Some Epistemic Extensions of G\"odel Fuzzy Logic

In this paper, we introduce some epistemic extensions of G\"odel fuzzy logic whose Kripke-based semantics have fuzzy values for both propositions and accessibility relations such that soundness and completeness hold. We adopt belief as our epistemic operator, then survey some fuzzy implications to justify our semantics for belief is appropriate. We give a fuzzy version of traditional muddy children problem and apply it to show that axioms of positive and negative introspections and Truth are not necessarily valid in our basic epistemic fuzzy models. In the sequel, we propose a derivation system $K_F$ as a fuzzy version of classical epistemic logic $K$. Next, we establish some other epistemic-fuzzy derivation systems $B_F, T_F, B_F^n$ and $T_F^n$ which are extensions of $K_F$, and prove that all of these derivation systems are sound and complete with respect to appropriate classes of Kripke-based models

Impacts of wave and tidal forcing on 3D nearshore processes on natural beaches. Part II. Sediment transport

This is the second of two papers on the 3D numerical modeling of nearshore hydro- and morphodynamics. In Part I, the focus was on surf and swash zone hydrodynamics in the cross-shore and longshore directions. Here, we consider nearshore processes with an emphasis on the effects of oceanic forcing and beach characteristics on sediment transport in the cross- and longshore directions, as well as on foreshore bathymetry changes. The Delft3D and XBeach models were used with four turbulence closures (viz., k-ε, k-L, ATM and H-LES) to solve the 3D Navier-Stokes equations for incompressible flow as well as the beach morphology. The sediment transport module simulates both bed load and suspended load transport of non-cohesive sediments. Twenty sets of numerical experiments combining nine control parameters under a range of bed characteristics and incident wave and tidal conditions were simulated. For each case, the general morphological response in shore-normal and shore-parallel directions was presented. Numerical results showed that the k-ε and H-LES closure models yield similar results that are in better agreement with existing morphodynamic observations than the results of the other turbulence models. The simulations showed that wave forcing drives a sediment circulation pattern that results in bar and berm formation. However, together with wave forcing, tides modulate the predicted nearshore sediment dynamics. The combination of tides and wave action has a notable effect on longshore suspended sediment transport fluxes, relative to wave action alone. The model’s ability to predict sediment transport under propagation of obliquely incident wave conditions underscores its potential for understanding the evolution of beach morphology at field scale. For example, the results of the model confirmed that the wave characteristics have a considerable effect on the cumulative erosion/deposition, cross-shore distribution of longshore sediment transport and transport rate across and along the beach face. In addition, for the same type of oceanic forcing, the beach morphology exhibits different erosive characteristics depending on grain size (e.g., foreshore profile evolution is erosive or accretive on fine or coarse sand beaches, respectively). Decreasing wave height increases the proportion of onshore to offshore fluxes, almost reaching a neutral net balance

Impacts of wave and tidal forcing on 3D nearshore processes on natural beaches. Part I: Flow and turbulence fields

The major objective of this study was to develop further understanding of 3D nearshore hydrodynamics under a variety of wave and tidal forcing conditions. The main tool used was a comprehensive 3D numerical model – combining the flow module of Delft3D with the WAVE solver of XBeach – of nearshore hydro- and morphodynamics that can simulate flow, sediment transport, and morphological evolution. Surf-swash zone hydrodynamics were modeled using the 3D Navier-Stokes equations, combined with various turbulence models (k-ε, k-L, ATM and H-LES). Sediment transport and resulting foreshore profile changes were approximated using different sediment transport relations that consider both bed- and suspended-load transport of non-cohesive sediments. The numerical set-up was tested against field data, with good agreement found. Different numerical experiments under a range of bed characteristics and incident wave and tidal conditions were run to test the model’s capability to reproduce 3D flow, wave propagation, sediment transport and morphodynamics in the nearshore at the field scale. The results were interpreted according to existing understanding of surf and swash zone processes. Our numerical experiments confirm that the angle between the crest line of the approaching wave and the shoreline defines the direction and strength of the longshore current, while the longshore current velocity varies across the nearshore zone. The model simulates the undertow, hydraulic cell and rip-current patterns generated by radiation stresses and longshore variability in wave heights. Numerical results show that a non-uniform seabed is crucial for generation of rip currents in the nearshore (when bed slope is uniform, rips are not generated). Increasing the wave height increases the peaks of eddy viscosity and TKE (turbulent kinetic energy), while increasing the tidal amplitude reduces these peaks. Wave and tide interaction has most striking effects on the foreshore profile with the formation of the intertidal bar. High values of eddy viscosity, TKE and wave set-up are spread offshore for coarser grain sizes. Beach profile steepness modifies the nearshore circulation pattern, significantly enhancing the vertical component of the flow. The local recirculation within the longshore current in the inshore region causes a transient offshore shift and strengthening of the longshore current. Overall, the analysis shows that, with reasonable hypotheses, it is possible to simulate the nearshore hydrodynamics subjected to oceanic forcing, consistent with existing understanding of this area. Part II of this work presents 3D nearshore morphodynamics induced by the tides and waves

KinView: A visual comparative sequence analysis tool for integrated kinome research

Multiple sequence alignments (MSAs) are a fundamental analysis tool used throughout biology to investigate relationships between protein sequence, structure, function, evolutionary history, and patterns of disease-associated variants. However, their widespread application in systems biology research is currently hindered by the lack of user-friendly tools to simultaneously visualize, manipulate and query the information conceptualized in large sequence alignments, and the challenges in integrating MSAs with multiple orthogonal data such as cancer variants and post-translational modifications, which are often stored in heterogeneous data sources and formats. Here, we present the Multiple Sequence Alignment Ontology (MSAOnt), which represents a profile or consensus alignment in an ontological format. Subsets of the alignment are easily selected through the SPARQL Protocol and RDF Query Language for downstream statistical analysis or visualization. We have also created the Kinome Viewer (KinView), an interactive integrative visualization that places eukaryotic protein kinase cancer variants in the context of natural sequence variation and experimentally determined post-translational modifications, which play central roles in the regulation of cellular signaling pathways. Using KinView, we identified differential phosphorylation patterns between tyrosine and serine/threonine kinases in the activation segment, a major kinase regulatory region that is often mutated in proliferative diseases. We discuss cancer variants that disrupt phosphorylation sites in the activation segment, and show how KinView can be used as a comparative tool to identify differences and similarities in natural variation, cancer variants and post-translational modifications between kinase groups, families and subfamilies. Based on KinView comparisons, we identify and experimentally characterize a regulatory tyrosine (Y177PLK4) in the PLK4 C-terminal activation segment region termed the P+1 loop. To further demonstrate the application of KinView in hypothesis generation and testing, we formulate and validate a hypothesis explaining a novel predicted loss-of-function variant (D523NPKCβ) in the regulatory spine of PKCβ, a recently identified tumor suppressor kinase. KinView provides a novel, extensible interface for performing comparative analyses between subsets of kinases and for integrating multiple types of residue specific annotations in user friendly formats

Doyne lecture 2016:intraocular health and the many faces of inflammation

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses

Cigarette Smoke-Related Hydroquinone Dysregulates MCP-1, VEGF and PEDF Expression in Retinal Pigment Epithelium in Vitro and in Vivo

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s) linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial derived factor (PEDF) in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ), a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and progression to CNV in smoker patients with dry AMD

Coastal lagoons and rising sea level: a review

Sea-level rise (SLR) poses a particularly ominous threat to human habitations and infrastructure in the coastal zone because 10% of the world's population lives in low-lying coastal regions within 10 m elevation of present sea level. There has been much discussion about projected (and the sources of projection) vs. measured SLR rates. Which rates should coastal scientists and managers apply in their studies, and what is the degree of confi- dence of such forecasts, are still open questions. This paper reviews the patterns and effects of relative SLR (RSLR) in coastal lagoons. Three main components are presented in the review: (a) a summary of the main approaches used in predicting medium- to long-term trends in RSLR, (b) a summary of the main evolutionary trends of coastal lagoons and the tools used to examine such trends, and (c) an identification of future research needs. The review reveals that the major source of uncertainty is how and when RSLR will manifest itself at different spatio-temporal scales in coastal lagoon systems, and how its effects can be mitigated. Most of the studies reviewed herein articulate a natural ‘defence’ mechanism of barriers in coastal lagoons by landward barrier retreat through continuous migration, and a gradual change in basin hypsometry during the retreat process. So far, only a relatively small number of detailed studies have integrated and quantified human impacts and coastal lagoon evolution induced by RSLR. We conclude that much more research about adaptation measures is needed, taking into consideration not only the physical and ecological systems but also social, cultural, and economic impacts. Future challenges include a downscaling of SLR approaches from the global level to regional and local levels, with a detailed application of coastal evolution prediction to individual coastal lagoon systemsinfo:eu-repo/semantics/publishedVersio

Improving predictions of swash dynamics in XBeach: The role of groupiness and incident-band runup

In predicting storm impacts on sandy coasts, possibly with structures, accurate runup and overtopping simulation is an important aspect. Recent investigations (Stockdon et al., 2014; Palmsten and Splinter, 2016) show that despite accurate predictions of the morphodynamics of dissipative sandy beaches, the XBeach model (Roelvink et al., 2009) does not correctly simulate the individual contributions of set-up, and infragravity and incident-band swash to the wave run-up. In this paper we describe an improved numerical scheme and a different way of simulating the propagation of directionally-spread short wave groups in XBeach to better predict the groupiness of the short waves and the resulting infragravity waves. The new approach is tested against field measurements from the DELILAH campaign at Duck, NC, and against video-derived runup measurements at Praia de Faro, a relatively steep sandy beach. Compared to the empirical fit by Vousdoukas et al. (2012) the XBeach model performs much better for more extreme wave conditions, which are severely underestimated by existing empirical formulations. For relatively steep beaches incident-band swash cannot be neglected and a wave-resolving simulation mode is required. Therefore in this paper we also test the non-hydrostatic, wave-resolving model within XBeach for runup and overtopping against three datasets. Results for a high-quality flume test show non-hydrostatic XBeach predicts the run-up height with good accuracy (maximum deviation 15%). A case with a very shallow foreshore typical for the Belgian coast at Wenduine was compared against detailed measurements. Overall the model shows correct behavior for this case. Finally, the model is tested against a large number (551) of physical model tests of overtopping from the CLASH database. For relatively high overtopping discharges the non-hydrostatic XBeach performs quite well, with increasing accuracy for increasing overtopping rates. However, for relatively low overtopping rates of less than 10–20 l/m/s, the model systematically underestimates measured overtopping rates

Bed composition generation for morphodynamic modeling: Case study of San Pablo Bay in California, USA

Applications of process-based morphodynamic models are often constrained by limited availability of data on bed composition, which may have a considerable impact on the modeled morphodynamic development. One may even distinguish a period of “morphodynamic spin-up” in which the model generates the bed level according to some ill-defined initial bed composition rather than describing the realistic behavior of the system. The present paper proposes a methodology to generate bed composition of multiple sand and/or mud fractions that can act as the initial condition for the process-based numerical model Delft3D. The bed composition generation (BCG) run does not include bed level changes, but does permit the redistribution of multiple sediment fractions over the modeled domain. The model applies the concept of an active layer that may differ in sediment composition above an underlayer with fixed composition. In the case of a BCG run, the bed level is kept constant, whereas the bed composition can change. The approach is applied to San Pablo Bay in California, USA. Model results show that the BCG run reallocates sand and mud fractions over the model domain. Initially, a major sediment reallocation takes place, but development rates decrease in the longer term. Runs that take the outcome of a BCG run as a starting point lead to more gradual morphodynamic development. Sensitivity analysis shows the impact of variations in the morphological factor, the active layer thickness, and wind waves. An important but difficult to characterize criterion for a successful application of a BCG run is that it should not lead to a bed composition that fixes the bed so that it dominates the “natural” morphodynamic development of the system. Future research will focus on a decadal morphodynamic hindcast and comparison with measured bathymetries in San Pablo Bay so that the proposed methodology can be tested and optimized