1,755 research outputs found
Headhunting: Evaluating the Disruptive Capacity of Leadership Decapitation on Terrorist Organizations
Leadership decapitation -- the practice of removing a leader from a position of authority through targeted killing (i.e. assassination) or arrest -- has long been a feature of counter-terrorism and counter-insurgency strategies the world over. Still, how effective is the practice of leadership decapitation in actually bringing a halt to, or even impeding, terrorist activity? Can removing top leaders of terrorist enclaves from power disrupt their groups to the point of organizational degradation or dissolution? And lastly, because no two terrorist groups are the same; when a terrorist group experiences leadership loss, how can the group be expected to react? Will they implode under exogenous pressure, reorient in a search for political viability, or something different altogether?
This paper endeavors to answer some of these questions by establishing a baseline of terrorist group typologies and motivations, distilling the key, generative factors that have proven to contribute to organizational death among terrorist groups, and provide a causal correlation between type of terrorist organization, and their probable response to leadership loss. Regardless of the ethical implications of leadership decapitation, this paper provides a mixed method analysis of the after-effects of leadership removal.
Similarly, this paper finds that certain terrorist groups, such as religiously motivated ones, are more likely to degrade or disband when a leader is removed, while others, like those who use terrorism as a tool to further a nationalist or separatist agenda, are less likely to be irreparably damaged when a leader is extricated. Finally, the conclusion offers some prescriptive policy implications for the findings within the paper
Malondialdehyde Acetaldehyde Adducts (MAA-Adducts) Direct Distinctive Pro-Inflammatory Responses in Endothelial and Macrophage Cell Lines
Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. At present, the mechanism(s) by which inflammation contributes to this disease isnot entirely understood. Inflammation is known to induce oxidative stress, of which one consequence is lipid peroxidation. This process leads to the production of malondialdehyde (MDA), which can subsequently break down to form acetaldehyde (AA). These two aldehyde by-products can covalently interact with the ε-amino group of lysineswithin proteins and lipoproteins leading to the formation of highly immunogenic malondialdehyde-acetaldehyde adducts (MAA-adducts). The aim of this study was to determine the in-vitro cytokine response of endothelial cells and macrophages treated with MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). In addition, cells isolated from mice with exposure to MAA and high fat diets were stained and imaged for uptake of the modified macromolecules of interest. We found that exposure of endothelial cells resulted in increased expression of IL-6, TNF-α, ICAM-1, VCAM-1, and MCP-1 in response to incubation with HSA-MAA; whereas, the same treatment of macrophages resulted in increased expression of IL-6, TNF-α, and IL-1b. LDL-MAA incubationresulted in increased TNF-α expression in macrophages, but MCP-1 was elevated in endothelial cells. Interestingly, the quantitative and qualitative uptake of triglycerides was increased in both endothelial and macrophage cells when exposed to LDL-MAA compared to LDL alone. The results of these studies demonstrate that different MAA-adducts elicit unique responses in different cell types. Additionally, the presence of MAA appears to modulate the cells leading to increased uptake of triglycerides and further progression of the inflammatory response.https://digitalcommons.unmc.edu/emet_posters/1003/thumbnail.jp
Scaling Laws for Impact Craters in Water
Tsunami waves from asteroid impacts into water are of concern from asteroids in the 200 m to 1 km diameter range because this spans the range from asteroids that will likely hit the surface and not airburst, but also be small enough that global climate effects will hopefully be minimal. Current estimates of impact tsunamis depend on either hydrocode simulations or on semi-analytical models. Unfortunately there is significant disagreement between these methods. One of the main reasons for the disparity is that the semi-analytical models such as Holsapple (1993) rely on experimental impacts into deep water. However for asteroids in the 200 - 1000 m range even the deep ocean basins can appear as shallow water impacts where the crater formed in the water reaches all the way to the sea floor. Another reason for the disparity arises from the linear interpolation of data across many orders of magnitude difference between Froude number (ratio of kinetic to gravitational energy) used in the laboratory experiments and what would be seen in an asteroid impact. The Gault & Sonett (1982) experiment shot millimeter sized glass spheres into water at 1 to 6 km/s and the Olevson (1969) experiment dropped millimeter sized water drops at a few meters per second. The goal of this work was to fill in the gaps and conduct experiments and simulations at the correct Froude numbers of interest, and in both deep and shallow water, to help resolve the disparity and extend the semi-analytical models
The Lantern Vol. 42, No. 1, Fall 1975
• The House • The Empty Man • Time • Corporea • Take Me • Elements of Nature • Hope • Acclimation • Road to Elat • Sinai • Jerusalem • Fatman • Ode to Grand Rapids • Ode to Cora • The Apple Cart • Next Time You\u27re Down South • Star Wreck • Eulogy to John Doe • A Postal Preoccupation • The Interview May Be Real (But Don\u27t Bet On It) • Winter Eve • My Love • God\u27s Children • A View From a Hill • Freedom For Us • Sleep Demonhttps://digitalcommons.ursinus.edu/lantern/1107/thumbnail.jp
Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program
Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset
Direct antioxidant properties of methotrexate: Inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging.
Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, supporting the concept that MAA-adducts not only serve as markers of oxidative stress but may have a direct role in the pathogenesis of inflammatory diseases. Because MAA-adducts are commonly detected in diseased tissues and are proposed to mitigate disease progression in both RA and CVD, we tested the hypothesis that MTX inhibits the generation of MAA-protein adducts by scavenging reactive oxygen species. Using a cell free system, we found that MTX reduces MAA-adduct formation by approximately 6-fold, and scavenges free radicals produced during MAA-adduct formation. Further investigation revealed that MTX directly scavenges superoxide, but not hydrogen peroxide. Additionally, using the Nrf2/ARE luciferase reporter cell line, which responds to intracellular redox changes, we observed that MTX inhibits the activation of Nrf2 in cells treated with MDA and AA. These studies define previously unrecognized mechanisms by which MTX can reduce inflammation and subsequent tissue damage, namely, scavenging free radicals, reducing oxidative stress, and inhibiting MAA-adduct formation
Finding Correlations of the Oxygen Reduction Reaction Activity of Transition Metal Catalysts with Parameters Obtained from Quantum Mechanics
To facilitate a less empirical approach to developing improved catalysts, it is important to correlate catalytic performance to surrogate properties that can be measured or predicted accurately and quickly, allowing experimental synthesis and testing of catalysts to focus on the most promising cases. Particularly hopeful is correlating catalysis performance to the electronic density of states (DOS). Indeed, there has been success in using just the center of the d-electron density, which in some cases correlates linearly with oxygen atom chemisorption energy, leading to a volcano plot for catalytic performance versus “d-band center”. To test such concepts we calculated the barriers and binding energies for the various reactions and intermediates involved in the oxygen reduction reaction (ORR) for all 12 transition metals in groups 8–11 (Fe–Cu columns). Our results show that the oxygen binding energy can serve as a useful parameter in describing the catalytic activity for pure metals, but it does not necessarily correlate with the d-band center. In addition, we find that the d-band center depends substantially on the calculation method or the experimental setup, making it a much less reliable indicator for ORR activity than the oxygen binding energy. We further examine several surfaces of the same pure metals to evaluate how the d-band center and oxygen binding energy depend on the surface
Novel Antioxidant Properties of Doxycycline
Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress
Using Photoelectron Spectroscopy and Quantum Mechanics to Determine d-Band Energies of Metals for Catalytic Applications
The valence band structures (VBS) of eight transition metals (Fe, Co, Ni, Cu, Pd, Ag, Pt, Au) were investigated by photoelectron spectroscopy (PES) using He I, He II, and monochromatized Al Kα excitation. The influence of final states, photoionization cross-section, and adsorption of residual gas molecules in an ultrahigh vacuum environment are discussed in terms of their impact on the VBS. We find that VBSs recorded with monochromatized Al Kα radiation are most closely comparable to the ground state density of states (DOS) derived from quantum mechanics calculations. We use the Al Kα-excited PES measurements to correct the energy scale of the calculated ground-state DOS to approximate the “true” ground-state d-band structure. Finally, we use this data to test the d-band center model commonly used to predict the electronic-property/catalytic-activity relationship of metals. We find that a simple continuous dependence of activity on d-band center position is not supported by our results (both experimentally and computationally)
Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque
Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens
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