Strength evaluation of cold-formed steel columns using the results of finite strip and finite element linear stability analysis

Most cold-formed steel columns display open and rather thin-walled cross-sections which mean that their structural behaviour is strongly affected by local and global buckling. Th e local mode, that occurs for shorter profi les, is characterized by (i) the local plate mode (LPM) characterized by the simultaneous flexural buckling of the web and fl anges and (ii) by the distortional mode (DM) characterized by the displacements of flange-stiff ener edges (that remain plane). The global mode occurring for long profi les is characterized by (i) the fl exural mode (FM) characterized by the translation of the whole section in the direction of the major principal axis and (ii) by the fl exural-torsional mode (FTM) characterized by the simultaneous translation and rotation of the whole section. Th e possibility of using the results of linear stability analysis in the national codes of thin-walled cold-formed steel structural elements (for instance, European and Brazilian Codes) arises, i.e. local and global buckling instability modes and corresponding bifurcation stresses determining the ultimate strength of members. Two powerful numerical methods are chosen to perform a linear stability analysis of a cold-formed steel structural member: (i) the Finite Strip Method, (i1) the Semi-Analytical Finite Strip Method (trigonometric functions are used in the approximation of displacement) used for simply supported boundary conditions, (i2) the Spline Finite Strip Method (‘spline’ functions are used in the approximation of displacement) used other boundary conditions and (ii) the Finite Element Method. The linear local and global stability results of for Z, C and rack cold-formed columns are used to obtain ultimate strength through the procedures adopted in the Eurocode 3, Part 1.3 and in the Brazilian Code (NBR 14.762/2001). The obtained numerical estimates by specifi cations are compared with experimental results available in literature. Šaltai formuotų plieninių kolonų laikomosios galios įvertinimas naudojant baigtinių strypų ir elementų tiesinio pastovumo skaičiavimo rezultatus Santrauka. Dauguma šaltai formuotų plieninių kolonų turi atvirus arba plonasienius skerspjūvius, todėl jų konstrukcinė elgsena daugiausia priklauso nuo vietinio arba bendrojo klupumo. Vietinis klupumas, kuris būdingas (1) trumpesniems profi liuočiams, gali būti apibūdinamas vietinės plokštelės modeliu (LPM), pasižyminčiu vienalaikiu lenkiamuoju juostų ir sienelių klupumu ir (2) iškraipomuoju modeliu (DM), kurį apibūdina juostų ir sąstandų kraštų (kurie išlieka plokšti) poslinkiai. Bendrasis klupumas, kuris būdingas ilgiems profi liuočiams apibūdinamas (1) lenkiamuoju modeliu (FM). Jam būdingas viso skerspjūvio išilgai pagrindinės ašies pasislinkimas ir (2) lenkiamasis sukamasis (FTM) modelis, kuris pasižymi viso skerspjūvio pasislinkimu ir pasisukimu. Nacionalinėse šaltai formuotų plonasienių plieninių elementų normose (taip pat Europos ir Brazilijos) yra galimybė taikyti tiesinį pastovumo skaičiavimą, t. y. nustatant ribin elemento laikomąją galią naudoti vietinio ir bendrojo klumpamojo nepastovumo modelius bei atitinkamus išsišakojimo įtempiu. Šaltai formuotų plieninių elementų tiesiniam pastovumui skaičiuoti pasirinkti du veiksmingi skaičiavimo metodai: 1. Baigtinių strypų metodas: 1.1-pusiau analitinis baigtinių strypų metodas (trigonometrinės funkcijos naudojamos poslinkiui aproksimuoti), kuris taikomas lankstinio atrėmimo kraštinėmis sąlygomis; 1.2-kreivinių baigtinių strypų metodas („kreivinės” funkcijos naudojamos poslinkiui aproksimuoti), taikomas kitokiomis kraštinėmis sąlygomis. 2. Baigtinių elementų metodas. Z ir C skerspjūvių ir spragotųjų šaltai formuotų kolonų tiesinio vietinio ir bendrojo pastovumo rezultatai naudojami nustatyti ribine laikomąją galią remiantis Eurokodo 3 (1.3 dalies) ir Brazilijos normų (NBR 14.762/2001) priimtomis metodikomis. Pagal instrukcijas gautieji skaitiniai įverčiai palyginti su literatūroje randamais eksperimentinių tyrimų rezultatais. Reikšminiai žodžiai: šaltai formuotas, baigtinis strypas, baigtinis elementas, vietinio klumpamojo nepastovumo modelis, bendrojo klumpamojo nepastovumo modelis, normų reikalavimai. First Published Online: 16 May 201

Pazopanib and trametinib as a synergistic strategy against osteosarcoma: Preclinical activity and molecular insights

Receptor tyrosine kinases (RTKs) inhibitors’ activity in advanced osteosarcoma is significant but short-lived. To prevent or at least delay drug resistance, we explored a vertical inhibition by combining drugs acting at different levels of the RTK pathways (pazopanib + trametinib). We studied pazopanib + trametinib antitumor activity both in vitro and in vivo (MNNG-HOS and KHOS xenografts in NOD/SCID mice) investigating the molecular mechanisms and potential escapes. The involvement of MAPK-PI3K pathways was validated by Nanostring technology, western blot and by silencing/overexpression experiments. Pazopanib targets were expressed on seven osteosarcoma cell lines and their pathways were activated. Pazopanib + trametinib exhibited synergistic antitumor activity by inducing apoptosis and inhibiting ERK1/2 and Akt. In vivo antitumor activity was shown in osteosarcoma-bearing mice. The drug combination significantly down-modulated RTK Ephrin Type-A Receptor 2 (EphA2) and Interleukin-7 Receptor (IL-7R), whereas induced mitogen-activated protein-kinase kinase (MAPKK) MEK6. EphA2 silencing significantly reduced osteosarcoma cell proliferation and migration, while impeding MEK6 up-regulation in the treated cells significantly increased the antitumor effect of the studied drugs. Moreover, the up-regulation of MEK6 reduced combination activity. Pazopanib + trametinib demonstrated synergistic antitumor effects in osteosarcoma models through ERK and Akt inhibition and EphA2 and IL-7R down-modulation. MEK6 up-regulation might evoke escaping mechanism

Crystal Structures of 3-halo-2-organochalcogenylbenzo[b]chalcogenophenes

The structure of the title compounds 3-bromo-2-(phenyl­sulfan­yl)benzo[b]thiophene (C(14)H(9)BrS(2); 1), 3-iodo-2-(phenyl­sulfan­yl)benzo[b]thio­phene (C(14)H(9)IS(2); 2), 3-bromo-2-(phenyl­selan­yl)benzo[b]seleno­phene (C(14)H(9)BrSe(2); 3), and 3-iodo-2-(phenyl­selan­yl)benzo[b]seleno­phene (C(14)H(9)ISe(2); 4) were determined by single-crystal X-ray diffraction; all structures presented monoclinic (P2(1)/c) symmetry. The phenyl group is distant from the halogen atom to minimize the steric hindrance repulsion for all structures. Moreover, the structures of 3 and 4 show an almost linear alignment of halogen–selenium–carbon atoms arising from the intra­molecular orbital inter­action between a lone pair of electrons on the halogen atom and the anti­bonding σ*(Se–C) orbital (n (halogen)→σ*(Se–C)). This inter­action leads to significant differences in the three-dimensional packing of the mol­ecules, which are assembled through π–π and C—H⋯π inter­actions. These data provide a better comprehension of the inter­molecular packing in benzo[b]chalcogenophenes, which is relevant for optoelectronic applications

Publisher Correction: Necroptosis Mediates Myofibre Death in Dystrophin-deficient Mice

The original version of this article contained an error in Fig. 3. In panel c, the labels 'mdx' and 'mdx Ripk3-/-' were inadvertently inverted. This has now been corrected in the PDF and HTML versions of the Article

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery