Clinical Significance of Pathogenicity of Somatic Mutations in Oral Leukoplakia: a Prospective Observational Study

Background. The vast majority of malignant neoplasms of the oral mucosa refer to squamous cell carcinomas. The development of squamous cell carcinoma of the oral mucosa is often promoted by previous potentially malignant diseases, with oral leukoplakia dominating among them.Objective. To determine the clinical significance of the pathogenicity of somatic mutations in oral mucosal leukoplakia.Methods. The study material included 24 samples of abnormal epithelium of the oral mucosa from leukoplakia patients. QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used for deoxyribonucleic acid (DNA) extraction from the samples. DNA sequencing was performed using IlluminaNextSeq 550 sequencer and TruSight™ Oncology 500 DNA Kit For Use with NextSeq (Illumina, USA). All DNA extractions from biological samples, preparation and sequencing of DNA libraries were performed step-by-step in strict accordance with the guidelines provided with the respective reagent kits. Bioinformatics analysis was carried out using specific software Illumina Base Space (Illumina, USA) and Galaxy Project (The Galaxy Community, a non-profit international project) according to current guidelines. The desired power of the study accounted for 90%. Two Proportions Z test was performed by means of The Sample Size Calculation of Statistica 12 (StatSoft, Inc.) with the set option “one-tailed hypothesis”, because it was initially assumed that pathogenic (oncogenic) genetic variants occur in the tissue of oral leukoplakia much more frequently than in the human reference genome used for sequence alignment.Results. The pathogenic somatic mutations in the TP53, KRAS, APC, NRAs and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000-11000) to be associated with the development of oral mucosal leukoplakia and low-grade epithelial dysplasia. The multiplicity of pathogenic and likely pathogenic genetic variants associated with epithelial dysplasia, as well as the fact that a number of variants do not occur in all patients, suggests that the same histotype of oral mucosal dysplasia may develop under the influence of different mutations.Conclusion. The pathogenic and likely pathogenic variants of the TP53, KRAS, APC, NRAS and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000–11000) to be associated with the development of leukoplakia and low-grade epithelial dysplasia

DISPOSAL OF CONTAMINATED DDT OF PHYTOMASS IN ANAEROBIC CONDITIONS

Встановлено, що хлорорганічні пестициди більшою мірою піддаються біорозкладанню в анаеробних умовах. Анаеробне компостування проводять у спеціальних бетонних ямах або траншеях з гідроізоляцією, які заповнюють компостною масою (поживний субстрат, ґрунт, пестициди та мінеральне підживлення, можливо, додаткове внесення відходів тваринного походження) з подальшим заливанням ями водою. Кислотність середовища підтримують у межах рН 6–8, використовуючи за потреби вапнування ґрунтів. Досліджено, що для виробництва біогазу можна використовувати всі органічні субстанції, що мають властивість розкладатися. Основним субстратом для ферментації на сільськогосподарських підприємствах є відходи тваринництва, наприклад гній, зокрема, рідкий, пташиний послід, також кукурудзяний силос. Більшість біогазових установок працює з рідким гноєм великої рогатої худоби.Оскільки вміст сухої речовини, вуглеводів, жиру та протеїну в рідкому гної відносно низький, основнийсубстрат піддають коферментації так званими косубстратами, внаслідок чого підвищується виробництво біогазу.За результатами досліджень встановлено, що якість біогазу залежить від вмісту в ньому метану або від співвідношення між CH4 і диоксидом вуглецю (CО2), який розчиняє біогаз і спричиняє його втрати під час зберігання.Установлено, что хлорорганические пестициды в большей степени подвержены биоразложению в анаэробных условиях. Анаэробное компостирование проводят в специальных бетонных ямах или траншеях с гидроизоляцией, которые заполняют компостной массой (питательный субстрат, почва, пестициды и минеральная подкормка, возможно, дополнительное внесение отходов животного происхождения) с последующей заливкой ямы водой. Кислотность среды поддерживают в пределах рН 6–8, используя при необходимости известкования почв. Доказано, что для производства биогаза можно использовать все органические субстанции, обладающие свойством разлагаться. Основным субстратом для ферментации в сельскохозяйственных предприятиях являются отходы животноводства, например навоз, в частности жидкий, птичий помет, также кукурузный силос. Большинство биогазовых установок работает с жидким навозом крупного рогатого скота. Так как содержание сухого вещества, углеводов, жира и протеина в жидком навозе относительно низкий, основной субстрат подвергают коферментации так называемыми косубстратами, в результате чего повышается производство биогаза. По результатам исследований установлено, что качество биогаза зависит от содержания в нем метана или от соотношения между CH4 и диоксидом углерода (CO2), который растворяет биогаз и вызывает его потери при хранении.The authors have defined that organochlorine pesticides are more biodegradable in anaerobic conditions. Anaerobic composting is carried out in special concrete pits or gutters with waterproofing, which fill the compost mass (nutrient substrate, soil, pesticides and mineral nutrition, possibly adding animal waste), and then pour water into the well. The acidity of the medium is maintained within the pH range of 6–8, if necessary, using soil liming. It was investigated that it is possible to use all organic substances with properties of decomposition for biogas production. The main substrate for fermentation in agricultural enterprises is animal waste, such as manure, including liquid, bird pomp and corn silage. Most biogas plants operate with a rare bovine cattle bug. Since the content of dry matter, carbohydrates, fat and protein in the liquid manure is relatively low, the main substrate is subjected to coenzymes of so-called co-substrates, which leads to an increase in the production of biogas. Anaerobic composting is carried out in special concrete pits or trenches with waterproofing, which fill the compost mass (nutrient substrate, soil, pesticides and mineral nutrition, possibly additional animal waste) followed by pouring water into the well. According to the results of the research it is revealed that the quality of biogas depends on the content of methane in it or on the ratio between CH4 and carbon dioxide (CO 2), which dissolves biogas and causes its loss in storage. It has been shown that one of the ways to use organic waste is biogas technology, which makes it possible to obtain highly effective organic fertilizers and energy (biogas). It was found that anaerobic decomposition was an effective way to dispose of plants containing DDT in their tissues. The processes of using DDT contaminated phytomass of cultural and wild species of plants are investigated

Germline mutations in patients with oral mucosal leukoplakia and squamous cell carcinoma: a prospective observational study

Background. The number of studies devoted to the molecular genetics of oral mucosal leukoplakia and squamous cell carcinoma is small, while the obtained results are usually preliminary in nature. We can assume the existence of region-specific pathogenic genetic variants involved in the development of oral mucosal leukoplakia and squamous cell carcinoma. With the knowledge of such variants, it would become possible to develop PCR (polymerase chain reaction) and NGS (next-generation sequencing) test systems for the detection of clinically significant germline mutations.Objectives — to identify pathogenic germline genetic variants in patients with oral mucosal leukoplakia accompanied by grade 1 epithelial dysplasia, as well as oral mucosal squamous cell carcinoma, using new-generation sequencing.Methods. Study design: prospective, observational, cross-sectional, without a control group. The sample included patients (48 persons) of either sex (18 years of age or older) with the following proven and morphologically confirmed diagnoses: oral mucosal leukoplakia accompanied by grade 1 squamous intraepithelial neoplasia of epithelium (24 people) and oral mucosal squamous cell carcinoma (24 people), who sought medical care at the Vitebsk Regional Clinical Dental Center and Vitebsk Regional Clinical Oncological Center in 2019–2020. The identified pathogenic and presumably pathogenic genetic variants involved in the development of these diseases were quantitatively assessed. The study was conducted at the Shareable Core Facilities GENOME of the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus. In order to isolate deoxyribonucleic acid (DNA) from blood samples, a QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used. The preparation of DNA libraries and sequencing were carried out by means of an Illumina NextSeq 550 sequencing system (Illumina, Inc., USA) using an Illumina Nextera DNA Exome kit (USA). Bioinformatic analysis was conducted using Illumina BaseSpace specialized software (USA) and Galaxy Project (Galaxy Community, an international non-profit project) in accordance with current guidelines. The obtained data were statistically processed employing specialized software packages Statistica 12 (StatSoft, Inc., USA) and MedCalc 18.9.1 (MedCalc Software, Ltd, Belgium).Results. Next-generation whole-exome sequencing of deoxyribonucleic acid samples isolated from the blood of patients with oral mucosal leukoplakia and squamous cell carcinoma has been conducted in the Republic of Belarus for the first time. The total number of unique germline genetic variants in the exome of both groups of patients was shown to be very high, yet most of them were not pathogenic. In the examined patients, the majority of germline mutations were found to be localized only in 19 exome genes: MAP2K3, DNAH5, HSPG2, OBSCN, SYNE1, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-A, HLA-B, PKD1L2, TTN, AHNAK2, PDE4DIP, MUC3A, MUC4, MUC12, MUC16, and MUC17. In both clinical groups, the greatest number of genetic variants (> 40% of the total number) was detected in MUC3A, MUC4, MUC12, and MUC16, responsible for the synthesis of the glycoprotein mucin family.Conclusion. Oral mucosal leukoplakia and squamous cell carcinoma can arise from the pathogenic variants of MUC3A, MUC4, MUC12, and MUC16

In vitro rhizogenesis of sugar beet microclones

The features of rhizogenesis of male-sterile simple hybrids, maternal components of sugar beet heterozosis hybrid and O-types of Darinka variety grown from seeds were investigated. The paper presents the results of studying the main basic nutrient media (B5–A1, B5–A2, B5–A3, B5–A4, B5–A5 and B5–A6) for rhizogenesis, in which the content of macro- and microelements has been reduced by three times, the content of sucrose is reduced by almost 6 times, the amount of agar is reduced by almost five times, while the vitamin РР content is increased by 1.6 times, and the BAP is completely removed. The largest number of rooted microclones was obtained with NAAs by the high indexes of average number of roots and medium indexes of average roots length. To the second, by the number of rooted microclones is assigned, media of 2,4–D, 2,4–DB containing, potassium salt of NAA and IBA were classified, while IAA was characterized by a lower efficiency. The possibilities of regulation of growth and development processes of sugar beet in vitro explants in favor of undifferentiated growth at the stage of proliferation or organogenesis (hemo- and rhizogenesis) have been determined. To improve the quality of rooting of sugar beet plants-regenerants, we have developed the method for dimming agarized nutrient medium with methylene blue at a 0.05% concentration, which made it possible to reduce the inhibitory effect of light on the development of lateral roots. The average index of micro-roots rooting for MS-forms was 81.5 %. The technology of adaptation of micro-roots rooting was developed, in which the plant material at the initial stage of growth had slight morphological changes in the puffer apparatus and stem, but by the end of the vegetation, the plants acquired the appearance characteristic of the donor plants of explants. The clone’s resiliency is reached about 100% in the soil. According to the variability of morphological characteristics in reproduced in vitro sugar beet plants of the MS-forms of the Darynka hybrid, all the plants grown from the regenerants were more, than seed progeny from seed sowing of the same component obtained as a result of the attachment of sterility to the corresponding O-type. It has been found that in vitro cultivation has not weakened, and in some cases even increased the mitotic index of meristem cells of young roots of sugar beet. Most genotypes have reduced the number of pathological mitoses, apparently due to the activation of reparative systems, but did not extend the duration of individual phases of mitosis; without increasing the number of anaphase with bridges and fragments, but changed the number of anaphases with other chromosomal abnormalities. In all variants of the experiment, where activation of growth processes has been observed, the lowest variability of the signs is observed, that is, under the influence of stimulants, which are part of nutrient media, obviously there is unification of cell populations

РАСЧЕТ ЗАЩИЩЕННОСТИ СИГНАЛА ТИПА OFDM ОТ ПОМЕХ НЕЛИНЕЙНОГО ПРОИСХОЖДЕНИЯ

The method of calculation of the security OFDM signal from interference nonlinear origin is described in this article. Such method based on the use of a generic method definition products nonlinearity output paths passing electrical signals with complex (non-smooth) instant dynamic characteristics and polyharmonic and / or modulated input action.Рассмотрена методика расчета защищенности сигнала типа OFDM от помех нелинейного происхождения, основанная на использовании универсального метода определения продуктов нелинейности на выходе трактов прохождения электрических сигналов со сложными (негладкими) мгновенными динамическими характеристиками и полигармоническом и/или модулированном входном воздействии

К ВОПРОСУ СОЗДАНИЯ ИНФОРМАЦИОННОЙ БАЗЫ ДАННЫХ ПО НАДЕЖНОСТИ ОСНОВНОГО ОБОРУДОВАНИЯ ТЭС

The paper shows main approaches accepted for formation of database on reliability of heat-power equipment applied at thermal power stations. The used methods of probability theory and up-to-date computer technologies have made it possible to develop software required for database formation and which is operating in dialogue format. The database users can determine the most fragile units parts of boilers and turbines during the operational process, indices of their operation and apply these factors in their practical activity.Показаны основные подходы, принятые при создании информационной базы данных по надежности теплоэнергетического оборудования тепловых электрических станций.Использованные методы теории вероятностей и современные компьютерные технологии позволили создать программное обеспечение по формированию базы данных, работающей в диалоговом формате. Пользователи базы могут определить наиболее уязвимые в процессе эксплуатации узлы и детали котлов и турбин, определить показатели их работы и использовать эти факторы в своей практической деятельности

Lanthanoid-doped quaternary garnets as phosphors for high brightness cathodoluminescence-based light sources

Gadolinium-yttrium- aluminum-gallium garnets (GYAGG) doped and codoped with Eu, Tb, and Ce were manufactured as ceramics to develop long-wavelength phosphors for high-brightness white light sources based on cathodoluminescence (CL). The CL light yield (LY) of Tb-doped ceramics at high-intensity electron beam excitation is shown to be more than twice as high as that of the conventional phosphor YAG:Ce, whereas codoping with Eu to redshift the chromaticity results in reducing the LY approximately to the level of YAG:Ce. The LY might be substantially improved by using a mix of Tb- and Eu-doped GYGAG powders instead of a single codoped GYGAG to produce ceramic phosphor. The high LY is explained by favorable contribution of Gd sublattice in excitation transfer to activator ions. Chromaticity of phosphors GYGAG:Tb, Eu can be tuned in a wide range by varying the ratio of Tb to Eu concentration. They are radiation resistant and stabile in the temperature range from 300 to 450 K. © 2022 The Author(s)Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-11-2021-070, 075-15-2021-1353, FEUZ-2020-0060This work was supported by the Ministry of Science and Higher Education of the Russian Federation (FEUZ-2020-0060, No. 075-15-2021-1353 & 075-11-2021-070)

Methodology for generating a global forest management layer

The first ever global map of forest management was generated based on remote sensing data. To collect training data, we launched a series of Geo-Wiki (https://www.geo-wiki.org/) campaigns involving forest experts from different world regions, to explore which information related to forest management could be collected by visual interpretation of very high-resolution images from Google Maps and Microsoft Bing, Sentinel time series and normalized difference vegetation index (NDVI) profiles derived from Google Earth Engine. A machine learning technique was then used with the visually interpreted sample (280K locations) as a training dataset to classify PROBA-V satellite imagery. Finally, we obtained a global wall-to-wall map of forest management at a 100m resolution for the year 2015. The map includes classes such as intact forests; forests with signs of management, including logging; planted forests; woody plantations with a rotation period up to 15 years; oil palm plantations; and agroforestry. The map can be used to deliver further information about forest ecosystems, protected and observed forest status changes, biodiversity assessments, and other ecosystem-related aspects

Global forest management data for 2015 at a 100 m resolution

Spatially explicit information on forest management at a global scale is critical for understanding the status of forests, for planning sustainable forest management and restoration, and conservation activities. Here, we produce the first reference data set and a prototype of a globally consistent forest management map with high spatial detail on the most prevalent forest management classes such as intact forests, managed forests with natural regeneration, planted forests, plantation forest (rotation up to 15 years), oil palm plantations, and agroforestry. We developed the reference dataset of 226 K unique locations through a series of expert and crowdsourcing campaigns using Geo-Wiki (https://www.geo-wiki.org/). We then combined the reference samples with time series from PROBA-V satellite imagery to create a global wall-to-wall map of forest management at a 100 m resolution for the year 2015, with forest management class accuracies ranging from 58% to 80%. The reference data set and the map present the status of forest ecosystems and can be used for investigating the value of forests for species, ecosystems and their services