A New Four‐Component L*‐Dependent Model for Radial Diffusion Based on Solar Wind and Magnetospheric Drivers of ULF Waves

The outer radiation belt is a region of space comprising highly energetic electrons. During periods of extreme space weather, the number and energy of these electrons can rapidly vary. During these periods as the electron energies and numbers become enhanced, they can pose a threat to satellite and space infrastructure. While we have an excellent understanding of the physical processes which drive radiation belt electron dynamics, we still have a limited ability to model and forecast radiation belt dynamics; this is a result of the complexity of Earth's radiation belt system. One of the key processes controlling radiation belt dynamics is Ultra Low Frequency (ULF) wave radial diffusion. In this work we detail the development a new model quantifying the strength of ULF wave radial diffusion in the outer radiation belt utilizing space base observations of the electric and magnetic fields in Earth's magnetosphere. Accurately quantifying ULF wave radial diffusion is fundamental to understanding radiation belt dynamics and any improvement or refinements in radial diffusion models can help to provide a better understanding of the complex radiation belt system and importantly improve hindcasts, nowcasts, and forecasts

Collagen reorganization at the tumor-stromal interface facilitates local invasion

BACKGROUND: Stromal-epithelial interactions are of particular significance in breast tissue as misregulation of these interactions can promote tumorigenesis and invasion. Moreover, collagen-dense breast tissue increases the risk of breast carcinoma, although the relationship between collagen density and tumorigenesis is not well understood. As little is known about epithelial-stromal interactions in vivo, it is necessary to visualize the stroma surrounding normal epithelium and mammary tumors in intact tissues to better understand how matrix organization, density, and composition affect tumor formation and progression. METHODS: Epithelial-stromal interactions in normal mammary glands, mammary tumors, and tumor explants in three-dimensional culture were studied with histology, electron microscopy, and nonlinear optical imaging methodologies. Imaging of the tumor-stromal interface in live tumor tissue ex vivo was performed with multiphoton laser-scanning microscopy (MPLSM) to generate multiphoton excitation (MPE) of endogenous fluorophores and second harmonic generation (SHG) to image stromal collagen. RESULTS: We used both laser-scanning multiphoton and second harmonic generation microscopy to determine the organization of specific collagen structures around ducts and tumors in intact, unfixed and unsectioned mammary glands. Local alterations in collagen density were clearly seen, allowing us to obtain three-dimensional information regarding the organization of the mammary stroma, such as radiating collagen fibers that could not have been obtained using classical histological techniques. Moreover, we observed and defined three tumor-associated collagen signatures (TACS) that provide novel markers to locate and characterize tumors. In particular, local cell invasion was found predominantly to be oriented along certain aligned collagen fibers, suggesting that radial alignment of collagen fibers relative to tumors facilitates invasion. Consistent with this observation, primary tumor explants cultured in a randomly organized collagen matrix realigned the collagen fibers, allowing individual tumor cells to migrate out along radially aligned fibers. CONCLUSION: The presentation of these tumor-associated collagen signatures allowed us to identify pre-palpable tumors and see cells at the tumor-stromal boundary invading into the stroma along radially aligned collagen fibers. As such, TACS should provide indications that a tumor is, or could become, invasive, and may serve as part of a strategy to help identify and characterize breast tumors in animal and human tissues

American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR

<p>Abstract</p> <p>Background</p> <p>Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.</p> <p>Methods</p> <p>Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.</p> <p>Results</p> <p>Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.</p> <p>Conclusions</p> <p>Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Parallel Implementation of Functional Languages Using Small Processes

We report work in progress on the implementation of languages that integrate concurrent and functional programming styles. A translation scheme is presented for mapping such languages into process networks using a simple notation based on communication between named processes. The translation of functional code is sequential, but parallelism arises from use of concurrency constructs in the source language. Early implementation experiments have used graph rewriting techniques, although work on a more direct implementation is in progress. 1 Introduction and Background This paper reports work done at ECRC in close collaboration with Bent Thomsen and Lone Leth. The work has focussed on techniques for implementing the Facile language [GPM89] which enhances the --calculus with primitives for process spawning and channel-based communication in the style of CCS [Mil80]. Recent work by Milner using the ß--calculus [MPW89] and its polyadic form [Mil91] shows that a --expression may be translate..

An Abstract Concept of Optimal Implementation

AbstractIn previous works, we introduced Stable Deterministic Residual Structures (SDRSs), Abstract Reduction Systems with an axiomatized residual relation which model orthogonal term and graph rewriting systems, and Deterministic Family Structures (DFSs), which add an axiomatized notion of redex-family to capture known sharing concepts in the λ-calculus and other orthogonal rewrite systems. In this paper, we introduce and study a concept of implementation of DFSs. We show that for any DFS F, its implementation FI is a non-duplicating DFSs with zig-zag as the family relation, where zig-zag is simply the symmetric and transitive closure of the residual relation on redexes with histories. Further, we show that sharing is compositional: the sharing in a DFS F can be decomposed into a weaker sharing F' (such as zig-zag) and a sharing in the implementation F'I of F' stronger than zig-zag. These results require study of the family relation in non-duplicating SDRSs. We show that zig-zag forms a family-relation in every non-duplicating SDRS, and that it is the only separable family relation in such SDRSs

The effect of test environment on usability testing

Improvements in networking and communication technologies enable the use of synchronous and asynchronous methods to support usability evaluation techniques when applied in different spatial and temporal situations. Usability testing has been described as the most frequent and appropriate technique used to evaluate website usability. One of the fundamental elements in the usability testing process is the test environment. When testing a website with remote users in their normal environments, other factors affect that environment (distraction, type of computer system and networking technologies) and may affect usability testing performance. A brief technical review of experimental studies (exploratory and comparative studies) based on the use of remote synchronous and asynchronous methods, is presented. A Review of literature leads to a discussion of some of the factors in remote usability evaluation environment and the reviewed literature reveals that there is a lack of studies investigating the effect of a user environment factors on usability testing, and a consequent failure to address them during usability evaluation