288 research outputs found

    Direct numerical simulations of ripples in an oscillatory flow

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    Sea ripples are small-scale bedforms which originate from the interaction of an oscillatory flow with an erodible sand bed. The phenomenon of sea ripple formation is investigated by means of direct numerical simulation in which the sediment bed is represented by a large number of fully-resolved spherical grains (i.e, the flow around each individual particle is accounted for). Two sets of parameter values (differing in the amplitude and frequency of fluid oscillations, among other quantities) are adopted which are motivated by laboratory experiments on the formation of laminar rolling-grain ripples. The knowledge on the origin of ripples is presently enriched by insights and by providing fluid- and sediment-related quantities that are difficult to obtain in the laboratory (e.g. particle forces, statistics of particle motion, bed shear stress). In particular, detailed analysis of flow and sediment bed evolution has confirmed that ripple wavelength is determined by the action of steady recirculating cells which tend to accumulate sediment grains into ripple crests. The ripple amplitude is observed to grow exponentially consistent with established linear stability analysis theories. Particles at the bed surface exhibit two kinds of motion depending on their position with respect to the recirculating cells: particles at ripple crests are significantly faster and show larger excursions than those lying on ripple troughs. In analogy with segregation phenomenon of polydisperse sediments the non-uniform distribution of the velocity field promotes the formation of ripples. The wider the gap between the excursion of fast and slow particles, the the larger the resulting growth rate of ripples. Finally, it is revealed that, in the absence of turbulence, the sediment flow rate is driven by both the bed shear stress and the wave-induced pressure gradient, the dominance of each depending on the phase of the oscillation period. In phases of maximum bed shear stress, the sediment flow rate correlates more with the Shields number while the pressure gradient tends to drive sediment bed motion during phases of minimum bed shear stress

    Interface-resolved direct numerical simulations of sediment transport in a turbulent oscillatory boundary layer

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    The flow within an oscillatory boundary layer, which approximates the flow generated by propagating sea waves of small amplitude close to the bottom, is simulated numerically by integrating the Navier-Stokes and continuity equations. The bottom is made up of spherical particles, free to move, which mimic sediment grains. The approach allows one to fully resolve the flow around the particles and to evaluate the forces and torques that the fluid exerts on their surface. Then, the dynamics of sediments is explicitly computed by means of the Newton-Euler equations. For the smallest value of the flow Reynolds number presently simulated, the flow regime turns out to fall in the intermittently turbulent regime such that turbulence appears when the free-stream velocity is close to its largest value but the flow recovers a laminar-like behaviour during the remaining phases of the cycle. For the largest value of the Reynolds number, turbulence is significant during almost the whole flow cycle. The evaluation of the sediment transport rate allows one to estimate the reliability of the empirical predictors commonly used to estimate the amount of sediments transported by sea waves. For large values of the Shields parameter, the sediment flow rate during the accelerating phases does not differ from that observed during the decelerating phases. However, for relatively small values of the Shields parameter, the amount of moving particles depends not only on the bottom shear stress but also on flow acceleration. Moreover, the numerical results provide information on the role that turbulent eddies have on sediment dynamics

    Tutela jurĂ­dica do meio ambiente na jurisprudĂȘncia da Corte Interamericana de Direitos Humanos

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    This paper aims to understand the interrelationships between the international environmental protection and the human rights protection systems, as well as the contributions of the jurisprudence of the Inter-American Court of Human Rights to the strengthening of the civil and political rights protection in cases involving environmental issues.Este ensayo tiene por finalidad el estudio de las relaciones entre los sistemas internacionales de protecciĂłn del medio ambiente y de los derechos humanos, asĂ­ como las contribuciones de la jurisprudencia de la Corte Interamericana de Derechos Humanos para el fortalecimiento de la protecciĂłn de los derechos civiles y polĂ­ticos en los casos relativos a la tutela ambiental.Este ensaio tem por finalidade compreender as inter-relaçÔes entre os sistemas de proteção internacional do meio ambiente e dos direitos humanos, bem assim as contribuiçÔes da jurisprudĂȘncia da Corte Interamericana de Direitos Humanos para o fortalecimento da proteção dos direitos civis e polĂ­ticos nos casos relativos Ă  tutela ambiental

    Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study

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    BACKGROUND: The long‐term course of ulcerative colitis after a severe attack is poorly understood. Second‐line rescue therapy with cyclosporine or infliximab is effective for reducing short‐term colectomy but the impact in the long‐term is controversial. OBJECTIVE: The purpose of this study was to evaluate the long‐term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. METHODS: This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow‐up visit or death. The primary end‐point was long‐term colectomy rate in patients avoiding early colectomy. RESULTS: From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow‐up was 44 months (interquartile range, 21–85). Colectomy‐free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid‐responders (log‐rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long‐term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to antitumour necrosis factor‐α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%). CONCLUSIONS: Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long‐term colectomy, especially if previously exposed to antitumour necrosis factor‐α agents or if rescue therapy during the acute attack was required because of steroid refractoriness

    Micro- and Nanoplastics’ Effects on Protein Folding and Amyloidosis

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    A significant portion of the world's plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood-brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications

    Mechanosensitive Enteric Neurons in the Myenteric Plexus of the Mouse Intestine

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    BACKGROUND: Within the gut the autonomous enteric nervous system (ENS) is able to sense mechanical stimuli and to trigger gut reflex behaviour. We previously proposed a novel sensory circuit in the ENS which consists of multifunctional rapidly adapting mechanosensitive enteric neurons (RAMEN) in the guinea pig. The aim of this study was to validate this concept by studying its applicability to other species or gut regions. METHODOLOGY/PRINCIPAL FINDINGS: We deformed myenteric ganglia in the mouse small and large intestine and recorded spike discharge using voltage sensitive dye imaging. We also analysed expression of markers hitherto proposed to label mouse sensory myenteric neurons in the ileum (NF145kD) or colon (calretinin). RAMEN constituted 22% and 15% of myenteric neurons per ganglion in the ileum and colon, respectively. They encoded dynamic rather than sustained deformation. In the colon, 7% of mechanosensitive neurons fired throughout the sustained deformation, a behaviour typical for slowly adapting echanosensitive neurons (SAMEN). RAMEN and SAMEN responded directly to mechanical deformation as their response remained unchanged after synaptic blockade in low Ca(++)/high Mg(++). Activity levels of RAMEN increased with the degree of ganglion deformation. Recruitment of more RAMEN with stronger stimuli may suggest low and high threshold RAMEN. The majority of RAMEN were cholinergic but most lacked expression of NF145kD or calretinin. CONCLUSIONS/SIGNIFICANCE: We showed for the first time that fundamental properties of mechanosensitive enteric neurons, such as firing pattern, encoding of dynamic deformation, cholinergic phenotype and their proportion, are conserved across species and regions. We conclude that RAMEN are important for mechanotransduction in the ENS. They directly encode dynamic changes in force as their firing frequency is proportional to the degree of deformation of the ganglion they reside in. The additional existence of SAMEN in the colon is likely an adaptation to colonic motor patterns which consist of phasic and tonic contractions

    Anti-Hu antibodies activate enteric and sensory neurons.

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    IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-ÎČ-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA. Ca(++) imaging experiments confirmed activation of enteric neurons but not enteric glia. These findings demonstrate a direct excitatory action of ANNA-1, in particular anti-HuD, on visceral sensory and enteric neurons, which involves nicotinic and P2X receptors. The results provide evidence for a novel link between nerve activation and symptom generation in patients with antibody-mediated gut dysfunction
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