Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II

MCoTl-I and MCoTl-II from the seeds of Momordica cochinchinensis are inhibitors of trypsin-like proteases and the only known members of the large family of squash inhibitors that are cyclic and contain an additional loop connecting the amino- and the carboxy-terminus. To investigate the contribution of macrocycle formation to biological activity, we synthesized a set of open-chain variants of MCoTl-II that lack the cyclization loop and contain various natural and non-natural amino acid substitutions in the reactive-site loop. Upon replacement of P1 lysine residue \#10 within the open-chain variant of MCoTl-II by the non-natural isosteric nucleo amino acid AlaG{[}beta-(guanin-9-yl)-L-alanine], a conformationally restricted arginine mimetic, residual inhibitory activity was detected, albeit reduced by four orders of magnitude. While the cyclic inhibitors MCoTl-I and MCoTl-II were found to be very potent trypsin inhibitors, with picomolar inhibition constants, the open-chain variants displayed an approximately 10-fold lower affinity. These data suggest that the formation of a circular backbone in the MCoTI squash inhibitors results in enhanced affinity and therefore is a determinant of biological activity

On the uncertainty of sea-ice isostasy

During late winter 2007, coincident measurements of sea ice were collected using various sensors at an ice camp in the Beaufort Sea, Canadian Arctic. Analysis of the archived data provides new insight into sea-ice isostasy and its related R-factor through case studies at three scales using different combinations of snow and ice thickness components. At the smallest scale (\u3c1 m; point scale), isostasy is not expected, so we calculate a residual and define this as �� (‘zjey’) to describe vertical displacement due to deformation. From 1 to 10 m length scales, we explore traditional isostasy and identify a specific sequence of thickness calculations which minimize freeboard and elevation uncertainty. An effective solution exists when the R-factor is allowed to vary: ranging from 2 to 12, with mean of 5.17, mode of 5.88 and skewed distribution. At regional scales, underwater, airborne and spaceborne platforms are always missing thickness variables from either above or below sea level. For such situations, realistic agreement is found by applying small-scale skewed ranges for the R-factor. These findings encourage a broader isostasy solution as a function of potential energy and length scale. Overall, results add insight to data collection strategies and metadata characteristics of different thickness products

Continuous GPS and broad-scale deformation across the Rhine Graben and the Alps

In order to study the ongoing tectonic deformation in the Rhine Graben area, we reconstruct the local crustal velocity and the strain rate field from GPS array solutions. Following the aim of this work, we compile the velocities of permanent GPS stations belonging to various networks (EUREF, AGNES, REGAL and RGP) in central western Europe. Moreover, the strain rate field is displayed in terms of principal axes and values, while the normal and the shear components of the strain tensor are calculated perpendicular and parallel to the strike of major faults. The results are compared with the fault plane solutions of earthquakes, which have occurred in this area. A broad-scale kinematic deformation model across the Rhine Graben is provided on the basis of tectonics and velocity results of the GPS permanent stations. The area of study is divided into four rigid blocks, between which there might be relative motions. The velocity and the strain rate fields are reconstructed along their borders, by estimating a uniform rotation for each block. The tectonic behaviour is well represented by the four-block model in the Rhine Graben area, while a more detailed model will be needed for a better reconstruction of the strain field in the Alpine regio

Quantum Decoherence, Entropy and Thermalization in Strong Interactions at High Energy

Entropy is generated in high-multiplying events by a dynamical separation of strongly interacting systems into partons and unobservable environment modes (almost constant field configurations) due to confinement.Comment: 45 pages, 2 figure

The alpine Swiss-French airborne gravity survey

In February 1998, a regional-scale, airborne gravity survey was carried out over the French Occidental Alps within the framework of the GéoFrance 3-D research program.The survey consisted of 18 NS and 16 EW oriented lines with a spacing of 10 and 20 km respectively, covering the whole of the Western French Alps (total area: 50 000 km2; total distance of lines flown: 10 000 km). The equipment was mounted in a medium-size aircraft (DeHavilland Twin Otter) flowing at a constant altitude of 5100 m a.s.l, and at a mean ground speed of about 280 km h−1. Gravity was measured using a LaCoste & Romberg relative, air/sea gravimeter (type SA) mounted on a laser gyro stabilized platform. Data from 5 GPS antennae located on fuselage and wings and 7 ground-based GPS reference stations were used to determine position and aircraft induced accelerations.The gravimeter passband was derived by comparing the vertical accelerations provided by the gravimeter with those estimated from the GPS positions. This comparison showed that the gravimeter is not sensitive to very short wavelength aircraft accelerations, and therefore a simplified formulation for computing airborne gravity measurements was developed. The intermediate and short wavelength, non-gravitational accelerations were eliminated by means of digital, exponential low-pass filters (cut-off wavelength: 16 km). An important issue in airborne gravimetry is the reliability of the airborne gravity surveys when compared to ground surveys. In our studied area, the differences between the airborne-acquired Bouguer anomaly and the ground upward-continued Bouguer anomaly of the Alps shows a good agreement: the rms of these differences is equal to 7.68 mGal for a spatial resolution of 8 km. However, in some areas with rugged topography, the amplitudes of those differences have a striking correlation with the topography. We then argue that the choice of an appropriate density (reduction by a factor of 10 per cent) for computing the ground topographic corrections over the highest mountains, results in significantly reducing the differences between airborne and ground upward-continued Bouguer anomalies, which shows that some of the misfit stems from errors in the ground dat

Impact of spatial aliasing on sea-ice thickness measurements

We explore spatial aliasing of non-Gaussian distributions of sea-ice thickness. Using a heuristic model and \u3e1000 measurements, we show how different instrument footprint sizes and shapes can cluster thickness distributions into artificial modes, thereby distorting frequency distribution, making it difficult to compare and communicate information across spatial scales. This problem has not been dealt with systematically in sea ice until now, largely because it appears to incur no significant change in integrated thickness which often serves as a volume proxy. Concomitantly, demands are increasing for thickness distribution as a resource for modeling, monitoring and forecasting air–sea fluxes and growing human infrastructure needs in a changing polar environment. New demands include the characterization of uncertainties both regionally and seasonally for spaceborne, airborne, in situ and underwater measurements. To serve these growing needs, we quantify the impact of spatial aliasing by computing resolution error (Er) over a range of horizontal scales (x) from 5 to 500 m. Results are summarized through a power law (Er = bxm) with distinct exponents (m) from 0.3 to 0.5 using example mathematical functions including Gaussian, inverse linear and running mean filters. Recommendations and visualizations are provided to encourage discussion, new data acquisitions, analysis methods and metadata formats