Ultra-high-frequency piecewise-linear chaos using delayed feedback loops

We report on an ultra-high-frequency (> 1 GHz), piecewise-linear chaotic system designed from low-cost, commercially available electronic components. The system is composed of two electronic time-delayed feedback loops: A primary analog loop with a variable gain that produces multi-mode oscillations centered around 2 GHz and a secondary loop that switches the variable gain between two different values by means of a digital-like signal. We demonstrate experimentally and numerically that such an approach allows for the simultaneous generation of analog and digital chaos, where the digital chaos can be used to partition the system's attractor, forming the foundation for a symbolic dynamics with potential applications in noise-resilient communications and radar

Horizontal Ionospheric Electron Density Gradients Observed by FORMOSAT-3/COSMIC TIP: Spatial Distributions and Effects on VLF Wave Propagation at Mid-Latitudes

We investigate the spatial variability of electron densities in the nightside ionosphere and its effects on very-low frequency (VLF) wave propagation using a suite of instruments from the FORMOSAT-3/Constellation Observing System for Meteorology Ionosphere and Climate (COSMIC) spacecraft.We use observations from the Tiny Ionospheric Photometer (TIP) instruments to infer the horizontal electron density gradients along each satellite track. We demonstrate that the OI 1356 _ radiance measured by the TIP instruments tracks the horizontal electron density structure well with high spatial resolution and unprecedented sensitivity. Accurate measurements of the horizontal electron density gradients are important for improving retrieved electron density profiles from GPS occultation and other tomographic remote sensing techniques. The processes underlying the variability in the large-scale, nightside electron density gradients are the main drivers of ionospheric weather. TIP observations reveal significant variability in both the small and large scale structure of the nightside ionosphere. The relative intensities, relative widths, and latitudinal separation of the northern and southern ionization crests of the Appleton anomalies show a high degree of longitudinal variation.We demonstrate how the TIP observations can be used to measure the horizontal gradient of the refractive index of whistler-mode VLF waves propagating in a cold, collisionless plasma. These measurements are critical for understanding how gradients in electron density associated with ionospheric structure such as depletions and the Appleton anomalies affect VLF wave propagation through the equatorial and mid-latitude ionosphere

Exploiting Laboratory and Heliophysics Plasma Synergies

Recent advances in space-based heliospheric observations, laboratory experimentation, and plasma simulation codes are creating an exciting new cross-disciplinary opportunity for understanding fast energy release and transport mechanisms in heliophysics and laboratory plasma dynamics, which had not been previously accessible. This article provides an overview of some new observational, experimental, and computational assets, and discusses current and near-term activities towards exploitation of synergies involving those assets. This overview does not claim to be comprehensive, but instead covers mainly activities closely associated with the authors’ interests and reearch. Heliospheric observations reviewed include the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI) on the National Aeronautics and Space Administration (NASA) Solar Terrestrial Relations Observatory (STEREO) mission, the first instrument to provide remote sensing imagery observations with spatial continuity extending from the Sun to the Earth, and the Extreme-ultraviolet Imaging Spectrometer (EIS) on the Japanese Hinode spacecraft that is measuring spectroscopically physical parameters of the solar atmosphere towards obtaining plasma temperatures, densities, and mass motions. The Solar Dynamics Observatory (SDO) and the upcoming Solar Orbiter with the Heliospheric Imager (SoloHI) on-board will also be discussed. Laboratory plasma experiments surveyed include the line-tied magnetic reconnection experiments at University of Wisconsin (relevant to coronal heating magnetic flux tube observations and simulations), and a dynamo facility under construction there; the Space Plasma Simulation Chamber at the Naval Research Laboratory that currently produces plasmas scalable to ionospheric and magnetospheric conditions and in the future also will be suited to study the physics of the solar corona; the Versatile Toroidal Facility at the Massachusetts Institute of Technology that provides direct experimental observation of reconnection dynamics; and the Swarthmore Spheromak Experiment, which provides well-diagnosed data on three-dimensional (3D) null-point magnetic reconnection that is also applicable to solar active regions embedded in pre-existing coronal fields. New computer capabilities highlighted include: HYPERION, a fully compressible 3D magnetohydrodynamics (MHD) code with radiation transport and thermal conduction; ORBIT-RF, a 4D Monte-Carlo code for the study of wave interactions with fast ions embedded in background MHD plasmas; the 3D implicit multi-fluid MHD spectral element code, HiFi; and, the 3D Hall MHD code VooDoo. Research synergies for these new tools are primarily in the areas of magnetic reconnection, plasma charged particle acceleration, plasma wave propagation and turbulence in a diverging magnetic field, plasma atomic processes, and magnetic dynamo behavior.United States. Office of Naval ResearchNaval Research Laboratory (U.S.

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Reactive oxygen species: a volatile driver of field cancerization and metastasis

Abstract Field cancerization and metastasis are the leading causes for cancer recurrence and mortality in cancer patients. The formation of primary, secondary tumors or metastasis is greatly influenced by multifaceted tumor-stroma interactions, in which stromal components of the tumor microenvironment (TME) can affect the behavior of the cancer cells. Many studies have identified cytokines and growth factors as cell signaling molecules that aid cell to cell communication. However, the functional contribution of reactive oxygen species (ROS), a family of volatile chemicals, as communication molecules are less understood. Cancer cells and various tumor-associated stromal cells produce and secrete a copious amount of ROS into the TME. Intracellular ROS modulate cell signaling cascades that aid in the acquisition of several hallmarks of cancers. Extracellular ROS help to propagate, amplify, and effectively create a mutagenic and oncogenic field which facilitate the formation of multifoci tumors and act as a springboard for metastatic tumor cells. In this review, we summarize our current knowledge of ROS as atypical paracrine signaling molecules for field cancerization and metastasis. Field cancerization and metastasis are often discussed separately; we offer a model that placed these events with ROS as the focal instigating agent in a broader “seed-soil” hypothesis

Tomographic Reconstruction of the Low-Latitude Nighttime Electron Density Using FORMOSAT-3/COMSIC Radio Occultation and UV Photometer Data

The Constellation Observing System for Meteorology, Ionosphere, and Climate (FORMOSAT-3/COSMIC) is a constellation of six microsatellites that was launched into low-Earth orbit on 14 April 2006. Each FORMOSAT-3/COSMIC satellite contains a GPS Occultation Experiment (GOX) GPS receiver and a Tiny Ionospheric Photometer (TIP), which measure the ionosphere. In previous papers of Dymond and Thomas (2001) and Dymond et al. (2000), an algorithm for tomographically inverting GPS occultation and UV radiometer measurements has been presented. We apply this algorithm to the inversion of recently acquired FORMOSAT-3/COSMIC data and present the results

Utility of human relevant preclinical animal models in navigating NAFLD to MAFLD paradigm

Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance

Lessons on Drug Development: A Literature Review of Challenges Faced in Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trials

NAFLD is the most common chronic liver disease worldwide, occurring in both obese and lean patients. It can lead to life-threatening liver diseases and nonhepatic complications, such as cirrhosis and cardiovascular diseases, that burden public health and the health care system. Current care is weight loss through diet and exercise, which is a challenging goal to achieve. However, there are no FDA-approved pharmacotherapies for NAFLD. This review thoroughly examines the clinical trial findings from 22 drugs (Phase 2 and above) and evaluates the future direction that trials should take for further drug development. These trialed drugs can broadly be categorized into five groups—hypoglycemic, lipid-lowering, bile-pathway, anti-inflammatory, and others, which include nutraceuticals. The multitude of challenges faced in these yet-to-be-approved NAFLD drug trials provided insight into a few areas of improvement worth considering. These include drug repurposing, combinations, noninvasive outcomes, standardization, adverse event alleviation, and the need for precision medicine with more extensive consideration of NAFLD heterogenicity in drug trials. Understandably, every evolution of the drug development landscape lies with its own set of challenges. However, this paper believes in the importance of always learning from lessons of the past, with each potential improvement pushing clinical trials an additional step forward toward discovering appropriate drugs for effective NAFLD management

Analysis on the relationship between cyber attacks and sociopolitical events (ARCASE)

A number of cyber-attacks have been increasing in the past half-decade. There are speculations that these attacks are associated with events in the physical domain. However, there is no empirical evidence to prove or disprove that the attacks in cyberspace are influenced by events happening in the physical world. Though there exist systems like Event Correlation for Forensics which deal with network data analysis, systems like these only deal with data analysis and usually does not deal with correlation between cyber-attacks and events or conflicts in the physical domain. The Analysis on the Relationship between Cyber Attacks and Sociopolitical Events (ARCASE) provides a better understanding to this phenomenon by giving proof whether a cyber-attack is influenced by events or conflicts happening in the physical domain. The ARCASE System formats data acquired from various sources into a uniform manner, processes these data for information, and interprets the information. The ARCASE System utilizes malicious network data to identify possible cyber-attacks from a country and adapts a metric of correlation to determine if a cyber-attack is related to a particular sociopolitical event. Through the analysis undertaken in the study, gives evidence of how sociopolitical events influence cyber-attacks between countries. By establishing the relationship between cyber-attacks and sociopolitical events, the study may be used as an aid in establishing cyber policies between countries as well as security mechanisms within organizations