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The paper studies the migration as a threat to international and national security in the development of globalization processes in modern society. The main causes of migration, which include motives of political, financial, social, psychological and motivational nature, are identified. The main centers of attraction of migrants in 2000-2019 are analyzed and it is established that the European continent is characterized by a high level of attraction of migrants during the last 20 years. The level of dependence between the transformation of the regulatory framework for migration processes and the total number of migrants in the European region and determined that during 2000-2010 there was an increase in migration flows by 22.28%, during 2010-2019 there is a positive trend, change in the number migrants to the European region is 17.65%, and the overall increase in migrants during 2000-2019 is 43.85%. The regulatory acts in the field of migration, which were implemented by the EU during 2000-2019, are analyzed. The main reasons for regulating migration processes are identified, such as: scale of migration flows, aggravation and increase of interethnic conflicts, threat of terrorist acts, increase of crime migrants 'established norms of behavior and cultural traditions, deterioration of psychological climate and relations with other countries, non-compliance with migrants' established norms of behavior and cultural traditions, non-compliance with migrants of host country legislation, and as a result slow process of integration of migrants into the host community. who come with food, shelter and solutions to their social problems. It is established that in order to reduce the intensity of the migration flow, the recipient countries are starting to introduce quotas for labor migration, such as age requirements, professional quotas and proof of qualification and language skills. The connection between migration and security in national security and defense strategies in the EU member states is determined.

Numerical model and procedure are developed to study the output optical performance of light-emitting diode (LED) in which injected current is spatially modulated by mesh-like top metal electrode. The mesh strips have rectangular crossection as in realistic LEDs. The finite element method is applied to obtain three-dimensional distributions of electric potential which are incorporated in the equations for total output power. The numerical procedure is applied to evaluate LED’s total output optical power at different geometric parameters of the electrode: the mesh pitch, the width, and the height of the top mesh-like electrodes. Modeling results demonstrate the effect of mesh pitch variation on the output optical power. In particular, at a certain value of the mesh pitch maximum total output optical power is revealed. The presented approach can be used in the optimization of the LEDs with designed metal electrodes.

The retinoblastoma protein (pRb/p105) tumor suppressor plays a pivotal role in cell cycle regulation by blockage of the G1-to-S-phase transition. pRb tumor suppressor activity is governed by a variety of posttranslational modifications, most notably phosphorylation by cyclin-dependent kinase (Cdk) complexes. Here we report a novel regulation of pRb through protein arginine methyltransferase 4 (PRMT4)-mediated arginine methylation, which parallels phosphorylation. PRMT4 specifically methylates pRb at the pRb C-terminal domain (pRb C(term)) on arginine (R) residues R775, R787, and R798 in vitro and R787 in vivo. Arginine methylation is important for efficient pRb C(term) phosphorylation, as manifested by the reduced phosphorylation of a methylation-impaired mutant, pRb (R3K). A methylmimetic form of pRb, pRb (R3F), disrupts the formation of the E2F-1/DP1-pRb complex in cells as well as in an isolated system. Finally, studies using a Gal4-E2F-1 reporter system show that pRb (R3F) expression reduces the ability of pRb to repress E2F-1 transcriptional activation, while pRb (R3K) expression further represses E2F-1 transcriptional activation relative to that for cells expressing wild-type pRb. Together, our results suggest that arginine methylation negatively regulates the tumor suppressor function of pRb during cell cycle control, in part by creating a better substrate for Cdk complex phosphorylation and disrupting the interaction of pRb with E2F-1.

Latent Kaposi's sarcoma-associated herpesvirus (KSHV) episomes are coated with viral latency-associated nuclear antigen (LANA). In contrast, LANA rapidly disassociates from episomes during reactivation. Lytic KSHV expresses polyadenylated nuclear RNA (PAN RNA), a long noncoding RNA (lncRNA). We report that PAN RNA promotes LANA-episome disassociation through an interaction with LANA which facilitates LANA sequestration away from KSHV episomes during reactivation. These findings suggest that KSHV may have evolved an RNA aptamer to regulate latent protein function.

Kaposi's sarcoma-associated herpesvirus (KSHV) latent genomes are tethered to host histones to form a minichromosome also known as an “episome.” Histones, which are core components of chromatin, are heavily modified by various histone-targeting enzymes. Posttranslational modifications of histones significantly influence accessibility of transcriptional factors and thus have profound effects on gene expression. Recent studies showed that epigenetic marks on the KSHV episome are well organized, exemplified by the absence of histone H3 lysine 9 (H3K9) methylation, a heterochromatic histone mark, from immediate early and latent gene promoters in naturally infected cells. The present study revealed a mechanistic insight into KSHV epigenome regulation via a complex consisting of LANA and the H3K9me1/2 histone demethylase JMJD1A/KDM3A. This complex was isolated from HeLa cell nuclear extracts stably expressing LANA and was verified by coimmunoprecipitation analyses and with purified proteins. LANA recruitment sites on the KSHV genome inversely correlated with H3K9me2 histone marks in naturally infected cells, and methylation of H3K9 significantly inhibited LANA binding to the histone H3 tail. Chromatin immunoprecipitation coupled with KSHV tiling arrays identified the recruitment sites of the complex, while depletion of LANA expression or overexpression of a KDM3A binding-deficient mutant decreased KDM3A recruitment to the KSHV genome. Finally, ablation of KDM3A expression from latently KSHV-infected cells significantly inhibited KSHV gene expression, leading to decreased KSHV replication during reactivation. Taken together, our results suggest that LANA may play a role in regulation of epigenetic marks on the KSHV genome, which is in part through association with the histone demethylase KDM3A.

Impact of mesh-like top metal electrode on output performance of light-emitting diode (LED) is studied using developed numerical model. Three-dimensional Laplace equation is solved by FEM method. Modeling results demonstrate that effect of mesh pitch variation dominates over strip height variation.

Light-emitting diode (LED) with nonuniform current injection caused by the mesh-like design of top metal electrode is studied numerically. Three-dimensional Laplace equation for electric potential is solved by finite element method. The numerical model incorporates mapped infinite element to account for potential decay far away from the LED structure and finite element model developed for boundary condition at semiconductor-air interface in the mesh opening. Simulation results demonstrate the effect of the mesh geometrical parameters on the total output power.

Array of field-effect transistors (FET) with asymmetric T-gates and floating electrodes fabricated on a single chip was used as terahertz (THz) detector. Nonresonant detection with strong photovoltaic response was realized due to excitation of electron plasma oscillations in the common channel of the FETs array. Voltage responsivities obtained by the array of FETs with floating electrodes surpass the photoresponse reported for the array of FETs connected in series by external wiring.

Blue-green InGaN/GaN light-emitting diodes (LEDs) with spatially nonuniform current injection were fabricated and tested. Broad electroluminescence (EL) spectra with equal peak intensities of blue and green emission lines and shallow trough between them were observed at elevated injected current. These features of EL-spectrum are believed to be caused by the mesh-like patterning of the electrode as it creates spatially nonunform electric potential which provides spatial modulation of the injected current along the QW-planes. The latter results not only in spatial nonuniformity of intensity of generated light along the QW-planes but due to screening of polarization field in the QWs causes also position-dependent blue shift of EL. The observed phenomenon can be used to control the EL spectra of dual-wavelength LEDs by the patterned electrodes.

The Kaposi sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a multifunctional protein with roles in gene regulation and maintenance of viral latency. Post-translational modification of LANA is important for functional diversification. Here, we report that LANA is subject to arginine methylation by protein arginine methyltransferase 1 in vitro and in vivo. The major arginine methylation site in LANA was mapped to arginine 20. This site was mutated to either phenylalanine (bulky hydrophobic, constitutive methylated mimetic) or lysine (positively charged, non-arginine methylatable) residues. The significance of the methylation in LANA function was examined in both the isolated form and in the context of the viral genome through the generation of recombinant KSHV. In addition, authentic LANA binding sites on the KSHV episome in naturally infected cells were identified using a whole genome KSHV tiling array. Although mutation of the methylation site resulted in no significant difference in KSHV LANA subcellular localization, we found that the methylation mimetic mutation resulted in augmented histone binding in vitro and increased LANA occupancy at identified LANA target promoters in vivo. Moreover, a cell line carrying the methylation mimetic mutant KSHV showed reduced viral gene expression relative to controls both in latency and in the course of reactivation. These results suggest that residue 20 is important for modulation of a subset of LANA functions and properties of this residue, including the hydrophobic character induced by arginine methylation, may contribute to the observed effects.

The small ubiquitin-like modifier (SUMO) is a protein that regulates a wide variety of cellular processes by covalent attachment of SUMO moieties to a diverse array of target proteins. Sumoylation also plays an important role in the replication of many viruses. Previously, we showed that Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a SUMO-ligase, K-bZIP, which catalyzes sumoylation of host and viral proteins. We report here that this virus also encodes a gene that functions as a SUMO-targeting ubiquitin-ligase (STUbL) which preferentially targets sumoylated proteins for degradation. K-Rta, the major transcriptional factor which turns on the entire lytic cycle, was recently found to have ubiquitin ligase activity toward a selected set of substrates. We show in this study that K-Rta contains multiple SIMs (SUMO interacting motif) and binds SUMOs with higher affinity toward SUMO-multimers. Like RNF4, the prototypic cellular STUbL, K-Rta degrades SUMO-2/3 and SUMO-2/3 modified proteins, including promyelocytic leukemia (PML) and K-bZIP. PML-NBs (nuclear bodies) or ND-10 are storage warehouses for sumoylated proteins, which negatively regulate herpesvirus infection, as part of the intrinsic immune response. Herpesviruses have evolved different ways to degrade or disperse PML bodies, and KSHV utilizes K-Rta to inhibit PML-NBs formation. This process depends on K-Rta's ability to bind SUMO, as a K-Rta SIM mutant does not effectively degrade PML. Mutations in the K-Rta Ring finger-like domain or SIM significantly inhibited K-Rta transactivation activity in reporter assays and in the course of viral reactivation. Finally, KSHV with a mutation in the Ring finger-like domain or SIM of K-Rta replicates poorly in culture, indicating that reducing SUMO-conjugates in host cells is important for viral replication. To our knowledge, this is the first virus which encodes both a SUMO ligase and a SUMO-targeting ubiquitin ligase that together may generate unique gene regulatory programs., Author Summary Protein modification by SUMO (small ubiquitin-like modifier), like phosphorylation, is now considered to be an important biochemical signal involved in nearly all cellular processes. Not surprisingly, it is also implicated in viral replication and host immune response. Timely turning on and off of SUMO signaling on viral and host proteins are important for virus to advance its replication. We previously described the identification of a viral SUMO E3 ligase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), which couples SUMO to recipient proteins. Here we report the discovery of a SUMO-targeting E3 ubiquitin ligase (STUbL) like function, also encoded by this virus. K-Rta preferentially degrades sumoylated proteins such as PML (promyelocytic leukemia) which negatively regulates viral replication. KSHV K-Rta is well recognized as a strong transcriptional factor and a trigger for viral reactivation. Recombinant KSHVs defective in reducing cellular SUMO conjugates are significantly compromised in their reactivation activity. Our finding not only uncovers a novel function of the transcriptional factor, K-Rta, but also points to the importance of dynamic regulation of the SUMO environment in herpesvirus replication.