Specifity of central character’s image creation in L. Sterne’s work ‘The life and opinions of Tristram Shandy, gentleman’

The article deals with specifity of central character’s image creation in L. Sterne’s novel ‘The Life and Opinions of Tristram Shandy, Gentleman’

Hypoxia-inducible factor: basic biology and involvement in cardiovascular pathology

Molecular epidemiological studies conducted to date reveal a close relationship between the polymorphism of the HIF system genes with a wide range of cardiovascular, inflammatory, and oncological diseases. The study of the HIF system can contribute to the discovery of new targets and methods of pharmacological effects for the treatment of cardiovascular, oncological, rheumatological, and endocrinological patholog

Influence of the shape of the particles covering the metal surface on the dispersion relations of surface plasmons

Abstract The Green function method was used for calculation of dispersion relations of surface plasmon generated at the metal surface covered by ellipsoidal particles. The influence of the shape of the particles on the surface plasmon dispersion relations was studied. It was established that both s-and p-polarized surface plasmons can be excited at the surface covered by the particles. It was shown that the shape of the particles covering the surface strongly influences on the surface plasmons dispersion

Stimulation of reparation in a linear wound model in rats by Bischofit gel

The article is to evaluate Bischofit gel reparative activity in a linear wound model in rat

Клиническое наблюдение редкого варианта поражения лабиринта: опухоль эндолимфатического мешка

Endolymphatic sac tumors are rare neoplasms originating from the endolymphatic epithelium of the intraosseous part of the endolymphatic duct and sac, typically characterized by slow growth and local destructive changes. We present a case of an endolymphatic sac tumor in a 28-year-old man who consulted an otoneurologist with complaints of progressive hearing loss and dizziness attacks and was referred for a CT scan of the temporal bones and MRI of the inner ear with delayed contrast enhancement. The data of otoneurological and radiological examinations before and after surgical treatment and the results of surgical treatment with histological verification of the tumor are presented. The objective of this case presentation is to demonstrate the usefulness of CT and MRI methods in detecting an endolymphatic sac tumor, to compare the results of otoneurological and radiological examinations and intraoperative and histological data followed by surgery. Radiological examination revealed a neoplasm of the right temporal bone with typical imaging characteristics of endolymphatic sac tumor. Surgery was performed, the mass was removed completely, and the endolymphatic sac tumor was histologically verified. Radiologic presentation includes a typically located area of bone destruction in the petrous part of the temporal bone in the area of the vestibular aqueduct, possibly with the spread of the tumor into the cerebellopontine angle, with a heterogeneous structure, with uneven contrast enhancement. Due to the rarity of this pathology, diagnosis in the early stages is often difficult, and for the correct interpretation of radiologic findings in patients with hearing loss and dizziness, knowledge of the normal anatomy of the temporal bone and awareness of rare variants of its lesions are of key importance. Timely examination of patients with suspected temporal bone lesions and correct diagnosis are the key to successful treatment and maintaining the quality of life in this group of patients.Опухоли эндолимфатического мешка — это редкие новообразования, исходящие из эндолимфатического эпителия внутрикостной части эндолимфатического протока и мешка, типичными для них являются медленный рост и локальные деструктивные изменения. Нами представлено наблюдение опухоли эндолимфатического мешка у мужчины 28 лет, который обратился к отоневрологу с жалобами на прогрессирующее снижение слуха и приступы головокружения и был направлен на лучевое обследование в объеме МСКТ височных костей и МРТ внутреннего уха с отсроченным контрастированием. Приведены данные отоневрологического, лучевого обследования до и после оперативного лечения и результаты оперативного лечения с гистологической верификацией опухоли. Цель данного наблюдения — продемонстрировать возможности лучевой диагностики (КТ и МРТ) в выявлении опухоли эндолимфатического мешка, сопоставить результаты отоневрологического и лучевого обследования и интраоперационные и гистологические данные. При лучевом обследовании выявлено новообразование височной кости с типичными визуализационными характеристиками опухоли эндолимфатического мешка. Проведено оперативное лечение, образование удалено, верифицирована опухоль эндолимфатического мешка. Лучевая семиотика ОЭМ включает наличие типично расположенной зоны остеодеструкции в каменистой части височной кости в зоне расположения водопровода преддверия, возможно распространение опухолевого компонента в область мостомозжечкового угла, гетерогенной структуры, с неравномерным накоплением контрастного препарата. В связи с редкостью данной патологии диагностика на ранних стадиях часто затруднена, а для верной интерпретации изменений при лучевом обследовании пациентов со снижением слуха и головокружением, знание нормальной лучевой анатомии височной кости и информированность о редких вариантах ее патологии имеют ключевое значение. Своевременное обследование пациентов с подозрением на образование височной кости и правильная постановка диагноза являются залогом успешного лечения и сохранения качества жизни у данной группы пациентов

Methodological implementation of mixed linear models in multi-locus genome-wide association studies

The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS

TLR9 Agonist Protects Mice from Radiation-Induced Gastrointestinal Syndrome

Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption of mucosal barrier, bacterial invasion, inflammation and sepsis. Intestinal macrophages could recognize invading bacterial DNA via TLR9 receptors and transmit regenerative signals to the neighboring crypt. We therefore investigated whether systemic administration of designer TLR9 agonist could ameliorate RIGS by activating TLR9.Male C57Bl6 mice were distributed in four experimental cohorts, whole body irradiation (WBI) (8.4-10.4 Gy), TLR9 agonist (1 mg/kg s.c.), 1 h pre- or post-WBI and TLR9 agonist+WBI+iMyd88 (pretreatment with inhibitory peptide against Myd88). Animals were observed for survival and intestine was harvested for histological analysis. BALB/c mice with CT26 colon tumors in abdominal wall were irradiated with 14 Gy single dose of whole abdominal irradiation (AIR) for tumor growth study.Mice receiving pre-WBI TLR9 agonist demonstrated improvement of survival after 10.4 Gy (p<0.03), 9.4 Gy (p<0.008) and 8.4 Gy (p<0.002) of WBI, compared to untreated or iMyd88-treated controls. Post-WBI TLR9 agonist mitigates up to 8.4 Gy WBI (p<0.01). Histological analysis and xylose absorption test demonstrated significant structural and functional restitution of the intestine in WBI+TLR9 agonist cohorts. Although, AIR reduced tumor growth, all animals died within 12 days from RIGS. TLR9 agonist improved the survival of mice beyond 28 days post-AIR (p<0.008) with significant reduction of tumor growth (p<0.0001).TLR9 agonist treatment could serve both as a prophylactic or mitigating agent against acute radiation syndrome and also as an adjuvant therapy to increase the therapeutic ratio of abdominal Radiation Therapy for Gastro Intestinal malignancies

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

Background: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells.Methods: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies.Results: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model.Conclusions: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer.Peer reviewedBiochemistry and Molecular Biolog

Профілактика, діагностика, лікування абсцесів та інфільтратів черевної порожнини у дітей

Objective. To improve the results of treatment of children with acute surgical disorders by the way of improving diagnostic procedures and surgical techniques and also postoperative rehabilitation of patients. Patients and methods. Results of treatment of 261 children with circumscribed forms of peritonitis are analyzed. The main group consisted of children who were treated in 2004-2013 years, control group - in the 1994-2003 years. For all children was used a set of clinical and laboratory investigations, including determination of leukocyte indices. For the improvement of the early diagnosis of abscesses and infiltrates of the abdomen were used ultrasonography, computed tomography and laparoscopy. Results. In children were dominate primary circumscribed peritonitis - 196 (75%) patients. As in primary so in secondary delineated peritonitis were predominated early forms of the disease. Abdominal abscesses in children dominated in 184 (70.5%) patients, and infiltrates diagnosed in 77 (29.5%) patients. The development of complications of peritonitis most often occurs in the age period from 11 to 14 years - 99 (37.9%) children. Infiltrates and abdominal abscesses in 1.5 times more often occur in boys. Conclusions. The clinical picture of peritonitis often has disguised character that requires additional methods of examination. The use of clinical and laboratory, modern radiological diagnostic methods allow improved the results of the diagnosis and treatment of patients and significantly reduce the number of postoperative septic complications. Key words: acute appendicitis, abdominal abscess, infiltration of the abdominal cavity, delimited peritonitis. Цель: улучшить результаты лечения детей с острой хирургической патологией путем усовершенствования диагностических мероприятий и хирургических технологий, и послеоперационную реабилитацию больных. Пациенты и методы. Проанализированы результаты лечения 261 ребенка с отграниченными формами перитонита. Основную группу составили дети, пролеченные в 2004–2013 гг., контрольную — в 1994–2003 годах. Всем детям применяли комплекс клинико-лабораторных исследований, в том числе определение лейкоцитарных индексов. Для улучшения ранней диагностики абсцессов и инфильтратов брюшной полости применяли ультрасонографию, компьютерную томографию, лапароскопию. Результаты. У детей преобладают первичные отграниченные перитониты — 196 (75%) пациентов. Как при первичных, так и при вторичных отграниченных перитонитах превалируют ранние формы заболевания. У детей преобладали абсцессы брюшной полости — 184 (70,5%) пациента, а инфильтраты диагностировали у 77 (29,5%) пациентов. Развитие осложнений перитонита чаще всего происходит в возрастном периоде от 11 до 14 лет — 99 (37,9%) детей. Инфильтраты и абсцессы брюшной полости в 1,5 раза чаще возникают у мальчиков. Выводы. Клиническая картина перитонита часто замаскирована, что требует дополнительных методов обследования. Применение клинико-лабораторных, современных лучевых методов диагностики позволило улучшить результаты диагностики и лечения больных и значительно сократить количество послеоперационных гнойно-септических осложнений. Ключевые слова: острый аппендицит, абсцесс брюшной полости, инфильтрат брюшной полости, отграниченный перитонит. Мета: поліпшити результати лікування дітей з гострою хірургічною патологією шляхом удосконалення діагностичних заходів та хірургічних технологій, та післяопераційну реабілітацію хворих. Пацієнти і методи. Проаналізовано результати лікування 261 дитини з відмежованими формами перитоніту. Основну групу склали діти, що пройшли лікування у 2004–2013 рр., контрольну — у 1994–2003 роках. Усім дітям застосовували комплекс клініко-лабораторних досліджень, у тому числі визначення лейкоцитарних індексів. Для поліпшення ранньої діагностики абсцесів та інфільтратів черевної порожнини застосовували ультрасонографію, комп'ютерну томографію, лапароскопію. Результати. У дітей переважають первинні відмежовані перитоніти — 196 (75%) пацієнтів. Як при первинних, так і при вторинних відмежованих перитонітах, превалюють ранні форми захворювання. У дітей превалювали абсцеси черевної порожнини — 184 (70,5%) пацієнти, а інфільтрати діагностували у 77 (29,5%) пацієнтів. Розвиток ускладнень перитоніту найчастіше відбувається у віковому періоді від 11 років до 14 років — 99 (37,9%) дітей. Інфільтрати та абсцеси черевної порожнини у 1,5 разу частіше виникають у хлопчиків. Висновки. Клінічна картина перитоніту часто замаскована, що вимагає додаткових методів обстеження. Застосування клініко-лабораторних, сучасних променевих методів діагностики дозволило покращити результати діагностики та лікування хворих та значно зменшити кількість післяопераційних гнійно-септичних ускладнень. Ключові слова: гострий апендицит, абсцес черевної порожнини, інфільтрат черевної порожнини, відмежований перитоніт.

CALCULATION OF EFFORTS OF DIGGING BY THE WORKING EQUIPMENT OF THE BULLDOZER

In the work a new design of the working equipment of the bulldozer is considered, which makes it possible to increase productivity, by capturing and transporting an extra blade of two pile at once. In this connection, it was necessary to compile a design scheme for determining the resistance to digging an extra blade. Was received the graph of the force dependence on the rod of the hydraulic cylinder from the stroke of the rod, when digging an additional blade