Experimental and numerical investigation of ratcheting and low-cycle fatigue in metal components

Structures loaded cyclically beyond their elastic limit experience gradual accumulation of plastic deformations or strains which may eventually lead to material deterioration and ductile fracture. Assessing the life expectancy of their structural members requires the development and implementation of appropriate material models into the finite element environment, using robust numerical integration schemes. It is the purpose of the present Thesis to investigate through rigorous numerical analyses and experimental testing the mechanical behaviour of metal components subjected to intense cyclic loading. Advanced numerical tools are developed to simulate multi-axial material ratcheting and cyclic plasticity-damage response in metal structural components. The ultra low-cycle fatigue of high-strength steel welded tubular joints is also investigated through large-scale experiments. An implicit numerical scheme is proposed in Chapter 2 for simulating the mechanical response of thin-walled structures subjected to inelastic cyclic loading. The constitutive model is formulated explicitly for plane stress conditions, accounts for combined kinematic/isotropic hardening and follows the von-Mises yield criterion. Emphasis is given to kinematic hardening part, which is described with an advanced multiple backstress model suitable for multi-axial material ratcheting simulation. Constitutive relations are integrated implicitly using the Euler-backward integration technique. Two main novelties of the algorithm refer to the incremental update of the internal variables through the solution of a single scalar equation, and the explicit formulation of the consistent tangent moduli. The numerical scheme is implemented into the finite element software ABAQUS (2016) as a material user-subroutine UMAT and its capabilities are demonstrated through the numerical simulation of large-scale experiments on pipe elbows, a characteristic mechanical component that experiences multi-axial ratcheting response. In the sequence, the proposed numerical scheme is employed to investigate the ratcheting collapse of dented externally pressurised tubular circular members subjected to cyclic axial loading. The numerical implementation of coupled cyclic plasticity-damage models is presented in Chapter 3, suitable for simulating low-cycle fatigue in metal components. Constitutive relations account for J2-flow theory with nonlinear kinematic/isotropic hardening, coupled with isotropic continuum damage mechanics. The damage potential is written in a general form, allowing for implementing any isotropic damage model reported in the literature. The constitutive relations are integrated implicitly considering in the most general case the 3D finite element formulation. An additional numerical scheme is proposed explicitly for plane stress conditions by extending the plane-stress projection method to the requirements of the model. Both numerical schemes feature computational efficiency as incremental update of internal variables is achieved through the solution of a single scalar equation. The integration algorithms are consistently linearised to ensure numerical robustness in large-scale computations. The proposed numerical schemes are implemented into ABAQUS (2016) software as user material subroutines UMAT and are validated against large-scale tests on pipe elbows that failed from ultra low-cycle fatigue. In the last part of the Thesis, the ultra low-cycle fatigue performance of welded tubular X-joints is examined, motivated by the need of safeguarding the integrity of offshore platforms under extreme loading conditions. Seven specimens, representing X-brace joints of a bottom-founded offshore tubular jacket with a scaling factor of 1:3 are tested under strong, fully-reversed cyclic in-plane bending. The seven specimens formed a through-thickness fatigue crack within less than 100 cycles, simulating extreme loading conditions. Rigorous finite element models are also developed, with emphasis on constitutive modelling, to simulate the cyclic loading procedure, providing very good comparisons in terms of load-displacement response and local strain predictions during the initial loading cycles. The experimental data are compared with a large dataset of low-cycle fatigue experiments on welded components, reported in the literature for mild and high-strength steel materials, as well as with existing design provisions

KEGGconverter: a tool for the in-silico modelling of metabolic networks of the KEGG Pathways database

<p>Abstract</p> <p>Background</p> <p>The KEGG Pathway database is a valuable collection of metabolic pathway maps. Nevertheless, the production of simulation capable metabolic networks from KEGG Pathway data is a challenging complicated work, regardless the already developed tools for this scope. Originally used for illustration purposes, KEGG Pathways through KGML (KEGG Markup Language) files, can provide complete reaction sets and introduce species versioning, which offers advantages for the scope of cellular metabolism simulation modelling. In this project, KEGGconverter is described, implemented also as a web-based application, which uses as source KGML files, in order to construct integrated pathway SBML models fully functional for simulation purposes.</p> <p>Results</p> <p>A case study of the integration of six human metabolic pathways from KEGG depicts the ability of KEGGconverter to automatically produce merged and converted to SBML fully functional pathway models, enhanced with default kinetics. The suitability of the developed tool is demonstrated through a comparison with other state-of-the art relevant software tools for the same data fusion and conversion tasks, thus illustrating the problems and the relevant workflows. Moreover, KEGGconverter permits the inclusion of additional reactions in the resulting model which represent flux cross-talk with neighbouring pathways, providing in this way improved simulative accuracy. These additional reactions are introduced by exploiting relevant semantic information for the elements of the KEGG Pathways database. The architecture and functionalities of the web-based application are presented.</p> <p>Conclusion</p> <p>KEGGconverter is capable of producing integrated analogues of metabolic pathways appropriate for simulation tasks, by inputting only KGML files. The web application acts as a user friendly shell which transparently enables the automated biochemically correct pathway merging, conversion to SBML format, proper renaming of the species, and insertion of default kinetic properties for the pertaining reactions. The tool is available at: <url>http://www.grissom.gr/keggconverter</url></p

KEGGconverter: a tool for the in-silico modelling of metabolic networks of the KEGG Pathways database

Journal URL: http://www.biomedcentral.com/bmcbioinformatics

CD90/Thy-1, a Cancer-Associated Cell Surface Signaling Molecule

CD90 is a membrane GPI-anchored protein with one Ig V-type superfamily domain that was initially described in mouse T cells. Besides the specific expression pattern and functions of CD90 that were described in normal tissues, i.e., neurons, fibroblasts and T cells, increasing evidences are currently highlighting the possible involvement of CD90 in cancer. This review first provides a brief overview on CD90 gene, mRNA and protein features and then describes the established links between CD90 and cancer. Finally, we report newly uncovered functional connections between CD90 and endoplasmic reticulum (ER) stress signaling and discuss their potential impact on cancer development

Repair of an inguinoscrotal hernia containing the urinary bladder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cases of patients with inguinoscrotal hernia containing the urinary bladder are very rare. These patients usually present with frequent episodes of urinary tract infection, difficulty in walking, pollakisuria and difficulty in initiating micturition because of incarceration of the urinary bladder into the scrotum.</p> <p>Case presentation</p> <p>We describe the case of an 80-year-old Caucasian man with an incarcerated urinary bladder into the scrotum who underwent surgical repair with mesh.</p> <p>Conclusions</p> <p>Diagnosis of such cases often requires not only clinical examination but also specialized radiological examinations to show the ectopic position of the urinary bladder. Surgical repair in these patients is a real challenge for surgeons.</p

The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

BACKGROUND: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. METHODS: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. RESULTS: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. CONCLUSIONS: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes

Thermogenic capacity of human white-fat: the actual picture

Presented at the 9th Greek Conference of Biochemistry and Physiology of Exercise, Thessaloniki, Greece, 18–20 October 2019Cold exposure and exercise may increase thermogenic capacity of white adipose tissue (WAT), which could subsequently enhance energy expenditure and body weight loss. We aimed to identify possible alterations in uncoupling protein 1 (UCP1)—the main biomarker of thermogenic activation—in human WAT due to both cold exposure and exercise, as well as the link between environmental temperature and thermogenic capacity of human WAT. MATERIAL &amp; METHOD: We conducted four human experimental studies and two systematic reviews and meta-analyses—PROSPERO registration CRD42019120116, CRD42019120213. RESULTS: UCP1 mRNA was higher in winter than in summer [t(30) = 2.232, p = 0.03] in human WAT and our meta-analysis showed a main effect of cold exposure on human UCP1 mRNA [standard mean difference (Std-md) = 1.81, confidence interval (CI) = 0.50–3.13, p = 0.007]. However, UCP1 mRNA/protein expressions displayed no associations with %fat mass or BMI (p &gt; 0.05, Cohen’s f2 &lt; 0.20). Both a 2-hour cooling and a non-cooling protocol preceding the positron emission tomography/computed tomography (PET/CT) measurements revealed no association between environmental temperature and standardised uptake value (SUVmax) of human WAT, as well as no mean differences in SUVmax-WAT-activity between winter and summer. An 8-week exercise program had no effect on UCP1 of human WAT or on body composition. Our meta-analysis also revealed: (a) no effect of chronic exercise on human UCP1 mRNA, (b) a main effect of chronic exercise on UCP1 protein concentrations (Std-md = 0.59, CI = 0.03–1.16, p = 0.04) and UCP1 mRNA (Std-md = 1.76, CI = 0.48–3.04, p = 0.007) in WAT of normal diet animals, c) a main effect of chronic exercise on UCP1 mRNA (Std-md = 2.94, CI = 0.24–5.65, p = 0.03) and UCP1 protein concentrations (Std-md = 2.06, CI = 0.07–4.05, p = 0.04) of high-fat diet animals. CONCLUSIONS: Cold exposure represents a main stimulus for increased thermogenic capacity in human white adipocytes; however, this may have no impact on body weight loss. Chronic exercise may represent no major stimulus for UCP1 induced in human white adipocytes, while in animals it increases UCP1 gene independently of their diet. Therefore, evidence from animal studies regarding UCP1 gene activation in white adipocytes may not be applicable in humans. Finally, the identification of human WAT thermogenic capacity via PET/CT examination may be optimal with both a cooling and a non-cooling protocol.Published onlin