PENGARUH JUMLAH PENDUDUK, INVESTASI DAN KONSUMSI RUMAH TANGGA TERHADAP PRODUK DOMESTIK REGIONAL BRUTO (PDRB) DI PROVINSI SUMATERA UTARA

This study examined the effect of population, investment, and household consumption on the Gross Regional Domestic Product (GRDP) in North Sumatra Province. The data analysis method used was quantitative data in the form of secondary data with a multiple linear regression model with E-views 10, where the total number of observations was 16, with the number of years consisting of 2004-2020. The results revealed that the population influenced GDRP in North Sumatra Province, Investment did not influence GRDP in North Sumatra Province, and Household consumption did not influence GRDP in North Sumatra Province

Utilizing simulation and optimization techniques to evaluate different CAR T cell therapy manufacturing paradigms

In an effort to understand major cost drivers and assess processing risk, Juno Therapeutics has developed a plant simulation of its global manufacturing network. With this simulation, Juno can assess the impact various control levers and sources of variability will have on key performance metrics. Juno has the ability to modify various aspects of its manufacturing operations, such as process design, staffing totals, shift schedules, facility configuration, and activity prioritization. Various sources of variability, such as time of patient specific raw material arrival at the plant, treatment rescheduling, and unit operation duration, will need to be mitigated in order to ensure robust manufacturing. In turn, with a representative simulation in place, optimization techniques can be leveraged in an effort to maximize the number of treated patients and revenue, while minimizing cost of goods and product cycle time. This work helps inform feasibility of future manufacturing paradigms and process design. An overview of Juno’s simulation and optimization methodology is presented here. Evaluations and trade-offs of point-of-care vs. centralized manufacturing and workstation vs. flexible facility configurations are presented

Long Tandem Arrays of Cassandra Retroelements and Their Role in Genome Dynamics in Plants

Retrotransposable elements are widely distributed and diverse in eukaryotes. Their copy number increases through reverse-transcription-mediated propagation, while they can be lost through recombinational processes, generating genomic rearrangements. We previously identified extensive structurally uniform retrotransposon groups in which no member contains the gag, pol, or env internal domains. Because of the lack of protein-coding capacity, these groups are non-autonomous in replication, even if transcriptionally active. The Cassandra element belongs to the non-autonomous group called terminal-repeat retrotransposons in miniature (TRIM). It carries 5S RNA sequences with conserved RNA polymerase (pol) III promoters and terminators in its long terminal repeats (LTRs). Here, we identified multiple extended tandem arrays of Cassandra retrotransposons within different plant species, including ferns. At least 12 copies of repeated LTRs (as the tandem unit) and internal domain (as a spacer), giving a pattern that resembles the cellular 5S rRNA genes, were identified. A cytogenetic analysis revealed the specific chromosomal pattern of the Cassandra retrotransposon with prominent clustering at and around 5S rDNA loci. The secondary structure of the Cassandra retroelement RNA is predicted to form super-loops, in which the two LTRs are complementary to each other and can initiate local recombination, leading to the tandem arrays of Cassandra elements. The array structures are conserved for Cassandra retroelements of different species. We speculate that recombination events similar to those of 5S rRNA genes may explain the wide variation in Cassandra copy number. Likewise, the organization of 5S rRNA gene sequences is very variable in flowering plants; part of what is taken for 5S gene copy variation may be variation in Cassandra number. The role of the Cassandra 5S sequences remains to be established

F. Venturi, Il populismo russo, i-iii, Mimesis, Milano 2021, pp. cxxix-375, 479, 460.

Book Revie

Diversity of long terminal repeat retrotransposon genome distribution in natural populations of the wild diploid wheat Aegilops speltoides

Background: The environment can have a decisive influence on the structure of the genome, changing it in a certain direction. Therefore, the genomic distribution of environmentally sensitive transposable elements may vary measurably across a species area. In the present research, we aimed to detect and evaluate the level of LTR retrotransposon intraspecific variability in Aegilops speltoides (2n=2x=14), a wild cross-pollinated relative of cultivated wheat. Results: The inter-retrotransposon amplified polymorphism (IRAP) protocol was applied to detect and evaluate the level of LTR retrotransposon intraspecific variability in Ae. speltoides and closely related species of sect. Sitopsis. IRAP analysis revealed significant diversity in TE distribution. Various genotypes from the same population significantly differ with respect to the patterns of the four explored LTR retrotransposons (WIS2, Wilma, Daniela, and Fatima). This diversity points to a constant ongoing process of LTR retrotransposon fraction restructuring in populations of Ae. speltoides throughout the species’ range and within single populations in time. Maximum changes were recorded in genotypes from small stressed populations. Principal component analysis showed that the dynamics of the Fatima element in populations of Ae. speltoides significantly differ from those of WIS2, Wilma, and Daniela. In terms of relationships between Sitopsis species, IRAP analysis of WIS2, Wilma, and Daniela elements revealed a grouping similar to groupings determined by other methods, with Ae. sharonensis and Ae. longissima forming a separate unit, Ae. speltoides appearing as a dispersed group, and Ae. bicornis being in an intermediate position. Conclusions: IRAP display data revealed dynamic changes in LTR retrotransposon fractions in the genome of Ae. speltoides. The process is permanent and population-specific, ultimately leading to the separation of small stressed populations from the main bunch.Peer reviewe

Образы и символы европейского ренессанса в творчестве Н.С. Гумилева

The Images-symbols of European Renaissance (mostly of his early period - quatrochento) occupy an important place in creation of prominent poet of the Russian «silver century» N. Gumilev. They are presented both in a poetry and prose and in correspondence of N.Gumilev. Italian quatrochento become the subject of discussion of N.Gumilev and poetess, revolutionary, publicist Laryssa Reysner.Образы-символы европейского Ренессанса (по большей части его начального периода - кватроченто) занимают важное место в творчестве выдающегося поэта русского «серебряного века» Н.С. Гумилева. Они представлены как в поэзии и прозе, так и в переписке Н.С. Гумилева. Итальянское кватроченто стало предметом дискуссии Н.С. Гумилева и поэтессы, революционерки, публициста Л.М. Рейснер

On Building Economic Development Patterns for Russia and Belorussia on the Basis of LAM-3 Econometric Model

The article deals with the results of econometric model building for Russian and Belorussian economic development using the LAM-3 methodology. LAM-3 is the most recent version of the Long-run Adjustment Model that is used for quarter-to-quarter modeling and forecasting to show the economic development of countries in Eastern Europe. The principles upon the LAM-3 models are built and the problems associated with the model-building processes are discussed. The models are used to depict the Russian and Belorussian economies in transition. The article describes the GIRAF software developed to be used in the LAM-3 series models and to assess the level of accuracy of the forecasts made for the economies of Russia and BelorussiaEconometric Modeling; Forecasting; Long-run Adjustment; Simulation; Transition Economy of Russia and Belarus

Ацеклофенак: терапевтическая эффективность при остеоартрозе

The place of aceclofenac in a group of nonsteroidal anti-inflammatory drugs and its efficacy in osteoarthrosis are discussed.Обсуждаются место ацеклофенака в группе нестероидных противовоспалительных препаратов и его эффективность при остео- артрозе

Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer

Drug development; Predictive biomarkers; Prostate cancerDesarrollo de fármacos; Biomarcadores predictivos; Cáncer de próstataDesenvolupament de fàrmacs; Biomarcadors predictius; Càncer de pròstataBackground Biomarkers predicting second-generation novel hormonal therapy (NHT) benefit relative to taxanes are critical for optimized treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) patients. These associations have not been reported simultaneously for common mCRPC genomic biomarkers. Objective To evaluate predictive associations of common genomic aberrations in mCRPC using an established comprehensive genomic profiling (CGP) system. Design, setting, and participants A retrospective cohort study used data from a deidentified US-based clinicogenomic database comprising patients treated in routine clinical practice between 2011 and 2020, evaluated with Foundation Medicine CGP in tissue biopsies obtained around the time of treatment decision. The main cohort included 180 NHT and 179 taxane lines of therapy (LOTs) from 308 unique patients. The sequential cohort comprised a subset of the main cohort NHT LOTs immediately followed by taxane from 55 unique patients. Outcome measurements and statistical analysis Prostate-specific antigen (PSA) response, time to next treatment (TTNT), and overall survival (OS) were assessed. Main cohort analyses were adjusted for known treatment assignment biases via inverse probability of treatment weighting (IPTW) in treatment interaction models. Results and limitations In the main cohort, patients with AR amplification (ARamp) or PTEN aberrations (PTENalt) had worse relative PSA response on NHT versus taxanes compared with patients without. Patients with ARamp, PTENalt, or RB1 aberrations (RB1alt) also had worse relative TTNT and OS on NHT but not on taxanes. In multivariable models for TTNT and OS adjusted via IPTW, ARamp, PTENalt, and RB1alt were shown as poor prognostic factors overall and demonstrated significant treatment interactions, indicating reduced hazards of therapy switch and death on taxanes versus NHT. Consistent associations favoring increased benefit from subsequent taxane despite prior NHT treatment line were observed only for ARamp in the sequential cohort, in which very few patients had RB1alt for assessment. Conclusions ARamp status is a candidate biomarker to predict poor effectiveness of NHT relative to taxanes in mCRPC in scenarios where both options are considered

Repetitive DNA in the Architecture, Repatterning, and Diversification of the Genome of Aegilops speltoides Tausch (Poaceae, Triticeae)

The genome’s adaptability to environmental changes, especially during rapid climatic fluctuations, underlies the existence and evolution of species. In the wild, genetic and epigenetic genomic changes are accompanied by significant alterations in the complex nuclear repetitive DNA fraction. Current intraspecific polymorphism of repetitive DNA is closely related to ongoing chromosomal rearrangements, which typically result from erroneous DNA repair and recombination. In this study, we addressed tandem repeat patterns and interaction/reshuffling both in pollen mother cell (PMC) development and somatogenesis in the wild diploid cereal Aegilops speltoides, with a focus on genome repatterning and stabilization. Individual contrasting genotypes were investigated using the fluorescent in situ hybridization (FISH) approach by applying correlative fluorescence and electron microscopy. Species-specific Spelt1 and tribe-specific Spelt52 tandem repeats were used as the markers for monitoring somatic and meiotic chromosomal interactions and dynamics in somatic interphase nuclei. We found that, the number of tandem repeat clusters in nuclei is usually lower than the number on chromosomes due to the associations of clusters of the same type in common blocks. In addition, tightly associated Spelt1–Spelt52 clusters were revealed in different genotypes. The frequencies of nonhomologous/ectopic associations between tandem repeat clusters were revealed in a genotype-/population-specific manner. An increase in the number of tandem repeat clusters in the genome causes an increase in the frequencies of their associations. The distal/terminal regions of homologous chromosomes are separated in nuclear space, and nonhomologous chromosomes are often involved in somatic recombination as seen by frequently formed interchromosomal chromatin bridges. In both microgametogenesis and somatogenesis, inter- and intrachromosomal associations are likely to lead to DNA breaks during chromosome disjunction in the anaphase stage. Uncondensed/improperly packed DNA fibers, mainly in heterochromatic regions, were revealed in both the meiotic and somatic prophases that might be a result of broken associations. Altogether, the data obtained showed that intraorganismal dynamics of repetitive DNA under the conditions of natural out-crossing and artificial intraspecific hybridization mirrors the structural plasticity of the Ae. speltoides genome, which is interlinked with genetic diversity through the species distribution area in contrasting ecogeographical environments in and around the Fertile Crescent