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991.
The ability to attribute 2nd-order mental states was investigated in 87 children drawn from preschool, kindergarten, 1st-grade, and 2nd-grade classes. Ss received 4 stories, 2 standard and 2 new, designed to test their understanding of 2nd-order mental states. The standard stories were modified versions of J. Perner and H. Wimmer's (see record 1985-25133-001) 2nd-order task. The new stories were made significantly simpler by reducing the number of characters, episodes, and scenes and by including a deception context. The main findings were that performance on the new stories was significantly better than on the standard stories and that nearly half of the preschoolers and almost all of the kindergartners were able to attribute 2nd-order beliefs. These findings contrast with those of earlier research (e.g., G. J. Hogrefe et al; see PA, Vol 73:26831 and Perner and Wimmer). (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
992.
The direction‐dependence of pyroelectric properties of (1 ? x)Bi1/2Na1/2TiO3 ? xBaTiO3 (BNT ? 100xBT) is investigated, using single crystal samples with well‐defined orientations for x = 0.036 and x = 0.063. The results are compared with those of temperature‐dependent measurements of the ferroelectric and dielectric hysteresis. The depolarization temperature Td of each crystal composition is found to depend on crystal orientation, a fact that is explained by differences in the stability of respective domain configurations. A rationalization is offered for the observation that Td differs from the ferroelectric‐relaxor transition temperature, depending on orientation. The hysteresis curves of BNT ? 3.6BT are typical for a rhombohedral system with a ferroelectric‐relaxor transition, with polarization reversal close to Td occurring in a multistep process that includes decay of ferroelectric domains into polar nanoregions and re‐formation of domains. BNT ? 6.3BT, a composition in the region of the morphotropic phase boundary, shows the same feature, but additionally is characterized by a field‐induced transition between rhombohedral and tetragonal symmetry. This combination results in an effective piezoelectric coefficient of pm/V.  相似文献   
993.
    
Flash sintering of ceramics is characterized by rapid sintering during simultaneous application of electric field and heat. Previous studies of flash sintering have been conducted in furnace environments, where sample temperatures are approximately uniform. In this work, we use highly dynamic heating from a scanning laser to initiate flash sintering while simultaneously applying a DC electric field. Onset of flash sintering is determined by a measurable increase in current through the sample. Our results show that stage I and stage II flash sintering can be initiated by laser heating. At low-to-moderate combinations of laser energies and applied electric fields, measured current rises slightly when the laser is scanned completely across the specimen from the positive to the negative electrodes. Microstructures for these samples show that powder consolidation is minimal in this regime (stage I flash sintering), and thus the observed current is likely due to onset of neck growth between powder particles rather than densification. At higher laser energies and fields, current rises steeply and microstructures show significant consolidation (stage II flash sintering). The demonstration that flash sintering occurs when ceramic is heated by laser-scanning supports future utilization of selective laser flash sintering as an additive manufacturing process.  相似文献   
994.
    
Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.  相似文献   
995.
    
Some nontuberculous mycobacteria (NTM) are considered opportunistic pathogens. Nevertheless, NTM infections are increasing worldwide, becoming a major public health threat. Furthermore, there is no current specific drugs to treat these infections, and the recommended regimens generally lack efficacy, emphasizing the need for novel antibacterial compounds. In this paper, we focused on the essential mycolic acids transporter MmpL3, which is a well-characterized target of several antimycobacterial agents, to identify new compounds active against Mycobacterium abscessus (Mab). From the crystal structure of MmpL3 in complex with known inhibitors, through an in silico approach, we developed a pharmacophore that was used as a three-dimensional filter to identify new putative MmpL3 ligands within databases of known drugs. Among the prioritized compounds, mefloquine showed appreciable activity against Mab (MIC = 16 μg/mL). The compound was confirmed to interfere with mycolic acids biosynthesis, and proved to also be active against other NTMs, including drug-resistant clinical isolates. Importantly, mefloquine is a well-known antimalarial agent, opening the possibility of repurposing an already approved drug, which is a useful strategy to reduce the time and cost of disclosing novel drug candidates.  相似文献   
996.
    
Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone endowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized several architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phenomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV–visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.  相似文献   
997.
    
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely suppress cytotoxic T lymphocytes. KRAS and MYC are important oncogenes associated with immune suppression and pose a challenge to successful therapies. Here, we targeted KRAS, through inhibition of downstream c-RAF with GW5074, and MYC expression via difluoromethylornithine (DFMO). DFMO alone and with GW5074 reduced in vitro PDAC cell viability. Both DFMO and GW5074 showed efficacy in reducing in vivo PDAC growth in an immunocompromised model. Results in immunocompetent syngeneic tumor-bearing mice showed that DFMO and combination treatment markedly decreased tumor size, but only DFMO increased survival in mice. To further investigate, immunohistochemical staining showed DFMO diminished MYC expression and increased tumor infiltration of macrophages, CD86+ cells, CD4+ and CD8+ T lymphocytes. GW5074 was not as effective in modulating the tumor infiltration of total CD3+ lymphocytes or tumor progression and maintained MYC expression. Collectively, this study highlights that in contrast to GW5074, the inhibition of MYC through DFMO may be an effective treatment modality to modulate PDAC immunosuppression.  相似文献   
998.
    
Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the pathological progression of DMD-associated DCM remains unclear. In skeletal muscle, a dramatic decrease in stem cells, so-called satellite cells, has been shown in DMD patients. Whether similar dysfunction occurs with cardiac muscle cardiovascular progenitor cells (CVPCs) in DMD remains to be explored. We hypothesized that the number of CVPCs decreases in the dystrophin-deficient heart with age and disease state, contributing to DCM progression. We used the dystrophin-deficient mouse model (mdx) to investigate age-dependent CVPC properties. Using quantitative PCR, flow cytometry, speckle tracking echocardiography, and immunofluorescence, we revealed that young mdx mice exhibit elevated CVPCs. We observed a rapid age-related CVPC depletion, coinciding with the progressive onset of cardiac dysfunction. Moreover, mdx CVPCs displayed increased DNA damage, suggesting impaired cardiac muscle homeostasis. Overall, our results identify the early recruitment of CVPCs in dystrophic hearts and their fast depletion with ageing. This latter depletion may participate in the fibrosis development and the acceleration onset of the cardiomyopathy.  相似文献   
999.
    
This paper presents the results of experimental and analytical studies of the failure mechanisms of stretchable perovskite light-emitting devices (PeLEDs). The multilayered PeLED structures consist of an anodic layer of poly(3,4-ethylenedioxythiophene):polystyrene-sulfonate (PEDOT:PSS), an emissive layer of methylammonium lead bromide (MAPbBr3), and a eutectic gallium–indium (EGaIn) cathodic layer, which are deposited onto treated polydimethylsiloxane substrates. The intrinsically nonstretchable MAPbBr3 and PEDOT:PSS are modified with poly(ethylene oxide). The failure mechanisms of the layered stretchable PeLED structures are then investigated under monotonic and cyclic deformations. The optical and scanning electron microscopy images show the deflection and propagation of cracks and wrinkles under applied strains. Cracking of perovskite crystal and debonding of films are also observed with increased cyclic deformation. The effects of the failure mechanisms on the optoelectronic properties of the devices are then studied. The in situ measured transmittance of the PEDOT:PSS (≈75%) reduces with increasing uniaxial strain, and then is increased close to its initial value when the strain is released. The turn-on voltage of the device increases with increasing number of cycles between 50 and 1000 cycles at 20% strain level. The fatigue lifetimes of the PeLED structures are used to explain the design of stretchable perovskite devices.  相似文献   
1000.
Federal and local officials have in recent years enacted programs to escalate the middle-class resettlement of city neighborhoods. Enamoured with the physical and economic benefits promised by the back-to-the-city movement, they have underestimated the shortcomings of this neighborhood revitalization strategy. The experience of Boston's South End with publicly supported middle-class resettlement illustrates the severe social and political strains that can develop between incumbents and more affluent “pioneers”—strains which can ultimately inflict damage on the neighborhood's poor. Officials must direct current resources to aid the cities' poorer residents and avoid stimulating gentrification until its adverse side effects can be controlled.  相似文献   
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