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

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

An Improved Link Model for Window Flow Control and Its Application to FAST TCP

This paper presents a link model which captures the queue dynamics in response to a change in a transmission control protocol (TCP) source's congestion window. By considering both self-clocking and the link integrator effect, the model generalizes existing models and is shown to be more accurate by both open loop and closed loop packet level simulations. It reduces to the known static link model when flows' round trip delays are identical, and approximates the standard integrator link model when there is significant cross traffic. We apply this model to the stability analysis of fast active queue management scalable TCP (FAST TCP) including its filter dynamics. Under this model, the FAST control law is linearly stable for a single bottleneck link with an arbitrary distribution of round trip delays. This result resolves the notable discrepancy between empirical observations and previous theoretical predictions. The analysis highlights the critical role of self-clocking in TCP stability, and the proof technique is new and less conservative than existing ones

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

Queue Dynamics With Window Flow Control

This paper develops a new model that describes the queueing process of a communication network when data sources use window flow control. The model takes into account the burstiness in sub-round-trip time (RTT) timescales and the instantaneous rate differences of a flow at different links. It is generic and independent of actual source flow control algorithms. Basic properties of the model and its relation to existing work are discussed. In particular, for a general network with multiple links, it is demonstrated that spatial interaction of oscillations allows queue instability to occur even when all flows have the same RTTs and maintain constant windows. The model is used to study the dynamics of delay-based congestion control algorithms. It is found that the ratios of RTTs are critical to the stability of such systems, and previously unknown modes of instability are identified. Packet-level simulations and testbed measurements are provided to verify the model and its predictions

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

Cardiovascular co-morbidity in rheumatic diseases

Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed

Internalized stigma of mental illness in Tehran

Abstract Purpose: There are an increasing number of studies on the subjective experience of stigma amongst mentally ill persons but still few coming from low-and middle-income countries, and very few from Muslim countries. The objective of this study was to look into the experience of internalized stigma in mentally ill persons in Tehran, Iran. Methods: A total of 138 patients with an affective disorder or schizophrenia from three psychiatric institutions in Tehran responded to the Internalized Stigma of Mental Illness Scale. This is a 29-item self-report questionnaire with good psychometric properties. An open-ended question about personal experiences of discrimination was included at the end of the questionnaire. Results: The experience of stigma because of mental illnesses was high in this Iranian sample. The level of stigma was similar to studies from Europe that used the same questionnaire. Conclusion: This is the first study of self-perceived stigma in mentally ill persons in Iran. Stigma is a reality even in an Islamic setting in spite of the teachings of the Koran and a rather well-developed mental health service. Implications: These results call for actions to reduce the experience of stigma in mentally ill persons in Iran