Influence of deformation on the structure and mechanical and corrosion properties of high-nitrogen austenitic 07Kh16AG13M3 steel

The correlation has been studied between the structure of a high-nitrogen austenitic Cr-Mn-N steel formed in the process of combined hardening treatment, including cold plastic deformation (CPD), and its mechanical and corrosion properties. The structure and properties of commercial high-nitrogen (0.8% N) 07Kh16AG13M3 steel is analyzed after rolling by CPD and aging at 500 and 800°C. It is shown that CPD of the steel occurs by dislocation slip and deformation twinning. Deformation twinning and also high resistance of austenite to martensitic transformations at true strains of 0.2 and 0.4 determine the high plasticity of the steel. The contribution of the structure imperfection parameters to the broadening of the austenite lines during CPD is estimated by X-ray diffraction. The main hardening factor is stated to be lattice microdistortions. Transmission electron microscopy study shows that heating of the deformed steel to 500°C leads to the formation of the intermediate CrN phase by a homogeneous mechanism, and the intermtallic χ phase forms along the austenite grain boundaries in the case of heating at 800°C. After hardening by all investigated technological schemes, exception for aging at 800°C, the steel does not undergo pitting corrosion and is slightly prone to a stress corrosion cracking during static bending tests, while aging at 800°C causes pitting corrosion at a pitting formation potential Epf = -0.25 V. © 2013 Pleiades Publishing, Ltd

Birth and death of protein domains: A simple model of evolution explains power law behavior

BACKGROUND: Power distributions appear in numerous biological, physical and other contexts, which appear to be fundamentally different. In biology, power laws have been claimed to describe the distributions of the connections of enzymes and metabolites in metabolic networks, the number of interactions partners of a given protein, the number of members in paralogous families, and other quantities. In network analysis, power laws imply evolution of the network with preferential attachment, i.e. a greater likelihood of nodes being added to pre-existing hubs. Exploration of different types of evolutionary models in an attempt to determine which of them lead to power law distributions has the potential of revealing non-trivial aspects of genome evolution. RESULTS: A simple model of evolution of the domain composition of proteomes was developed, with the following elementary processes: i) domain birth (duplication with divergence), ii) death (inactivation and/or deletion), and iii) innovation (emergence from non-coding or non-globular sequences or acquisition via horizontal gene transfer). This formalism can be described as a birth, death and innovation model (BDIM). The formulas for equilibrium frequencies of domain families of different size and the total number of families at equilibrium are derived for a general BDIM. All asymptotics of equilibrium frequencies of domain families possible for the given type of models are found and their appearance depending on model parameters is investigated. It is proved that the power law asymptotics appears if, and only if, the model is balanced, i.e. domain duplication and deletion rates are asymptotically equal up to the second order. It is further proved that any power asymptotic with the degree not equal to -1 can appear only if the hypothesis of independence of the duplication/deletion rates on the size of a domain family is rejected. Specific cases of BDIMs, namely simple, linear, polynomial and rational models, are considered in details and the distributions of the equilibrium frequencies of domain families of different size are determined for each case. We apply the BDIM formalism to the analysis of the domain family size distributions in prokaryotic and eukaryotic proteomes and show an excellent fit between these empirical data and a particular form of the model, the second-order balanced linear BDIM. Calculation of the parameters of these models suggests surprisingly high innovation rates, comparable to the total domain birth (duplication) and elimination rates, particularly for prokaryotic genomes. CONCLUSIONS: We show that a straightforward model of genome evolution, which does not explicitly include selection, is sufficient to explain the observed distributions of domain family sizes, in which power laws appear as asymptotic. However, for the model to be compatible with the data, there has to be a precise balance between domain birth, death and innovation rates, and this is likely to be maintained by selection. The developed approach is oriented at a mathematical description of evolution of domain composition of proteomes, but a simple reformulation could be applied to models of other evolving networks with preferential attachment

Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: Post-hoc analysis of a randomised controlled trial

PUBLISHED 25 August 2022Objective: Populations with knee osteoarthritis (KOA) are at increased risk of cardiovascular disease, due to higher prevalence of risk factors including dyslipidaemia, where statins are commonly prescribed. However, the effect of statins on muscles and symptoms in this population is unknown. Thus, this study examined the effect of atorvastatin on muscle properties in patients with symptomatic KOA. Design: Post-hoc analysis of a 2-year multicentre randomised, double-blind, placebo-controlled trial. Setting: Australian community. Participants: Participants aged 40–70 years (mean age 55.7 years, 55.6% female) with KOA who met the American College of Rheumatology clinical criteria received atorvastatin 40 mg daily (n = 151) or placebo (n = 153). Main outcome measures: Levels of creatinine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT) at 1, 6, 12, and 24 months; muscle strength (by dynamometry) at 12 and 24 months; vastus medialis cross-sectional area (CSA) on magnetic resonance imaging at 24 months; and self-reported myalgia. Results: There were no significant between-group differences in CK and AST at all timespoints. The atorvastatin group had higher ALT than placebo group at 1 (median 26 vs. 21, p = 0.004) and 6 (25 vs. 22, p = 0.007) months without significant between-group differences at 12 and 24 months. Muscle strength increased in both groups at 24 months without between-group differences [mean 8.2 (95% CI 3.5, 12.9) vs. 5.9 (1.3, 10.4), p = 0.49]. Change in vastus medialis CSA at 24 months favoured the atorvastatin group [0.11 (−0.10, 0.31) vs. −0.23 (−0.43, −0.03), p = 0.02] but of uncertain clinical significance. There was a trend for more myalgia in the atorvastatin group (8/151 vs. 2/153, p = 0.06) over 2 years, mostly occurring within 6 months (7/151 vs. 1/153, p = 0.04). Conclusions: In those with symptomatic KOA, despite a trend for more myalgia, there was no clear evidence of an adverse effect of atorvastatin on muscles, including those most relevant to knee joint health.Yuan Z. Lim, Flavia M. Cicuttini, Anita E. Wluka, Graeme Jones, Catherine L. Hill, Andrew B. Forbes, Andrew Tonkin, Sofia Berezovskaya, Lynn Tan, Changhai Ding and Yuanyuan Wan

High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

<p>Abstract</p> <p>Background</p> <p>In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed <it>de novo </it>in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients.</p> <p>Methods</p> <p>We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186).</p> <p>Results</p> <p>Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates.</p> <p>Conclusion</p> <p>Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.</p

Overexpression of HMGA1 promotes anoikis resistance and constitutive Akt activation in pancreatic adenocarcinoma cells

HMGA1 proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. Roles of HMGA1 in mediating the malignant phenotype of this cancer are poorly understood. We tested the hypothesis that overexpression of HMGA1 promotes resistance to anoikis (apoptosis induced by anchorage deprivation) in pancreatic cancer cells. HMGA1 cDNA was stably transfected into MiaPaCa2 human pancreatic adenocarcinoma cells (which have low baseline expression levels of HMGA1). Cells were grown in suspension on PolyHEMA-coated plates and their susceptibility to anoikis was assayed using flow cytometry. Overexpression of HMGA1 was associated with marked reductions in susceptibility to anoikis in concert with increases in Akt phosphorylation (Ser473) and in Akt kinase activity and with reductions in caspase 3 activation. Inhibition of phosphoinositidyl-3 (PI3-K)/Akt pathway with either the small molecule inhibitor LY294002 or dominant-negative Akt resulted in reversal of anoikis resistance induced by HMGA1 overexpression. Further, RNA interference-mediated HMGA1 silencing in MiaPaCa2 and BxPC3 (a human pancreatic adenocarcinoma cell line with high baseline levels of HMGA1 expression) cells resulted in significant increases in susceptibility to anoikis. Our findings suggest HMGA1 promotes anoikis resistance through a PI3-K/Akt-dependent mechanism. Given the putative associations between anoikis resistance and metastatic potential, HMGA1 represents a potential therapeutic target in pancreatic adenocarcinoma

Effects of climate and land-use changes on fish catches across lakes at a global scale

Globally, our knowledge on lake fisheries is still limited despite their importance to food security and livelihoods. Here we show that fish catches can respond either positively or negatively to climate and land-use changes, by analyzing time-series data (1970–2014) for 31 lakes across five continents. We find that effects of a climate or land-use driver (e.g., air temperature) on lake environment could be relatively consistent in directions, but consequential changes in a lake-environmental factor (e.g., water temperature) could result in either increases or decreases in fish catch in a given lake. A subsequent correlation analysis indicates that reductions in fish catch was less likely to occur in response to potential climate and land-use changes if a lake is located in a region with greater access to clean water. This finding suggests that adequate investments for water-quality protection and water-use efficiency can provide additional benefits to lake fisheries and food security

Invading Basement Membrane Matrix Is Sufficient for MDA-MB-231 Breast Cancer Cells to Develop a Stable In Vivo Metastatic Phenotype

1 - ArticleIntroduction: The poor efficacy of various anti-cancer treatments against metastatic cells has focused attention on the role of tumor microenvironment in cancer progression. To understand the contribution of the extracellular matrix (ECM) environment to this phenomenon, we isolated ECM surrogate invading cell populations from MDA-MB-231 breast cancer cells and studied their genotype and malignant phenotype. Methods: We isolated invasive subpopulations (INV) from non invasive populations (REF) using a 2D-Matrigel assay, a surrogate of basal membrane passage. INV and REF populations were investigated by microarray assay and for their capacities to adhere, invade and transmigrate in vitro, and to form metastases in nude mice. Results: REF and INV subpopulations were stable in culture and present different transcriptome profiles. INV cells were characterized by reduced expression of cell adhesion and cell-cell junction genes (44% of down regulated genes) and by a gain in expression of anti-apoptotic and pro-angiogenic gene sets. In line with this observation, in vitro INV cells showed reduced adhesion and increased motility through endothelial monolayers and fibronectin. When injected into the circulation, INV cells induced metastases formation, and reduced injected mice survival by up to 80% as compared to REF cells. In nude mice, INV xenografts grew rapidly inducing vessel formation and displaying resistance to apoptosis. Conclusion: Our findings reveal that the in vitro ECM microenvironment per se was sufficient to select for tumor cells with a stable metastatic phenotype in vivo characterized by loss of adhesion molecules expression and induction of proangiogenic and survival factors

Результаты лучевой терапии в сочетании с капецитабином и оксалиплатином в лечении больных плоскоклеточным раком анального канала: непосредственные и отдаленные результаты

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2  twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2  on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.Введение. Плоскоклеточный рак анального канала (ПРАК) является редкой локализацией в структуре заболеваемости злокачественными новообразованиями во всем мире. Современным стандартом лечения ПРАК является сочетание лучевой терапии (ЛТ) с химиотерапией митомицином или цисплатином с препаратами фторпиримидинового ряда. Один из эффективных лекарственных режимов с меньшим профилем токсичности – сочетание оксалиплатина и капецитабина в комбинации с ЛТ. Цель исследования – ретроспективная оценка результатов комбинированного лечения 74 пациентов с ПРАК с использованием препаратов оксалиплатин и капецитабин. Методы. В исследование включены 74 пациента (мужчины – 12,2 %, женщины – 87,8 %) с ПРАК I–III стадии. Всем больным проводили мегавольтную конвенциональную ЛТ до СОД 50 Гр (2×25) и бустом 10 Гр на зону анального канала. С 1 по 14-й и с 22 по 36-й дни облучения назначали пероральный прием капецитабина в дозе 825 мг/м2 дважды в день в сочетании с внутривенным введением оксалиплатина 50 мг/м2  в 1, 8, 22, 29-й дни ЛТ. При наличии остаточной опухоли через 6 мес после завершения ХЛТ выполняли хирургические вмешательства. Результаты. ЛТ во всех случаях завершена в полном объеме, завершенность химиотерапии составила 78,4 % больных. Лучевые реакции отмечены у всех пациентов, однако реакции III–IV степени – у 11 (14,9 %) больных. В группу динамического наблюдения включены 64 (86,5 %) пациента с полным клиническим ответом. Оценка поздних лучевых повреждений по шкале RTOG (LENT SOMA) проведена у 49 пациентов. У 48 (98,0 %) больных было отмечено хотя бы одно лучевое повреждение, в том числе осложнения III–IV степени зарегистрированы у 12 (24,5 %) пациентов. Постлучевые изменения костной ткани отмечены у 19 (38,8 %) пациентов, 7 больным потребовалось эндопротезирование тазобедренных суставов. При медиане наблюдения 40 мес (3–82) кумулятивная 3-летняя частота местных рецидивов, общая и безрецидивная 3-летняя выживаемость составили 15,3 ± 4,5; 73,7 ± 5,7 и 53,5 ± 6,4 % соответственно, Заключение. Комбинированное лечение ПРАК, основанное на сочетании ЛТ с химиотерапией препаратами оксалиплатин и капецитабин, удовлетворительно переносится пациентами. Необходимы дополнительные клинические исследования с использованием данного режима химиотерапии в сочетании с современными методиками ЛТ