105 research outputs found

    Beach profile evolution towards equilibrium from varying initial morphologies

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    The evolution of different initial beach profiles towards the same final beach configuration is investigated based on large-scale experimental data. The same wave condition was performed three times, each time starting from a different initial profile morphology. The three different initial profiles are an intermediate energy profile with an offshore bar and a small swash berm, a plane profile and a low energy profile with a large berm. The three cases evolve towards the same final (equilibrium) profile determined by the same wave condition. This implies that the same wave condition generates different sediment transport patterns. Largest beach changes and differences in hydrodynamics occur in the beginning of the experimental cases, highlighting the coupling between morphology and hydrodynamics for beach evolution towards the same profile. The coupling between morphology and hydrodynamics that leads to the same final beach profile is associated with differences in sediment transport in the surf and swash zone, and is explained by the presence of bar and berm features. A large breaker bar and concave profile promote wave energy dissipation and reduce the magnitudes of the mean near-bed flow velocity close to the shoreline limiting shoreline erosion. In contrast, a beach profile with reflective features, such as a large berm and a small or no bar, increases negative velocity magnitudes at the berm toe promoting shoreline retreat. The findings are summarised in a conceptual model that describes how the beach changes towards equilibrium from two different initial morphologies

    Bed level motions and sheet flow processes in the swash zone: Observations with a new conductivity-based concentration measuring technique (CCM+)

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    Detailed measurements of bed level motions and sheet flow processes in the lower swash are presented. The measurements are obtained during a large-scale wave flume experiment focusing on swash zone sediment transport induced by bichromatic waves. A new instrument (CCM+) provides detailed phase-averaged measurements of sheet flow concentrations, particle velocities, and bed level evolution during a complete swash cycle. The bed at the lower swash location shows a clear pattern of rapid erosion during the early uprush and progressive accretion during the middle backwash phase. Sheet flow occurs during the early uprush and mid and late backwash phases. Sheet flow sediment fluxes during these instances are highest in the pick-up layer. Sediment entrainment from the pick-up layer occurs not only during instances of high horizontal shear velocities but also in occurrence of wave–backwash interactions. As opposed to oscillatory sheet flow, the pivot point elevation of the sheet flow layer is time-varying during a swash event. Moreover, the upper sheet flow layer concentrations do not mirror the concentrations in the pick-up layer. Both differences suggest that in the lower swash zone the dynamics of the upper sheet flow layer are not only controlled by vertical sediment exchange (such as in oscillatory sheet flows) but are strongly affected by horizontal advection processes induced by the non-uniformity of the flow

    Mesoscopic spin confinement during acoustically induced transport

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    Long coherence lifetimes of electron spins transported using moving potential dots are shown to result from the mesoscopic confinement of the spin vector. The confinement dimensions required for spin control are governed by the characteristic spin-orbit length of the electron spins, which must be larger than the dimensions of the dot potential. We show that the coherence lifetime of the electron spins is independent of the local carrier densities within each potential dot and that the precession frequency, which is determined by the Dresselhaus contribution to the spin-orbit coupling, can be modified by varying the sample dimensions resulting in predictable changes in the spin-orbit length and, consequently, in the spin coherence lifetime.Comment: 10 pages, 2 figure

    Sand transport processes and bed level changes induced by two alternating laboratory swash events

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    Sand transport processes and net transport rates are studied in a large-scale laboratory swash zone. Bichromatic waves with a phase modulation were generated, producing two continuously alternating swash events that have similar offshore wave statistics but which differ in terms of wave-swash interactions. Measured sand suspension and sheet flow dynamics show strong temporal and spatial variability, related to variations in flow velocity and locations of wave capture and wave-backwash interactions. Suspended and sheet flow layer transport rates in the lower swash zone are generally of same magnitude, but sheet flow exceeds the suspended load transport by up to a factor four during the early uprush. The bed level near the inner surf zone is relatively steady during a swash cycle, but changes of (cm/s) are measured near the mid swash zone where wave-swash interactions lead to strongly non-uniform flows. The two alternating swash events produce a dynamic equilibrium, with bed level changes up to a few mm induced by single swash events, but with net morphodynamic change over multiple events that is two orders of magnitude lower. Most of the intra-swash and the single-event-averaged bed level changes in the swash zone are caused by a redistribution of sediment within the swash. The transport of sediment across the surf-swash boundary is minor at intra-swash time scale, but becomes increasingly significant at swash-averaged time scales or longer (i.e., averaged over multiple swash events)

    Physics and Applications of Laser Diode Chaos

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    An overview of chaos in laser diodes is provided which surveys experimental achievements in the area and explains the theory behind the phenomenon. The fundamental physics underpinning this behaviour and also the opportunities for harnessing laser diode chaos for potential applications are discussed. The availability and ease of operation of laser diodes, in a wide range of configurations, make them a convenient test-bed for exploring basic aspects of nonlinear and chaotic dynamics. It also makes them attractive for practical tasks, such as chaos-based secure communications and random number generation. Avenues for future research and development of chaotic laser diodes are also identified.Comment: Published in Nature Photonic

    Sprouty4 Is an Endogenous Negative Modulator of TrkA Signaling and Neuronal Differentiation Induced by NGF

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    The Sprouty (Spry) family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF

    Towards the clinical implementation of pharmacogenetics in bipolar disorder.

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    BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

    The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1

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    The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function

    Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

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    In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma
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