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

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

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

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

OBJECTIVE: To measure intracellular and tissue pH in periarticular soft tissue during different phases of antigen induced arthritis in the rat. METHODS: pH was calculated using the following values: (1) the distribution of [14C]-dimethyl-oxazolidinedione; (2) the total tissue water and the extracellular space water volume, which was measured as [14C]-sucrose distribution in nephrectomized rats. Ex

Gel electrolytes based on amphiphilic copolymethacrylates containing ethylene oxide (EO)(n) side chains as ionophilic units and fluorocarbon (CF,), side chains as ionophobic units showed a substantial increase in ion conductivity, as compared to corresponding gels based on homopolymers of (EO),, methacrylate. The highest ion conductivity was found for a gel based on a copolymer composed of 24 wt%

Vertical movement of snowmelt water through snowpacks is modelled by applying the kinematic wave theory. Analytical solutions are obtained for moisture flux, particle velocity, time history and velocity of meltwater front and total moisture content for a single melt event assuming that the melt rate is constant. These solutions are extended to the case involving more than one event.

Purpose: To compare the outcome of endovascular aneurysm repair (EVAR) versus conventional open repair (OR) in patients with a short, angulated or otherwise challenging proximal neck. Methods: The definition of a challenging proximal neck was based on diameter (>= 28 mm), length (= 60 degrees), shape (reverse tapered or bulging), and thrombus lining (>50%). Between January 2005 and December 2007,

Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR)

We developed a simple one-step dual-label immunoassay for simultaneous measurement of the free, noncomplexed form of prostate-specific antigen (PSA) and total PSA. The assay is based on time-resolved fluorescence and includes a stable fluorescent chelate of Eu to label a monoclonal antibody (mAb) that detects only free PSA, whereas a second mAb labeled with a fluorescent chelate of Tb provides equ

The short-term evolutionary effect of pheromone-based mating disruption on the mating ability of the Indian meal moth, Plodia interpunctella, was investigated. Three independent selection lines were established, and the mating ability of moths in plastic tents treated with high doses of pheromone and in control tents was compared for two consecutive generations. In addition, the heritability of th

PURPOSE: Hypoxia is considered to be a major driving force behind tumor angiogenesis. The stabilization and activation at hypoxia of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha and the concomitant induction of expression of vascular endothelial growth factor (VEGF) and other proangiogenic factors provide a molecular frame for hypoxia-driven tumor angiogenesis. This study has investigat

This article presents a systematic and extensive empirical study on the presence of Markov switching dynamics in three dollar-based exchange rates. A Monte Carlo approach is adopted to circumvent the statistical inference problem inherent to the test of regime-switching behavior. Two data frequencies, two sample periods, and various specifications are considered. Quarterly data yield inconclusive

To analyze complex and noncomplex cardiac malformations regarding prevalence and in relation to demographic variables, we pooled data on infants (age I year or younger) with congenital cardiovascular defects from three large birth defect registries in California, Sweden, and France. Altogether. 12.932 infants had one or more congenital heart defects out of 4.4 million live births and stillbirths.

This paper empirically studies the effects of fiscal policy shocks on private consumption. Further, it investigates if the initial financing needs of the government or previous fiscal deficits affect that relationship. We use yearly data between 1970 and 2000 for 40 countries, of which 19 are industrialized and 21 are developing countries. In general, the estimation results seem to indicate that g

The grafting of functional polymers to the pore surface of macroporous monolithic polyacrylamide cryogels was found to be an efficient and convenient method for the preparation of macroporous polyacrylamide gels, so-called cryogels (pAAm cryogels), with both controlled extent of functional group incorporated and with tailored surface chemistries. Anion-exchange polymer chains of poly(2-(dimethylam

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young a