Plasmonic Nanospectroscopy for Thermal Analysis of Organic Semiconductor Thin Films.

Organic semiconductors are key materials for the next generation thin film electronic devices like field-effect transistors, light-emitting diodes, and solar cells. Accurate thermal analysis is essential for the fundamental understanding of these materials, for device design, stability studies, and quality control because the desired nanostructures are often far from thermodynamic equilibrium and therefore tend to evolve with time and temperature. However, classical experimental techniques are insufficient because the active layer of most organoelectronic device architectures is typically only on the order of a hundred nanometers or less. Scrutinizing the thermal properties in this size range is, however, critical because strong deviations of the thermal properties from bulk values due to confinement effects and pronounced influence of the substrate become significant. Here, we introduce plasmonic nanospectroscopy as an experimental approach to scrutinize the thickness dependence of the thermal stability of semicrystalline, liquid-crystalline, and glassy organic semiconductor thin films down to the sub-100 nm film thickness regime. In summary, we find a pronounced thickness dependence of the glass transition temperature of ternary polymer/fullerene blend thin films and their constituents, which can be resolved with exceptional precision by the plasmonic nanospectroscopy method, which relies on remarkably simple instrumentation.

Photo-degradation in air of the active layer components in a thiophene-quinoxaline copolymer:fullerene solar cell.

We have studied the photo-degradation in air of a blend of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and poly[2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt-thiophene-2,5-diyl] (TQ1), and how the photo-degradation affects the solar cell performance. Using near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, changes to the electronic structure of TQ1 and PCBM caused by illumination in ambient air are investigated and compared between the pristine materials and the blend. The NEXAFS spectra show that the unoccupied molecular orbitals of TQ1 are not significantly changed by the exposure of pristine TQ1 to light in air, whereas those of PCBM are severely affected as a result of photo-induced degradation of PCBM. Furthermore, the photo-degradation of PCBM is accelerated by blending it with TQ1. While the NEXAFS spectrum of TQ1 remains unchanged upon illumination in air, its valence band spectrum shows that the occupied molecular orbitals are weakly affected. Yet, UV-Vis absorption spectra demonstrate photo-bleaching of TQ1, which is attenuated in the presence of PCBM in blend films. Illumination of the active layer of TQ1:PCBM solar cells prior to cathode deposition causes severe losses in electrical performance.

Benefits and challenges of electronic package leaflet (ePL) - review of ePL pilots in hospital settings in Europe.

Inclusion of package leaflets in paper format is a legal requirement in European Union (EU), therefore the electronic package leaflet (ePL) is a relatively unknown phenomenon in medicinal products in Europe. Introduction of ePL only would be a more sustainable format of providing the product information than paper package leaflet. Furthermore, ePL would support health care professionals' comprehension of product use through electronic searchability and facilitate access to up-to-date product information in respective language used. It could also help us to tackle the availability issues and be a further step towards common packages. With this commentary, our aim is to review the ongoing ePL pilots in hospital settings in Europe and identify the benefits and challenges of ePL. Based on our review, there is a broad general support for the removal of paper package leaflets from hospital products. Packages without paper package leaflets are considered more sustainable due to savings in production and materials. Furthermore, ePL could be a facilitator for common packages in EU-countries with the benefit of reducing pharmaceutical waste and drug shortages. The most important benefit from both pharmaceutical industry and healthcare professionals' interest is that current and on-line updated product information is always electronically available, especially from drug safety perspective.

T regulatory cells in B-cell malignancy - tumour support or kiss of death?

It is well established that T regulatory (Treg) cells counteract tumour immunity. However, conflicting results describing the role of Treg cells in haematological tumours warrant further investigations to clarify the interactions between Treg cells and the tumour. B-cell malignancy derives from different stages of B-cell development and differentiation in which T cells play a profound role. The transformed B cell may still be in need of T-cell help to thrive but simultaneously they may be recognized and destroyed by cytotoxic lymphocytes. Recent reports demonstrate that Treg cells can suppress and even kill B cells as part of their normal function to rescue the body from autoimmunity. An emerging body of evidence points out that Treg cells not only inhibit tumour-specific T cells but may also have a role in suppressing the progression of the B-cell tumour. In this review, we discuss the origin and function of Treg cells and their role in patients with B-cell tumours.

Both CD4+ FoxP3+ and CD4+ FoxP3- T cells from patients with B-cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro.

Cytotoxic CD4(+) T cells have been found in patients with chronic lymphocytic leukaemia (CLL) and seem to be involved in the regulation of malignant B cells. The CD4(+) T regulatory cells (Tregs) can regulate various immune cells, including B cells, by inducing their apoptosis. Hence, different subgroups of CD4(+) T cells may be involved in the regulation of malignant B cells. In this study, the cytotoxic phenotype and function of various CD4(+) T-cell subgroups were investigated in patients with B-cell malignancies. Peripheral blood was collected from patients with CLL, various B-cell lymphomas, healthy adult donors, children with precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) and from healthy children. CD4(+) T cells (CD3(+) CD4(+) FoxP3(-)), Tregs (CD3(+) CD4(+) CD127(low) FoxP3(+)) and CD127(high) FoxP3(+) T cells (CD3(+) CD4(+) CD127(high) FoxP3(+)) were analysed for their expression of the cytolytic markers CD107a and Fas ligand. Patients with CLL had increased CD107a expression on all tested T-cell subgroups compared with healthy donors. Similar results were found in patients with B-cell lymphomas whereas the CD107a expression in children with pre-B ALL was no different from that in healthy controls. Fas ligand expression was similar between patient cells and cells of healthy donors. CD4(+) T cells and Tregs from patients with CLL and healthy donors were subsequently purified and cultured in vitro with autologous B cells. Both subgroups lysed B cells and killing was confirmed by granzyme ELISAs. In conclusion, cytotoxic populations of CD4(+) T cells, including Tregs, are present in patients with B-cell malignancy and may be an important factor in immune-related disease control.

T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies.

Interleukin-2 (IL-2) is one of the most studied cytokines driving T-cell proliferation, activation and survival. It binds to the IL-2 receptor consisting of three chains, the α (CD25), ß and common γ (γc). The binding of the CD25 chain to IL-2 is necessary to expose high-affinity binding sites for the ß and γc chains, which, in turn, are responsible for downstream signalling. A high level of soluble CD25 (sCD25) has been associated with a poor prognosis in patients with non-Hodgkin's lymphoma. The function and source of origin of this soluble receptor is not well investigated. In the present study we hypothesized that T regulatory (Treg) cells may release CD25 to act as a decoy receptor for IL-2, thereby depriving T-effector cells of IL-2. Peripheral blood from patients with B-cell malignancies (n = 26) and healthy controls (n = 27) was investigated for the presence and function of FoxP3(+) Treg cells and sCD25 by multi-colour flow cytometry and enzyme-linked immunosorbent assay. Further, the proliferative capacity of T cells was evaluated with or without the presence of recombinant sCD25. The results demonstrate that Treg cells from patients had lower CD25 expression intensity and that they released CD25 in vitro. Further, high levels of Treg cells correlated with sCD25 plasma concentration. Recombinant sCD25 could suppress T-cell proliferation in vitro. In conclusion, the release of sCD25 by Treg cells may be a mechanism to deprive IL-2 and thereby inhibit anti-tumour T-cell responses.

Fullerene Aggregation in Thin Films of Polymer Blends for Solar Cell Applications.

We report on the effects of the film morphology on the fluorescence spectra for a thin film including a quinoxaline-based co-polymer (TQ1) and a fullerene derivative ([6,6]-phenyl-C71-butyric acid methyl ester-PC70BM). The ratio between the polymer and the fullerene derivative, as well as the processing solvent, were varied. Besides the main emission peak at 700 nm in the fluorescence spectra of thin films of this phase-separated blend, a broad emission band is observed with a maximum at 520⁻550 nm. The intensity of this emission band decreases with an increasing degree of mixing in the film and becomes most prominent in thicker films, films with high PC70BM content, and films that were spin-coated from solvents with lower PC70BM solubility. We assign this emission band to aggregated PC70BM.

Enhanced thermal stability of a polymer solar cell blend induced by electron beam irradiation in the transmission electron microscope.

We show by in situ microscopy that the effects of electron beam irradiation during transmission electron microscopy can be used to lock microstructural features and enhance the structural thermal stability of a nanostructured polymer:fullerene blend. Polymer:fullerene bulk-heterojunction thin films show great promise for use as active layers in organic solar cells but their low thermal stability is a hindrance. Lack of thermal stability complicates manufacturing and influences the lifetime of devices. To investigate how electron irradiation affects the thermal stability of polymer:fullerene films, a model bulk-heterojunction film based on a thiophene-quinoxaline copolymer and a fullerene derivative was heat-treated in-situ in a transmission electron microscope. In areas of the film that exposed to the electron beam the nanostructure of the film remained stable, while the nanostructure in areas not exposed to the electron beam underwent large phase separation and nucleation of fullerene crystals. UV-vis spectroscopy shows that the polymer:fullerene films are stable for electron doses up to 2000kGy.

Enhanced thermal stability of a polymer solar cell blend induced by electron beam irradiation in the transmission electron microscope.

We show by in situ microscopy that the effects of electron beam irradiation during transmission electron microscopy can be used to lock microstructural features and enhance the structural thermal stability of a nanostructured polymer:fullerene blend. Polymer:fullerene bulk-heterojunction thin films show great promise for use as active layers in organic solar cells but their low thermal stability is a hindrance. Lack of thermal stability complicates manufacturing and influences the lifetime of devices. To investigate how electron irradiation affects the thermal stability of polymer:fullerene films, a model bulk-heterojunction film based on a thiophene-quinoxaline copolymer and a fullerene derivative was heat-treated in-situ in a transmission electron microscope. In areas of the film that exposed to the electron beam the nanostructure of the film remained stable, while the nanostructure in areas not exposed to the electron beam underwent large phase separation and nucleation of fullerene crystals. UV-vis spectroscopy shows that the polymer:fullerene films are stable for electron doses up to 2000kGy.

Mapping fullerene crystallization in a photovoltaic blend: an electron tomography study.

The formation of fullerene crystals represents a major degradation pathway of polymer/fullerene bulk-heterojunction thin films that inexorably deteriorates their photovoltaic performance. Currently no tools exist that reveal the origin of fullerene crystal formation vertically through the film. Here, we show that electron tomography can be used to study nucleation and growth of fullerene crystals. A model bulk-heterojunction blend based on a thiophene-quinoxaline copolymer and a fullerene derivative is examined after controlled annealing above the glass transition temperature. We image a number of fullerene nanocrystals, ranging in size from 70 to 400 nanometers, and observe that their center is located close to the free-surface of spin-coated films. The results show that the nucleation of fullerene crystals predominately occurs in the upper part of the films. Moreover, electron tomography reveals that the nucleation is preceded by more pronounced phase separation of the blend components.

T regulatory cells lacking CD25 are increased in MS during relapse.

Dysregulation of inflammatory responses is considered to be a key element in autoreactive immune responses. T regulatory cells (Tregs) are important to maintain self-tolerance and the role of CD4(+)CD25(+)FoxP3(+) Tregs in autoimmunity has been extensively investigated. Recently, it was shown that Tregs in systemic lupus erythematosus lacked CD25 but were biologically functional. These data warrants for further investigation of CD25(- ) Tregs in human autoimmunity. We analyzed relapsing-remitting multiple sclerosis (MS) patients by multicolor flow cytometry for the expression of CD3, CD4, IL2R (CD25), FoxP3, and the IL7R (CD127). Further, the level of Tregs was compared in remitting and relapsing patients and correlated with disease duration. Patients in relapse exhibited higher levels of FoxP3-positive Tregs lacking CD25 compared to healthy controls (p < 0.05), indicating that Tregs attempt to restrain immune activity during relapse. The proportion of Tregs tended to be decreased with disease duration, while CD25(+)CD4(+) and CD25(+)CD8(+) effector T-cell proportions were elevated and positively correlated with overall disease duration (p < 0.05). In conclusion, while MS patients in remission have normal levels of Tregs of different phenotype, relapsing patients show an increased proportion of systemic CD25(-)FoxP3(+) Tregs. With time, the proportion of Tregs decrease while effector T cells expand.

AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial.

PURPOSE: Immunotherapy with Bacillus Calmette-Guerin (BCG) instillation is recommended for high-risk, non-muscle invasive bladder cancer. Bacillus Calmette-Guerin is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40 ligand (AdCD40L) has shown efficacy in tumor models. CD40 ligand stimulates systemic immunity and may be effective in local and invasive human disease. EXPERIMENTAL DESIGN: Patients with invasive bladder cancer scheduled for cystectomy or patients with T(a) tumors were enrolled in a phase I/IIa trial. Patients were treated with three cycles of intrabladder Clorpactin WCS-90 prewash, followed by AdCD40L instillation 1 week apart. Safety, gene transfer, immune effects, and antitumor responses were monitored. RESULTS: All eight recruited patients were treated as scheduled, and therapy was well tolerated. The main adverse effect was transient local pain during prewash. Postoperatively, urinary tract infections and one case of late septicemia with elevated potassium were reported. No adverse events were ascribed to vector therapy. Gene transfer was detected in biopsies, and bladders were heavily infiltrated with T cells. The effector marker IFN-gamma increased in biopsies, whereas levels of circulating T regulatory cells were reduced. Histologic evaluation indicated that AdCD40L therapy reduced the load of malignant cells. CONCLUSIONS: To our knowledge, this is the first report on immunogene therapy in bladder cancer and the first using AdCD40L in vivo. Local AdCD40L gene therapy was safe, boosted immune activation, and should be further evaluated as a single or an adjuvant therapy for urothelial malignancies.

Local AdCD40L gene therapy is effective for disseminated murine experimental cancer by breaking T-cell tolerance and inducing tumor cell growth inhibition.

CD40 ligand (CD40L) is one of the most potent stimulators of Th1-type immunity through its maturation of dendritic cells that, in turn, stimulate effector cells such as T cells and NK cells. Lately, CD40-mediated cell growth inhibition and apoptosis have been in focus for the development of novel cancer treatment regiments, including recombinant soluble CD40L or CD40-stimulating antibodies. In this study, intravesical CD40L gene transfer through adenoviral vectors (AdCD40L) was used to treat an aggressive model of disseminated bladder cancer (MB49/C57BL/6). Three weekly AdCD40L vector instillations increased overall survival of tumor-bearing mice (mean 18.5 d, control mice 13 d). Furthermore, bladder tumors were eradicated (2 of 10) simultaneously as lung metastases (6 of 10) were cleared. FoxP3 levels were similar in the tumors of AdCD40L-treated mice and control mice but the tumor-infiltrating effector T cells in AdCD40L-treated mice were cytotoxic (CD107a+) in contrast to those in control-treated tumors. Furthermore, AdCD40L gene therapy could induce cell growth inhibition and cell death in the MB49 tumor cells in vitro and in vivo. However, this effect was not potent enough to cure growing tumors in immunodeficient mice. In conclusion, AdCD40L gene therapy is potent for disseminated cancer both by activation of T cells and controlling tumor cell growth and viability.