Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

Effect of water on the oxygen barrier properties of poly(ethylene terephthalate) and polylactide films

The aim of this work was to study the variations in the oxygen diffusion, solubility, and permeability coefficients of polylactide (PLA) films at different temperatures (5, 23, and 40°C) and water activities (0–0.9). The results were compared with the oxygen diffusion, solubility, and permeability coefficients obtained for poly(ethylene terephthalate) (PET) films under the same experimental conditions. The water sorption isotherm for PLA films was also determined. Diffusion coefficients were determined with the half‐sorption time method. Also, a consistency test for continuous‐flow permeability experimental data was run to obtain the diffusion coefficient with the lowest experimental error and to confirm that oxygen underwent Fickian diffusion in the PLA films. The permeability coefficients were obtained from steady‐state permeability experiments. The results indicated that the PLA films absorbed very low amounts of water, and no significant variation of the absorbed water with the temperature was found. The oxygen permeability coefficients obtained for PLA films (2–12 × 10^?18 kg m/m² s Pa) were higher than those obtained for PET films (1–6 × 10^?19 kg m/m² s Pa) at different temperatures and water activities. Moreover, the permeability coefficients for PLA and PET films did not change significantly with changes in the water activity at temperatures lower than 23°C. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1790–1803, 2004     

The effects of bleached and unbleached rosemary oleoresins on light-sensitized oxidation of soybean oil

Bleached and unbleached forms of a rosemary oleoresin (RO) in stripped and nonstripped soybean oil behave both as antioxidant and prooxidant in a light-induced oxidative system. At 0.02 and 0.05% levels, RO had the greatest antioxidant activity, while at 0.01 and 0.5% levels it had the highest prooxidant activity in both stripped and nonstripped soybean oil. Treatment of both soybean oil systems with tertiary butylhydroquinone controlled light-induced oxidation of the oil better than did the oleoresin treatments. The prooxidant activity of the 0.5% RO level was probably due to an excess of prooxidant components being carried into the oil at that level, whereas the reduced antioxidant activity at 0.01% was probably due to the low initial level of active antioxidant components being added to the oil. Published as Journal Series No. 10072, Nebraska Agricultural Research Division, Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583-0919.     

Construction, properties and specific fluorescent labeling of a bovine prothrombin mutant engineered with a free C-terminal cysteine

To define the role of phosphatidylserine-induced conformationalchanges in prothrombin activation during blood coagulation,a recombinant bovine prothrombin was constructed, characterizedand shown to have a globally native-like conformation. We introduceda cysteine to replace the penultimate residue (Gly581) of apreviously constructed active site mutant, and expressed thedouble mutant in Chinese hamster ovary cells at the level of0.6 µg/ml of cell culture medium. Specific labeling withfluorescein maleimide was accomplished by limited reductionwith dithiothreitol to free the engineered cysteine while maintainingthe native-like functional properties of the molecule. The averagestoichiometry of labeling was 0.84 probe/protein. The locationof the probe at the C-terminus was confirmed by proteolysisby native thrombin, by Taipan venom, and by carboxypeptidaseY. Both the double mutant and labeled prothrombin could be activatedby snake venoms and the prothrombinase but, as expected, thedouble mutant meizothrombin did not autolyze as does nativemeizothrombin. Thus, for the first time, a native-like but specificallylabeled prothrombin has been constructed. This molecule willbe an essential tool for elucidating the structural role ofmembranes during prothrombin activation. In addition, the methodsdescribed might be usefully applied to labeling of an odd, engineeredcysteine in other disulfide bond-containing proteins.     

Structuration bridging diffusion of innovations and gender relations theories: a case of paradigmatic pluralism in IS research

This paper discusses the adoption of a pluralist theoretical framework – one that is also multiparadigmatic – for conducting and publishing information system (IS) research. The discussion is illustrated by a single case study involving the Australian cotton industry. The theoretical framework is informed by three sociological theories, each with its particular paradigmatic assumptions: structuration theory as a meta‐theory, and diffusion of innovations and gender relations as lower‐level theories from notionally opposing paradigms. Theoretical pluralism helped to produce rich findings, illuminating both the social nature of women farmers' roles, the materiality of the cotton farming context, the characteristics of the decision support systems in use and the recursive way in which human agency and institutional pressures shape each other. Because users of so‐called divergent paradigms often face criticism based on the incommensurability issue, one of the main contributions of this paper is to discuss the value of a pluralist and multiparadigmatic theoretical framework in dealing with complex IS social phenomena.     

Relationship between cell morphology and impact strength of microcellular foamed high‐density polyethylene/polypropylene blends

Polymer blends, such as those resulting from recycling postconsumer plastics, often have poor mechanical properties. Microcellular foams have been shown to have the potential to improve properties, and permit higher‐value uses of mixed polymer streams. In this study, the effects of microcellular batch processing conditions (foaming time and temperature) and HDPE/PP blend compositions on the cell morphology (the average cell size and cell‐population density) and impact strength were studied. Optical microscopy was used to investigate the miscibility and crystalline morphology of the HDPE/PP blends. Pure HDPE and PP did not foam well at any processing conditions. Blending facilitated the formation of microcellular structures in polyolefins because of the poorly bonded interfaces of immiscible HDPE/PP blends, which favored cell nucleation. The experimental results indicated that well‐developed microcellular structures are produced in HDPE/PP blends at ratios of 50:50 and 30:70. The cell morphology had a strong relationship with the impact strength of foamed samples. Improvement in impact strength was associated with well‐developed microcellular morphology. Polym. Eng. Sci. 44:1551–1560, 2004. © 2004 Society of Plastics Engineers.     

A comparison of pyrrolidide and picolinyl ester derivatives for the identification of fatty acids in natural samples by gas chromatography-mass spectrometry

The pyrrolidide and picolinyl ester derivatives of the fatty acids in two natural lipid samples rich in unsaturated fatty acids, pig testis lipids and cod liver oil were satisfactorily resolved on capillary columns of fused silica coated with stationary phases of varying polarity. The picolinyl esters, in particular, when subjected to gas chromatography-mass spectrometry on a column containing a cross-linked methyl silicone, gave distinctive mass spectra, which could be interpreted in terms of both the numbers and positions of the double bonds.     

An International Collaborative Study on Trypsin Inhibitor Assay for Legumes,Cereals, and Related Products

For determining trypsin inhibitor activity (TIA) in soy products, the American Oil Chemists' Society (AOCS) Method Ba 12-75 has been used. It measures differences in absorbance at 410 nm of bovine trypsin activity toward a synthetic substrate (Nα-benzoyl-DL-arginine-p-nitroanilide) in the absence and presence of an inhibitor. Recently, a significantly improved method was developed (JAOCS, 2019, 96:635–645), featuring 5 mL of total assay volume, enzyme-last sequence, and single inhibitor level in duplicate. It is proposed as the AOCS Method Ba 12a-2020. As a part of the AOCS method approval process, a collaborative study involving 12 international laboratories was conducted to evaluate the performance of the proposed method. The study involved measuring TIA in 10 selected test samples plus a blind duplicate. They included soybeans, pulses, cereals, and their processed products (flours, concentrates, and isolates). After rigorous statistical treatment of the data, only three outliers were removed from the data of two samples. Repeatability relative standard deviations (RSDr) for the 11 samples ranged from 0.99% to 5.52%. Reproducibility RSD (RSD_R) ranged from 7.07% to 22.92%, with seven samples having RSD_R around 10% or less. The remaining four samples had very low TIA, and their RSD_R values ranged from 13.34% to 22.92%. The study has demonstrated reliable performance of the proposed AOCS method. Several collaborators carried out additional experiments addressing some aspects of the method, leading to further refinements. The proposed method is undergoing evaluation by the AOCS Uniform Methods Committee for adoption as an Official Method for measuring TIA in various legume and grain products.     

Hydrocarbon condensation modelling to mitigate fluid coker cyclone fouling

FLUID COKING is a continuous process that thermally converts heavy hydrocarbons, such as oil sands bitumen, to lighter and higher‐value products by horizontal spray injection onto a fluidized bed of hot coke particles. The cyclone sections of commercial fluid coker reactors experience fouling during typical operation, which limits unit run lengths. The main objective of this work is to improve fluid coker reliability by proposing cyclone fouling mitigation strategies based on practical operation modifications. This study developed a process simulation in Aspen Plus to establish the combined impact of vapour‐liquid equilibrium, endothermic thermal cracking reactions, pressure changes, and overall fluid dynamics in the selected fluid coker control volumes. The hydrocarbon composition was defined by applying an assay characterization of distillation data for representative hydrocarbon streams. Case studies were performed to determine the sensitivity of the predicted temperatures and hydrocarbon condensate flow rates for: (a) the burner‐to‐fluid coker transfer line temperature; (b) the hot coke flow rate; (c) hot coke entrainment from the freeboard region; and (d) scouring coke flow rate in the horn chamber. The scouring coke flow rate was identified as the most promising process lever to mitigate fluid coker cyclone fouling.     

Poly(vinylidene fluoride) with zinc oxide and carbon nanotubes applied to pressure sheath layers in oil and gas pipelines

In this work, PVDF composites containing 0.2% (m/m) of carbon nanotubes (MWCNTs), PVDF with 5.0% (m/m) of zinc oxide (ZnO), and composites containing both particles in the same contents in the matrix were melt processed in a mini-extruder machine with double screws, using the counter-rotation mode. Composites were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), dynamic-mechanical analysis (DMA), and contact angle tests (CA). The samples presented the predominance of the α phase, with an increased degree of crystallinity as well as an increase in dimensional stability by incorporating both fillers, showing a synergistic effect between these particles, as shown on FTIR, DSC, and XRD results. SEM images showed a good dispersion of high aspect ratio particles. In general, DMA and TGA analysis showed that composites had not decreased their thermal and mechanical performance when compared to neat PVDF. Results of CA analysis showed an increase in the hydrophobicity of the sample containing MWCNTs. Permeability tests were also performed using a differential pressure system, combining high temperature and pressure, obtaining permeability measures and time lag. This work presents an alternative of composite materials, suggesting its application in the internal pressure sheath layers of oil and gas flexible pipes.