Mode Coupling at around M-Point in PZT

The question of the microscopic origin of the M-superstructure and additional satellite peaks in the Zr-rich lead zirconate-titanate is discussed for nearly 50 years. Clear contradiction between the selection rules of the critical scattering and the superstructure was found preventing unambiguous attributing of the observed superstructure either to the rotation of the oxygen octahedra or to the antiparallel displacements of the lead cations. Detailed analysis of the satellite pattern explained it as the result of the incommensurate phase transition rather than antiphase domains. Critical dynamics is the key point for the formulated problems. Recently, the oxygen tilt soft mode in the PbZr0.976Ti0.024O3 (PZT2.4) was found. But this does not resolve the extinction rules contradiction. The results of the inelastic X-ray scattering study of the phonon spectra of PZT2.4 around M-point are reported. Strong coupling between the lead and oxygen modes resulting in mode anticrossing and creation of the wide flat part in the lowest phonon dispersion curves is identified. This flat part corresponds to the mixture of the displacements of the lead and oxygen ions and can be an explanation of the extinction rules contradiction. Moreover, a flat dispersion surface is a typical prerequisite for the incommensurate phase transition.     

Brief Report: RedChIP identifies noncoding RNAs associated with genomic sites occupied by Polycomb and CTCF proteins

Nuclear noncoding RNAs (ncRNAs) are key regulators of gene expression and chromatin organization. The progress in studying nuclear ncRNAs depends on the ability to identify the genome-wide spectrum of contacts of ncRNAs with chromatin. To address this question, a panel of RNA–DNA proximity ligation techniques has been developed. However, neither of these techniques examines proteins involved in RNA–chromatin interactions. Here, we introduce RedChIP, a technique combining RNA–DNA proximity ligation and chromatin immunoprecipitation for identifying RNA–chromatin interactions mediated by a particular protein. Using antibodies against architectural protein CTCF and the EZH2 subunit of the Polycomb repressive complex 2, we identify a spectrum of cis- and trans-acting ncRNAs enriched at Polycomb- and CTCF-binding sites in human cells, which may be involved in Polycomb-mediated gene repression and CTCF-dependent chromatin looping. By providing a protein-centric view of RNA–DNA interactions, RedChIP represents an important tool for studies of nuclear ncRNAs.     

Three‐way parallel group independent component analysis: Fusion of spatial and spatiotemporal magnetic resonance imaging data

Advances in imaging acquisition techniques allow multiple imaging modalities to be collected from the same subject. Each individual modality offers limited yet unique views of the functional, structural, or dynamic temporal features of the brain. Multimodal fusion provides effective ways to leverage these complementary perspectives from multiple modalities. However, the majority of current multimodal fusion approaches involving functional magnetic resonance imaging (fMRI) are limited to 3D feature summaries that do not incorporate its rich temporal information. Thus, we propose a novel three‐way parallel group independent component analysis (pGICA) fusion method that incorporates the first‐level 4D fMRI data (temporal information included) by parallelizing group ICA into parallel ICA via a unified optimization framework. A new variability matrix was defined to capture subject‐wise functional variability and then link it to the mixing matrices of the other two modalities. Simulation results show that the three‐way pGICA provides highly accurate cross‐modality linkage estimation under both weakly and strongly correlated conditions, as well as comparable source estimation under different noise levels. Results using real brain imaging data identified one linked functional–structural–diffusion component associated to differences between schizophrenia and controls. This was replicated in an independent cohort, and the identified components were also correlated with major cognitive domains. Functional network connectivity revealed visual–subcortical and default mode‐cerebellum pairs that discriminate between schizophrenia and controls. Overall, both simulation and real data results support the use of three‐way pGICA to identify multimodal spatiotemporal links and to pursue the study of brain disorders under a single unifying multimodal framework.     

Three-Dimensional Endoscopy-Assisted Excision and Reconstruction for Metastatic Disease of the Dorsal and Lumbar Spine: Early Results

BackgroundThe aim of this study was to explore the role of three-dimensional (3D) endoscopy in surgical management of metastatic disease of the dorsal and lumbar spine.MethodsThis is a prospective study on 33 patients (15 men and 18 women, mean age of 61.6 ± 8.9 years) with biopsy-proven metastatic disease of the spine managed by sequential/staged posterior decompression-stabilization, followed by 3D endoscopy-assisted anterior corpectomy and stabilization with a mesh cage. All patients had significant extradural compression or spinal instability or both. Sixteen patients had neurological deficits. Visual analog scale (VAS), Frenkel grade (neurological deficits), Karnofsky performance status scale, and the 36-item short-form health survey (SF-36) were used for assessment preoperatively and at 3, 6, and 12 months from surgery.ResultsAt a mean follow-up of 1.7 ± 0.7 years from surgery, 18 patients were alive. VAS showed significant improvement at the latest follow-up compared to preoperative levels (4.39 vs. 6.61, p = 0.001). Karnofsky status did not show any significant improvement. Frenkel grade improved in 5 patients, deteriorated in 4 patients, and remained unchanged in 24 patients. Regarding SF-36 parameters, general health showed deterioration, but role functioning—physical, role functioning—emotional, social functioning, and body pain showed statistically significant improvement. There was no change in physical health, viability, and mental health. Subjectively the surgeons felt better depth perception and smoother surgical experience with the 3D optics technology. The only complication was delayed wound healing in three patients who had a previous history of radiotherapy to the surgical site.Conclusions3D endoscopy is a valuable tool in the management of metastatic spinal disease requiring excision and reconstruction using the combined posterior and anterior approaches. These early results warrant confirmation with more data and longer follow-ups.     

Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis

Liver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation of cell metabolism, growth, and inflammatory activation. We previously reported that a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multiple sclerosis (MS). Since astrocyte activation and metabolic function have important roles in regulating neuroinflammation and neuropathology, we examined the serine/threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encephalomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte-selective conditional knockout (het-cKO) model was used. While disease incidence was similar, disease severity was worsened in het-cKO mice. RNAseq analysis identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het-cKO mice relating to mitochondrial function, confirmed by alterations in mitochondrial complex proteins and reductions in mRNAs related to astrocyte metabolism. Enriched pathways included major histocompatibility class II genes, confirmed by increases in MHCII protein in spinal cord and cerebellum of het-cKO mice. We observed increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal cords of het-cKO mice, associated with reduced expression of choline acetyltransferase, accumulation of immunoglobulin-γ, and reduced expression of factors involved in motor neuron survival. In vitro, LKB1-deficient astrocytes showed reduced metabolic function and increased inflammatory activation. These data suggest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency, can exacerbate demyelinating disease by loss of metabolic support and increase in the inflammatory environment.     

Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m² for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.     

Mathematical Modeling and Experimental Substantiation of the Gas Release Process in the Production of Non-Autoclaved Aerated Concrete

The widespread use of aerated concrete in construction has led to the emergence of many types and compositions. However, additional research should fill theoretical gaps in the phenomenon of gas release during the formation of the structure of aerated concrete. Based on theoretical analysis and experimental studies, the article proposes a mathematical model of the swelling process based on the physicochemical laws of convection and molecular diffusion of hydrogen from a mixture and the conditions of swelling, precipitation, and stabilization of the mixture. An improved method for the manufacture of aerated concrete is proposed, which consists of introducing cement pre-hydrated for 20–30 min into the composition of the aerated concrete mixture and providing improved gas-holding capacity and increased swelling of the mixture, reducing the average density of aerated concrete up to 29% and improving heat-shielding properties up to 31%. At the same time, the small dynamics of a decrease in the strength properties of aerated concrete were observed, which is confirmed by an increased structural quality factor (CSQ) of up to 13%. As a result, aerated concrete has been obtained that meets the requirements of environmental friendliness and has improved mechanical and physical characteristics. Economic efficiency is to reduce the cost of production of aerated concrete and construction in general by about 15%.     

Evaluation of Mechanical and Electrical Performance of Aging Resistance ZTA Composites Reinforced with Graphene Oxide Consolidated by SPS

This paper presents a study of Al₂O₃–ZrO₂ (ZTA) nanocomposites with different contents of reduced graphene oxide (rGO). The influence of the rGO content on the physico-mechanical properties of the oxide composite was revealed. Graphene oxide was obtained using a modified Hummers method. Well-dispersed ZTA-GO nanopowders were produced using the colloidal processing method. Using spark plasma sintering technology (SPS), theoretically dense composites were obtained, which also reduced GO during SPS. The microstructure, phase composition, and physico-mechanical properties of the sintered composites were studied. The sintered ZTA composite with an in situ reduced graphene content of 0.28 wt.% after the characterization showed improved mechanical properties: bending strength was 876 ± 43 MPa, fracture toughness—6.8 ± 0.3 MPa·m^1/2 and hardness—17.6 ± 0.3 GPa. Microstructure studies showed a uniform zirconia distribution in the ZTA ceramics. The study of the electrical conductivity of reduced graphene oxide-containing composites showed electrical conductivity above the percolation threshold with a small content of graphene oxide (0.28 wt.%). This electrical conductivity makes it possible to produce sintered ceramics by electrical discharge machining (EDM), which significantly reduces the cost of manufacturing complex-shaped products. Besides improved mechanical properties and EDM machinability, 0.28 wt.% rGO composites demonstrated high resistance to hydrothermal degradation.     

Protective Effect of Comaruman, a Pectin of Cinquefoil Comarum palustre L., on Acetic Acid-Induced Colitis in Mice

The efficacy of comaruman CP, a pectin of marsh cinquefoil Comarum palustre L., was investigated using a model of acetic acid-induced colitis in mice. Mice were administered comaruman CP orally 2 days prior to rectal injection of 5% acetic acid and examined for colonic damage 24 hr later. Colonic inflammation was characterized by macroscopical injury, higher levels of myeloperoxidase activity, enhanced vascular permeability, and diminution of colonic mucus. Oral administration of comaruman CP was found to prevent progression of colitis. Colonic macroscopic scores and the total square of damage were significantly reduced in mice treated with CP compared with the vehicle-treated colitis group. Peroral pretreatment of mice with comaruman CP was shown to decrease tissue myeloperoxidase activity in colons compared with the colitis group. Comaruman CP was found to stimulate production of mucus by colons of normal and colitis mice. Comaruman CP decreased the inflammatory status of normal mice as elicited by reduction of vascular permeability and adhesion of peritoneal neutrophils and macrophages. Thus, a preventive effect of comaruman on acetic acid-induced colitis in mice was detected. Reduction of neutrophil infiltration and enhancement of colon-bound mucus may be implicated in the protective effect of comaruman.