Predicting Multi-actor collaborations using Hypergraphs

Social networks are now ubiquitous and most of them contain interactions involving multiple actors (groups) like author collaborations, teams or emails in an organizations, etc. Hypergraphs are natural structures to effectively capture multi-actor interactions which conventional dyadic graphs fail to capture. In this work the problem of predicting collaborations is addressed while modeling the collaboration network as a hypergraph network. The problem of predicting future multi-actor collaboration is mapped to hyperedge prediction problem. Given that the higher order edge prediction is an inherently hard problem, in this work we restrict to the task of predicting edges (collaborations) that have already been observed in past. In this work, we propose a novel use of hyperincidence temporal tensors to capture time varying hypergraphs and provides a tensor decomposition based prediction algorithm. We quantitatively compare the performance of the hypergraphs based approach with the conventional dyadic graph based approach. Our hypothesis that hypergraphs preserve the information that simple graphs destroy is corroborated by experiments using author collaboration network from the DBLP dataset. Our results demonstrate the strength of hypergraph based approach to predict higher order collaborations (size>4) which is very difficult using dyadic graph based approach. Moreover, while predicting collaborations of size>2 hypergraphs in most cases provide better results with an average increase of approx. 45% in F-Score for different sizes = {3,4,5,6,7}

High Frequency Study of Magnetic Nanostructures

The work in this thesis is divided in three parts. In part one we developed electrodeposition method of Nickel Nanowire in commercial AAO template in constant current (Galvanostatic) mode, further we tried to estimate the growth rate from theory, from saturation magnetization and direct measurement from SEM image. In part two we focused on using the Vector Network Analyzer (VNA) to measure the Ferromagnetic Resonance (FMR))of various magnetic Nanowire arrays. We employed different measurement geometries using microstripline and coplanar waveguide as microwave transmission lines. In part three our aim was to study the magnetic properties of complex ferromagnetic system, especially the effect of interactions on dynamic properties of magnetic nanostructures (nanowire arrays and exchange biased ferromagnetic-antiferromagnetic multilayers). Our effort was centered on using ferromagnetic resonance to understand the dynamic response of these systems

High Frequency Study of Magnetic Nanostructures

The work in this thesis is divided in three parts. In part one we developed electrodeposition method of Nickel Nanowire in commercial AAO template in constant current (Galvanostatic) mode, further we tried to estimate the growth rate from theory, from saturation magnetization and direct measurement from SEM image. In part two we focused on using the Vector Network Analyzer (VNA) to measure the Ferromagnetic Resonance (FMR))of various magnetic Nanowire arrays. We employed different measurement geometries using microstripline and coplanar waveguide as microwave transmission lines. In part three our aim was to study the magnetic properties of complex ferromagnetic system, especially the effect of interactions on dynamic properties of magnetic nanostructures (nanowire arrays and exchange biased ferromagnetic-antiferromagnetic multilayers). Our effort was centered on using ferromagnetic resonance to understand the dynamic response of these systems

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