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This article is the second step in our research into the Symbol Grounding Problem (SGP). In a previous work, we defined the main condition that must be satisfied by any strategy in order to provide a valid solution to the SGP, namely the zero semantic commitment condition (Z condition). We then showed that all the main strategies proposed so far fail to satisfy the Z condition, although they provide several important lessons to be followed by any new proposal. Here, we develop a new solution of the SGP. It is called praxical in order to stress the key role played by the interactions between the agents and their environment. It is based on a new theory of meaning—Action-based Semantics (AbS)—and on a new kind of artificial agents, called two-machine artificial agents (AM2). Thanks to their architecture, AM2s implement AbS, and this allows them to ground their symbols semantically and to develop some fairly advanced semantic abilities, including the development of semantically grounded communication and the elaboration of representations, while still respecting the Z condition.
Luciano Floridi (Corresponding author)Email:
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Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.  相似文献   
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This paper reports on the preparation and characterization of stable poly(vinyl alcohol) (PVA)-based dry hollow microparticles, readily convertible to gas-filled microballoons (MBs) in water suspension. The rehydrated MBs can be used as ultrasound contrast agents and for targeted drug delivery, while the dry MBs are suitable for encapsulation of biologically active gases. The MBs powder material is obtained by freeze-drying the as-prepared telechelic PVA-shelled MBs aqueous dispersion. The microstructure of the lyophilized MBs as well as of the starting and the reconstituted MBs in water suspension was examined using transmission electron microscopy (TEM), scanning electron microscopy (SEM), scanning transmission X-ray microspectroscopy (STXM) and confocal laser scanning microscopy (CLSM). STXM observations below and above the oxygen K-edge reveal that 80% of the MBs originating from the lyophilized particles are gas-filled. Moreover, local carbon K near-edge X-ray absorption fine structure spectroscopy (NEXAFS) measurements evidenced that the chemical composition of the polymeric shell is preserved during the freeze-drying process and subsequent shelf storage for at least more than one year.  相似文献   
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Coprecipitation of arsenic with iron or aluminum occurs in natural environments and is a remediation technology used to remove this toxic metalloid from drinking water and hydrometallurgical solutions. In this work, we studied the nature, mineralogy, and reactivity toward phosphate of iron-arsenate coprecipitates formed at As(V)/Fe(III) molar ratios (R) of 0, 0.01, or 0.1 and at pH 4.0, 7.0, and 10.0 aged for 30 or 210 days at 50 degrees C and studied the desorption of arsenate. At R = 0, goethite and hematite (with ferrihydrite at pH 4.0 and 7.0) crystallized, whereas at R = 0.01, the formation of ferrihydrite increased and hematite crystallization was favored over goethite. In some samples, the morphology of hematite changed from rounded platy crystals to ellipsoids. At R = 0.1, ferrihydrite formed in all the coprecipitates and remained unchanged even after 210 days of aging. The surface area and chemical composition of the precipitates were affected by pH, R, and aging. Chemical dissolution of the samples showed that arsenate was present mainly in ferrihydrite, but at R = 0.01, it was partially incorporated into the structures of crystalline Fe oxides. The sorption of phosphate on to the coprecipitates was affected not only by the mineralogy and surface area of the samples but also by the amounts of arsenate present in the oxides. The samples formed at pH 4.0 and 7.0 and at R = 0.1 sorbed lower amounts of phosphate than the precipitates obtained at R = 0 or 0.01, despite the former having a larger surface area and showing only a presence of short-range ordered materials. This is mainly due to the fact that in the coprecipitates at R = 0.1 arsenate occupied many sorption sites, thus preventing phosphate sorption. Less than 20% of the arsenate present in the coprecipitates formed at R = 0.1 was removed by phosphate and more from the samples synthesized at pH 7.0 or 10.0 than at pH 4.0. Moreover, we found that more arsenate was desorbed by phosphate from a ferrihydrite on which arsenate was added than from an iron-arsenate coprecipitate, attributed to the partial occlusion of some arsenate anions into the framework of the coprecipitate. XPS analyses confirmed these findings.  相似文献   
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The aim of the present work was to obtain experimental reference data in controlled, simple systems collected under MILD combustion. The combustion processes evolving under such conditions show behaviors specific to unique ranges of operating conditions that are not predictable using the available kinetic mechanisms.  相似文献   
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We report an investigation into analogues of the thrombin binding aptamer (TBA). Individual thymidines were replaced by the unusual residue 5‐hydroxymethyl‐2′‐deoxyuridine (hmU). This differs from the canonical thymidine by a hydroxyl group on the 5‐methyl group. NMR and CD data clearly indicate that all TBA derivatives retain the ability to fold into the “chair‐like” quadruplex structure. The presence of the hmU residue does not significantly affect the thermal stability of the modified aptamers compared to the parent, except for analogue H9 , which showed a marked increase in melting temperature. Although all TBA analogues showed decreased affinities to thrombin, H3 , H7 , and H9 proved to have improved anticoagulant activities. Our data open up the possibility to enhance TBA biological properties, simply by introducing small chemical modifications.  相似文献   
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Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability  相似文献   
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Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.  相似文献   
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