The low efficiency and fast degradation of devices from ink-jet printing process hinders the application of quantum dot light emitting diodes on next generation displays. Passivating the trap states caused by both anion and cation under-coordinated sites on the quantum dot surface with proper ligands for ink-jet printing processing reminds a problem. Here we show, by adapting the idea of dual ionic passivation of quantum dots, ink-jet printed quantum dot light emitting diodes with an external quantum efficiency over 16% and half lifetime of more than 1,721,000 hours were reported for the first time. The liquid phase exchange of ligands fulfills the requirements of ink-jet printing processing for possible mass production. And the performance from ink-jet printed quantum dot light emitting diodes truly opens the gate of quantum dot light emitting diode application for industry.

Oesophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, due to the lack of effective treatment methods. Immunotherapeutic approaches based on tumour-infiltrating lymphocytes (TILs) have demonstrated that durable responses are produced in some patients with solid tumours, which suggests the potential feasibility of clinical application of immunotherapy for ESCC. However, many of the basic characteristics of TILs in ESCC are poorly understood, including clonality, specificity and spatial heterogeneity of the response of TILs, which depends on the interaction between antigens and T cell receptors (TCRs). We used ultra-deep sequencing of rearranged genes in TCR β-chain (TCRβ) to profile the basic characteristics of T cells in tumour tissues (four to six regions from each tumour) as well as matched adjacent normal tissue and peripheral blood from seven patients diagnosed with primary ESCC. We found that T cell clones within ESCCs were quite different from those of the peripheral blood and even the adjacent normal tissues in general. Although there was a relatively higher degree of overlap of intratumoural TCRβ repertoires than those between the tumour and other tissues, intratumoural TCRβ repertoires were spatially heterogeneous. Due to the restricted sampling, high-throughput TCRβ sequencing could characterize the diversity and composition of a limited (compartment-dependent) fraction of the respective T cell clones in any individual ESCC, expanding our understanding of immune behaviour and immune response and shedding more light on ESCC immunotherapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either TSC1 or TSC2 tumor suppressor gene. TSC1 and TSC2 products, Harmatin and Tuberin, form the functional complex to serve as the negative regulator for insulin-induced phosphorylation of S6 kinase and elF4E-binding protein 1. High-risk human papillomavirus (HPV) infection is the necessary cause for cervical cancer. E6 oncoprotein encoded by HPV plays a pivotal role in carcinogenesis by interference with the host intracellular protein functions. In this study, we show that HPV16 E6 interacts with tumor suppressor gene TSC2 product, Tuberin, and results in the phosphorylation of S6 kinase and S6 even in the absence of insulin. The overexpression of Tuberin overcomes the effect of E6 on S6 kinase phosphorylation. Binding with HPV16 E6 causes the proteasome-mediated degradation of Tuberin. A DILG motif and an ELVG motif located in the carboxyl-terminal of Tuberin are required for E6 binding. In addition, the Tuberin interaction region in E6 has been mapped in the amino-terminal portion of HPV16 E6, which is different from the binding domain with p53. These results provide a possible link between E6-induced oncogenesis and the insulin-stimulated cell proliferation signaling pathway. Human papillomaviruses (HPVs)1 infect epithelial cells and induce epithelial tumors or benign lesions (1). Based on their clinical outcomes, HPVs are grouped into high-risk and lowrisk types. The high-risk types, such as HPV16, HPV18, HPV31, HPV33, have been identified as the cause of cervical carcinoma (2). Two oncoproteins encoded by HPVs E6 and E7 are able to immortalize human epithelial cells in vitro (3). The transgenic mice carrying the E6 gene under the control of the keratin promoter developed skin cancer (4). Moreover, E6 and E7 oncoproteins were found in HPV-infected malignant tumors (5), indicating that E6 and E7 functions are required for tumorigenesis.E6 interacts with a variety of host cell proteins and interferes with their functions. The high-risk HPV E6 proteins bind to tumor suppressor protein p53 for degradation (6). This observation provides an important functional clue in which E6 contributes to cell transformation. Several studies showed that additional E6 activities are required to reach full transformation potential (7,8). A growing number of E6 targets involved in the broad spectrum of cellular functions have been identified (9) including the transcriptional coactivator p300/CREB-binding protein (10, 11), hMcm7 (12, 13), , and E6TP1 (15) and others. Thus, E6 interferes with multiple cellular pathways leading to malignant transformation. However, the mechanism that coordinates E6 targeting cellular activities and leads to tumorigenesis currently remains unclear.Tuberous sclerosis complex (TSC) is an inheritable genetic disorder characterized by the formation of benign tumors in multiple organs (16). Genetic studies show that TSC is caused by mutations in either the TSC1 or TSC2 tumor suppressor gene (17,18). TSC1 encodes a 130-kDa pro...

Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

Purpose: CD19-specific chimeric antigen receptor (CAR) T-cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway. Patients and Methods: Here, we generated a novel anti-CD19 CAR-expressing PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR). We then conducted a phase Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma. Results: We found that CD19-PD-1/CD28-CAR T cells had superior T-cell proliferation, cytokine production, and sequentially capability of killing PD-L1+ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven patients with complete remission (41.2%). At a median follow-up 15 months, median overall survival for all patients was not reached. Remarkably, no severe neurologic toxicity or cytokine release syndrome was observed. Conclusions: This first-in-human study demonstrates the tolerability, safety, and encouraging efficacy of CD19-PD-1/CD28-CART in PD-L1+ large B-cell lymphoma.

To investigate the potential role of human papillomavirus (HPV) infection in the pathogenesis of esophageal carcinomas in the Anyang area of China, we have evaluated specimens collected by balloon cytology examination from volunteers in two regions with significantly different incidences of esophageal carcinoma. 138 donors were from a village in a county with an esophageal carcinoma (EC) age-adjusted mortality rate of 132x10(5), the remaining 68 were resident in a second village from another county with an EC mortality rate of 52x10(5). Specimens were evaluated using both polymerase chain reaction (PCR) amplification and in situ hybridization (ISH) protocols. PCR results showed that the prevalence of the human papillomavirus type 16 (HPV-16) E6 gene in the high incidence area was 1.9-fold higher than that of the low incidence area (72 and 37%, respectively, P < 0.01). Moreover, the positive rate corresponded with pathology grade. Similar results were obtained with the HPV-16 E7 gene. As the cells undergoing cytopathological progress, the HPV-16 E6 positive rate was increased, in both villages. In contrast to HPV-16 E6 and E7, detection of the HPV L1 gene was consistently lower, and its prevalence decreased with increasing dysplasia grades (P < 0.05). By ISH analyses, the expression rate of HPV-16 E6 in the specimens collected from the high incidence area was 2.2-fold higher than those from the low incidence area (49 versus 22%, respectively; P < 0.05), and transcription of the E6 gene paralleled cytopathology. HPV-18 was also detected in 17 and 15% of the specimens from the high and low incidence areas, respectively, but most of these samples were also simultaneously HVP-16 positive. These results suggest that HVP-16 plays a causative role in the high incidence of esophageal cancer in the Anyang region of CHINA:

Glioblastoma multiforme is the most prevalent type of adult brain tumor and one of the deadliest tumors known to mankind. The genetic understanding of glioblastoma multiforme is, however, limited, and the molecular mechanisms that facilitate glioblastoma multiforme cell survival and growth within the tumor microenvironment are largely unknown. We applied digital karyotyping and single nucleotide polymorphism arrays to screen for copy-number changes in glioblastoma multiforme samples and found that the most frequently amplified region is at chromosome 7p11.2. The high resolution of digital karyotyping and single nucleotide polymorphism arrays permits the precise delineation of amplicon boundaries and has enabled identification of the minimal region of amplification at chromosome 7p11.2, which contains two genes, EGFR and SEC61γ. SEC61γ encodes a subunit of a heterotrimeric protein channel located in the endoplasmic reticulum (ER). In addition to its high frequency of gene amplification in glioblastoma multiforme, SEC61γ is also remarkably overexpressed in 77% of glioblastoma multiforme but not in lower-grade gliomas. The small interfering RNA-mediated knockdown of SEC61γ expression in tumor cells led to growth suppression and apoptosis. Furthermore, we showed that pharmacologic ER stress agents induce SEC61γ expression in glioblastoma multiforme cells. Together, these results indicate that aberrant expression of SEC61γ serves significant roles in glioblastoma multiforme cell survival likely via a mechanism that is involved in the cytoprotective ER stress-adaptive response to the tumor microenvironment. [Cancer Res 2009;69(23):9105-11]

It is well known that pressure is an important parameter in the SCWO process, because it produces changes in the phase behavior and thermodynamics properties of the system. The influence of pressure on the oxidation efficiency of feeds containing isopropyl alcohol as fuel and acetic acid as waste was studied in an autothermal adiabatic transpiring wall reactor at pilot‐plant scale, at pressures from 13 to 25 Mpa, and temperatures from 600 to 750°C. It was found that reaction temperature decreased between 40 and 100°C, when pressure was lowered, and, subsequently TOC removal decreased. At higher‐temperatures, the decreasing of TOC removal due to pressure difference was reduced. The process was simulated at different pressures using a mathematical model previously developed for the reactor. The Anderko‐Pitzer EoS, especially developed for aqueous systems at high‐temperatures and pressures, was used to have accurate values of the heat capacities of the reaction mixture. It was found that having into account only the effect of pressure in the thermodynamical properties and in the concentration of the reagents, the experimental results could not be explained. Thus, the influence of the pressure in the reaction rate equation had to be considered. Results were qualitatively reproduced considering the reaction rate constant variable with pressure, using a constant volume of activation of −1400 cm3/mol. © 2006 American Institute of Chemical Engineers AIChE J, 2006