxygenic photosynthesis and aerobic respiration in Cyanobacteria

The origin of oxygenic photosynthesis in Cyanobacteria led to the rise of oxygen on Earth ~2.3 billion years ago, profoundly altering the course of evolution by facilitating the development of aerobic respiration and complex multicellular life. Here we report the genomes of 41 uncultured organisms related to the photosynthetic Cyanobacteria (class Oxyphotobacteria), including members of the class Melainabacteria and a new class of Cyanobacteria (class Sericytochromatia) that is basal to the Melainabacteria and Oxyphotobacteria. All members of the Melainabacteria and Sericytochromatia lack photosynthetic machinery, indicating that phototrophy was not an ancestral feature of the Cyanobacteria and that Oxyphotobacteria acquired the genes for photosynthesis relatively late in cyanobacterial evolution. We show that all three classes independently acquired aerobic respiratory complexes, supporting the hypothesis that aerobic respiration evolved after oxygenic photosynthesis

Pulsed flows at the high-altitude cusp poleward boundary, and associated ionospheric convection and particle signatures, during a cluster - FAST - SuperDARN - sondrestrom conjunction under a southwest

Particle and magnetic field observations during a magnetic conjunction Cluster 1-FAST-Søndrestrøm within the field of view of SuperDARN radars on 21 January 2001 allow us to draw a detailed, comprehensive and self-consistent picture at three heights of signatures associated with transient reconnection under a steady south-westerly IMF (clock angle ≈130◦). Cluster 1 was outbound through the high altitude (∼12RE ) exterior northern cusp tailward of the bifurcation line (geomagnetic Bx>0) when a solar wind dynamic pressure release shifted the spacecraft into a boundary layer downstream of the cusp. The centerpiece of the investigation is a series of flow bursts observed there by the spacecraft, which were accompanied by strong field pertur- bations and tailward flow deflections. Analysis shows these to be Alfven waves. We interpret these flow events as being due to a sequence of reconnected flux tubes, with field-aligned currents in the associated Alfven waves carrying stresses to the underlying ionosphere, a view strengthened by the other observations. At the magnetic footprint of the region of Cluster flow bursts, FAST observed an ion energy- latitude disperison of the stepped cusp type, with individual cusp ion steps corresponding to individual flow bursts. Simultaneously, the SuperDARN Stokkseyri radar observed very strong poleward-moving radar auroral forms (PMRAFs) which were conjugate to the flow bursts at Cluster. FAST was traversing these PMRAFs when it observed the cusp ion steps. The Søndrestrøm radar observed pulsed ionospheric flows (PIFs) just poleward of the convection reversal boundary. As at Cluster, the flow was eastward (tailward), implying a coherent eastward (tailward) motion of the hypothesized open flux tubes. The joint Søndrestrøm and FAST observations indicate that the open/closed field line boundary was equatorward of the convection reversal boundary by ∼2 deg. The unprecedented accuracy of the conjunction argues strongly for the validity of the interpretation of the various signatures as resulting from transient reconnection. In particular, the cusp ion steps arise on this pass from this origin, in consonance with the original pulsating cusp model. The observations point to the need of extending current ideas on the response of the ionosphere to transient reconnection. Specifically, it argues in favor of re-establishing the high-latitude boundary layer downstream of the cusp as an active site of momentum transfer

Mechanical Control of Spin States in Spin-1 Molecules and the Underscreened Kondo Effect

The ability to make electrical contact to single molecules creates opportunities to examine fundamental processes governing electron flow on the smallest possible length scales. We report experiments in which we controllably stretch individual cobalt complexes having spin S = 1, while simultaneously measuring current flow through the molecule. The molecule's spin states and magnetic anisotropy were manipulated in the absence of a magnetic field by modification of the molecular symmetry. This control enabled quantitative studies of the underscreened Kondo effect, in which conduction electrons only partially compensate the molecular spin. Our findings demonstrate a mechanism of spin control in single-molecule devices and establish that they can serve as model systems for making precision tests of correlated-electron theories.Comment: main text: 5 pages, 4 figures; supporting information attached; to appear in Science

Surgical management and longterm follow-up of non-parasitic hepatic cysts

BACKGROUND: Despite the increasing use of laparoscopic techniques, the optimal surgical approach for cystic liver disease has not been well defined. This study aims to determine the optimum operative approach for these patients. METHODS: Data were identified from the Lothian Surgical Audit, case note review and general practitioner contact. Patients were contacted and asked to complete the SF-36 questionnaire on quality of life. RESULTS: A total of 102 patients (67 with simple cysts, 31 with polycystic liver disease [PCLD], four with cystic tumours) underwent 62 laparoscopic deroofings, 15 open deroofings, 36 resections and one liver transplant between June 1985 and April 2006. The median follow-up was 77 months (range 3–250 months). Morbidity and recurrent symptom rates after laparoscopic surgery were greater in PCLD patients compared with simple cyst patients, at 31% (four patients) vs. 15% (seven patients) and 85% (11 patients) vs. 29% (24 patients), respectively. Four patients with simple cysts and eight with PCLD required further surgery. All patients with simple cysts had comparable quality of life after surgery. Patients with recurrent symptoms after surgery for PCLD had a significantly better quality of life following laparoscopic deroofing than after resection. CONCLUSIONS: Most simple cysts can be managed laparoscopically, but there is a definite role for open resection in some patients. Open deroofing is the preferred approach for a dominant cyst pattern in PCLD, whereas resection is necessary for diffuse cystic disease

A lower bound for the BCS functional with boundary conditions at infinity

We consider a many-body system of fermionic atoms interacting via a local pair potential and subject to an external potential within the framework of BCS theory. We measure the free energy of the whole sample with respect to the free energy of a reference state which allows us to define a BCS functional with boundary conditions at infinity. Our main result is a lower bound for this energy functional in terms of expressions that typically appear in Ginzburg-Landau functionals.Comment: 32 page

Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis

PURPOSE: Colon cancer is one of the most common human malignancies, yet studies have only begun to identify the multiple mechanisms that underlie the development of this tumor. In this study, we have identified a novel mechanism, dysregulation of endocytic sorting, which promotes colon cancer development. EXPERIMENTAL DESIGN: Immunohistochemical and microarray analyses were done on human colon cancer tissue specimens to determine the levels of one endocytic protein, sorting nexin 1 (SNX1). SW480 cells, a human colon cancer cell line that retains a relatively high level of SNX1 expression, were used to assess the effects of down-regulating this protein by small hairpin RNA. Activation of signal transduction cascades was evaluated in these cells using Western blotting, and multiple functional assays were done. RESULTS: We determined by immunohistochemistry that the level of SNX1 was significantly down-regulated in 75% of human colon cancers. In corroborative studies using microarray analysis, SNX1 message was significantly decreased (log(2) ratio less than -1) for 8 of 19 colon carcinomas. Cell lines with reduced SNX1 levels showed increased proliferation, decreased apoptosis, and decreased susceptibility to anoikis. They also showed increased activation of epidermal growth factor receptor and extracellular signal-regulated kinase 1/2 in response to epidermal growth factor. This increased activation was abolished by inhibition of endocytosis. CONCLUSIONS: These data suggest that loss of SNX1 may play a significant role in the development and aggressiveness of human colon cancer, at least partially through the mechanism of increased signaling from endosomes. Further, these findings suggest that dysregulation of endocytic proteins may represent a new paradigm in the process of carcinogenesis.Fil: Nguyen, Lananh N.. University of Washington; Estados UnidosFil: Holdren, Matthew S.. University of Washington; Estados UnidosFil: Nguyen, Anthony P.. Baylor College of Medicine; Estados UnidosFil: Furuya, Momoko H.. University of Washington; Estados UnidosFil: Bianchini, Michele. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Levy, Estrella Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Liu, Annie. University of Washington; Estados UnidosFil: Guncay, Gabriela D.. University of Washington; Estados UnidosFil: Campbell, Jean S.. University of Washington; Estados UnidosFil: Parks, W. Tony. University of Washington; Estados Unido