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Re-discovering PDE3 inhibitors - New opportunities for a long neglected target

The PDE3 enzymes or "low Kin cGMP-inhibited phosphodiesterases" have long been established as important mediators of cellular physiology, and synthetic PDE3 inhibitors have been critical to the delineation of the enzymes' roles. Yet despite decades of progress on the biology of these enzymes, the medicinal chemistry landscape relating to PDE3 inhibitors has remained essentially unchanged since the

Chemo-enzymatic epoxidation of oleic acid and methyl oleate in solvent-free medium

Chemo-enzymatic epoxidation of oleic acid (OA) and its methyl ester has been performed using hydrogen peroxide and immobilized lipase from Candida antarctica (Novozym(R) 435). The purpose of the study was to characterize the reaction under solvent-free conditions. The reaction temperature had a significant impact on epoxidation of OA. At lower temperatures, the substrate conversion was hindered by

Remnant magnetoresistance in ferromagnetic (Ga,Mn)As nanostructures

The authors show a magnetoresistive effect that appears in a lithographically shaped, three-arm nanostructure fabricated from ferromagnetic (Ga,Mn)As layers. The effect, related to a rearrangement of magnetic domain walls between different pairs of arms in the structure, is revealed as a dependence of zero-field resistance on the direction of the previously applied magnetic field. This effect coul

Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia

This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s

Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro

Clearance of the amyloid-P peptide (A beta) as a remedy for Alzheimer's disease (AD) is a major target in on-going clinical trials. In vitro studies confirmed that A beta is taken up by rodent astrocytes, but knowledge on human astrocyte-mediated A beta clearance is sparse. Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internaliza

Compensatory endocytosis in chromaffin cells

Exocytosis occurs via fusion of secretory granules with the cell membrane, whereupon the granule content is at least partially released and the granule membrane is temporarily added to the plasma membrane. Exocytosis is balanced by compensatory endocytosis to achieve net equilibrium of the cell surface area and to recycle and redistribute components of the exocytosis machinery. The underlying mole

Three methods for determining the area-depth relationship of Lake Poopó, a large shallow lake in Bolivia

Lake Poopó in Bolivia is a large, extremely shallow lake. The lake surface area is ≈3000 km2 at its spill-over level, although it could dry out at times. The lake water level varies with the regional rains and with the water inflow from the Desaguadero River. This study focuses on using and comparing three different approaches to determine the hypsographic curve for the lake. As the lake is extrem

Drug resistance in Mycobacterium tuberculosis strains isolated from re-treatment cases of pulmonary tuberculosis in Ethiopia: susceptibility to first-line and alternative drugs

SETTING: Addis Ababa Tuberculosis Demonstration and Training Center, Ethiopia. OBJECTIVES: To determine the pattern of drug resistance among re-treatment cases of pulmonary tuberculosis (TB), to determine the risk factors associated with multi-drug resistant (MDR) TB, and to propose re-treatment regimens based on the patterns of susceptibility to first-line and alternative drugs. DESIGN: One hundr

Collisional properties of trapped cold chromium atoms

We report on calculations of the elastic cross section and thermalization rate for collision between two maximally spin-polarized chromium atoms in the cold and ultracold regimes, relevant to buffer-gas and magneto-optical cooling. We calculate ab initio potential-energy curves for Cr-2 and the van der Waals coefficient C-6, and construct interaction potentials between two colliding Cr atoms. We e

Surface phase diagram and temperature induced phase transitions of Sn/Cu(100)

Room temperature deposition of Sn on Cu(100) gives rise to a rich variety of surface reconstructions in the submonolayer coverage range. In this work, we report a detailed investigation on the phases appearing and their temperature stability range by using low-energy electron diffraction and surface X-ray diffraction. Previously reported reconstructions in the submonolayer range are p(2 x 2) (for

Photosynthesis of ATP - Electrons, proton pumps, rotors, and poise

Light-driven electron transport is coupled to ATP synthesis in chloroplasts. While the nature of the coupling and the structures of key components are now known, there has long been disagreement over pathways of electron transport. Recent results now put an old idea back on the agenda -cyclic electron transport around photosystem 1.

Air pollution and risk of lung cancer in a prospective study in Europe

To estimate the relationship between air pollution and lung cancer, a nested case-control study was set up within EPIC (European Prospective Investigation on Cancer and Nutrition). Cases had newly diagnosed lung cancer, accrued after a median follow-up of 7 years among the EPIC exsmokers (since at least 10 years) and never smokers. Three controls per case were matched. Matching criteria were gende

Ramet demography in a ring-forming clonal sedge

1 In a calcareous dry grassland community in central Europe genets of the clonal sedge Carex humilis form very distinct rings of densely aggregated ramets. As genet growth form is generated by ramet population dynamics, ramet demography must be studied in order to understand how rings develop. We analysed how ramet demography in C. humilis depends on ramet position within the ring and how this is

Macroporous elastic polyacrylamide monolith columns: processing under compression and scale-up

Macroporous gel (MG) monoliths are novel stationary media with a combination of unique properties such as continuous system of interconnected macropores and high elasticity. Due to the large (1-100 mu m) and highly interconnected pores, the polyacrylamide (pAAm) MG monolith columns have low backpressure and can be processed at high flow rates. The highly open macroporous structure with elastic por

Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon cancer cells.

It is well documented that prolonged inflammatory conditions, particularly those relating to the colon, have been shown to induce cancer. We have previously demonstrated that the pro-inflammatory mediator leukotriene D-4 (LTD4) induces survival and proliferation in intestinal cells and that its receptor, CysLT(1), is upregulated in human colon cancer tissue. Here we demonstrate, for the first time

Comparison of the cost of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin

The relative costs were analysed of (1) no prophylaxis against deep vein thrombosis (DVT), (2) selective treatment of DVT after confirmation of diagnosis, (3) general prophylaxis with standard low-dose unfractionated heparin and (4) general prophylaxis with low molecular weight heparin (LMWH) in patients undergoing elective general abdominal surgery or elective hip surgery. The mean calculated cos

Wax esters produced by solvent-free energy-efficient enzymatic synthesis and their applicability as wood coatings

The study aimed at developing a process for making a wood coating wax based on the principles of green chemistry. The research was conducted within the Swedish interdisciplinary research programme Greenchem. Wax esters are attractive since they are non-hazardous, biodegradable and can be produced in an atom-efficient process from building blocks obtained from renewable resources. Four wax esters w

Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)-family integrins through novel integrin-binding mechanisms

The LW blood group glycoprotein, ICAM-4, is a member of the intercellular adhesion molecule (ICAM) family expressed in erythroid cells. To begin to address the function of this molecule, ligands for ICAM-4 on hemopoietic and nonhemopoietic cell lines were identified. Peptide inhibition studies suggest that adhesion of cell lines to an ICAM-4-Fc construct is mediated by an LDV-inhibitable integrin