Spectral analysis and sonification of simulation data generated in a frequency domain experiment

In this thesis, we evaluate the frequency domain approach for data farming and assess the possibility of analyzing complex data sets using data sonification. Data farming applies agent-based models and simulation, computing power, and data analysis and visualization technologies to help answer complex questions in military operations. Sonification is the use of data to generate sound for analysis. We apply a frequency domain experiment (FDE) to a combat simulation and analyze the output data set using spectral analysis. We compare the results from our FDE with those obtained using another experimental design on the same combat scenario. Our results confirm and complement the earlier findings. We then develop an auditory display that uses data sonification to represent the simulation output data set with sound. We consider the simulation results from the FDE as a waveshaping function and generate sounds using sonification software. We characterize the sonified data by their noise, signal, and volume. Qualitatively, the sonified data match the corresponding spectra from the FDE. Therefore, we demonstrate the feasibility of representing simulation data from the FDE with our sonification. Finally, we offer suggestions for future development of a multimodal display that can be used for analyzing complex data sets.http://archive.org/details/spectralnalysisn109459805Lieutenant, United States NavyApproved for public release; distribution is unlimited

Ethical Control of Unmanned Systems: lifesaving/lethal scenarios for naval operations

Prepared for: Raytheon Missiles & Defense under NCRADA-NPS-19-0227This research in Ethical Control of Unmanned Systems applies precepts of Network Optional Warfare (NOW) to develop a three-step Mission Execution Ontology (MEO) methodology for validating, simulating, and implementing mission orders for unmanned systems. First, mission orders are represented in ontologies that are understandable by humans and readable by machines. Next, the MEO is validated and tested for logical coherence using Semantic Web standards. The validated MEO is refined for implementation in simulation and visualization. This process is iterated until the MEO is ready for implementation. This methodology is applied to four Naval scenarios in order of increasing challenges that the operational environment and the adversary impose on the Human-Machine Team. The extent of challenge to Ethical Control in the scenarios is used to refine the MEO for the unmanned system. The research also considers Data-Centric Security and blockchain distributed ledger as enabling technologies for Ethical Control. Data-Centric Security is a combination of structured messaging, efficient compression, digital signature, and document encryption, in correct order, for round-trip messaging. Blockchain distributed ledger has potential to further add integrity measures for aggregated message sets, confirming receipt/response/sequencing without undetected message loss. When implemented, these technologies together form the end-to-end data security that ensures mutual trust and command authority in real-world operational environments—despite the potential presence of interfering network conditions, intermittent gaps, or potential opponent intercept. A coherent Ethical Control approach to command and control of unmanned systems is thus feasible. Therefore, this research concludes that maintaining human control of unmanned systems at long ranges of time-duration and distance, in denied, degraded, and deceptive environments, is possible through well-defined mission orders and data security technologies. Finally, as the human role remains essential in Ethical Control of unmanned systems, this research recommends the development of an unmanned system qualification process for Naval operations, as well as additional research prioritized based on urgency and impact.Raytheon Missiles & DefenseRaytheon Missiles & Defense (RMD).Approved for public release; distribution is unlimited

Applying Apriori algorithm to explore long-term care services usage status—Variables based on the combination of patients with dementia and their caregivers

PurposeThe aim of this study was to identify the combination of patients with dementia and their caregivers' characteristics associated with long-term care (LTC) services usage.Patients and methodsA cross-sectional study was conducted with 475 patients with mild, moderate, and severe dementia at Changhua Christian Hospital, Taiwan. Eleven types of variables from patients with dementia, nine types of variables from patients' caregivers, and 15 types of LTC services were used for this study. The Apriori algorithm was employed to identify the attributes from the patients and their caregivers who used a particular LTC service from a comprehensive viewpoint.ResultsA total of 75 rules were generated by the Apriori algorithm with support of 2%, confidence of 80%, and lift >1. Among these rules, 25 rules belonged to home personal care services which were summarized further into four general rules for home personal care services. On the other hand, 50 rules belonged to assistive devices that were summarized further into 21 general rules based on their similarities. Patient's walking ability, patient's emotional liability, unemployed or retired caregivers, caregivers' feelings with either helplessness or hopelessness, and caregivers who cared for patients with dementia solely were found to be the critical variables to use home personal care services. In contrast, patient's walking ability, age, and severity as well as caregivers' age, mood, marital status, caregiving burden, and the patient being cared for mainly by a foreign care helper were found to be the critical variables to use assistive devices.ConclusionThis study showed preliminary results on the LTC service usage from patients with dementia and their caregivers residing in the community. Understanding the patient–caregiver dyad's profile leads the service providers, policymakers, and the referral team to tailor service provisions better to meet the needs and identify the potential target groups. The findings in this study serve as references to reduce caregivers' burden as well as to improve the quality of care for patients with dementia

Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.

Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate

Nanoparticle conversion to biofilms: in vitro demonstration using serum-derived mineralo-organic nanoparticles

Aims: Mineralo-organic nanoparticles (NPs) detected in biological fluids have been described as precursors of physiological and pathological calcifications in the body. Our main objective was to examine the early stages of mineral NP formation in body fluids. Materials & methods: A nanomaterial approach based on atomic force microscopy, dynamic light scattering, electron microscopy and spectroscopy was used. Results: The mineral particles, which contain the serum proteins albumin and fetuin-A, initially precipitate in the form of round amorphous NPs that gradually grow in size, aggregate and coalesce to form crystalline mineral films similar to the structures observed in calcified human arteries. Conclusion: Our study reveals the early stages of particle formation and provides a platform to analyze the role(s) of mineralo-organic NPs in human tissues

The Yang-Tonifying Herbal Medicine Cynomorium songaricum

Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS) is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO) levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases

Glycogen synthase kinase-3β inactivation inhibits tumor necrosis factor-α production in microglia by modulating nuclear factor κB and MLK3/JNK signaling cascades

<p>Abstract</p> <p>Background</p> <p>Deciphering the mechanisms that modulate the inflammatory response induced by microglial activation not only improves our insight into neuroinflammation but also provides avenues for designing novel therapies that could halt inflammation-induced neuronal degeneration. Decreasing glycogen synthase kinase-3β (GSK-3β) activity has therapeutic benefits in inflammatory diseases. However, the exact molecular mechanisms underlying GSK-3β inactivation-mediated suppression of the inflammatory response induced by microglial activation have not been completely clarified. Tumor necrosis factor-α (TNF-α) plays a central role in injury caused by neuroinflammation. We investigated the regulatory effect of GSK-3β on TNF-α production by microglia to discern the molecular mechanisms of this modulation.</p> <p>Methods</p> <p>Lipopolysaccharide (LPS) was used to induce an inflammatory response in cultured primary microglia or murine BV-2 microglial cells. Release of TNF-α was measured by ELISA. Signaling molecules were analyzed by western blotting, and activation of NF-κB and AP-1 was measured by ELISA-based DNA binding analysis and luciferase reporter assay. Protein interaction was examined by coimmunoprecipitation.</p> <p>Results</p> <p>Inhibition of GSK-3β by selective GSK-3β inhibitors or by RNA interference attenuated LPS-induced TNF-α production in cultured microglia. Exploration of the mechanisms by which GSK-3β positively regulates inflammatory response showed that LPS-induced IκB-α degradation, NF-κBp65 nuclear translocation, and p65 DNA binding activity were not affected by inhibition of GSK-3β activity. However, GSK-3β inactivation inhibited transactivation activity of p65 by deacetylating p65 at lysine 310. Furthermore, we also demonstrated a functional interaction between mixed lineage kinase 3 (MLK3) and GSK-3β during LPS-induced TNF-α production in microglia. The phosphorylated levels of MLK3, MKK4, and JNK were increased upon LPS treatment. Decreasing GSK-3β activity blocked MLK3 signaling cascades through disruption of MLK3 dimerization-induced autophosphorylation, ultimately leading to a decrease in TNF-α secretion.</p> <p>Conclusion</p> <p>These results suggest that inactivation of GSK-3β might represent a potential strategy to downregulate microglia-mediated inflammatory processes.</p

Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation.

Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications

Controlled Synthesis of Organic/Inorganic van der Waals Solid for Tunable Light-matter Interactions

Van der Waals (vdW) solids, as a new type of artificial materials that consist of alternating layers bonded by weak interactions, have shed light on fascinating optoelectronic device concepts. As a result, a large variety of vdW devices have been engineered via layer-by-layer stacking of two-dimensional materials, although shadowed by the difficulties of fabrication. Alternatively, direct growth of vdW solids has proven as a scalable and swift way, highlighted by the successful synthesis of graphene/h-BN and transition metal dichalcogenides (TMDs) vertical heterostructures from controlled vapor deposition. Here, we realize high-quality organic and inorganic vdW solids, using methylammonium lead halide (CH3NH3PbI3) as the organic part (organic perovskite) and 2D inorganic monolayers as counterparts. By stacking on various 2D monolayers, the vdW solids behave dramatically different in light emission. Our studies demonstrate that h-BN monolayer is a great complement to organic perovskite for preserving its original optical properties. As a result, organic/h-BN vdW solid arrays are patterned for red light emitting. This work paves the way for designing unprecedented vdW solids with great potential for a wide spectrum of applications in optoelectronics