Network regression with predictive clustering trees

Network data describe entities represented by nodes, which may be connected with (related to) each other by edges. Many network datasets are characterized by a form of autocorrelation, where the value of a variable at a given node depends on the values of variables at the nodes it is connected with. This phenomenon is a direct violation of the assumption that data are independently and identically distributed. At the same time, it offers an unique opportunity to improve the performance of predictive models on network data, as inferences about one entity can be used to improve inferences about related entities. Regression inference in network data is a challenging task. While many approaches for network classification exist, there are very few approaches for network regression. In this paper, we propose a data mining algorithm, called NCLUS, that explicitly considers autocorrelation when building regression models from network data. The algorithm is based on the concept of predictive clustering trees (PCTs) that can be used for clustering, prediction and multi-target prediction, including multi-target regression and multi-target classification. We evaluate our approach on several real world problems of network regression, coming from the areas of social and spatial networks. Empirical results show that our algorithm performs better than PCTs learned by completely disregarding network information, as well as PCTs that are tailored for spatial data, but do not take autocorrelation into account, and a variety of other existing approaches.     

DTA measurements of normal-incommensurate phase transition in (NH4)2ZnCl4 and K2ZnCl4 crystals

Differential thermal analysis (DTA) was applied to determine the changes in enthalpy and entropy of (NH₄)₂ZnCl₄ and K₂ZnCl₄ crystals at their phase transition from the orthorhombic normal phase to the incommensurate phase. The temperature of this transition, T _i , is 406 K for (NH₄)₂ZnCl₄ and 555 K for K₂ZnCl₄ and the entropy changes (S/R) are 0.053 and 0.035, respectively. The low value obtained for S/R is characteristic of incommensurate phase transitions. The results were compared with the data reported for other crystals of the A₂BX₄ family. Thermal properties of the crystals of the A₂ZnCl₄ subgroup were found to the correlated with the length of A-Cl bonds.     

A model with length scales for composites with periodic structure. Steady state heat conduction problem

A new high-order model for analysing distribution of temperature in periodic composites is proposed. The original scalar elliptic problem with Y-periodic coefficients (Y is a cube) is replaced with a vectorial elliptic problem of constant coefficients. The unknown fields are: the averaged distribution of temperature and the vector field which stands for perturbation of the temperature within the cells of periodicity. The recovery of temperature in the original composite is given by the approximation: 0(x)=0(x) +h ^a (x/) _a (x) analogous with the first terms of the two-scale asymptotic expansion known from the homogenization theory. The functions h are defined as approximations of the solutions to the basic cell problems. In contrast to the two-scale expansion the expression for satisfies the boundary condition.     

Structure, hyperfine interactions and magnetization studies of mechanically alloyed Fe50Ge50 and Fe62Ge38

X-ray diffraction, Mössbauer spectroscopy and magnetization measurements were used to study the structure and some magnetic properties of Fe₅₀Ge₅₀ and Fe₆₂Ge₃₈ prepared by mechanical alloying from the elemental powders. In both cases in the early stages of milling the intermediate paramagnetic FeGe₂ phase was formed. The mechanical alloying process of Fe₅₀Ge₅₀ resulted in the formation of the paramagnetic FeGe (B20) phase with an average crystallite size of about 15 nm. In the case of the Fe₆₂Ge₃₈, the ferromagnetic Fe₅Ge₃ (β) phase with a Curie temperature of about 430 K was obtained. The average crystallite size was about 9 nm. The average hyperfine magnetic field of about 16 T allowed it to determine that more than four germanium atoms exist in the nearest environment of the ⁵⁷Fe isotopes in the Fe₅Ge₃ phase.     

Effect of Aminated Chitosan-Coated Fe3O4 Nanoparticles with Applicational Potential in Nanomedicine on DPPG,DSPC, and POPC Langmuir Monolayers as Cell Membrane Models

An adsorption process of magnetite nanoparticles functionalized with aminated chitosan (Fe₃O₄-AChit) showing application potential in nanomedicine into cell membrane models was studied. The cell membrane models were formed using a Langmuir technique from three selected phospholipids with different polar head-groups as well as length and carbon saturation of alkyl chains. The research presented in this work reveals the existence of membrane model composition-dependent regulation of phospholipid-nanoparticle interactions. The influence of the positively charged Fe₃O₄-AChit nanoparticles on a Langmuir film stability, phase state, and textures is much greater in the case of these formed by negatively charged 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) than those created by zwitterionic 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC). The adsorption kinetics recorded during penetration experiments show that this effect is caused by the strongest adsorption of the investigated nanoparticles into the DPPG monolayer driven very likely by the electrostatic attraction. The differences in the adsorption strength of the Fe₃O₄-AChit nanoparticles into the Langmuir films formed by the phosphatidylcholines were also observed. The nanoparticles adsorbed more easily into more loosely packed POPC monolayer.     

Analytical and experimental analysis of deep drawing process for bimetal elements

The paper presents the concepts of solving of deep drawing process for bimetal elements of sheet materials. The inertia forces, plastic hardening behaviour of the deformed material and dynamic stress are utilized in the problems of plasticity. The experimental results and general conclusion are presented at the end of the paper.     

Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.