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Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, “KLL”) and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer+ CD8+ T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry. TCRβ (TRB) sequencing was performed on tetramer+ cells from PBMCs or TILs (n = 14) and matched tumors (n = 12). Functional avidity of T-cell clones was determined by IFNγ production. We identified KLL tetramer+ T cells in 14% of PBMC and 21% of TIL from MCC patients. TRB repertoires were strikingly diverse (397 unique TRBs were identified from 12 patients) and mostly private (only one TCRb clonotype shared between two patients). An increased fraction of KLL-specific TIL (>1.9%) was associated with significantly increased MCC-specific survival P = 0.0009). T-cell cloning from four patients identified 42 distinct KLL-specific TCRa/b pairs. T-cell clones from patients with improved MCC-specific outcomes were more avid (P < 0.05) and recognized an HLA-appropriate MCC cell line. T cells specific for a single MCPyV epitope display marked TCR diversity within and between patients. Intratumoral infiltration by MCPyV-specific T cells was associated with significantly improved MCC-specific survival, suggesting that augmenting the number or avidity of virus-specific T cells may have therapeutic benefit. Cancer Immunol Res; 5(2); 137–47. ©2017 AACR.

Purpose: Merkel cell polyomavirus (MCPyV) is prevalent in the general population, integrates into most Merkel cell carcinomas (MCC), and encodes oncoproteins required for MCC tumor growth. We sought to characterize T-cell responses directed against viral proteins that drive this cancer as a step toward immunotherapy.Experimental Design: Intracellular cytokine cytometry, IFN-γ enzyme-linked immunospot (ELISPOT) assay, and a novel HLA-A*2402–restricted MCPyV tetramer were used to identify and characterize T-cell responses against MCPyV oncoproteins in tumors and blood of MCC patients and control subjects.Results: We isolated virus-reactive CD8 or CD4 T cells from MCPyV-positive MCC tumors (2 of 6) but not from virus-negative tumors (0 of 4). MCPyV-specific T-cell responses were also detected in the blood of MCC patients (14 of 27) and control subjects (5 of 13). These T cells recognized a broad range of peptides derived from capsid proteins (2 epitopes) and oncoproteins (24 epitopes). HLA-A*2402–restricted MCPyV oncoprotein processing and presentation by mammalian cells led to CD8-mediated cytotoxicity. Virus-specific CD8 T cells were markedly enriched among tumor infiltrating lymphocytes as compared with blood, implying intact T-cell trafficking into the tumor. Although tetramer-positive CD8 T cells were detected in the blood of 2 of 5 HLA-matched MCC patients, these cells failed to produce IFN-γ when challenged ex vivo with peptide.Conclusions: Our findings suggest that MCC tumors often develop despite the presence of T cells specific for MCPyV T-Ag oncoproteins. The identified epitopes may be candidates for peptide-specific vaccines and tumor- or virus-specific adoptive immunotherapies to overcome immune evasion mechanisms in MCC patients. Clin Cancer Res; 17(21); 6671–80. ©2011 AACR.

A PA@COF membrane prepared by vapor-assisted conversion at room temperature showed good separation ability for filtering various water-in-oil emulsions.

A NiCu@C core–shell nanostructure supported on Al2O3 delivers superior catalytic performance for selective hydrogenation of acetylene.

The development of non-noble metal catalysts for selective hydrogenation still remains a challenge. Herein, NiCu@carbon core-shell nanoparticles supported on Al

Covalent functionalization has been demonstrated to be an effective strategy to improve the stability of monolayer black phosphorus (BP); however, the effect of chemical functionalization on the ca...

A COF-like conjugated microporous polymer by a directly linked single bond for high performance super-capacitors.

We report the preparation of a two-dimensional superhydrophobic covalent organic framework (COF)-coated cotton fabric via a rapid one-step method at room temperature. The COF-coated fabric was found to have stable superhydrophobicity and remarkable water-in-oil emulsion separation capacity with ultra-high flux under only gravity.

Hydrogen has emerged as one of the most promising players in the future energy system for a better life due to multiple advantages, it is important to identify the most sustainable technology for producing hydrogen among several alternatives. This study aims to propose a novel multi-criteria decision making (MCDM) framework for prioritizing hydrogen production technologies under data uncertainties by combining the methods of interval best-worst method (IBWM), interval entropy technique (IET), and interval best-worst projection (IBWP). In the framework, the IBWM and the IET methods were integrated to offer a comprehensive weighting result by capturing both the uncertain subjective judgments and uncertain objective information regarding the importance of multiple criteria; the IBWP approach was introduced to offer a rigorous ranking result by aggregating both the absolute performance and relative balance of the alternatives regarding the multi-criteria system in uncertain conditions. An illustrative case considering five hydrogen production technologies was studied to verify the feasibility of the proposed framework, while results comparisons and sensitivity analysis were implemented to indicate the necessities and advantages of the developed MCDM methods.

The increasingly serious energy crisis and environmental pollution caused by the excessive use of fossil fuels have been prompting China to aggressively seek a clean and self-sufficient energy source in the future. In the past decades, hydrogen has emerged as a promising alternative due to its advantages of cleanliness, abundance, high energy density, and high conversion efficiency. However, several challenges have to be overcome for China's successful transition to hydrogen economy. In this paper, the hydrogen supply chain is firstly described to help the readers to clearly understand the hydrogen economy. Subsequently, the feasibility of hydrogen economy is discussed by reviewing viewpoints from the literature. Finally, the challenges of China's transition to hydrogen economy are detailed summarized and discussed, and the strategies for China to develop hydrogen economy were compared with that of Japan and Australia.

A novel two-stage multi-criteria decision making (MCDM) method is proposed with the aim to select the most sustainable hydrogen production technology (HPT) by considering the preference information on both attributes and alternatives. In the first stage of the method, the initial sustainability ranking of the alternative HPTs was achieved by using the FBWM (Fuzzy Best-Worst Method) to determine the weights of the criteria and the fuzzy TOPSIS (Technique for Order Performance by Similarity to Ideal Solution) method to prioritize the sustainability of alternative HPTs. While, in the second stage, a novel Preference Ranking Linear Programming Method (PRLPM) was used to acquire the final sustainability ranking according to the alternative preference information by following the principle of the outranking method. The proposed method was illustrated by a case study with 8 HTPs, demonstrating that the developed two-stage MCDM method can reflect the alternative preference of the decision-maker more accurately for selecting the most preferred alternative among various HTPs.

Hydrogen has attracted considerable attention as a clean and renewable energy carrier to potentially solve the increasingly serious problems of energy security and environmental pollution. As it can be produced from diverse feedstocks by using a variety of technologies, this study aims to develop a novel multi-criteria decision making (MCDM) mathematical framework for the sustainability assessment of multiple hydrogen production technologies (HPTs). In the proposed method, the criteria weights were determined by combining the grey relational analysis (GRA) and DEMATEL method, which can realize a relatively objective weighting process by considering the causal relationships among criteria. Moreover, the alternatives are also ranked by using the GRA approach to attain the grey correlation coefficients as indicators, which measures the closeness of the corresponding alternative with the ideal scheme. Finally, the developed MCDM method was illustrated by the sustainability prioritization of 9 HPTs.

The skin at the site of HSV-2 reactivation is enriched for HSV-2 specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells we studied skin biopsies and HSV-2-reactive CD4+ T cells from peripheral blood mononuclear cells (PBMCs) by T-cell receptor (TCR) sequencing before and after vaccination with a replication-incompetent whole virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ T cell sequences from PBMCs increased from a median of 0.03% (range 0-0.09%) to 0.6% (range 0-1.3%) of the total skin TCR repertoire after the first vaccine dose. We found sustained expansion after vaccination in unique, skin-based T-cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. While detection of skin clonotypes in the blood was related to abundance in the skin it was not related to expansion after vaccination. In one participant a switch in immunodominance was observed after vaccination with the emergence of a newly dominant TCRa/b pair in skin that was not detected in blood. We confirmed that the newly dominant clonotype was derived from an HSV-specific CD4+ T cell by creation of a synthetic TCR in a Jurkat-based cell line with a NR4A1-mNeonGreen reporter system. Our data indicate that the skin in areas of HSV-2 reactivation possesses an oligoclonal TCR repertoire that is distinct from the circulation with prominent clonotypes infrequently detected in the circulation by standard methods. Defining the influence of therapeutic vaccination on the HSV-2-specific TCR repertoire requires tissue-based evaluation.

Organic conjugated materials combining high conductivity with strong solid-state emission are highly desired for organic electronic applications, yet still rather rare. Herein, a novel luminogen (TEN) comprised by linking naphthalene diimides and tri-phenyl ethylene with vinyl bridges is reported. TEN exhibits aggregation-induced emission (AIE) behavior of a strong near-infrared fluorescence over 700 nm and the efficiency above 60.5% in the solid state, while also shows promising application in vivo bio-imaging with good permeability and extremely low background. Single crystal of TEN reveals intra- and inter-molecular C–H···O hydrogen bonds, contributing to an inclined molecular stacking along the a -axis of the cell, creating a 1D charge carrier transporting channel under a short π-π interaction distance of 3.42 A, which might benefit the solid emission and charge transport ability simultaneously. Solution processed bottom contact, top gate organic field effect transistors based on TEN reveal a high ambipolar charge transport ability with the hole mobility up to 0.13 cm2 V−1 s−1 and electron mobility up to 0.010 cm2 V−1 s−1. Further atomic force microscopy and X-ray diffraction analysis on TEN thin film confirm the existence of the 1D π-π stacking channel, suggesting the stacking geometry revealed in crystal crucial for facilitating high charge carrier mobility while preserving the strong solid emission at the same time.

UiO-66 metal–organic frameworks (MOFs) are unstable in some harsh aqueous environments, which limit their practical applications. We demonstrate a postsynthetic modification methodology to transform hydrophilic Zr­(Hf)-UiO-66 into superhydrophobic Zr­(Hf)-UiO-66-SH-y (SH = thiol, y = fluoroalkyl) by introducing long fluoroalkyl chains into organic linkers through a thiol–ene click reaction. Water contact angles of the four modified UiO-66 MOFs are all larger than 150°. The grafted low-surface-energy fluorine-containing groups become an effective protective shield for the MOFs, making them exhibit remarkable stability in extreme conditions such as alkaline (pH = 12), saturated HCl, and high concentration of NaCl solution (20 wt %). The Zr-UiO-66 MOFs grafted with 1H,1H,2H-perfluoro-1-hexene have high CO2 adsorption contents of 1.54 and 2.88 mmol·g–1 at 298 and 273 K, respectively. Moreover, the superhydrophobic MOFs also showed potential application in oil/water separation.

Large amounts of gas mixtures of CO2 and hydrocarbons are generated in the CO2 enhanced oil recovery (CO2-EOR) process, and their separation is very challenging due to the formation of a minimum bo...

The dynamic and static hysteresis properties as well as loss properties of grain oriented (GO) silicon steel sheet are measured under the AC-DC hybrid excitation containing both DC bias and harmonic components. The influence of the DC-biasing magnetic field, harmonic orders and phase shift angles on the iron loss is analyzed in depth based on the experimental data under different excitations. A dynamic hysteresis model and the parameter identification method is presented to simulate the asymmetrical hysteresis curve with minor loops. According to the equivalence between loss separation and field separation, the static part of magnetic field intensity are calculated by an improved Preisach model, while the dynamic parts are obtained by fitting the classical loss as well as excess loss. The consistency between simulation and measurement verifies the effectiveness and accuracy of the proposed method.

Organic semiconductors possessing both strong solid emission and charge transport ability are crucial for certain applications such as organic light-emitting transistors and injection lasers, yet t...

In this study, an accurately and digitally regulated allosteric nanoswitch based on the conformational control of two DNA hairpins was developed. By switching between UV irradiation and blue light conditions, the second molecular beacon (H#2) would bind/separate with a repression sequence (RES) via the introduced PTG molecules (a photosensitive azobenzene derivative), resulting in the target aptamer sequence in the first molecular beacon (H#1) not being able/being able to hold the stem-loop configuration, hence losing/regaining the ability to bind with the target. Importantly, we successfully monitor conformation changes of the nanoswitch by an elegant mathematical model for connecting Ki (the dissociation constant between RES and H#2) with Kd (the overall equilibrium constant of the nanoswitch binding the target), hence realizing "observing" DNA structure across dimensions from "structural visualization" to digitization and, accurately, digitally regulating DNA structure from digitization to "structural visualization".

Stable Zr-UiO-67 is prepared by introducing a fluorine-containing layer on its surface through a polymeric network assisted post-synthetic modification (PSM) strategy. The stability of the MOFs in acidic, alkaline and saline environments is improved because of the existence of a protective layer. The MOFs are superlyophobic towards liquids with a surface tension threshold of over 48 mN m-1, making them a potential choice for separating various liquid-liquid mixtures and emulsions.

Dynamic and static hysteresis properties as well as loss properties of oriented silicon steel sheet under the sinusoidal excitation and multi-harmonic excitation are measured respectively. Then, we simulate the static hysteresis and loss properties by Preisach model. Next, we propose an improved method of excess loss parameter extraction under sinusoidal excitation based on the equivalent relationship between loss separation and magnetic field separation, which is more accurate to predict the dynamic hysteresis properties as well as loss properties than traditional method. Based on above improved method, the field quantity expression corresponding to the excess loss under multi-harmonic excitation was constructed, thus we propose a dynamic hysteresis model of oriented silicon steel sheet under arbitrary complex multi-harmonic excitation. We verified the accuracy and effectiveness of the improved dynamic hysteresis model and the loss prediction algorithm proposed in this paper by comparing the predicted results with the measured ones under all kinds of working conditions.