To understand the effect of topological defects on the Li adsorption on graphene, we have performed first-principles calculations to study the adsorption and diffusion of a lithium adatom on graphene ...with (5, 0)|(3, 3), (2, 1)|(2, 1), and (2, 0)|(2, 0) grain boundaries (GBs). Our results show that the adsorption of a Li adatom on defect-free graphene is endothermic with respect to the bulk Li and the adsorption of a Li adatom on the GBs of graphene is exothermic. In particular, the presence of a (2, 0)|(2, 0) GB leads to a decrease of about 0.92 eV in the adsorption energy of a Li adatom on graphene. This suggests that GBs would significantly enhance the Li adsorption on graphene. In three cases of GBs, the energy barrier for the diffusion of a Li adatom along the boundary is lower than that perpendicular to the boundary, indicating that a Li adatom tends to diffuse along the boundary and to migrate from nonboundary sites toward the boundary zone. The difference charge density and the Bader charge analysis both show there is a significant charge transfer from the Li adatom to its nearest neighboring carbon atoms.
Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in ...their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q(+) pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
In this work, uniaxial compressive strength test combined with AE monitoring and post-test CT scanning techniques were performed to investigate the influence of interbed orientation on the mechanical ...properties, energy evolution and fracture pattern of anisotropic marble obtained from Lilou iron mine. The marble samples were cored along angles of 0°, 15°, 30°, 45°, 60°, and 90° with respect to the interbeds. The experimental results suggested that the interbed structure in marble have a significant influence on the geomechanical properties, AE pattern, dissipated and released energy, and crack pattern. The stress–strain behaviors present anisotropy and they show “U” shape against interbed orientation. The AE events, dissipated energy and released energy first decreases and then increases with increasing orientation, they get to the minimum for the sample with an interbed orientation of 30°. Post-test CT scanning and macroscopic fracture morphology description reveal the crack morphology and the reason of energy anisotropy. The final failure morphology is the external expression of energy dissipation and release, crack pattern is the simplest for the 30° orientation sample. The most striking founding is that it is the crack tortuosity degree not the crack number that determines the energy dissipation and release characteristics. For the sample with curved crack after failure, the released energy is much more than samples with straight cracks. The experimental results in this work prove the importance of interbed structure on the anisotropic mechanical responses and energy mechanism, fracture evolution is structure dependent.
Background
Several methods have been used to detect defects or debonds nondestructively in materials or construction. Each of these nondestructive testing methods has advantages and limitations. ...Generally, they are suitable for testing a certain range or a specific type of material and structure and some of them require careful analysis to identify the features of the defects.
Objective
The present work proposes a nondestructive testing method based on electro-acoustic technique (NDTPEA) to detect internal defects of dielectric materials, which can identify the defects from the original stress wave generated at the internal defect surface.
Methods
Electric polarization occurs in the dielectric under the action of a high-voltage electric field. When the intensity of the electric field changes suddenly, the polarization charge generates a stress wave. If there are defects, such as cracks and debonding, in the medium, the position and size of the internal defects of the insulating material can be determined according to the stress wave.
Results
The waveform and velocity of stress wave is measured by a PVDF film. According to the velocity and time of the stress wave in the dielectric, the position of the internal defects or debonding of the specimen can be determined. The maximum error for measuring the wave transmission time is 1 ns, and the maximum measurement error in the defect thickness direction was 0.00253 mm.
Conclusions
In the NDTPEA, the detected wave originates from the vibration of the polarized charge at the defect, i.e., the defect is the source of the stress wave. The measured stress wave does not undergo any reflection or refraction, and the waveform is truly regular, without coupling factors. The wave shape and time characteristics can all reflect the characteristics of the defects.
Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44
CD24
fractions, ...mammospheres, ALDH1
populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.
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A number of observations have been reported on chemical capture and catalysis of anchoring materials for lithium-sulfur batteries. Here, we propose the design principles for the ...chemical functioned graphene as an anchor material to realize both strong chemical trapping and catalysis. Through the first principle, the periodic law is calculated from the theory. Seven different co-doping series were investigated, e.g. MN4@graphene (M = V, Cr, Mn, Fe, Co, Ni, and Cu). From binding energy, partial density of state, and charge density difference analysis, the FeN4 and CrN4 co-doped graphene show good performance for the lithium–sulfur battery from both strong anchoring and catalytic effects. For the most kinds of Li2Sx (x = 1, 2, 4, 6, 8) absorption, two combinations can be achieved, including S-bonding and Li-bonding. The competition between the MS and the NLi shows the main difference of the co-doped configurations. Moreover, the S-bonding systems have better performance for both moderate chemical trapping and strong catalysis. The binding energies of Li2Sx and Li decomposed properties considered as the key descriptors for the rational design of lithium–sulfur battery. Lastly, we offer design rules for high performance lithium–sulfur batteries based on the chemical functional graphene materials.
We present a measurement of the angular power spectrum of the cosmic microwave background (CMB) using data from the South Pole Telescope (SPT). The data consist of 790 deg2 of sky observed at 150 GHz ...during 2008 and 2009. Here we present the power spectrum over the multipole range 650 < l < 3000, where it is dominated by primary CMB anisotropy. We combine this power spectrum with the power spectra from the seven-year Wilkinson Microwave Anisotropy Probe (WMAP) data release to constrain cosmological models. We find that the SPT and WMAP data are consistent with each other and, when combined, are well fit by a spatially flat, Delta *LCDM cosmological model. The SPT+WMAP constraint on the spectral index of scalar fluctuations is ns = 0.9663 ? 0.0112. We detect, at ~5 Delta *s significance, the effect of gravitational lensing on the CMB power spectrum, and find its amplitude to be consistent with the Delta *LCDM cosmological model. We explore a number of extensions beyond the Delta *LCDM model. Each extension is tested independently, although there are degeneracies between some of the extension parameters. We constrain the tensor-to-scalar ratio to be r < 0.21 (95% CL) and constrain the running of the scalar spectral index to be dns /dln k = --0.024 ? 0.013. We strongly detect the effects of primordial helium and neutrinos on the CMB; a model without helium is rejected at 7.7 Delta *s, while a model without neutrinos is rejected at 7.5 Delta *s. The primordial helium abundance is measured to be Yp = 0.296 ? 0.030, and the effective number of relativistic species is measured to be N eff = 3.85 ? 0.62. The constraints on these models are strengthened when the CMB data are combined with measurements of the Hubble constant and the baryon acoustic oscillation feature. Notable improvements include ns = 0.9668 ? 0.0093, r < 0.17 (95% CL), and N eff = 3.86 ? 0.42. The SPT+WMAP data show a mild preference for low power in the CMB damping tail, and while this preference may be accommodated by models that have a negative spectral running, a high primordial helium abundance, or a high effective number of relativistic species, such models are disfavored by the abundance of low-redshift galaxy clusters.
Albumen height, albumen weight (AW), eggshell color (ESC), eggshell index, eggshell strength, eggshell thickness, eggshell weight (ESW), egg weight (EW), Haugh units, and yolk weight (YW) were ...measured in 2,272 eggs collected 3 d sequentially from 920 brown-egg dwarf layers caged individually. The restricted maximum likelihood procedure was applied to estimate heritabilities and genotypic and phenotypic correlations for these egg quality traits. Heritabilities of albumen height, AW, ESC, eggshell index, eggshell strength, eggshell thickness, ESW, EW, Haugh units, and YW were 0.51, 0.59, 0.46, 0.40, 0.24, 0.34, 0.64, 0.63, 0.41, and 0.45, respectively. The genetic correlations between EW and AW, YW, and ESW were high ranging from 0.67 to 0.97, whereas those for ESC with external and internal egg quality traits were low ranging from -0.23 to 0.13. Thus although heritabilities for these traits were moderate to high, genetic correlations with ESC were low, suggesting a minor relationship between shell color and physical attributes of the shell as well as internal egg quality in brown-egg dwarf layers.
Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG ...trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from transcriptional inhibition and axonal transport deficits mediated by mutant huntingtin, have been suggested as critical factors underlying selective neurodegeneration in both HD patients and HD mouse models. BDNF activates its high-affinity receptor TrkB and promotes neuronal survival; restoring BDNF signaling is thus of particular therapeutic interest. In the present study, we evaluated the ability of a small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and its synthetic derivative 4'-dimethylamino-7,8- dihydroxyflavone (4'-DMA-7,8-DHF) to protect neurons in the well-characterized N171-82Q HD mouse model. We found that chronic administration of 7, 8-DHF (5 mg/kg) or 4'-DMA-7,8-DHF (1 mg/kg) significantly improved motor deficits, ameliorated brain atrophy and extended survival in these N171-82Q HD mice. Moreover, 4'-DMA-7,8-DHF preserved DARPP32 levels in the striatum and rescued mutant huntingtin-induced impairment of neurogenesis in the N171-82Q HD mice. These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of HD.
Thymidylate synthase (TS) has a predictive role in pemetrexed treatment of mesothelioma; however, additional chemoresistance mechanisms are poorly understood. Here, we explored the role of the ...reduced-folate carrier (RFC/SLC19A1) and proton-coupled folate transporter (PCFT/SLC46A1) in antifolate resistance in mesothelioma.
PCFT,RFC andTS RNA and PCFT protein levels were determined by quantitative RT-PCR of frozen tissues and immunohistochemistry of tissue-microarrays, respectively, in two cohorts of pemetrexed-treated patients. Data were analyzed byt-test, Fisher’s/log-rank test and Cox proportional models. The contribution of PCFT expression andPCFT-promoter methylation to pemetrexed activity were evaluated in mesothelioma cells and spheroids, through 5-aza-2′-deoxycytidine-mediated demethylation and siRNA-knockdown.
Pemetrexed-treated patients with lowPCFT had significantly lower rates of disease control, and shorter overall survival (OS), in both the test (N=73, 11.3 versus 20.1months,P=0.01) and validation (N=51, 12.6 versus 30.3months,P=0.02) cohorts. Multivariate analysis confirmedPCFT-independent prognostic role. Low-PCFT protein levels were also associated with shorter OS. Patients with both low-PCFT and high-TS levels had the worst prognosis (OS, 5.5months), whereas associations were neither found forRFC nor in pemetrexed-untreated patients.PCFT silencing reduced pemetrexed sensitivity, whereas 5-aza-2′-deoxycytidine overcame resistance.
These findings identify for the first time PCFT as a novel mesothelioma prognostic biomarker, prompting prospective trials for its validation. Moreover, preclinical data suggest that targetingPCFT-promoter methylation might eradicate pemetrexed-resistant cells characterized by low-PCFT expression.
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