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

Implementation of Provably Stable MaxNet

MaxNet TCP is a congestion control protocol that uses explicit multi-bit signalling from routers to achieve desirable properties such as high throughput and low latency. In this paper we present an implementation of an extended version of MaxNet. Our contributions are threefold. First, we extend the original algorithm to give both provable stability and rate fairness. Second, we introduce the MaxStart algorithm which allows new MaxNet connections to reach their fair rates quickly. Third, we provide a Linux kernel implementation of the protocol. With no overhead but 24-bit price signals, our implementation scales from 32 bit/s to 1 peta-bit/s with a 0.001% rate accuracy. We confirm the theoretically predicted properties by performing a range of experiments at speeds up to 1 Gbit/sec and delays up to 180 ms on the WAN-in-Lab facility

The effects of matter density uncertainties on neutrino oscillations in the Earth

We compare three different methods to evaluate uncertainties in the Earth's matter density profile, which are relevant to long baseline experiments, such as neutrino factories.Comment: 3 pages, 1 figure. Talk given at the NuFact'02 Workshop, London, 1-6 July, 200

Resource Management in Diffserv On DemAnd (RODA) PHR

The purpose of this draft is to present the Resource Management in Diffserv (RMD) On DemAnd (RODA) Per Hop Reservation (PHR) protocol. The RODA PHR protocol is used on a per-hop basis in a Differentiated Services (Diffserv) domain and extends the Diffserv Per Hop Behavior (PHB) with resource provisioning and control

Effects of hydrogen bonding on supercooled liquid dynamics and the implications for supercooled water

The supercooled state of bulk water is largely hidden by unavoidable crystallization, which creates an experimentally inaccessible temperature regime - a 'no man's land'. We address this and circumvent the crystallization problem by systematically studying the supercooled dynamics of hydrogen bonded oligomeric liquids (glycols), where water corresponds to the chain-ends alone. This novel approach permits a 'dilution of water' by altering the hydrogen bond concentration via variations in chain length. We observe a dynamic crossover in the temperature dependence of the structural relaxation time for all glycols, consistent with the common behavior of most supercooled liquids. We find that the crossover becomes more pronounced for increasing hydrogen bond concentrations, which leads to the prediction of a marked dynamic transition for water within 'no man's land' at T~220 K. Interestingly, the predicted transition thus takes place at a temperature where a so called 'strong-fragile' transition has previously been suggested. Our results, however, imply that the dynamic transition of supercooled water is analogous to that commonly observed in supercooled liquids. Moreover, we find support also for the existence of a secondary relaxation of water with behavior analogous to that of the secondary relaxation observed for the glycols.Comment: 20 pages, 5 figures; corrected typos, title changed, small clarifying text changes, two labels removed from Fig. 2

Taxonomy and evolutionary relationships within species of section Rimosae (Inocybe) based on ITS, LSU and mtSSU sequence data

The present study aimed at elucidating the structure of Inocybe subg. Inosperma sect. Rimosae but included also representatives from subg. Mallocybe and the genus Auritella. Phylogenetic relationships were inferred using ITS, LSU and mtSSU sequence data. The analyses recovered the ingroup as a monophyletic, strongly supported clade. The results indicate that recognizing Auritella on the genus level renders Inocybe paraphyletic. The species traditionally placed in sect. Rimosae were found to be distributed over two strongly supported clades, Maculata and Rimosae s.s. The Maculata clade clusters with sect. Cervicolores and the two represent subg. Inosperma in a strict sense. Rimosae s.s. emerges as an independent, supported clade well separated from Inosperma s.s. Twenty-one terminal groups were correlated with morphologically distinct species. In addition several taxa on single branches and minor less supported clades were recovered. A key to the identified species of the Maculata and Rimosae s.s. clades which occur in Northwest Europe is provided

Antimicrobial resistance and Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) genotypes in N. gonorrhoeae during 2012-2014 in Karachi, Pakistan

Background: Globally, increasing antimicrobial resistance (AMR) in Neisseria gonorrhoea has led to decreased treatment options for gonorrhoea. Continuous monitoring of resistance is crucial to determine evolving resistance trends in Neisseria gonorrhoea and to suggest treatment recommendations. Quality assured gonococcal AMR data from Pakistan are mainly lacking. This study was performed to determine prevalence and trends of gonococcal AMR and molecular epidemiology of local strains during 2012-2014 in Karachi, Pakistan. Methods: Gonococcal isolates (n = 100) were obtained from urogenital specimens submitted to the Aga Khan University Laboratory, Karachi, Pakistan. Antimicrobial susceptibility was determined using Etest and molecular epidemiology was assessed by N. gonorrhoeae multiantigen sequence typing (NG-MAST). Quality control was performed using N. gonorrhoeae WHO reference strains C, F, G, K, L, M, N, O, and P, and ATCC 49226. Results: Susceptibility to spectinomycin, ceftriaxone and cefixime was 100 % and to azithromycin was 99 %. All isolates had low ceftriaxone MICs, i.e., ≤0.032 mg/L. Resistance to ciprofloxacin, tetracycline and penicillin G were 86 %, 51 % and 43 %, respectively. NG-MAST analysis identified 74 different sequence types (STs). Conclusions: A highly diversified gonococcal population, 74 NG-MAST STs (62 novel STs) with an increased resistance to penicillin G, ciprofloxacin and tetracycline circulated in Karachi, Pakistan. Fortunately, no resistance to ceftriaxone was detected. Accordingly, ceftriaxone can continuously be recommended as the treatment of choice. However it is recommended to increase the dose of ceftriaxone from 125 mg intramuscularly to 250 mg intramuscularly due to ceftriaxone MIC creep and emerging resistance reported in the region. Furthermore, due to the high level of resistance to ciprofloxacin (86 %) it is essential to exclude ciprofloxacin from the recommended first-line therapy. It is imperative to significantly broaden the gonococcal AMR monitoring with participation from other laboratories and cities in Pakistan

Comparisons of Blockage Widths of Ideally Hard Cylinders of Different Cross-Sectional Shapes

In some applications the electromagnetic waves radiating from or being received by an antenna are obstructed by some mechanical structure. If the structure is part of or close to an antenna, the obstruction may represent aperture blockage causing increased sidelobes and reduced gain of the antenna. For example, the blocking structures can be struts or masts supporting the feed in reflectarrays or in reflectors. Usually in antennas, the direction of the incident wave is known, so the struts can be designed to reduce the blockage for a given direction of incidence