Orientations of BCFW Charts on the Grassmannian

The Grassmannian formulation of $\mathcal{N}=4$ super Yang-Mills theory expresses tree-level scattering amplitudes as linear combinations of residues from certain contour integrals. BCFW bridge decompositions using adjacent transpositions simplify the evaluation of individual residues, but orientation information is lost in the process. We present a straightforward algorithm to compute relative orientations between the resulting coordinate charts, and we show how to generalize the technique for charts corresponding to sequences of any not-necessarily-adjacent transpositions. As applications of these results, we demonstrate the existence of a signed boundary operator that manifestly squares to zero and prove via our algorithm that any residues appearing in the tree amplitude sum are decorated with appropriate signs so all non-local poles cancel exactly, not just mod 2 as in previous works.Comment: 34 pages, 35 figure

Human KATP channelopathies: diseases of metabolic homeostasis

Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. KATP channels are metabolism-gated biosensors functioning as molecular rheostats that adjust membrane potential-dependent functions to match cellular energetic demands. Vital in the adaptive response to (patho)physiological stress, KATP channels serve a homeostatic role ranging from glucose regulation to cardioprotection. Accordingly, genetic variation in KATP channel subunits has been linked to the etiology of life-threatening human diseases. In particular, pathogenic mutations in KATP channels have been identified in insulin secretion disorders, namely, congenital hyperinsulinism and neonatal diabetes. Moreover, KATP channel defects underlie the triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP channelopathies implicated in patients with mechanical and/or electrical heart disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been associated with late-onset diabetes and as a risk factor for maladaptive cardiac remodeling in the community-at-large and abnormal cardiopulmonary exercise stress performance in patients with heart failure. The overall mutation frequency within KATP channel genes and the spectrum of genotype–phenotype relationships remain to be established, while predicting consequences of a deficit in channel function is becoming increasingly feasible through systems biology approaches. Thus, advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy

Liquefaction Analysis of Lower San Fernando Darn Using Strength Ratios

Olson (2000) evaluated 33 liquefaction flow failure case histories to assess the yield strength ratio and liquefied strength ratio mobilized during the failures. Using back-analysis procedures developed by Olson (2000), yield and liquefied shear strengths are shown to be proportional to the pre-failure vertical effective stress and are related to standard and cone penetration resistances. This paper examines the triggering of liquefaction and subsequent flow failure of Lower San Fernando Dam using yield and liquefied strength ratios. The yield strength ratio is used to correctly predict the occurrence of liquefaction in the upstream hydraulic fill of the dam, and the liquefied shear strength ratio is used to correctly predict the subsequent flow failure of the upstream slope. The relationships for the yield and liquefied ratios are presented, and their application to existing or new structures is illustrated using the Lower San Fernando Dam case history

MICROCOMPUTER BUDGET MANAGEMENT SYSTEM

The enterprise budget, whole farm cash flow, and income statement are fundamental tools of farm and ranch management. The "Microcomputer Budget Management System" (MBMS) is a microcomputer software package that facilitates the storage and use of information for crop and livestock budgeting. It performs the calculations for several enterprise budgeting formats and for preparation of whole farm resource use reports and financial statements. The MBMS also includes internal machinery and irrigation cost calculation routines. MBMS was developed for use by extension staff, researchers, lenders, consultants, and operators of diversified farms and ranches with many enterprises that use enterprise and whole farm budgeting for analysis and planning activities. The flexibility and detailed nature of the program requires the user to have knowledge of enterprise budgeting and operation of complex computer programs. This paper presents a discussion of the features and capabilities of the software and the computational procedures used in the cost calculations.Research and Development/Tech Change/Emerging Technologies,

NMR Dynamics Investigation of Ligand-Induced Changes of Main and Side-Chain Arginine N-H’s in Human Phosphomevalonate Kinase

Phosphomevalonate kinase (PMK) catalyzes phosphoryl transfer from adenosine triphosphate (ATP) to mevalonate 5-phosphate (M5P) on the pathway for synthesizing cholesterol and other isoprenoids. To permit this reaction, its substrates must be brought proximal, which would result in a significant and repulsive buildup of negative charge. To facilitate this difficult task, PMK contains 17 arginines and eight lysines. However, the way in which this charge neutralization and binding is achieved, from a structural and dynamics perspective, is not known. More broadly, the role of arginine side-chain dynamics in binding of charged substrates has not been experimentally defined for any protein to date. Herein we report a characterization of changes to the dynamical state of the arginine side chains in PMK due to binding of its highly charged substrates, ATP and M5P. These studies were facilitated by the use of arginine-selective labeling to eliminate spectral overlap. Model-free analysis indicated that while substrate binding has little effect on the arginine backbone dynamics, binding of either substrate leads to significant rigidification of the arginine side chains throughout the protein, even those that are \u3e8 Å from the binding site. Such a global rigidification of arginine side chains is unprecedented and suggests that there are long-range electrostatic interactions of sufficient strength to restrict the motion of arginine side chains on the picosecond-to-nanosecond time scale. It will be interesting to see whether such effects are general for arginine residues in proteins that bind highly charged substrates, once additional studies of arginine side-chain dynamics are reported

Dilaton Effective Action with N=1\mathcal{N}=1 Supersymmetry

We clarify the structure of the four-dimensional low-energy effective action that encodes the conformal and $U(1)$ R-symmetry anomalies in an $\mathcal{N}=1$ supersymmetric field theory. The action depends on the dilaton, $\tau$, associated with broken conformal symmetry, and the Goldstone mode, $\beta$, of the broken $U(1)$ R-symmetry. We present the action for general curved spacetime and background gauge field up to and including all possible four-derivative terms. The result, constructed from basic principles, extends and clarifies the structure found by Schwimmer and Theisen in arXiv:1011.0696 using superfield methods. We show that the Goldstone mode $\beta$ does not interfere with the proof of the four-dimensional $a$-theorem based on $2 \to 2$ dilaton scattering. In fact, supersymmetry Ward identities ensure that a proof of the $a$-theorem can also be based on $2 \to 2$ Goldstone mode scattering when the low-energy theory preserves $\mathcal{N}=1$ supersymmetry. We find that even without supersymmetry, a Goldstone mode for any broken global $U(1)$ symmetry cannot interfere with the proof of the four-dimensional $a$-theorem.Comment: 18 page

Development of carbon nanotube-based sensor to monitor crack growth in cracked aluminum structures underneath composite patching

This paper presents the design of a carbon nanotube-based sensor to detect crack propagation in aluminum structures underneath composite patching. Initial tests are utilized to determine the correct procedure and materials to properly fabricate a carbon nanotube (CNT) sensor, which is then placed in between a composite patch and the aluminum structure. CNTs have been utilized as sensors in previous studies but only for sensing crack propagation within the composite itself. This study focuses on crack propagation in the base material and is not concerned with the composite. In this application, the composite is only a patch and can be replaced if damaged. This study utilizes both tension and fatigue testing to determine the usefulness of the CNT sensor. The CNT sensor is shown to be effective in giving an indication of the crack propagation in the aluminum. Correlation is done between the propagation length and the increase in resistance in the CNT sensor for tensile testing as the crack width is large enough to obtain an appreciable resistance change.http://archive.org/details/developmentofcar1094542700Outstanding ThesisLieutenant, United States NavyApproved for public release; distribution is unlimited

Substrate Induced Structural and Dynamics Changes in Human Phosphomevalonate Iinase and Implications for Mechanism

Phosphomevalonate kinase (PMK) catalyzes an essential step in the mevalonate pathway, which is the only pathway for synthesis of isoprenoids and steroids in humans. PMK catalyzes transfer of the γ-phosphate of ATP to mevalonate 5-phosphate (M5P) to form mevalonate 5-diphosphate. Bringing these phosphate groups in proximity to react is especially challenging, given the high negative charge density on the four phosphate groups in the active site. As such, conformational and dynamics changes needed to form the Michaelis complex are of mechanistic interest. Herein, we report the characterization of substrate induced changes (Mg-ADP, M5P, and the ternary complex) in PMK using NMR-based dynamics and chemical shift perturbation measurements. Mg-ADP and M5P Kd\u27s were 6–60 μM in all complexes, consistent with there being little binding synergy. Binding of M5P causes the PMK structure to compress (τc = 13.5 nsec), whereas subsequent binding of Mg-ADP opens the structure up (τc = 15.6 nsec). The overall complex seems to stay very rigid on the psec-nsec timescale with an average NMR order parameter of S2 ∼0.88. Data are consistent with addition of M5P causing movement around a hinge region to permit domain closure, which would bring the M5P domain close to ATP to permit catalysis. Dynamics data identify potential hinge residues as H55 and R93, based on their low order parameters and their location in extended regions that connect the M5P and ATP domains in the PMK homology model. Likewise, D163 may be a hinge residue for the lid region that is homologous to the adenylate kinase lid, covering the “Walker-A” catalytic loop. Binding of ATP or ADP appears to cause similar conformational changes; however, these observations do not indicate an obvious role for γ-phosphate binding interactions. Indeed, the role of γ-phosphate interactions may be more subtle than suggested by ATP/ADP comparisons, because the conservative O to NH substitution in the β-γ bridge of ATP causes a dramatic decrease in affinity and induces few chemical shift perturbations. In terms of positioning of catalytic residues, binding of M5P induces a rigidification of Gly21 (adjacent to the catalytically important Lys22), although exchange broadening in the ternary complex suggests some motion on a slower timescale does still occur. Finally, the first nine residues of the N-terminus are highly disordered, suggesting that they may be part of a cleavable signal or regulatory peptide sequence. Proteins 2009. © 2008 Wiley-Liss, Inc

Molecular Docking and NMR Binding Studies to Identify Novel Inhibitors of Human Phosphomevalonate Kinase

Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based 1H–15N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (Kd). Tight binding compounds with Kd’s ranging from 6–60 μM were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development