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Funder: Max Williamson Fund, Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features.

L1 retrotransposons can pose a threat to genome integrity. The host has evolved to restrict L1 replication. However, mechanisms underlying L1 propagation out of the host surveillance remains unclear. Here, we propose an evolutionary survival strategy of L1, which exploits RNA m6A modification. We discover that m6A ‘writer’ METTL3 facilitates L1 retrotransposition, whereas m6A ‘eraser’ ALKBH5 suppresses it. The essential m6A cluster that is located on L1 5′ UTR serves as a docking site for eukaryotic initiation factor 3 (eIF3), enhances translational efficiency and promotes the formation of L1 ribonucleoprotein. Furthermore, through the comparative analysis of human- and primate-specific L1 lineages, we find that the most functional m6A motif-containing L1s have been positively selected and became a distinctive feature of evolutionarily young L1s. Thus, our findings demonstrate that L1 retrotransposons hijack the RNA m6A modification system for their successful replication. L1 is a group of active retrotransposons in humans. Here the authors show that m6A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M6A motifs are more enriched in evolutionary young L1s.

Neoantigen burden is regarded as a fundamental determinant of response to immunotherapy. However, its predictive value remains in question because some tumours with high neoantigen load show resistance. Here, we investigate our patient cohort together with a public cohort by our algorithms for the modelling of peptide-MHC binding and inter-cohort genomic prediction of therapeutic resistance. We first attempt to predict MHC-binding peptides at high accuracy with convolutional neural networks. Our prediction outperforms previous methods in > 70% of test cases. We then develop a classifier that can predict resistance from functional mutations. The predictive genes are involved in immune response and EGFR signalling, whereas their mutation patterns reflect positive selection. When integrated with our neoantigen profiling, these anti-immunogenic mutations reveal higher predictive power than known resistance factors. Our results suggest that the clinical benefit of immunotherapy can be determined by neoantigens that induce immunity and functional mutations that facilitate immune evasion., Predicting response to cancer immunotherapy is still a challenge. Here, the authors show that their method of predicting MHC-binding peptides, combined with profiling anti-immunogenic mutations, can better predict the clinical benefit of immunotherapy.

Amine-based silica sorbents for CO 2 capture prepared by an impregnation method generally show high adsorption capacity, but physical and chemical degradation for long-term operation are critical problems such as leaching and evaporation of amines, and urea formation, respectively. A strategy to form crosslinks between the impregnated amines was introduced to prevent these problems. Crosslinkers with two amine-reactive groups such as epoxy and halide were used to prepare crosslinked polyethyleneimine (PEI)-impregnated sorbents. A viscosity increase was observed in all crosslinked PEIs. The structure and the amine ratio of the crosslinked PEIs were investigated by 13 C NMR analysis. The highest reaction selectivity to primary amines and the formation of hydroxyl groups were observed for 1,3-butadienediepoxide (BDDE). In addition, BDDE-crosslinked PEI-impregnated sorbents exhibited the most stable long-term stability with the highest CO 2 adsorption capacity and the smallest weight gain after regeneration by simulated temperature swing adsorption (TSA) operations; the hydroxyl groups produced from BDDE-crosslinked PEI enhanced the CO 2 utilization by acting as proton acceptors. The effect of the BDDE content was investigated. The advanced physical stability was observed by an increase in the viscosity at high temperatures or gelation with increasing amounts of BDDE. The BDDE-crosslinked PEI-impregnated sorbents with the appropriate amount of BDDE showed an outstanding stability for the cyclic adsorption capacity (determined by simulated TSA operations) and resistance to urea formation (indicated by in situ infrared analysis).

Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy., Demethylation of the genome is found in cancer. Here, the authors show that genomic demethylation entails changes in promoter methylation and gene expression associated with immune escape and suggest that the epigenetic alterations may be an important determinant of responses to immunotherapy.

Amine double-functionalized adsorbents were fabricated using silica gel as supports and their capabilities for CO2 capture were examined. Aminopropyltrimethoxysilane (1N-APS), and N1-(3-trimethoxysilylpropyl)diethylenetriamine (3N-APS) were used as grafted amine compounds, and tetraethylenepentamine and polyethyleneimine were used as impregnated species. The influence of double-functionalization method on the CO2 adsorption performance and textural properties of adsorbents was investigated. The adsorption capacity, the amine efficiency, and the thermal stability of double-functionalized sorbents depend strongly upon molecular variables associated with two different functional states (i.e., chemically grafted and physically impregnated amines). The temperature dependence of adsorption isotherms reveals that the CO2 adsorption behavior in the double-functionalized adsorbents follow the diffusion limitation model proposed by Xu et al. (Energy Fuels 16:1463–1469, 2002) where the CO2 adsorption is helped by the diffusion of impregnated amines. It is also found that the adsorption isotherm in the double-functionalized sorbent system with a proper choice for grafted and impregnated amines is nearly independent of temperature, which may offer a novel means to fabricate practically useful sorbents that can be used in a wide range of temperature without loss of CO2 adsorption capacity.

(3-Aminopropyl)trimethoxysilane (APS)-silica gels were prepared by a one-pot process using sodium silicate as a low-cost source of silica. XRD and SEM analyses revealed that the APS-silica gels were particles with diameters of around 100–200 nm. Furthermore, the introduction of amine groups was confirmed by FT-IR spectroscopy and CO2 uptake measurements. The adsorption properties of the gels were improved by addition of the surfactants hexadecyltrimethylammonium bromide (CTAB), Pluronic F127, and Pluronic P123, which acted as pore forming agents. Using Brunauer–Emmett–Teller (BET) analyses, we confirmed that both the surface area and pore volume were improved on addition of these surfactants. The larger surface area resulted in a greater number of amine groups being exposed on the outer surface of the APS-silica gels; therefore, CO2 uptake increased as the amount of surfactant used was increased. The APS-silica gels with F127 and P123 had pores from the porous particles with 5–11 nm diameters and gaps bet...

Ethylenediamine was grafted onto a polystyrene surface to study the relationship between amine density and amine efficiency. Amine-tethered polystyrene was synthesized in two steps: (1) chloromethy...

Organic-inorganic composite membranes were prepared with sulfonated poly(ether ether ketone) (SPEEK) and different amounts of silica to improve chemical stability and vanadium hindrance for a vanadium redox flow battery. The durability of the prepared composite membrane was verified using a self-made dummy cell system and fully charged vanadium cathode half-cell electrolyte, which contained oxidative vanadium ions (VO2+). The prepared composite membranes, with covalent crosslinking between the organic polymer and inorganic particles, resulted in reduced vanadium permeability and enhanced chemical stability. Ion exchange capacity, water uptake, proton conductivity, and vanadium permeability decreased with increasing silica content. Selectivity was defined to consider both permeability and proton conductivity and resulted in a membrane that exhibited both high proton conductivity and low ion permeability simultaneously. The prepared 1 wt% silica composite membrane showed 133-fold higher selectivity compared with that of a Nafion112 membrane. After the stability test, the composite membrane showed little change compared to the membrane before the stability test, which confirmed the commercial prospect of SPEEK/SiO2 composite membrane for a vanadium redox flow battery.

In this study, the Janus silica particles were prepared by grafting reaction based on the sol-gel method. Before the surface modification reaction, the silica particles were trapped in the PS layer and some fraction of their surface were only reacted with APTES. XPS analysis confirmed that the nitrogen compounds were introduced on the surface of the Janus particles, and the curve fitting of nitrogen confirmed that the compounds were the amine groups. From the result of SEM analysis, there were no differences in the size and the surface morphology and no formation of the APTES clusters. Based on these results, it was confirmed that the Janus silica particles were prepared using PS trapping layer.

In this study, highly luminescent carbon dots with diameters of 3–5 nm were synthesized via the carbonization of citric acid, and the effects of surface passivation and carbonization temperature on the optical properties were investigated. A red-shift in the emission wavelength was observed with increasing excitation wavelength, and oleylamine-capped carbon dots showed the highest quantum yield of approximately 43% when excited at 380 nm, whereas the reaction temperature had no influence on the emission wavelength and morphology of the dots. Additionally, I–III–VI AgInS2 nanocrystals (NCs) were prepared by thermal decomposition at a low temperature, and the emission wavelength was tuned by adjusting the growth temperature or introducing Zn ions, which enhanced the quantum yield up to 50%. For carbon dot application, a white LED was fabricated by combining a 380 nm UV LED with the carbon dots and Zn-doped AgInS2 NCs. White light from this LED exhibited an excellent color rendering index of greater than 95 with a warm color temperature, and demonstrated its potential for use in solid state lighting.

Rheological properties of the polystyrene (PS) and poly(methyl methacrylate) (PMMA) blends were studied by Advanced Rheometric Expansion System (ARES). Storage modulus and loss modulus of the PS and PMMA blends were measured, and the interfacial tension of the PS and PMMA blends were obtained with various emulsion models by using the storage modulus and loss modulus of the blends. The value of interfacial tension estimated from the Palierne emulsion model was found to be 2.0 mN/m. Also, the interfacial tension between PS and PMMA was calculated by a theoretical model. The values of interfacial tension of the PS and PMMA blends obtained by the experiment and theoretical model were found to be in good agreement.

Crystallization behavior and rheological properties of blends of bisphenol-A polycarbonate (PC) and polypropylene (PP) prepared by screw extrusion have been investigated by differential scanning calorimetry (DSC), polarized-light microscopy, scanning electron microscopy, and a Rheometrics Mechanical Spectrometer. In the study of thermal analysis of PC-PP blends by DSC, double crystallization peaks were observed in the PC-rich compositions. In the study of spherulite of 7/3 PC-PP blend, large droplets (>25 μm) of PP were crystallized between 115°C and 105°C, and then small droplets (

The thermal properties of blends of poly(ether ether ketone) (PEEK) and poly(ether imide) (PEI) prepared by screw extrusion were investigated by differential scanning calorimetry. From the thermal analysis of amorphous PEEK–PEI blends which were obtained by quenching in liquid nitrogen, a single glass transition temperature (Tg) and negative excess heat capacities of mixing were observed with the blend composition. These results indicate that there is a favorable interaction between the PEEK and PEI in the blends and that there is miscibility between the two components. From the Lu and Weiss equation and a modified equation from this work, the polymer–polymer interaction parameter (χ12) of the amorphous PEEK–PEI blends was calculated and found to range from −0.058 to −0.196 for the extruded blends with the compositions. The χ12 values calculated from this work appear to be lower than the χ12 values calculated from the Lu and Weiss equation. The χ12 values calculated from the Tg method both ways decreased with increase of the PEI weight fraction. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 733–739, 1999

Blends of a thermotropic liquid crystalline polymer (LCP) with poly(ether imide) (PEI), poly(ether ether ketone) (PEEK), polysulfone (PSF) and polyarylsulfone (PAS) prepared by screw extrusion have been investigated by differential scanning calorimeter and dynamic mechanical thermal analysis. From the measured glass transition temperature (Tg) and specific heat increment (ΔCp) at the Tg, it appears that the LCP dissolves more in the PEI- and PEEK-rich phases than does the PEI and PEEK in the LCP-rich phase. From the DSC study of PSF-LCP and PAS-LCP blends, the Tg(PSF) and Tg(PAS) of each blends are almost constant with blend composition. Therefore, it is concluded that PSF and PAS are immiscible with LCP. The polymer-polymer interaction parameter (χ12) and the degree of disorder (y/x1) of LCP have been investigated using the Flory lattice theory in which the anisotropy of LCP is considered. The χ12 values have been calculated from the Tg data and found to be 0.181 ± 0.004 at 593 K for the PEI-LCP blends and 0.069 ± 0.006 at 623 K for the PEEK-LCP blends. Using the previously presented method, the χ12 and y/x1 in partially miscible systems have been determined.

In this study, the yellow emitting cubic structure of Sr0.95Zn0.05Se:Eu2+ phosphors were prepared by high temperature solid state reaction. The Sr0.95Zn0.05Se:Eu2+ phosphors exhibited strong excitation intensity under 400-460 nm region, and broad band emission appeared at around 545-600 nm due to the d-f transition of Eu2+. To enhance the red emission, HDA/TOP/TOPO capped CdSe/ZnS NCs were synthesized via fast nucleation and slow growth method. The narrow emission peak was located at 615 nm with 69% of high quantum yield. Bright white emission was generated by combining a 460 nm InGaN LED chip with CdSe/ZnS NCs and Sr0.95Zn0.05Se:Eu2+ hybrid phosphors. The fabricated white LEDs showed warm white light with acceptable CIE chromaticity coordinate variation from (0.343, 0.255) at 20 mA to (0.335, 0.250) at 50 mA. The addition of CdSe/ZnS NCs contributed to the extension of white light spectrum by supplement of the red region. The color rendering index was largely enhanced from 41.7 to 79.7 compared to the Sr0.95Zn0.05Se:Eu2+ based phosphors white LED.

White light-emitting diodes (LEDs) were fabricated using GaN-based 380-nm UV LEDs precoated with the composite of blue-emitting polymer (poly[(9,9-dihexylfluorenyl-2,7-diyl)-alt-co-(2-methoxy-5-{2-ethylhexyloxy)-1 ,4-phenylene)]), yellow green-emitting polymer (poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadiazole)]), and 605-nm red-emitting quantum dots (QDs). CdSe cores were obtained by solvothermal route using CdO, Se precursors and ZnS shells were synthesized by using diethylzinc, and hexamethyldisilathiane precursors. The optical properties of CdSe/ZnS QDs were characterized by UV-visible and photoluminescence (PL) spectra. The structural data and composition of the QDs were transmission electron microscopy (TEM), and EDX technique. The quantum yield and size of the QDs were 58.7% and about 6.7 nm, respectively. Three-band white light was generated by hybridizing blue (430 nm), green (535 nm), and red (605 nm) emission. The color-rendering index (CRI) of the device was extremely improved by introducing the QDs. The CIE-1931 chromaticity coordinate, color temperature, and CRI of a white LED at 20 mA were (0.379, 0.368), 3969 K, and 90, respectively.