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While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.Memristive systems can provide a novel strategy to conquer the von Neumann bottleneck by evaluating information where data are located in situ. To meet the rising of artificial neural network (ANN) demand, the implementation of memristor arrays capable of performing matrix multiplication requires highly reproducible devices with low variability and high reliability. Hence, we present an Ag/CuO/SiO2/p-Si heterostructure device that exhibits both resistive switching (RS) and negative differential resistance (NDR). The memristor device was fabricated on p-Si and Indium Tin Oxide (ITO) substrates via cost-effective ultra-spray pyrolysis (USP) method. The quality of CuO nanoparticles was recognized by studying Raman spectroscopy. The topology information was obtained by scanning electron microscopy. The resistive switching and negative differential resistance were measured from current-voltage characteristics. The results were then compared with the Ag/CuO/ITO device to understand the role of native oxide. The interface barrier and traps associated with the defects in the native silicon oxide limited the current in the negative cycle. The barrier confined the filament rupture and reduced the reset variability. Reset was primarily influenced by the filament rupture and detrapping in the native oxide that facilitated smooth reset and NDR in the device. The resistive switching originated from traps in the localized states of amorphous CuO. The set process was mainly dominated by the trap-controlled space-charge-limited; this led to a transition into a Poole-Frenkel conduction. This research opens up new possibilities to improve the switching parameters and promote the application of RS along with NDR.Bio-based composites made of poly(l-lactic acid) (PLLA) and pine wood were prepared by melt extrusion. The composites were compatibilized by impregnation of wood with γ-aminopropyltriethoxysilane (APE). Comparison with non-compatibilized formulation revealed that APE is an efficient compatibilizer for PLLA/wood composites. Pine wood particles dispersed within PLLA act as nucleating agents able to start the growth of PLLA crystals, resulting in a faster crystallization rate and increased crystal fraction. Moreover, the composites have a slightly lower thermal stability compared to PLLA, proportional to filler content, due to the lower thermal stability of wood. Molecular dynamics was investigated using the solid-state 1H NMR technique, which revealed restrictions in the mobility of polymer chains upon the addition of wood, as well as enhanced interfacial adhesion between the filler and matrix in the composites compatibilized with APE. The enhanced interfacial adhesion in silane-treated composites was also proved by scanning electron microscopy and resulted in slightly improved deformability and impact resistance of the composites.Learning and behavioral difficulties often emerge during the first years of primary school and are one of the most important issues of concern for families and schools. The study was aimed at investigating the co-occurrence of difficulties between academic learning and emotional-behavioral control in typically developing school children and the moderating role of sex. A sample of 640 second-grade school children participated in the study. This study used the Strengths and Difficulties Questionnaire to measure the emotional and behavioral difficulties and a battery of objective and standardized tests to evaluate the learning skills in children. In this sample 7% to 16% of children performed below the normal range in reading and/or arithmetic tests. Mixed models showed that children's hyperactive behaviors were positively related to both reading and math difficulties, and emotional problems correlated negatively with reading accuracy. The more children displayed behavioral difficulties, the more they were exposed to the risk of worsening reading and math performance, especially for girls. The result that among different emotional-behavioral problems within the school setting, hyperactivity behaviors and emotional difficulties are related to learning difficulties with a moderate effect of sex, needs to be taken into account in screening and prevention programs for learning difficulties in order to not disregard the complexity of the associated profiles.The Convention on the Rights of Persons with Disabilities have proclaimed the basic right of people to make one's own choices, have an effective participation and inclusion. Research in the field of disability have stressed self-determination as a key construct because of its impact on their quality of life and the achievement of desired educational and adulthood related outcomes. Self-determination development must be promoted through specific strategies and especially, by providing tailored opportunities to practice those skills. Providing these opportunities across environments could be especially relevant as a facilitator of self-determination development. This manuscript aims to ascertain if opportunities at home and in the community to engage in self-determined actions are mediating the relationship between people intellectual disability level and their self-determination. AM580 research buy Results have confirmed direct effects of intellectual disability level on self-determination scores. Indirect effects also predicted self-determination and almost all its related components (self-initiation, self-direction, self-regulation, self-realization, and empowerment) through opportunities in the community and at home. Autonomy was predicted by the intellectual disability level through an indirect effect of opportunities at home, but not in the community. These results highlight the need for further research to better operationalize and promote contextually rooted opportunities for people with intellectual disability to become more self-determined.The main issue of wood is its sensitivity to Relative Humidity (RH) variations, affecting its dimensional stability, and thus leading to crack formations and propagations. In situ structural health monitoring campaigns imply the use of portable noninvasive techniques such as acoustic emission, used for real-time detection of energy released when cracks form and grow. This paper proposes a calibration method, i.e., acoustic emission, as an early warning tool for estimating the length of new formed cracks. The predictability of ductile and brittle fracture mechanisms based on acoustic emission features was investigated, as well as climate-induced damage effect, leading to a strain-hardening mechanism. Tensile tests were performed on specimens submitted to a 50% RH variation and coated with chemicals to limit moisture penetration through the radial surfaces. Samples were monitored for acoustic emission using a digital camera to individuate calibration curves that correlated the total emitted energy with the crack propagation, specifically during brittle fracture mechanism, since equations provide the energy to create a new surface as the crack propagates. The dynamic surface energy value was also evaluated and used to define a Locus of Equilibrium of the energy surface rate for crack initiation and arrest, as well as to experimentally demonstrate the proven fluctuation concept.Glycine- and proline-rich proteins (GPRPs) comprise a small conserved family that is widely distributed in the plant kingdom. GPRPs are relatively short peptides ( less then 200 amino acids) that contain three typical domains, including an N-terminal XYPP-repeat domain, a middle hydrophobic domain rich in alanine, and a C-terminal HGK-repeat domain. These proteins have been proposed to play fundamental roles in plant growth and environmental adaptation, but their functions remain unknown. In this study, we selected an Arabidopsis GPRP (AtGPRP3) to profile the physiological role of GPRPs. Transcripts of AtGPRP3 could be detected in the whole Arabidopsis plant, but greater amounts were found in the rosette, followed by the cauline. The AtGPRP3GFP fusion protein was mainly localized in the nucleus. The overexpression and knockout of AtGPRP3, respectively, retarded and accelerated the growth of Arabidopsis seedlings, while the increase in the growth rate of atgprp3 plants was offset by the complementary expression of AtGPRP3. CAT2 and CAT3, but not CAT1, interacted with AtGPRP3 in the nuclei of Arabidopsis protoplasts. The knockout of CAT2 by CRISPR-Cas9 retarded the growth of the Arabidopsis seedlings. Together, our data suggest that AtGPRP3 negatively regulates plant growth, potentially through CAT2 and CAT3.Mycobacterium avium subsp. hominissuis (MAH) is a common intracellular pathogen that infects immunocompromised individuals and patients with pre-existing chronic lung diseases, such as cystic fibrosis, who develop chronic and persistent pulmonary infections. The metabolic remodeling of MAH in response to host environmental stresses or within biofilms formed in bronchial airways plays an important role in development of the persistence phenotype contributing to the pathogen's tolerance to antibiotic treatment. Recent studies suggest a direct relationship between bacterial metabolic state and antimicrobial susceptibility, and improved antibiotic efficacy has been associated with the enhanced metabolism in bacteria. In the current study, we tested approximately 200 exogenous carbon source-dependent metabolites and identified short-chain fatty acid (SCFA) substrates (propionic, butyric and caproic acids) that MAH can utilize in different physiological states. Selected SCFA enhanced MAH metabolic activity in planktonic and sessile states as well as in the static and established biofilms during nutrient-limited condition. The increased bacterial growth was observed in all conditions except in established biofilms. We also evaluated the influence of SCFA on MAH susceptibility to clinically used antibiotics in established biofilms and during infection of macrophages and found significant reduction in viable bacterial counts in vitro and in cultured macrophages, suggesting improved antibiotic effectiveness against persistent forms of MAH.Focused electron beam induced deposition (FEBID) is a direct-write nanofabrication technique able to pattern three-dimensional magnetic nanostructures at resolutions comparable to the characteristic magnetic length scales. FEBID is thus a powerful tool for 3D nanomagnetism which enables unique fundamental studies involving complex 3D geometries, as well as nano-prototyping and specialized applications compatible with low throughputs. In this focused review, we discuss recent developments of this technique for applications in 3D nanomagnetism, namely the substantial progress on FEBID computational methods, and new routes followed to tune the magnetic properties of ferromagnetic FEBID materials. We also review a selection of recent works involving FEBID 3D nanostructures in areas such as scanning probe microscopy sensing, magnetic frustration phenomena, curvilinear magnetism, magnonics and fluxonics, offering a wide perspective of the important role FEBID is likely to have in the coming years in the study of new phenomena involving 3D magnetic nanostructures.
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