Three dimensional MHD Modeling of Vertical Kink Oscillations in an Active Region Plasma Curtain

Observations on 2011 August 9 of an X6.9-class flare in active region (AR) 11263 by the Atmospheric Imaging Assembly (AIA) on-board the Solar Dynamics Observatory (SDO), were followed by a rare detection of vertical kink oscillations in a large-scale coronal active region plasma curtain in EUV coronal lines. The damped oscillations with periods in the range 8.8-14.9 min were detected and analyzed recently. Our aim is to study the generation and propagation of the MHD oscillations in the plasma curtain taking into account realistic 3D magnetic and density structure of the curtain. We also aim at testing and improving coronal seismology for more accurate determination of the magnetic field than with standard method. We use the observed morphological and dynamical conditions, as well as plasma properties of the coronal curtain based on Differential Emission Measure (DEM) analysis to initialize a 3D MHD model of its vertical and transverse oscillations by implementing the impulsively excited velocity pulse mimicking the flare generated nonlinear fast magnetosonic propagating disturbance interacting with the curtain obliquely. The model is simplified by utilizing initial dipole magnetic field, isothermal energy equation, and gravitationally stratified density guided by observational parameters. Using the 3D MHD model, we are able to reproduce the details of the vertical oscillations and study the process of their excitation by nonlinear fast magnetosonic pulse, propagation, and damping, finding agreement with the observations. We estimate the accuracy of simplified slab-based coronal seismology by comparing the determined magnetic field strength to actual values from the 3D MHD modeling results and demonstrate the importance of taking into account more realistic magnetic geometry and density for improving coronal seismology

Exploitation of costimulatory SA-4-1BBL in the development of therapeutic cancer vaccines.

Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. Despite the development of various strategies to treat cancer, it remains one of the most deadly diseases worldwide due to the limited effects of treatments available. The limited efficacy of these current treatment modalities, such as surgery, radiotherapy, and chemotherapy, are often due to their association with adverse side effects arising from lack of specificity for tumors, and most importantly their failure of eliminating residual and micro-metastatic tumors, which can lead to recurrences. Therefore, there is a dire need to develop tumor-specific therapies that not only eliminate primary tumors, but also micro-metastasis and prevent recurrences. In this regard, therapeutic cancer vaccines based on tumor-associated antigens (TAAs) has evolved as a promising approach due to their safety profile, ease of production, storage, transportation, administration to a broad patient population and most importantly establishment and/or maintenance of long-term immunological memory critical for the control of recurrences, a major cause of cancer death. However, despite theoretical promise, development of therapeutic cancer vaccines has been facing numerous set-backs mostly due to the weak immunogenicity of T AAs, tolerance to self-T AAs and various immune evasion mechanisms employed by progressing tumors. Therefore, we hypothesized that use of natural costimulatory ligands of TNF family as adjuvant may overcome these limitations due to their effect on cells of innate, adaptive, and regulatory immunity without any sign of toxicity. The tumor necrosis factor receptor (TNFR)/TNF superfamily represents a crucial group of costimulatory receptor/ligands as most of the receptors of this family are inducibly expressed on various immune cells. Costimulatory receptors that are inducibly expressed or upregulated on activated T cells may serve as preferred targets for immunomodulation due to their potential to selectively target antigen-experienced T cells for expansion, survival, and establishment of long-term immunological memory. Among these family members, 4-1BB/4-1BBL signaling has recently been much appreciated as its signaling provides the essential survival signals, particularly in CD8+ T cells. 4-1BB signaling into T cells allows CD8+ T cell expansion, cytokine production, development of CTL effector function, and prevention of apoptotic cell death by up-regulating anti-apoptotic Bcl-xL and Bcl-2 molecules. As the aim of tumor immunotherapy is to generate long-lasting immune response, particularly CD8+ T cell specific response, for the destruction of tumor cells, in this project, we focused on the utilization of 4-1 BBL either alone or in combination with other immunomodulators, as a component of TAA-based subunit vaccines and tested its efficacy in preclinical mice tumor models. First, we report that a single immunization with a therapeutic vaccine formulation containing novel form of soluble SA-4-1BBL, and survivin (SVN), a bona fide self antigen, resulted into the eradication of SVN-expressing 3LL tumors in 75% of mice in the absence of autoimmunity. The efficacy of vaccine was further improved to complete tumor eradication with an additional vaccination 6 days after the first vaccination. CD8+ T cells and NK cells effector function was found to be critical for the efficacy of vaccine, but not the CD4 + T cells. Next, we tested the vaccine formulation containing combination of SA-4-IBBL and toll-like receptor 4 agonist monophosphoryl lipid A (MPL) with distinct mechanisms of action as a novel adjuvant system. A single immunization with both adjuvants and HPV E7 protein resulted in eradication of 100% of E7 expressing TC-1 tumors. Combined adjuvants had better therapeutic efficacy over the individual adjuvants, while SA-4-1BBL monotherapy outperformed MPL, 80% vs. 50%. Similarly, a single vaccination with SVN resulted in control/eradication of established 3LL pulmonary metastases that was further improved by a booster injection. The therapeutic efficacy of combined adjuvants as well as SA-4-1BBL as monotherapy was achieved in the absence of detectable toxicity and correlated with enhanced CD8+ T cell function and increased intratumoral CD8+ T effector/CD4+FoxP3+ T regulatory cell ratio. In marked contrast, vaccination with MPL as monotherapy resulted in an unfavorable intratumoral CD8+ T effector/CD4+FoxP3+ T regulatory cell ratio that played a definitive role in vaccine efficacy. Depletion of T regulatory cells improved MPL efficacy to 100%, whereas elimination of CD8+ T cells totally abrogated the efficacy of combined adjuvants. In last, we report that combination of SA-4-1BBL and SA-OX40L, another member of TNF ligand family, was also able to eradicate TC-I tumors in 100% of mice. This efficacy was mainly dependent on CD8+ T cells as depletion of these cells completely abrogated the efficacy. Importantly, combination of these two ligands was also able to eradicate a 3-4 mm established tumors in 50% of mice. Taken together, these data provide important mechanistic insight into the mode of action of SA-4-1BBL alone or in combination either MPL or SA-OX40L adjuvants and demonstrate its utility as a novel adjuvant system for the development of therapeutic TAA-based subunit cancer vaccines with significant clinical implications. These data also shed lights into the mode of action of MPL and SA-OX40L as a part of vaccine adjuvant systems and set the stage for their utilization in the development of new vaccine strategies

Numerical Simulations of the Decaying Transverse Oscillations in the Cool Jet

We describe a 2.5D MHD simulation describing the evolution of cool jets triggered by initial vertical velocity perturbations in the solar chromosphere. We implement random velocity pulses of amplitude 20-50 km/s between 1 Mm and 1.5 Mm, along with various switch-off periods between 50 s and 300 s. The applied vertical velocity pulses create a series of magnetoacoustic shocks steepening above TR. These shocks interact with each other in the inner corona, leading to complex localized velocity fields. The upward propagation of such perturbations creates low-pressure regions behind them, which propel a variety of cool jets and plasma flows. We study the transverse oscillations of a representative cool jet J1 , which moves up to the height of 6.2 Mm above the TR from its origin point. During its evolution, the plasma flows make the spine of jet J1 radially inhomogeneous, which is visible in the density and Alfv\'en speed smoothly varying across the jet. The highly dense J1 supports the propagating transverse wave of period of approximately 195 s with a phase speed of about 125 km/s. In the distance-time map of density, it is manifested as a transverse kink wave. However, the careful investigation of the distance-time maps of the x- and z-components of velocity reveals that these transverse waves are actually the mixed Alfv\'enic modes. The transverse wave shows evidence of damping in the jet. We conclude that the cross-field structuring of the density and characteristic Alfv\'en speed within J1 causes the onset of the resonant conversion and leakage of the wave energy outward to dissipate these transverse oscillations via resonant absorption. The wave energy flux is estimated as approximately of 1.0 x 10^6 ergs cm^{-2} s^{-1}. This energy, if it dissipates through the resonant absorption into the corona where the jet is propagated, is sufficient energy for the localized coronal heating.Comment: "Physics", 17 Pages, 6 Figures; in Special Issue in the Honor of Professor Marcel Goossens on the occasion of his 75th birthda

Plasma flows in the cool loop systems

We study the dynamics of low-lying cool loop systems for three datasets as observed by the Interface Region Imaging Spectrograph (IRIS). Radiances, Doppler shifts and line widths are investigated in and around observed cool loop systems using various spectral lines formed between the photosphere and transition region (TR). Footpoints of the loop threads are either dominated by blueshifts or redshifts. The co-spatial variation of velocity above the blue-shifted footpoints of various loop threads shows a transition from very small upflow velocities ranging from (-1 to +1) km/s in the Mg\,{\sc ii} k line (2796.20~\AA; formation temperature: log (T/K) = 4.0) to the high upflow velocities from (-10 to -20) km/s in Si\,{\sc iv}. Thus, the transition of the plasma flows from red-shift (downflows) to the blue-shift (upflows) is observed above the footpoints of these loop systems in the spectral line C\,{\sc ii} (1334.53~\AA; \log (T/K) = 4.3) lying between Mg\,{\sc ii} k and Si\,{\sc iv} (1402.77~\AA; log (T / K) = 4.8). This flow inversion is consistently observed in all three sets of the observational data. The other footpoint of loop system always remains red-shifted indicating downflowing plasma. The multi-spectral line analysis in the present paper provides a detailed scenario of the plasma flows inversions in cool loop systems leading to the mass transport and their formation. The impulsive energy release due to small-scale reconnection above loop footpoint seems to be the most likely cause for sudden initiation of the plasma flows evident at TR temperatures.Comment: 29 Pages, 14 figures, The Astrophysical Journal (in press