Formation of a submicrocrystalline structure in austenitic 08Kh18N10T steel during equal-channel angular pressing followed by heating

The structure and mechanical properties of austenitic 08KhN10T steel subjected to equal-channel angular pressing (ECAP) at room temperature (? = 3.2) and subsequent heating are studied. In the course of ECAP, the steel undergoes a martensitic transformation; the martensite content reaches 45%. Upon heating, martensite (ferrite) transforms into austenite. The partly submicrocrystalline oriented structure of the 08Kh18N10T steel in the austenitic (55%)-martensitic (45%) state (formed upon ECAP) provides its high strain hardening (σ_0.2 = 1315 N/mm²), as compared to the initial state (σ_0.2 = 250 N/mm²), and high plasticity δ = 11%. After heating to 550°C, the steel has a predominantly submicrocrystalline austenitic (80%)-ferritic (20%) structure, σ_0.2 = 1090 N/mm², and δ = 11%.     

Microstructure and magnetic properties of <Emphasis Type="Italic">R</Emphasis>-Fe-B-Cu (<Emphasis Type="Italic">R</Emphasis> = Pr,Nd) alloys deformed by equal-channel angular pressing and subsequent hot upsetting

Effects of equal-channel angular pressing with controlled back pressure (ECAP-BP) and subsequent upsetting on the formation of the texture, magnetic properties, and changes in the microstructure of R-Fe-B-Cu (17–20 at. % R, R = Pr, Nd) alloys have been investigated. It has been shown that, under the action of ECAP-BP at 470°C, a high coercive force H _c arises and a diametral texture is formed in the Pr-Fe-B-Cu alloys. Application of hot compression to alloys processed by ECAP-BP increases the degree of texture if the compression is applied in the direction of the initial texture axis or reorientes the texture axis in the direction of compression if the compression is applied in the direction perpendicular to the initial texture. It has been established that to obtain a high level of magnetic hysteresis properties in the Nd-Fe-B-Cu alloys, the combined hot deformation of these alloys should be carried out at temperatures above 500°C.     

Chemical preparation of an isotopically enriched superoxide dismutase and its characterization as a standard for species-specific isotope dilution analysis

The development of methods to analyze accurately and precisely individual metalloproteins is of increasing importance. Here we describe for the first time the chemical preparation and characterization of an isotopically enriched metalloenzyme containing two different metal isotopes. Its evaluation as a standard in species-specific isotope dilution analysis by HPLC coupled to inductively coupled plasma mass spectrometry is carefully evaluated. Our model enzyme bovine superoxide dismutase (SOD) contains both Cu and Zn and is remarkably stable at high temperatures and even under denaturing conditions. The enzyme's metal cofactors were removed under a range of different conditions and replaced with isotopically enriched 65Cu and 68Zn. Depending on the conditions, various isotopic ratios differing from the natural Cu and Zn abundances were obtained for the reconstituted enzyme. Both the wild type and isotopically enriched enzyme had the same migration pattern on native 1D-PAGE. Using an enzyme activity test, we showed that the incorporated 65Cu was bound to the right SOD-binding site, since the measured activity correlated directly with the amount of Cu incorporated. Mixing the native and the isotopically enriched enzyme standard with free enriched 65Cu and 68Zn or a metal chelator did not result in any exchange or loss of the metals from the enzyme at neutral pH. This verifies the stability of the enzyme metal center under the chosen conditions. The isotopically enriched enzyme standard was spiked into a wild type SOD solution to evaluate its use for species-specific isotope dilution experiments. To our knowledge, this is the first report of the chemical preparation of a metalloenzyme containing two different isotopically enriched metals. We provide evidence that the incorporated isotopically enriched metals are bound to the right binding site of SOD using an specific enzymatic activity assay.     

Ionic Liquid Approach Toward Manufacture and Full Recycling of All‐Cellulose Composites

All‐cellulose composites (ACCs) are prepared from high‐strength rayon fibers and cellulose pulp. The procedure comprises the use of a pulp cellulose solution in the ionic liquid (IL) 1‐ethyl‐3‐methyl imidazolium acetate ([EMIM][OAc]) as a precursor for the matrix component. High‐strength rayon fibers/fabrics are embedded in this solution of cellulose in the IL followed by removal of the IL. Different concentrations of cellulose in the IL are investigated and the mechanical properties of the final ACCs are determined via tensile, bending, and impact testing. ACCs prepared in this study show mechanical properties comparable to thermoplastic glass fiber‐reinforced plastics. Apart from being bio‐based, they possess several advantages such as biodegradability and full recyclability. The recycling of ACCs is successfully demonstrated in several cycles by using the recycled cellulose for subsequent matrix preparation.     

Sequential Targeting of PLK1 and PARP1 Reverses the Resistance to PARP Inhibitors and Enhances Platin-Based Chemotherapy in BRCA-Deficient High-Grade Serous Ovarian Cancer with KRAS Amplification

Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.     

Structure and properties of steel St3 after hot equal-channel angular pressing

Conclusions 1. The process of warm deformation of steel St3 by the method of equal-channel angular pressing (ECAP) with channels intersecting at an angle of 90° yields an ultrafinegrain structure with grains 0.25–0.45 μm in size. 2. The ultrafine-grain structure of low-carbon steel St3 increases the strength to σ_0.2=700 − 850 MPa at a quite satisfactory ductility (δ=10 − 15%), which corresponds to the strength level of low-alloy high-strength steels. 3. The performance of ECAP under conditions close to pure shear makes it possible to obtain a quite uniform distribution of the microhardness over the cross section of the specimen. Translated from Metallovedenie i Termicheskaya Obrabotka Metallov, No. 9, pp. 31 – 35, September, 2000.     

Solid Particle Effects in Centi-scale Slurry Bubble Columns

Both solid particles and column diameter affect the gas holdup and flow regimes in slurry bubble columns, but investigations of the combined effects are not to be found. This study shows the simultaneous impacts on the overall gas holdup and flow regime transitions and determines the dominant effects in slurry bubble columns on the centi-scale containing solid particle concentrations up to 20 vol %. Additional tomography measurements are presented to visualize the gas phase flow and the spatial gas phase distribution in the column.     

The Discovery of New Cyanobactins from Cyanothece PCC 7425 Defines a New Signature for Processing of Patellamides

Cyanobactins, including patellamides, are a group of cyanobacterial post‐translationally modified ribosomal cyclic peptides. The final product should in theory be predictable from the sequence of the precursor peptide and the associated tailoring enzymes. Understanding the mechanism and recognition requirements of these enzymes will allow their rational engineering. We have identified three new cyanobactins from a Cyanothece PCC 7425 culture subjected to a heat shock. One of these compounds revealed a novel signature signal for ThcA, the subtilisin‐like serine protease that is homologous to the patellamide protease PatA. The crystal structure of the latter and modelling studies allow rationalisation of the recognition determinants for both enzymes, consistent with the ribosomal biosynthetic origin of the new compounds.     

Species-Dependent Metabolism of Benzo[c]Chrysene Mediated by c-DNA-Expressed Human,Rodent and Fish Cytochrome P450 Enzymes

The metabolism of benzo[c]chrysene (B[c]Ch) with various cytochrome P450 (CYP) enzymes including rat 1A1, 1A2, 2B1 and 2E1, human 1A1, 1A2, 2A6, 1B1, 3A4 and 2E1, mouse 1B1, and scup fish 1A1 expressed in Chinese hamster V79 cells has been investigated to clarify the role of individual enzymes in the regioselective oxidation of B[c]Ch and the species dependency. In six cell lines expressing individual CYP enzymes from four different species B[c]Ch was metabolized to several isomeric phenols and trans?dihydrodiols. However, cell lines expressing human 3A4, 2A6 and 2E1 or rat 1A2, 2B1 and 2E1 were metabolically in-competent towards B[c]Ch. Among the trans?dihydrodiols the 9,10-isomer could be detected in cells expressing human, rat and fish CYP 1A1 and to a minor extent in cells with human 1A2, but not in cells expressing human and mouse CYP 1B1. The latter two cell lines produced high amounts of the bay region 3,4-dihydrodiol, whereas the K-region 7,8-dihydrodiol was a minor metabolite. Oxidation of B[c]Ch to the 1,2-dihydrodiol could not be catalyzed by any of the CYP enzymes investigated except fish 1A1. Our results suggest that metabolic activation of B[c]Ch is initiated predominantly by CYP 1A1 to result selectively in the formation of fjord region 9,10-dihydrodiol 11,12-epoxides regardless of the species involved. The activation of B[c]Ch appears to be limited by a low regioselectivity for the 9,10-oxidation.     

Identification and quantification of arsenolipids using reversed-phase HPLC coupled simultaneously to high-resolution ICPMS and high-resolution electrospray MS without species-specific standards

Although it has been known for decades that arsenic forms fat-soluble arsenic compounds, only recent attempts to identify the compounds have been successful by using a combination of fractionation and elemental and molecular mass spectrometry. Here we show that arsenolipids can directly be identified and quantified in biological extracts using reversed-phase high-performance liquid chromatography (RP-HPLC) simultaneously online-coupled to high-resolution inductively coupled plasma mass spectrometry (ICPMS) and high-resolution electrospray mass spectrometry (ES-MS) without having a lipophilic arsenic standard available. Using a methanol gradient for the separation made it necessary to use a gradient-dependent arsenic response factor for the quantification of the fat-soluble arsenic species in the extract. The response factor was obtained by using the ICPMS signal of known concentration of arsenic. The arsenic response was used to determine species-specific response factors for the different arsenic species. The retention time for the arsenic species was utilized to mine the ES-MS data for accurate mass and their tandem mass spectrometry (MS/MS) fragmentation pattern to give information of molecular formula and structure information. The majority of arsenolipids, found in the hexane phase of fish meal from capelin ( Mallotus villosus ) was in the form of three dimethylarsinoyl hydrocarbons (C(23)H(38)AsO, C(17)H(38)AsO, C(19)H(42)AsO) with minor amounts of dimethylarsinoyl fatty acids (C(17)H(36)AsO(3), C(23)H(38)AsO(3), C(24)H(38)AsO(3)). One of the dimethylarsinoyl fatty acids (C(24)H(38)AsO(3)), with an even number of carbon in the fatty acid chain, was identified for the first time in this work. This molecular formula is unusual and in contrast to all previously identified arsenic-containing fatty acids with odd numbers of carbon.