High-output-impedance current-mode multiphase sinusoidal oscillator employing current differencing transconductance amplifier-based allpass filters

This article presents a multiphase sinusoidal oscillator using current differencing transconductance amplifier (CDTA)-based allpass filters. The oscillation condition and oscillation frequency can be orthogonally controlled. The proposed circuit provides 2n – phase signals (n≥2) that are equally spaced in phase and of equal amplitude. The circuit requires one CDTA, two resistors and one capacitor for each phase and no additional current amplifier. Owing to high-output impedances, the proposed circuit enables easy cascading in current-mode configurations. The effects of the nonidealities of the CDTA-allpass sections were also studied. The results of PSpice simulations are presented, demonstrating their consistency with theoretical assumptions.     

KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

Uveal melanoma (UM) is an ocular tumor with a dismal prognosis. Despite the availability of precise molecular and cytogenetic techniques, clinicopathologic features with limited accuracy are widely used to predict metastatic potential. In 51 UM tissues, we assessed a correlation between the expression of nine proteins evaluated by immunohistochemistry (IHC) (Melan-A, S100, HMB45, Cyclin D1, Ki-67, p53, KIT, BCL2, and AIFM1) and the presence of UM-specific chromosomal rearrangements measured by multiplex ligation-dependent probe amplification (MLPA), to find IHC markers with increased prognostic information. Furthermore, mRNA expression and DNA methylation values were extracted from the whole-genome data, achieved by analyzing 22 fresh frozen UM tissues. KIT positivity was associated with monosomy 3, increasing the risk of poor prognosis more than 17-fold (95% CI 1.53–198.69, p = 0.021). A strong negative correlation was identified between mRNA expression and DNA methylation values for 12 of 20 analyzed positions, five located in regulatory regions of the KIT gene (r = −0.658, p = 0.001; r = −0.662, p = 0.001; r = −0.816; p < 0.001; r = −0.689, p = 0.001; r = −0.809, p < 0.001, respectively). DNA methylation β values were also inversely associated with KIT protein expression (p = 0.001; p = 0.001; p = 0.015; p = 0.025; p = 0.002). Our findings, showing epigenetic deregulation of KIT expression, may contribute to understanding the past failure to therapeutically target KIT in UM.     

Insight into Bortezomib Focusing on Its Efficacy against P-gp-Positive MDR Leukemia Cells

In this paper, we compared the effects of bortezomib on L1210 (S) cells with its effects on P-glycoprotein (P-gp)-positive variant S cells, which expressed P-gp either after selection with vincristine (R cells) or after transfection with a human gene encoding P-gp (T cells). Bortezomib induced the death-related effects in the S, R, and T cells at concentrations not exceeding 10 nM. Bortezomib-induced cell cycle arrest in the G2/M phase was more pronounced in the S cells than in the R or T cells and was related to the expression levels of cyclins, cyclin-dependent kinases, and their inhibitors. We also observed an increase in the level of polyubiquitinated proteins (via K48-linkage) and a decrease in the gene expression of some deubiquitinases after treatment with bortezomib. Resistant cells expressed higher levels of genes encoding 26S proteasome components and the chaperone HSP90, which is involved in 26S proteasome assembly. After 4 h of preincubation, bortezomib induced a more pronounced depression of proteasome activity in S cells than in R or T cells. However, none of these changes alone or in combination sufficiently suppressed the sensitivity of R or T cells to bortezomib, which remained at a level similar to that of S cells.     

Z Copy‐Controlled Gain‐Current Differencing Buffered Amplifier and its applications

The Z Copy‐Controlled Gain‐Current Differencing Buffered Amplifier (ZC‐CG‐CDBA) is introduced in the paper. In addition to the well‐known CDBA, the input Current Differencing Unit (CDU) is modified and completed by special circuits. Analogously to the conventional CDBA, the z terminal is internally connected to the input of voltage buffer. The current gain from the difference input p, n to the output z can be controlled electronically or by an external device. In addition, an independent high‐impedance output zc is available, providing difference current I_p?I_n. In the paper, the extension of application range of the ZC‐CG‐CDBA compared with the conventional CDBA is referred to. The novel circuit element is assembled from commercial integrated circuits and its principle is verified experimentally on a universal second‐order filter. Copyright © 2010 John Wiley & Sons, Ltd.     

Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multidrug-Resistance Proteins

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure–activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.     

Reduced graphene oxide–poly(methyl methacrylate) nanocomposite as a supercapacitor

An exhaustive study on a nanocomposite–poly(methyl methacrylate) matrix material as a supercapacitor is presented. The study includes morphological, structural, and electrochemical characterization. Different electrolytes were used, for which both pseudocapacitance (for reduced graphene oxide) and electric double‐layer capacitance (for functionalized graphene) were observed. An optimum nanocomposite weight percentage was found (2%), and the best performance with highest capacitance (30.4 F/g) was seen for the electrolyte including the smallest anions (OH^?), being among the best values for similar systems, that is, a nanocomposite/nonconductive polymer matrix. In addition, a model is presented that explains the underlying electron transport mechanism. The results are promising for the construction of supercapacitors based on novel nanocomposite–poly(methyl methacrylate) matrix materials. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46685     

Simultaneous determination of quality parameters of biodiesel/diesel blends using HATR-FTIR spectra and PLS, iPLS or siPLS regressions

Partial least-squares (PLS), interval partial least squares (iPLS) and synergy partial least squares (siPLS) regressions were used to simultaneous determination of quality parameters of biodiesel/diesel blends. Biodiesel amount, specific gravity, sulfur content and flash point were evaluated using spectroscopic data in the mid-infrared region obtained with a horizontal attenuated total reflectance (HATR) accessory. Eighty-five binary blends were prepared using biodiesel and two types of diesel, in concentrations from 0.2 to 30% (v/v). Fifty-seven samples were used as a calibration set, whereas 28 samples were used as an external validation set. All samples were characterized using the appropriated standard methods. The specific gravity values at 20 °C were in the range of 848.2-866.2 kg/m³. Flash point values lay between 47.0 and 79.5 °C. Sulfur content values varied from 312 to 1351 mg/kg. Raw spectra of the samples were corrected by multiplicative scatter correction (MSC) and were pre-processed using a mean-centered procedure. Algorithms iPLS and siPLS were able to select the most adequate spectral region for each property studied. For all the properties studied, the siPLS algorithm produced better models than the full-spectrum PLS, selecting the most important bands. The quantification of biodiesel was performed using two spectral regions between 650-1909 cm⁻¹ and 2746-3165 cm⁻¹, and an excellent correlation coefficient of R² = 0.9996 was obtained. The specific gravity was determined from the spectral region from 650 to 1070 cm⁻¹, which yielded a very good correlation coefficient of R² = 0.9987. The sulfur content was evaluated from the spectral regions of 1070-1491 cm⁻¹ and 2746-3165 cm⁻¹. A very good correlation coefficient of R² = 0.9995 was obtained, regardless of whether the samples were formulated with metropolitan or countryside diesel. Finally, the flash point was determined from the spectral region between 756 and 968 cm⁻¹ and a very good correlation coefficient of R² = 0.9982 was obtained.     

Comparative study of the Effect of Oxygen and Oxygen/Ozone mixtures on the Electrochemical behaviour of different Metals

The effect of dissolved ozone on the electrochemical behaviour of heat exchanger structural materials (carbon steel, stainless steel, copper, 70:30 copper–nickel, aluminium brass and titanium grade 1) was studied to evaluate the possibility of using ozone as sole biocide in cooling water treatment. With this purpose, voltammetric and open circuit potential (OCP) against time measurements at different ozone concentrations between 0.1 and 1.2 ppm were made. Results show different electrochemical responses according to the metal characteristics and the solution composition. First, the passivity of titanium and stainless steel was not affected by ozone. A linear OCP against log time relationship was found for titanium, suggesting the growth of a barrier film in both O₂ and O₂/O₃ solutions. Mild steel does not passivate in synthetic cooling water either with O₂ or O₂/O₃ in the solution. In the presence of ozone the breakdown of passivity is facilitated and makes the repassivation difficult. Ozone enhances the dissolution of Cu₂O and the formation of Cu(II) species leading to less protective films. Both processes are strongly influenced by the pH. Finally, the dissolution of aluminium brass is higher than that of copper or copper–nickel.     

Are Changes in the Percentage of Specific Leukocyte Subpopulations Associated with Endogenous DNA Damage Levels in Testicular Cancer Patients?

Chemoresistance of germ cell tumors (GCTs) represents an intensively studied property of GCTs that is the result of a complicated multifactorial process. One of the driving factors in this process is the tumor microenvironment (TME). Intensive crosstalk between the DNA damage/DNA repair pathways and the TME has already been reported. This study aimed at evaluating the interplay between the immune TME and endogenous DNA damage levels in GCT patients. A cocultivation system consisting of peripheral blood mononuclear cells (PBMCs) from healthy donors and GCT cell lines was used in an in vitro study. The patient cohort included 74 chemotherapy-naïve GCT patients. Endogenous DNA damage levels were measured by comet assay. Immunophenotyping of leukocyte subpopulations was performed using flow cytometry. Statistical analysis included data assessing immunophenotypes, DNA damage levels and clinicopathological characteristics of enrolled patients. The DNA damage level in PBMCs cocultivated with cisplatin (CDDP)-resistant GCT cell lines was significantly higher than in PBMCs cocultivated with their sensitive counterparts. In GCT patients, endogenous DNA damage levels above the cutoff value were independently associated with increased percentages of natural killer cells, CD16-positive dendritic cells and regulatory T cells. The crosstalk between the endogenous DNA damage level and specific changes in the immune TME reflected in the blood of GCT patients was revealed. The obtained data contribute to a deeper understanding of ongoing interactions in the TME of GCTs.