Prompt acceleration of ions by oblique turbulent shocks in solar flares

Solar flares often accelerate ions and electrons to relativistic energies. The details of the acceleration process are not well understood, but until recently the main trend was to divide the acceleration process into two phases. During the first phase elctrons and ions are heated and accelerated up to several hundreds of keV simultaneously with the energy release. These mildly relativistic electrons interact with the ambient plasma and magnetic fields and generate hard X-ray and radio radiation. The second phase, usually delayed from the first by several minutes, is responsible for accelerating ions and electrons to relativistic energies. Relativistic electrons and ions interact with the solar atmosphere or escape from the Sun and generate gamma ray continuum, gamma ray line emission, neutron emission or are detected in space by spacecraft. In several flares the second phase is coincident with the start of a type 2 radio burst that is believed to be the signature of a shock wave. Observations from the Solar Maximum Mission spacecraft have shown, for the first time, that several flares accelerate particles to all energies nearly simultaneously. These results posed a new theoretical problem: How fast are shocks and magnetohydrodynamic turbulence formed and how quickly can they accelerate ions to 50 MeV in the lower corona? This problem is discussed

Energetic ion acceleration at collisionless shocks

An example is presented from a test particle simulation designed to study ion acceleration at oblique turbulent shocks. For conditions appropriate at interplanetary shocks near 1 AU, it is found that a shock with theta sub B n = 60 deg is capable of producing an energy spectrum extending from 10 keV to approx. 1 MeV in approx 1 hour. In this case total energy gains result primarily from several separate episodes of shock drift acceleration, each of which occurs when particles are scattered back to the shock by magnetic fluctuations in the shock vicinity

Role of alveolar macrophages in chronic obstructive pulmonary disease

Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response during infection and injury, AMs actively coordinate the resolution of inflammation through efferocytosis of apoptotic cells. Any perturbation of this process can lead to deleterious responses. In chronic obstructive pulmonary disease (COPD), there is an accumulation of airway macrophages that do not conform to the classic M1/M2 dichotomy. There is also a skewed transcriptome profile that favors expression of wound-healing M2 markers, which is reflective of a deficiency to resolve inflammation. Endogenous mediators that can promote an imbalance in inhibitory M1 vs. healing M2 macrophages are discussed, as they are the plausible mechanisms underlying why AMs fail to effectively resolve inflammation and restore normal lung homeostasis in COPD

Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities

Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen species (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis are discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities

Particle Acceleration in an Evolving Network of Unstable Current Sheets

We study the acceleration of electrons and protons interacting with localized, multiple, small-scale dissipation regions inside an evolving, turbulent active region. The dissipation regions are Unstable Current Sheets (UCS), and in their ensemble they form a complex, fractal, evolving network of acceleration centers. Acceleration and energy dissipation are thus assumed to be fragmented. A large-scale magnetic topology provides the connectivity between the UCS and determines in this way the degree of possible multiple acceleration. The particles travel along the magnetic field freely without loosing or gaining energy, till they reach a UCS. In a UCS, a variety of acceleration mechanisms are active, with the end-result that the particles depart with a new momentum. The stochastic acceleration process is represented in the form of Continuous Time Random Walk (CTRW), which allows to estimate the evolution of the energy distribution of the particles. It is found that under certain conditions electrons are heated and accelerated to energies above 1 MeV in much less than a second. Hard X-ray (HXR) and microwave spectra are calculated from the electrons' energy distributions, and they are found to be compatible with the observations. Ions (protons) are also heated and accelerated, reaching energies up to 10 MeV almost simultaneously with the electrons. The diffusion of the particles inside the active region is extremely fast (anomalous super-diffusion). Although our approach does not provide insight into the details of the specific acceleration mechanisms involved, its benefits are that it relates acceleration to the energy release, and it well describes the stochastic nature of the acceleration process.Comment: 37 pages, 10 figures, one of them in color; in press at ApJ (2004

Targeting pro-resolution pathways to combat chronic inflammation in COPD

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. Paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise COPD airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. Excessive production of leukocyte mobilising cytokines such as CXCL8 (IL-8) and leukotriene B4 (LTB4) in response to environmental stimuli (cigarette smoke and microbial products) are thought to maintain chronic inflammation, in conjunction with inefficient macrophage clearance of microbes and apoptotic neutrophils. In this perspective, we discuss an alternative view on why inflammation persists with a focus on why pro-resolution mediators such as lipoxin A4 (LXA4), D-series resolving and Annexin A1 fail to effectively switch off inflammation in COPD. These pro-resolving mediators converge on the G-protein coupled receptor, ALX/FPR2. This receptor is particularly relevant to COPD as the complex milieu of exogenous and host-derived mediators within the inflamed airways include agonists that potently activate ALX/FPR2, including Serum Amyloid A (SAA) and the cathelicidin, LL-37. There is emerging evidence to suggest that ALX/FPR2 can exist in alternative receptor conformations in an agonist-biased manner, which facilitates alternate functional receptor behaviors. Hence, the development of more stable pro-resolving analogs provides therapeutic opportunities to address ALX/FPR2 conformations to counteract pathogenic signaling and promote non-phlogistic clearance pathways essential for resolution of inflammation

Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators

Serum Amyloid A induces toll-like receptor 2-dependent inflammatory cytokine expression and atrophy in C2C12 skeletal muscle myotubes

Background Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. Results SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. Conclusions These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of m

Particle acceleration

Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV

Automated LASCO CME catalog for solar cycle 23: are CMEs scale invariant?

In this paper we present the first automatically constructed LASCO CME catalog, a result of the application of the Computer Aided CME Tracking software (CACTus) on the LASCO archive during the interval September 1997 - January 2007. We have studied the CME characteristics and have compared them with similar results obtained by manual detection (CDAW CME catalog). On average CACTus detects less than 2 events per day during solar minimum up to 8 events during maximum, nearly half of them being narrow (< 20 degrees). Assuming a correction factor, we find that the CACTus CME rate is surprisingly consistent with CME rates found during the past 30 years. The CACTus statistics show that small scale outflow is ubiquitously observed in the outer corona. The majority of CACTus-only events are narrow transients related to previous CME activity or to intensity variations in the slow solar wind, reflecting its turbulent nature. A significant fraction (about 15%) of CACTus-{\it only} events were identified as independent events, thus not related to other CME activity. The CACTus CME width distribution is essentially scale invariant in angular span over a range of scales from 20 to 120 degrees while previous catalogues present a broad maximum around 30 degrees. The possibility that the size of coronal mass outflows follow a power law distribution could indicate that no typical CME size exists, i.e. that the narrow transients are not different from the larger well-defined CMEs.Comment: 13 pages. ApJ, accepte