Vestergaardmccann1176

Peptide stapling chemistry represents an attractive strategy to promote the clinical translation of protein epitope mimetics, but its use has not been applied to natural cytotoxic peptides (NCPs) to produce new oncolytic peptides. Based on a wasp venom peptide, a series of stapled anoplin peptides (StAnos) were prepared. The optimized stapled Ano-3/3s were shown to be protease-resistant and exerted superior tumor cell-selective cytotoxicity by rapid membrane disruption. In addition, Ano-3/3s induced tumor ablation in mice through the direct oncolytic effect and subsequent stimulation of immunogenic cell death. This synergistic oncolytic-immunotherapy effect is more remarkable on melanoma than on triple-negative breast cancer in vivo. The efficacies exerted by Ano-3/3s on melanoma were further characterized by CD8+ T cell infiltration, and the addition of anti-CD8 antibodies diminished the long-term antitumor effects. In summary, these results support stapled peptide chemistry as an advantageous method to enhance the NCP potency for oncolytic therapy.The most common surface hopping dynamics algorithms require velocity adjustment after hopping to ensure total-energy conservation. Based on the semiclassical analysis, this adjustment must be made parallel to the nonadiabatic coupling vector's direction. Nevertheless, this direction is not always known, and the common practice has been to adjust the velocity in either the linear momentum or velocity directions. selleck inhibitor This paper benchmarks surface hopping dynamics of photoexcited ethylene with velocity adjustment in several directions, including those of the nonadiabatic coupling vector, the momentum, and the energy gradient difference. It is shown that differences in time constants and structural evolution fall within the statistical uncertainty of the method considering up to 500 trajectories in each dynamics set, rendering the three approaches statistically equivalent. For larger ensembles beyond 1000 trajectories, significant differences between the results arise, limiting the validity of adjustment in alternative directions. Other possible adjustment directions (velocity, single-state gradients, angular momentum) are evaluated as well. Given the small size of ethylene, the results reported in this paper should be considered an upper limit for the error caused by the choice of the velocity-adjustment direction on surface hopping dynamics.The presence of polymer transfer residues on graphene surfaces is a major bottleneck to overcome for the commercial and industrial viability of devices incorporating graphene layers. In particular, how clean the surface must be to recover high (>2500 W/mK) thermal conductivity and maximize the heat spreading capability of graphene for thermal management applications remains unclear. Here, we present the first systematic study of the impact of different levels of polymer residues on the in-plane thermal conductivity (κr) of single-layer graphene (SLG) fabricated by chemical vapor deposition (CVD). Control over the quantity of surface residue was achieved by varying the length of time each sample was rinsed in toluene to remove the poly(methyl methacrylate) (PMMA) support layer. The level of residue contamination was assessed using atomic force microscopy (AFM) and optical characterization. The thermal conductivity of the suspended SLG was measured using an optothermal Raman technique. We observed that the presence of polymer surface residue has a significant impact on the thermal properties of SLG, with the most heavily contaminated sample exhibiting a κr as low as (905 +155/-100) W/mK. Even without complete eradication of surface residues, a thermal conductivity as high as (3100 +1400/-900) W/mK was recovered, where the separation between adjacent clusters was sufficiently large (>700 nm). The proportion of the SLG surface covered by residues and the mean separation distance between clusters were found to be key factors in determining the level of κr suppression. This work has important implications for future large-scale graphene fabrication and transfer, particularly where graphene is to be used as a heat spreading layer in devices. The possibility of new opportunities for manipulation of the thermal properties of SLG via PMMA nanopatterning is also raised.A novel software has been created to comprehensively characterize covalent modifications of DNA through mass spectral analysis of enzymatically hydrolyzed DNA using the neutral loss of 2'-deoxyribose, a nearly universal MS2 fragmentation process of protonated 2'-deoxyribonucleosides. These covalent modifications termed DNA adducts form through xenobiotic exposures or by reaction with endogenous electrophiles and can induce mutations during cell division and initiate carcinogenesis. DNA adducts are typically present at trace levels in the human genome, requiring a very sensitive and comprehensive data acquisition and analysis method. Our software, wSIM-City, was created to process mass spectral data acquired by a wide selected ion monitoring (wSIM) with gas-phase fractionation and coupled to wide MS2 fragmentation. This untargeted approach can detect DNA adducts at trace levels as low as 1.5 adducts per 109 nucleotides. This level of sensitivity is sufficient for comprehensive analysis and characterization of DNA modifications in human specimens.The parallel application of aroma extract dilution analysis to the volatiles isolated from a sample of fermented cocoa seeds with a pronounced moldy-musty off-flavor and to the volatiles isolated from a flawless reference sample revealed (-)-geosmin, 4-methoxy-2,5-dimethylfuran-3(2H)-one, 1H-indole, and 3-methyl-1H-indole as potential off-flavor compounds on the basis of their odor quality and higher flavor dilution factors in off-flavor cocoa than in the reference sample. Quantitation of the four compounds in nine off-flavor cocoa samples and calculation of odor activity values (ratio of the concentrations to the odor threshold values) suggested the crucial roles of (-)-geosmin and 3-methyl-1H-indole for the off-flavor. In the chocolate industry, their quantitation can be used to objectively assess the off-flavor at the level of incoming goods inspection. Because both compounds are inhomogeneously distributed between the testa and the embryo, separate quantitation in the two parts of the seeds is required.