SILHIL Replication of Electric Aircraft Powertrain Dynamics and Inner-Loop Control for V&V of System Health Management Routines

Software-in-the-loop and Hardware-in-the-loop testing of failure prognostics and decision making tools for aircraft systems will facilitate more comprehensive and cost-effective testing than what is practical to conduct with flight tests. A framework is described for the offline recreation of dynamic loads on simulated or physical aircraft powertrain components based on a real-time simulation of airframe dynamics running on a flight simulator, an inner-loop flight control policy executed by either an autopilot routine or a human pilot, and a supervisory fault management control policy. The creation of an offline framework for verifying and validating supervisory failure prognostics and decision making routines is described for the example of battery charge depletion failure scenarios onboard a prototype electric unmanned aerial vehicle

A Pathogenic Role for Splenic B1 Cells in SIV Disease Progression in Rhesus Macaques

B1 cells spontaneously produce protective natural antibodies which provide the first line of defense against a variety of pathogens. Although these natural antibodies share similar autoreactive features with several HIV-1 broadly neutralizing antibodies, the role of B1 cells in HIV/SIV disease progression is unknown. We report the presence of human-like B1 cells in rhesus macaques. During chronic SIV infection, we found that the frequency of splenic CD11b+ B1 cells positively correlated with plasma SIV viral load and exhausted T cells. Mechanistically, we discovered that splenic CD11b+ B1 cells express PD-L2 and IL-10, and were able to induce PD-1 upregulation on CD4+ T cells in vitro. These findings suggest that splenic CD11b+ B1 cells may contribute to the regulation of SIV plasma viral load by enhancing T cell exhaustion. Therefore, understanding the mechanisms that govern their function in rhesus macaques may lead to novel therapeutic strategies for impeding HIV/SIV disease progression

Abstract Number ‐ 65: US Comprehensive Stroke Center Utilization of FAST and BEFAST Mnemonics for Public Education

Introduction Symptom recognition and timely access to treatment are critical components of acute stroke care systems. Two mnemonics widely used in public educational campaigns for recognizing stroke symptoms include FAST (Face‐Arm‐Speech‐Time) and BEFAST (Balance‐Eyes‐Face‐Arm Speech‐Time). The FAST mnemonic, endorsed by the AHA/ASA can miss up to 14% of strokes. BEFAST includes common posterior circulation stroke symptoms and has been implemented by several Comprehensive Stroke Centers (CSCs). Methods We sought to analyze the pattern of public educational materials available on the websites US CSCs. The Joint Commission (JC) quality check website compiles a list containing the names and locations of the country’s 217 JC‐certified CSCs, which was downloaded in August, 2022. Each CSC’s website was searched for educational material containing FAST and BEFAST mnemonics for stroke symptom recognition. Results The FAST mnemonic was listed by 35%of CSCs, the BEFAST by 58%, with 7% listing no specific mnemonic. The highest portion of CSCs using BEFAST was in western (65%) and southeastern (63%) states. The highest percentage of CSCs with no listed mnemonic were in the northeastern (14%) and southeastern (13%) states. Conclusions Consistency is critical in shaping public health education related to stroke symptoms. Our study suggests further effort is needed to unify the public messaging on stroke recognition

Effects of Blockade of Muscarinic Receptors and Nicotinic Receptors on Spatial Discrimination

Previous studies reported that blocking muscarinic receptors disrupts performance in spatial working memory task, and that performance impairment worsens when the delay period gets longer, suggesting that spatial working memory is sensitive to muscarinic receptor blockade. The present study compared the effects of muscarinic receptor antagonist (scopolamine) and nicotinic receptor antagonist (mecamylamine) on visuospatial discrimination using a spatial task without a delay component. Wistar rats were trained on a visuospatial task that required a correct barpress opposite to the cue location. Once the animals reached a behavioral criterion (\u3e85% correct, 2 consecutive sessions), the drug phase began. On the day of testing, the animals received either a single dose of scopolamine (0.25-1.0 mg/kg, i.p.), mecamylamine (2.5-10mg/kg, i.p.), or saline in a counterbalanced manner. The same behavioral criterion (\u3e85% correct, 2 consecutive sessions) was required between injections. We found that scopolamine disrupted correct responses in a dose-dependent manner and increased response latencies. Mecamylamine failed to affect correct responses. Our data are consistent with previous report that successful performance in spatial discrimination depends on activation of muscarinic receptors. Given the absence of a delay in our task, our results provide critical evidence that performance deficit after scopolamine reflects deficits in reference memory rather than working memory

E4orf1 Suppresses E1B-Deleted Adenovirus Vaccine-Induced Immune Responses

As demonstrated by the recent COVID pandemic, vaccines can reduce the burden arising from infectious agents. Adenoviruses (Ads) with deletion of the early region 1B55K (ΔE1B Ad) are currently being explored for use in vaccine delivery. ΔE1B Ads are different from Ads with deletions in early region 1 and early region 3 (ΔE1/E3) used in most Ad vaccine vectors in that they contain the Ad early region 1A (E1A), and therefore the ability to replicate. Common to almost all Ads that are being explored for clinical use is the Ad early region 4 (E4). Among the E4 genes is open reading frame 1 (E4orf1), which mediates signals through the PI3-kinase/Akt pathway that is known to modulate immune responses. This suggests that E4orf1 might also modulate immune responses, although it has remained unexplored in ΔE1B Ad. Here, we show that cells infected with an E1B55K and E4orf1-deleted (ΔE41) Ad exhibited reduced levels of phosphorylated Akt (Ser473 and Thr308)) and expressed different intrinsic innate immune cytokines from those induced in cells infected with an E4orf1-containing, ΔE1B parental Ad that exhibited elevated levels of phosphorylated Akt. Rhesus macaques immunized with a ΔE41 Ad that expressed rhFLSC (HIV-1BaL gp120 linked to rhesus CD4 D1 and D2), exhibited higher levels of rhFLSC-specific interferon γ-producing memory T-cells, higher titers of rhFLSC-specific IgG1 binding antibody in serum, and antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC) with greater killing capacity than the ΔE1B Ad. Therefore, E4orf1, perhaps by acting through the PI3-kinase/Akt pathway, limits intrinsic innate and system-wide adaptive immune responses that are important for improved ΔE1B Ad-based vaccines