The Biochemical Assessment of Mitochondrial Respiratory Chain Disorders

Mitochondrial respiratory chain (MRC) disorders are a complex group of diseases whose diagnosis requires a multidisciplinary approach in which the biochemical investigations play an important role. Initial investigations include metabolite analysis in both blood and urine and the measurement of lactate, pyruvate and amino acid levels, as well as urine organic acids. Recently, hormone-like cytokines, such as fibroblast growth factor-21 (FGF-21), have also been used as a means of assessing evidence of MRC dysfunction, although work is still required to confirm their diagnostic utility and reliability. The assessment of evidence of oxidative stress may also be an important parameter to consider in the diagnosis of MRC function in view of its association with mitochondrial dysfunction. At present, due to the lack of reliable biomarkers available for assessing evidence of MRC dysfunction, the spectrophotometric determination of MRC enzyme activities in skeletal muscle or tissue from the disease-presenting organ is considered the ‘Gold Standard’ biochemical method to provide evidence of MRC dysfunction. The purpose of this review is to outline a number of biochemical methods that may provide diagnostic evidence of MRC dysfunction in patients.     

Mathematical model of magnesium ignition in an extended range of parameters

A mathematical model of ignition of a magnesium particle with allowance for a heterogeneous chemical reaction is proposed. The model allows the final particle temperature after its ignition to be found and takes into account the region of the thermal influence of the particle on the gas. A stationary solution is found, which makes it possible to propose a classification of the thermal history of the particle-gas system. The mathematical model is consistent with experimental data on the dependence of the ignition delay on the gas pressure and particle radius and on the dependence of the limiting temperature on the particle radius and the ambient pressure. The mathematical model also reveals the effect of the size of the gas layer around the particle on the integral parameters of ignition. __________ Translated from Fizika Goreniya i Vzryva, Vol. 44, No. 5, pp. 64–71, September–October, 2008.     

D-核糖发酵液活性炭吸附脱色工艺和表征

以枯草芽胞杆菌发酵生产D-核糖的发酵液为脱色体系，用简易和准确测定发酵液中的吸光度表征发酵液中的色素浓度，阐述发酵液吸附脱色工艺参数的计算。根据实验确定340nm为最合适吸光度测定波长，建立了吸光度与发酵液中的色素浓度之间的函数关系。用活性炭脱色在间歇操作条件下最佳吸附时间为30min，操作温度为50℃，pH为3．5。建立色素吸附等温线和计算式，其等温线类型为L型。     

基于EKF和UKF算法非均匀介质热物性参数重建

将无迹卡尔曼滤波技术(unscented Kalman filter, UKF)用于求解一维介质热物性参数反演问题;也对利用扩展卡尔曼滤波技术(extended Kalman filter, EKF)反演一维介质中热导率问题进行了研究。首先给出了正问题模型,然后详细介绍了EKF算法和UKF算法的基本原理。最后为了验证当前算法的可行性,采用UKF算法重建了介质内部随位置变化的热导率,并采用EKF算法重建了介质内部随时间变化的热导率。计算结果表明,UKF算法和EKF算法均能较为准确地反演介质的热导率。为了减小重建结果的时间滞后,建议使用较小的测量误差协方差R。     

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs, that are involved in the multistep process of carcinogenesis, contributing to all established hallmarks of cancer. In this review, implications of miRNAs in hematological malignancies and their clinical utilization fields are discussed. As components of the complex regulatory network of gene expression, influenced by the tissue microenvironment and epigenetic modifiers, miRNAs are “micromanagers” of all physiological processes including the regulation of hematopoiesis and metabolic pathways. Dysregulated miRNA expression levels contribute to both the initiation and progression of acute leukemias, the metabolic reprogramming of malignantly transformed hematopoietic precursors, and to the development of chemoresistance. Since they are highly stable and can be easily quantified in body fluids and tissue specimens, miRNAs are promising biomarkers for the early detection of hematological malignancies. Besides novel opportunities for differential diagnosis, miRNAs can contribute to advanced chemoresistance prediction and prognostic stratification of acute leukemias. Synthetic oligonucleotides and delivery vehicles aim the therapeutic modulation of miRNA expression levels. However, major challenges such as efficient delivery to specific locations, differences of miRNA expression patterns between pediatric and adult hematological malignancies, and potential side effects of miRNA-based therapies should be considered.     

An extended Kalman filtering approach with a criterion to set its tuning parameters; application to a catalytic reactor

In this work, the problem of tuning Kalman filters is addressed. Such tuning usually consists of finding the values of the model and measurements covariance matrices by trial and error methods till satisfactory results have been obtained. Here, we propose a new method to endow the model covariance matrix with physical meaning, enabling a more systematic gain tuning procedure. Simulation examples for a simulated non-isothermal continuous reactor and for an experimental reactor where carbon monoxide oxidation takes place are presented.     

Biomass screw feeding with tapered and extended sections

Successful feeding is critical to biomass utilization processes such as gasification and combustion, but feeding is difficult due to the adverse effects of heterogeneity, physical characteristics and moisture content of the particles. The objectives of the present study were to define blockage mechanisms and plug seal with the aid of tapered and extended sections. Wood pellets, sawdust, hog fuel and wood shavings were delivered by a screw feeder/lock hopper system. The experimental results showed that tapered and extended sections increased torque requirements significantly while improving the plug seal to the reactor, with performance depending on biomass physical properties and screw feeder characteristics.     

Assessment of well trajectory effect on slug flow parameters using CFD tools

Abstract

Oil and gas industry uses different well trajectories to enhance reservoir production rates. However, two-phase flow characterization can significantly change due to the well configuration. This study assesses this effect on slug flow development using computational fluid dynamics. An orthogonal mesh was used to assure well modeling of the slug flow dynamics. Slug flow parameters such as frequency and length were predicted using the VOF model. Four well trajectories were analyzed: toe-down, toe-up, and one-undulation with a hump or sump. Results revealed a vertical–lateral sections interaction, which increases slug length and decreases slug frequency on the horizontal pipeline. Moreover, using a toe-down well over an only-horizontal trajectory causes an increment in the slug length up to two times. Finally, a severe slugging condition was predicted in the toe-up well configuration.     

Assessment of formulation parameters needed for successful vitamin C entrapped polycaprolactone nanoparticles

Vitamin C (Vit.C)-entrapped polycaprolactone (PCL) nanoparticles (Vit.C–PCNs) were prepared by encapsulation of Vit.C into PCL-based nanoparticles (PCNs) which were prepared using double emulsion method with two steps. First, the inner aqueous phase (W₁) was added to dichloromethane solution containing PCL with homogenization to form primary emulsion (W₁/O) which was emulsified with the outer aqueous phase (W₂) containing polyvinyl alcohol as stabilizer to attain the double emulsion (W₁/O/W₂). Versatile parameters were investigated to reach to the most successful formulation for Vit.C–PCNs, such as time, effect of speed of homogenization on drug encapsulation efficiency, etc.     

Batch foaming of chain extended PLA with supercritical CO2: Influence of the rheological properties and the process parameters on the cellular structure

This study has been dedicated to the foaming of modified poly (lactic acid) with supercritical CO₂. The first part of this work consisted in a rheological modification of neat PLA through chain extension. Improvement of the melt viscosity and elasticity has been achieved by the use of an epoxy additive during a reactive extrusion process. Rheological characterizations confirmed an increase of the melt strength due to this chain extension process. Foaming was then performed on the neat and modified PLAs using a batch process with supercritical CO₂ as blowing agent. The investigation of the foaming temperature revealed an enlarged processing window for modified PLAs compared to neat PLA. Depending on the foaming parameters, foams with a cellular structure ranging from macro scale to micro scale have been obtained. A concomitant effect of the CO₂-plasticization and the crystallisation on the melt rheology could explain this wide range of cellular morphologies.     

ATR-FTIR Spectroscopy for the Assessment of Biochemical Changes in Skin Due to Cutaneous Squamous Cell Carcinoma

Nonmelanoma skin cancers represent 95% of cutaneous neoplasms. Among them, squamous cell carcinoma (SCC) is the more aggressive form and shows a pattern of possible metastatic profile. In this work, we used Fourier transform infrared spectroscopy (FTIR) spectroscopy to assess the biochemical changes in normal skin caused by squamous cell carcinoma induced by multi-stage chemical carcinogenesis in mice. Changes in the absorption intensities and shifts were observed in the vibrational modes associated to proteins, indicating changes in secondary conformation in the neoplastic tissue. Hierarchical cluster analysis was performed to evaluate the potential of the technique to differentiate the spectra of neoplastic and normal skin tissue, so that the accuracy obtained for this classification was 86.4%. In this sense, attenuated total reflection (ATR)-FTIR spectroscopy provides a useful tool to complement histopathological analysis in the clinical routine for the diagnosis of cutaneous squamous cell carcinoma.     

Biobased chain extended polyurethane and its composites with silk fiber

The biobased chain extended polyurethane (PU) was synthesized by reacting castor oil based polyol with different diisocyanates [toluene‐2,4‐diisocyanate (TDI) and hexamethylene diisocyanate (HMDI)] and chain extender such as glutaric acid. Biocomposites have been fabricated by incorporating the silk fiber into both TDI‐ and HMDI‐based PUs. The effect of incorporation of silk fiber into TDI‐ and HMDI‐based neat PU on the physicomechanical properties such as density, surface hardness, tensile strength, and percentage elongation have been investigated. The dynamic mechanical properties and the thermal stability of neat PUs and the silk fiber incorporated PU composites have been evaluated. The TDI‐based neat PU has showed higher mechanical properties compared to HMDI‐based PU. The incorporation of 10% silk fiber into TDI‐ and HMDI‐based PU resulted in an enhancement of tensile strength by 1.8 and 2.2 folds, respectively. The incorporation of silk fiber into biobased chain extended PU increased the glass transition temperature (T_g) of the resultant biocomposites. The morphology of tensile fractured neat PUs and their biocomposites with silk fiber was studied using scanning electron microscope (SEM). POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers     

Impact of Histone Modifications and Their Therapeutic Targeting in Hematological Malignancies

Hematologic malignancies are a large and heterogeneous group of neoplasms characterized by complex pathogenetic mechanisms. The abnormal regulation of epigenetic mechanisms and specifically, histone modifications, has been demonstrated to play a central role in hematological cancer pathogenesis and progression. A variety of epigenetic enzymes that affect the state of histones have been detected as deregulated, being either over- or underexpressed, which induces changes in chromatin compaction and, subsequently, affects gene expression. Recent advances in the field of epigenetics have revealed novel therapeutic targets, with many epigenetic drugs being investigated in clinical trials. The present review focuses on the biological impact of histone modifications in the pathogenesis of hematologic malignancies, describing a wide range of therapeutic agents that have been discovered to target these alterations and are currently under investigation in clinical trials.     

Assessment of interatomic parameters for the reproduction of borosilicate glass structures via DFT-GIPAW calculations

Borates and borosilicates are potential candidates for the design and development of glass formulations with important industrial and technological applications. A major challenge that retards the pace of development of borate/borosilicate based glasses using predictive modeling is the lack of reliable computational models to predict the structure-property relationships in these glasses over a wide compositional space. A major hindrance in this pursuit has been the complexity of boron-oxygen bonding due to which it has been difficult to develop adequate B–O interatomic potentials. In this article, we have evaluated the performance of three B–O interatomic potential models recently developed by Bauchy et al [J. Non-Cryst. Solids, 2018, 498, 294–304], Du et al [J. Am. Ceram. Soc. https://doi.org/10.1111/jace.16082 ] and Edèn et al [Phys. Chem. Chem. Phys., 2018, 20, 8192–8209] aiming to reproduce the short-to-medium range structures of sodium borosilicate glasses in the system 25 Na₂O x B₂O₃ (75 − x) SiO₂ (x = 0-75 mol%). To evaluate the different force fields, we have computed at the density functional theory level the NMR parameters of ¹¹B, ²³Na, and ²⁹Si of the models generated with the three potentials and the simulated MAS NMR spectra compared with the experimental counterparts. It was observed that the rigid ionic models proposed by Bauchy and Du can both reliably reproduce the partitioning between BO₃ and BO₄ species of the investigated glasses, along with the local environment around sodium in the glass structure. However, they do not accurately reproduce the second coordination sphere of silicon ions and the Si–O–T (T = Si, B) and B-O-T distribution angles in the investigated compositional space which strongly affect the NMR parameters and final spectral shape. On the other hand, the core-shell parameterization model proposed by Edén underestimates the fraction of BO₄ species of the glass with composition 25Na₂O 18.4B₂O₃ 56.6SiO₂ but can accurately reproduce the shape of the ¹¹B and ²⁹Si MAS-NMR spectra of the glasses investigations due to the narrower B–O–T and Si-O-T bond angle distributions. Finally, the effect of the number of boron atoms (also distinguishing the BO₃ and BO₄ units) in the second coordination sphere of the network former cations on the NMR parameters have been evaluated.     

Assessment of conformational parameters as predictors of limited proteolytic sites in native protein structures

Despite the importance of limited proteolysis in biological systems it isoften difficult to rationalize why a proteinase hydrolyses a particularbond, given a simple sequence specificity alone. Understanding of thestructural properties limiting the proteolysis represents a first step onthe pathway to control and manipulation of this phenomena. An expanded setof nick-sites in proteins of known tertiary structure, cut by both narrowand broad specificity proteinases, has been generated yielding a robustdata set of strictly limited sites. A critical evaluation of an expandedset of conformational parameters revealed a strong correlation with limitedproteolytic sites, although they are only modest predictors in isolation.The overall predictive power is significantly improved when theconformational parameters are combined in a weighted predictive scheme thatpermits their relative importance to be compared via a Metropolis searchprotocol. A subset of the parameters performs equally well demonstratingthe key determinants of susceptibility. The derived predictive algorithmhas been made available via the internet. Its utility for predicting othersurface-correlated features is also discussed.     

Assessment of resin adhesives aging by means of rheological parameters,Inverse Gas Chromatography,and FTIR

In this study, the rheological parameters as well as Flory–Huggins parameter determined by Inverse Gas Chromatography (IGC) were applied for assessment of the changes occurring during storage of the resole resin and their composites. It was proved that storage of resole and its composites at the low temperature (about 10°C) can slow significantly the process of their aging. Main idea of research was to determine time dependence of rheological properties for resole resin. These data should enable to extend shelf life of resin containing products. The rheological properties of samples were studied by the determination of flow curve. Share rate was changed from 10 to 500 1/s. Samples were examined in following intervals (increasing storage time): immediately after preparing the sample and then after storage, respectively: after two, four, eight, and twelve weeks. To extend shelf life of resin, it was mixed with different additives: zeolite Micro 20, Mg(OH)₂, PAF, synthetic zeolites: sodium form Z1, hydrogen form Z2. Flory–Huggins parameter determined by use of IGC let to assess physicochemical changes occurring in resole and its composites during storage. IGC turned out to be more sensitive method for assessment of changes occurring during resin aging than rheological measurements. FTIR technique was used to assess chemical changes occurring during resoles compositions storage. It indicated that oxidation reaction can occur during resoles composite aging.     

Adoptive Immunotherapy Strategies with Cytokine-Induced Killer (CIK) Cells in the Treatment of Hematological Malignancies

Cytokine-induced killer (CIK) cells are a heterogeneous population of immune effector cells that feature a mixed T- and Natural killer (NK) cell-like phenotype in their terminally-differentiated CD3⁺CD56⁺ subset. The easy availability, high proliferation rate and widely major histocompatibility complex (MHC)-unrestricted antitumor activity of CIK cells contribute to their particularly advantageous profile, making them an attractive approach for adoptive immunotherapy. CIK cells have shown considerable cytotoxicity against both solid tumors and hematological malignancies in vitro and in animal studies. Recently, initial clinical experiences demonstrated the feasibility and efficacy of CIK cell immunotherapy in cancer patients, even at advanced disease stages. Likewise, the clinical application of CIK cells in combination with standard therapeutic procedures revealed synergistic antitumor effects. In this report, we will focus our consideration on CIK cells in the treatment of hematological malignancies. We will give insight into the latest advances and future perspectives and outline the most prominent results obtained in 17 clinical studies. Overall, CIK cells demonstrated a crucial impact on the treatment of patients with hematological malignancies, as evidenced by complete remissions, prolonged survival durations and improved quality of life. However, up to now, the optimal application schedule eventually favoring their integration into clinical practice has still to be developed.