Kramers-Kronig, Bode, and the meaning of zero

The implications of causality, as captured by the Kramers-Kronig relations between the real and imaginary parts of a linear response function, are familiar parts of the physics curriculum. In 1937, Bode derived a similar relation between the magnitude (response gain) and phase. Although the Kramers-Kronig relations are an equality, Bode's relation is effectively an inequality. This perhaps-surprising difference is explained using elementary examples and ultimately traces back to delays in the flow of information within the system formed by the physical object and measurement apparatus.Comment: 8 pages; American Journal of Physics, to appea

Cystatins as calpain inhibitors: Engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of μ-calpain

Within the cystatin superfamily, only kininogen domain 2 (KD2) is able to inhibit μ- and m-calpain. In an attempt to elucidate the structural requirements of cystatins for calpain inhibition, we constructed recombinant hybrids of human stefin B (an intracellular family 1 cystatin) with KD2 and Delta L110 deletion mutants of chicken cystatin-KD2 hybrids. Substitution of the N-terminal contact region of stefin B by the corresponding KD2 sequence resulted in a calpain inhibitor of K-i = 188 nM. Deletion of L110, which forms a beta -bulge in family 1 and 2 cystatins but is lacking in KD2, improved inhibition of mu -calpain 4- to 8-fold. All engineered cystatins were temporary inhibitors of calpain due to slow substrate-like cleavage of a single peptide bond corresponding to Gly9-Ala10 in chicken cystatin. Biomolecular interaction analysis revealed that, unlike calpastatin, the cystatin-type inhibitors do not bind to the calmodulin-like domain of the small subunit of calpain, and their interaction with the mu -calpain heterodimer is completely prevented by a synthetic peptide comprising subdomain B of calpastatin domain 1. Based on these results we propose that (i) cystatin-type calpain inhibitors interact with the active site of the catalytic domain of calpain in a similar cystatin-like mode as with papain and (ii) the potential for calpain inhibition is due to specific subsites within the papain-binding regions of the general cystatin fold

Dynamical overlap fermions, results with hybrid Monte-Carlo algorithm

We present first, exploratory results of a hybrid Monte-Carlo algorithm for dynamical, n_f=2, four-dimensional QCD with overlap fermions. As expected, the computational requirements are typically two orders of magnitude larger for the dynamical overlap formalism than for the more conventional (Wilson or staggered) formulations.Comment: 13 pages, 2 figure

String amplitudes in arbitrary dimensions

We calculate gravitational dressed tachyon correlators in non critcal dimensions. The 2D gravity part of our theory is constrained to constant curvature. Then scaling dimensions of gravitational dressed vertex operators are equal to their bare conformal dimensions. Considering the model as d+2 dimensional critical string we calculate poles of generalized Shapiro-Virasoro amplitudes.Comment: 14 page

Quantitative analysis of cell types during growth and morphogenesis in Hydra

Tissue maceration was used to determine the absolute number and the distribution of cell types in Hydra. It was shown that the total number of cells per animal as well as the distribution of cells vary depending on temperature, feeding conditions, and state of growth. During head and foot regeneration and during budding the first detectable change in the cell distribution is an increase in the number of nerve cells at the site of morphogenesis. These results and the finding that nerve cells are most concentrated in the head region, diminishing in density down the body column, are discussed in relation to tissue polarity

Magnetic properties of Quantum Corrals from first principles calculations

We present calculations for electronic and magnetic properties of surface states confined by a circular quantum corral built of magnetic adatoms (Fe) on a Cu(111) surface. We show the oscillations of charge and magnetization densities within the corral and the possibility of the appearance of spin--polarized states. In order to classify the peaks in the calculated density of states with orbital quantum numbers we analyzed the problem in terms of a simple quantum mechanical circular well model. This model is also used to estimate the behaviour of the magnetization and energy with respect to the radius of the circular corral. The calculations are performed fully relativistically using the embedding technique within the Korringa-Kohn-Rostoker method.Comment: 14 pages, 9 figures, submitted to J. Phys. Cond. Matt. special issue on 'Theory and Simulation of Nanostructures

Design of small-molecule active-site inhibitors of the S1A family proteases as procoagulant and anticoagulant drugs

Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose–response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring, but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains. Efforts are now underway to develop DOACs that inhibit components of the intrinsic and extrinsic coagulation cascades upstream of thrombin and fX. Evidence from humans and from transgenic animal models suggests that this strategy may provide a better therapeutic margin between antithrombotic and antihemostatic effects. Here the design of active-site inhibitors of S1A proteases involved in coagulation and fibrinolysis is summarized