Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA^high, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA^high at higher risk of progression and death.     

Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples

The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, β-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency’s Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and β-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.     

A Dual Physical Cross-Linking Strategy to Construct Tough Hydrogels with High Strength,Excellent Fatigue Resistance,and Stretching-Induced Strengthening Effect

Hydrogels with excellent stiffness, toughness, anti-fatigue, and self-recovery properties are regarded as promising water-containing materials. In this work, a dual physically cross-linked (DPC) sodium alginate (SA)/poly[acrylamide (AAm)-acrylic acid (AAc)-octadecyl methacrylate (OMA)]-Fe³⁺ hydrogel is reported, which is constructed by hydrophobic association (HA) and ionic coordination (IC). The optimal DPC hydrogel demonstrates excellent mechanical performance: tensile modulus of 0.65 MPa, tensile strength of 3.31 MPa, elongation at break of 1547%, and toughness of 27.8 MJ m^–3. SA/P(AAm-AAc-OMA)-Fe³⁺ DPC hydrogels also exhibit prominent anti-fatigue and self-recovery performance (99.1–109.7% modulus recovery and 90.4–108.9% dissipated energy recovery after resting for 5 min without additional stimuli at ambient temperature) through the reconstruction of reversible physical cross-linking. Some of the SA/P(AAm-AAc-OMA)-Fe³⁺ DPC hydrogels even exhibit a stretching-induced strengthening effect, which is similar to the performance of muscle—“the more training, the more strength.” Hence, the combination of HA and IC will provide an effective approach to design DPC hydrogels with desirable mechanical performances and a longer service life for wider applications of soft materials.     

Determination of heavy metals and volatile aromatic compounds in used engine oils and sludges

Assessment of contaminant releases during utilization of used oils is essential for the determination of environmental acceptability. These paper reports the results of the study examining a toxic metal leachability from used engine oil and sludge samples employing leaching test (TCLP). The leaching test indicated that lead in oil samples exceeded 5-ppm concentration level what qualified them as a toxic waste. The samples of contaminated sludge were found to contain high concentration of total lead, barium and chromium, but the leaching test showed concentration below regulatory limit. The total content of benzene, ethylbenzene, toluene, and xylenes (BETX), and naphthalene in used oil and sludge samples was also determined and was found not to be a significant factor to contamination.     

Kinetics of the Initial Stage of Sintering from Shrinkage Data: Simultaneous Determination of Activation Energy and Kinetic Model from a Single Nonisothermal Experiment

A new method for the kinetic analysis of the initial stage of sintering for constant-heating-rate data has been proposed. Unlike all of the methods previously reported in the literature, this new method proposed here allows the simultaneous determination of the activation energy and the kinetic model from a single dilatometric curve recorded under a linear-heating-rate program. The proposed method has been tested with simulated sintering curves and experimental results have been obtained for the sintering of a rutile sample.     

Surface Pretreatments of Silicon Nitride for CVD Diamond Deposition

The efficiency of different surface pretreatments (four standard chemical etchings and four diamond powder abrasive procedures) on silicon nitride (Si₃N₄) substrates for chemical vapor deposition (CVD) of diamond has been systematically investigated. Blank Si₃N₄ samples were polished with colloidal silica (∼0.25 μm). Diamond nucleation and growth runs were conducted in a microwave plasma chemical vapor deposition apparatus for 10 min and 6 h, respectively. Superior results concerning nucleation density ( N _d∼ 10¹⁰ cm⁻² after 10 min), film uniformity, and grain size (below 2 μm after 6 h) were obtained for the mechanically microflawed samples, revealing that chemical etchings (hot and cold strong acids, molten base or CF₄ plasma) are not crucial for good CVD diamond quality on Si₃N₄.     

Activity of gold towards methylamine electrooxidation

The kinetics of methylamine oxidation at a gold electrode in contact with an alkaline electrolyte solution was studied. The adsorptive behaviour of substrate molecules was determined by changes in the differential capacitance of the double layer at the electrode/solution interface. The electrooxidation of methylamine occurs only in the potential range of gold oxide layer formation. The general reaction pathways of methylamine oxidation on the gold electrode is proposed.     

Fast finite difference Poisson solvers on heterogeneous architectures

In this paper we propose and evaluate a set of new strategies for the solution of three dimensional separable elliptic problems on CPU–GPU platforms. The numerical solution of the system of linear equations arising when discretizing those operators often represents the most time consuming part of larger simulation codes tackling a variety of physical situations. Incompressible fluid flows, electromagnetic problems, heat transfer and solid mechanic simulations are just a few examples of application areas that require efficient solution strategies for this class of problems. GPU computing has emerged as an attractive alternative to conventional CPUs for many scientific applications. High speedups over CPU implementations have been reported and this trend is expected to continue in the future with improved programming support and tighter CPU–GPU integration. These speedups by no means imply that CPU performance is no longer critical. The conventional CPU-control–GPU-compute pattern used in many applications wastes much of CPU’s computational power. Our proposed parallel implementation of a classical cyclic reduction algorithm to tackle the large linear systems arising from the discretized form of the elliptic problem at hand, schedules computing on both the GPU and the CPUs in a cooperative way. The experimental result demonstrates the effectiveness of this approach.     

Effects of physical refining on contents of waxes and fatty alcohols of refined olive oil

Changes in the contents of waxes and fatty alcohols during deodorization/physical refining of bleached olive oil were studied. Experiments were carried out with 1.85% acidity oil, which was physically refined in a discontinuous deodorizer of 250-kg maximum capacity using nitrogen as stripping gas instead of steam. The variables studied were load and temperature of oil in the deodorizer as well as N₂ flow. Analyses of waxes and alcohols were carried out at different operation times. The maximum content of wax was always observed when the oil reached the deodorization temperature. The variation in the wax content depended on temperature and N₂ flow. Wax decomposition started and continued during the operating time, and a progressive decrease, which was pronounced between 3 and 4 h, was observed. Small changes in waxes were observed between 4 and 5 h. Total content of fatty alcohols diminished throughout the operating time, and changes did not depend on the variables studied.