Proton Magnetic Resonance Spectroscopy Reveals Neuroprotection by Oral Minocycline in a Nonhuman Primate Model of Accelerated NeuroAIDS

Background: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. Methodology/Principal Findings: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. Conclusions/Significance: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus

Maritime domain protection in the Straits of Malacca

Includes supplementary materialHostile acts of maritime piracy and terrorism have increased worldwide in recent years, and the global impacts of a successful attack on commercial shipping in the Straits of Malacca make it one of the most tempting target locations for maritime terrorism. In an attempt to develop a system of systems to defeat and prevent terrorism in the Straits of Malacca, this study developed three significant commercial shipping attack scenarios (Weapons of Mass Destruction (WMD) shipment, Ship As a Weapon (SAW), and Small Boat Attack (SBA)), and used a Systems Engineering Design Process (SEDP) to design alternative architectures that offered promising ways to defeat these attacks. Maritime Domain Protection (MDP) architecture alternatives combined five separate systems: a Land Inspection System, a Sensor System, a Command and Control, Communications, and Intelligence (C3I) System, a Response Force System, and a Sea Inspection System. Individual models for each system were developed and combined into overarching integrated architecture models to evaluate overall performance. The study results showed that solutions tended to be threat-specific, and current capabilities were mixed. While solutions were found to effectively reduce risk in all threat scenarios, these sometimes came at great expense. Alternatively, cost-effective solutions were also found for each scenario, but these sometimes gave limited performance