bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerosol and Cloud Microphysical Characteristics of Rifts and Gradients in Maritime Stratocumulus Clouds
Authors: Sharon Tarah M. , Albrecht Bruce A. , Jonsson Haflidi H. , Minnis Patrick , Khaiyer Mandana M. , van Reken Timothy M. , Seinfeld John , Flagan Rick
Published: April 2006

A cloud rift is characterized as a large-scale, persistent area of broken, low-reflectivity stratocumulus clouds usually surrounded by a solid deck of stratocumulus. A rift observed off the coast of California was investigated using an instrumented aircraft to compare the aerosol, cloud microphysical, and thermodynamic properties in the rift with those of the surrounding solid stratocumulus deck. The microphysical characteristics in the solid stratocumulus deck differ substantially from those of a broken, cellular rift where cloud droplet concentrations are a factor of 2 lower than those in the solid cloud. Furthermore, cloud condensation nuclei (CCN) concentrations were found to be about 3 times greater in the solid-cloud area compared with those in the rift. Although drizzle was observed near cloud top in parts of the solid stratocumulus cloud, the largest drizzle rates were associated with the broken clouds within the rift area and with extremely large effective droplet sizes retrieved from satellite data. Minimal thermodynamic differences between the rift and solid cloud deck were observed. In addition to marked differences in particle concentrations, evidence of a mesoscale circulation near the solid cloud–rift boundary is presented. This mesoscale circulation may provide a mechanism for maintaining a rift, but further study is required to understand the initiation of a rift and the conditions that may cause it to fill. A review of results from previous studies indicates similar microphysical characteristics in rift features sampled serendipitously. These observations indicate that cloud rifts are depleted of aerosols through the cleansing associated with drizzle and are a manifestation of natural processes occurring in marine stratocumulus.
Diagnosing Monthly Mean Boundary Layer Properties from Reanalysis Data Using a Bulk Boundary Layer Model
Authors: Ahlgrimm Maike , Randall David A.
Published: April 2006

The mixed-layer approach to modeling the planetary boundary layer (PBL) is particularly well suited to inversion-topped PBLs, such as the stratocumulus-topped boundary layer found off the west coast of America in the subtropical Pacific Ocean at northern and southern latitudes. However, a strong temperature inversion near 850 hPa (the trade wind inversion) is not confined to the stratocumulus regimes, but has been observed over most parts of the subtropical–tropical Pacific Ocean. In this paper, the authors test the ability of a simple bulk boundary layer model (BBLM) to diagnose entrainment velocity, cumulus mass flux, and surface latent heat flux from monthly mean reanalysis data. The PBL depth is estimated from Geoscience Laser Altimeter System data. The model is based on the conservation equations for mass, total water mixing ratio, and moist static energy.

The BBLM diagnoses entrainment velocities between 1 and 8 mm s−1 in the stratocumulus and trade wind regions, with increasing rates toward the west. Large cumulus mass fluxes (1.3–2 cm s−1) mark the ITCZ and South Pacific convergence zone. Unreasonably large surface latent heat fluxes are diagnosed in regions where the vertical resolution of both model and input data are insufficient to represent the sharp gradients of moist conservable variables and winds across the PBL top. The results demonstrate that the potential exists to extract useful information about the large-scale structure of PBL physical processes by combining available observations with simple models.
Interaction of an Asymmetric Double Vortex and Trochoidal Motion of a Tropical Cyclone with the Concentric Eyewall Structure
Authors: Oda Masahito , Nakanishi Mikio , Naito Gen’ichi
Published: April 2006

Radar echo images demonstrate that mature tropical cyclones frequently have a concentric eyewall structure, which consists of the inner eyewall, echo-free moat, and outer eyewall regions. Near the inner and outer eyewalls, well-defined wind maxima are generally observed. This indicates that two large vertical vorticity regions exist just inside radii of the two wind maxima near the inner and outer eyewalls. Therefore, the concentric eyewall structure can be considered to be a double vortex composed of the inner vortex and the outer vortex ring. In this study, the contour dynamics model is used on the f plane to analyze the characteristics of flows with either a symmetric double vortex or an asymmetric one, and examined the relationship between the movement of the inner vortex in an asymmetric double vortex and a trochoidal motion of a tropical cyclone with an asymmetric concentric eyewall structure.

Results show that, depending on the degree of an interaction of a double vortex, the evolution of the inner vortex is classified into three patterns: the first is that the center of the inner vortex is stationary, which is seen only for the symmetric double vortex; the second is that the track of the center of the inner vortex draws a circle; and the third is that it draws a spiral. A numerical experiment based on an observed flow around Typhoon Herb was also performed. The time evolution of the double vortex is very similar to that of radar echo intensity of Typhoon Herb. Also the rotation period and amplitude of the inner vortex in the numerical experiment were comparable with those of the trochoidal motion in the observation. These suggest that, in tropical cyclones with the concentric eyewall structure, the interaction of an asymmetric double vortex can become a cause of trochoidal motion.
Multiple Regimes and Low-Frequency Oscillations in the Northern Hemisphere’s Zonal-Mean Flow
Authors: Kravtsov S. , Robertson A. W. , Ghil M.
Published: April 2006

This paper studies multiple regimes and low-frequency oscillations in the Northern Hemisphere zonal-mean zonal flow in winter, using 55 yr of daily observational data. The probability density function estimated in the phase space spanned by the two leading empirical orthogonal functions exhibits two distinct, statistically significant maxima. The two regimes associated with these maxima describe persistent zonal-flow states that are characterized by meridional displacements of the midlatitude jet, poleward and equatorward of its time-mean position. The geopotential height anomalies of either regime have a pronounced zonally symmetric component, but largest-amplitude anomalies are located over the Atlantic and Pacific Oceans. High-frequency synoptic transients participate in the maintenance of and transitions between these regimes.

Significant oscillatory components with periods of 147 and 72 days are identified by spectral analysis of the zonal-flow time series. These oscillations are described by singular spectrum analysis and the multitaper method. The 147-day oscillation involves zonal-flow anomalies that propagate poleward, while the 72-day oscillation only manifests northward propagation in the Atlantic sector. Both modes mainly describe changes in the midlatitude jet position and intensity. In the horizontal plane though, the two modes exhibit synchronous centers of action located over the Atlantic and Pacific Oceans. The two persistent flow regimes are associated with slow phases of either oscillation.
Aerosol Optical Properties and Particle Size Distributions on the East Coast of the United States Derived from Airborne In Situ and Remote Sensing Measurements
Authors: Reidmiller David R. , Hobbs Peter V. , Kahn Ralph
Published: April 2006

Airborne in situ measurements of vertical profiles and horizontal transects of aerosol optical and physical properties, obtained during the Chesapeake Lighthouse and Aircraft Measurements for Satellites (CLAMS) field campaign off the East Coast of the United States during the summer of 2001, are presented. Most of the measurements were obtained in relatively clean air dominated by airflows that had passed over Canada and the northern Atlantic Ocean. Results from the 17 July and 2 August 2001 flights are presented; on these days, the aerosol loading was relatively high. In the lower troposphere, ω0 values at a wavelength of 550 nm were consistently above 0.93 throughout the field experiment, indicating the dominance of weakly absorbing aerosol. Particle number size distributions are presented and discussed for transects at altitudes ∼0.05–3.5 km above mean sea level. Particles with diameters (Dp) <0.1 μm made up the majority of the aerosol number. Accumulation mode particles dominate the number size, surface area, and volume distributions. The variability of optical and physical aerosol parameters was analyzed on horizontal scales of ∼1–4 km. There was little horizontal variability in the single-scattering albedo (ω0), aerosol optical depth (AOD), and accumulation mode size, but greater variability in particle number concentration. Comparisons of the airborne measurements with remotely sensed aerosol parameters, such as ω0 and effective particle radius (reff), derived from the Multiangle Imaging Spectroradiometer (MISR) aboard the Terra satellite were generally in good agreement. Overall, the MISR retrievals captured both the similarities and the differences between the properties of the aerosols measured on 17 July and 2 August.
Parameterization of the Autoconversion Process. Part II: Generalization of Sundqvist-Type Parameterizations
Authors: Liu Yangang , Daum Peter H. , McGraw R. , Wood R.
Published: April 2006

Existing Sundqvist-type parameterizations, which only consider dependence of the autoconversion rate on cloud liquid water content, are generalized to explicitly account for the droplet concentration and relative dispersion of the cloud droplet size distribution as well. The generalized Sundqvist-type parameterization includes the more commonly used Kessler-type parameterization as a special case, unifying the two different types of parameterizations for the autoconversion rate. The generalized Sundqvist-type parameterization is identical with the Kessler-type parameterization presented in Part I beyond the autoconversion threshold, but exhibits a more realistic, smooth transition in the vicinity of the autoconversion threshold (threshold behavior) in contrast to the discontinuously abrupt transition embodied in the Kessler-type parameterization. A new Sundqvist-type parameterization is further derived by applying the expression for the critical radius derived from the kinetic potential theory to the generalized Sundqvist-type parameterization. The new parameterization eliminates the need for defining the driving radius and for prescribing the critical radius associated with Kessler-type parameterizations. The two-part structure of the autoconversion process raises questions regarding model-based empirical parameterizations obtained by fitting simulation results from detailed collection models with a single function.
Thinking big (and small) about energetic materials
Authors: Dlott D. D.
Published: April 2006

A significant recent development in the field of energetic materials has been the introduction of nanotechnology. Nanoparticle based materials have the potential of releasing more than twice as much energy as the best molecular explosives. The possibility of developing nanoenergetic materials that are optimised for specific applications by controlling the spatial organisation on length scales ranging from nanometres to metres is discussed. To do so a fundamental understanding of the relationships between structure and performance that does not yet exist is required. Experimental measurements using molecular spectroscopy with high time and space resolution are presented that help clarify the fundamental mechanisms of reaction between fuel nanoparticles and surrounding oxidisers, and the relationships between nanoenergetic structure and performance properties such as the energy release rate and the reaction propagation rate.
Properties of metals at high rates of strain
Authors: Edwards M.
Published: April 2006

The literature concerning the behaviour of metals at strain rates from quasi-static to ultrahigh is reviewed. Deformation mechanisms that are operative include twinning and adiabatic shear banding. These are functions of material strength, composition and microstructure. Behaviour of metals at ultra-high strain rates can be determined from the examination of soft captured shaped charge jets, as well as plate and hypervelocity impacts where shock pressures can be tens of GPa. Fracture phenomena seen at high strain rates include fragmentation and spalling. For brittle materials fragmentation is a function of material fracture toughness, as well as strain rate, while for ductile metals, material fracture strength and fracture strain appear to be important. The spall strength of metals appears to be very structure sensitive with small changes in thermomechanical processing or impurity content changing spall strength markedly.
Product design of particulate energetic materials
Authors: Teipel U.
Published: April 2006

The quality and internal microstructure of crystals have a great influence on the sensitivity of energetic materials. Moreover, their particle size and particle size distribution are of great importance to processing technology. Particle properties can especially be influenced by applying different crystallisation techniques, such as cooling crystallisation, membrane crystallisation, emulsion crystallisation, etc. The goal of the investigation reported was to determine the interrelationship between the properties of grown crystals and process parameters. Special attention was directed to the qualitative and quantitative examination of crystal defects and their dependence on the experimental conditions. The morphology and structure of crystals were calculated by molecular modelling. The effect of crystal defects on the sensitivity of the material was tested on different collectives of particles with varying amount of crystal defects.
Crystal sensitivities of energetic materials
Authors: Walley S. M. , Field J. E. , Greenaway M. W.
Published: April 2006

Organic and inorganic explosives were first developed and put into service in the 19th century, before there was much understanding of how the energy release mechanisms differed from those of the long established gunpowder. Theoretical advances in the understanding of shock waves combined with improvements in photographic and electronic techniques led to the hypothesis that a detonation is a shock wave maintained by the rapid release of chemical energy. Studies of accidental ignitions/initiations showed that explosive events can occur even when the energy input is much less than that required to heat the bulk explosive to the deflagration temperature. Hence, the highly fruitful idea of the localised hot spot was conceived. Apart from electrical stimuli, the main hot spot mechanisms are currently accepted as being adiabatic asymmetric collapse of gas spaces (producing gas heating, jetting, viscoplastic work) and the rubbing together of surfaces as in friction or adiabatic shear. Initiation mechanisms are also connected with the anisotropy of plasticity and fracture in explosive crystals. Decomposition of molecules can take place as they are forced past each other in a deforming crystal. There is, however, still much to discover about reaction pathways. Novel optical and electron microscopy techniques have given a great deal of new and precise information about displacements and failure mechanisms when explosive crystals are bonded together using polymers. The deflagration–detonation transition (DDT) has been extensively studied in model one- and two-dimensional systems.
Improving reliability of heat and fluid flow calculation during conduction mode laser spot welding by multivariable optimisation
Authors: De A. , DebRoy T.
Published: April 2006

Several uncertain parameters affect the reliability of heat transfer and fluid flow calculations during conduction mode laser spot welding because their values cannot be prescribed from fundamental principles. These parameters include absorptivity of the laser beam, effective thermal conductivity and effective viscosity of liquid metal in the weld pool. Values of these parameters are usually adjusted by trial and error so that the computed results agree with the corresponding experimental values. Here it is shown that by integrating multivariable constrained optimisation with convective heat transfer and fluid flow calculations, the values of the uncertain parameters can be obtained from a limited volume of experimental data. The optimisation technique requires numerically calculated sensitivity values of weld dimensions with respect to absorptivity, effective thermal conductivity and effective viscosity and minimises the discrepancy between the predicted and the measured weld dimensions. The numerical heat transfer and fluid flow model embodying the optimised values of the uncertain parameters could accurately compute values of weld dimensions for new welding conditions. Reliability of heat transfer and fluid flow calculations can be significantly enhanced by determining the values of uncertain parameters from a limited volume of experimental data using a multivariable optimisation technique with a numerical heat transfer and fluid flow model.
Effect of boundary conditions and heat source distribution on temperature distribution in friction stir welding
Authors: Simar A. , Lecomte-Beckers J. , Pardoen T. , de Meester B.
Published: April 2006

Welding experiments on Al-6005A have been carried out using a fully instrumented milling machine. The power input was calculated from the measured torque and forces. The thermal cycles were measured at various locations close to the weld centreline. A finite element pseudo-steady-state uncoupled thermal model was developed, taking into account the influence of the welding parameters on the power input. The distribution of the total power input between surface and volume heat sources was also studied. The measured and predicted thermal cycles are in good agreement when proper contact conditions between the workpiece and the backing plate are introduced.
Thermal and metal transfer behaviours in pulsed current gas metal arc weld deposition of Al–Mg alloy
Authors: Ghosh P. K. , Goyal V. K. , Dhiman H. K. , Kumar M.
Published: April 2006

The control of pulsed current gas metal arc (GMA) welding is highly critical owing to the simultaneous influence of the pulse parameters on thermal and metal transfer behaviours of the process. An analytical model has been developed to provide a theoretical understanding of the influence of pulse parameters on the behaviour of metal transfer and thermal characteristics in pulsed current GMA welding using Al–Mg filler wire. The variations in thermal and metal transfer behaviours with changes in pulse parameters have been satisfactorily analysed considering a summarised influence of pulse parameters defined by a dimensionless factor φ = ( I b/ I p) ft b, proposed previously. A large number of process parameters have been considered, as a result of using four different GMA welding power sources. The hypothesis has been verified using some previously reported experimental results. The theoretical model may be useful in the control of pulse parameters to achieve desired behaviours of thermal and metal transfer under different conditions of weld fabrication, thereby facilitating more universal application of GMA welding.
The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia
Authors: Palmqvist Lars , Argiropoulos Bob , Pineault Nicolas , Abramovich Carolina , Sly Laura M. , Krystal Gerald , Wan Adrian , Humphries R. Keith
Published: April 2006

In leukemogenesis, several genetic changes conferring a proliferative and/or survival advantage to hematopoietic progenitor cells in addition to a block in differentiation are required. Here, we demonstrate that overexpression of the wild-type (wt) Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions (NUP98-HOXA10 and NUP98-HOXD13) to induce aggressive acute myeloid leukemia (AML). We used a mouse transplantation model to show their synergism in cotransduced bone marrow cells as well as in a cellular model of leukemic progression. Furthermore, our data support the finding that Meis1 overexpression leads to marked elevation in Flt3 transcription and extend it to the context of NUP98-HOX–induced leukemia. Together, these results support a multistep model where the synergism between NUP98-HOX and wt-Flt3 is the result of the ability of Flt3 to increase proliferation of myeloid progenitors blocked in differentiation by NUP98-HOX fusions and reveal a direct role for wt-Flt3 in the pathobiology of AML. Given the similarities in the leukemogenic role of native HOX and NUP98-fused HOX genes, our results underscore the clinical significance of the recurrent co-overexpression of wt-FLT3 and HOX in human leukemia and suggest that specific FLT3 inhibitors could be useful in treatment of HOX-induced AML or acute lymphoblastic leukemia (ALL).
CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation
Authors: Ravasi Saula , Citro Simona , Viviani Barbara , Capra Valérie , Rovati G Enrico
Published: April 2006

Background

Cysteine-containing leukotrienes (cysteinyl-LTs) are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC) proliferation. We used human ASMC (HASMC) to identify the signal transduction pathway(s) of the leukotriene D4 (LTD4)-induced DNA synthesis.

Methods

Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R) and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS) was estimated by measuring dichlorodihydrofluorescein (DCF) oxidation.

Results

We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX) and phosphoinositide 3-kinase (PI3K) inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC) abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation.

Conclusion

Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF-R through the intervention of PI3K and ROS. While PI3K and ROS involvement is an early event, the activation of Src occurs downstream of EGF-R activation and is followed by the classical Ras-ERK1/2 signaling pathway to control G1 progression and cell proliferation.
Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 in mice
Authors: Lu Jiahai , Guo Zhongmin , Pan Xinghua , Wang Guoling , Zhang Dingmei , Li Yanbin , Tan Bingyan , Ouyang Liping , Yu Xinbing
Published: April 2006

Background

Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab')2 fragments by pepsin digestion of IgGs.

Methods

The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab')2 fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab')2 fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE) assay and in a BALB/c mouse model by survival rate assay.

Results

By the protocol for 'enhanced pepsin digestion', total 16 g F(ab')2 fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab')2 fragments had a HI titer of 1:1024, and the neutralization titre of F(ab')2 reached 1: 2048. The in vivo assay showed that 100 μg of the F(ab')2 fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus.

Conclusion

The availability of highly purified H5N1-specific F(ab')2 fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials.
The role of endothelin-1 in hyperoxia-induced lung injury in mice
Authors: Habre Walid , Peták Ferenc , Ruchonnet-Metrailler Isabelle , Donati Yves , Tolsa Jean-Francois , Lele Eniko , Albu Gergely , Beghetti Morice , Barazzone-Argiroffo Constance
Published: April 2006

Background

As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1) receptors in these adverse changes.

Methods

Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10 mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs) was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 μg). Changes in the airway resistance (Raw) and in the tissue damping (G) and elastance (H) of a constant-phase tissue compartment were identified from Zrs by model fitting.

Results

The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 ± 1.6 pg/ml) relative to those exposed to room air (1.6 ± 0.3 pg/ml, p < 0.05). TEZ administration prevented the hyperoxia-induced increases in G (13.1 ± 1.7 vs. 9.6 ± 0.3 cmH2O/l, p < 0.05) and H (59 ± 9 vs. 41 ± 5 cmH2O/l, p < 0.05) and inhibited the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to ET-1, whereas it elevated the reactivity of the tissues.

Conclusion

These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage.
Cigarette smoke exposure facilitates allergic sensitization in mice
Authors: Moerloose Katrien B , Robays Lander J , Maes Tania , Brusselle Guy G , Tournoy Kurt G , Joos Guy F
Published: April 2006

Background

Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained.

Objective

The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization.

Methods

BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied within vivorecall experiments.

Results

Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4+T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena.

Conclusion

In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction.
Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Gan Wen Qi , Man SF Paul , Postma Dirkje S , Camp Patricia , Sin Don D
Published: April 2006

Background

Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men. Whether female adult smokers are biologically more susceptible to COPD is unknown. This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.

Methods

A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1on at least two different time points, and presented FEV1data stratified by gender and smoking status in adults.

Results

Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants). There was heterogeneity in gender-related results across the studies. However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers. Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2= 0.56; p = 0.008). Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).

Conclusion

As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers. Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.
Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema
Authors: Demedts Ingel K , Demoor Tine , Bracke Ken R , Joos Guy F , Brusselle Guy G
Published: April 2006

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress. Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD. There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients. Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema. Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung. Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.

In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed. The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema.
Sigma: multiple alignment of weakly-conserved non-coding DNA sequence
Authors: Siddharthan Rahul
Published: April 2006

Background

Existing tools for multiple-sequence alignment focus on aligning protein sequence or protein-coding DNA sequence, and are often based on extensions to Needleman-Wunsch-like pairwise alignment methods. We introduce a new tool, Sigma, with a new algorithm and scoring scheme designed specifically for non-coding DNA sequence. This problem acquires importance with the increasing number of published sequences of closely-related species. In particular, studies of gene regulation seek to take advantage of comparative genomics, and recent algorithms for finding regulatory sites in phylogenetically-related intergenic sequence require alignment as a preprocessing step. Much can also be learned about evolution from intergenic DNA, which tends to evolve faster than coding DNA. Sigma uses a strategy of seeking the best possible gapless local alignments (a strategy earlier used by DiAlign), at each step making the best possible alignment consistent with existing alignments, and scores the significance of the alignment based on the lengths of the aligned fragments and a background model which may be supplied or estimated from an auxiliary file of intergenic DNA.

Results

Comparative tests of sigma with five earlier algorithms on synthetic data generated to mimic real data show excellent performance, with Sigma balancing high "sensitivity" (more bases aligned) with effective filtering of "incorrect" alignments. With real data, while "correctness" can't be directly quantified for the alignment, running the PhyloGibbs motif finder on pre-aligned sequence suggests that Sigma's alignments are superior.

Conclusion

By taking into account the peculiarities of non-coding DNA, Sigma fills a gap in the toolbox of bioinformatics.
The 3of5 web application for complex and comprehensive pattern matching in protein sequences
Authors: Seiler Markus , Mehrle Alexander , Poustka Annemarie , Wiemann Stefan
Published: April 2006

Background

The identification of patterns in biological sequences is a key challenge in genome analysis and in proteomics. Frequently such patterns are complex and highly variable, especially in protein sequences. They are frequently described using terms of regular expressions (RegEx) because of the user-friendly terminology. Limitations arise for queries with the increasing complexity of patterns and are accompanied by requirements for enhanced capabilities. This is especially true for patterns containing ambiguous characters and positions and/or length ambiguities.

Results

We have implemented the 3of5 web application in order to enable complex pattern matching in protein sequences. 3of5 is named after a special use of its main feature, the novel n-of-m pattern type. This feature allows for an extensive specification of variable patterns where the individual elements may vary in their position, order, and content within a defined stretch of sequence. The number of distinct elements can be constrained by operators, and individual characters may be excluded. The n-of-m pattern type can be combined with common regular expression terms and thus also allows for a comprehensive description of complex patterns. 3of5 increases the fidelity of pattern matching and finds ALL possible solutions in protein sequences in cases of length-ambiguous patterns instead of simply reporting the longest or shortest hits. Grouping and combined search for patterns provides a hierarchical arrangement of larger patterns sets. The algorithm is implemented as internet application and freely accessible. The application is available at http://dkfz.de/mga2/3of5/3of5.html.

Conclusion

The 3of5 application offers an extended vocabulary for the definition of search patterns and thus allows the user to comprehensively specify and identify peptide patterns with variable elements. The n-of-m pattern type offers an improved accuracy for pattern matching in combination with the ability to find all solutions, without compromising the user friendliness of regular expression terms.
Genetic algorithm learning as a robust approach to RNA editing site prediction
Authors: Thompson James , Gopal Shuba
Published: April 2006

Background

RNA editing is one of several post-transcriptional modifications that may contribute to organismal complexity in the face of limited gene complement in a genome. One form, known as C → U editing, appears to exist in a wide range of organisms, but most instances of this form of RNA editing have been discovered serendipitously. With the large amount of genomic and transcriptomic data now available, a computational analysis could provide a more rapid means of identifying novel sites of C → U RNA editing. Previous efforts have had some success but also some limitations. We present a computational method for identifying C → U RNA editing sites in genomic sequences that is both robust and generalizable. We evaluate its potential use on the best data set available for these purposes: C → U editing sites in plant mitochondrial genomes.

Results

Our method is derived from a machine learning approach known as a genetic algorithm. REGAL (RNA Editing site prediction by Genetic Algorithm Learning) is 87% accurate when tested on three mitochondrial genomes, with an overall sensitivity of 82% and an overall specificity of 91%. REGAL's performance significantly improves on other ab initio approaches to predicting RNA editing sites in this data set. REGAL has a comparable sensitivity and higher specificity than approaches which rely on sequence homology, and it has the advantage that strong sequence conservation is not required for reliable prediction of edit sites.

Conclusion

Our results suggest that ab initio methods can generate robust classifiers of putative edit sites, and we highlight the value of combinatorial approaches as embodied by genetic algorithms. We present REGAL as one approach with the potential to be generalized to other organisms exhibiting C → U RNA editing.
Development of an unbiased statistical method for the analysis of unigenic evolution
Authors: Behrsin Colleen D , Brandl Chris J , Litchfield David W , Shilton Brian H , Wahl Lindi M
Published: April 2006

Background

Unigenic evolution is a powerful genetic strategy involving random mutagenesis of a single gene product to delineate functionally important domains of a protein. This method involves selection of variants of the protein which retain function, followed by statistical analysis comparing expected and observed mutation frequencies of each residue. Resultant mutability indices for each residue are averaged across a specified window of codons to identify hypomutable regions of the protein. As originally described, the effect of changes to the length of this averaging window was not fully eludicated. In addition, it was unclear when sufficient functional variants had been examined to conclude that residues conserved in all variants have important functional roles.

Results

We demonstrate that the length of averaging window dramatically affects identification of individual hypomutable regions and delineation of region boundaries. Accordingly, we devised a region-independent chi-square analysis that eliminates loss of information incurred during window averaging and removes the arbitrary assignment of window length. We also present a method to estimate the probability that conserved residues have not been mutated simply by chance. In addition, we describe an improved estimation of the expected mutation frequency.

Conclusion

Overall, these methods significantly extend the analysis of unigenic evolution data over existing methods to allow comprehensive, unbiased identification of domains and possibly even individual residues that are essential for protein function.
Predicting population coverage of T-cell epitope-based diagnostics and vaccines
Authors: Bui Huynh-Hoa , Sidney John , Dinh Kenny , Southwood Scott , Newman Mark J , Sette Alessandro
Published: April 2006

Background

T cells recognize a complex between a specific major histocompatibility complex (MHC) molecule and a particular pathogen-derived epitope. A given epitope will elicit a response only in individuals that express an MHC molecule capable of binding that particular epitope. MHC molecules are extremely polymorphic and over a thousand different human MHC (HLA) alleles are known. A disproportionate amount of MHC polymorphism occurs in positions constituting the peptide-binding region, and as a result, MHC molecules exhibit a widely varying binding specificity. In the design of peptide-based vaccines and diagnostics, the issue of population coverage in relation to MHC polymorphism is further complicated by the fact that different HLA types are expressed at dramatically different frequencies in different ethnicities. Thus, without careful consideration, a vaccine or diagnostic with ethnically biased population coverage could result.

Results

To address this issue, an algorithm was developed to calculate, on the basis of HLA genotypic frequencies, the fraction of individuals expected to respond to a given epitope set, diagnostic or vaccine. The population coverage estimates are based on MHC binding and/or T cell restriction data, although the tool can be utilized in a more general fashion. The algorithm was implemented as a web-application available at http://epitope.liai.org:8080/tools/population.

Conclusion

We have developed a web-based tool to predict population coverage of T-cell epitope-based diagnostics and vaccines based on MHC binding and/or T cell restriction data. Accordingly, epitope-based vaccines or diagnostics can be designed to maximize population coverage, while minimizing complexity (that is, the number of different epitopes included in the diagnostic or vaccine), and also minimizing the variability of coverage obtained or projected in different ethnic groups.
Predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays
Authors: Matsui Shigeyuki
Published: April 2006

Background

Genetic markers hold great promise for refining our ability to establish precise prognostic prediction for diseases. The development of comprehensive gene expression microarray technology has allowed the selection of relevant marker genes from a large pool of candidate genes in early-phased, developmental prognostic marker studies. The primary analytical task in such studies is to select a small fraction of relevant genes, typically from a list of significant genes, for further investigation in subsequent studies.

Results

We develop a methodology for predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays. Key components in this methodology include building prediction models, assessing predictive performance of prediction models, and assessing significance of prediction results. As particular specifications, we assume Cox proportional hazard models with a compound covariate. For assessing predictive accuracy, we propose to use the cross-validated log partial likelihood. To assess significance of prediction results, we apply permutation procedures in cross-validated prediction. As an additional key component peculiar to prognostic prediction, we also consider incorporation of standard prognostic factors. The methodology is evaluated using both simulated and real data.

Conclusion

The developed methodology for prognostic prediction using a subset of significant genes can provide new insights based on predictive capability, possibly incorporating standard prognostic factors, in selecting a fraction of relevant genes for subsequent studies.
2DDB – a bioinformatics solution for analysis of quantitative proteomics data
Authors: Malmström Lars , Marko-Varga György , Westergren-Thorsson Gunilla , Laurell Thomas , Malmström Johan
Published: April 2006

Background

We present 2DDB, a bioinformatics solution for storage, integration and analysis of quantitative proteomics data. As the data complexity and the rate with which it is produced increases in the proteomics field, the need for flexible analysis software increases.

Results

2DDB is based on a core data model describing fundamentals such as experiment description and identified proteins. The extended data models are built on top of the core data model to capture more specific aspects of the data. A number of public databases and bioinformatical tools have been integrated giving the user access to large amounts of relevant data. A statistical and graphical package, R, is used for statistical and graphical analysis. The current implementation handles quantitative data from 2D gel electrophoresis and multidimensional liquid chromatography/mass spectrometry experiments.

Conclusion

The software has successfully been employed in a number of projects ranging from quantitative liquid-chromatography-mass spectrometry based analysis of transforming growth factor-beta stimulated fi-broblasts to 2D gel electrophoresis/mass spectrometry analysis of biopsies from human cervix. The software is available for download at SourceForge.
PPSP: prediction of PK-specific phosphorylation site with Bayesian decision theory
Authors: Xue Yu , Li Ao , Wang Lirong , Feng Huanqing , Yao Xuebiao
Published: April 2006

Background

As a reversible and dynamic post-translational modification (PTM) of proteins, phosphorylation plays essential regulatory roles in a broad spectrum of the biological processes. Although many studies have been contributed on the molecular mechanism of phosphorylation dynamics, the intrinsic feature of substrates specificity is still elusive and remains to be delineated.

Results

In this work, we present a novel, versatile and comprehensive program, PPSP (Prediction of PK-specific Phosphorylation site), deployed with approach of Bayesian decision theory (BDT). PPSP could predict the potential phosphorylation sites accurately for ~70 PK (Protein Kinase) groups. Compared with four existing tools Scansite, NetPhosK, KinasePhos and GPS, PPSP is more accurate and powerful than these tools. Moreover, PPSP also provides the prediction for many novel PKs, say, TRK, mTOR, SyK and MET/RON, etc. The accuracy of these novel PKs are also satisfying.

Conclusion

Taken together, we propose that PPSP could be a potentially powerful tool for the experimentalists who are focusing on phosphorylation substrates with their PK-specific sites identification. Moreover, the BDT strategy could also be a ubiquitous approach for PTMs, such as sumoylation and ubiquitination, etc.