Transparent flexible graphene triboelectric nanogenerators as new promising applications of chemical vapor deposition‐grown graphene are successfully demonstrated. The work function and friction are decisive factors to understand the difference in output performance depending on the number of layers of graphene. In this work, we were able to power an LCD, LEDs, and an EL display using the electrical power output of the graphene triboelectric nanogenerator without any external energy source.

The preparation of ferroelectric polymer–metallic nanowire composite nanofiber triboelectric layers is described for use in high‐performance triboelectric nanogenerators (TENGs). The electrospun polyvinylidene fluoride (PVDF)–silver nanowire (AgNW) composite and nylon nanofibers are utilized in the TENGs as the top and bottom triboelectric layers, respectively. The electrospinning process facilitates uniaxial stretching of the polymer chains, which enhances the formation of the highly oriented crystalline β‐phase that forms the most polar crystalline phase of PVDF. The addition of AgNWs further promotes the β‐phase crystal formation by introducing electrostatic interactions between the surface charges of the nanowires and the dipoles of the PVDF chains. The extent of β‐phase formation and the resulting variations in the surface charge potential upon the addition of nanowires are systematically analyzed using X‐ray diffraction (XRD) and Kelvin probe force microscopy techniques. The ability of trapping the induced tribocharges increases upon the addition of nanowires to the PVDF matrix. The enhanced surface charge potential and the charge trapping capabilities of the PVDF–AgNW composite nanofibers significantly enhance the TENG output performances. Finally, the mechanical stability of the electrospun nanofibers is dramatically enhanced while maintaining the TENG performances by applying thermal welding near the melting temperature of PVDF.

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay.

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To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

Transparent ZrO 2 -polydimethylsiloxane (PDMS) nanocomposites with high refractive index were prepared by dispersing ZrO 2 nanoparticles in a PDMS matrix via ligand molecule engineering. The ligand molecule consists of a diamine head group that adsorbs strongly onto the ZrO 2 nanoparticles, and a siloxane tail group with a double-tailed structure that can be easily stretched within the PDMS matrix and yields a greater steric hindrance compared to single-tailed structure. The transmission electron micrograph shows that the designed Si-based ligand molecule has a role to play in keeping ZrO 2 nanoparticles fully-dispersed even after the ZrO 2 nanoparticles were transferred into the PDMS matrix. UV-vis spectra indicate that ZrO 2 -PDMS nanocomposite had a high transparency of 93.3% in the whole visible range. The refractive index of the ZrO 2 -PDMS nanocomposite could be varied from 1.39 to 1.65 simply by increasing the ZrO 2 content from 0 to 20.8% v/v.

The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N = 4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH). Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5’ fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular target therapy.

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.