4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells

Chronic and acute myeloid leukemia evade immune system surveillance and induce immunosuppression by expanding proleukemic Foxp31 regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse, and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers of effector proleukemic Tregs. Using mouse model of leukemia-like disease, we found that Rab27adependent secretion of leukemic EVs promoted leukemia engraftment, which was associated with higher abundance of activated, immunosuppressive Tregs. Leukemic EVs attenuated mTOR-S6 and activated STAT5 signaling, as well as evoked significant transcriptomic changes in Tregs. We further identified specific effector signature of Tregs promoted by leukemic EVs. Leukemic EVs-driven Tregs were characterized by elevated expression of effector/tumor Treg markers CD39, CCR8, CD30, TNFR2, CCR4, TIGIT, and IL21R and included 2 distinct effector Treg (eTreg) subsets: CD301CCR8hiTNFR2hi eTreg1 and CD391TIGIThi eTreg2. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive Tregs and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms

Analysis of Crystal Lattice Deformation by Ion Channeling

A model of dislocations has been developed for the use in Monte Carlo simulations of ion channeling spectra obtained for defected crystals. High resolution transmission electron microscopy micrographs show that the dominant type of defects in the majority of ion irradiated crystals are dislocations. The RBS/channeling spectrum is then composed of two components: one is due to direct scattering on randomly displaced atoms and the second one is related to beam defocussing on dislocations, which produce predominantly crystal lattice distortions, i.e. bent channels. In order to provide a correct analysis of backscattering spectra for the crystals containing dislocations we have modied the existing Monte Carlo simulation code McChasy. A new version of the code has been developed by implementing dislocations on the basis of the PeierlsNabarro model. Parameters of the model have been determined from the high resolution transmission electron microscopy data. The newly developed method has been used to study the Ar-ion bombarded SrTiO3 samples. The best t to the Rutherford backscattering/channeling spectra has been obtained by optimizing the linear combination of two kinds of defects: displaced atoms and bent channels. The great virtue of the Monte Carlo simulation is that unlike a traditional dechanneling analysis it allows quantitative analysis of crystals containing a mixture of dierent types of defects

Origin and production of silver in early medieval Poland

Modern archaeology makes use of analytical methods in order to answer questions about deposit and technological provenience of artefacts. This paper discusses selected and the most interesting, results obtained during the completion of a research project which focuses on silver from the 10th and 11th centuries in Poland. In total, 200 silver artefacts known from Polish hoards (found in Kalisz-Dobrzec, Nowa Obra, Wolsztyn District, Zalesie, Olsztyn District, Słuszków and Jastrzębniki, Kalisz District, Kalisz-Rajsków and Stojkowo, Kołobrzeg District and Naruszewo, Płońsk District) were studied. A micro-invasion LA-ICP-MS (Laser Inductively Coupled Plasma Mass Spectrometry) was used for determinining lead isotope ratios in silver. The data obtained were evaluated using statistical methods which allowed reliable isotopic ratios in inhomogeneous alloy to be obtained. In order to study the provenance of silver, the obtained lead isotope ratios in the artefacts were compared with those of silver deposits. The use of SEM-EDX allowed the tracing of morphological changes and the measurement of quantitative elemental composition of coins, raw silver and jewellery according to technological traits

Accelerators in materials research

Abstract Since at least forty years accelerators of charged particles no longer belong to nuclear physics exclusively. This is especially true for accelerators at energies below 1 GeV. The vast majority of accelerators in this energy range is used for materials research and medicine. In materials research the applications are principally twofold: modifications of solids and surface layer microanalysis. Two most important challenges for materials research at the beginning of XXI century as determined by the Materials Research Society are: development of materials able to repair human body and development of materials for new electronic devices able to cope with the enormous amount of information to be stored and transmitted. The role of accelerators with regard to the challenges of modern technology will be discussed