Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur

Surgery remains the best option for the management of pain in patients with chronic pancreatitis: a systematic review and meta-analysis

Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients

A conserved role for kinesin-5 in plant mitosis

The mitotic spindle of vascular plants is assembled and maintained by processes that remain poorly explored at a molecular level. Here, we report that AtKRP125c, one of four kinesin-5 motor proteins in arabidopsis, decorates microtubules throughout the cell cycle and appears to function in both interphase and mitosis. In a temperature-sensitive mutant, interphase cortical microtubules are disorganized at the restrictive temperature and mitotic spindles are massively disrupted, consistent with a defect in the stabilization of anti-parallel microtubules in the spindle midzone, as previously described in kinesin-5 mutants from animals and yeast. AtKRP125c introduced into mammalian epithelial cells by transfection decorates microtubules throughout the cell cycle but is unable to complement the loss of the endogenous kinesin-5 motor (Eg5). These results are among the first reports of any motor with a major role in anastral spindle structure in plants and demonstrate that the conservation of kinesin-5 motor function throughout eukaryotes extends to vascular plants

Maximal Sharing in the Lambda Calculus with letrec

Increasing sharing in programs is desirable to compactify the code, and to avoid duplication of reduction work at run-time, thereby speeding up execution. We show how a maximal degree of sharing can be obtained for programs expressed as terms in the lambda calculus with letrec. We introduce a notion of `maximal compactness' for lambda-letrec-terms among all terms with the same infinite unfolding. Instead of defined purely syntactically, this notion is based on a graph semantics. lambda-letrec-terms are interpreted as first-order term graphs so that unfolding equivalence between terms is preserved and reflected through bisimilarity of the term graph interpretations. Compactness of the term graphs can then be compared via functional bisimulation. We describe practical and efficient methods for the following two problems: transforming a lambda-letrec-term into a maximally compact form; and deciding whether two lambda-letrec-terms are unfolding-equivalent. The transformation of a lambda-letrec-term $L$ into maximally compact form $L_0$ proceeds in three steps: (i) translate L into its term graph $G = [[ L ]]$; (ii) compute the maximally shared form of $G$ as its bisimulation collapse $G_0$; (iii) read back a lambda-letrec-term $L_0$ from the term graph $G_0$ with the property $[[ L_0 ]] = G_0$. This guarantees that $L_0$ and $L$ have the same unfolding, and that $L_0$ exhibits maximal sharing. The procedure for deciding whether two given lambda-letrec-terms $L_1$ and $L_2$ are unfolding-equivalent computes their term graph interpretations $[[ L_1 ]]$ and $[[ L_2 ]]$, and checks whether these term graphs are bisimilar. For illustration, we also provide a readily usable implementation.Comment: 18 pages, plus 19 pages appendi

Shape coexistence at the proton drip-line: First identification of excited states in 180Pb

Excited states in the extremely neutron-deficient nucleus, 180Pb, have been identified for the first time using the JUROGAM II array in conjunction with the RITU recoil separator at the Accelerator Laboratory of the University of Jyvaskyla. This study lies at the limit of what is presently achievable with in-beam spectroscopy, with an estimated cross-section of only 10 nb for the 92Mo(90Zr,2n)180Pb reaction. A continuation of the trend observed in 182Pb and 184Pb is seen, where the prolate minimum continues to rise beyond the N=104 mid-shell with respect to the spherical ground state. Beyond mean-field calculations are in reasonable correspondence with the trends deduced from experiment.Comment: 5 pages, 4 figures, submitted to Phys.Rev.

Boundary conditions at a fluid - solid interface

We study the boundary conditions at a fluid-solid interface using molecular dynamics simulations covering a broad range of fluid-solid interactions and fluid densities, and both simple and chain-molecule fluids. The slip length is shown to be independent of the type of flow, but rather is related to the fluid organization near the solid, as governed by the fluid-solid molecular interactions.Comment: REVtex, to appear in Physical Review Letter

Very high rotational frequencies and band termination in 73Br

Rotational bands in 73Br have been investigated up to spins of 65/2 using the EUROBALL III spectrometer. One of the negative-parity bands displays the highest rotational frequency 1.85 MeV reported to date in nuclei with mass number greater than 25. At high frequencies, the experimental dynamic moment of inertia for all bands decrease to very low values, indicating a loss of collectivity. The bands are described in the configuration-dependent cranked Nilsson-Strutinsky model. The calculations indicate that one of the negative-parity bands is observed up to its terminating single-particle state at spin 63/2. This result establishes the first band termination case in the A = 70 mass region.Comment: 6 pages, 6 figures, submitted to Phys. Rev. C as a Rapid Communicatio

The GREAT triggerless total data readout method

Recoil decay tagging (RDT) is a very powerful method for the spectroscopy of exotic nuclei. RDT is a delayed coincidence technique between detectors usually at the target position and at the focal plane of a spectrometer. Such measurements are often limited by dead time. This paper describes a novel triggerless data acquisition method, which is being developed for the Gamma Recoil Electron Alpha Tagging (GREAT) spectrometer, that overcomes this limitation by virtually eliminating dead time. Our solution is a total data readout (TDR) method where all channels run independently and are associated in software to reconstruct events. The TDR method allows all the data from both target position and focal plane to be collected with practically no dead-time losses. Each data word is associated with a timestamp generated from a global 100-MHz clock. Events are then reconstructed in real time in the event builder using temporal and spatial associations defined by the physics of the experimen