Inflammation, complement activation and endothelial function in stable and unstable coronary artery disease

Background: Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease (CAD). Apart from traditional risk factors complement activation and inflammation may trigger and sustain endothelial dysfunction. We sought to assess the association between endothelial function, high sensitivity C-reactive protein (hs-CRP) and markers of complement activation in patients with either stable or unstable coronary artery disease. Methods: We prospectively recruited 78 patients, 35 patients with stable angina pectoris (SAP) and 43 patients with unstable angina pectoris (UAP). Endothelial function was assessed as brachial artery reactivity (BAR). Hs-CRP, C3a, C5a, and C1-Inhibitor (C1 inh.) were measured enzymatically. Results: Patients with IJAP showed higher median levels of hs-CRP and C3a compared to patients with SAP, while BAR was not significantly different between patient groups. In UAP patients, hs-CRP was significantly correlated with cholesterol (r = 0.27, p < 0.02), C3a (r = 0.32, p < 0.001) and C1 INH.(r = 0.41, p < 0.003), but not with flow mediated dilatation (r = 0.09, P = 0.41). Hs-CRP and C1 INH.were found to be independant predictors of IJAP in a backward stepwise logistic regression model. Conclusions: We conclude that both hs-CRP, a marker of inflammation and C3a, a marker of complement activation are elevated in patients with UAP, but not in patients with SAP. (c) 2005 Elsevier B.V. All rights reserved.

On the chaotic instability of a nonsliding liquid-filled top with a small spheroidal base via Melnikov-Holmes-Marsden integrals

Chaotic orientations of a top containing a fluid filled cavity are investigated analytically and numerically under small perturbations. The top spins and rolls in nonsliding contact with a rough horizontal plane and the fluid in the ellipsoidal shaped cavity is considered to be ideal and describable by finite degrees of freedom. A Hamiltonian structure is established to facilitate the application of Melnikov-Holmes-Marsden (MHM) integrals. In particular, chaotic motion of the liquid-filled top is identified to be arisen from the transversal intersections between the stable and unstable manifolds of an approximated, disturbed flow of the liquid-filled top via the MHM integrals. The developed analytical criteria are crosschecked with numerical simulations via the 4th Runge-Kutta algorithms with adaptive time steps.

Cyclic MrIA: A stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the, beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

Depression and cardiovascular morbidity and mortality: cause or consequence?

Background Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association. Methods and results Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General. Health Questionnaire score greater than or equal to5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P

Using the EM Algorithm to Train Neural Networks: Misconceptions and a New Algorithm for Multiclass Classification

The expectation-maximization (EM) algorithm has been of considerable interest in recent years as the basis for various algorithms in application areas of neural networks such as pattern recognition. However, there exists some misconceptions concerning its application to neural networks. In this paper, we clarify these misconceptions and consider how the EM algorithm can be adopted to train multilayer perceptron (MLP) and mixture of experts (ME) networks in applications to multiclass classification. We identify some situations where the application of the EM algorithm to train MLP networks may be of limited value and discuss some ways of handling the difficulties. For ME networks, it is reported in the literature that networks trained by the EM algorithm using iteratively reweighted least squares (IRLS) algorithm in the inner loop of the M-step, often performed poorly in multiclass classification. However, we found that the convergence of the IRLS algorithm is stable and that the log likelihood is monotonic increasing when a learning rate smaller than one is adopted. Also, we propose the use of an expectation-conditional maximization (ECM) algorithm to train ME networks. Its performance is demonstrated to be superior to the IRLS algorithm on some simulated and real data sets.

Existence and uniqueness of Q-processes with a given finite μ-invariant measure

Let Q be a stable and conservative Q-matrix over a countable state space S consisting of an irreducible class C and a single absorbing state 0 that is accessible from C. Suppose that Q admits a finite mu-subinvariant measure in on C. We derive necessary and sufficient conditions for there to exist a Q-process for which m is mu-invariant on C, as well as a necessary condition for the uniqueness of such a process.

Investigating the relationship between internet privacy concerns and online purchase behavior

Many organizations now emphasize the use of technology that can help them get closer to consumers and build ongoing relationships with them. The ability to compile consumer data profiles has been made even easier with Internet technology. However, it is often assumed that consumers like to believe they can trust a company with their personal details. Lack of trust may cause consumers to have privacy concerns. Addressing such privacy concerns may therefore be crucial to creating stable and ultimately profitable customer relationships. Three specific privacy concerns that have been frequently identified as being of importance to consumers include unauthorized secondary use of data, invasion of privacy, and errors. Results of a survey study indicate that both errors and invasion of privacy have a significant inverse relationship with online purchase behavior. Unauthorized use of secondary data appears to have little impact. Managerial implications include the careful selection of communication channels for maximum impact, the maintenance of discrete “permission-based” contact with consumers, and accurate recording and handling of data.

A commentary on the impacts of metals and metalloids in the environment upon the metabolism of drugs and chemicals

The salient feature of metals is that unlike organic compounds they do not degrade in the environment and barely move from one environmental matrix to another. Human interventions take these compounds from their stable and non-bioavailable geological matrix into situations of biological accessibility. Studies in the 1970s and the 1980s of metal bioavailability and impacts of metals and metalloids were driven by the process of abatement of lead in the environment. Humans have clear and identifiable sources of exposure from fuels, food and leaded water pipes to lead. Interventions started at that time have dramatically lowered human lead exposure. Attention has now shifted to other metals, in particular, cadmium, which has seen increasing use. It is generally accepted that food crops grown on cadmium containing soils or soils naturally rich in this metal are the major source of exposure to humans other than exposure from smoking of cigarettes. This mini-review gives a summary and commentary on early studies on effects of lead on haem metabolism that provide us the clue to why investigations of the impacts of other toxic heavy metals and metalloids such as cadmium and arsenic on different human cytochrome P450 forms have become of great interest at the current time. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner

Tertiapin, a short peptide from honey bee venom, has been reported to specifically block the inwardly rectifying K+ (Kir) channels, including G protein-coupled inwardly rectifying potassium channel (GIRK) 1 + GIRK4 heteromultimers and ROMK1 homomultimers. In the present study, the effects of a stable and functionally similar derivative of tertiapin, tertiapin-Q, were examined on recombinant human voltage-dependent Ca2+-activated large conductance K+ channel (BK or MaxiK; alpha-subunit or hSlo1 homomultimers) and mouse inwardly rectifying GIRK1 + GIRK2 (i.e., Kir3.1 and Kir3.2) heteromultimeric K+ channels expressed in Xenopus oocytes and in cultured newborn mouse dorsal root ganglion (DRG) neurons. In two-electrode voltage-clamped oocytes, tertiapin-Q (1-100 nM) inhibited BK-type K+ channels in a use- and concentration-dependent manner. We also confirmed the inhibition of recombinant GIRK1 + GIRK2 heteromultimers by tertiapin-Q, which had no effect on endogenous depolarization- and hyperpolarization-activated currents sensitive to extracellular divalent cations (Ca2+, Mg2+, Zn2+, and Ba2+) in defolliculated oocytes. In voltage-clamped DRG neurons, tertiapin-Q voltage- and use-dependently inhibited outwardly rectifying K+ currents, but Cs+-blocked hyperpolarization-activated inward currents including I-H were insensitive to tertiapin-Q, baclofen, barium, and zinc, suggesting absence of functional GIRK channels in the newborn. Under current-clamp conditions, tertiapin-Q blocked the action potential after hyperpolarization (AHP) and increased action potential duration in DRG neurons. Taken together, these results demonstrate that the blocking actions of tertiapin-Q are not specific to Kir channels and that the blockade of recombinant BK channels and native neuronal AHP currents is use-dependent. Inhibition of specific types of Kir and voltage-dependent Ca2+-activated K+ channels by tertiapin-Q at nanomolar range via different mechanisms may have implications in pain physiology and therapy.

Optimal control, geometry, and quantum computing

We prove upper and lower bounds relating the quantum gate complexity of a unitary operation, U, to the optimal control cost associated to the synthesis of U. These bounds apply for any optimal control problem, and can be used to show that the quantum gate complexity is essentially equivalent to the optimal control cost for a wide range of problems, including time-optimal control and finding minimal distances on certain Riemannian, sub-Riemannian, and Finslerian manifolds. These results generalize the results of [Nielsen, Dowling, Gu, and Doherty, Science 311, 1133 (2006)], which showed that the gate complexity can be related to distances on a Riemannian manifold.

Pattern analysis on grain yield performance of Chinese and CIMMYT spring wheat cultivars sown in China and CIMMYT

Understanding the relationships among testing environments is essential for better targeting cultivars to production environments. To identify patterns of cultivar, environment, cultivar-by-environment interactions, and opportunities for indirect selection for grain yield, a set of 25 spring wheat cultivars from China and the International Maize and Wheat Improvement Center (CIMMYT) was evaluated in nine environments in China and four management environments at CIMMYT in Cd. Obregon, Mexico, during two wheat seasons. Genetic background and original environment were the main factors influencing grain yield performance of the cultivars. Baviacora M 92, Xinchun 2 and Xinchun 6 showed relatively more stable and higher grain yields, whereas highly photoperiod sensitive cultivars Xinkehan 9, Kefeng 6 and Longmai 19 proved consistently inferior across environments, except in Harbin and Keshan, the two high latitude environments. Longmai 26, also from high latitude environments in the northeastern Heilongjiang province, was however probably not as photoperiodicly sensitive as other cultivars; from that region, and produced much higher grain yield and expressed a broader adaptation. None of the environments reported major diseases. Pattern analyses revealed that photoperiod response and planting option on beds were the two main factors underlying the observed interactions for grain yield. The production environment of planting on the flat in Mexico grouped together with Huhhot and Urumqi in both wheat seasons, indicating an indirect response to selection for grain yield in this CIMMYT managed environment could benefit the two Chinese environments. Both the environment of planting on the flat with Chinese Hejin and Yongning, and the three CIMMYT enviromnents planting on raised beds with Chinese Yongning grouped together only in one season, showing that repeatability may not be stable in this case.

Trends for in situ and invasive melanoma in Queensland, Australia, 1982-2002

Objectives Queensland, the north-eastern state of Australia, has the highest incidence of melanoma in the world. Control measures started earlier here than probably anywhere else in the world; early detection programmes started in the 1960s and primary prevention in the 1980s. Data from the population-based Queensland Cancer Registry therefore provide an internationally unique data source with which to assess trends for in situ and invasive melanomas and to consider the implications for early detection and primary prevention. Methods We used Poisson regression to estimate the annual percentage change in rates across 21 years of incidence data for in situ and invasive lesions, stratified by age and sex. Joinpoint analyses were used to assess whether there had been a statistically significant change in the trends. Results In situ melanomas increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%, 8.9%) per year among females. The incidence of invasive lesions also increased, but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid data on thickness was only available for 1991 to 2002 and for this period thin-invasive lesions were increasing faster than thick-invasive lesions (for example, among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower proportionate increase for the most recent years for both in-situ and invasive lesions, but this did not achieve statistical significance. Among people younger than 35 years, the incidence of invasive melanoma was stable and there was a suggestion of a birth cohort effect from about 1958. Mortality rates were stable across all ages, and there was a suggestion of decreasing rates among young women, although this did not achieve statistical significance. Conclusion Age-standardised incidence is continuing to increase and this, in combination with a shift to proportionately more in situ lesions, suggests that the stabilisation of mortality rates is due, in large part, to earlier detection. For primary prevention, after a substantial period of sustained effort in Queensland, there is some suggestive, but not definitive, evidence that progress is being made. Incidence rates are stabilising in those younger than 35 years and the proportionate increase for both in situ and invasive lesions appears to be lower for the most recent period compared with previous periods. However, even taking the most favourable view of these trends, primary prevention is unlikely to lead to decreases in the overall incidence rate of melanoma for at least another 20 years. Consequently, the challenge for primary prevention programmes will be to maintain momentum over the long term. If this can be achieved, the eventual public-health benefits are likely to be substantial.

Integration of sulphate reduction, autotrophic denitrification and nitrification to achieve low-cost excess sludge minimisation for Hong Kong sewage

An integrated anaerobic-aerobic treatment system of sulphate-laden wastewater was proposed here to achieve low sludge production, low energy consumption and effective sulphide control. Before integrating the whole system, the feasibility of autotrophic denitrification utilising dissolved sulphide produced during anaerobic treatment of sulphate rich wastewater was studied here. An upflow anaerobic sludge blanket reactor was operated to treat sulphate-rich synthetic wastewater (TOC = 100 mg/L and sulphate = 500 mg/L) and its effluent with dissolved sulphide and external nitrate solution were fed into an anoxic biofilter. The anaerobic reactor was able to remove 77-85% of TOC at HRT of 3 h and produce 70-90 mg S/L sulphide in dissolved form for the subsequent denitrification. The performance of anoxic reactor was stable, and the anoxic reactor could remove 30 mg N/L nitrate at HRT of 2 h through autotrophic denitrification. Furthermore, sulphur balance for the anoxic filter showed that more than 90% of the removed sulphide was actually oxidised into sulphate, thereby there was no accumulation of sulphur particles in the filter bed. The net sludge productions were approximately 0.15 to 0.18 g VSS/g COD in the anaerobic reactor and 0.22 to 0.31 g VSS/g NO3--N in the anoxic reactor. The findings in this study will be helpful in developing the integrated treatment system to achieve low-cost excess sludge minimisation.