Residual stresses in thermite welded rails: significance of additional forging

The aluminothermic welding (ATW) process is the most commonly used welding process for welding rails (track) in the field. The large amount of weld metal added in the ATW process may result in a wide uneven surface zone on the rail head, which may, in rare cases, lead to irregularities in wear and plastic deformation due to high dynamic wheel-rail forces as wheels pass. The present paper studies the introduction of additional forging to the ATW process, intended to reduce the width of the zone affected by the heat input, while not creating a more detrimental residual stress field. Simulations using a novel thermo-mechanical FE model of the ATW process show that addition of a forging pressure leads to a somewhat smaller width of the zone affected by heat. This is also found in a metallurgical examination, showing that this zone (weld metal and heat-affected zone) is fully pearlitic. Only marginal differences are found in the residual stress field when additional forging is applied. In both cases, large tensile residual stresses are found in the rail web at the weld. Additional forging may increase the risk of hot cracking due to an increase in plastic strains within the welded area

Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

Simple Summary Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers-NDUFS1 and ATP5O-for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

Background: Pen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13. Methodology/Principal Findings: Serum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A 148 –E 166) and S22 (A 243 –K 274) were recognized by sera from 90 % and 100 % of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T 261 –K 274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity

BH3-only proteins are dispensable for apoptosis induced by pharmacological inhibition of both MCL-1 and BCL-XL.

The impressive selectivity and efficacy of BH3 mimetics for treating cancer has largely been limited to BCL-2 dependent hematological malignancies. Most solid tumors depend on other anti-apoptotic proteins, including MCL-1, for survival. The recent description of S63845 as the first specific and potent MCL-1 inhibitor represents an important therapeutic advance, since MCL-1 is not targeted by the currently available BH3 mimetics, Navitoclax or Venetoclax, and is commonly associated with chemoresistance. In this study, we confirm a high binding affinity and selectivity of S63845 to induce apoptosis in MCL-1-dependent cancer cell lines. Furthermore, S63845 synergizes with other BH3 mimetics to induce apoptosis in cell lines derived from both hematological and solid tumors. Although the anti-apoptotic BCL-2 family members in these cell lines interact with a spectrum of pro-apoptotic BH3-only proteins to regulate apoptosis, these interactions alone do not explain the relative sensitivities of these cell lines to BH3 mimetic-induced apoptosis. These findings necessitated further investigation into the requirement of BH3-only proteins in BH3 mimetic-mediated apoptosis. Concurrent inhibition of BCL-XL and MCL-1 by BH3 mimetics in colorectal HCT116 cells induced apoptosis in a BAX- but not BAK-dependent manner. Remarkably this apoptosis was independent of all known BH3-only proteins. Although BH3-only proteins were required for apoptosis induced as a result of BCL-XL inhibition, this requirement was overcome when both BCL-XL and MCL-1 were inhibited, implicating distinct mechanisms by which different anti-apoptotic BCL-2 family members may regulate apoptosis in cancer

Numerical Investigation on the Crucible Discharge of Steel and Slag During the Aluminothermic Welding Process

The aluminothermic reaction is a type of self-propagating high-temperature synthesis to produce high quality metals and metal oxides en route. The main use of the aluminothermic reaction is in the field of railway welding. The multiphase flow of steel, slag and air in differently shaped crucibles has been numerically investigated in this work with the volume-of-fluid method. The simulations were carried out with the multiphase solver of the open source toolbox OpenFOAM. To validate the numerical results of the three-dimensional simulations, an experiment was carried out to investigate the discharge of a water-oil system from the crucible. A comparison to a numerical 3D simulation showed reasonable accurate results. It can be said that the solver is capable of predicting the point of the oil penetration of the water phase in the experiment

Quantitative interactome of a membrane Bcl-2 network identifies a hierarchy of complexes for apoptosis regulation

The Bcl-2 proteins form a complex interaction network that controls mitochondrial permeabilization and apoptosis. The relative importance of different Bcl-2 complexes and their spatio-temporal regulation is debated. Using fluorescence cross-correlation spectroscopy to quantify the interactions within a minimal Bcl-2 network, comprised by cBid, Bax, and Bcl-xL, we show that membrane insertion drastically alters the pattern of Bcl-2 complexes, and that the C-terminal helix of Bcl-xL determines its binding preferences. At physiological temperature, Bax can spontaneously activate in a self-amplifying process. Strikingly, Bax also recruits Bcl-xL to membranes, which is sufficient to retrotranslocate Bax back into solution to secure membrane integrity. Our study disentangles the hierarchy of Bcl-2 complex formation in relation to their environment: Bcl-xL association with cBid occurs in solution and in membranes, where the complex is stabilized, whereas Bcl-xL binding to Bax occurs only in membranes and with lower affinity than to cBid, leading instead to Bax retrotranslocation.The permeabilization of the mitochondrial outer membrane to induce apoptosis is regulated by complex interactions between Bcl-2 family members. Here the authors develop a quantitative interactome of a membrane Bcl-2 network and identify a hierarchy of protein complexes in apoptosis induction.publishe

Residual stresses in thermite welded rails: significance of additional forging

The aluminothermic welding (ATW) process is the most commonly used welding process for welding rails (track) in the field. The large amount of weld metal added in the ATW process may result in a wide uneven surface zone on the rail head, which may, in rare cases, lead to irregularities in wear and plastic deformation due to high dynamic wheel-rail forces as wheels pass. The present paper studies the introduction of additional forging to the ATW process, intended to reduce the width of the zone affected by the heat input, while not creating a more detrimental residual stress field. Simulations using a novel thermo-mechanical FE model of the ATW process show that addition of a forging pressure leads to a somewhat smaller width of the zone affected by heat. This is also found in a metallurgical examination, showing that this zone (weld metal and heat-affected zone) is fully pearlitic. Only marginal differences are found in the residual stress field when additional forging is applied. In both cases, large tensile residual stresses are found in the rail web at the weld. Additional forging may increase the risk of hot cracking due to an increase in plastic strains within the welded area.Railway Engineerin

Bax retrotranslocation potentiates Bcl-x_L's antiapoptotic activity and is essential for switch-like transitions between MOMP competency and resistance

The rapid, typically all-or-none process of mitochondrial outer membrane permeabilization (MOMP) constitutes a primary cell death decision that is controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP decisions are governed by and emanate from the dynamic interplay of pro- and antiapoptotic Bcl-2 family members remains incompletely understood. In particular, it is unclear to which extent the shuttling of Bcl-2 family species between lipid and aqueous phases contributes to regulating MOMP sensitivity. Here, we studied the interplay of tBid, Bax, and Bcl-xL, using a combined approach of deterministic mathematical modeling and retrospective as well as prospective experimental testing of model predictions. Systems modeling of the tBid–Bax interplay and their fluxes between cytosol and mitochondrial membranes reproduced experimental data on tBid-triggered Bax activation and oligomerization highly accurately. Extending these studies to analyze the cell-protective role of Bcl-xL strikingly revealed that the activity of Bcl-xL to retrotranslocate activated Bax from membranes back into the cytosol is essential to reproduce or correctly predict experimental outcomes. These included the potency of Bcl-xL in suppressing Bax oligomerization, its role in limiting Bax membrane recruitment, the resistance threshold to low concentrations of MOMP triggers as well as a response potentiaton arising from combinations of tBid and sensitizer BH3-only peptides. Importantly, retrotranslocation activity of Bcl-xL is necessary to strictly separate conditions of MOMP competency and resistance. Our results therefore identify Bax retrotranslocation by Bcl-xL as an indispensable component of the molecular switch by which Bcl-2 family members govern cellular death decisions.publishe

Formation of Bi₂Ir nanoparticles in a microwave-assisted polyol process revealing the suboxide Bi₄Ir₂O

Intermetallic phases are usually obtained by crystallization from the melt. However, phases containing elements with widely different melting and boiling points, as well as nanoparticles, which provide a high specific surface area, are hardly accessible via such a high-temperature process. The polyol process is one option to circumvent these obstacles by using a solution-based approach at moderate temperatures. In this study, the formation of Bi2Ir nanoparticles in a microwave-assisted polyol process was investigated. Solutions were analyzed using UV-Vis spectroscopy and the reaction was tracked with synchrotron-based in situ powder X-ray diffraction (PXRD). The products were characterized by PXRD and high-resolution transmission electron microscopy. Starting from Bi(NO3)(3) and Ir(OAc)(3), the new suboxide Bi4Ir2O forms as an intermediate phase at about 160 degrees C. Its structure was determined by a combination of PXRD and quantum-chemical calculations. Bi4Ir2O decomposes in vacuum at about 250 degrees C and is reduced to Bi2Ir by hydrogen at 150 degrees C. At about 240 degrees C, the polyol process leads to the immediate reduction of the two metal-containing precursors and crystallization of Bi2Ir nanoparticles

Structural and magnetic properties of P25 TiO2 nanoparticles doped by Co

The present work reports on the structural and magnetic properties of TiO2 P25 Degussa powder doped with cobalt. Dissolution of cobalt in TiO2 matrix was achieved by precipitation of tris(diethyldithiocarbamato) cobalt (III) (CoDtc - Co[S2CN(C2H5)(2)](3) in chloroform (CHCl3) and consequent thermal treatment. Five different Co atomic percentage contents were chosen, e.g., 0.5%, 1%, 2%, 5% and 10%. It was shown that cobalt atoms are uniformly distributed across TiO2 matrix and exhibit antiferromagnetic interactions at low temperatures.Center of Marine Science (CCMAR)Fundacao para a Ciencia e a Tecnologia (FCT), PortugalPortuguese Foundation for Science and Technology [UID/QUI/00100/2019]FCT, PortugalPortuguese Foundation for Science and Technology [UID/NAN/50024/2013]Slovak Academy of SciencesMinistry of Education [2/0141/16, 1/0340/18, 2/0016/17]Slovak Research and Development AgencySlovak Research and Development Agency [APVV-015-0453]COSTEuropean Cooperation in Science and Technology (COST) [CA15119 NANOUPTAKE]MagBioVin project (FP7-ERAChairs-Pilot Call-2013) [621375]info:eu-repo/semantics/publishedVersio