Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice.

Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity

A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.

It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity. We reported that Gpr120 is the functional receptor for these fatty acids and that ω-3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4). However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future

Recommended Roles For Uninhabited Team Members Within Mixed-Initiative Combat Teams

Trust in automation is a well-researched topic that is particularly important when planning mixed initiative interaction. When working with teams comprised of both human and non-human team members, the amount of trust the operator places in the automation often determines which parts of the interaction can be automated and the optimal level of automation. The mixed-initiative community has created numerous systems that leverage trust in automation, but results have been inconclusive. After examining the primary factors that impact trust in automated systems, we make several recommendations regarding the assignment of roles for human and non-human mixed-initiative team members. © 2010 IEEE

What can VR do for U? Virtual Reality for Training Uninhabited Aircraft Systems

The proliferation of Uninhabited Aircraft Systems (UAS) during forward deployed military operations presents compelling challenges to the training community. This presentation will examine how Virtual Reality (VR) technologies may be employed to instantiate novel training approaches targeted at UAS team coordination and tactics. The RQ-11 Raven-B, and its associated training issues will be used to illustrate challenges facing the U.S. Marine Corps. VR solutions currently applied to this domain and emerging research efforts will also be discussed

What Can Vr Do For U? Virtual Reality For Training Uninhabited Aircraft Systems

The proliferation of Uninhabited Aircraft Systems (UAS) during forward deployed military operations presents compelling challenges to the training community. This presentation will examine how Virtual Reality (VR) technologies may be employed to instantiate novel training approaches targeted at UAS team coordination and tactics. The RQ-11 Raven-B, and its associated training issues will be used to illustrate challenges facing the U.S. Marine Corps. VR solutions currently applied to this domain and emerging research efforts will also be discussed

Blending Systems Engineering Principles And Simulation-Based Design Techniques To Facilitate Military Prototype Development

Tactical communications represent a critical skill set to military training at the individual service level and to the joint military community. As the complexity of the operational environment increases, the methods and devices employed to address tactical communications training follow suit. One mitigation approach incorporates simulation tools by merging live training elements with virtual, or simulated, training devices. Thus, integrating live and virtual components is particularly important to the tactical communications training domain. A logical step in the advancement of live-to-virtual (LV) communications is the development of a device capable of merging, managing, and allocating multiple requests for live radio resources in a dynamic live, virtual, constructive (LVC) configuration. This paper details the application of systems engineering principles and simulation-based design to the development of a prototype Integrated Live-to-Virtual Communications Server (ILVCS). A detailed discussion of the developmental approach and its impact upon cost, schedule, and technical risks is provided. © 2007 IEEE

Virtual Reality In The Training Environment

This chapter explores the role of virtual reality (VR) systems in the military training environment. It begins with a discussion of some of the current and future training challenges that VR can solve. These include enabling the warfighter to continue training despite the ever-increasing operational tempo and enabling the military to provide low-cost deployable training systems. In order to provide a framework for understanding these challenges, and some of the ongoing efforts that address them, a real-world VR application is described. Once this framework is established, the chapter then moves to an exploration of the enabling technologies that can be brought to bear on these challenges. This includes both instructional technologies as well as hardware/software technologies. Each technology is matched with a discussion regarding how these technologies can be integrated into a single VR training system within the detailed real-world example application. This chapter ends with a brief discussion of future directions for VR-based training technologies