Vacancy formation in Fe-Al of B2 and DO3 alloys

The positron lifetime spectroscopy is employed to study vacancy formation in intermetallic phases of DO3 and B2 structures from Fe-Al system as a function of Al concentration, ternary additive (Cr) and their thermal treatment. Lifetime spectra were fitted en block by a simple trapping model encoded directly to the software (computer program LT-9). In the investigated range of Al concentration (28, 38, 42, and 45 at%) only two types of defects are found. In DO3 region a single type of defects (characterized by positron lifetime ¿1 = 170 § 2 ps) is detected and indicated as vacancies in the Fe sublattice (VFe). In B2 region a small amount of an additional type of defects (characterized by positron lifetime ¿2 = 214 § 13 ps) appears. Supposedly, these are vacancies in Al sublattice (VAl). For Fe28Al and Fe28Al5Cr samples changes in VFe concentration are determined as a function of the sample composition, annealing time at 1000±C and quenching the samples to air and oil. The defect concentration increases with increase in Al content. For FeAl with Al above 38 at%, the total concentration of defects is so high that positrons are exclusively trapped by defects. Therefore the concentrations VAl and VFe cannot be determined separately. However, the ratio of VAl concentration to VFe concentration is estimated as a function of Al content

The bidirectional tumor - mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Introduction: Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor-derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells. Methods: MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model. Results: Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1α. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model. Conclusions: This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo

Properties of neutron doped multicrystalline silicon for solar cells

The technology of neutron transmutation doping of silicon wafers in MARIA nuclear research reactor is described. The studies of the radiation defects performed with positron annihilation confirmed that divacancies dominate in the irradiated material. Thermal treatment of irradiated silicon at 700-1000°C produces void - phosphorus complexes and void aggregates. The resistivity of the samples produced by neutron transmutation doping was found to be uniform within 2.5% limits. The severe reduction of the minority carrier lifetime in irradiated samples was confirmed

PD-1 is a marker of activation on tumor infiltrating NK cells in head and neck cancer

Co-inhibitory immune checkpoint receptors have become important targets for cancer immunotherapy. Programmed death 1 (PD-1) has been well-characterized on T cells in many cancer types, including head and neck cancer (HNC), for its ability to mediate activation and eventually T cell exhaustion in the tumor microenvironment. However, PD-1 expression on NK cells, which are crucial innate immune effector cells against cancer, remains largely undefined. In the setting of HNC, NK cells mediate lysis of EGFR-overexpressing tumor targets via cetuximab-mediated antibody dependent cytotoxicity (ADCC). Indeed, cetuximab has shown to be clinically effective but only to a modest extent. Therefore, it is necessary to investigate how cetuximab modulates activation of immune effector cell infiltrates in the tumor microenvironment in order to improve or extend its therapeutic efficacy. We hypothesized that expression of PD-1 per se on NK cells may constitute a marker of a chronically activated phenotype, which is suppressed only after ligation by its cognate ligand programmed death ligand-1 (PD-L1). Thus, tumor cell-expressing PD-L1 may present as a crucial mediator of immunosuppression in the tumor microenvironment decreasing cytotoxicity of cetuximab activated PD-1 expressing NK cells. Herein, using The Cancer Genome Atlas (TCGA) data for 500 HNC patients' tumors, we found that PD-1 expression correlates with NK activation markers. Indeed, HNC patients also exhibit higher levels of circulating and tumor infiltrating PD-1+ NK cells, and neoadjuvant cetuximab treatment increased this frequency in vitro and in vivo in a prospective Phase II trial. In addition, anti-PD-1 mAb nivolumab enhanced cetuximab mediated NK cell activation and HNC cell lysis. Therefore, blocking PD-L1/PD-1 axis may be a useful approach to reverse immune evasion of HNC tumors to cetuximab therapy by reversing NK cell dysfunction

Ordering process of Fe28Al and Fe28Al5Cr alloys

Purpose: The comparison of ordering process in Fe28Al and Fe28Al5Cr alloys annealed for 8, 16 and 48 hours at 1000°C was performed. The composition of studied alloys is closed to one of Fe3Al phase. Design/methodology/approach: The studied alloys were melted in induction furnace under vacuum. Next the alloys were gravitatively casted into cylindrical graphite moulds. The alloy samples were annealed at 1000°C for 8, 16 and 48 hours. The ordering process was analyzed by X-ray diffraction, Mössbauer spectroscopy and positron annihilation methods. Findings: Different behaviour of Fe28Al and Fe28Al5Cr alloys during annealing for 8, 16 and 48 hours at 1000°C was found. The Fe3Al phase of DO3 type structure was stated only in the sample of Fe28Al alloy annealed for 48 hours. The FeAl phase appeared to be the main phase in the other samples. Research limitations/implications: The applied investigation methods appeared to be useful in the studies of long range ordering process. Application of Rietveld refinement method enabled the verification of qualitative phase analysis and the determination of lattice constant parameters. Relatively great grain sizes in studied samples made the exact determination of long range ordering parameters difficult. Practical implications: The information on the phase transformation during the heat treatment of alloys, including long range ordering, are of prime importance for technological processing. The structures with long range ordering significantly affect the properties of alloys with intermetallic phases. Originality/value: Good correlation between the results of X-ray diffraction, Mōssbauer spectroscopy and positron annihilation methods were obtained. Addition of chromium made the long range ordering process slower

Photo-CIDNP in the reaction center of the diatom Cyclotella meneghiniana observed by 13C MAS NMR

Solid state NMR/Biophysical Organic Chemistr

Current approaches and future role of high content imaging in safety sciences and drug discovery

High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore high content imaging is considered a promising technology to address the challenges for the Toxicity testing in the 21st century approach. Currently high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging in academia, pharmaceutical industry and regulatory bodies with the objective to compile the state-of-the-art of the technology in the different institutions. They defined technical and methodological gaps, addressed the need for quality control, suggested control compounds and acceptance criteria, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.JRC.I.5-Systems Toxicolog

Das Tumormikromilieu bei Speicheldrüsenkarzinomen – mögliche Konsequenzen für neue Therapiekonzepte

Hintergrund Speicheldrüsenkarzinome („salivary gland carcinomas“, SGC) sind seltene Tumoren, die aufgrund ihrer histologischen Vielfalt und den in Abhängigkeit vom Subtyp unterschiedlichen Krankheitsverläufen eine Herausforderung für Diagnostik und Therapie darstellen. Über die Zusammensetzung des Tumormikromilieus (TME) bei SGC ist bislang wenig bekannt. Ein umfassenderes Verständnis der relevanten molekularen Veränderungen und immunologischen Prozesse des Tumors sowie des umgebenden Stromas könnte dazu beitragen, die therapeutische Effizienz – beispielsweise durch eine adjuvante Immunmodulation – zu verbessern. Methoden In diesem Manuskript wurden Ergebnisse aus Studien zusammengefasst, die sich mit der Zusammensetzung des TME bei SGC beschäftigen. Ergebnisse Das Immunzellinfiltrat der verschiedenen Tumorentitäten ist unterschiedlich. Bei einem Drittel der SGC wurde eine Expression des Oberflächenzellrezeptors LAG3 („lymphocyte activation gene 3“) auf tumorinfiltrierenden Lymphozyten beobachtet. LAG3 inhibiert – ähnlich wie CTLA‑4 („cytotoxic T‑lymphocyte antigen 4“) und PD‑1 („programmed cell death 1 protein“) – die zelluläre Proliferation, Aktivierung und Homöostase von antitumoral wirksamen T‑Zellen. Höhere Expressionen sind dabei insbesondere bei den prognostisch ungünstigeren Entitäten wie den Speichelgangkarzinomen und Adenokarzinomen NOS („not otherwise specified“) zu beobachten. Schlussfolgerungen LAG3 ist insbesondere bei aggressiven Entitäten und fortgeschrittenen Tumoren nachzuweisen. Folglich könnte eine Therapie mit LAG3-Inhibitoren eine Therapie bei fortgeschrittenen und metastasierten SGC unterstützen