Laboratory studies in cross-species lung transplantation

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.     

Medium and substitution pattern effects on the action of hydroxyflavones as photoprotectors against singlet molecular oxygen-mediated photooxidation of fats

The ability of mono-, di-, tri-and tetra-hydroxyflavones (7-and 3-hy-droxyflavones, 7, 8-dihydroxyflavone, baicalein and fisetin) to act as photoprotectors against singlet molecular oxygen [O²(Δ_g)]-initiated photooxidation of fats has been established by a kinetic study. The overall quenching rate constants for a series of five hydroxyflavones perfectly parallel their respective behaviour as inhibitors of the sensitized photooxidation of linoleic acid. The best antioxidative effect was exerted by 7-hydroxyflavone which does not chemically react with O²(¹Δ_g). Nevertheless for the remaining flavonoids of the series, the physical deactivation of O²(¹Δ_g) largely prevails over the chemical process. As for the cases of phenols and related hydroxy-aromatic derivatives, the ionization of the -OH group in the flavones, dramatically accelerates the rate of photooxidation. Under these conditions, the 7-hydroxyflavone also reacts effectively with O²(¹Δ_g). Given that flavonoids are natural oil components, this medium effect should be taken into account during the oil-refining process, in order to avoid the flavonoid photodestruction.     

Urban design and conflicting city images of Brazil: Rio de Janeiro and Curitiba

Imageability of places, cities and countries is strongly influenced by tourist and political portraits in the media. As human cognition relies on inferential perception and contrasting categories, marketing strategies exploit partial truths and conflicting city images to direct public perceptions. This article addresses the relationship between international perception, image building and urban design in the case of Brazil and the cities of Rio de Janeiro and Curitiba. Their contrasting images as exploited by the international media expose only partial truths. In fact, these images represent complementary development contradictions that co-exist in any major city today.     

On the control of complementary-slackness juggling mechanicalsystems

Studies the feedback control of a class of complementary-slackness hybrid mechanical systems. Roughly, the systems we study are composed of an uncontrollable part (the “object”) and a controlled one (the “robot”), linked by a unilateral constraint and an impact rule. A systematic and general control design method for this class of systems is proposed. The approach is a nontrivial extension of the one degree-of-freedom (DOF) juggler control design. In addition to the robot control, it is also useful to study some intermediate controllability properties of the object's impact Poincare mapping, which generally takes the form of a nonlinear discrete-time system. The force input mainly consists of a family of dead-beat feedback control laws, introduced via a recursive procedure, and exploiting the underlying discrete-time structure of the system. The main goal of the paper is to highlight the role of various physical and control properties characteristic of the system on its stabilizability properties and to propose solutions in certain cases     

Analysis of the cyclic short-term variation of indoor power line channels

The purpose of this paper is to analyze the properties of indoor power line communications channels when they are used for broadband transmission. It will be shown that these channels exhibit a short-term variation, due to the fact that high-frequency parameters of electrical devices depend on the instantaneous amplitude of mains voltage. This phenomenon leads to a channel model proposal based on a linear periodically time-varying system and cyclostationary random noise. A measurement system, designed to capture these time variations in real power networks, and some of the most significant results obtained with it, are presented. In addition, a statistical analysis of the measurements performed in several indoor power line scenarios is included, so that the relevance of time variations in actual channels can be evaluated.     

Quality of Service Networking for High Performance Grid Applications

This paper reports on different efforts to provide quality of service (QoS) Networking to Grid applications done in the context of the MB-NG, GRS and DataTAG EU projects. These are leading edge network research projects involving more that 50 researchers in the UK, Europe and North America, concerned with the development and testing of protocols and standards for the next generation of high speed networks. We have implemented and tested the Differentiated Services Architecture (DiffServ) in a multi-domain, 2.5 Gbits/s network (the first such deployment) defining appropriate Service Level Agreements (SLAs) to be used between administrative domains to guarantee end-to-end Quality of Service. We characterised several hardware implementations of DiffServ and concluded on their appropriateness for several network scenarios. Since current and future Grid applications will have to use modified mechanisms of congestion control we have evaluated old and new TCP implementations over a Differentiated Services Networks. These quality of service tests have also included innovative MPLS (Multi-Protocol Label Switching) experiments to establish guaranteed bandwidth connections to Grid applications in a fast and efficient way. We have also developed a software based bandwidth broker architecture for Grids based on IETF standards which allows applications to transparently request dynamic and advanced reservations and implemented it in a real experimental network. We finally report on experiences delivering Quality of Service networking to high performance applications like Particle Physics data transfer and High Performance Computation. This includes quantitative results on the performance improvements that QoS brought to real data transfers in the context of High Performance Computing.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

Water: A key resource in energy production

Water and energy are the key resources required for both economic and population growth, and yet both are increasingly scarce. The distribution of water takes large amounts of energy, while the production of energy requires large amounts of water in processes such as thermal plant cooling systems or raw materials extraction. This study analyzes the water needs for energy production in Spain according to the energy source sector (electricity, transportation or domestic) and process type (extraction and refining of raw materials or thermal plant use). Current and future water needs are quantified according to energy demand and technology mix evolution. Hypothetical scenarios that simulate the risks of promoting specific energy policies are also analyzed. Results show that the combination of energy resources used in Spain is projected to be more than 25% more water consumptive in 2030 than in 2005 under ceteris paribus conditions. Renewable energies are mixed in terms of their consequences on the water supply; wind power can reduce water withdrawal, while the biofuels production is a water-intensive process.     

Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments

OBJECTIVE: To evaluate an experimental heroin maintenance programme. Design: Randomised trial. SETTING: Outpatient clinic in Geneva, Switzerland. SUBJECTS: Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments. INTERVENTION: Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance). Main outcome measures: Self reported drug use, health status (SF-36), and social functioning. RESULTS: 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up. CONCLUSIONS: A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.