bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPLEXITY AND GENERALIZED EXPONENTIAL RELAXATION: MEMORY VERSUS RENEWAL
Authors: GRIGOLINI PAOLO
Published: November 2008

We illustrate two distinct approaches to the Mittag–Leffler relaxation, as a mathematical expression suitable for the interpretation of real data produced by complex systems, and especially those of physiological interest. The first approach is based on interpreting the fluctuation–dissipation process under study as obtained via Subordination to the Ordinary Fluctuation–Dissipation (SOFD) process. The second approach rests on the Generalized Langevin Equation (GLE). We prove that in the real cases of truncated time series the two theories generate a survival probability in the form of a stretched exponential, and that this property makes it hard to assess if a given time series obeys the GLE or the SOFD prescription. Some conjectures are made on the possibility of distinguishing the GLE from the SOFD predictions through the analysis of a single time series.
DETECTION OF BROWNIAN PARTICLES (EULERIAN AND LAGRANGIAN STATISTICS OF IMPURITY PARTICLE IN ATMOSPHERE)
Authors: GRIBOVA EVGENIYA Z.
Published: November 2008

We study passive admixture spreading in the atmosphere considering regular (with the wind) and stochastic motion of the particles. The probability distribution of velocities on a boundary of a given spatial region (detector) is found for particles of a passive admixture. The connection between this probability distribution and the solution of the classical problem on the probability distribution of the coordinates and velocity of a Brownian particle at a fixed moment is determined. The dependence of the obtained probability density on the relation among the parameters of the problem under consideration is discussed. Some specific examples are presented. Potential applications of the results are in ecological and meteorological problems.
DYNAMICS AND SYNCHRONIZATION OF NOISE PERTURBED ENSEMBLES OF PERIODICALLY ACTIVATED NEURON CELLS
Authors: BELYKH VLADIMIR N. , PANKRATOVA EVGENIYA V. , MOSEKILDE ERIK
Published: November 2008

The role of noise for a single neuron and for an ensemble of mutually coupled neurons is investigated. For a single element we show that an increase in noise intensity in the regime of irregular firing enhances the coherence of the neuronal response. For this regime of spiking a study of the collective behavior for a chain composed of n mutually coupled Hodgkin–Huxley elements that are subjected simultaneously to sinusoidal drive and to a common random forcing is performed. The conditions for complete synchronization for this case are examined both within the framework of a theoretical approach based on the connection graph stability method and through numerical simulation.
NONDIVERGENT STATISTICAL QUANTUM ELECTRODYNAMICS
Authors: EFREMOV G. F. , SHARKOV V. V. , KRUPENNIKOV D. V.
Published: November 2008

Quantum space-time nonlocality, i.e. retardation of the interaction between an electron and its own radiation field at distances about the Compton wavelength, is established. By taking into account a finite variance of electron-coordinate increment in the intrinsic coordinate system, the radiative damping coefficient is obtained as a divergence-free function of frequency that is not subject to the well-known paradoxes of the classical theory of radiative damping. A relation between radiative damping and the electromagnetic mass of the electron is found.
NOISE INDUCED PHENOMENA IN POINT JOSEPHSON JUNCTIONS
Authors: GORDEEVA ANNA V. , PANKRATOV ANDREY L. , SPAGNOLO BERNARDO
Published: November 2008

We present the analysis of the mean switching time and its standard deviation of short overdamped Josephson junctions, driven by a direct current and a periodic signal. The effect of noise enhanced stability is investigated. It is shown that fluctuations may both decrease and increase the switching time.
DYNAMICS OF RADIATIVE POINT DEFECTS IN GALLIUM ARSENIDE DURING RELAXATION OF LOCAL HEATING
Authors: PANKRATOV E. L. , OBOLENSKY S. V.
Published: November 2008

In this paper we have analyzed the dynamics of redistribution of the radiative point defects in gallium arsenide during relaxation of the local heating in a semiconductor sample, generated by a radiative particle in the initial stage of stabilization of clusters of defects. We calculated: (i) the maximum heating temperature of a semiconductor sample, and (ii) the point defect diffusion coefficient corresponding to the maximum temperature.
INFLUENCE OF LENGTH ON THE NOISE DELAYED SWITCHING OF LONG JOSEPHSON JUNCTIONS
Authors: FEDOROV K. G. , PANKRATOV A. L. , SPAGNOLO B.
Published: November 2008

The transient dynamics of long overlap Josephson junctions in the frame of the sine-Gordon model with a white noise source is investigated. The effect of noise delayed decay is observed for the case of overdamped sine-Gordon equation. It is shown that this noise induced effect, in the range of small noise intensities, vanishes for junction lengths greater than several Josephson penetration lengths.
A MULTIVARIATE REGIME SWITCHING APPROACH TO THE RELATION BETWEEN THE STOCK MARKET, THE INTEREST RATE AND OUTPUT
Authors: KANAS ANGELOS
Published: November 2008

This paper presents empirical evidence that the relation between stock returns, real activity and interest rates for the US is regime dependent. Fixed exchange rates, and interest rate targeting are associated with a regime in which the joint behavior of these three variables is characterized by low volatility, whilst monetary aggregates targeting is associated with a high volatility regime. Both the contemporaneous and the dynamic relations change across regimes. Regime-dependent dynamic effects arise from interest rates to real activity, from stock returns to real activity and interest rates, and from real activity to interest rates. Dynamic impulse responses also vary across regimes.
A SCENARIO ANALYSIS OF THE RISK PREMIUM IN G7 COUNTRIES
Authors: OMRAN MOHAMMED , POINTON JOHN
Published: November 2008

In this investigation over 144,000 simulations are undertaken of country equity risk premia, based on a scenario analysis of the uncertainty surrounding the period of non-sustainable growth in earnings and stock returns. Final estimates, from the larger data-sets in Japan, the US and the UK, are around 3–6% in nominal terms, and compare well with other methodologies. However, except for Canada, the smaller data-sets in France, Germany and Italy reveal much higher risk premia than expected. Furthermore, given the spreads in estimates generally, the issue of sustainability is still contentious.
A NOTE ON THE RISK-PREMIUM PROCESS IN AN EQUILIBRIUM
Authors: SEKINE JUN
Published: November 2008

Results in He–Leland (1993) are extended and properties of the risk-premium process in an equilibrium are examined in a pure exchange economy with a representative agent: for example, (i) the risk-premium process is characterized by using a martingale representation of the reciprocal of a terminal marginal utility, (ii) it is expressed as a (conditional) expected value including the relative risk aversion coefficient of a terminal utility and the Jacobian matrix process of the state variables, and, (iii) a "mean-reverting" property relates to the monotonic decreasing property of the relative risk aversion coefficient.
Marin Cureau de la Chambre on the Natural Cognition of the Vegetative Soul: An Early Modern Theory of Instinct
Authors: Wild Markus
Published: November 2008

According to Marin Cureau de La Chambre—steering a middleway between the Aristotelian and the Cartesian conception of the soul—everything that lives cognizes and everything that cognizes is alive. Cureau sticks with the general tripart distinction of vegetative, sensitive, and intellectual soul. Each part of the soul has its own cognition. Cognition is the way in which living beings regulate bodily equilibirum and environmental navigation. This regulative activity is gouverned by acquired or by innate images. Natural cognition (or instinct) is cognition by innate images only. Cureau develops a highly originel theory of natural (or 'specialized') instinct. His theory attempts to explain five features of instinct (innateness, specialization, species-specifitiy, coerciveness, teleological nature). According to my interpretation, Cureau proposes a species of what is called a 'teleosemantic theory' of innate cognition.
The Temple of Ištar at Old Babylonian Alalakh
Authors: Lauinger Jacob
Published: November 2008

The temple of Ištar is well attested in the Old Babylonian (level VII) texts from Alalakh. However, it is not evident from these attestations whether the temple was an autonomous institution or part of the palace administration. This article demonstrates first that an excavated temple dating to the level VII occupation is the same temple of Ištar known from the texts; and second that the excavated temple contained an archive documenting a store of the palace's silver. These conclusions affirm that the temple of Ištar lay within the purview of the palace administration. The article ends by suggesting that the palace may have encompassed the temple not just administratively but also architecturally.
Simulating the climatic effects on vegetation: approaches, issues and challenges
Authors: Guoping Tang  , Bartlein Patrick J.
Published: November 2008

Vegetation modelling has been viewed as a major approach for examining the dynamics of vegetation under climatic change. However, the characterization of uncertainty of model results is still a key issue. In order to improve future model-based research, it is important to synthesize the current approaches and the issues that arise in vegetation modelling and to propose potential strategies for improving model-based research. This study first reviews the progress of vegetation models from static-equilibrium to transient-dynamic and to current coupled multi-objective vegetation models. Then, the four main sources leading to the uncertainty of model results are described, including (1) factors related to vegetation models (their structure, assumption and parameterization), (2) the data used to run a model, (3) the approaches used to validate model results, and (4) the spatiotemporal scaling issues involved in vegetation modelling. Finally, four strategies are proposed for improving future model-based research. These include improvements in the model structure and parameterization, enhancement of the quality of analytical data, improvement of the analytical approaches, and continued development of coupled dynamic vegetation models. Using a literature synthesis, this study provides researchers with a general guidance on applying vegetation models for simulating the effects of climatic variations on terrestrial vegetation.
Study on Glass Fabric Reinforced Polytetrafluoroethylene Composites Infused with Melted Cyanate Ester Resin
Authors: Penggang Ren , Guozheng Liang , Zengping Zhang
Published: November 2008

Melted bisphenol A dicyanate ester (BADCy) resin was infused into glass fabric/ PTFE(GF/PTFE) wave-transparent composites to improve the mechanical properties of GF/PTFE composites. The influence of the infusing process, the porosity of GF/PTFE composites, and the content of infused BADCy resin on the dielectric and mechanical properties of GF/PTFE composites was studied. The fracture surfaces of the broken specimens were also examined by scanning electron microscopy (SEM). It was found that when the porosity of GF/PTFE composites was 25%, the infused temperature is 85°C, and the vacuum is 0.01 MPa, the infused contents of BADCy in GF/PTFE/BADCy composites could reach 14.4%. The tensile strength, flexural strength, and interlaminar shear strength (ILSS) of GF/PTFE composites were improved from 81.6, 64.4, and 4.8 MPa to 186.6, 163.5, and 26.2 MPa, respectively. At the same time, the dielectric constant (ε) and tangent dielectric loss angle (tan δ) of GF/PTFE composites increased slightly. The wet/hot and environment-resistant investigation showed that the GF/PTFE composites infused by BADCy resin possessed low water absorption, small coefficient of thermal expansion(CTE), and good anti-environment properties.
Performance Evaluation of Treated—Untreated Jute—Carbon and Glass—Carbon Hybrid Composites of Bisphenol-C based Mixed Epoxy—Phenolic Resins
Authors: Patel V.A. , Bhuva B.D. , Parsania P.H.
Published: November 2008

Jute—carbon and glass—carbon hybrid composites of mixed matrix material [epoxy resin of bisphenol-C (EBC) and bisphenol-C-formaldehyde (BCF) of 50 wt% of the fibers] have been prepared by hand lay-up technique at 150°C under 7.6MPa pressure for 2h. Alkali-treated jute fibers have been acrylated to improve their physico-chemical properties. Tensile strength, flexural strength, electric strength, and volume resistivity of untreated (JCEBCF-50), treated (TJCEBCF-50) jute—carbon and glass—carbon (GCEBCF-50) composites are 10 MPa, 17 MPa, 1.60 kV/mm, and 5.9 × 1012 Ω-cm; 14.65 MPa, 19.33 MPa, 2.09 kV/mm, and 6.79 × 1012 Ω-cm; and 21.4 MPa, 24.53 MPa, 1.62 kV/mm, and 5.71 × 1012 Ω-cm, respectively. Alkali treatment and acrylation of jute fibers resulted in 46.50, 13.71, 24.40, and 15.15% improvement in tensile, flexural, electric strengths and volume resistivity, respectively. Water uptake tendency of jute—carbon composite is considerably reduced upon alkali treatment and acrylation of jute fiber. Observed equilibrium water content in all the three composites is HCl > H2O > NaCl. Observed reduction in water uptake in TJCEBCF-50 is due to esterification of hydrophilic OH groups. In boiling water saturation time is reduced 20 times for JCEBCF-50 and TJCEBCF-50, and 16 times for GCEBCF-50 without any damage. Hybrid composites may be useful for low load bearing application and also in marine field.
Comparison of Reinforcing Efficiency between Recycled Newspaper (RNP)/Carbon Black (CB) and Recycled Newspaper (RNP)/Silica Hybrid Filled Polypropylene (PP)/Natural Rubber (NR) Composites
Authors: Osman H. , Ismail H. , Mariatti M.
Published: November 2008

Comparison was made between properties of recycled newspaper (RNP)/carbon black (CB) and recycled newspaper (RNP)/silica hybrid filled polypropylene (PP)/natural rubber (NR) composites. The properties of composites consisting of processing characteristics, mechanical properties, thermal analysis via thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), scanning electron microscopy (SEM) morphology and water absorption were studied. The results revealed that the incorporation of CB and silica in the weight ratio of RNP/CB and RNP/silica hybrid has increased stabilization torque of the composites. Certain mechanical properties of the composites such as tensile strength and elongation at break (EB) were found increased, while Young’s modulus decreased with increasing CB and silica content. The incorporation of CB in the weight ratio of RNP/CB hybrid shows higher stabilization torque, tensile strength, elongation at break (EB) compared with RNP/silica hybrid of the PP/NR composites. However, RNP/silica hybrid exhibited higher Young’s modulus than RNP/CB hybrid of the PP/NR composites. TGA and DSC results indicate that primary and secondary peak of DTG curve, initial degradation temperature (T0), degradation temperature (Tdeg), melting temperature (Tm), heat of fusion of composites (ΔHf(com)), crystallinity of composites (Xcom) and PP (XPP) increased, while total weight loss and thermal degradation rate decreased for both hybrid composites. The RNP/silica hybrid is likely to be more thermal resistance and more crystalline than RNP/CB hybrid of the composites. A correlation between the increment of tensile strength and morphology of the composites was also studied. Results show that the presence of CB and silica has increased interfacial interaction between polymer and filler of the composites.
Computational Modeling and Numerical Simulation of Flow-Induced Crystallization Kinetics During Injection Molding of Polyethylene Terephthalate
Authors: Zhou Ying-Guo , Shen Chang-Yu , Liu Cun-Tai , Li Qian , Turng Lih-Sheng
Published: November 2008

A flow-induced crystallization kinetics model for semi-crystalline polymer polyethylene terephthalate (PET) was proposed based on the hypothesis that the energy of dissipation speeds up crystallization. By assuming that the effect of flow on crystallization only influenced the crystallization rate constant, the basic quiescent-state crystallization equation could be directly applied to the model flow-induced crystallization kinetics. The model predicts most of the features of flow-induced crystallization and can be easily used, especially when the real manufacturing process is considered because unknown parameters can be kept to a minimum. As an illustrative example, the injection molding of a PET part was simulated, during which the development of crystallization was controlled through the temperature of the mold resulting in a feasible method, through which transparent PET products were produced.
Failure Behavior of Composite Laminates with Multi-Pin Loaded Holes
Authors: Karakuzu Ramazan , Icten Bulent Murat , Tekinşen Özer
Published: November 2008

The aim of this study is to determine the failure behavior of laminated glass—epoxy composite plate which is subjected to a traction force by four pins. The failure load and failure mode of composite plates which have the stacking sequence of [0/90/±45]S has been observed experimentally. The ratio of edge distance from the hole center to pin diameter (E/D), the ratio of longitudinal holes distance to pin diameter (F/D) and the ratio of transverse holes distance to pin diameter (G/D) were selected as parameters. The results showed that the specimens except for E/D = 2 have similar behavior in terms of failure loads and failure modes.
Effects of pesticide exposure on the human immune system
Authors: Corsini E , Liesivuori J , Vergieva T , Van Loveren H , Colosio C
Published: November 2008

Epidemiological evidence from Western countries indicates that the prevalence of diseases associated with alterations in the immune response, such as asthma, certain autoimmune diseases and cancer, are increasing to such an extent that it cannot be attributed to improved diagnostics alone. There is some concern that this trend could be, at least, partially attributable to new or modified patterns of exposures to chemicals, including pesticides. The purpose of this article is to review the evidence on pesticide immunotoxicity in humans. Overall, the available data are inadequate to draw firm conclusions on the immunotoxic risk associated with pesticide exposure. The available studies on the effects of pesticides on the human immune system have several limitations, including limited data on exposure levels, heterogeneity of the applied methods, and difficulties in assessing the prognostic significance of observed slight changes and in the interpretation of the reported findings. Further studies are needed and preferably as prospective studies, comparing pre- and post-exposure data in the same group of subjects and including an appropriate non-exposed control group. More knowledge is required regarding the prognostic significance of the small changes observed.
Asthmatic symptoms after exposure to ethylenebisdithiocarbamates and other pesticides in the Europit field studies
Authors: Boers D , van Amelsvoort L , Colosio C , Corsini E , Fustinoni S , Campo L , Bosetti C , La Vecchia C , Vergieva T , Tarkowski M , Liesivuori J , Steerenberg P , van Loveren H
Published: November 2008

We conducted a multicenter prospective study to assess the effects of occupational exposure to ethylenebisdithiocarbamate fungicides and/or other pesticides on self-reported asthma and asthmatic symptoms. This multicenter study was conducted among 248 workers exposed to pesticides and 231 non-exposed workers from five field studies. The five field studies were carried out in The Netherlands, Italy, Finland, and two studies in Bulgaria. Subjects constituting this cohort completed a self-administered questionnaire at baseline (before the start of exposure). Ethylenethiourea in urine was determined to assess exposure to ethylenebisdithiocarbamates. In multivariate analyses adjusted for all potential confounders (age, education, residence, smoking, gender, and field study), we found inverse associations, all not statistically significant, between occupational exposure to pesticides and asthma diagnosis (OR 0.41; 95% CI 0.15–1.11), complains of chest tightness (OR 0.60; 95% CI 0.36–1.02), wheeze (OR 0.56; 95% CI 0.32–0.98), asthma attack (OR 0.52; 95% CI 0.12–2.25), and asthma medication (OR 0.79; 95% CI 0.25–2.53). Furthermore, we reported null associations for multivariate analysis using ethylenethiourea as determinant for exposure. Although exposure to pesticides remains a potential health risk, our results do not suggest an association between exposure to ethylenebisdithiocarbamates and/or other pesticides used in our study on asthma and asthmatic symptoms.
A Comparative Study of Damage Variables in Continuum Damage Mechanics
Authors: Voyiadjis George Z. , Kattan Peter I.
Published: November 2008

In this work, various definitions of the damage variables are examined and compared. In particular, special emphasis is given to a new damage variable that is defined in terms of the elastic stiffness of the material. Both the scalar and tensorial cases are investigated. The scalar definition of the new damage variable was used recently by many researchers. However, the generalization to tensors and general states of deformation and damage is new and appears here for the first time. In addition, transformation laws for various elastic constants are derived. Finally, the cases of plane stress, plane strain, and isotropic elasticity are examined in detail. In these cases it is shown that only two independent damage parameters are needed to describe the complete state of damage in the material. In this work, a physical basis is sought for the damage tensor [M] that is used to link the damage state of the material with effective undamaged configuration. The authors and numerous other researchers have used different paths including fabric tensors (Voyiadjis and Kattan, 2006a; Voyiadjis et al., 2007) to connect the two configurations. However, the approach presented here provides for a strong physical basis for this missing link.
What insights have new imaging techniques given into aggressive forms of MS – different forms of MS or different from MS?
Authors: Pichiecchio A , Tavazzi E , Maccabelli G , Precupanu CM , Romani A , Roccatagliata L , Luccichenti G , Bergamaschi R , Bastianello S
Published: November 2008

“Aggressive” multiple sclerosis (MS) is still a challenging diagnosis, in spite of the relevant progresses concerning the comprehension of the disease mechanisms, especially through pathology studies and the advent of conventional magnetic resonance imaging (MRI). Some reviews have been already published on their clinical and therapeutical aspects, but no systematic review is available in literature about the neuroradiological features, using both conventional and advanced techniques. In particular, advanced MRI techniques, namely diffusion-weighted and tensor imaging, magnetization transfer imaging, and proton magnetic resonance spectroscopy, are giving new insights to find specific and appropriate radiological parameters that can help in targeting the diagnosis. We report a review of literature on the neuroradiological findings of aggressive forms of MS, focusing specifically on the role of advanced MRI techniques in the diagnostic phase and during follow-up.
Determinants of health promotion action in primary health care: Comparative study of health and home care personnel in four municipalities in Finland
Authors: Simonsen-Rehn Nina , Laamanen Ritva , Sundell Jari , Brommels Mats , Suominen Sakari
Published: November 2008

Aims: The purpose of this paper is to contribute to understanding which factors influence health promotion action in primary health care (PHC) on the municipal, i.e. local, level. Methods: A cross-sectional mail survey of all PHC personnel in four municipalities in Finland in 2002. The data were analysed by descriptive statistics, and univariate and multivariate logistic regression analyses. Results: A total of 417 (response rate 57%) healthcare professionals participated in the study; 65% of the personnel working in ambulatory care, 52% working in home care and 44% working in inpatient care were engaged in health promotion action (=higher than median engagement). Factors independently associated with engagement in health promotion were organizational values, reflected in perceived skill discretion and social support from coworkers, and the personnel's competence, reflected in knowledge about the health and living conditions of the population served. Further, the opportunities, reflected in cooperation with partners outside the organization were strongly associated with engagement in health promotion action. Conclusions: The results suggest that working conditions such as possibilities for skill usage, reflection and development as well as collegial support enable higher engagement in health promotion action in PHC. However, access to data on the local population's health and living conditions, in addition to opportunities to cooperate with decision makers and partners in the community turned out to be as important. This should be taken into consideration when striving to reorient health services to health promotion.
Issuing sickness certificates: A difficult task for physicians: A qualitative analysis of written statements in a Swedish survey
Authors: Gerner Ulla , Alexanderson Kristina
Published: November 2008

Background: There is scientific evidence, but limited, that physicians experience sickness certification tasks as problematic. More knowledge is needed about physicians' own opinions on this matter. Aim: To further describe the experiences of physicians regarding their task of sickness certification. Methods: Qualitative analyses of 622 written responses to an open-ended question on physicians' own opinions about sickness certification given in a comprehensive questionnaire that comprised 83 close-ended items about this matter. The questionnaire was sent to 7665 physicians in Sweden and the response rate was 71%. Results: The physicians stated that they found it difficult to provide sickness certificates and expressed frustration over an altered concept of disease, problems in assessing work capacity, lack of time, labour market issues, limited resources for care and rehabilitation, and lack of management and support in their work. They also felt that their authority has diminished and that it was hard to combine the two roles of being patients' advocate and a medical expert. Consequently, they felt distressed and suggested that several types of changes be made, including transfer of sickness certification tasks to specialized physicians, multi-professional teams, or specialized clinics, and introduction of specific guidelines for certification. Conclusions: Physicians state several types of problems related to sickness certification tasks and many lack support in handling these problems. Such support needs to be improved, and scientifically studied.
`Dress as a man'
Authors: Tagg Brendon
Published: November 2008

This article is based on 13 open-ended interviews with current and former executive council members of the New Zealand Men's Netball Association (NZMNA). The article disputes the established view that regional women's netball associations and New Zealand's national netball association, Netball New Zealand (NNZ), fostered men's netball competitions in the early 1980s. The article instead argues that men's netball was developed by players prevented from participating in women's competitions. The article also suggests that the limited existing literature relating to the NZMNA fails to acknowledge much of the detail and character of the early association, including the critical influences of gay and transgender players and the cultural influences of Māori (New Zealand's indigenous people) and Pacific Islanders. Only more recently have flamboyant displays and marginalized masculinities been excluded, thereby rendering the NZMNA netball competitions a relatively hetero-normative domain.
Review: Antioxidant therapeutic advances in COPD
Authors: Rahman Irfan
Published: November 2008

Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of morbidity and mortality. Cigarette smoke-induced oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine and carbocysteine; Nrf2 activators; and dietary polyphenols (curcumin, resveratrol, and green tea catechins/quercetin) have been reported to increase intracellular thiol status along with induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD.
Review: Pharmacotherapy of obstructive sleep apnea
Authors: Jayaraman Gnananadh , Sharafkhaneh Hossein , Hirshkowitz Max , Sharafkhaneh Amir
Published: November 2008

Obstructive sleep apnea (OSA) is associated with serious comorbid illnesses and diminished quality of life. At this time, continuous positive airway pressure (CPAP) therapy is the treatment of choice. However, only half of those individuals who accept CPAP are still using it at the end of one year. Furthermore, efficacy for improving self-reported sleepiness appears to be greater for patients with severe sleep apnea and severe sleepiness than other patient groups. Some patients, notwithstanding optimized therapy and therapeutic adherence continue experiencing excessive daytime somnolence. Consequently, other treatment modalities have developed, including oral appliances, surgery and pharmacotherapy. It is widely believed, albeit not empirically demonstrated, that an effective medication to treat OSA would elicit better acceptance and adherence than having to use a machine for many hours on a nightly basis. Nonetheless, paucity of data (i.e. lack of large-scale randomized controlled trials), variability of perceived and actual benefits, and adverse side-effects of the drugs thus far tested have prevented the use of pharmacotherapy until now. In this paper we review the outcome data from published trials designed to evaluate efficacy and safety of various medications proposed for treating obstructive sleep apnea.
Review: Novel targets in the management of pneumonia
Authors: Díaz Luis A. , Mortensen Eric M. , Anzueto Antonio , Restrepo Marcos I.
Published: November 2008

Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases in the US. It accounts each year for 500,000 hospitalizations and 45,000 deaths and represents one of the most common causes of intensive care unit (ICU) admission. The mortality rate due to severe CAP has shown little improvement in the past three decades, remaining between 21% and 58% in patients admitted to the intensive care unit. Antimicrobial agents are the cornerstone of therapy against CAP, but there are some novel antibiotic and nonantibiotic therapies that have been recently tested that may potentially impact outcomes of patients with severe CAP. We will review the most recent data regarding novel therapies in patients with the highest risk of death such as those with severe CAP.
Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms
Authors: Sommer N. , Dietrich A. , Schermuly R. T. , Ghofrani H. A. , Gudermann T. , Schulz R. , Seeger W. , Grimminger F. , Weissmann N.
Published: November 2008

Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler–Liljestrand mechanism, is a physiological response to alveolar hypoxia which distributes pulmonary capillary blood flow to alveolar areas of high oxygen partial pressure.

Impairment of this mechanism may result in hypoxaemia. Under conditions of chronic hypoxia generalised vasoconstriction of the pulmonary vasculature in concert with hypoxia-induced vascular remodelling leads to pulmonary hypertension. Although the principle of HPV was recognised decades ago, its exact pathway still remains elusive. Neither the oxygen sensing process nor the exact pathway underlying HPV is fully deciphered yet. The effector pathway is suggested to include L-type calcium channels, nonspecific cation channels and voltage-dependent potassium channels, whereas mitochondria and nicotinamide adenine dinucleotide phosphate oxidases are discussed as oxygen sensors. Reactive oxygen species, redox couples and adenosine monophosphate-activated kinases are under investigation as mediators of hypoxic pulmonary vasoconstriction. Moreover, the role of calcium sensitisation, intracellular calcium stores and direction of change of reactive oxygen species is still under debate.

In this context the present article focuses on the basic mechanisms of hypoxic pulmonary vasoconstriction and also outlines differences in current concepts that have been suggested for the regulation of hypoxic pulmonary vasoconstriction.
Periodic leg movements in Cheyne–Stokes respiration
Authors: Manconi M. , Vitale G. , Ferri R. , Zucconi M. , Ferini-Strambi L.
Published: November 2008

Periodic leg movements during sleep (PLMS) are repetitive jerks of the lower limbs. Their occurrence can be isolated or part of various sleep disorders, such as restless legs syndrome (RLS), narcolepsy and obstructive sleep apnoea. Dopamine agonists are very effective in suppressing PLMS in RLS from the first night of administration. PLMS are often associated with cortical and autonomic arousals and may contribute to sleep disruption.

Herein, a case of association between PLMS, Cheyne-Stokes respiration (CSR) and severe insomnia is described.

Repeated polysomnographic studies demonstrated a clear synchronisation between PLMS and hyperventilation episodes, and the complete recovery of CSR, sleep quality and PLMS during nocturnal ventilation. In the same patient, pharmacological treatment with a dopamine agonist was ineffective on both PLMS and CSR.

These results suggest that periodic leg movements during sleep coupled with central breathing events, similar to those observed in conjunction with obstructive events, may have a different origin in terms of neurotransmitter and pathway implicated, compared with periodic leg movements during sleep in restless legs syndrome, and are resolved by treatment of the respiratory abnormalities.
Epithelial fibroblast triggering and interactions in pulmonary fibrosis
Authors: Noble P. W.
Published: November 2008

Idiopathic pulmonary fibrosis (IPF) is characterised by repeated injury to the alveolar epithelium with loss of lung epithelial cells and abnormal tissue repair, resulting in excessive accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix components and distortion of lung architecture, eventually leading to respiratory failure.

There is growing circumstantial evidence to suggest that in IPF the alveolar epithelium is prone to undergoing programmed cell death following repeated injury, although the mechanism for inducing epithelial apoptosis is, as yet, unknown. Potentially, one explanation may be the formation of misfolded proteins and an unfolded protein response-mediated apoptosis in alveolar epithelial cells (AECs), in response to abnormal protein production and aggregation.

Epithelial apoptosis is accompanied by damage to the basement membrane leading to the release of growth factors and chemokines, which recruit fibroblasts to the site of injury (fibroblastic foci). Instead of AECs healing by repair, myofibroblast proliferation and extracellular matrix deposition continues unabated in IPF.

The transformation of epithelial cells into mesenchymal cells, a process known as epithelial-mesenchymal transition, which allows direct communication between cells, is a possible explanation for the activation of alveolar epithelial cells in idiopathic pulmonary fibrosis. The present article discusses this process and other potential mechanisms by which epithelial cell injury can lead to fibroblast recruitment and accumulation in idiopathic pulmonary fibrosis.
Gene expression profiling: can we identify the right target genes?
Authors: Loyd J. E.
Published: November 2008

Gene expression profiling allows the simultaneous monitoring of the transcriptional behaviour of thousands of genes, which may potentially be involved in disease development. Several studies have been performed in idiopathic pulmonary fibrosis (IPF), which aim to define genetic links to the disease in an attempt to improve the current understanding of the underlying pathogenesis of the disease and target pathways for intervention.

Expression profiling has shown a clear difference in gene expression between IPF and normal lung tissue, and has identified a wide range of candidate genes, including those known to encode for proteins involved in extracellular matrix formation and degradation, growth factors and chemokines.

Recently, familial pulmonary fibrosis cohorts have been examined in an attempt to detect specific genetic mutations associated with IPF. To date, these studies have identified families in which IPF is associated with mutations in the gene encoding surfactant protein C, or with mutations in genes encoding components of telomerase.

Although rare and clearly not responsible for the disease in all individuals, the nature of these mutations highlight the importance of the alveolar epithelium in disease pathogenesis and demonstrate the potential for gene expression profiling in helping to advance the current understanding of idiopathic pulmonary fibrosis.
Gap junctions in the ovary of Drosophila melanogaster: localization of innexins 1, 2, 3 and 4 and evidence for intercellular communication via innexin-2 containing channels
Authors: Bohrmann Johannes , Zimmermann Jennifer
Published: November 2008

Background

In the Drosophila ovary, germ-line and soma cells are interconnected via gap junctions. The main gap-junction proteins in invertebrates are members of the innexin family. In order to reveal the role that innexins play in cell-cell communication during oogenesis, we investigated the localization of innexins 1, 2, 3 and 4 using immunohistochemistry, and analyzed follicle development following channel blockade.

Results

We found innexin 1 predominantly localized to the baso-lateral domain of follicle cells, whereas innexin 2 is positioned apico-laterally as well as apically between follicle cells and germ-line cells. Innexin 3 was observed laterally in follicle cells and also in nurse cells, and innexin 4 was detected in the oolemma up to stage 8 and in nurse-cell membranes up to stage 12. In order to test whether innexins form channels suitable for intercellular communication, we microinjected innexin antibodies in combination with a fluorescent tracer into the oocyte of stage-10 follicles. We found that dye-coupling between oocyte and follicle cells was largely reduced by innexin-2 antibodies directed against the intracellular C-terminus as well as against the intracellular loop. Analyzing in vitro, between stages 10 and 14, the developmental capacities of follicles following microinjections of innexin-2 antibodies revealed defects in follicle-cell differentiation, nurse-cell regression, oocyte growth and choriogenesis.

Conclusion

Our results suggest that all analyzed innexins are involved in the formation of gap junctions in the ovary. While innexins 2 and 3 are colocalized between soma cells, innexins 2 and 4 are colocalized between soma and germ-line cells. Innexin 2 is participating in cell-cell communication via hemichannels residing in the oolemma. It is obvious that gap-junctional communication between germ-line and soma cells is essential for several processes during oogenesis.
Evolution of the mitochondrial genome in snakes: Gene rearrangements and phylogenetic relationships
Authors: Yan Jie , Li Hongdan , Zhou Kaiya
Published: November 2008

Background

Snakes as a major reptile group display a variety of morphological characteristics pertaining to their diverse behaviours. Despite abundant analyses of morphological characters, molecular studies using mitochondrial and nuclear genes are limited. As a result, the phylogeny of snakes remains controversial. Previous studies on mitochondrial genomes of snakes have demonstrated duplication of the control region and translocation oftrnLto be two notable features of the alethinophidian (all serpents except blindsnakes and threadsnakes) mtDNAs. Our purpose is to further investigate the gene organizations, evolution of the snake mitochondrial genome, and phylogenetic relationships among several major snake families.

Results

The mitochondrial genomes were sequenced for four taxa representing four different families, and each had a different gene arrangement. Comparative analyses with other snake mitochondrial genomes allowed us to summarize six types of mitochondrial gene arrangement in snakes. Phylogenetic reconstruction with commonly used methods of phylogenetic inference (BI, ML, MP, NJ) arrived at a similar topology, which was used to reconstruct the evolution of mitochondrial gene arrangements in snakes.

Conclusion

The phylogenetic relationships among the major families of snakes are in accordance with the mitochondrial genomes in terms of gene arrangements. The gene arrangement inRamphotyphlops braminusmtDNA is inferred to be ancestral for snakes. After the divergence of the earlyRamphotyphlopslineage, three types of rearrangements occurred. These changes involve translocations within theIQMtRNA gene cluster and the duplication of the CR. All phylogenetic methods support the placement ofEnhydris plumbeaoutside of the (Colubridae + Elapidae) cluster, providing mitochondrial genomic evidence for the familial rank of Homalopsidae.
ProSeeK: A web server for MLPA probe design
Authors: Pantano Lorena , Armengol Lluís , Villatoro Sergi , Estivill Xavier
Published: November 2008

Background

The technological evolution of platforms for detecting genome-wide copy number imbalances has allowed the discovery of an unexpected amount of human sequence that is variable in copy number among individuals. This type of human variation can make an important contribution to human diversity and disease susceptibility. Multiplex Ligation-dependent Probe Amplification (MLPA) is a targeted method to assess copy number differences for up to 40 genomic loci in one single experiment. Although specific MLPA assays can be ordered from MRC-Holland (the proprietary company of the MLPA technology), custom designs are also developed in many laboratories worldwide. After our own experience, an important drawback of custom MLPA assays is the time spent during the design of the specific oligonucleotides that are used as probes. Due to the large number of probes included in a single assay, a number of restrictions need to be met in order to maximize specificity and to increase success likelihood.

Results

We have developed a web tool for facilitating and optimising custom probe design for MLPA experiments. The algorithm only requires the target sequence in FASTA format and a set of parameters, that are provided by the user according to each specific MLPA assay, to identify the best probes inside the given region.

Conclusion

To our knowledge, this is the first available tool for optimizing custom probe design of MLPA assays. The ease-of-use and speed of the algorithm dramatically reduces the turn around time of probe design. ProSeeK will become a useful tool for all laboratories that are currently using MLPA in their research projects for CNV studies.
Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues
Authors: Zhou Donghui , Pan Gang , Zheng Chen , Zheng Jingjing , Yian Liping , Teng Xiaodong
Published: November 2008

Background

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase that is activated by a serum-derived, macrophage stimulating protein (MSP) growth factor and is expressed in many malignant tumors. The aim of the present study was to reveal the protein expression profile of RON and its relationship with clinicopathological characteristics of gastric carcinoma and prognosis.

Methods

Gastric carcinoma tissue from 98 patients, along with 29 specimens of paraneoplastic tissue and 10 specimens of normal gastric mucosa, were examined by immunohistochemistry (IHC). Western blot analysis of 19 samples of gastric carcinoma tissue and corresponding paraneoplastic tissue, 8 specimens of normal gastric mucosa, and 2 specimens of normal lymph node samples also detected expression of a splice variant of RON, RONΔ165. All samples obtained were accompanied by patient follow-up data that ranged from 3 to 89 months (median time: 22 months).

Results

The rate of positive RON expression differed significantly between gastric carcinoma tissues [56.1%, (55/98)] and paraneoplastic tissues [25.6%, (8/29)] (p = 0.007). In contrast, RON expression was absent in normal gastric mucosa samples. RON expression positively correlated with the invasive depth of the tumor (p = 0.019), perigastric lymph nodes metastasis (p = 0.019), and TNM stage (p = 0.001). However, RON expression was independent of tumor growth pattern according to Bormann criteria (p = 0.209), histopathological grade (p = 0.196), and incidence of distant metastasis (p = 0.400). RON expression was not related to a patient's survival rate (p = 0.195). RONΔ165 was strongly expressed in fresh gastric carcinoma tissue, corresponding paraneoplastic tissue, and perigastric lymph nodes with metastatic carcinoma. In contrast, expression of RONΔ165 was not observed in normal gastric mucosa and normal lymph node tissue samples.

Conclusion

RON expression is significant in gastric carcinoma tissue and corresponding paraneoplastic tissue, but is not expressed in normal gastric mucosa. Expression of RONΔ165 was similarly observed in gastric carcinoma tissue and in metastases present in lymph node tissues. We hypothesize that RON and its splice variant play an important role in the occurrence, progression, and metastasis of gastric carcinoma, and therefore may represent a useful marker to evaluate the biological activity of gastric carcinoma.