Asp295 Stabilizes the Active-Site Loop Structure of Pyruvate Dehydrogenase, Facilitating Phosphorylation of Ser292 by Pyruvate Dehydrogenase-Kinase

We have developed an in vitro system for detailed analysis of reversible phosphorylation of the plant mitochondrial pyruvate dehydrogenase complex, comprising recombinant Arabidopsis thalianaα2β2-heterotetrameric pyruvate dehydrogenase (E1) plus A. thaliana E1-kinase (AtPDK). Upon addition of MgATP, Ser292, which is located within the active-site loop structure of E1α, is phosphorylated. In addition to Ser292, Asp295 and Gly297 are highly conserved in the E1α active-site loop sequences. Mutation of Asp295 to Ala, Asn, or Leu greatly reduced phosphorylation of Ser292, while mutation of Gly297 had relatively little effect. Quantitative two-hybrid analysis was used to show that mutation of Asp295 did not substantially affect binding of AtPDK to E1α. When using pyruvate as a variable substrate, the Asp295 mutant proteins had modest changes in kcat, Km, and kcat/Km values. Therefore, we propose that Asp295 plays an important role in stabilizing the active-site loop structure, facilitating transfer of the γ-phosphate from ATP to the Ser residue at regulatory site one of E1α

Smeared versus localised sources in flux compactifications

We investigate whether vacuum solutions in flux compactifications that are obtained with smeared sources (orientifolds or D-branes) still survive when the sources are localised. This seems to rely on whether the solutions are BPS or not. First we consider two sets of BPS solutions that both relate to the GKP solution through T-dualities: (p+1)-dimensional solutions from spacetime-filling Op-planes with a conformally Ricci-flat internal space, and p-dimensional solutions with Op-planes that wrap a 1-cycle inside an everywhere negatively curved twisted torus. The relation between the solution with smeared orientifolds and the localised version is worked out in detail. We then demonstrate that a class of non-BPS AdS_4 solutions that exist for IASD fluxes and with smeared D3-branes (or analogously for ISD fluxes with anti-D3-branes) does not survive the localisation of the (anti) D3-branes. This casts doubts on the stringy consistency of non-BPS solutions that are obtained in the limit of smeared sources.Comment: 23 pages; v2: minor corrections, added references, version published in JHE

Bearing signal separation enhancement with application to helicopter transmission system

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Bearing vibration signal separation is essential for fault detection of gearboxes, especially where the vibration is nonstationary, susceptible to background noise, and subjected to an arduous transmission path from the source to the receiver. This paper presents a methodology for improving fault detection via a series of vibration signal processing techniques, including signal separation, synchronous averaging (SA), spectral kurtosis (SK), and envelope analysis. These techniques have been tested on experimentally obtained vibration data acquired from the transmission system of a CS-29 Category A helicopter gearbox operating under different bearing damage conditions. Results showed successful enhancement of bearing fault detection on the second planetary stage of the gearbo

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients The ROADMAP Study 2-Year Results

OBJECTIVES The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BACKGROUND The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. METHODS The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance \u3e= 75 m. RESULTS Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p \u3c 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 +/- 5% vs. 41 +/- 5%; p \u3c 0.001), but there was no difference in intent-to-treat survival (70 +/- 5% vs. 63 +/- 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. CONCLUSIONS Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802

Brane/flux annihilation transitions and nonperturbative moduli stabilization

By extending the calculation of Kahler moduli stabilization to account for an embiggened antibrane, we reevaluate brane/flux annihilation in a warped throat with one stabilized Kahler modulus. We find that depending on the relative size of various fluxes three things can occur: the decay process proceeds unhindered, the anti-D3-branes are forbidden to decay classically, or the entire space decompactifies. Additionally, we show that the Kahler modulus receives a contribution from the collective 3-brane tension. This allows for a significant change in compactified volume during the transition and possibly mitigates some fine tuning otherwise required to achieve large volume.Comment: 25 pages, 6 figures, LaTeX. v2: references adde

Compton scattering in Noncommutative Space-Time at the NLC

We study the Compton scattering in the noncommutative counter part of QED (NC QED). Interactions in NC QED have momentum dependent phase factors and the gauge fields have Yang Mills type couplings, this modifies the cross sections and are different from the commuting Standard Model. Collider signals of noncommutative space-time are studied at the Next Linear Collider (NLC) operating in the $e \gamma$ mode. Results for different polarised cases are presented and it is shown that the Compton process can probe the noncommutative scale in the range of 1 - 2.5 TeV for typical proposed NLC energies.Comment: 12 pages, 5 Postscript figures, version to appear in Phys. Rev.

Brane Boxes, Anomalies, Bending and Tadpoles

Certain classes of chiral four-dimensional gauge theories may be obtained as the worldvolume theories of D5-branes suspended between networks of NS5-branes, the so-called brane box models. In this paper, we derive the stringy consistency conditions placed on these models, and show that they are equivalent to anomaly cancellation of the gauge theories. We derive these conditions in the orbifold theories which are T-dual to the elliptic brane box models. Specifically, we show that the expression for tadpoles for unphysical twisted Ramond-Ramond 4-form fields in the orbifold theory are proportional to the gauge anomalies of the brane box theory. Thus string consistency is equivalent to worldvolume gauge anomaly cancellation. Furthermore, we find additional cylinder amplitudes which give the $\beta$-functions of the gauge theory. We show how these correspond to bending of the NS-branes in the brane box theory.Comment: 14 pages, 3 epsf figures. Minor changes, references adde

Water sorption mechanisms for MIS materials.

The fundamental processes that control the amount of water sorbed by impure plutonium-containing materials after calcination are reviewed. Of particular interest is the amount of and rate of moisture sorption at 1000 PPMv (parts-per-million vapor; -3% RH at 25 'C) and 10,000 PPMv (32% RH at 25 'C). Pure plutonium oxide powders will remain below the 0.5 wt% criterion for packaging in the DOE 3013 Standard at both water vapor concentrations [I]. Deliquescent salts that have been observed in calcined materials by DOES Materials Identification and Surveillance (MIS) program will exceed the 0.5 wt% criterion at 10,000 PPMv and will meet that standard at 1,000 PPMv. Hydrated salts will exceed the 0.5 wt% criterion at all technologically achievable water vapor concentrations if allowed to reach equilibrium. Controlling the moisture availability by controlling the atmospheric content at 1000 PPM' and limiting the access to atmospheric moisture after stabilization through the use of a properly configured stabilization boat will minimize moisture uptake by these materials