Experiments on crack propagation and threshold at defects in press-fits of railway axles

Fatigue strength under fretting fatigue is one of the open problems in the area of fatigue. In the case of railway wheel-axle press-fits, there are no records of recent failures because design rules are today based on making the shape of geometrical transitions the most stressed point. However, it is important to analyze correctly the acceptability of defects and micro-cracks at press-fits. In this paper, after a preliminary presentation of the results obtained by a new criterion for predicting the non-propagation of cracks under rolling contact fatigue conditions, a new series of experiments on full-scale axle press-fits containing artificial defects is presented and discussed. Results show the modified Dang Van criterion is adequate for describing the development of natural cracks and cracks from artificial defects. The latter, characterized by a depth of 250 350 m, are competitors of fretting cracks naturally developed from surface scars and surface damage

Hidatidosis ósea: nuestra casuística

Se revisan los resultados de 16 casos de hidatidosis musculoesquelética tratados en la Unidad de Sépticos del Aparato Locomotor del Hospital Universitario "La Fe" de Valencia en el período 1972-1989. Las dificultades diagnósticas fueron importantes, siendo en 5 de los casos un diagnóstico operatorio. Analizados los métodos de tratamiento se llega a la conclusión de que la curación definitiva sólo se consigue con la resección completa y amplia de la lesión. Los curetajes, acompañados o no de aseptizaciones químicas, suelen dar recidivas. Se recomienda combinar el tratamiento médico con el quirúrgico.The results of 16 cases of musculoskeletal hydatidosis treated in the locomotive Apparatus Septic Unit of the Valencia University Hospital "La Fe" between 1972 and 1989 wer e reviewed. The diagnostic difficulties wer e marked and 5 cases wer e diagnosed at surgery. After analyzing the therapeutical approaches, it is drawn the conclusion that a definitive healing is achieved only when an extensive and complete resection is done. Curettage, with and without chemical aseptization, generally results in recurrence. A combined medical and surgical treatment is recommended

Surface resonant modes in colloidal photonic crystals

Herein we report an experimental and theoretical optical analysis of the effect of growing a dielectric slab on the surface of photonic colloidal crystals. Optical spectroscopy shows an enhancement of the transmitted intensity for certain frequencies within the photonic pseudogap. Simulations based on a scalar wave approximation fairly reproduce the experimental results and provide a description of the interplay between the features arising from the presence of the surface slab and the finite size of the photonic crystal. The experimental observations are explained by the excitation of photon resonant states at the crystal boundary. Our work demonstrates that the amplitude of light waves penetrating the crystal with frequencies lying within the pseudogap range can be greatly modified by rather simple means

Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies

Railway wheel tread damage and axle bending stress – Instrumented wheelset measurements and numerical simulations

A combination of instrumented wheelset measurements and numerical simulations of axle bending stresses is used to investigate the consequences of evolving rolling contact fatigue (RCF) damage on a passenger train wheelset. In a field test campaign, stresses have been monitored using a wheelset with four strain gauges mounted on the axle, while the evolution of wheel tread damage (out-of-roundness) has been measured on regular occasions. The strain signals are post-processed in real time and stress variations are computed. Based on a convolution integral approach, the measured wheel out-of-roundness has been used as input to numerical simulations of vertical dynamic wheelset–track interaction and axle stresses. Simulated and measured axle stresses are compared for cases involving combinations of low or high levels of rail roughness and the measured levels of RCF damage. The study enhances the understanding of how wheel tread damage and track quality influence axle stress amplitudes

Oleocanthal Exerts Antitumor Effects on Human Liver and Colon Cancer Cells Through ROS Generation

The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW480) cell lines was used. Cells were treated with OC, and cell viability and apoptosis were evaluated. Compared with classical commercially available COX inhibitors (ibuprofen, indomethacin, nimesulide), OC was more effective in inducing cell growth inhibition in HCC and CRC cells. Moreover, OC inhibited colony for mation and i nduced ap optosis, as confirmed by PARP cleavage, activation of caspases 3/7 and chromatin condensation. OC treatment in a dose dependent-manner induced expression of \uce\ub3H2AX, a marker of DNA damage, increased intracellular ROS production and caused mitochondrial depolarization. Moreover, the effects of OC were suppressed by the ROS scavenger N-acetyl-L-cysteine. Finally, OC was not toxic in primary normal human hepatocytes. In conclusion, OC treatment was found to exert a potent anticancer activity against HCC and CRC cells. Taken together, our findings provide preclinical support of the chemotherapeutic potential of EVOO against cancer

Structural analysis for the design of a lightweight composite railway axle

The unsprung masses associated with the axles of a railway vehicle result in costly impact damage to the rail infrastructure. A hybrid metallic-composite (HMC) railway axle is evaluated using finite element analysis. The axle mass is 74 kg, 63% lighter than an equivalent hollow steel axle. The HMC railway axle comprises a full length, carbon fibre reinforced, epoxy matrix composite tube with secondary overwrapping for stiffness and EA1N grade steel collars creating the wheel seats and journal surfaces. Maximum axle deflection is 1.72 mm with a misalignment at the journals of 0.21°, potentially requiring a bearing reassessment. Nominal bending stress in the axle is 99.3 MPa (Tsai-Wu damage index of 0.18). Peak bending and torsional stresses result in Tsai-Wu damage indexes of 0.71 and 0.42, respectively. The methodology in this paper can be extended to the design of future lightweight composite shafts to benefit many other industries

Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer and hence, GSK-3 is often inactivated. Moreover, GSK-3 also interacts with WNT/\u3b2-catenin signaling and \u3b2-catenin and other proteins in this pathway are targets of GSK-3. GSK-3 can modify NF-\u3baB activity which is often expressed at high levels in cancer cells. Multiple pharmaceutical companies developed small molecule inhibitors to suppress GSK-3 activity. In addition, various natural products will modify GSK-3 activity. This review will focus on the effects of small molecule inhibitors and natural products on GSK-3 activity and provide examples where these compounds were effective in suppressing cancer growth

Effects of the Mutant TP53 Reactivator APR-246 on Therapeutic Sensitivity of Pancreatic Cancer Cells in the Presence and Absence of WT-TP53

The TP53 tumor suppressor is mutated in ~75% of pancreatic cancers. The mutant TP53 protein in pancreatic ductal adenocarcinomas (PDAC) promotes tumor growth and metastasis. Attempts have been made to develop molecules that restore at least some of the properties of wildtype (WT) TP53. APR-246 is one such molecule, and it is referred to as a mutant TP53 reactivator. To understand the potential of APR-246 to sensitize PDAC cells to chemotherapy, we introduced a vector encoding WT-TP53 into two PDAC cell lines, one lacking the expression of TP53 (PANC-28) and one with a gain-of-function (GOF) mutant TP53 (MIA-PaCa-2). APR-246 increased drug sensitivity in the cells containing either a WT or mutant TP53 protein with GOF activity, but not in cells that lacked TP53. The introduction of WT-T53 into PANC-28 cells increased their sensitivity to the TP53 reactivator, chemotherapeutic drugs, and signal transduction inhibitors. The addition of WT-TP53 to PDAC cells with GOF TP53 also increased their sensitivity to the drugs and therapeutics, indicating that APR-246 could function in cells with WT-TP53 and GOF TP53. These results highlight the importance of knowledge of the type of TP53 mutation that is present in cancer patients before the administration of drugs which function through the reactivation of TP53