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The results of the experimental study of the mechanical properties and structure of the Co-9.5Al-2.9Mo-4Nb, Co-9.1Al-5.2Mo-4.7Nb, and Co-8.9Al-6.5Mo-9.3Nb alloys were presented. The Young’s moduli in the studied alloy samples were found to be smaller than those of Ni3Al-based and Co3(Al,W)-based alloys. The eutectic structure was observed in all studied alloys. Cuboids of the Co3(Al,Nb,Mo) intermetallic compound with L12 crystal structure were found by TEM study.

Features of the structure and phase transformations in single-crystal nickel alloys 1, 2 after long high-temperature exposures were considered in this paper. The results and studies of the residual mechanical properties of alloys after exposure are given. Nanophase hardening of single-crystal heat resistant nickel alloys was also considered. The method of heat treatment of single-crystal high-temperature nickel alloys was developed based on the studies. It provides an increase in the strength properties of alloys by 20...30%, due to the formation of bulk nanophases (γn + γ'n). The data obtained on structural and phase changes in high-temperature nickel alloys make it possible to evaluate the stability of the structural state of alloys.

Feminism is one of the most important ideologies in the contemporary society. It influences not only the inter-political process but also international one. The word “feminism” has been named word of the year by the American dictionary Merriam-Webster in 2017

To study the mechanism of space stem formation, the high‐speed direct imaging technique and Schlieren photography are used to simultaneously observe the space stems in a 1.35‐m air gap under the lightning impulse voltage. It is found that the average length and diameter of the space stem is approximately 5 and 0.5 mm, which is about 1/3 of the length and 1/10 of the diameter of the local luminous region respectively. Moreover, the space stem exhibits a non‐uniform distributed temperature with a maximum value of several hundred Kelvin for tens of microseconds. Accordingly, a possible mechanism is proposed that the space stem is formed at the primary corona streamer boundary as a result of the propagation of a secondary ionization wave from the HV electrode and survives long enough (to finish the polarization) due to the fast gas heating and production of atomic oxygen. It is well known that negative leaders in the air develop in a step‐wise manner, with each step originating from a space stem. However, the mechanism of space stem formation is still unknown, one of the main reasons being the lack of experimental observations. For this reason, this paper carries out laboratory research to observe the optical and thermal properties of space stems. The observations reveal that the local luminous region at the primary corona streamer boundary is not fully heated into the space stem, but only about 1/3 of its length. If based on conventional direct images, the measured length and diameter of space stems would be 2.5 and 10 times larger than the actual values, respectively. The reconstructed temperature field shows that the axial temperature and diameter of the space stem are not uniformly distributed, with higher temperatures and smaller diameters at the end away from the HV electrode. Finally, a new possible mechanism is proposed for the space stem formation, in which the secondary ionization wave from the HV electrode contributes to the initial formation of the space stem, and then the voltage changes help the space stem survive long enough to finish the polarization. Only a section of the local luminous region at the primary corona streamer boundary is heated to form a space stem, but not all of itThe temperature field of a space stem is reconstructed for the first time and presents a non‐uniform distributionA secondary ionization wave may contribute to the space stem formation at the primary corona streamer burst boundary Only a section of the local luminous region at the primary corona streamer boundary is heated to form a space stem, but not all of it The temperature field of a space stem is reconstructed for the first time and presents a non‐uniform distribution A secondary ionization wave may contribute to the space stem formation at the primary corona streamer burst boundary

Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harboring clonal EZH2mutation from rarer cases with subclonal mutations. Overall, the high incidence of EZH2mutations in FL and their stability during disease progression makes FL an appropriate disease to evaluate EZH2 targeted therapy.

Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harboring clonal EZH2 mutation from rarer cases with subclonal mutations. Overall, the high incidence of EZH2 mutations in FL and their stability during disease progression makes FL an appropriate disease to evaluate EZH2 targeted therapy.

ABSTRACTCyclic vomiting syndrome (CVS) is a functional disorder that may occur in any age group of patients. In the past the disorder was considered to be fairly uncommon, of unknown etiology. Most cases of CVS have been described as sporadic, but family history may be an important factor. Here we present an 18-year-old male patient with symptoms of recurrent spells of intense vomiting. The objective of this study was to determine the presence of mtDNA polymorphisms in a patient with a pediatric-onset CVS as an indication of genetic association that confers an increased risk towards disease pathogenesis.

ABSTRACTAutism is a severe neurodevelopmental disorder with both genetic and epigenetic etiological elements. Currently it is unclear how many genes are associated with autism and how strong the evidence is. Micro-RNA gene expression profiling is considered a promising tool for discovery of autism-related genes and biological pathways because of the dynamic nature of the whole blood transcriptome. The objective of this study was to identify miRNA expression changes in children with autism compared to general population controls. In the present study, we examined miRNA gene expression changes applying custom-made LC Science miRNA expression profiling service, using pooled whole blood-derived total RNA samples in order to evaluate possible miRNA transcripts and networks of molecules associated with the disease. Here, we report molecular evidence for a differentially expressed miR486-3p which has shown brain-specific expression with possible roles in human neuronal differentiation. This study outlines altered miRNAs expression levels observed in peripheral whole blood from autism patients, a finding which suggests that dysregulation of miRNAs may contribute to autism phenotype. Potential and validated target genes for these microRNAs were shown, which include several autism susceptibility genes. The miRNA expression changes involved may help to define the etiology, genetics, and clinical phenotype, as well as the outcome in autism. Further molecular analysis on miRNA gene expression changes will give a more detailed picture about the miRNA associated mechanism in autism.

The theory of reflection image formation at coherent slant illumination is specified for the case of confined objects. The approach is based on the parabolic wave equation with a boundary condition posed on an object surface that is tilted in respect to the beam k-vector. The result is obtained in the form of a new propagation integral. 3D simulation of coherent reflection imaging at grazing angles of illumination in a lens optical scheme is performed and discussed.

TheINK4b-ARF-INK4alocus encodes for two cyclin-dependent kinase inhibitors, p15INK4band p16INK4aand a regulator of the p53 pathway, ARF. In addition ANRIL, a non-coding RNA, is also transcribed from the locus. ARF, p15INK4band p16INK4aare well-established tumor suppressors which function is frequently disabled in human cancers. Recent studies showed that single nucleotide polymorphisms mapping in the vicinity of ANRIL are linked to a wide spectrum of conditions, including cardiovascular disease, ischemic stroke, type 2 diabetes, frailty and Alzheimer’s disease. The INK4b-ARF-INK4alocus is regulated by Polycomb repressive complexes (PRCs), and its expression can be invoked by activating signals. Other epigenetic modifiers such as the histone demethylases JMJD3 and JHDM1B, the SWI/SNF chromatin remodeling complex and DNA methyltransferases regulate the locus interplaying with PRCs. In view of the intimate involvement of the INK4b-ARF-INK4alocus on disease, to understand its regulation is the first step for manipulate it to therapeutic benefit.

A design of a polarizing all-glass Bragg fiber with a microstructure core has been proposed for the first time. This design provides suppression of high-order modes and of one of the polarization states of the fundamental mode. The polarizing fiber was fabricated by a new, simple method based on a combination of the modified chemical vapor deposition (MCVD) process and the rod-in-tube technique. The mode field area has been found to be about 870?μm^2 near λ=1064?nm. The polarization extinction ratio better than 13?dB has been observed over a 33% wavelength range (from 1 to 1.4?μm) after propagation in a 1.7?m fiber piece bent to a radius of 70?cm.

The myeloid/lymphoid or mixed-lineage leukaemia 2 (MLL2) histone methyltransferase (referred to as Mll4 in mice) forms part of a large multiprotein complex, which catalyses the methylation of lysine 4 on histone H3 (H3K4). High levels of this histone modification are detected at promoter regions of actively transcribed genes. Loss-of-function mutations in MLL2 have been identified in 80-90% of follicular lymphoma (FL) cases. These mutations are distributed throughout the coding region and lead to the loss of the C-terminal catalytic SET domain and reduction in H3K4 methylation. We generated a Mll4 knockout (Mll4-/-) mouse model to elucidate the effects of Mll4 loss on B cell development and understand how mutations in this gene contribute to FL pathogenesis.Cre:ERT2-mediated recombination was used to induce the deletion of exons 2–4 of Mll4 in adult mice. CD19+ B lymphocytes were purified from the spleens of wild-type (Mll4WT) and Mll4-/- mice and confirmed the loss of Mll4 mRNA and protein by quantitative RT-PCR (qRT-PCR) and immunoblotting, respectively. As expected, B cells lacking Mll4 (Mll4ΔB/ΔB) exhibited a global reduction in H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3), compared with normal B cells. Gene expression profiling (GEP) using the GeneChip® Mouse Genome 430 2.0 Array (n=5 Mll4WT + 5 Mll4-/- mice) was carried out to determine the transcriptional changes upon loss of Mll4. We identified >200 genes differentially expressed (>2-fold) between Mll4WT and Mll4ΔB/ΔB CD19+ B cells. The top 40 candidate genes (p<0.05) were verified in an independent series of experiments using qRT-PCR. We noted a significant decrease in the expression of the transcription factor lymphoid enhancer-binding factor 1 (Lef1) and the histone acetyltransferase nuclear receptor coactivator 3 (Ncoa3). The downregulation of these genes is consistent with published data, as the promoters of both are marked by H3K4me3 in normal mouse CD19+ B cells. Lef1 is a key regulator of lymphoid differentiation, while Ncoa3 depletion has been shown to induce B-cell lymphoma in mice as a result of constitutive NF-κB activation. A significant number of genes (p<0.001) involved in cell cycle and immune response were upregulated in Mll4ΔB/ΔB CD19+ B cells. Furthermore, loss of Mll4 led to an elevated expression (2.4-fold) of activation-induced cytidine deaminase (Aicda), an enzyme required for germinal centre-derived lymphomagenesis. Immunophenotyping was used to examine the role of Mll4 at different stages of B cell development. We detected a significant reduction in the number of pre-B cells (B220+CD43–IgM–) in the bone marrow of Mll4-/- mice (n=12), compared with their littermate controls (n=10; p<0.01), although this did not affect the number of peripheral mature splenic B cells (B220+IgM+). Mll4 loss had an adverse effect on immune response, with CD19+ B cells failing to induce expression of the MHC-II, CD86, CD40 and CD69 activation markers upon in vitro stimulation with lipopolysaccharide and interleukin 4.Our findings provide the first insight into the potential mechanistic link between MLL2 loss and the onset of FL using a mouse model. Mll4-/- mice do not develop any lymphoproliferative disorders, but show defects in B cell development and an impaired immune response. Furthermore, loss of Mll4 leads to the global depletion of H3K4 methylation in mouse B lymphocytes, thus affecting the expression of Lef1, Ncoa3 and Aicda. Although these MLL2/Mll4 target genes have defined roles in B cell biology, their contribution to the pathogenesis of FL will depend on when MLL2 mutations arise during FL development.No relevant conflicts of interest to declare.

The myeloid/lymphoid or mixed-lineage leukaemia 2(MLL2) histone methyltransferase (referred to as Mll4 in mice) forms part of a large multiprotein complex, which catalyses the methylation of lysine 4 on histone H3 (H3K4). High levels of this histone modification are detected at promoter regions of actively transcribed genes. Loss-of-function mutations in MLL2have been identified in 80-90% of follicular lymphoma (FL) cases. These mutations are distributed throughout the coding region and lead to the loss of the C-terminal catalytic SET domain and reduction in H3K4 methylation. We generated a Mll4knockout (Mll4-/-) mouse model to elucidate the effects of Mll4loss on B cell development and understand how mutations in this gene contribute to FL pathogenesis.

Kohlmann: MLL Munich Leukemia Laboratory: Employment. Gribben:Celgene: Honoraria. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

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