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ABSTRACTIntestinal dysbiosis can lead to the induction of systemic immune-mediated inflammatory diseases, such as Crohn’s disease Although archaea are part of the commensal microbiota, they are still one of the least studied microorganisms. The aim of our study was the standardization of the optimal conditions and primers for sequencing of the gut archaeome using Next Generation Sequencing, and evaluation of the differences between the composition of archaea in patients and healthy volunteers, as well as analysis of the changes that occur in the archaeome of patients depending on disease activity. Newly diagnosed patients were characterized by similar archeal profiles at every taxonomic level as in healthy individuals (the dominance of Methanobacteriaat the class level, and Methanobrevibacterat the genus level). In turn, in patients previously diagnosed with Crohn’s disease (both in active and remission phase), an increased prevalence of Thermoplasmata, Thermoprotei, Halobacteria(at the class level), and Halococcus, Methanospaeraor Picrophilus(at the genus level) were observed. Furthermore, we have found a significant correlation between the patient’s parameters and the individual class or species of Archaea. Our study confirms changes in archaeal composition in pediatric patients with Crohn’s disease, however, only in long-standing disease. At the beginning of the disease, the archeal profile is similar to that of healthy people. However, in the chronic form of the disease, significant differences in the composition of archaeome begin to appear. It seems that some archaea may be a good indicator of the chronicity and activity of Crohn’s disease.

B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells. We proved that during combined treatment, inhibition of constitutive signal transducer and activator of transcription (STAT) 5 activation by IM allowed the specific enhancement of the STAT1 dependent, direct upregulation of BCL6 by IFNγ in CML cells. By using colony-forming assay, we found that IFNγ enhanced the ex vivocolony or cluster-forming capacity of human CML stem cells in the absence or presence of IM, respectively. Furthermore, inhibition of the transcriptional repressor function of BCL6 in the presence of IM and IFNγ almost completely blocked the cluster formation of human CML stem cells. On the other hand, by using small interfering RNA knockdown of BCL6, we demonstrated that in an IM-treated CML line the antiapoptotic effect of IFNγ was independent of BCL6 upregulation. We found that IFNγ also upregulated several antiapoptotic members of the BCL2 and BIRC gene families in CML cells, including the long isoform of MCL1, which proved to be essential for the antiapoptotic effect of IFNγ in an IM-treated CML line. Our results suggest that combination of TKIs with BCL6 and MCL1 inhibitors may potentially lead to the complete eradication of CML stem cells.

β‐SiC nano‐powder (30 nm) was densified and thereafter deformed in a Spark Plasma Sintering apparatus. High strain rates, ∼ 1x\.10–3/s, were achieved during densification and deformation of the SiC nanoceramics. It was found that dynamic grain sliding, a rapid process that stimulates grain sliding lubricated by a liquid phase but does not activate grain‐boundary migration, is a common mechanism responsible for both processes.

Abstract.: We study the heat flow in the loop space of a closed Riemannian manifoldMas an adiabatic limit of the Floer equations in the cotangent bundle. Our main application is a proof that the Floer homology of the cotangent bundle, for the Hamiltonian function kinetic plus potential energy, is naturally isomorphic to the homology of the loop space.

AbstractThe viral interleukin-10 promoter (vIL-10p), overlapping the rep* element in the EpsteinBarr virus (EBV) genome, is a promoter element active mostly in the late phase of the lytic cycle and immediately upon infection of B cells. rep* was, through transfection experiments with small plasmids, characterised as a cis element supporting oriP replicative function. In this study, in vivo protein binding and CpG methylation at rep*/vIL-10p were analysed in five cell lines that harbour strictly latent EBV genomes. Contrary to the invariably unmethylated dyad symmetry element (DS) of oriP, rep*/vIL-10p was highly methylated and showed only traces of protein binding in all examined cell lines. This result is in agreement with vIL-10p being an inactive promoter of EBV genomes, and makes it less likely that rep* functions as a replicative element of latent EBV genomes.

Optical absorption at the insulating gap in the parent phase of cuprate superconductors shows a broad exciton-like peak near 1.7 eV, followed by a gradual decrease in absorption persisting 1 eV above the gap. By using ultraviolet laser lines to excite Raman spectra, we have found a Raman peak 0.2 eV below the first absorption peak in insulating cuprates. The Raman peak is much narrower than the absorption peak and hasA2g symmetry. We assign it to an exciton consisting of a hole transition from Cu to a linear combination of Cudxy and nearest neighbor Opπ orbitals. We have also studied the resonance Raman profile for two-magnon Raman scattering in the same samples. We find a sharp resonance feature at about 2.7 eV, and little Raman intensity for photon energies at the 1.7 eV absorption peak. The state created at the peak must therefore be an inappropriate intermediate state for the double spin-flip Raman process.

The impact of freeze-casting on the porosity, pore distribution, and phase composition was studied and compared with conventional shaping techniques. A bimodal pore size distribution was observed in freeze-cast + freeze-dried samples, in contrast to the unimodal one in freeze-cast + air-dried and conventionally prepared samples. The densification of freeze-cast + freeze-dried samples started at about 50 °C higher than their conventional counterparts (∼870 °C vs. 920 °C). Diffusion seems to be a key parameter for the phase transformation of HAP into β-TCP during sintering. The residual HAP content in the sintered samples was influenced by used freezing rate and varied from 4 % to 30 % (unimodal samples), and from 7 % to 16 % (bimodal samples). Although further experiments must be carried out, our results showed that the freeze-casting parameters affect the resulting porosity and phase composition regardless of whether the freeze-drying or air-drying was used afterwards.

This note deals with the problem of constructing a full order observer for a linear retarded functional differential equation with general delays in the state and output variables. The observer is introduced as an abstract evolution equation and then shown to be equivalent to an equation of delay type. The transposed of this equation solves the feedback stabilization problem for retarded systems with general delays in the state and input variables.