Controlling Boron Diffusion during Rapid Thermal Annealing with CoImplantation by Amphoteric Impurity Atoms

A model for simulating the rapid thermal annealing of silicon structures implanted with boron and carbon is developed. The model provides a fair approximation of the process of boron diffusion in silicon, allowing for such effects as the electric field, the impact of the implanted carbon, and the clustering of boron. The migration process of interstitials is described according to their drift in the field of internal elastic stress

Notes on Stein-Sahi representations and some problems of non L2L^2 harmonic analysis

We discuss one natural class of kernels on pseudo-Riemannian symmetric spaces.Comment: 40p

Мутации в гене PIK3CA при раке молочной железы с низкой экспрессией белка HER2 / neu

Introduction. Disturbances in the PI3K-dependent (PI3K – phosphoinositide 3‑kinase) cascade are characteristic of all types of breast cancer. In particular, 30–40 % of patients with advanced / metastatic hormone-positive HER2‑negative (HER2 – human epidermal growth factor receptor 2) breast cancer carry PIK3CA mutations in tumor cells. The detection of these mutations in patients with hormone-positive HER2‑negative breast cancer is of great clinical importance, since they are a predictor of tumor sensitivity to the PI3K inhibitor alpelisib. According to the HER2 / neu protein expression status, all patients with hormone-positive HER2‑negative breast cancer can be divided into two groups – with low expression of HER2 / neu (scores 0, 1+ or 2+ per immunohistochemical analysis and negative result of in situ hybridization) and with a complete lack of expression of this protein.Aim. To establish whether there are differences in the nature and prevalence of PIK3CA mutations in patients in these two groups.Materials and methods. The study was carried out on 32 breast cancer samples with a luminal HER2‑negative immunophenotype, which were divided into two groups – with low HER2 / neu expression (n = 15) and with a complete absence of HER2 / neu expression (n = 17). PIK3CA mutations were determined using the commercially available cobas PIK3CA MutationTest kit (Roche, Switzerland) by real-time polymerase chain reaction on paraffin block material (tissue biopsy).Results. Mutations of the PIK3CA gene were detected in 37.5 % of cases, of which p.E542K mutation was detected in 2 cases; p.E545X – in 3, p.H1047X – in 6 and p.N345K – in 1. Analysis of the mutational status of both groups revealed statistically significant differences in the quantitative distribution of PIK3CA mutations. The frequency of PIK3CA mutations was significantly higher in tumors with low expression of HER2 / neu (p = 0.0268). Thus, characteristic genetic changes have been identified for a group of patients with HER2‑low breast cancer. These changes are potential targets for therapy, which is important for clinical practice, as it opens up new therapeutic possibilities for breast cancer patients with low HER2 / neu expression.Введение. Нарушения в PI3K-зависимом каскаде (PI3K – фосфоинозитид-3-киназа) характерны для всех типов рака молочной железы (РМЖ). В частности, 30–40 % пациенток с распространенным / метастатическим гормонпозитивным HER2-отрицательным (HER2 – human epidermal growth factor receptor 2; рецептор эпидермального фактора роста, тип 2) РМЖ несут мутации PIK3CA в опухолевых клетках. Обнаружение этих мутаций у пациенток с гормон-позитивным HER2-отрицательным РМЖ имеет большое клиническое значение, поскольку они являются предиктором чувствительности опухоли к ингибитору PI3K алпелисибу. По статусу экспрессии белка HER2 / neu всех больных с гормон-позитивным HER2-отрицательным РМЖ можно разделить на 2 группы: с низкой экспрессией HER2 / neu (оценками 0, 1+ или 2+ по данным иммуногистохимического исследования и отрицательным результатом гибридизации in situ) и отсутствием экспрессии этого белка.Цель работы – установить, существуют ли различия в характере и распространенности мутаций в гене PIK3CA у пациентов с низкой экспрессией HER2 / neu и отсутствием экспрессии этого белка.Материалы и методы. Исследованы 32 образца люминального HER2-отрицательного иммунофенотипа РМЖ, которые по характеру экспрессии HER2 / neu разделены на 2 группы: с низкой экспрессией HER2 / neu (n = 15) и ее отсутствием (n = 17). Наличие мутаций в гене PIK3CA определяли с помощью коммерчески доступного набора cobas PIK3CA MutationTest (Roche, Швейцария) методом полимеразной цепной реакции в режиме реального времени на материале из парафиновых блоков (тканевой биопсии).Результаты. Мутации в гене PIK3CA выявлены в 37,5 % случаев, из них в 2 случаях определена мутация p.E542K, в 3 – p.E545Х, в 6 – p.H1047Х, в 1 – p.N345K. При анализе мутационного статуса обеих групп обнаружены статистически значимые различия по количественному распределению мутаций в гене PIK3CA. Частота этих мутаций была достоверно выше в опухолях с низкой экспрессией HER2 / neu (р = 0,0268).Заключение. Таким образом, выявлены характерные генетические изменения у пациенток с РМЖ с низкой экспрессией HER2 / neu. Эти изменения являются потенциальными мишенями для таргетной терапии, что важно для клинической практики, поскольку открывает новые возможности в лечении больных РМЖ с низкой экспрессией HER2 / neu

Prognostic role of hemostasis-regulating genetic factors and their interaction with conventional risk factors at the early stages of coronary heart disease development

Aim. To investigate the prognostic role of selected single nucleotide polymorphisms in hemostasis-regulating genes and to clarify their interaction with conventional risk factors, RF (smoking, arterial hypertension (AH), hypercholesterolemia (HCH), obesity (O)) at the early stages of coronary heart disease (CHD) development, with or without subsequent myocardial infarction (MI). Material and methods. The study included 977 men aged 20–55 years: 375 CHD patients (189 and 186 with or without previous MI, respectively) and 602 individuals without cardiovascular disease (CVD). Exclusion criteria were diabetes mellitus and impaired glucose tolerance. The authors analysed the polymorphisms of thrombocyte receptor genes GPIa (C807T) and GPIIIa (PLA1/PLA2); coagulation and fibrinolytic protein genes for factor VII (R353Q) and factor XIII (V34L); and the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism. The association of these polymorphisms with conventional RF (smoking, AH, HCH, and O) was also investigated. To identify genetic variations, a restriction fragment length polymorphism assay, allele-specific assay, and fluorescence primer-probe assay were used. Results. Increased CHD risk was associated with the TT genotype of GPIa (p=0,0001; OR=10,2). The LL genotype of FXIII (p=0,03; OR=0,48) and QQ genotype of FVII (p=0,01; OR=0,12) were linked to reduced CHD risk. The combination of FXIII L allele and FVII Q allele was associated with a lower MI risk in CHD patients (p=0,03; OR=0,33). In participants with HCH, the PLA2/PLA2 genotype of GPIIIa was linked to increased MI risk for CHD patients (p=0,01; OR=6,0). Conclusion. The algorithm for predicting the genetic CHD risk may incorporate the assessment of the genetic polymorphism of GPIa (C807T), GPIIIa (PLA1/PLA2), factor XIII (V34L), and factor VII (R353Q). The study results did not confirm the negative effect of the PAI-1 gene 4G/5G polymorphism on CHD risk

Specific features of embryonic development of Trichuris skrjabini (Baskakov, 1924) nematode eggs parasitizing in sheep

Specific features of embryonic development of eggs isolated from gonads of Trichuris skrjabini nematodes females, obtained during helminthological opening in sheep, were studied. It is proved that during the growth and development of this species of trichurises eggs there are significant changes in the metric indices of their length and width, as well as in the length and width of their lids. It is determined that at 27 °С in laboratory conditions T. skrjabini eggs become infectious during 51 days with survival rate of 80.0±0.82 % (20.0±0.81% of eggs stop in development and subsequently die). The embryogenesis process has six morphologically distinct stages: protoplast (from the 1st to the 12th day); blastomeres formation (from the 6th to the 24th day); bean-like embryo (from the 12th to the 33d day), tadpole-like embryo (from the 15th to the 36th day); larval formation (from the 27th to the 48th day); and mobile larva (from the 27th to the 51st day). The development of T. skrjabini eggs to the infectious stage in laboratory conditions is characterized by their lengthening to 75.7±0.36 μm (by 2.0%, р < 0.05), narrowing to 37.3±0.30 μm (by 2.4%, р < 0.05) and lengthening to 12.2±0.42 μm (by 16.4%, р < 0.01) and thinning to 12.1±0.10 μm (by 5.5 %, р < 0.01) of the egg lids. The changes of egg shell thickness were not statistically significant. Considering the data on the morphological structure and the period of nematodosis pathogens eggs development it is possible to plan the time of taking measures to prevent and control trichurosis in sheep

The Efficacy of HGF/VEGF Gene Therapy for Limb Ischemia in Mice with Impaired Glucose Tolerance: Shift from Angiogenesis to Axonal Growth and Oxidative Potential in Skeletal Muscle

Background: Combined non-viral gene therapy (GT) of ischemia and cardiovascular disease is a promising tool for potential clinical translation. In previous studies our group has developed combined gene therapy by vascular endothelial growth factor 165 (VEGF165) + hepatocyte growth factor (HGF). Our recent works have demonstrated that a bicistronic pDNA that carries both human HGF and VEGF165 coding sequences has a potential for clinical application in peripheral artery disease (PAD). The present study aimed to test HGF/VEGF combined plasmid efficacy in ischemic skeletal muscle comorbid with predominant complications of PAD-impaired glucose tolerance and type 2 diabetes mellitus (T2DM). Methods: Male C57BL mice were housed on low-fat (LFD) or high-fat diet (HFD) for 10 weeks and metabolic parameters including FBG level, ITT, and GTT were evaluated. Hindlimb ischemia induction and plasmid administration were performed at 10 weeks with 3 weeks for post-surgical follow-up. Limb blood flow was assessed by laser Doppler scanning at 7, 14, and 21 days after ischemia induction. The necrotic area of m.tibialis anterior, macrophage infiltration, angio- and neuritogenesis were evaluated in tissue sections. The mitochondrial status of skeletal muscle (total mitochondria content, ETC proteins content) was assessed by Western blotting of muscle lysates. Results: At 10 weeks, the HFD group demonstrated impaired glucose tolerance in comparison with the LFD group. HGF/VEGF plasmid injection aggravated glucose intolerance in HFD conditions. Blood flow recovery was not changed by HGF/VEGF plasmid injection either in LFD or HFD conditions. GT in LFD, but not in HFD conditions, enlarged the necrotic area and CD68+ cells infiltration. However, HGF/VEGF plasmid enhanced neuritogenesis and enlarged NF200+ area on muscle sections. In HFD conditions, HGF/VEGF plasmid injection significantly increased mitochondria content and ETC proteins content. Conclusions: The current study demonstrated a significant role of dietary conditions in pre-clinical testing of non-viral GT drugs. HGF/VEGF combined plasmid demonstrated a novel aspect of potential participation in ischemic skeletal muscle regeneration, through regulation of innervation and bioenergetics of muscle. The obtained results made HGF/VEGF combined plasmid a very promising tool for PAD therapy in impaired glucose tolerance conditions

Controlling Boron Diffusion during Rapid Thermal Annealing with CoImplantation by Amphoteric Impurity Atoms

A model for simulating the rapid thermal annealing of silicon structures implanted with boron and carbon is developed. The model provides a fair approximation of the process of boron diffusion in silicon, allowing for such effects as the electric field, the impact of the implanted carbon, and the clustering of boron. The migration process of interstitials is described according to their drift in the field of internal elastic stress