Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-β1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

Cuticular lipids of the booklouse,Liposcelis bostrychophila: hydrocarbons,aldehydes, fatty acids,and fatty acid amides

The booklouse, Liposcelis bostrychophila, is an increasingly common pest of stored food products worldwide. We report here the cuticular lipid composition of this pest (the first report of the hydrocarbons of any member of the Order Psocoptera and the first report of fatty acid amides as cuticular components for any insect). No unsaturated hydrocarbons were present. A homologous series of n-alkanes (C₂₁–C₃₄), monomethyl alkanes (3-, 4-, 5-, 7-, 9-, 11-, 12-, 13- and 15-methyl-) with a carbon chain range of C₂₈–C₄₂, and dimethyl alkanes (3, 7-; 9, 13-; 11, 15-; 13, 17-; 9, 21-; 11, 19-; and 13, 21-); with a carbon number range of C₃₁–C₄₃ were identified. The relative abundances of these hydrocarbons were low, comprising approximately 0.0125% of total biomass. The amides were a homologous series (C₁₆–C₂₂ in chain length), with the major amide being stearoyl amide. In addition to the amides, free fatty acids (C_16:1, C_16:0, C_18:2, C_18:1, and C_18:0 in chain length) and three straight chain aldehydes (C₁₅, C₁₆, and C_17:1 in chain length) also occurred as cuticular components. These findings are discussed in terms of the chemical and physiological ecology of this species.     

Anionic Clays as Potential Slow-Release Fertilizers: Nitrate Ion Exchange

Several nitrate containing anionic clays were synthesized at different temperatures and the kinetics of NO₃ ^– release were determined to test their suitability as slow-release N fertilizers. A sample (Mg:Al = 2:1) synthesized at 60°C with smaller particle size released 75, 86 and 100% of its NO₃ ^– in 1, 3 and 7 days, respectively when equilibrated with a simulated soil solution. On the other hand, the 175°C/2 hrs sample with larger particle size released 65, 77 and 84% of its nitrate in 1, 3 and 7 days, respectively. Another anionic clay (synthesized at 175°C/24 hrs) of higher charge density (Mg:Al = 2:1) containing NO₃ ^– was equilibrated with a 0.012 N NaCl or Na₂CO₃ to test the role of different anions in releasing the NO₃ ^– anion from the interlayers. The results showed that Cl^– released more NO₃ ^– than did CO₃ ^2– from this anionic clay after all the treatment times probably as a result of the CO₃ ^2– anion blocking the release of NO₃ ^– from the interior of the crystals. When a lower charge density (Mg:Al = 3:1) sample (synthesized at 175°C/48 hrs) was equilibrated with 0.02N solution of anions the release of nitrate was as follows: Cl^– < F^– < SO₄ ⁼ CO₃ ^2–. These results suggest that the divalent SO₄ ⁼ and CO₃ ^2– anions are more effective in the release of NO₃ ^– from this lower charge density anionic clay. Time-resolved structural analysis of NO₃ ^– exchange with CO₃ ^2– in the above anionic clay using synchrotron x-ray diffraction showed that ion exchange is rapid because of small crystal size and lower charge density. Thus the release of NO₃ ^– from anionic clays is an interplay among the type of anions present in soil solution, their concentration, pH of soil solution, the charge density and crystal size of anionic clay etc.     

石墨防爆片静态变形及应力分析

本文旨在通过对石墨防爆片的变形、应力分布及爆破压力的试验研究,探讨以石墨电极为原材料加工石墨防爆片的可行性。文中运用有限单元法及薄板理论对该防爆破片的应力分布做了初步分析,并以电测和爆破试验验证了以薄板理论为基础的爆破压力计算公式,可供进一步研究时参考。     

Efficient clustering of uncertain data streams

Clustering uncertain data streams has recently become one of the most challenging tasks in data management because of the strict space and time requirements of processing tuples arriving at high speed and the difficulty that arises from handling uncertain data. The prior work on clustering data streams focuses on devising complicated synopsis data structures to summarize data streams into a small number of micro-clusters so that important statistics can be computed conveniently, such as Clustering Feature (CF) (Zhang et al. in Proceedings of ACM SIGMOD, pp 103–114, 1996) for deterministic data and Error-based Clustering Feature (ECF) (Aggarwal and Yu in Proceedings of ICDE, 2008) for uncertain data. However, ECF can only handle attribute-level uncertainty, while existential uncertainty, the other kind of uncertainty, has not been addressed yet. In this paper, we propose a novel data structure, Uncertain Feature (UF), to summarize data streams with both kinds of uncertainties: UF is space-efficient, has additive and subtractive properties, and can compute complicated statistics easily. Our first attempt aims at enhancing the previous streaming approaches to handle the sliding-window model by using UF instead of old synopses, inclusive of CluStream (Aggarwal et al. in Proceedings of VLDB, 2003) and UMicro (Aggarwal and Yu in Proceedings of ICDE, 2008). We show that such methods cannot achieve high efficiency. Our second attempt aims at devising a novel algorithm, cluUS , to handle the sliding-window model by using UF structure. Detailed analysis and thorough experimental reports on synthetic and real data sets confirm the advantages of our proposed method.     

Preparation and flame resistance properties of revolutionary self-extinguishing epoxy nanocomposites based on layered double hydroxides

Layered double hydroxides/epoxy (LDHs/EP) nanocomposites were prepared from organo-modified LDHs, a diglycidyl ether of bisphenol A monomer (DGEBA) and amine curing agents. The organo-modified LDHs were obtained by ionic exchange of a magnesium-aluminum carbonate LDH in an acid medium. X-ray diffraction and transmission electron microscopy showed a dispersion of the layers at a nanometer scale, indicating the formation of LDH/EP nanocomposites. The thermal degradation and flame resistance properties of LDH/EP nanocomposites, montmorillonite-epoxy (MMT/EP) nanocomposites, LDH/EP microcomposites and aluminum hydroxide-epoxy microcomposites were compared by thermogravimetrical analyses, simultaneous thermal analyses, UL94 and cone calorimeter tests. Only LDH/EP nanocomposites showed self-extinguishing behavior in the horizontal UL94 test; LDH/EP microcomposites and MMT/EP nanocomposites samples burned completely showing that the unique flame resistance of LDH/EP nanocomposites is related to both the level of dispersion and the intrinsic properties of LDH clay. Furthermore, cone calorimeter revealed intumescent behavior for LDH/EP nanocomposites and a higher reduction in the peak heat release rate compared to MMT/EP nanocomposites.     

Enhancing decisions with life cycle analysis for risk management

Although corporate financial distress is an infrequent occurrence, it has an extremely debilitating effect on the stability of a firm when it does occur. For this reason, an accurate risk assessment mechanism is needed in numerous industry sectors, particularly in financial institutions and banking. Based on corporation life cycle theory and risk management, this study develops a risk pre-warning model, namely the RSVMDT model, to eliminate serious financial punching and to examine the effectiveness of transparency and the full disclosure index (TFDI) during each life cycle stage. The RSVMDT model includes three techniques: random forest (RF), support vector machines (SVMs), and decision trees (DTs). The RF is used to determine the essential attributes of firms and therefore decrease the computational complexity of financial analysis and improve the classification accuracy. The SVM is employed as a classifier to identify corporations in financial distress. Finally, the DT is utilized as a rule generator that allows decision makers to adjust the financial structures of firms at specific life cycle stages. Together, these three techniques can increase the probability of corporate survival in a highly competitive environment. Additionally, the study further evaluates the importance of the TFDI during a turbulent economy. The public sectors can benefit from this evaluation by formulating future policies based on the rules derived from the developed RSVMDT model.     

Morphology of craters at hypervelocity impact in isotropic composites with inclusions

Results of a study of hypervelocity impact in model disperse-reinforced composites with an epoxy or aluminum matrix with metallic (Al and Pb) or ceramic (SiO₂) inclusions are reported. The goal of the present study is to find materials that possess a higher resistance to penetration of a high-velocity projectile compared with materials of separate components. This resistance is characterized by the ratio of the depth of a crater in a sufficiently thick target to the diameter of a spherical projectile. For two composites studied, we show that in impact of a steel particle with a velocity ranging from3 to11km/sec, the crater depth is approximately one projectile diameter smaller than that for lead or aluminum targets. Lavrent’ev Institute of Hydrodynamics, Siberian Division, Russian Academy of Sciences, Novosibirsk 630090. Translated from Fizika Goreniya i Vzryva, Vol. 33, No. 3, pp. 139–151, May–June, 1997.