Antithrombin properties of C-terminus of hirudin using synthetic unsulfated Nα-acetyl-hirudin45–65

AbstractUnsulfated Nα-acetyl-hirudin45–65 (MDL 27 589), which corresponds to the C-terminus of hirudin1–65, was synthesized by solid-phase methods. The synthetic peptide was able to inhibit fibrin formation and the release of fibrinopeptide A from fibrinogen by thrombin. The catalytic site of thrombin was not perturbed by the synthetic peptide as H-D-Phe-Pip-Arg-pNA hydrolysis (amidase activity) was not affected. The binding of synthetic peptide and thrombin was assessed by isolation of the complex on gel-filtration chromatography. A single binding site with a binding affinity (Ka) of approx. 1.0 × 105 M−1 was observed for thrombin-hirudin45–65 interaction. The data suggest that the C-terminal residues 45–65 of hirudin contain a binding domain which recognizes thrombin and yet does not bind to the catalytic site of the enzyme

Inferring a DNA sequence from erroneous copies

AbstractWe suggest a novel approach for efficiently reconstructing an original DNA sequence from erroneous copies

Small weight bases for Hamming codes

AbstractWe present constructions of bases for a Hamming code having small width and height, i.e. number of 1s in each row and column in the corresponding matrix. Apart from being combinatorially interesting in their own right, these bases also lead to improved embeddings of a hypercube of cliques into a same-sized hypercube

Numerical methods for the TSD equation in conservation law form

The Transonic Small Disturbance (TSD) Equation is a common model equation for describing subsonic and supersonic flow close to the local speed of sound (transonic). In transonic flow there is an embedded region of locally supersonic flow inside an otherwise subsonic flow. The supersonic region is usually terminated by a shock discontinuity. The success of a numerical scheme for transonic flow prediction depends on its capability of capturing all the flow details and non-linearities including sharp shock profiles without oscillations near the shock. Most of the important phenomena in the TSD equation occur in the stream-wise direction. The nonlinearity and changes in the region of influence depend only on the stream-wise derivation. A suitable one-dimensional model equation derived from the TSD Equation is used. The one-dimensional equation is written in conservation law form. This nonlinear system of equations models the transition from supersonic to subsonic flow. In the numerical calculations the discretised problem is treated as a series of Riemann problems. We will investigate various techniques for solving these Riemann problems. It will be shown that the techniques do not allow non-physical expansion shocks to develop and that the techniques smooth out expansion shocks when these non-physical shocks are present in the initial velocity profile. A comparison will be made between the schemes based on the sharpness of the resulting shock profiles

Repeated mild injury causes cumulative damage to hippocampal cells

An interesting hypothesis in the study of neurotrauma is that repeated traumatic brain injury may result in cumulative damage to cells of the brain. However, post-injury sequelae are difficult to address at the cellular level in vivo. Therefore, it is necessary to complement these studies with experiments conducted in vitro. In this report, the effects of single and repeated traumatic injury in vitro were investigated in cultured mouse hippocampal cells using a well characterized model of stretch-induced injury. Cell damage was assessed by the level of propidium iodide (PrI) uptake and retention of fluorescein diacetate (FDA). Uninjured control wells displayed minimal PrI uptake and high levels of FDA retention. Mild, moderate and severe levels of stretch caused increasing amounts of PrI uptake, respectively, when measured at 15 min and 24 h post-injury, indicating increased cellular damage with increasing amounts of stretch. For repeated injury studies, cultures received a second injury 1 h after the initial insult. Repeated mild injury caused a slight increase in PrI uptake compared with single injury at 15 min and 24 h post-injury, which was evident primarily in glial cells. However, the neurites of neurones in cultures that received repeated insults showed signs of damage that were not evident after a single mild injury. The release of neurone-specific enolase (NSE) and S-100beta protein, two common clinical markers of CNS damage, was also measured following the repeated injuries paradigm. When measured at 6 h post-injury, both NSE and S-100beta were found to be elevated after repeated mild injuries when compared with the single injury group. These results suggest that cells of the hippocampus may be susceptible to cumulative damage following repeated mild traumatic insults. Both glial cells and neurones appear to exhibit increased signs of damage after repetitive injury. To our knowledge, this study represents the first report on the effects of repeated mechanical insults on specific cells of the brain using an in vitro model system. The biochemical pathways of cellular degradation following repeated mild injuries may differ considerably from those that are activated by a single mild insult. Therefore, we hope to use this model in order to investigate secondary pathways of cellular damage after repeated mild traumatic injury, and as a rapid and economical means of screening possibilities for treatment strategies, including pharmaceutical intervention