4,643 research outputs found
Corporate Financing in Great Britain
Background: The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA). Methodology/Principal Findings: The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH) activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 mu M, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component) of 34 mu M. Conclusions/Significance: The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer
Particle Induced X-Ray Emission Microanalysis of Root Samples from Beech (Fagus sylvatica)
Beech seedlings (Fagus Sylvatica) were grown in a nutrient solution to which AlCl3 had been added. The experiments were designed to evaluate the effect of aluminum on the localization of elements in plant root tissue. Cross-sections of roots were analyzed with micro-PIXE (particle induced X-ray emission) and Rutherford backscattering (RBS) simultaneously. A proton beam of either 30x30 μm2 or 5x5 μm2 was scanned over the samples, and quantitative elemental maps were created. Aluminum was found to accumulate in high concentrations (percent levels) in the epidermis and the outer layer of the cortex, when the nutrient solution held 1.0 mM AlCl3. It was also obvious that calcium was depleted where aluminum accumulated. The distribution of aluminum was inhomogeneous, and therefore, it was necessary to analyze the total area of the cross-section and not only look at a small part of it, for example along a diametrical line
Correlation-induced conductance suppression at level degeneracy in a quantum dot
The large, level-dependent g-factors in an InSb nanowire quantum dot allow
for the occurrence of a variety of level crossings in the dot. While we observe
the standard conductance enhancement in the Coulomb blockade region for aligned
levels with different spins due to the Kondo effect, a vanishing of the
conductance is found at the alignment of levels with equal spins. This
conductance suppression appears as a canyon cutting through the web of direct
tunneling lines and an enclosed Coulomb blockade region. In the center of the
Coulomb blockade region, we observe the predicted correlation-induced
resonance, which now turns out to be part of a larger scenario. Our findings
are supported by numerical and analytical calculations.Comment: 5 pages, 4 figure
Temperature dependence of binary and ternary recombination of H3+ ions with electron
We study binary and the recently discovered process of ternary He-assisted
recombination of H3+ ions with electrons in a low temperature afterglow plasma.
The experiments are carried out over a broad range of pressures and
temperatures of an afterglow plasma in a helium buffer gas. Binary and
He-assisted ternary recombination are observed and the corresponding
recombination rate coefficients are extracted for temperatures from 77 K to 330
K. We describe the observed ternary recombination as a two-step mechanism:
First, a rotationally-excited long-lived neutral molecule H3* is formed in
electron-H3+ collisions. Second, the H3* molecule collides with a helium atom
that leads to the formation of a very long-lived Rydberg state with high
orbital momentum. We present calculations of the lifetimes of H3* and of the
ternary recombination rate coefficients for para and ortho-H3+. The
calculations show a large difference between the ternary recombination rate
coefficients of ortho- and para-H3+ at temperatures below 300 K. The measured
binary and ternary rate coefficients are in reasonable agreement with the
calculated values.Comment: 15 page
Load-Balancing for Parallel Delaunay Triangulations
Computing the Delaunay triangulation (DT) of a given point set in
is one of the fundamental operations in computational geometry.
Recently, Funke and Sanders (2017) presented a divide-and-conquer DT algorithm
that merges two partial triangulations by re-triangulating a small subset of
their vertices - the border vertices - and combining the three triangulations
efficiently via parallel hash table lookups. The input point division should
therefore yield roughly equal-sized partitions for good load-balancing and also
result in a small number of border vertices for fast merging. In this paper, we
present a novel divide-step based on partitioning the triangulation of a small
sample of the input points. In experiments on synthetic and real-world data
sets, we achieve nearly perfectly balanced partitions and small border
triangulations. This almost cuts running time in half compared to
non-data-sensitive division schemes on inputs exhibiting an exploitable
underlying structure.Comment: Short version submitted to EuroPar 201
Характеристика сили нервових процесів у плавців
OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence. METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1) 1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315). RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05]. CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease
p53 mutations in urinary bladder cancer
We have screened for mutations in exons 5–8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1–G2a) and 106 (56%) were highly malignant (G2b–G4 or ≥T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant. © 2001 Cancer Research Campaign http://www.bjcancer.co
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