The “third body” approach to joining of metals by simple shear under pressure

A continuum mechanics approach to cold welding (CW) of metals under shear is considered. The main idea is to treat a weld joint as an extra material-a “third body” in its own right. Its properties stem from plastic co‐deformation of the two contacting alloys. The mechanical characteristics of the weld joint, i.e., its strength and plasticity in the complex stress state, are determined by the deformation history of the “third body.” The proposed approach enables a unified description of the CW process itself, as well as the subsequent variation of shape of the composite material with the weld joint.Volkswagen Foundatio

Геологическое строение, нефтегазоносность и подсчет запасов газа пласта ПК1 Антипаютинского газового месторождения (ЯНАО)

На основе комплексной интерпретации данных сейсморазведки 3D, данных ГИС и испытания пласта в разведочных скважинах обосновано геологическое строение газовой залежи пласта ПК1 Антипаютинского месторождения. Проведен обобщающий анализ результатов лабораторных исследований кернов, пластовых флюидов, промыслово-геофизических и газогидродинамических исследований изучаемого объекта. Построены карты кровли коллекторов пласта ПК1, поверхности межфлюидного контакта, эффективных газонасыщенных толщин пласта. Дано обоснование подсчётных параметров, определяемых по данным ГИС (коэффициенты пористости, газонасыщенности, эффективные газонасыщенные толщины). На основе построенной детальной геологической модели проведён дифференцированный подсчёт запасов газа.On the basis of complex interpretation this seismic exploration 3D, data of GIS and test of layer in prospecting wells the geological structure of a gas deposit of PK1 layer of the Antipayutinsky field is proved. The generalizing analysis of results of laboratory researches of cores, formation fluids, trade and geophysical and gas-hydrodynamic researches of the studied object is carried out. Cards of a roof of collectors of PK1 layer, a surface of interfluid contact, effective gas-saturated thickness of layer are constructed. Justification of the subcalculating parameters determined by data of GIS (coefficients of porosity, gas saturation, effective gas-saturated thickness) is given. On the basis of the constructed detailed geological model the differentiated calculation of reserves of ga

Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells

Aptamers represent an emerging strategy to deliver cargo molecules, including dyes, drugs, proteins or even genes, into specific target cells. Upon binding to specific cell surface receptors aptamers can be internalized, for example by macropinocytosis or receptor mediated endocytosis. Here we report the in vitro selection and characterization of RNA aptamers with high affinity (Kd = 20 nM) and specificity for the human IL-6 receptor (IL-6R). Importantly, these aptamers trigger uptake without compromising the interaction of IL-6R with its natural ligands the cytokine IL-6 and glycoprotein 130 (gp130). We further optimized the aptamers to obtain a shortened, only 19-nt RNA oligonucleotide retaining all necessary characteristics for high affinity and selective recognition of IL-6R on cell surfaces. Upon incubation with IL-6R presenting cells this aptamer was rapidly internalized. Importantly, we could use our aptamer, to deliver bulky cargos, exemplified by fluorescently labeled streptavidin, into IL-6R presenting cells, thereby setting the stage for an aptamer-mediated escort of drug molecules to diseased cell populations or tissues

Systematic identification of MACC1-driven metabolic networks in colorectal cancer

MACC1 is a prognostic and predictive metastasis biomarker for more than 20 solid cancer entities. However, its role in cancer metabolism is not sufficiently explored. Here, we report on how MACC1 impacts the use of glucose, glutamine, lactate, pyruvate and fatty acids and show the comprehensive analysis of MACC1-driven metabolic networks. We analyzed concentration-dependent changes in nutrient use, nutrient depletion, metabolic tracing employing (13)C-labeled substrates, and in vivo studies. We found that MACC1 permits numerous effects on cancer metabolism. Most of those effects increased nutrient uptake. Furthermore, MACC1 alters metabolic pathways by affecting metabolite production or turnover from metabolic substrates. MACC1 supports use of glucose, glutamine and pyruvate via their increased depletion or altered distribution within metabolic pathways. In summary, we demonstrate that MACC1 is an important regulator of metabolism in cancer cells

Elevated Flt3L predicts long-term survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms

BACKGROUND: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predictive surrogate marker of host tumoral immune response and might enable the stratification of patients with otherwise comparable tumor features. METHODS: We evaluated Flt3L gene expression in tumor tissue as well as circulating Flt3L levels as potential biomarkers in a cohort of 54 patients with GEP-NEN. RESULTS: We detected a prominent induction of Flt3L gene expression in individual G2 and G3 NEN, but not in G1 neuroendocrine tumors (NET). Flt3L mRNA expression levels in tumor tissue predicted the disease-related survival of patients with highly proliferative G2 and G3 NEN more accurately than the conventional criteria of grading or NEC/NET differentiation. High level Flt3L mRNA expression was associated with the increased expression of genes related to immunogenic cell death, lymphocyte effector function and dendritic cell maturation, suggesting a less tolerogenic (more proinflammatory) phenotype of tumors with Flt3L induction. Importantly, circulating levels of Flt3L were also elevated in high grade NEN and correlated with patients' progression-free and disease-related survival, thereby reflecting the results observed in tumor tissue. CONCLUSIONS: We propose Flt3L as a prognostic biomarker for high grade GEP-NEN, harnessing its potential as a marker of an inflammatory tumor microenvironment. Flt3L measurements in serum, which can be easily be incorporated into clinical routine, should be further evaluated to guide patient stratification and treatment decisions

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo

BACKGROUND: Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors such as bortezomib. METHODS AND RESULTS: In this study, we assessed several combined treatment modalities in vitro and in vivo. By cell-based functional analyses, in a 3D in ovo and an orthotopic mouse model, we demonstrated sensitizing effects of bortezomib combined with cisplatin, radiation and peptide receptor radionuclide therapy (PRRT). By gene expression profiling and western blot, we explored the underlying mechanisms, which resulted in an impaired DNA damage repair. Therapy-induced DNA damage triggered extrinsic proapoptotic signaling as well as the induction of cell cycle arrest, leading to a decreased vital tumor volume and altered tissue composition shown by magnetic resonance imaging and F-18-FDG-PET in vivo, however with no significant additional benefit related to PRRT alone. CONCLUSIONS: We demonstrated that bortezomib has short-term sensitizing effects when combined with DNA damaging therapy by interfering with DNA repair in vitro and in ovo. Nevertheless, due to high tumor heterogeneity after PRRT in long-term observations, we were not able to prove a therapeutic advantage of bortezomib-combined PRRT in an in vivo mouse model

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? – A preclinical assessment in vitro and in vivo

Background: Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors suc

Совершенствование системы вознаграждения персонала бюджетного учреждения на основе комплексной оценки его деятельности

Объектом исследования является МБОУ 슫СОШ № 18슻 Цель работы - является оценка системы вознаграждения труда персонала бюджетного учреждения, ее оптимизации на основе комплексной оценке его деятельности В процессе исследования проводились способы группировки и сравнения, графические и аналитические методы. В результате исследования были выявлены недостатки и предложен комплекс мер по их устранению. Степень внедрения: сделать систему оплаты труда взаимосвязанной с конкретным результатом каждого работника и учреждения в целом. Область применения: бюджетные учреждения. Экономическая эффективность работы заключается в объективной оценке оплаты труда в бюджетном учреждении и в разработке практических рекомендаций по совершенствованию системы оплаты труда в анализируемом учреждении.The object of study is MBOU "SOSH № 18" Purpose - is to assess the remuneration system of the personnel budget of the institution, its optimization on the basis of a comprehensive assessment of its activities In the process of investigation the methods of grouping and comparison of graphical and analytical methods. The study revealed shortcomings and proposed the complex of measures on their elimination. Level of implementation: to make the wage system is interconnected with the concrete result of each employee and the institution as a whole. Scope: budget companies. Economic efficiency is an objective assessment of remuneration in budgetary institutions and in the development of practical recommendations for improving the system of remuneration in the analyzed institution