On Solving L-SR1 Trust-Region Subproblems

In this article, we consider solvers for large-scale trust-region subproblems when the quadratic model is defined by a limited-memory symmetric rank-one (L-SR1) quasi-Newton matrix. We propose a solver that exploits the compact representation of L-SR1 matrices. Our approach makes use of both an orthonormal basis for the eigenspace of the L-SR1 matrix and the Sherman-Morrison-Woodbury formula to compute global solutions to trust-region subproblems. To compute the optimal Lagrange multiplier for the trust-region constraint, we use Newton's method with a judicious initial guess that does not require safeguarding. A crucial property of this solver is that it is able to compute high-accuracy solutions even in the so-called hard case. Additionally, the optimal solution is determined directly by formula, not iteratively. Numerical experiments demonstrate the effectiveness of this solver.Comment: 2015-0

Variations in the phosphorus content of estuarine waters of the Chesapeake Bay near Solomons Island, Maryland

Studies by Cowles and Brambel (1938), Newcombe and Lang (1939), and Newcombe, Horne and Shepherd (1939) have provided information on the quantitative methods for estimating inorganic phosphorus and, also, on the vertical and horizontal distribution of this nutrient substance in the waters of the Chesapeake Bay...

Observations on the alkalinity of estuarine waters of the Chesapeake Bay near Solomons Island, Maryland

Kolthoff (1926) without particular reference to sea water has defined buffer capacity (alkalinity, in the case of added strong base) of a solution quantitatively as the number of equivalents of added strong base or strong acid required to change the pH of one liter of solution one unit. Buch, in 1930, redefined this concept with reference to sea water as the number of moles of carbonic acid which must be added to one liter of the water in order to change its pH by one unit

Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating.

L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals

Shape-Changing Trust-Region Methods Using Multipoint Symmetric Secant Matrices

In this work, we consider methods for large-scale and nonconvex unconstrained optimization. We propose a new trust-region method whose subproblem is defined using a so-called "shape-changing" norm together with densely-initialized multipoint symmetric secant (MSS) matrices to approximate the Hessian. Shape-changing norms and dense initializations have been successfully used in the context of traditional quasi-Newton methods, but have yet to be explored in the case of MSS methods. Numerical results suggest that trust-region methods that use densely-initialized MSS matrices together with shape-changing norms outperform MSS with other trust-region methods

Editorial: Adenylyl Cyclase Isoforms as Potential Drug Targets

Editorial on the Research Topic Adenylyl cyclase isoforms as potential drug target

High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain

Physiological Roles of Mammalian Transmembrane Adenylyl Cyclase Isoforms

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gαs so it was long assumed that all ACs are activated by Gαs-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form prearranged signaling complexes with specific GPCRs that contribute to cAMP signaling compartments. This compartmentation allows for a diversity of cellular and physiological responses by enabling unique signaling events to be triggered by different pools of cAMP. Isoform specific pharmacological activators or inhibitors are lacking for most ACs, making knockdown and overexpression the primary tools for examining the physiological roles of a given isoform. Much progress has been made in understanding the physiological effects mediated through individual transmembrane ACs. GPCR-AC-cAMP signaling pathways play significant roles in regulating functions of every cell and tissue, so understanding each AC isoform\u27s role holds potential for uncovering new approaches for treating a vast array of pathophysiological conditions

The effects of cyclic and dynamic loading on the fracture resistance of nuclear piping steels. Technical report, October 1992--April 1996

This report presents the results of the material property evaluation efforts performed within Task 3 of the IPIRG-2 Program. Several related investigations were conducted. (1) Quasi-static, cyclic-load compact tension specimen experiments were conducted using parameters similar to those used in IPIRG-1 experiments on 6-inch nominal diameter through-wall-cracked pipes. These experiments were conducted on a TP304 base metal, an A106 Grade B base metal, and their respective submerged-arc welds. The results showed that when using a constant cyclic displacement increment, the compact tension experiments could predict the through-wall-cracked pipe crack initiation toughness, but a different control procedure is needed to reproduce the pipe cyclic crack growth in the compact tension tests. (2) Analyses conducted showed that for 6-inch diameter pipe, the quasi-static, monotonic J-R curve can be used in making cyclic pipe moment predictions; however, sensitivity analyses suggest that the maximum moments decrease slightly from cyclic toughness degradation as the pipe diameter increases. (3) Dynamic stress-strain and compact tension tests were conducted to expand on the existing dynamic database. Results from dynamic moment predictions suggest that the dynamic compact tension J-R and the quasi-static stress-strain curves are the appropriate material properties to use in making dynamic pipe moment predictions