254 research outputs found

    Optimal strategies to steer and control water waves

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    In this paper, we propose a new method for controlling surface water waves and their interaction with floating bodies. A floating target rigid body is surrounded by a control region where we design three control strategies of increasing complexity: an active strategy based on controlling the pressure at the air–water interface and two passive strategies where an additional controlled floating device is designed. Such device is modeled both as a membrane and as a thin plate and the effect of this modeling choice on the performance of the overall controlled system is analyzed. We frame this problem as an optimal control problem where the underlying state dynamics is represented by a system of coupled partial differential equations describing the interaction between the surface water waves and the floating target body in the frequency domain. An additional intermediate coupling is then added when considering the control floating device. The optimal control problem then aims at minimizing a cost functional which weights the unwanted motions of the floating body. A system of first-order necessary optimality conditions is derived and numerically solved using the finite element method. The efficacy of this new method for reducing hydrodynamic loads on floating objects has been shown through numerical simulations

    Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism

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    Background: We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis. Methods: Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice. Results: Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice. Conclusions: Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability. © 2012 Corridoni et al

    Previous Crop Impacts Winter Wheat Sowing Dates, Available Water at Sowing, and Grain Yield

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    Cropping systems choices can directly affect the sowing date for winter wheat, which is among the most important variables that determine attainable yields in the U.S. Central Great Plains. Our objective was to investigate the effect of the previous crop on winter wheat grain yield through the modulation of sowing date and its impact on plant available water at sowing, and temperatures during the critical period for yield determination. A no-tillage rainfed field experiment was established in 2019 at Ashland Bottoms, KS. Winter wheat was sown either after summer fallow, full-season soybean, double-cropped soybean, or corn—thus, resulting in a range in sowing dates of 270–326 days of the year (September 27 to November 22). The optimum sowing date for the site based on grain yield was estimated at day of year 296 ± 5 (October 18 to 28). Winter wheat after summer fallow and after a fullseason soybean crop resulted in the greatest yields, whether sown at the optimum date or slightly later than optimum. Winter wheat yield was positively related to plant available water at sowing. Later sowing dates were most likely to reduce plant available water at sowing, and could delay wheat’s development resulting in higher temperatures occurring during the critical period for yield determination (i.e., the days surrounding anthesis). Later sowing also shortened grain filling duration due to an overall later cycle and elevated temperatures. Thus, adjusting winter wheat sowing dates is the first step that determines the crop’s yield potential through improved plant available water at sowing, and reduced temperatures during the critical period for yield determination. When following a summer crop, winter wheat should be sown as soon as the previous crop is harvested to try to mitigate these negative effects of late sowing

    Extrados Strengthening of Single-Leaf Vaults Against Seismic Actions

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    Single-leaf vaults are acknowledged among the most vulnerable components of historical masonry constructions with respect to earthquake loads, particularly when featuring large span to thickness ratios, as in the case of single leaf covering the main nave of churches. These elements often require structural strengthening against seismic actions. In this paper, two different extradostechniques are tested: lightweight plywood restraining elements and FRP laminates embedded in a lime mortar layer. The techniques are tested on single leaf vaults having a very unfavorable span to thickness ratio. A previous study on less slender vaults, showed that lightweight plywood centerings, applying passive confinement to the vault extrados, inhibit the onset of the typical four-hinges failure mechanism. This lightweight, dry solution can be easily prefabricated, transferred and assembled at the construction site. The technique is reversible and fully compliant with the major preservation principles. FRP is also effective against the onset of the failure mechanism but entails larger deformations of the retrofitted vault, which may be detrimental in the case of possible decorations. The solution requires special man labor to ensure correct smoothening and cleaning of the vault extrados and to trigger effective bond between the mortar and the vault extrados. Both solutions are shown to enable small relative displacements of the vault springing, which may follow the deformation of possible internal ties. The effectiveness of these retrofit techniques was comparatively verified through experimental tests on single-leaf barrel vault stripes at 1:2 scale subjected to cyclic distributed unsymmetrical loads and through comparison with the seismic response of a reference unreinforced single-leaf vault

    Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System

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    The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced pluripotent stem cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSCs, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids solely composed by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 1 week. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSCderived liver organoid model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals

    Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis

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    L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1−/− bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin–IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies

    Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism

    Get PDF
    Background: We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis. Methods: Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice. Results: Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice. Conclusions: Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability

    Towards a synthetic tutor assistant: The EASEL project and its architecture

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    Robots are gradually but steadily being introduced in our daily lives. A paramount application is that of education, where robots can assume the role of a tutor, a peer or simply a tool to help learners in a specific knowledge domain. Such endeavor posits specific challenges: affective social behavior, proper modelling of the learner’s progress, discrimination of the learner’s utterances, expressions and mental states, which, in turn, require an integrated architecture combining perception, cognition and action. In this paper we present an attempt to improve the current state of robots in the educational domain by introducing the EASEL EU project. Specifically, we introduce the EASEL’s unified robot architecture, an innovative Synthetic Tutor Assistant (STA) whose goal is to interactively guide learners in a science-based learning paradigm, allowing us to achieve such rich multimodal interactions

    Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis

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    Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment
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