Influence of stress ratio on residual stress evolution near cold-expanded hole due to low-cycle fatigue by crack compliance data

Modified version of the crack compliance method is used for determination of stress intensity factor (SIF) related to narrow notches emanating from cold-expanded holes. These notches are inserted at different stages of low-cycle fatigue under constant external load. It is shown how residual SIF values, generated by residual stress field influence, can be separated from total experimental SIF values. Residual SIF values, obtained at different stage of low-cycle fatigue with the same stress range Δσ  = 350 MPa but different stress  R = –0.4 and  R = –1.0, provide quantitative description of residual stress evolution near cold-expanded hole. It shown that maximal residual stress relaxation of order 20 per cent occurs at 95 lifetime per cent for both loading programs

Damage accumulation near the cold-expanded hole due to high-cycle fatigue by crack compliance method

The novel destructive method is implemented for quantitative assessment of fatigue damage accumulation in the stress concentration zone accompanied by residual stress due to cold expansion of the through-thickness hole. Damage accumulation is reached by preliminary cyclic loading of plane specimens with cold-expanded holes. Narrow notches, emanating from the hole edge at different stages of high-cycle fatigue, serve to manifest a damage level. These notches are inserted without applying external load. Deformation response to local material removing, caused by pure residual stress influence, is measured by electronic speckle pattern interferometry (ESPI) in terms of in-plane displacement components. Normalized values of the notch mouth open displacement (NMOD), in-plane displacement component at the initial point of the notch acting in the notch direction (U0), in-plane displacement component at the final point of the notch acting in the notch direction (U1) and the stress intensity factor (SIF) are used as current damage indicators. Numerical integration of curves, describing an evolution of each fracture mechanics parameter over lifetime, produces the damage accumulation function in an explicit form. It is established that all four fracture mechanics parameters give very close results

Quantitative description of low-cycle fatigue damage accumulation in contact interaction zone by local strain evolution

The novel non-destructive method for quantitative description of low-cycle fatigue damage accumulation is expanded to a case of contact interaction in the stress concentration area. Investigated objects are plane aluminium specimens with the centred hole filled by cylindrical steel inclusion. The specimen is subjected to cyclic pull-push loading. The key point, that defines scientific novelty and powerfulness of the developed approach, consists of involving local deformation parameters as current damage indicators. Required strain values follow from distributions of all three displacement components along the filled hole edge measured by reflection hologram interferometry. The data, which are derived at different stages of low-cycle fatigue for the single specimen, provide normalized dependencies of local strain values from number of loading cycle, which are a source of damage accumulation functions. These functions are constructed for the specimen with the filled hole and geometrically analogous specimen with the open hole. Obtained data quantitatively describe a difference in damage accumulation rates for two cases.     &nbsp

Residual stresses near cold-expanded hole at different stages of high-cycle fatigue by crack compliance data

Experimental method for a characterization of high-cycle fatigue evolution of residual stress near cold-expanded hole is developed and implemented. The technique is based on simultaneous measurements of deformation response to narrow notch, inserted in residual stress field, on opposite specimen’s faces by electronic speckle-pattern interferometry (ESPI). Two-side measurements of notch opening displacements are performed when a single notch, emanating from cold-expanded hole edge, is inserted. The transition from in-plane displacement component to residual stress intensity factor (SIF) values follows from the relationships of modified version of the crack compliance method. The approach provides a difference in residual stress values referred to mandrel entrance and exit surface. Notches are inserted at different stages of low-cycle fatigue without applying external load. The results obtained describe fine nuances of residual stress evolution, which cannot be considered as monotonic relaxation

The effect of low-cycle fatigue on evolution of fracture mechanics parameters in residual stress field caused by cold hole expansion

Localized displacement measurements based on electronic speckle-pattern interferometry are used to obtain crack mouth opening displacement (CMOD), stress intensity factor (SIF) and T-stress values during crack growth around cold-expanded holes. The specimens with a central open hole are made from 2024 aluminium alloy. The expansion level is 5% of nominal interference. The results are obtained for the same stress range   = 350 MPa, but different stress ratio R = –0.4 and R = –1.0. A sequence of narrow notches, inserted under the constant external load, serves for crack modelling at different stages of cyclic loading. Initial experimental data represent in-plane displacement component values measured in the vicinity of the crack tip. The transition from in-plane displacement components to SIF and T-stress values follows from the relationships of modified version of the crack compliance method. The crack length curves of CMOD, SIF and T-stress profiles are obtained for different stages of cyclic loading. These data provide the construction of dependencies of fracture mechanics parameters for cracks of fixed lengths from the loading cycle number

Liver Disease and Hemostasis (Review) Part 2. Cholestatic Liver Disease and Hemostasis

The presence or development of liver disorders can significantly complicate the course of critical illness and terminal conditions. Systemic hemostatic disorders are common in Intensive Care Units patients with cholestatic liver diseases, so the study of the mechanisms of their development can contribute to the understanding of the development of multiorgan failure in critical illness.The review discusses current data on changes in hemostatic parameters in patients with cholestatic liver diseases, proposes a mechanism for the development of such disorders, which involve interactions of phospholipids with platelet and endotheliocyte membranes. It is suggested that a trend for thrombosis in patients with cholestatic liver disease is due to increased accumulation of bile acids in the systemic circulation. Available data demonstrate that the antiphospholipid syndrome may predispose to the formation of blood clots due to alterations of phospholipid composition of membranes of platelets and vascular endothelial cells by circulating antiphospholipid antibodies. Clarifying the mechanisms contributing to changes of the blood coagulation system parameters in liver disorders will aid to development of optimal correction of hemostatic disorders in patients with chronic liver diseases

Зависимость течения и исхода сепсиса от генетического варианта 3`-области гена аквапорина 4 (AQP4) и коморбидности

Aquaporins 4 and 5 are proteins that form water channels in the cell membrane, participate in the transfer and migration of immune cells, being expressed on many cell types including CNS astrocytes, kidney cells, lungs, and the immune system. We have previously shown that AQP5 genetic polymorphism is associated with different outcomes of abdominal sepsis. Since another common aquaporin protein, AQP4, is also expressed on the surface of immunocompetent cells, determining cell motility, it was suggested that AQP4 may also be important in the pathogenesis of sepsis, and that AQP4 polymorphism may predetermine sepsis severity and outcome. AQP4 rs1058427 genetic polymorphism has not been studied earlier.The aim of the study was to determine the effects of region 3` polymorphism in the AQP4 gene on the clinical course and outcome of sepsis.Materials and methods. The prospective study included 290 ICU patients from three clinical hospitals in Moscow aged 18-75 years with clinical signs of sepsis (SEPSIS-3, 2016).Results. It was found that the minor T allele of the AQP4 rs1058427 gene provides strong protection against septic shock, as among GG genotype carriers septic shock developed in 66%, but in presence of the minor T allele this number dropped two-fold (p=0.009, Fisher’s exact test, OR=1.99, 95% CI: 1.12-3.55, n=290). There was a significant association between AQP4 rs1058427 genetic polymorphism and 30-day hospital mortality in a subgroup of patients with more severe organ dysfunction and higher comorbidity burden (cardiovascular diseases, type II diabetes mellitus) requiring extracorporeal treatment modalities and ventilator support for 5 or more days (n=66). Carriers of the minor T allele showed better survival rates as compared AQP4 rs1058427 GG genotype carriers (5 deaths out of 10 and 47 deaths out of 56, respectively, p=0.003, Fisher’s exact test, n=66, OR=5.22, 95% CI: 1.25-21.82, P=0.009, log-rank criterion).Conclusion. The minor AQP4 rs1058427 T allele is associated with protection against septic shock and better survival in sepsis in a group of ICU patients with high comorbidity burden requiring extracorporeal life support interventions.Аквапорины 4 и 5 - белки, образующие водный канал в мембране клетки, участвующие в движении и миграции иммунных клеток и выявляющиеся на поверхности астроцитов ЦНС, клеток почек, легких, иммунной системы. Ранее мы показали, что генетический полиморфизм AQP5 ассоциируется с различными исходами абдоминального сепсиса. Поскольку другой распространенный аквапорин - белок AQP4 тоже экспрессируется на поверхности иммунокомпетентных клеток, определяя клеточную подвижность, предположили, что и он может иметь значение в патогенезе сепсиса, а полиморфизм AQP4 - определять тяжесть течения и исход сепсиса. Ранее генетический полиморфизм AQP4 rs1058427 при сепсисе не исследовали.Целью исследования явилось определение вклада полиморфизма 3`-области гена AQP4 в течение и исход сепсиса.Материалы и методы. В проспективное исследование включили 290 пациентов ОРИТ трех клинических больниц г. Москвы в возрасте 18-75 лет с клиническими признаками сепсиса (СЕПСИС-3, 2016).Результаты. Обнаружили, что минорный аллель T гена AQP4 rs1058427 защищает от развития септического шока при сепсисе. Среди пациентов-носителей генотипа GG септический шок развился у 66 %, у пациентов с минорной аллелью T – только в половине случаев (Р=0,009, ТМФ, ОШ=1,99, 95% ДИ: 1,12-3,55, n=290). В группе пациентов с более тяжелыми органными нарушениями и высокой частотой коморбидных состояний (сердечно-сосудистые заболевания, сахарный диабет второго типа), нуждающихся в экстракорпоральных методов лечения и находившихся на ИВЛ 5 и более суток (n=66), была обнаружена значимая ассоциация генетического полиморфизма AQP4 rs1058427 и 30-дневной госпитальной летальности. Носители минорного аллеля T выживали чаще по сравнению с пациентами генотипа AQP4 rs1058427 GG (5 летальных исходов из 10 и 47 летальных исходов из 56, соответственно, P=0,003, ТМФ, n=66, ОШ=5,22, 95% ДИ: 1,25- 21,82, P=0,009, лог-ранговый критерий). Заключение. Минорный аллель AQP4 rs1058427 T ассоциируется с защитой от развития септического шока и лучшей выживаемостью при сепсисе в группе пациентов ОРИТ с выраженной коморбидностью и нуждающихся в экстракорпоральных методах жизнеобеспечения

Differential contribution of the m7G-cap to the 5′ end-dependent translation initiation of mammalian mRNAs

Many mammalian mRNAs possess long 5′ UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5′ UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5′ UTRs with so-called ‘cellular IRESes’ demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5′ UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5′ UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated

The Drosophila Gap Gene Network Is Composed of Two Parallel Toggle Switches

Drosophila “gap” genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5–7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants