Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli

Priming and activating immune stimuli have profound effects on macrophages, however, studies generally evaluate stimuli in isolation rather than in combination. In this study we have investigated the effects of pro-inflammatory and anti-inflammatory stimuli either alone or in combination on macrophage metabolism. These stimuli include host factors such as IFNγ and ovalbumin-immunoglobulin immune complexes, or pathogen factors such as LPS. Untargeted LC-MS based metabolomics provided an in-depth profile of the macrophage metabolome, and revealed specific changes in metabolite abundance upon either individual stimuli or combined stimuli. Here, by factoring in an interaction term in the linear model, we define the metabolome interactome. This approach allowed us to determine whether stimuli interact in a synergistic or antagonistic manner. In conclusion this study demonstrates a robust approach to interrogate immune-metabolism, especially systems that model host-pathogen interactions

Human Herpesviridae Methods of Natural Killer Cell Evasion

Human herpesviruses cause diseases of considerable morbidity and mortality, ranging from encephalitis to hematologic malignancies. As evidence emerges about the role of innate immunity and natural killer (NK) cells in the control of herpesvirus infection, evidence of viral methods of innate immune evasion grows as well. These methods include interference with the ligands on infected cell surfaces that bind NK cell activating or inhibitory receptors. This paper summarizes the most extensively studied NK cell receptor/ligand pairs and then describes the methods of NK cell evasion used by all eight herpesviruses through these receptors and ligands. Although great strides have been made in elucidating their mechanisms, there is still a disparity between viruses in the amount of knowledge regarding innate immune evasion. Further research of herpesvirus innate immune evasion can provide insight for circumventing viral mechanisms in future therapies

Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity

Preclinical models of Alzheimer’s disease (AD) suggest APOE modulates brain function in structures vulnerable to AD pathophysiology. However, genome-wide association studies now demonstrate that AD risk is shaped by a broader polygenic architecture, estimated via polygenic risk scoring (AD-PRS). Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown. In a large sample (N = 608) of young, asymptomatic individuals, we measure the impact of both (i) APOE and (ii) AD-PRS on a vulnerable cortico-limbic scene-processing network heavily implicated in AD pathophysiology. Integrity of this network, which includes the hippocampus (HC), is fundamental for maintaining cognitive function during ageing. We show that AD-PRS, not APOE, selectively influences activity within the HC in response to scenes, while other perceptual nodes remained intact. This work highlights the impact of polygenic contributions to brain function beyond APOE, which could aid potential therapeutic/interventional strategies in the detection and prevention of AD

Orbital Simulations on Deflecting Near-Earth Objects by Directed Energy

Laser ablation of a Near Earth Object (NEO) on a collision course with Earth produces a cloud of ejecta which exerts a thrust on the NEO, deflecting it from its original trajectory. Ablation may be performed from afar by illuminating an Earth-targeting asteroid or comet with a stand-off “DE-STAR” system consisting of a large phased-array laser in Earth orbit. Alternatively, a much smaller stand-on “DE-STARLITE” system may travel alongside the target, slowly deflecting it from nearby over a long period. This paper presents orbital simulations comparing the effectiveness of both systems across a range of laser and NEO parameters. Simulated parameters include magnitude, duration and, for the stand-on system, direction of the thrust, as well as the type, size and orbital characteristics of the target NEO. These simulations indicate that deflection distance is approximately proportional to the magnitude of thrust and to the square of the duration of ablation, and is inversely proportional to the mass. Furthermore, deflection distance shows strong dependence on thrust direction with the optimal direction of thrust varying with the duration of laser activity. As one example, consider a typical 325m asteroid: beginning 15 yr in advance, just 2N of thrust from a ∼ 20kW stand-on DE-STARLITE system is sufficient to deflect the asteroid by 2R⊕. Numerous scenarios are discussed as is a practical implementation of such a system consistent with current launch vehicle capabilities

Orbital simulations of laser-propelled spacecraft

Spacecraft accelerate by directing propellant in the opposite direction. In the traditional approach, the propellant is carried on board in the form of material fuel. This approach has the drawback of being limited in Delta v by the amount of fuel launched with the craft, a limit that does not scale well to high Delta v due to the massive nature of the fuel. Directed energy photon propulsion solves this problem by eliminating the need for on-board fuel storage. We discuss our system which uses a phased array of lasers to propel the spacecraft which contributes no mass to the spacecraft beyond that of the reflector, enabling a prolonged acceleration and much higher final speeds. This paper compares the effectiveness of such a system for propelling spacecraft into interplanetary and interstellar space across various laser and sail configurations. Simulated parameters include laser power, optics size and orbit as well as payload mass, reflector size and the trajectory of the spacecraft. As one example, a 70 GW laser with 10 km optics could propel a 1 kg craft past Neptune (~30 au) in 5 days at 4% the speed of light, or a 1 g “wafer-sat” past Mars (~0.5 au) in 20 minutes at 21% the speed of light. However, even lasers down to 2 kW power and 1 m optics show noticeable effect on gram-class payloads, boosting their altitude in low Earth orbits by several kilometers per day which is already sufficient to be of practical use

Compliance and Usability of an Asthma Home Monitoring System

Asthma monitoring is an important aspect of patient self-management. However, due to its repetitive nature, patients can find long-term monitoring te-dious. Mobile health can provide an avenue to monitor asthma without needing high levels of active engagement, and instead rely on passive monitoring. In our recent AAMOS-00 study, we collected mobile health data over six months from 22 asthma patients using passive and active monitoring technology, including smartwatch, peak flow measurements, and daily asthma diaries. Compliance to smartwatch monitoring was found to lie between the compliance to complete daily asthma diaries and measuring daily peak flow. However, some study participants faced technical issues with the devices which could have af-fected the relative compliance of the monitoring tasks. Moreover, as evidenced by standard usability questionnaires, we found that the AAMOS-00 study’s data collection system was similar in quality to other studies and published apps

Specific "scientific" data structures, and their processing

Programming physicists use, as all programmers, arrays, lists, tuples, records, etc., and this requires some change in their thought patterns while converting their formulae into some code, since the "data structures" operated upon, while elaborating some theory and its consequences, are rather: power series and Pad\'e approximants, differential forms and other instances of differential algebras, functionals (for the variational calculus), trajectories (solutions of differential equations), Young diagrams and Feynman graphs, etc. Such data is often used in a [semi-]numerical setting, not necessarily "symbolic", appropriate for the computer algebra packages. Modules adapted to such data may be "just libraries", but often they become specific, embedded sub-languages, typically mapped into object-oriented frameworks, with overloaded mathematical operations. Here we present a functional approach to this philosophy. We show how the usage of Haskell datatypes and - fundamental for our tutorial - the application of lazy evaluation makes it possible to operate upon such data (in particular: the "infinite" sequences) in a natural and comfortable manner.Comment: In Proceedings DSL 2011, arXiv:1109.032

Koinonia

Leadership Spotlight FeaturesDeveloping Servant Leaders: The Tale of Two Questions, Kevin Johnson Life at the Cross Roads: Living out the Eternal in the Midst of the Temporal, Brent Ellis Leadership Process vs. Results (Regardless of Culture, Country or Gender), Rebecca Sok Leading During Times of Conflict: Lessons from the Early Church, Carl Ruby From Fiction to Fact, Benjamin Kulpa Thinking TheologicallyCharismatic Boy Meets Reformed Girl, Michael and Stephanie Santarosa Book ReviewsA Review of Integrity: The Courage to Face the Demands of Reality (by Henry Cloud), reviewed by Aaron Damiani Leadership Can Be Taught (by Sharon Daloz Parks), reviewed by Laura M. Rodeheaver FeaturesThe President\u27s Corner Editor\u27s Desk Regional Updateshttps://pillars.taylor.edu/acsd_koinonia/1011/thumbnail.jp