Separable Hamiltonian equations on Riemann manifolds and related integrable hydrodynamic systems

A systematic construction of St\"{a}ckel systems in separated coordinates and its relation to bi-Hamiltonian formalism are considered. A general form of related hydrodynamic systems, integrable by the Hamilton-Jacobi method, is derived. One Casimir bi-Hamiltonian case is studed in details and in this case, a systematic construction of related hydrodynamic systems in arbitrary coordinates is presented, using a cofactor method and soliton symmetry constraints.Comment: to appear in Journal of Geometry and Physic

Prediction of failure modes during deep drawing of metal sheets with nickel coating

To optimize the process parameters, it is necessary to exactly predict failure modes during deep drawing of coated metal sheets, where two main failure forms are fracture and wrinkling. In this paper, finite element simulations based on continuous damage mechanics were used to study the failure behavior during a cylindrical deep drawing of metal sheets with nickel coating. It is shown that taking the effect of blank holder force into account, these two failure modes can be predicted. The simulation results are well consistent with that obtained from experiments

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Formability analysis of pre-strained AA5754-O sheet metal using Yld96 plasticity theory: Role of amount and direction of uni-axial pre-strain

Automotive industries are very much interested in formability of different pre-strained aluminum alloy sheets in the context of multistage stamping to fabricate complex components. In the present work, different uni-axial pre-strains of 6.4% and 12.2% were induced in AA5754-O aluminum alloy both along rolling direction (RD) and transverse direction (TD). The true stress-strain response, limiting dome height (LDH) and strain based forming limit diagram (ε-FLD) of as received and all pre-strained materials were evaluated experimentally. The anisotropy constitutive material model was developed using the Yld96 plasticity theory in-conjunction with the Hollomon isotropic hardening law to predict the yield strength evolution of the pre-strained materials. Also, it was found that the limiting strains in ε-FLD shifted significantly depending on the amount and direction of uni-axial pre-strain. Hence, the limiting strains of the as-received materials were transposed into stress space to estimate the stress based forming limit diagram (σ-FLD) using the anisotropy constitutive material model. Further, the dynamic shifts of ε-FLDs of four different pre-strained materials were predicted by successfully decoupling the σ-FLD of as-received materials within root mean square error of 0.008. Finite element models of both uni-axial pre-straining and subsequent LDH tests were developed, and the forming behavior of the pre-strained materials were predicted implementing the Yld96 plasticity model and estimated σ-FLD. It was found that LDH was significantly influenced by the amount of pre-strain, and the maximum thinning location shifted close to pole in the case of 12.2% pre-strained materials. However, the effect of uni-axial pre-strain direction on both LDH and maximum thinning location in AA5754-O material was very negligible

Managing and exploiting stress in the antibody factory

Like us, our cells have evolved strategies to cope with, and sometimes utilize, stress. Molecular analyses of plasma cell biogenesis, lifestyle and death suggest that protein synthesis‐dependent stress is utilised to integrate differentiation, function and lifespan control. Plasma cells are short‐lived professional secretory cells, each of them capable of releasing several thousands antibodies per second. Their differentiation from B lymphocytes entails the spectacular enlargement of the endoplasmic reticulum (ER), finalized to sustain massive Ig production. Nonetheless, symptoms of ER stress are evident, and the UPR‐related transcription factor XBP‐1 is essential for differentiation. Surprisingly, the development of such an efficient factory is matched by a decrease in proteasomes. The unbalanced load/capacity ratio leads to accumulation of polyubiquitinated molecules and predisposes plasma cells to apoptosis. Exuberant antibody secretion imposes considerable stress on metabolic and redox homeostasis. Collectively, these stressful conditions may link plasma cell death to antibody production, providing a molecular counter for secreted molecules, as well as an explanation for the peculiar sensitivity of myeloma cells towards proteasome inhibitors

Calcineurin Interacts with PERK and Dephosphorylates Calnexin to Relieve ER Stress in Mammals and Frogs

Background: The accumulation of misfolded proteins within the endoplasmic reticulum (ER) triggers a cellular process known as the Unfolded Protein Response (UPR). One of the earliest responses is the attenuation of protein translation. Little is known about the role that Ca 2+ mobilization plays in the early UPR. Work from our group has shown that cytosolic phosphorylation of calnexin (CLNX) controls Ca 2+ uptake into the ER via the sarco-endoplasmic reticulum Ca 2+-ATPase (SERCA) 2b. Methodology/Principal Findings: Here, we demonstrate that calcineurin (CN), a Ca 2+ dependent phosphatase, associates with the (PKR)-like ER kinase (PERK), and promotes PERK auto-phosphorylation. This association, in turn, increases the phosphorylation level of eukaryotic initiation factor-2 a (eIF2-a) and attenuates protein translation. Data supporting these conclusions were obtained from co-immunoprecipitations, pull-down assays, in-vitro kinase assays, siRNA treatments and [ 35 S]-methionine incorporation measurements. The interaction of CN with PERK was facilitated at elevated cytosolic Ca 2+ concentrations and involved the cytosolic domain of PERK. CN levels were rapidly increased by ER stressors, which could be blocked by siRNA treatments for CN-Aa in cultured astrocytes. Downregulation of CN blocked subsequent ER-stress-induced increases in phosphorylated elF2-a. CN knockdown in Xenopus oocytes predisposed them to induction of apoptosis. We also found that CLNX was dephosphorylated by CN when Ca 2+ increased. These data were obtained from [c 32 P]-CLN

Improving the power performance of urine-fed microbial fuel cells using PEDOT-PSS modified anodes

© 2020 The Authors The need for improving the energy harvesting from Microbial Fuel Cells (MFCs) has boosted the design of new materials in order to increase the power performance of this technology and facilitate its practical application. According to this approach, in this work different poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT-PSS) modified electrodes have been synthesised and evaluated as anodes in urine-fed MFCs. The electrochemical synthesis of PEDOT-PSS was performed by potentiostatic step experiments from aqueous solution at a fixed potential of 1.80 V (vs. a reversible hydrogen electrode) for different times: 30, 60, 120 and 240 s. Compared with other methods, this technique allowed us not only to reduce the processing time of the electrodes but also better control of the chemical composition of the deposited polymer and therefore, obtain more efficient polymer films. All modified anodes outperformed the maximum power output by MFCs working with the bare carbon veil electrode but the maximum value was observed when MFCs were working with the PEDOT-PSS based anode obtained after 30 s of electropolymerisation (535.1 µW). This value was 24.3% higher than using the bare carbon veil electrode. Moreover, the functionality of the PEDOT-PSS anodes was reported over 90 days working in continuous mode

Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide

BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer