Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κ B-Dependent Mechanism

PubMed Central

Patterson, E. K.; Yao, L. J.; Ramic, N.; Lewis, J. F.; Cepinskas, G.; McCaig, L.; Veldhuizen, R. A. W.; Yamashita, C. M.

2013-01-01

In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hypothesized that lung-derived mediators generated by mechanical ventilation (MV) are amplified by peripheral organs in a “feed forward” mechanism of systemic inflammation. Herein, lung-derived mediators were collected from 129X1/SVJ mice after 2 hours of MV while connected to the isolated perfused mouse lung model setup. Exposure of liver endothelial cells to lung-derived mediators resulted in a significant increase in G-CSF, IL-6, CXCL-1, CXCL-2, and MCP-1 production compared to noncirculated control perfusate media (P < 0.05). Furthermore, inhibition of the NF-κB pathway significantly mitigated this response. Changes in gene transcription were confirmed using qPCR for IL-6, CXCL-1, and CXCL-2. Additionally, liver tissue obtained from mice subjected to 2 hours of in vivo MV demonstrated significant increases in hepatic gene transcription of IL-6, CXCL-1, and CXCL-2 compared to nonventilated controls. Collectively, this data demonstrates that lung-derived mediators, generated in the setting of MV, are amplified by downstream organs in a feed forward mechanism of systemic inflammation. PMID:23606793

Reproducibility of Echocardiograph-Derived Multilevel Left Ventricular Apical Twist Mechanics.

PubMed

Stewart, Glenn M; Yamada, Akira; Kavanagh, Justin J; Haseler, Luke J; Chan, Jonathan; Sabapathy, Surendran

2016-02-01

Left ventricular (LV) twist mechanics are routinely assessed via echocardiography in clinical and research trials investigating the function of obliquely oriented myocardial fibers. However, echocardiograph-derived measures of LV twist may be compromised by nonstandardized acquisition of the apical image. This study examined the reproducibility of echocardiograph-derived parameters of apical twist mechanics at multiple levels of the apical myocardium. Two sets of 2D LV parasternal short-axis images were obtained in 30 healthy subjects (24 men; 19-57 year) via echocardiography. Images were acquired immediately distal to the papillary muscles (apical image 1), immediately above the point of LV cavity obliteration at end systole (apical image 3), and midway between apical image 1 and apical image 3 (apical image 2). Repeat scans were performed within 1 hour, and twist mechanics (rotation and rotation rate) were calculated via frame-by-frame tracking of natural acoustic echocardiographic markers (speckle tracking). The magnitude of apical rotation increased progressively toward the apex (apical image 1: 4.2 ± 2.1°, apical image 2: 7.2 ± 3.9°, apical image 3: 11.8 ± 4.6°). apical images 1, 2, and 3 each had moderate to good correlations between repeat scans (ICC: 0.531-0.856). When apical images 1, 2, and 3 were averaged, rotation was 7.7 ± 2.7° and between-scan correlation was excellent (ICC: 0.910). Similar results were observed for systolic and diastolic rotation rates. Averaging multiple standardized apical images, tending progressively toward the apex, generated the most reproducible rotation indices and may be optimal for the assessment of LV twist mechanics across therapeutic, interventional, and research studies; however, care should be taken given the influence of acquisition level on the magnitude of apical rotation. © 2015, Wiley Periodicals, Inc.

Experimental and Theoretical Insights into the Inhibition Mechanism of Prion Fibrillation by Resveratrol and its Derivatives.

PubMed

Li, Lanlan; Zhu, Yongchang; Zhou, Shuangyan; An, Xiaoli; Zhang, Yan; Bai, Qifeng; He, Yong-Xing; Liu, Huanxiang; Yao, Xiaojun

2017-12-20

Resveratrol and its derivatives have been shown to display beneficial effects to neurodegenerative diseases. However, the molecular mechanism of resveratrol and its derivatives on prion conformational conversion is poorly understood. In this work, the interaction mechanism between prion and resveratrol as well as its derivatives was investigated using steady-state fluorescence quenching, Thioflavin T binding assay, Western blotting, and molecular dynamics simulation. Protein fluorescence quenching method and Thioflavin T assay revealed that resveratrol and its derivatives could interact with prion and interrupt prion fibril formation. Molecular dynamics simulation results indicated that resveratrol can stabilize the PrP 127-147 peptide mainly through π-π stacking interactions between resveratrol and Tyr128. The hydrogen bonds interactions between resveratrol and the PrP 127-147 peptide could further reduce the flexibility and the propensity to aggregate. The results of this study not only can provide useful information about the interaction mechanism between resveratrol and prion, but also can provide useful clues for further design of new inhibitors inhibiting prion aggregation.

Mechanisms of Nanoparticle Mediated siRNA Transfection by Melittin-Derived Peptides

PubMed Central

Hou, Kirk K.; Pan, Hua; Ratner, Lee; Schlesinger, Paul H.; Wickline, Samuel A.

2014-01-01

Traditional peptide-mediated siRNA transfection via peptide transduction domains exhibits limited cytoplasmic delivery of siRNA due to endosomal entrapment. This work overcomes these limitations with the use of membrane-destabilizing peptides derived from melittin for the knockdown of NFkB signaling in a model of adult T-Cell leukemia/lymphoma. While the mechanism of siRNA delivery into the cytoplasmic compartment by peptide transduction domains has not been well studied, our analysis of melittin derivatives indicates that concurrent nanocomplex disassembly and peptide-mediated endosomolysis are crucial to siRNA transfection. Importantly, in the case of the most active derivative, p5RHH, this process is initiated by acidic pH, indicating that endosomal acidification after macropinocytosis can trigger siRNA release into the cytoplasm. These data provide general principles regarding nanocomplex response to endocytosis which may guide the development of peptide/siRNA nanocomplex-based transfection. PMID:24053333

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

PubMed Central

Kralova, Jarmila; Kolar, Michal; Kahle, Michal; Truksa, Jaroslav; Lettlova, Sandra; Balusikova, Kamila; Bartunek, Petr

2017-01-01

The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design. PMID:28295025

Derivation of the Schrodinger Equation from the Hamilton-Jacobi Equation in Feynman's Path Integral Formulation of Quantum Mechanics

ERIC Educational Resources Information Center

Field, J. H.

2011-01-01

It is shown how the time-dependent Schrodinger equation may be simply derived from the dynamical postulate of Feynman's path integral formulation of quantum mechanics and the Hamilton-Jacobi equation of classical mechanics. Schrodinger's own published derivations of quantum wave equations, the first of which was also based on the Hamilton-Jacobi…

Microstructure and mechanical properties of horns derived from three domestic bovines.

PubMed

Zhang, Quan-bin; Li, Chun; Pan, Yan-ting; Shan, Guang-hua; Cao, Ping; He, Jia; Lin, Zhong-shi; Ao, Ning-jian; Huang, Yao-xiong

2013-12-01

The microstructure and mechanical properties of horns derived from three domestic bovines (buffalo, cattle and sheep) were examined. The effects of water content, sampling position and orientation of three bovid horns on mechanical properties were systematically investigated by uniaxial tension and micron indentation tests. Meanwhile, the material composition and metal element contents were determined by Raman spectroscopy and elemental analysis respectively, and the microstructures of the horns were measured by scanning electron microscopy (SEM). Results show that the mechanical properties of horns have negative correlation with water contents and depend on sampling position and orientation. The spatial variations of the mechanical properties in horns are attributed to the different keratinization degrees in the proximal, middle and distal parts. And the mechanical properties of horns in the longitudinal direction are better than those in transverse. Among the three kinds of horns, the mechanical properties of buffalo horn are the best, followed by cattle horn, and those in sheep horn are the worst. This is due to the differences in material composition, metal element, and the microstructures of the horns. But the mechanical properties of buffalo horns are not dependent on the source of the buffalo. Therefore, regular engineered buffalo keratinous materials with standard mechanical properties can be obtained from different buffalo horns by using proper preparation methods. © 2013.

Embryonic stem cell-derived osteocytes are capable of responding to mechanical oscillatory hydrostatic pressure.

PubMed

Ehnes, D D; Price, F D; Shrive, N G; Hart, D A; Rancourt, D E; zur Nieden, N I

2015-07-16

Osteoblasts can be derived from embryonic stem cells (ESCs) by a 30 day differentiation process, whereupon cells spontaneously differentiate upon removal of LIF and respond to exogenously added 1,25α(OH)2 vitamin D3 with enhanced matrix mineralization. However, bone is a load-bearing tissue that has to perform under dynamic pressure changes during daily movement, a capacity that is executed by osteocytes. At present, it is unclear whether ESC-derived osteogenic cultures contain osteocytes and whether these are capable of responding to a relevant cyclic hydrostatic compression stimulus. Here, we show that ESC-osteoblastogenesis is followed by the generation of osteocytes and then mechanically load ESC-derived osteogenic cultures in a compression chamber using a cyclic loading protocol. Following mechanical loading of the cells, iNOS mRNA was upregulated 31-fold, which was consistent with a role for iNOS as an immediate early mechanoresponsive gene. Further analysis of matrix and bone-specific genes suggested a cellular response in favor of matrix remodeling. Immediate iNOS upregulation also correlated with a concomitant increase in Ctnnb1 and Tcf7l2 mRNAs along with increased nuclear TCF transcriptional activity, while the mRNA for the repressive Tcf7l1 was downregulated, providing a possible mechanistic explanation for the noted matrix remodeling. We conclude that ESC-derived osteocytes are capable of responding to relevant mechanical cues, at least such that mimic oscillatory compression stress, which not only provides new basic understanding, but also information that likely will be important for their use in cell-based regenerative therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Derivation of Performance Statements for the Automotive Mechanics Basic Trade Course: Research Documentation.

ERIC Educational Resources Information Center

Fox, A. P.; Kuhl, D. H.

A project was conducted to derive a comprehensive list of the performances of a competence mechanic to satisfy the planning needs of automotive engineering lecturers, curriculum committees, researchers, course designers, and staff developers. A list of 127 tasks together with information about their relative importance and the frequency with which…

FTIR spectra and mechanical strength analysis of some selected rubber derivatives.

PubMed

Gunasekaran, S; Natarajan, R K; Kala, A

2007-10-01

Rubber materials have wide range of commercial applications such as, infant diapers, famine hygiene products, drug delivery devices and incontinency products such as rubber tubes, tyres, etc. In the present work, studies on mechanical properties of some selected rubber materials viz., natural rubber (NR), styrene butadiene rubber (SBR), nitrile butadiene rubber (NBR) and ethylene propylene diene monomer (EPDM) have been carried out in three states viz., raw, vulcanized and reinforced. To enhance the quality of rubber elastomers, an attempt is made to prepare new elastomers called polyblends. In the present study an attempt is made to blend NR with NBR and with EPDM. We here report, a novel approach for the evaluation of various physico-mechanical properties such as mechanical strength, tensile strength, elongation and hardness. The method is simple, direct and fast and involves infrared spectral measurements for the evaluation of these properties. With the applications of modern infrared spectroscopy, the mechanical strength of these rubber materials have been analyzed by calculating the internal standards among the methyl and methylene group vibrational frequencies obtained from FTIR spectroscopy. Also the tensile strength measurements carried out by universal testing machine. The results pertaining physico-mechanical properties of the rubber derivatives undertaken in the present study obtained by IR-based method are in good agreement with data resulted from the standard methods.

FTIR spectra and mechanical strength analysis of some selected rubber derivatives

NASA Astrophysics Data System (ADS)

Gunasekaran, S.; Natarajan, R. K.; Kala, A.

2007-10-01

Rubber materials have wide range of commercial applications such as, infant diapers, famine hygiene products, drug delivery devices and incontinency products such as rubber tubes, tyres, etc. In the present work, studies on mechanical properties of some selected rubber materials viz., natural rubber (NR), styrene butadiene rubber (SBR), nitrile butadiene rubber (NBR) and ethylene propylene diene monomer (EPDM) have been carried out in three states viz., raw, vulcanized and reinforced. To enhance the quality of rubber elastomers, an attempt is made to prepare new elastomers called polyblends. In the present study an attempt is made to blend NR with NBR and with EPDM. We here report, a novel approach for the evaluation of various physico-mechanical properties such as mechanical strength, tensile strength, elongation and hardness. The method is simple, direct and fast and involves infrared spectral measurements for the evaluation of these properties. With the applications of modern infrared spectroscopy, the mechanical strength of these rubber materials have been analyzed by calculating the internal standards among the methyl and methylene group vibrational frequencies obtained from FTIR spectroscopy. Also the tensile strength measurements carried out by universal testing machine. The results pertaining physico-mechanical properties of the rubber derivatives undertaken in the present study obtained by IR-based method are in good agreement with data resulted from the standard methods.

Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms

PubMed Central

Azam, Mohammed Shariful; Choi, Jinkyung; Lee, Min-Sup; Kim, Hyeung-Rak

2017-01-01

There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceutical applications. Many types of bioactive secondary metabolites from marine algae, including phlorotannins, sulfated polysaccharides, carotenoids, and meroterpenoids, have already been documented for their potential applications in the pharmaceutical industry. Among these metabolites, phlorotannins from brown algae have been widely screened for their pharmaceutical and hypopigmenting effects. Unfortunately, the majority of these articles did not have detailed investigations on molecular targets, which is critical to fulfilling the criteria for their cosmeceutical and pharmaceutical use. Very recently, a few meroterpenoids have been discovered from Sargassum sp., with the examination of their anti-melanogenic properties and mechanisms. Despite the scarcity of in vivo and clinical investigations of molecular mechanistic events of marine algae-derived hypopigmenting agents, identifying the therapeutic targets and their validation in humans has been a major challenge for future studies. In this review, we focused on available data representing molecular mechanisms underlying hypopigmenting properties of potential marine brown alga-derived compounds. PMID:28946635

O the Derivation of the Schroedinger Equation from Stochastic Mechanics.

NASA Astrophysics Data System (ADS)

Wallstrom, Timothy Clarke

The thesis is divided into four largely independent chapters. The first three chapters treat mathematical problems in the theory of stochastic mechanics. The fourth chapter deals with stochastic mechanisms as a physical theory and shows that the Schrodinger equation cannot be derived from existing formulations of stochastic mechanics, as had previously been believed. Since the drift coefficients of stochastic mechanical diffusions are undefined on the nodes, or zeros of the density, an important problem has been to show that the sample paths stay away from the nodes. In Chapter 1, it is shown that for a smooth wavefunction, the closest approach to the nodes can be bounded solely in terms of the time -integrated energy. The ergodic properties of stochastic mechanical diffusions are greatly complicated by the tendency of the particles to avoid the nodes. In Chapter 2, it is shown that a sufficient condition for a stationary process to be ergodic is that there exist positive t and c such that for all x and y, p^{t} (x,y) > cp(y), and this result is applied to show that the set of spin-1over2 diffusions is uniformly ergodic. In stochastic mechanics, the Bopp-Haag-Dankel diffusions on IR^3times SO(3) are used to represent particles with spin. Nelson has conjectured that in the limit as the particle's moment of inertia I goes to zero, the projections of the Bopp -Haag-Dankel diffusions onto IR^3 converge to a Markovian limit process. This conjecture is proved for the spin-1over2 case in Chapter 3, and the limit process identified as the diffusion naturally associated with the solution to the regular Pauli equation. In Chapter 4 it is shown that the general solution of the stochastic Newton equation does not correspond to a solution of the Schrodinger equation, and that there are solutions to the Schrodinger equation which do not satisfy the Guerra-Morato Lagrangian variational principle. These observations are shown to apply equally to other existing formulations of

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals

PubMed Central

Lynch, Maureen E.; Chiou, Aaron E.; Lee, Min Joon; Marcott, Stephen C.; Polamraju, Praveen V.; Lee, Yeonkyung

2016-01-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis. PMID:27401765

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals.

PubMed

Lynch, Maureen E; Chiou, Aaron E; Lee, Min Joon; Marcott, Stephen C; Polamraju, Praveen V; Lee, Yeonkyung; Fischbach, Claudia

2016-08-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.

Benzene Exposures and Risk Potential for Vehicle Mechanics from Gasoline and Petroleum-Derived Products.

PubMed

Williams, Pamela R D; Mani, Ashutosh

2015-01-01

Benzene exposures among vehicle mechanics in the United States and abroad were characterized using available data from published and unpublished studies. In the United States, the time-weighted-average (TWA) airborne concentration of benzene for vehicle mechanics averaged 0.01-0.05 ppm since at least the late 1970s, with maximal TWA concentrations ranging from 0.03 to 0.38 ppm. Benzene exposures were notably lower in the summer than winter and in the Southwest compared to other geographic regions, but significantly higher during known gasoline-related tasks such as draining a gas tank or changing a fuel pump or fuel filter. Measured airborne concentrations of benzene were also generally greater for vehicle mechanics in other countries, likely due to the higher benzene content of gasoline and other factors. Short-term airborne concentrations of benzene frequently exceeded 1 ppm during gasoline-related tasks, but remained below 0.2 ppm for tasks involving other petroleum-derived products such as carburetor and brake cleaner or parts washer solvent. Application of a two-zone mathematical model using reasonable input values from the literature yielded predicted task-based benzene concentrations during gasoline and aerosol spray cleaner scenarios similar to those measured for vehicle mechanics during these types of tasks. When evaluated using appropriate biomarkers, dermal exposures were found to contribute little to total benzene exposures for this occupational group. Available data suggest that vehicle mechanics have not experienced significant exposures to benzene in the workplace, except perhaps during short-duration gasoline-related tasks, and full-shift benzene exposures have remained well below current and contemporaneous occupational exposure limits. These findings are consistent with epidemiology studies of vehicle mechanics, which have not demonstrated an increased risk of benzene-induced health effects in this cohort of workers. Data and information presented

Influence of wood-derived biochar on the physico-mechanical and chemical characteristics of agricultural soils

NASA Astrophysics Data System (ADS)

Ahmed, Ahmed S. F.; Raghavan, Vijaya

2018-01-01

Amendment of soil with biochar has been shown to enhance fertility and increase crop productivity, but the specific influence of biochar on soil workability remains unclear. Select physico-mechanical and chemical properties of clay loam and sandy loam soils were measured after amendment with wood-derived biochar of two particle size ranges (0.5-425 and 425-850 µm) at five dosages ranging from 0.5 to 10% dry weight. Whereas the clay loam soil workability decreased when the finer wood-derived biochar was applied at rates of 6 or 10%, soil fertility was not enhanced. The sandy loam soil, due to Proctor compaction, significantly decreased in bulk density with 6 and 10% wood-derived biochar amendments indicating higher soil resistance to compaction.

Nanofriction: Skating on hot surfaces

NASA Astrophysics Data System (ADS)

Meyer, Ernst; Gnecco, Enrico

2007-03-01

Simulations of nanoscale sharp tips sliding on a salt surface predict vanishing friction at temperatures close to the melting temperature, as the tip skates on a layer of liquefied salt. This insight opens the way to applications in MEMS, NEMS and auto/aerospace engines.

Nanofriction in Cavity Quantum Electrodynamics

NASA Astrophysics Data System (ADS)

Fogarty, T.; Cormick, C.; Landa, H.; Stojanović, Vladimir M.; Demler, E.; Morigi, Giovanna

2015-12-01

The dynamics of cold trapped ions in a high-finesse resonator results from the interplay between the long-range Coulomb repulsion and the cavity-induced interactions. The latter are due to multiple scatterings of laser photons inside the cavity and become relevant when the laser pump is sufficiently strong to overcome photon decay. We study the stationary states of ions coupled with a mode of a standing-wave cavity as a function of the cavity and laser parameters, when the typical length scales of the two self-organizing processes, Coulomb crystallization and photon-mediated interactions, are incommensurate. The dynamics are frustrated and in specific limiting cases can be cast in terms of the Frenkel-Kontorova model, which reproduces features of friction in one dimension. We numerically recover the sliding and pinned phases. For strong cavity nonlinearities, they are in general separated by bistable regions where superlubric and stick-slip dynamics coexist. The cavity, moreover, acts as a thermal reservoir and can cool the chain vibrations to temperatures controlled by the cavity parameters and by the ions' phase. These features are imprinted in the radiation emitted by the cavity, which is readily measurable in state-of-the-art setups of cavity quantum electrodynamics.

Statistical mechanics of neocortical interactions. Derivation of short-term-memory capacity

NASA Astrophysics Data System (ADS)

Ingber, Lester

1984-06-01

A theory developed by the author to describe macroscopic neocortical interactions demonstrates that empirical values of chemical and electrical parameters of synaptic interactions establish several minima of the path-integral Lagrangian as a function of excitatory and inhibitory columnar firings. The number of possible minima, their time scales of hysteresis and probable reverberations, and their nearest-neighbor columnar interactions are all consistent with well-established empirical rules of human short-term memory. Thus, aspects of conscious experience are derived from neuronal firing patterns, using modern methods of nonlinear nonequilibrium statistical mechanics to develop realistic explicit synaptic interactions.

Thermo-mechanical behaviors of thermoplastic starch derived from sugar palm tree (Arenga pinnata).

PubMed

Sahari, J; Sapuan, S M; Zainudin, E S; Maleque, M A

2013-02-15

In recent years, increasing environmental concerns focused greater attention on the development of biodegradable materials. A thermoplastic starch derived from bioresources, sugar palm tree was successfully developed in the presence of biodegradable glycerol as a plasticizer. Sugar palm starch (SPS) was added with 15-40 w/w% of glycerol to prepare workable bioplastics and coded as SPS/G15, SPS/G20, SPS/G30 and SPS/G40. The samples were characterized for thermal properties, mechanical properties and moisture absorption on exposure to humidity were evaluated. Morphological studies through scanning electron microscopy (SEM) were used to explain the observed mechanical properties. Generally, the addition of glycerol decrease the transition temperature of plasticized SPS. The mechanical properties of plasticized SPS increase with the increasing of glycerol but up to 30 w/w%. Meanwhile, the water absorption of plasticized SPS decrease with increasing of glycerol. Copyright © 2012 Elsevier Ltd. All rights reserved.

Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2.

PubMed

Denel-Bobrowska, Marta; Łukawska, Małgorzata; Bukowska, Barbara; Gajek, Arkadiusz; Oszczapowicz, Irena; Marczak, Agnieszka

2018-02-01

Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome 20S activity were evaluated by fluorimetric methods. The effects on the cell cycle and phosphatidylserine externalization were measured by flow cytometry. O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect on initiating apoptosis in all tested cells. Externalization of phosphatidylserine was significantly higher following O-DOX treatment compared with control cells and cells incubated with DOX. The intracellular accumulation and uptake of the derivatives were similar to those of the reference drugs. Tested compounds are able to activate proteasome 20S activity. Our results extended the understanding of the toxicity, mechanism of action, and biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin, including their effects on cell cycle, apoptosis and DNA degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cis-to- Trans Isomerization of Azobenzene Derivatives Studied with Transition Path Sampling and Quantum Mechanical/Molecular Mechanical Molecular Dynamics.

PubMed

Muždalo, Anja; Saalfrank, Peter; Vreede, Jocelyne; Santer, Mark

2018-04-10

Azobenzene-based molecular photoswitches are becoming increasingly important for the development of photoresponsive, functional soft-matter material systems. Upon illumination with light, fast interconversion between a more stable trans and a metastable cis configuration can be established resulting in pronounced changes in conformation, dipole moment or hydrophobicity. A rational design of functional photosensitive molecules with embedded azo moieties requires a thorough understanding of isomerization mechanisms and rates, especially the thermally activated relaxation. For small azo derivatives considered in the gas phase or simple solvents, Eyring's classical transition state theory (TST) approach yields useful predictions for trends in activation energies or corresponding half-life times of the cis isomer. However, TST or improved theories cannot easily be applied when the azo moiety is part of a larger molecular complex or embedded into a heterogeneous environment, where a multitude of possible reaction pathways may exist. In these cases, only the sampling of an ensemble of dynamic reactive trajectories (transition path sampling, TPS) with explicit models of the environment may reveal the nature of the processes involved. In the present work we show how a TPS approach can conveniently be implemented for the phenomenon of relaxation-isomerization of azobenzenes starting with the simple examples of pure azobenzene and a push-pull derivative immersed in a polar (DMSO) and apolar (toluene) solvent. The latter are represented explicitly at a molecular mechanical (MM) and the azo moiety at a quantum mechanical (QM) level. We demonstrate for the push-pull azobenzene that path sampling in combination with the chosen QM/MM scheme produces the expected change in isomerization pathway from inversion to rotation in going from a low to a high permittivity (explicit) solvent model. We discuss the potential of the simulation procedure presented for comparative calculation of

Application of bioethanol derived lignin for improving physico-mechanical properties of thermoset biocomposites.

PubMed

Bajwa, Dilpreet S; Wang, Xinnan; Sitz, Evan; Loll, Tyler; Bhattacharjee, Sujal

2016-08-01

Lignin is the most abundant of renewable polymers next to cellulose with a global annual production of 70million tons, largely produced from pulping and second generation biofuel industries. Low value of industrial lignin makes it an attractive biomaterial for wide range of applications. The study investigated the application of wheat straw and corn stover based lignin derived from ethanol production for use in thermoset biocomposites. The biocomposite matrix constituted a two component low viscosity Araldite(®)LY 8601/Aradur(®) 8602 epoxy resin system and the lignin content varied from 0 to 25% by weight fraction. The analysis of the physical and mechanical properties of the biocomposites show bioethanol derived lignin can improve selective properties such as impact strength, and thermal stability without compromising the modulus and strength attributes. Copyright © 2016 Elsevier B.V. All rights reserved.

Hexapeptide Derivatives of Glycopeptide Antibiotics: Tools for Mechanism of Action Studies

PubMed Central

Allen, Norris E.; LeTourneau, Deborah L.; Hobbs, Joe N.; Thompson, Richard C.

2002-01-01

Hexapeptide (des-N-methylleucyl) derivatives of LY264826 were prepared in order to examine further the role of N-substituted hydrophobic side chains in defining the mechanisms of action of semisynthetic glycopeptide antibiotics. The hexapeptide of LY264826 binds to the cell wall intermediate analog l-Lys-d-Ala-d-Ala with a 100-fold lower affinity than LY264826 and inhibits Micrococcus luteus almost 200-fold more poorly than LY264826 does. Alkylation of the 4-epi-vancosamine moiety of the disaccharide significantly enhanced the antibacterial activity of the hexapeptide. Alkylation did not affect the binding affinity for d-alanyl-d-alanine residues; however, it did enhance dimerization 7,000-fold and enhanced binding to bacterial membrane vesicles noticeably compared with the levels of dimerization and binding for the unsubstituted hexapeptide. The findings from this study complement those presented in an earlier report (N. E. Allen, D. L. LeTourneau, and J. N. Hobbs, Jr., J. Antibiot. 50:677-684, 1997) and are consistent with the conclusion that the enhanced antibacterial activities of semisynthetic glycopeptide antibiotics derive from the ability of the hydrophobic side chain to markedly affect both dimerization and binding to bacterial membranes. PMID:12121903

Comparative antimicrobial activity and mechanism of action of bovine lactoferricin-derived synthetic peptides.

PubMed

Liu, Yifan; Han, Feifei; Xie, Yonggang; Wang, Yizhen

2011-12-01

Lactoferricin B (LfcinB), a 25 residue peptide derived from the N-terminal of bovine lactoferrin (bLF), causes depolarization of the cytoplasmic membrane in susceptible bacteria. Its mechanism of action, however, still needs to be elucidated. In the present study, synthetic LfcinB (without a disulfide bridge) and LfcinB (C-C; with a disulfide bridge) as well as three derivatives with 15-, 11- and 9-residue peptides were prepared to investigate their antimicrobial nature and mechanisms. The antimicrobial properties were measured via minimum inhibitory concentration (MIC) determinations, killing kinetics assays and synergy testing, and hemolytic activities were assessed by hemoglobin release. Finally, the morphology of peptide-treated bacteria was determined by atomic force microscopy (AFM). We found that there was no difference in MICs between LfcinB and LfcinB (C-C). Among the derivatives, only LfcinB15 maintained nearly the same level as LfcinB, in the MIC range of 16-128 μg/ml, and the MICs of LfcinB11 (64-256 μg/ml) were 4 times more than LfcinB, while LfcinB9 exhibited the lowest antimicrobial activity. When treated at MIC for 1 h, many blebs were formed and holes of various sizes appeared on the cell surface, but the cell still maintained its integrity. This suggested that LfcinB had a major permeability effect on the cytoplasmic membrane of both Gram-positive and Gram-negative bacteria, which also indicated it may be a possible intracellular target. Among the tested antibiotics, aureomycin increased the bactericidal activity of LfcinB against E. coli, S. aureus and P. aeruginosa, but neomycin did not have such an effect. We also found that the combination of cecropin A and LfcinB had synergistic effects against E. coli.

Systematic and Automated Development of Quantum Mechanically Derived Force Fields: The Challenging Case of Halogenated Hydrocarbons.

PubMed

Prampolini, Giacomo; Campetella, Marco; De Mitri, Nicola; Livotto, Paolo Roberto; Cacelli, Ivo

2016-11-08

A robust and automated protocol for the derivation of sound force field parameters, suitable for condensed-phase classical simulations, is here tested and validated on several halogenated hydrocarbons, a class of compounds for which standard force fields have often been reported to deliver rather inaccurate performances. The major strength of the proposed protocol is that all of the parameters are derived only from first principles because all of the information required is retrieved from quantum mechanical data, purposely computed for the investigated molecule. This a priori parametrization is carried out separately for the intra- and intermolecular contributions to the force fields, respectively exploiting the Joyce and Picky programs, previously developed in our group. To avoid high computational costs, all quantum mechanical calculations were performed exploiting the density functional theory. Because the choice of the functional is known to be crucial for the description of the intermolecular interactions, a specific procedure is proposed, which allows for a reliable benchmark of different functionals against higher-level data. The intramolecular and intermolecular contribution are eventually joined together, and the resulting quantum mechanically derived force field is thereafter employed in lengthy molecular dynamics simulations to compute several thermodynamic properties that characterize the resulting bulk phase. The accuracy of the proposed parametrization protocol is finally validated by comparing the computed macroscopic observables with the available experimental counterparts. It is found that, on average, the proposed approach is capable of yielding a consistent description of the investigated set, often outperforming the literature standard force fields, or at least delivering results of similar accuracy.

Experimental and theoretical study on DPPH radical scavenging mechanism of some chalcone quinoline derivatives

NASA Astrophysics Data System (ADS)

Hamlaoui, Ikram; Bencheraiet, Reguia; Bensegueni, Rafik; Bencharif, Mustapha

2018-03-01

In this study, the antioxidant capacity of three chalcone derivatives was evaluated by DPPH free radical scavenging. Experimental data showed low antioxidant activity (IC50±SD) of these molecules in comparison with BHT. The mechanism of DPPH radical scavenging elucidated by means of density functional theory (DFT) calculations. The tested compounds and their corresponding radicals and anions were optimized using B3LYP functional with 6-31G (d,p) basis set in the gas phase. The C-PCM model was used to perform solvent medium calculations. On the basis of theoretical calculations, it was shown that HAT mechanism was predominant in the gas phase, whereas SET-PT and SPLET mechanisms were favored in the presence of the solvent. Moreover, the HOMO orbitals and spin density distribution was evaluated to predict the probable sites for free radical attack.

Unexpected Reduction of Iminoquinone and Quinone Derivatives in Positive Electrospray Ionization Mass Spectrometry and Possible Mechanism Exploration

NASA Astrophysics Data System (ADS)

Pei, Jiying; Hsu, Cheng-Chih; Zhang, Ruijie; Wang, Yinghui; Yu, Kefu; Huang, Guangming

2017-08-01

Unexpected reduction of iminoquinone (IQ) and quinone derivatives was first reported during positive electrospray ionization mass spectrometry. Upon increasing spray voltage, the intensities of IQ and quinone derivatives decreased drastically, accompanying the increase of the intensities of the reduction products, amodiaquine (AQ) and phenol derivatives. To gain more insight into the mechanism of such reduction, we explored the experimental factors that are influential to corona discharge (CD). The results show that experimental parameters that favor severe CD, including metal spray emitter, using water as spray solvent, sheath gas with low dielectric strength (e.g., nitrogen), and shorter spray tip-to-mass spectrometer inlet distance, facilitated the reduction of IQ and quinone derivatives, implying that the reduction should be closely related to CD in the gas phase. [Figure not available: see fulltext.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oakdale, James S.; Ye, Jianchao; Smith, William L.

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

DOE PAGES

Oakdale, James S.; Ye, Jianchao; Smith, William L.; ...

2016-11-28

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Kinetics and the mass transfer mechanism of hydrogen sulfide removal by biochar derived from rice hull.

PubMed

Shang, Guofeng; Liu, Liang; Chen, Ping; Shen, Guoqing; Li, Qiwu

2016-05-01

The biochar derived from rice hull was evaluated for its abilities to remove hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The biochar derived from rice hull was evaluated for its abilities to remove hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The different pyrolysis temperature has great influence on the adsorption of H2S. At the different pyrolysis temperature, the H2S removal efficiency of rice hull-derived biochar was different. The adsorption capacities of biochar were 2.09 mg·g(-1), 2.65 mg·g(-1), 16.30 mg·g(-1), 20.80 mg·g(-1), and 382.70 mg·g(-1), which their pyrolysis temperatures were 100 °C, 200 °C, 300 °C, 400 °C and 500 °C respectively. Based on the Yoon-Nelson model, it analyzed the mass transfer mechanism of hydrogen sulfide adsorption by biochar. The paper focuses on the biochar derived from rice hull-removed hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The different pyrolysis temperatures have great influence on the adsorption of H2S. At the different pyrolysis temperatures, the H2S removal efficiency of rice hull-derived biohar was different. The adsorption capacities of biochar were 2.09, 2.65, 16.30, 20.80, and 382.70 mg·g(-1), and their pyrolysis temperatures were 100, 200, 300, 400, and 500 °C, respectively. Based on the Yoon-Nelson model, the mass transfer mechanism of hydrogen sulfide adsorption by biochar was analyzed.

Intraplate Stress Field in South America Derived from Earthquake Focal Mechanisms

NASA Astrophysics Data System (ADS)

Dias, F. L.; Assumpcao, M.

2017-12-01

We present an updated compilation of earthquake focal mechanisms in Brazil together with the sub-Andean region through more obtained solutions together with published results from the literature and catalogs of international agencies. Stress orientations from breakouts and in-situ measurements were also compiled. The focal mechanisms were classified according to WSM (World Stress Map) criteria.For Brazil, we have 82 earthquakes with the mechanism that has been determined since 1978, begin that three new from this study. Focal mechanisms in Brazil show reverse, strike-slip and normal faulting while all events in the sub-Andean region have reverse (majority) or strike-slip mechanisms. For sub-Andean region have reverse (majority) or strike-slip mechanisms. Normal mechanisms can be found only in high attitudes. The mechanisms were grouped by proximity to be inverted for the stress tensor. We use the bootstrap technique to analyze the stability of the tensor. In SE Brazil and the Chaco-Pantanal basins, S1 tends to be oriented roughly E-W with S2 approximately equal to S3. This stress pattern changes to purely compressional (both SHmax and Shmin larger than Sv) in the São Francisco craton. A rotation of SHmax from E-W to SE-NW is suggested towards the Amazon region. Along the Atlantic margin, the regional stresses are affected by coastal effects. This coastal effect tends to make SHmax parallel to the coastline and Shmin (usually S3) perpendicular to the coastline. Few breakout data and in-situ measurements are available in Brazil and are generally consistent with the pattern derived from the earthquake focal mechanisms. In the sub-Andean region, the intermediate principal stress (S2) is also compressional, a feature that is not always reproduced in numerical models published in the literature. In mid-plate South America stresses seem to vary in nature and orientation. Although numerical models of global lithospheric stresses tend to reproduce the main large

Differential Uptake Mechanisms of Fluorescent Substrates into Stem-Cell-Derived Serotonergic Neurons.

PubMed

Matthaeus, Friederike; Schloss, Patrick; Lau, Thorsten

2015-12-16

The actions of the neurotransmitters serotonin, dopamine, and norepinephrine are partly terminated by diffusion and in part by their uptake into neurons via the selective, high-affinity transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET), respectively. There is also growing evidence that all three monoamines are taken up into neurons by low-affinity, high-capacity organic cation transporters (OCT) and the plasma membrane monoamine transporter (PMAT). Pharmacological characterization of these low-affinity recombinant transporter proteins in heterologous expression systems has revealed that they are not antagonized by classical inhibitors of SERT, DAT, or NET but that decynium-22 (D22) antagonizes OCT3 and PMAT, whereas corticosterone and progesterone selectively inhibit OCT3. Here, we show that SERT, PMAT, and OCT3, but not OCT1 and OCT2, are coexpressed in murine stem cell-derived serotonergic neurons. Using selective antagonists, we provide evidence that uptake of the fluorescent substrates FFN511, ASP+, and 5-HT into stem cell-derived serotonergic neurons is mediated differentially by these transporters and also involves an as yet unknown transport mechanism.

The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

PubMed

Hu, Jing; Wu, Tian-Ming; Li, Hong-Ze; Zuo, Ze-Ping; Zhao, Ying-Lan; Yang, Li

2017-08-01

Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. Copyright © 2017. Published by Elsevier Ltd.

Hybrid anticancer 1,2-diazine derivatives with multiple mechanism of action. Part 3.

PubMed

Antoci, Vasilichia; Mantu, Dorina; Cozma, Danut Gabriel; Usru, Cornelia; Mangalagiu, Ionel I

2014-01-01

Antitumour chemotherapy is nowadays a very active field of research, DNA targeting drugs being the most widely used group in therapy. The design, synthesis and anticancer activity of a new class of anticancer derivatives with pyrrolo-1,2-diazine and benzoquinone skeleton is presented. The synthesis is direct and efficient, involving an alkylation followed by a [3+2] dipolar cycloaddition. The penta- and tetra-cyclic pyrrolo-1,2-diazine were evaluated for their in vitro anticancer activity against an NCI 60 human tumour cell line panel. The pentacyclic-1,2-diazine exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM and Breast Cancer MCF7. We hypothesize that these molecules will exert their anticancer activity through multiple mechanisms of action: intercalating the DNA, inhibiting the topoisomerase enzymes and, destroying the DNA strands via electron transfer mechanism. However, the intercalation with the DNA seems to prevail in competition with the others mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Foundations of Quantum Mechanics: Derivation of a dissipative Schrödinger equation from first principles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonçalves, L.A.; Olavo, L.S.F., E-mail: olavolsf@gmail.com

Dissipation in Quantum Mechanics took some time to become a robust field of investigation after the birth of the field. The main issue hindering developments in the field is that the Quantization process was always tightly connected to the Hamiltonian formulation of Classical Mechanics. In this paper we present a quantization process that does not depend upon the Hamiltonian formulation of Classical Mechanics (although still departs from Classical Mechanics) and thus overcome the problem of finding, from first principles, a completely general Schrödinger equation encompassing dissipation. This generalized process of quantization is shown to be nothing but an extension ofmore » a more restricted version that is shown to produce the Schrödinger equation for Hamiltonian systems from first principles (even for Hamiltonian velocity dependent potential). - Highlights: • A Quantization process independent of the Hamiltonian formulation of quantum Mechanics is proposed. • This quantization method is applied to dissipative or absorptive systems. • A Dissipative Schrödinger equation is derived from first principles.« less

An Introductory Organic Chemistry Review Homework Exercise: Deriving Potential Mechanisms for Glucose Ring Opening in Mutarotation

ERIC Educational Resources Information Center

Murdock, Margaret; Holman, R. W.; Slade, Tyler; Clark, Shelley L. D.; Rodnick, Kenneth J.

2014-01-01

A unique homework assignment has been designed as a review exercise to be implemented near the end of the one-year undergraduate organic chemistry sequence. Within the framework of the exercise, students derive potential mechanisms for glucose ring opening in the aqueous mutarotation process. In this endeavor, 21 general review principles are…

Bone-Derived Stem Cells Repair the Heart after Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms

PubMed Central

Duran, Jason M.; Makarewich, Catherine A.; Sharp, Thomas E.; Starosta, Timothy; Fang, Zhu; Hoffman, Nicholas E.; Chiba, Yumi; Madesh, Muniswamy; Berretta, Remus M.; Kubo, Hajime; Houser, Steven R.

2013-01-01

Rationale Autologous bone marrow- or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is key toward improving clinical outcomes. Objective To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results Cortical bone stem cells (CBSCs) and cardiac-derived stem cells (CDCs) were isolated from EGFP+ transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction (MI) with injection of CBSCs (n=67), CDCs (n=36) or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor) and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to CDC- or saline-treated MI controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle and endothelial cells could be identified in CBSC- but not in CDC-treated animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions CBSCs improve survival, cardiac function, and attenuate remodeling through two mechanisms:1) secretion of pro-angiogenic factors that stimulate endogenous neovascularization, and 2) differentiation into functional adult myocytes and vascular cells. PMID:23801066

Structure Properties and Mechanisms of Action of Naturally Originated Phenolic Acids and Their Derivatives against Human Viral Infections.

PubMed

Wu, Yi-Hang; Zhang, Bing-Yi; Qiu, Li-Peng; Guan, Rong-Fa; Ye, Zi-Hong; Yu, Xiao-Ping

2017-01-01

A great effort has been made to develop efficacious antiviral drugs, but many viral infections are still lack of efficient antiviral therapies so far. The related exploration of natural products to fight viruses has been raised in recent years. Natural compounds with structural diversity and complexity offer a great chance to find new antiviral agents. Particularly, phenolic acids have attracted considerable attention owing to their potent antiviral abilities and unique mechanisms. The aim of this review is to report new discoveries and updates pertaining to antiviral phenolic acids. The relevant references on natural phenolic acids were searched. The antiviral phenolic acids were classified according to their structural properties and antiviral types. Meanwhile, the antiviral characteristics and structure-activity relationships of phenolic acids and their derivatives were summarized. The review finds that natural phenolic acids and their derivatives possessed potent inhibitory effects on multiple virus in humans such as human immunodeficiency virus, hepatitis C virus, hepatitis B virus, herpes simplex virus, influenza virus and respiratory syncytial virus. In particular, caffeic acid/gallic acid and their derivatives exhibited outstanding antiviral properties by a variety of modes of action. Naturally derived phenolic acids especially caffeic acid/gallic acid and their derivatives may be regarded as novel promising antiviral leads or candidates. Additionally, scarcely any of these compounds has been used as antiviral treatment in clinical practice. Therefore, these phenolic acids with diverse skeletons and mechanisms provide us an excellent resource for finding novel antiviral drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Statistical Mechanical Derivation of Jarzynski's Identity for Thermostated Non-Hamiltonian Dynamics

NASA Astrophysics Data System (ADS)

Cuendet, Michel A.

2006-03-01

The recent Jarzynski identity (JI) relates thermodynamic free energy differences to nonequilibrium work averages. Several proofs of the JI have been provided on the thermodynamic level. They rely on assumptions such as equivalence of ensembles in the thermodynamic limit or weakly coupled infinite heat baths. However, the JI is widely applied to NVT computer simulations involving finite numbers of particles, whose equations of motion are strongly coupled to a few extra degrees of freedom modeling a thermostat. In this case, the above assumptions are no longer valid. We propose a statistical mechanical approach to the JI solely based on the specific equations of motion, without any further assumption. We provide a detailed derivation for the non-Hamiltonian Nosé-Hoover dynamics, which is routinely used in computer simulations to produce canonical sampling.

Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyake, Yoshiaki; Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama; Furumatsu, Takayuki, E-mail: matino@md.okayama-u.ac.jp

Highlights: {yields} CCN2/CTGF localizes to the ligament-to-bone interface, but is not to the midsubstance region of human anterior cruciate ligament (ACL). {yields} Mechanical stretch induces higher increase of CCN2/CTGF gene expression and protein secretion in ACL interface cells compared with ACL midsubstance cells. {yields} CCN2/CTGF treatment stimulates the proliferation of ACL interface cells. -- Abstract: Anterior cruciate ligament (ACL)-to-bone interface serves to minimize the stress concentrations that would arise between two different tissues. Mechanical stretch plays an important role in maintaining cell-specific features by inducing CCN family 2/connective tissue growth factor (CCN2/CTGF). We previously reported that cyclic tensile strain (CTS)more » stimulates {alpha}1(I) collagen (COL1A1) expression in human ACL-derived cells. However, the biological function and stress-related response of CCN2/CTGF were still unclear in ACL fibroblasts. In the present study, CCN2/CTGF was observed in ACL-to-bone interface, but was not in the midsubstance region by immunohistochemical analyses. CTS treatments induced higher increase of CCN2/CTGF expression and secretion in interface cells compared with midsubstance cells. COL1A1 expression was not influenced by CCN2/CTGF treatment in interface cells despite CCN2/CTGF stimulated COL1A1 expression in midsubstance cells. However, CCN2/CTGF stimulated the proliferation of interface cells. Our results suggest that distinct biological function of stretch-induced CCN2/CTGF might regulate region-specific phenotypes of ACL-derived cells.« less

Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism

PubMed Central

Mazet, Muriel; Perozzo, Remo; Bergamini, Christian; Prati, Federica; Fato, Romana; Lenaz, Giorgio; Capranico, Giovanni; Brun, Reto; Bakker, Barbara M.; Michels, Paul A. M.; Scapozza, Leonardo; Bolognesi, Maria Laura; Cavalli, Andrea

2013-01-01

Background and Methodology Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED50 of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. Principal Findings A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC50 values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. Conclusions and Significance Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands. PMID:23350008

Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship.

PubMed

Roohbakhsh, Ali; Iranshahy, Milad; Iranshahi, Mehrdad

2016-01-01

The anti-cancer properties of liquorice have been attributed, at least in part, to glycyrrhizin (GL). However, GL is not directly absorbed through the gastrointestinal tract. It is hydrolyzed to 18-β-glycyrrhetinic acid (GA), the pharmacologically active metabolite, by human intestinal microflora. GA exhibits remarkable cytotoxic and anti-tumor properties. The pro-apoptotic targets and mechanisms of action of GA have been extensively studied over the past decade. In addition, GA is an inexpensive and available triterpene with functional groups (COOH and OH) in its structure, which make it an attractive lead compound for medicinal chemists to prepare a large number of analogues. To date, more than 400 cytotoxic derivatives have been prepared on the basis of GA scaffold, including 128 cytotoxic derivatives with IC50 values less than 30 µM. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC50s ≤ 1 µM. Studies have shown that the introduction of a double bound at the C1-C2 position combined with an electronegative functional group, such as CN, CF3 or iodine at C2 position, and the oxidation of the hydroxyl group of C3 to the carbonyl group, significantly increased cytotoxicity. This review describes the cytotoxic and anti-tumor properties of GA and its derivatives, targets and mechanisms of action and provides insight into the structure-activity relationship of GA derivatives.

Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder☆

PubMed Central

Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

2013-01-01

The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression. PMID:25206732

Antibacterial Derivatives of Marine Algae: An Overview of Pharmacological Mechanisms and Applications

PubMed Central

Shannon, Emer; Abu-Ghannam, Nissreen

2016-01-01

The marine environment is home to a taxonomically diverse ecosystem. Organisms such as algae, molluscs, sponges, corals, and tunicates have evolved to survive the high concentrations of infectious and surface-fouling bacteria that are indigenous to ocean waters. Both macroalgae (seaweeds) and microalgae (diatoms) contain pharmacologically active compounds such as phlorotannins, fatty acids, polysaccharides, peptides, and terpenes which combat bacterial invasion. The resistance of pathogenic bacteria to existing antibiotics has become a global epidemic. Marine algae derivatives have shown promise as candidates in novel, antibacterial drug discovery. The efficacy of these compounds, their mechanism of action, applications as antibiotics, disinfectants, and inhibitors of foodborne pathogenic and spoilage bacteria are reviewed in this article. PMID:27110798

A detailed kinetic mechanism including methanol and nitrogen pollutants relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coda Zabetta, Edgardo; Hupa, Mikko

2008-01-15

A detailed chemical kinetic mechanism for the simulation of the gas-phase combustion and pyrolysis of biomass-derived fuels was compiled by assembling selected reaction subsets from existing mechanisms (parents). The mechanism, here referred to as ''AaA,'' includes reaction subsets for the oxidation of hydrogen (H{sub 2}), carbon monoxide (CO), light hydrocarbons (C{sub 1} and C{sub 2}), and methanol (CH{sub 3}OH). The mechanism also takes into account reaction subsets of nitrogen pollutants, including the reactions relevant to staged combustion, reburning, and selective noncatalytic reduction (SNCR). The AaA mechanism was validated against suitable experimental data from the literature. Overall, the AaA mechanism gavemore » more accurate predictions than three other mechanisms of reference, although the reference mechanisms performed better occasionally. The predictions from AaA were also found to be consistent with the predictions of its parent mechanisms within most of their range of validity, thus transferring the validity of the parents to the inheriting mechanism (AaA). In parametric studies the AaA mechanism predicted that the effect of methanol on combustion and pollutants is often similar to that of light hydrocarbons, but it also showed that there are important exceptions, thus suggesting that methanol should be taken into account when simulating biomass combustion. To our knowledge, the AaA mechanism is currently the only mechanism that accounts for the chemistry of methanol and nitrogen relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels. (author)« less

Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denel-Bobrowska, Marta, E-mail: mdenel@biol.uni.lo

Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay. We evaluated apoptosis-inducing ability by double-staining with fluorescent probes (Hoechst 33258/propidium iodide), and by determining expression levels of genes involved in programmed cell death by reverse transcription-polymerase chain reaction. Genotoxicities of the compounds were tested by comet assays. Oxazolinoanthracyclines demonstrated high anti-tumor activity. O-DOX had significantlymore » higher cytotoxicity, apoptosis-inducing ability, and genotoxicity compared with parental doxorubicin (DOX) in all tested conditions, while O-DAU activity differed among cell lines. The mechanism of oxazoline analog action appeared to involve the mitochondrial pathway of programmed cell death. These results provide further information about oxazoline derivatives of commonly used anthracycline chemotherapy agents. O-DOX and O-DAU have the ability to induce apoptosis in tumor cells. - Highlights: • Substituted amino group increased the anticancer activity of anthracyclines. • Mitochondrial apoptotic pathway seems to be involved in the mechanism of action. • Favorable biological properties of oxazoline derivatives were confirmed.« less

Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

PubMed Central

Hu, Bin; El Haj, Alicia J; Dobson, Jon

2013-01-01

Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors—platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation. PMID:24065106

Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism.

PubMed

Yang, Jian; Chen, Gang; Li, Long Long; Pan, Wei; Zhang, Fang; Yang, Jingxiang; Wu, Shuwen; Tien, Po

2013-05-01

A series of chiral gossypol derivatives and its analogs were synthesized and tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol derivatives and its analogs were more active against H5N1 than the corresponding (-)-gossypol derivatives and its analogs. Through a simple chemical modification with amino acids, less active chiral gossypol could be converted into more active derivatives, and most of chiral gossypol derivatives were more potent against H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral gossypol derivatives and its analogs might impair the virus entry step of cell infection, likely targeting to HA2 protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural dynamics and quantum mechanical aspects of shikonin derivatives as CREBBP bromodomain inhibitors.

PubMed

Mitra, Sarmistha; Dash, Raju

2018-05-04

The Proteins involved in the chemical modification of lysine residues in histone, is currently being excessively focused as the therapeutic target for the treatment of cell related diseases like cancer. Among these proteins, the epigenetic reader, CREB-binding protein (CREBBP) bromodomain is one of the most prominent targets for effective anticancer drug design, which is responsible for the reorganization of acetylated histone lysine residues. Therefore, this study employed an integrative approach of structure based drug design, in combination with Molecular Dynamics (MD) and QM/MM study to identify as well as to describe the binding mechanism of two shikonin derivatives, acetylshikonin and propionylshikonin as inhibitors of CREBBP bromodomain. Here induced fit docking strategy was employed to explore the important intrinsic interactions of ligands with CREBBP bromodomain, consistently molecular dynamics simulation with two different methods and binding energy calculations by MM-GBSA and MM-PBSA were adopted to determine the stability of intermolecular interactions between protein and ligands. The results showed that both these derivatives made direct contacts with the important conserved residues of the active site, where propionylshikonin demonstrated stronger binding and stability than acetylshikonin, according to molecular dynamics simulation and binding free energy calculations. Further, QM/MM energy calculation was employed to study the chemical reactivity of the propionylshikonin and also to describe the mechanism of non bonded interactions between the propionylshikonin and CREBBP bromodomain. Though this study demands in vitro and in vivo experiments to evaluate the efficiency of the compound, these insights would assist to design more potent CREBBP bromodomain inhibitor, guiding the site of modification of propionylshikonin moiety for designing selective inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of addition of plants-derived polyamide 11 elastomer on the mechanical and tribological properties of hemp fiber reinforced polyamide 1010 composites

NASA Astrophysics Data System (ADS)

Mukaida, Jun; Nishitani, Yosuke; Kitano, Takeshi

2015-05-01

For the purpose of developing the new engineering materials such as structural materials and tribomaterials based on all plants-derived materials, the effect of the addition of plant-derived polyamide 11 Elastomer (PA11E) on the mechanical and tribological properties of hemp fiber(HF) reinforced polyamide 1010 (HF/PA1010) composites was investigated. PA1010 and PA11E (except the polyether groups used as soft segment) were made from plant-derived castor oil. Hemp fiber was surface-treated by two types of treatment: alkali treatment by NaOH solution and surface treatment by ureido silane coupling agent. HF/PA1010/PA11E ternary composites were extruded by a twin screw extruder and injection-molded. Their mechanical properties such as tensile, bending, Izod impact and tribological properties by ring-on-plate type sliding wear testing were evaluated. The effect of the addition of PA11E on the mechanical and tribological properties of HF/PA1010 composite differed for each property. Izod impact strength and specific wear rate improved with the addition of PA11E although tensile strength, modulus, and friction coefficient decreased with PA11E. It follows from these results that it may be possible to develop the new engineering materials with sufficient balance between mechanical and tribological properties.

Multiscaling behavior of atomic-scale friction

NASA Astrophysics Data System (ADS)

Jannesar, M.; Jamali, T.; Sadeghi, A.; Movahed, S. M. S.; Fesler, G.; Meyer, E.; Khoshnevisan, B.; Jafari, G. R.

2017-06-01

The scaling behavior of friction between rough surfaces is a well-known phenomenon. It might be asked whether such a scaling feature also exists for friction at an atomic scale despite the absence of roughness on atomically flat surfaces. Indeed, other types of fluctuations, e.g., thermal and instrumental fluctuations, become appreciable at this length scale and can lead to scaling behavior of the measured atomic-scale friction. We investigate this using the lateral force exerted on the tip of an atomic force microscope (AFM) when the tip is dragged over the clean NaCl (001) surface in ultra-high vacuum at room temperature. Here the focus is on the fluctuations of the lateral force profile rather than its saw-tooth trend; we first eliminate the trend using the singular value decomposition technique and then explore the scaling behavior of the detrended data, which contains only fluctuations, using the multifractal detrended fluctuation analysis. The results demonstrate a scaling behavior for the friction data ranging from 0.2 to 2 nm with the Hurst exponent H =0.61 ±0.02 at a 1 σ confidence interval. Moreover, the dependence of the generalized Hurst exponent, h (q ) , on the index variable q confirms the multifractal or multiscaling behavior of the nanofriction data. These results prove that fluctuation of nanofriction empirical data has a multifractal behavior which deviates from white noise.

The potential mechanism of Bursal-derived BPP-II on the antibody production and avian pre-B cell.

PubMed

Feng, Xiuli; Cao, Ruibing; Zhou, Bin; Liu, Qingtao; Liu, Ke; Liu, Xiaodong; Zhang, Yuanpeng; Gu, Jinyan; Miao, Denian; Chen, Puyan

2013-03-01

The bursa of Fabricius is critical for the normal development of the B lymphocytes responsible for antibody production. However, the mechanism of the bursal-derived bioactive factor on B cell development is little reported. In this paper, chicks were immunized with BPP-II and AIV vaccine or AIV antigen, and antibody and IL-4 production were detected. The results showed that BPP-II played strongly inducing roles on the humoral immune responses. To investigate the gene expression at transcriptional level, avian pre-B lymphocyte DT40 cells were treated with BPP-II, and were analyzed with the gene microarray. The results proved that BPP-II treatment regulated 11 pathways, in which homologous recombination is a vital mechanism which is involved in antibody Ig gene conversion and diversification during B cell development. These results suggested Bursal-derived biological active factor BPP-II might be involved in the antibody production processes and B cell development, which is vital to the humoral central immune organ, the bursa of Fabricius. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structure-mechanical property correlations in mechanochromic luminescent crystals of boron difluoride dibenzoylmethane derivatives.

PubMed

Krishna, Gamidi Rama; Devarapalli, Ramesh; Prusty, Rajesh; Liu, Tiandong; Fraser, Cassandra L; Ramamurty, Upadrasta; Reddy, Chilla Malla

2015-11-01

The structure and mechanical properties of crystalline materials of three boron difluoride dibenzoylmethane (BF2dbm) derivatives were investigated to examine the correlation, if any, among mechanochromic luminescence (ML) behaviour, solid-state structure, and the mechanical behaviour of single crystals. Qualitative mechanical deformation tests show that the crystals of BF2dbm( (t) Bu)2 can be bent permanently, whereas those of BF2dbm(OMe)2 exhibit an inhomogeneous shearing mode of deformation, and finally BF2dbmOMe crystals are brittle. Quantitative mechanical analysis by nano-indentation on the major facets of the crystals shows that BF2dbm( (t) Bu)2 is soft and compliant with low values of elastic modulus, E, and hardness, H, confirming its superior suceptibility for plastic deformation, which is attributed to the presence of a multitude of slip systems in the crystal structure. In contrast, both BF2dbm(OMe)2 and BF2dbmOMe are considerably stiffer and harder with comparable E and H, which are rationalized through analysis of the structural attributes such as the intermolecular interactions, slip systems and their relative orientation with respect to the indentation direction. As expected from the qualitative mechanical behaviour, prominent ML was observed in BF2dbm( (t) Bu)2, whereas BF2dbm(OMe)2 exhibits only a moderate ML and BF2dbmOMe shows no detectable ML, all examined under identical conditions. These results confirm that the extent of ML in crystalline organic solid-state fluorophore materials can be correlated positively with the extent of plasticity (low recovery). In turn, they offer opportunities to design new and improved efficient ML materials using crystal engineering principles.

Derivative chameleons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk

2012-07-01

We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly thismore » points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.« less

Cargo-shell and cargo-cargo couplings govern the mechanics of artificially loaded virus-derived cages

NASA Astrophysics Data System (ADS)

Llauró, Aida; Luque, Daniel; Edwards, Ethan; Trus, Benes L.; Avera, John; Reguera, David; Douglas, Trevor; Pablo, Pedro J. De; Castón, José R.

2016-04-01

Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers.Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two

Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells.

PubMed

Miyake, Yoshiaki; Furumatsu, Takayuki; Kubota, Satoshi; Kawata, Kazumi; Ozaki, Toshifumi; Takigawa, Masaharu

2011-06-03

Anterior cruciate ligament (ACL)-to-bone interface serves to minimize the stress concentrations that would arise between two different tissues. Mechanical stretch plays an important role in maintaining cell-specific features by inducing CCN family 2/connective tissue growth factor (CCN2/CTGF). We previously reported that cyclic tensile strain (CTS) stimulates α1(I) collagen (COL1A1) expression in human ACL-derived cells. However, the biological function and stress-related response of CCN2/CTGF were still unclear in ACL fibroblasts. In the present study, CCN2/CTGF was observed in ACL-to-bone interface, but was not in the midsubstance region by immunohistochemical analyses. CTS treatments induced higher increase of CCN2/CTGF expression and secretion in interface cells compared with midsubstance cells. COL1A1 expression was not influenced by CCN2/CTGF treatment in interface cells despite CCN2/CTGF stimulated COL1A1 expression in midsubstance cells. However, CCN2/CTGF stimulated the proliferation of interface cells. Our results suggest that distinct biological function of stretch-induced CCN2/CTGF might regulate region-specific phenotypes of ACL-derived cells. Copyright © 2011 Elsevier Inc. All rights reserved.

Nanofrictional behavior of amorphous, polycrystalline and textured Y-Cr-O films

NASA Astrophysics Data System (ADS)

Gervacio-Arciniega, J. J.; Flores-Ruiz, F. J.; Diliegros-Godines, C. J.; Broitman, E.; Enriquez-Flores, C. I.; Espinoza-Beltrán, F. J.; Siqueiros, J.; Cruz, M. P.

2016-08-01

Differences in friction coefficients (μ) of ferroelectric YCrO3, textured and polycrystalline films, and non-ferroelectric Y-Cr-O films are analyzed. The friction coefficient was evaluated by atomic force microscopy using a simple quantitative procedure where the dependence of friction force with the applied load is obtained in only one topographical image. A simple code was developed with the MATLAB® software to analyze the experimental data. The code includes a correction of the hysteresis in the forward and backward scanning directions. The quantification of load exerted on the sample surface was obtained by finite element analysis of the AFM cantilever starting from its experimental dynamic information. The results show that the ferroelectric YCrO3 film deposited on a Pt(150 nm)/TiO2(30 nm)/SiO2/Si (100) substrate is polycrystalline and has a lower friction coefficient than the deposited on SrTiO3 (110), which is highly textured. From a viewpoint of industrial application in ferroelectric memories, where the writing process is electrical or mechanically achieved by sliding AFM tips on the sample, polycrystalline YCrO3 films seem to be the best candidates due to their lower μ.

ON THE DYNAMICAL DERIVATION OF EQUILIBRIUM STATISTICAL MECHANICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prigogine, I.; Balescu, R.; Henin, F.

1960-12-01

Work on nonequilibrium statistical mechanics, which allows an extension of the kinetic proof to all results of equilibrium statistical mechanics involving a finite number of degrees of freedom, is summarized. As an introduction to the general N-body problem, the scattering theory in classical mechanics is considered. The general N-body problem is considered for the case of classical mechanics, quantum mechanics with Boltzmann statistics, and quantum mechanics including quantum statistics. Six basic diagrams, which describe the elementary processes of the dynamics of correlations, were obtained. (M.C.G.)

The mechanisms of substance P-mediated migration of bone marrow-derived mesenchymal stem cell-like ST2 cells.

PubMed

Dubon, Maria Jose; Park, Ki-Sook

2016-04-01

Substance P (SP) is known to induce the mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) and thus participates in wound repair. However, the cellular and molecular mechanisms responsible for the SP-mediated migration of BM-MSCs were not fully understood. In the present study, we studied the molecular mechanisms that mediate the migration of the BM-derived MSC-like cell line ST2 in response to SP. Using a migration assay and western blot analysis, we noted that SP induced the chemotactic migration of ST2 cells through the intrinsic activation of extracellular signal-regulated kinases (ERKs) and protein kinase B (Akt), the phosphorylated expression levels of which were increased. We noted that Src is involved in the SP-mediated migration of ST2 cells and that focal adhesion kinase (FAK) was activated in the ST2 cells following SP treatment. Membrane ruffling increased in the ST2 cells after SP treatment, as was clearly demonstrated by immunocytochemical analysis. Importantly, using a blocking antibody against N-cadherin (GC-4), we studied cell migration and noted that SP mediated the migration of the ST2 cells through N-cadherin. The present study thus advanced our understanding of the mechanisms through which SP induces BM-MSC migration.

The temporal derivative of expected utility: a neural mechanism for dynamic decision-making.

PubMed

Zhang, Xian; Hirsch, Joy

2013-01-15

Real world tasks involving moving targets, such as driving a vehicle, are performed based on continuous decisions thought to depend upon the temporal derivative of the expected utility (∂V/∂t), where the expected utility (V) is the effective value of a future reward. However, the neural mechanisms that underlie dynamic decision-making are not well understood. This study investigates human neural correlates of both V and ∂V/∂t using fMRI and a novel experimental paradigm based on a pursuit-evasion game optimized to isolate components of dynamic decision processes. Our behavioral data show that players of the pursuit-evasion game adopt an exponential discounting function, supporting the expected utility theory. The continuous functions of V and ∂V/∂t were derived from the behavioral data and applied as regressors in fMRI analysis, enabling temporal resolution that exceeded the sampling rate of image acquisition, hyper-temporal resolution, by taking advantage of numerous trials that provide rich and independent manipulation of those variables. V and ∂V/∂t were each associated with distinct neural activity. Specifically, ∂V/∂t was associated with anterior and posterior cingulate cortices, superior parietal lobule, and ventral pallidum, whereas V was primarily associated with supplementary motor, pre and post central gyri, cerebellum, and thalamus. The association between the ∂V/∂t and brain regions previously related to decision-making is consistent with the primary role of the temporal derivative of expected utility in dynamic decision-making. Copyright © 2012 Elsevier Inc. All rights reserved.

The Temporal Derivative of Expected Utility: A Neural Mechanism for Dynamic Decision-making

PubMed Central

Zhang, Xian; Hirsch, Joy

2012-01-01

Real world tasks involving moving targets, such as driving a vehicle, are performed based on continuous decisions thought to depend upon the temporal derivative of the expected utility (∂V/∂t), where the expected utility (V) is the effective value of a future reward. However, those neural mechanisms that underlie dynamic decision-making are not well understood. This study investigates human neural correlates of both V and ∂V/∂t using fMRI and a novel experimental paradigm based on a pursuit-evasion game optimized to isolate components of dynamic decision processes. Our behavioral data show that players of the pursuit-evasion game adopt an exponential discounting function, supporting the expected utility theory. The continuous functions of V and ∂V/∂t were derived from the behavioral data and applied as regressors in fMRI analysis, enabling temporal resolution that exceeded the sampling rate of image acquisition, hyper-temporal resolution, by taking advantage of numerous trials that provide rich and independent manipulation of those variables. V and ∂V/∂t were each associated with distinct neural activity. Specifically, ∂V/∂t was associated with anterior and posterior cingulate cortices, superior parietal lobule, and ventral pallidum, whereas V was primarily associated with supplementary motor, pre and post central gyri, cerebellum, and thalamus. The association between the ∂V/∂t and brain regions previously related to decision-making is consistent with the primary role of the temporal derivative of expected utility in dynamic decision-making. PMID:22963852

Effects of hypergravity on adipose-derived stem cell morphology, mechanical property and proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tavakolinejad, Alireza; Rabbani, Mohsen, E-mail: m.rabbani@eng.ui.ac.ir; Janmaleki, Mohsen

2015-08-21

Alteration in specific inertial conditions can lead to changes in morphology, proliferation, mechanical properties and cytoskeleton of cells. In this report, the effects of hypergravity on morphology of Adipose-Derived Stem Cells (ADSCs) are indicated. ADSCs were repeatedly exposed to discontinuous hypergravity conditions of 10 g, 20 g, 40 g and 60 g by utilizing centrifuge (three times of 20 min exposure, with an interval of 40 min at 1 g). Cell morphology in terms of length, width and cell elongation index and cytoskeleton of actin filaments and microtubules were analyzed by image processing. Consistent changes observed in cell elongation index as morphological change. Moreover, cell proliferation wasmore » assessed and mechanical properties of cells in case of elastic modulus of cells were evaluated by Atomic Force Microscopy. Increase in proliferation and decrease in elastic modulus of cells are further results of this study. Staining ADSC was done to show changes in cytoskeleton of the cells associated to hypergravity condition specifically in microfilament and microtubule components. After exposing to hypergravity, significant changes were observed in microfilaments and microtubule density as components of cytoskeleton. It was concluded that there could be a relationship between changes in morphology and MFs as the main component of the cells. - Highlights: • Hypergravity (10 g, 20 g, 40 g and 60 g) affects on adipose derived stem cells (ADSCs). • ADSCs after exposure to the hypergravity are more slender. • The height of ADSCs increases in all test groups comparing their control group. • Hypergravity decreases ADSCs modulus of elasticity and cell actin fiber content. • Hypergravity enhances proliferation rate of ADSCs.« less

Cargo–shell and cargo–cargo couplings govern the mechanics of artificially loaded virus-derived cages†

PubMed Central

Llauró, Aida; Luque, Daniel; Edwards, Ethan; Trus, Benes L.; Avera, John; Reguera, David; Douglas, Trevor

2016-01-01

Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers’ stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo–shell and cargo–cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo–cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers. PMID:27091107

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives

PubMed Central

Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

2008-01-01

benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties. PMID:18549472

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

PubMed

Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

2008-06-12

after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

USDA-ARS?s Scientific Manuscript database

Probiotics are health-promoting bacteria which may protect the intestines from injury and inflammatory diseases but our understanding of the mechanisms for probiotic action are limited. In this study, we hypothesized that a protein, known as p40, which is derived from the probiotic bacteria, Lactoba...

Capacity and mechanisms of ammonium and cadmium sorption on different wetland-plant derived biochars.

PubMed

Cui, Xiaoqiang; Hao, Hulin; Zhang, Changkuan; He, Zhenli; Yang, Xiaoe

2016-01-01

The objective of this study was to investigate the relationship between Cd(2+)/NH4(+) sorption and physicochemical properties of biochars produced from different wetland plants. Biochars from six species of wetland plants (i.e., Canna indica, Pennisetum purpureum Schum, Thalia dealbata, Zizania caduciflora, Phragmites australis and Vetiveria zizanioides) were obtained at 500°C and characterized, and their sorption for ammonium and cadmium was determined. There were significant differences in elemental composition, functional groups and specific surface area among the biochars derived from different wetland plant species. Sorption of ammonium and cadmium on the biochars could be described by a pseudo second order kinetic model, and the simple Langmuir model fits the isotherm data better than the Freundlich or Temkin model. The C. indica derived biochar had the largest sorption capacity for NH4(+) and Cd(2+), with a maximum sorption of 13.35 and 125.8mgg(-1), respectively. P. purpureum Schum derived biochar had a similar maximum sorption (119.3mgg(-1)) for Cd(2+). Ammonium sorption was mainly controlled by cation exchange, surface complexation with oxygen-containing functional groups and the formation of magnesium ammonium phosphate compounds, whereas for Cd(2+) sorption, the formation of cadmium phosphate precipitates, cation exchange and binding to oxygen-containing groups were the major possible mechanisms. In addition, the sorption of ammonium and cadmium was not affected by surface area and microporosity of the biochars. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanism of Resistance to an Antitubercular 2-Thiopyridine Derivative That Is Also Active against Burkholderia cenocepacia

PubMed Central

Scoffone, Viola C.; Spadaro, Francesca; Udine, Claudia; Makarov, Vadim; Fondi, Marco; Fani, Renato; De Rossi, Edda; Riccardi, Giovanna

2014-01-01

The discovery of new compounds that are able to inhibit the growth of Burkholderia cenocepacia is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against Mycobacterium tuberculosis and to have good activity toward B. cenocepacia was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in B. cenocepacia antibiotic resistance. PMID:24395233

Brain-Derived Neurotrophic Factor in Alzheimer's Disease: Risk, Mechanisms, and Therapy.

PubMed

Song, Jing-Hui; Yu, Jin-Tai; Tan, Lan

2015-12-01

Brain-derived neurotrophic factor (BDNF) has a neurotrophic support on neuron of central nervous system (CNS) and is a key molecule in the maintenance of synaptic plasticity and memory storage in hippocampus. However, changes of BDNF level and expression have been reported in the CNS as well as blood of Alzheimer's disease (AD) patients in the last decade, which indicates a potential role of BDNF in the pathogenesis of AD. Therefore, this review aims to summarize the latest progress in the field of BDNF and its biological roles in AD pathogenesis. We will discuss the interaction between BDNF and amyloid beta (Aβ) peptide, the effect of BDNF on synaptic repair in AD, and the association between BDNF polymorphism and AD risk. The most important is, enlightening the detailed biological ability and complicated mechanisms of action of BDNF in the context of AD would provide a future BDNF-related remedy for AD, such as increment in the production or release of endogenous BDNF by some drugs or BDNF mimics.

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies.

PubMed

Ashraf, Zaman; Rafiq, Muhammad; Nadeem, Humaira; Hassan, Mubashir; Afzal, Samina; Waseem, Muhammad; Afzal, Khurram; Latip, Jalifah

2017-01-01

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver-Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.

Mechanical Behavior of a Hi-Nicalon(tm)/SiC Composite Having a Polycarbosilane Derived Matrix

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.; Calomino, Anthony M.; McCue, Terry R.

1999-01-01

Polymer infiltration of a rigidized preform, followed by pyrolysis to convert the polymer to a ceramic, potentially offers a lower cost alternative to CVD. It also offers more moderate temperature requirements than melt infiltration approaches, which should minimize potential fiber damage during processing. However, polymer infiltration and pyrolysis results in a more microcracked matrix. Preliminary mechanical property characterization, including elevated temperature (1204 C) tensile, 500 h stress rupture behavior and low cycle fatigue, was conducted on Hi-Nicalon (TM)/Si-C-(O) composites having a dual layer BN/SiC interface and a matrix derived by impregnation and pyrolysis of allylhydridopolycarbosilane (AHPCS). Microstructural evaluation of failure surfaces and of polished transverse and longitudinal cross sections of the failed specimens was used to identify predominant failure mechanisms. In stress rupture testing at 1093 C, the failure was interface dominated, while at 1204 C in both stress rupture and two hour hold/fatigue tests failure was matrix dominated, resulting in specimen delamination.

Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication.

PubMed

Qin, Yiwen; Peng, Yuanzhen; Zhao, Wei; Pan, Jianping; Ksiezak-Reding, Hanna; Cardozo, Christopher; Wu, Yingjie; Divieti Pajevic, Paola; Bonewald, Lynda F; Bauman, William A; Qin, Weiping

2017-06-30

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Unravelling the effects of mechanical physiological conditioning on cardiac adipose tissue-derived progenitor cells in vitro and in silico.

PubMed

Llucià-Valldeperas, Aida; Bragós, Ramon; Soler-Botija, Carolina; Roura, Santiago; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Perea-Gil, Isaac; Bayes-Genis, Antoni

2018-01-11

Mechanical conditioning is incompletely characterized for stimulating therapeutic cells within the physiological range. We sought to unravel the mechanism of action underlying mechanical conditioning of adipose tissue-derived progenitor cells (ATDPCs), both in vitro and in silico. Cardiac ATDPCs, grown on 3 different patterned surfaces, were mechanically stretched for 7 days at 1 Hz. A custom-designed, magnet-based, mechanical stimulator device was developed to apply ~10% mechanical stretching to monolayer cell cultures. Gene and protein analyses were performed for each cell type and condition. Cell supernatants were also collected to analyze secreted proteins and construct an artificial neural network. Gene and protein modulations were different for each surface pattern. After mechanostimulation, cardiac ATDPCs increased the expression of structural genes and there was a rising trend on cardiac transcription factors. Finally, secretome analyses revealed upregulation of proteins associated with both myocardial infarction and cardiac regeneration, such as regulators of the immune response, angiogenesis or cell adhesion. To conclude, mechanical conditioning of cardiac ATDPCs enhanced the expression of early and late cardiac genes in vitro. Additionally, in silico analyses of secreted proteins showed that mechanical stimulation of cardiac ATDPCs was highly associated with myocardial infarction and repair.

Spectroscopic and quantum-mechanical study of enol-enol tautomerism of 3-acetyltetramic acid derivatives

NASA Astrophysics Data System (ADS)

Gromak, V. V.; Avakyan, V. G.; Lakhvich, O. F.

2000-03-01

By the method of IR spectroscopy, Raman spectroscopy, and nonempirical (basis 3-21G//3-21G(d,p)) and semiempirical (approximations AM1 and PM3) quantum-mechanical methods the tautomeric structure of a series of 3-acetyltetramic acid derivatives has been investigated. It is shown that all the investigated compounds exist in vapor, in solution, and in the crystalline state mainly in the form of exo-enols among which the prevalent form is that in which lactam carbonyl participates in intrachelate hydrogen bonding. Complete series of relative stabilities of possible tautomeric forms of the investigated compounds have been established. General conlusions on the structure of 5-membered ring β,β'-triketones have been formulated.

Stick-slip nanofriction in cold-ion traps

NASA Astrophysics Data System (ADS)

Mandelli, Davide; Vanossi, Andrea; Tosatti, Erio

2013-03-01

Trapped cold ions are known to form linear or planar zigzag chains, helices or clusters depending on trapping conditions. They may be forced to slide over a laser induced corrugated potential, a mimick of sliding friction. We present MD simulations of an incommensurate 101 ions chain sliding subject to an external electric field. As expected with increasing corrugation, we observe the transition from a smooth-sliding, highly lubric regime to a strongly dissipative stick-slip regime. Owing to inhomogeneity the dynamics shows features reminiscent of macroscopic frictional behaviors. While the chain extremities are pinned, the incommensurate central part is initially free to slide. The onset of global sliding is preceded by precursor events consisting of partial slips of chain portions further from the center. We also look for frictional anomalies expected for the chain sliding across the linear-zigzag structural phase transition. Although the chain is too short for a proper critical behavior, the sliding friction displays a frank rise near the transition, due to opening of a new dissipative channel via excitations of transverse modes. Research partly sponsored by Sinergia Project CRSII2 136287/1.

Molecular Adaptation Mechanisms Employed by Ethanologenic Bacteria in Response to Lignocellulose-derived Inhibitory Compounds

PubMed Central

Ibraheem, Omodele; Ndimba, Bongani K.

2013-01-01

Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

Elucidation of the binding mechanism of coumarin derivatives with human serum albumin.

PubMed

Garg, Archit; Manidhar, Darla Mark; Gokara, Mahesh; Malleda, Chandramouli; Suresh Reddy, Cirandur; Subramanyam, Rajagopal

2013-01-01

Coumarin is a benzopyrone which is widely used as an anti-coagulant, anti-oxidant, anti-cancer and also to cure arthritis, herpes, asthma and inflammation. Here, we studied the binding of synthesized coumarin derivatives with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence spectroscopy, circular dichroism spectroscopy, molecular docking and molecular dynamics simulation studies. By addition of coumarin derivatives to HSA the maximum fluorescence intensity was reduced due to quenching of intrinsic fluorescence upon binding of coumarin derivatives to HSA. The binding constant and free energy were found to be 1.957±0.01×10(5) M(-1), -7.175 Kcal M(-1) for coumarin derivative (CD) enamide; 0.837±0.01×10(5) M(-1), -6.685 Kcal M(-1) for coumarin derivative (CD) enoate, and 0.606±0.01×10(5) M(-1), -6.49 Kcal M(-1) for coumarin derivative methylprop (CDM) enamide. The CD spectroscopy showed that the protein secondary structure was partially unfolded upon binding of coumarin derivatives. Further, the molecular docking studies showed that coumarin derivatives were binding to HSA at sub-domain IB with the hydrophobic interactions and also with hydrogen bond interactions. Additionally, the molecular dynamics simulations studies contributed in understanding the stability of protein-drug complex system in the aqueous solution and the conformational changes in HSA upon binding of coumarin derivatives. This study will provide insights into designing of the new inspired coumarin derivatives as therapeutic agents against many life threatening diseases.

Thermal, dielectric characteristics and conduction mechanism of azodyes derived from quinoline and their copper complexes.

PubMed

El-Ghamaz, N A; Diab, M A; El-Bindary, A A; El-Sonbati, A Z; Nozha, S G

2015-05-15

A novel series of (5-(4'-derivatives phenyl azo)-8-hydroxy-7-quinolinecarboxaldehyde) (AQLn) (n=1, p-OCH3; n=2, R=H; and n=3; p-NO2) and their complexes [Cu(AQLn)2]·5H2O are synthesized and investigated. The optimized bond lengths, bond angles and the calculated quantum chemical parameters for AQLn are investigated. HOMO-LUMO energy gap, absolute electronegativities, chemical potentials, and absolute hardness are also calculated. The thermal properties, dielectric properties, alternating current conductivity (σac) and conduction mechanism are investigated in the frequency range 0.1-100kHz and temperature range 293-568K for AQL1-3 and 318-693K for [Cu(AQL1-3)2]·5H2O complexes. The thermal properties are of ligands (AQLn) and their Cu(II) complexes investigated by thermogravimetric analysis (TGA). The temperature and frequency dependence of the real and the imaginary part of the dielectric constant are studied. The values of the thermal activation energy of conduction mechanism for AQLn and their complexes [Cu(AQLn)2]·5H2O under investigation are calculated at different test frequencies. The values of thermal activation energies ΔE1 and ΔE2 for AQLn and [Cu(AQLn)2]·5H2O decrease with increasing the values of frequency. The ac conductivity is found to be depending on the chemical structure of the compounds. Different conduction mechanisms have been proposed to explain the obtained experimental data. The small polaron tunneling (SPT) is the dominant conduction mechanism for AQL1 and its complex [Cu(AQL1)2]·5H2O. The quantum mechanical tunneling (QMT) is the dominant conduction mechanism for AQL2 and its complex [Cu(AQL2)2]·5H2O. The correlated barrier hopping (CBH) is the dominant conduction mechanism for AQL3 and its complex [Cu(AQL3)2]·5H2O, and the values of the maximum barrier height (Wm) are calculated. Copyright © 2015 Elsevier B.V. All rights reserved.

Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters.

PubMed

Weems, Peyton W; Goodman, Robert L; Lehman, Michael N

2015-04-01

Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of the bioactive and mechanical behavior of dental ceramic/sol-gel derived bioactive glass mixtures.

PubMed

Abbasi, Zahra; Bahrololoum, Mohammad E; Bagheri, Rafat; Shariat, Mohammad H

2016-02-01

Dental ceramics can be modified by bioactive glasses in order to develop apatite layer on their surface. One of the benefits of such modification is to prolong the lifetime of the fixed dental prosthesis by preventing the formation of secondary caries. Dental ceramic/sol-gel derived bioactive glass mixture is one of the options for this modification. In the current study, mixtures of dental ceramic/bioactive glass with different compositions were successfully produced. To evaluate their bioactive behavior, prepared samples were immersed in a simulated body fluid at various time intervals. The prepared and soaked specimens were characterized using Fourier transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Since bioactive glasses have deleterious effects on the mechanical properties of dental ceramics, 3-point bending tests were used to evaluate the flexural strength, flexural strain, tangent modulus of elasticity and Weibull modulus of the specimens in order to find the optimal relationship between mechanical and bioactive properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

PubMed

Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

2016-07-01

Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chip-based comparison of the osteogenesis of human bone marrow- and adipose tissue-derived mesenchymal stem cells under mechanical stimulation.

PubMed

Park, Sang-Hyug; Sim, Woo Young; Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation.

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

PubMed

Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

Pleuromutilin and its derivatives-the lead compounds for novel antibiotics.

PubMed

Tang, Y-Z; Liu, Y-H; Chen, J-X

2012-01-01

Due to the rapid onset of resistance to most antibacterial drugs, research efforts are focusing on new classes of antibacterials with different mechanisms of action from clinically used antibacterials. Pleuromutilin derivatives have received more and more scientific attention for their unique mechanism of action. Two pleuromutilin derivatives, tiamulin and valnemulin have been successfully developed as antibiotics for veterinary use. Retapamulin, another pleuromutilin derivative has been approved for use in humans in April 2007 by Food and Drug Administration (FDA). It has been shown that there is rarely cross-resistance between pleuromutilin derivatives and other antimicrobial agents, and the development of resistance bacterial is still low. This review will demonstrate mechanism of action of pleuromutilin derivatives and reveal the structure-activity relationship (SAR) of pleuromutilin derivatives. Additionally, the pleuromutilin antibacterial derivative agents in the market, such as tiamulin, valnemulin and retapamulin, will be discussed. It is proposed that new antibacterial agents might be developed from pleuromutilin derivatives in the future.

ATLID beam steering mechanism and derived new piezoelectric-based devices for optical applications

NASA Astrophysics Data System (ADS)

Bourgain, F.; Barillot, F.; Belly, C.; Claeyssen, F.

2015-09-01

In Space & Defence (as well as in many others fields), there is a trend for miniaturisation in active optics requiring new actuators. Applications also often require the ability to withstand high vibrations and shocks levels, as well as vacuum compatibility for space applications. A new generation of small and smart actuators such as piezoelectric (piezo) actuators, are resolving this trend, thanks to their capacity to offer high energy density and to support both extreme and various requirements. This paper first presents the BSM mechanism and its requirements, the technologies involved in the design and the validation campaign results. Secondly, a derived XY piezoelectric positioning stage based on the same APA® and associated Strain Gage sensing technology is presented with its associated performances. Finally, a new piezoelectric motor based on the APA® technology, which allows the combination of long stroke while maintaining high resolution positioning of optical elements, is presented with experimental performances.

Synthesis, Antitumor Activity, and Mechanism of Action of 6-Acrylic Phenethyl Ester-2-pyranone Derivatives

PubMed Central

Fang, Sai; Chen, Lei; Yu, Miao; Cheng, Bao; Lin, Yongsheng; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung; Gu, Qiong; Xu, Jun

2015-01-01

Based on the scaffolds of caffeic acid phenethyl ester (CAPE) as well as bioactive lactone-containing compounds, 6-acrylic phenethyl ester-2-pyranone derivatives were synthesized and evaluated against five tumor cell lines (HeLa, C6, MCF-7, A549, and HSC-2). Most of the new derivatives exhibited moderate to potent cytotoxic activity. Moreover, HeLa cell lines showed higher sensitivity to these compounds. Particularly, compound 5o showed potent cytotoxic activity (IC50 = 0.50 – 3.45 μM) against the five cell lines. Further investigation on the mechanism of action showed that 5o induced apoptosis, arrested the cell cycle at G2/M phases in HeLa cells, and inhibited migration through disruption of the actin cytoskeleton. In addition, ADME properties were also calculated in silico, and compound 5o showed good ADMET properties with good absorption, low hepatotoxicity, and good solubility, and thus, could easily be bound to carrier proteins, without inhibition of CYP2D6. A structure-activity relationship (SAR) analysis indicated that compounds with ortho-substitution on the benzene ring exhibited obviously increased cytotoxic potency. This study indicated that compound 5o is a promising compound as an antitumor agent. PMID:25800703

Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation

PubMed Central

Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L.

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation. PMID:23029565

Distinct Mechanisms Produce Functionally Complementary Actions of Neuropeptides that are Structurally Related but Derived from Different Precursors

PubMed Central

Vilim, F.S.; Sasaki, K.; Rybak, J.; Alexeeva, V.; Cropper, E.; Jing, J.; Orekhova, I.V.; Brezina, V.; Price, D.; Romanova, E.V.; Rubakhin, S.S.; Hatcher, N.; Sweedler, J.V.; Weiss, K.R.

2010-01-01

Many bioactive neuropeptides containing RFamide at their C-terminus have been described in both invertebrates and vertebrates. To obtain insight into the functional logic of RFamide signaling, we investigate it here in the feeding system of Aplysia. We focus on the expression, localization, and actions of two families of RFamide peptides, the FRFamides and FMRFamide, in the central neuronal circuitry and the peripheral musculature that generate the feeding movements. We describe the cloning of the FRFamide precursor protein and show that the FRFamides and FMRFamide are derived from different precursors. We map the expression of the FRFamide and FMRFamide precursors in the feeding circuitry using in-situ hybridization and immunostaining, and confirm proteolytic processing of the FRFamide precursor by mass spectrometry. We show that the two precursors are expressed in different populations of sensory neurons in the feeding system. In a representative feeding muscle, we demonstrate the presence of both FRFamides and FMRFamide and their release, probably from the processes of the sensory neurons in the muscle. Both centrally and in the periphery, the FRFamides and FMRFamide act in distinct ways, apparently through distinct mechanisms, that nevertheless, from an overall functional perspective, their actions are complementary. Together, the FRFamides and FMRFamide convert feeding motor programs from ingestive to egestive, and depress feeding muscle contractions. We conclude that these structurally related peptides, even though derived from different precursors, expressed in different neurons, and acting through different mechanisms, remain related to each other in the functional roles that they play in the system. PMID:20053896

Mechanism for excitation-dependent photoluminescence from graphene quantum dots and other graphene oxide derivates: consensus, debates and challenges

NASA Astrophysics Data System (ADS)

Gan, Zhixing; Xu, Hao; Hao, Yanling

2016-04-01

Luminescent nanomaterials, with wide applications in biosensing, bioimaging, illumination and display techniques, have been consistently garnering enormous research attention. In particular, those with wavelength-controllable emissions could be highly beneficial. Carbon nanostructures, including graphene quantum dots (GQDs) and other graphene oxide derivates (GODs), with excitation-dependent photoluminescence (PL), which means their fluorescence color could be tuned simply by changing the excitation wavelength, have attracted lots of interest. However the intrinsic mechanism for the excitation-dependent PL is still obscure and fiercely debated presently. In this review, we attempt to summarize the latest efforts to explore the mechanism, including the quantum confinement effect, surface traps model, giant red-edge effect, edge states model and electronegativity of heteroatom model, as well as the newly developed synergistic model, to seek some clues to unravel the mechanism. Meanwhile the controversial difficulties for each model are further discussed. Besides this, the challenges and potential influences of the synthetic methodology and development of the materials are illustrated extensively to elicit more thought and constructive attempts toward their application.

Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media

PubMed Central

Peng, Hao-Fan; Liu, Jin Yu

2011-01-01

Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation. PMID:21083418

Induction of Osteogenic Differentiation of Adipose Derived Stem Cells by Microstructured Nitinol Actuator-Mediated Mechanical Stress

PubMed Central

Strauß, Sarah; Dudziak, Sonja; Hagemann, Ronny; Barcikowski, Stephan; Fliess, Malte; Israelowitz, Meir; Kracht, Dietmar; Kuhbier, Jörn W.; Radtke, Christine; Reimers, Kerstin; Vogt, Peter M.

2012-01-01

The development of large tissue engineered bone remains a challenge in vitro, therefore the use of hybrid-implants might offer a bridge between tissue engineering and dense metal or ceramic implants. Especially the combination of the pseudoelastic implant material Nitinol (NiTi) with adipose derived stem cells (ASCs) opens new opportunities, as ASCs are able to differentiate osteogenically and therefore enhance osseointegration of implants. Due to limited knowledge about the effects of NiTi-structures manufactured by selective laser melting (SLM) on ASCs the study started with an evaluation of cytocompatibility followed by the investigation of the use of SLM-generated 3-dimensional NiTi-structures preseeded with ASCs as osteoimplant model. In this study we could demonstrate for the first time that osteogenic differentiation of ASCs can be induced by implant-mediated mechanical stimulation without support of osteogenic cell culture media. By use of an innovative implant design and synthesis via SLM-technique we achieved high rates of vital cells, proper osteogenic differentiation and mechanically loadable NiTi-scaffolds could be achieved. PMID:23236461

SU-E-P-45: An Analytical Formula for Deriving Mechanical Iso-Center of Rotational Gantry Treatment Unit Rotational Gantry Treatment Unit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Bues, M

2015-06-15

Purpose: To present an analytical formula for deriving mechanical isocenter (MIC) of a rotational gantry treatment unit. The input data to the formula is obtained by a custom-made device. The formula has been implemented and used in an operational proton therapy facility since 2005. Methods: The custom made device consisted of 3 mutually perpendicular dial indicators and 5 clinometers, to obtain displacement data and gantry angle data simultaneously. During measurement, a steel sphere was affixed to the patient couch, and the device was attached to the snout rotating with the gantry. The displacement data and angle data were obtained simultaneouslymore » at angular increments of less than 1 degree. The analytical formula took the displacement and angle as input and derived the positions of dial indicator tips (DIT) position in room-fixed coordinate system. The formula derivation presupposes trigonometry and 3-dimentional coordinate transformations. Due to the symmetry properties of the defining equations, the DIT position can be solved for analytically without using mathematical approximations. We define the mean of all points in the DIT trajectory as the MIC. The formula was implemented in computer code, which has been employed during acceptance test, commissioning, as well as routine QA practice in an operational proton facility since 2005. Results: It took one minute for the custom-made device to acquire the measurement data for a full gantry rotation. The DIT trajectory and MIS are instantaneously available after the measurement. The MIC Result agrees well with vendor’s Result, which came from a different measurement setup, as well as different data analysis algorithm. Conclusion: An analytical formula for deriving mechanical isocenter was developed and validated. The formula is considered to be absolutely accurate mathematically. Be analyzing measured data of radial displacements as function of gantry angle, the formula calculates the MI position in room

Structure-Derived Proton-Transfer Mechanism of Action Human Pyruvate Dehydrogenase

NASA Technical Reports Server (NTRS)

Ciszak, Ewa; Dominiak, Paulina

2003-01-01

The derivative of vitamin B1 thiamin pyrophosphate (TPP) is a cofactor of pyruvate dehydrogenase (E1p) that is involved in decarboxylation of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine residue of dihydrolipoamide acetyltransferase. The structure of E1p recently determined in our laboratory revealed patterns of association of foul subunits and specifics of two TPP binding sites. The mechanism of action in part includes a conserved hydrogen bond between the N1' atom of the aminopyrimidine ring of the cofactor and the carboxylate group of Glu59 from the beta subunits, and a V-conformation of the cofactor that brings the N4' atom of the aminopyrimidine ring to the distance of the intramolecular hydrogen bond formed with the C2-atom of the thiazolium moiety. The carboxylate group of Glu59 is the local proton acceptor that enables proton translocation within the aminopyrimidine ring and stabilization of the rare N4' - iminopyrimidine tautomer. Based on the analysis of E1p structure, we postulate that the protein environment drives N4' - amino/N4' - imino dynamics resulting in a concerted shuttle-like movement of the subunits. We also propose that this movement of the subunits is strictly coordinated with the two enzymatic reactions carried out in E1p by each of the two cofactor sites. It is proposed that these reactions are in alternating phases such that when one active site is involved in decarboxylation, the other is involved in acetylation of lipoyl noiety.

Biomechanics of a convergently derived prey-processing mechanism in fishes: evidence from comparative tongue bite apparatus morphology and raking kinematics.

PubMed

Konow, Nicolai; Sanford, Christopher P J

2008-11-01

A tongue-bite apparatus (TBA) governs raking behaviors in two major and unrelated teleost lineages, the osteoglossomorph and salmoniform fishes. We present data on comparative morphology and kinematics from two representative species, the rainbow trout (Oncorhynchus mykiss) and the Australian arowana (Scleropages jardinii), which suggest that both the TBA and raking are convergently derived in these lineages. Similar TBA morphologies were present, except for differences in TBA dentition and shape of the novel cleithrobranchial ligament (CBL), which is arc-shaped in O. mykiss and straight in S. jardinii. Eight kinematic variables were used to quantify motion magnitude and maximum-timing in the kinematic input mechanisms of the TBA. Five variables differed inter-specifically (pectoral girdle retraction magnitude and timing, cranial and hyoid elevation and gape-distance timing), yet an incomplete taxon separation across multivariate kinematic space demonstrated an overall similarity in raking behavior. An outgroup analysis using bowfin (Amia calva) and pickerel (Esox americanus) to compare kinematics of raking with chewing and prey-capture provided robust quantitative evidence of raking being a convergently derived behavior. Support was also found for the notion that raking more likely evolved from the strike, a functionally distinct behavior, than from chewing, an alternative prey-processing behavior. Based on raking kinematic and muscle-activity data, we propose biomechanical models of the three input mechanisms that govern kinematics of the basihyal output mechanism during the raking power stroke: (1) cranial elevation protracts the upper TBA jaw from the lower (basihyal) TBA jaw; (2) basihyal retraction is caused directly by contraction of the sternohyoideus (SH); (3) hypaxial shortening, relayed via the pectoral girdle and SH-CBL complex, is an indirect basihyal retraction mechanism modeled as a four-bar linkage. These models will aid future analyses mapping

Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants

PubMed Central

Duclot, Florian; Kabbaj, Mohamed

2015-01-01

Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, promoting vulnerability or resilience to the development of depressive-like symptoms. Although the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of MDD remains unclear, its modulation of the efficacy of antidepressants is clearly established. Therefore, in this review, we focus on the epigenetic mechanisms regulating the expression of BDNF in humans and in animal models of depression, and discuss their role in individual differences in vulnerability to depression and response to antidepressant drugs. PMID:25568448

Robust Derivation of Risk Reduction Strategies

NASA Technical Reports Server (NTRS)

Richardson, Julian; Port, Daniel; Feather, Martin

2007-01-01

Effective risk reduction strategies can be derived mechanically given sufficient characterization of the risks present in the system and the effectiveness of available risk reduction techniques. In this paper, we address an important question: can we reliably expect mechanically derived risk reduction strategies to be better than fixed or hand-selected risk reduction strategies, given that the quantitative assessment of risks and risk reduction techniques upon which mechanical derivation is based is difficult and likely to be inaccurate? We consider this question relative to two methods for deriving effective risk reduction strategies: the strategic method defined by Kazman, Port et al [Port et al, 2005], and the Defect Detection and Prevention (DDP) tool [Feather & Cornford, 2003]. We performed a number of sensitivity experiments to evaluate how inaccurate knowledge of risk and risk reduction techniques affect the performance of the strategies computed by the Strategic Method compared to a variety of alternative strategies. The experimental results indicate that strategies computed by the Strategic Method were significantly more effective than the alternative risk reduction strategies, even when knowledge of risk and risk reduction techniques was very inaccurate. The robustness of the Strategic Method suggests that its use should be considered in a wide range of projects.

Mechanism of salt-induced activity enhancement of a marine-derived laccase, Lac15.

PubMed

Li, Jie; Xie, Yanan; Wang, Rui; Fang, Zemin; Fang, Wei; Zhang, Xuecheng; Xiao, Yazhong

2018-04-01

Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

PubMed Central

Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, M. Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2011-01-01

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria–derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40’s effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation. PMID:21606592

Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor.

PubMed

Patel, Ami V; Krimm, Robin F

2012-05-01

The number of neurons in the geniculate ganglion that are available to innervate taste buds is regulated by neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF). Our goal for the current study was to examine the timing and mechanism of NT-4-mediated regulation of geniculate neuron number during development. We discovered that NT-4 mutant mice lose 33% of their geniculate neuronal cells between E10.5 and E11.5. By E11.5, geniculate axons have just reached the tongue and do not yet innervate their gustatory targets; thus, NT-4 does not function as a target-derived growth factor. At E11.5, no difference was observed in proliferating cells or the rate at which cells exit the cell cycle between NT-4 mutant and wild type ganglia. Instead, there was an increase in TUNEL-labeling, indicating an increase in cell death in Ntf4(-/-) mice compared with wild types. However, activated caspase-3, which is up-regulated in the absence of BDNF, was not increased. This finding indicates that cell death initiated by NT-4-removal occurs through a different cell death pathway than BDNF-removal. We observed no additional postnatal loss of taste buds or neurons in Ntf4(-/-) mice. Thus, during early embryonic development, NT-4 produced in the ganglion and along the projection pathway inhibits cell death through an activated caspase-3 independent mechanism. Therefore, compared to BDNF, NT-4 plays distinct roles in gustatory development; differences include timing, source of neurotrophin, and mechanism of action. Published by Elsevier Inc.

Optical and mechanical behaviors of glassy silicone networks derived from linear siloxane precursors

NASA Astrophysics Data System (ADS)

Jang, Heejun; Seo, Wooram; Kim, Hyungsun; Lee, Yoonjoo; Kim, Younghee

2016-01-01

Silicon-based inorganic polymers are promising materials as matrix materials for glass fiber composites because of their good process ability, transparency, and thermal property. In this study, for utilization as a matrix precursor for a glass-fiber-reinforced composite, glassy silicone networks were prepared via hydrosilylation of linear/pendant Si-H polysiloxanes and the C=C bonds of viny-lterminated linear/cyclic polysiloxanes. 13C nuclear magnetic resonance spectroscopy was used to determine the structure of the cross-linked states, and a thermal analysis was performed. To assess the mechanical properties of the glassy silicone networks, we performed nanoindentation and 4-point bending tests. Cross-linked networks derived from siloxane polymers are thermally and optically more stable at high temperatures. Different cross-linking agents led to final networks with different properties due to differences in the molecular weights and structures. After stepped postcuring, the Young's modulus and the hardness of the glassy silicone networks increased; however, the brittleness also increased. The characteristics of the cross-linking agent played an important role in the functional glassy silicone networks.

Derivation of mechanical characteristics for Ni/Au intermetallic surface with SAC305 solder

NASA Astrophysics Data System (ADS)

Kim, Jong-Min; Lee, Hyun-Boo; Chang, Yoon-Suk; Choi, Jae-Boong

2013-03-01

Many surface finish methods are used to connect a substrate with the electric components of IT products in the micro-packaging process, and various types of lead-free solder have been developed as alternative materials to lead-based solder to reduce environmental contamination. However, there has been little research on the mechanical properties of the inter-metallic surface which is generated in the bumping process between the lead-free solder and surface films such as Ni/Au. The present work is to derive the material properties of a Ni/Au inter-metallic surface with SAC305 solder. A series of indentation tests were carried out by changing four nano-scale indentation depths and two strain rates. Also, a reverse algorithm method was adopted to determine the elastic-plastic stress-strain curve based on the load-displacement curve from the indentation test data. As a result of the material characterization effort, the mean elastic modulus, yield strength and strain hardening exponent of IMC with Ni/Au finish were determined.

Systems biology derived source-sink mechanism of BMP gradient formation

PubMed Central

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei

2017-01-01

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development. PMID:28826472

Systems biology derived source-sink mechanism of BMP gradient formation.

PubMed

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei; Umulis, David; Mullins, Mary C

2017-08-09

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development.

Bioactive peptides derived from human milk proteins--mechanisms of action.

PubMed

Wada, Yasuaki; Lönnerdal, Bo

2014-05-01

Human milk contains a multitude of bioactive proteins with very diverse functions, which are beneficial for the rapidly growing neonate. The large variety of bioactivities is accomplished by the combination of bioactive proteins per se and gastrointestinal release of bioactive peptides derived from them. The bioactivities exerted by these peptides include enhancement of mineral absorption, immunomodulation, opioid, antihypertensive and antimicrobial activities. Notably, several of the activities are not attributed to the parental proteins, but exclusively to released bioactive peptides. This article reviews studies on bioactive peptides derived from major human milk proteins, such as caseins, α-lactalbumin and lactoferrin, during gastrointestinal digestion. Studies of bovine milk counterparts are also cited as a comparison. Copyright © 2014. Published by Elsevier Inc.

A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models

PubMed Central

Lappano, Rosamaria; Rosano, Camillo; Pisano, Assunta; Santolla, Maria Francesca; De Francesco, Ernestina Marianna; De Marco, Paola; Dolce, Vincenza; Ponassi, Marco; Felli, Lamberto; Cafeo, Grazia; Kohnke, Franz Heinrich; Abonante, Sergio; Maggiolini, Marcello

2015-01-01

ABSTRACT Estrogens regulate numerous pathophysiological processes, mainly by binding to and activating estrogen receptor (ER)α and ERβ. Increasing amounts of evidence have recently demonstrated that G-protein coupled receptor 30 (GPR30; also known as GPER) is also involved in diverse biological responses to estrogens both in normal and cancer cells. The classical ER and GPER share several features, including the ability to bind to identical compounds; nevertheless, some ligands exhibit opposed activity through these receptors. It is worth noting that, owing to the availability of selective agonists and antagonists of GPER for research, certain differential roles elicited by GPER compared with ER have been identified. Here, we provide evidence on the molecular mechanisms through which a calixpyrrole derivative acts as a GPER antagonist in different model systems, such as breast tumor cells and cancer-associated fibroblasts (CAFs) obtained from breast cancer patients. Our data might open new perspectives toward the development of a further class of selective GPER ligands in order to better dissect the role exerted by this receptor in different pathophysiological conditions. Moreover, calixpyrrole derivatives could be considered in future anticancer strategies targeting GPER in cancer cells. PMID:26183213

A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models.

PubMed

Lappano, Rosamaria; Rosano, Camillo; Pisano, Assunta; Santolla, Maria Francesca; De Francesco, Ernestina Marianna; De Marco, Paola; Dolce, Vincenza; Ponassi, Marco; Felli, Lamberto; Cafeo, Grazia; Kohnke, Franz Heinrich; Abonante, Sergio; Maggiolini, Marcello

2015-10-01

Estrogens regulate numerous pathophysiological processes, mainly by binding to and activating estrogen receptor (ER)α and ERβ. Increasing amounts of evidence have recently demonstrated that G-protein coupled receptor 30 (GPR30; also known as GPER) is also involved in diverse biological responses to estrogens both in normal and cancer cells. The classical ER and GPER share several features, including the ability to bind to identical compounds; nevertheless, some ligands exhibit opposed activity through these receptors. It is worth noting that, owing to the availability of selective agonists and antagonists of GPER for research, certain differential roles elicited by GPER compared with ER have been identified. Here, we provide evidence on the molecular mechanisms through which a calixpyrrole derivative acts as a GPER antagonist in different model systems, such as breast tumor cells and cancer-associated fibroblasts (CAFs) obtained from breast cancer patients. Our data might open new perspectives toward the development of a further class of selective GPER ligands in order to better dissect the role exerted by this receptor in different pathophysiological conditions. Moreover, calixpyrrole derivatives could be considered in future anticancer strategies targeting GPER in cancer cells. © 2015. Published by The Company of Biologists Ltd.

Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

NASA Astrophysics Data System (ADS)

Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

2018-03-01

Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

PubMed Central

Ribatti, D; Nico, B; Pezzolo, A; Vacca, A; Meazza, R; Cinti, R; Carlini, B; Parodi, F; Pistoia, V; Corrias, M V

2006-01-01

Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-γ (IFN-γ) gene transfer dampens ACN tumorigenicity. As IFN-γ represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-γ and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-γ xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-γ xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-γ was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds. PMID:16721359

Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer.

PubMed

Berchem, Guy; Noman, Muhammad Zaeem; Bosseler, Manon; Paggetti, Jerome; Baconnais, Sonia; Le Cam, Eric; Nanbakhsh, Arash; Moussay, Etienne; Mami-Chouaib, Fathia; Janji, Bassam; Chouaib, Salem

2016-04-01

Tumor-derived microvesicles (TD-MVs) are key mediators which are shed by cancer cells and can sensitize neighboring cells in the tumor microenvironment. TD-MVs are extracellular vesicles composed of exosomes and MVs and promote cancer invasion and metastasis. Intratumoral hypoxia is an integral component of all solid tumors. The relationship between hypoxic tumor-shed MVs and NK-mediated cytotoxicity remains unknown. In this paper, we reported that MVs derived from hypoxic tumor cells qualitatively differ from those derived from normoxic tumor cells. Using multiple tumor models, we showed that hypoxic MVs inhibit more NK cell function as compared to normoxic MVs. Hypoxic TD-MVs package two immunosuppressive factors involved in the impairment of natural killer (NK) cell cytotoxicity against different tumor cells in vitro and in vivo . We showed that following their uptake by NK cells, hypoxic TD-MVs transfer TGF-β1 to NK cells, decreasing the cell surface expression of the activating receptor NKG2D, thereby inhibiting NK cell function. MicroRNA profiling revealed the presence of high levels of miR-210 and miR-23a in hypoxic TD-MVs. We demonstrated that miR-23a in hypoxic TD-MVs operates as an additional immunomosuppressive factor, since it directly targets the expression of CD107a in NK cells. To our knowledge, this is the first study to show that hypoxic tumor cells by secreting MVs can educate NK cells and decrease their antitumor immune response. This study highlights the existence of a novel mechanism of immune suppression mediated by hypoxic TD-MVs and further improves our understanding of the immunosuppressive mechanisms prevailing in the hypoxic tumor microenvironment.

Thermal degradation and plasticizing mechanism of poly(vinyl chloride) plasticized with a novel cardanol derived plasticizer

NASA Astrophysics Data System (ADS)

Chen, J.; Nie, X. A.; Jiang, J. C.; Zhou, Y. H.

2018-01-01

A natural plasticizer cardanol derivatives glycidyl ether (CGE) was synthesized and employed as a plasticizer for the poly(vinyl chloride). The effect of CGE on thermal degradation of PVC films and its plasticizing mechanism were firstly reported. The molecular structure of CGE was characterized with Fourier transform infrared spectroscopy (FTIR). Thermal properties, degradation properties and compatibility of the PVC films were investigated by Differential scanning calorimeter analysis (DSC), Thermogravimetric analysis (TGA) and FTIR, respectively. Compared with the commercial plasticizers dioctylphthalate (DOP), CGE can endow PVC film with a decrease of 4.31 °C in glass transition temperature (Tg), an increase of 24.01 °C and 25.53 °C in 10% weight loss (T 10) and 50% weight loss (T 50) respectively, and a higher activetion energy of thermal degradation (Ea ).

Investigation into 9(S)-HPODE-derived allene oxide to cyclopentenone cyclization mechanism via diradical oxyallyl intermediates

PubMed Central

Hebert, Sebastien P.; Cha, Jin K.; Brash, Alan R.; Schlegel, H. Bernhard

2016-01-01

The cyclopentane core is ubiquitous among a large number of biologically relevant natural products. Cyclopentenones have been shown to be versatile intermediates for the stereoselective preparation of highly substituted cyclopentane derivatives. Allene oxides are oxygenated fatty acids which are involved in the pathways of cyclopentenone biosynthesis in plants and marine invertebrates; however, their cyclization behavior is not well understood. Recent work by Brash and co-workers (J. Biol. Chem. 2013, 288, 20797) revealed an unusual cyclization property of the 9(S)-HPODE-derived allene oxides: the previously unreported 10Z-isomer cyclizes to a cis-dialkylcyclopentenone in hexane/isopropyl alcohol (100:3,v/v), but the known 10E-isomer does not yield cis-cyclopentenone under the same conditions. The mechanism for cyclization has been investigated for unsubstituted and methyl substituted vinyl allene oxide using a variety of methods including CASSCF, ωB97xD, and CCSD(T) and basis sets up to cc-pVTZ. The lowest energy pathway proceeds via homolytic cleavage of the epoxide ring, formation of an oxyallyl diradical, which closes readily to a cyclopropanone intermediate. The cyclopropanone opens to the requisite oxyallyl which closes to the experimentally observed product, cis-cyclopentenone. The calculations show that the open shell, diradical pathway is lower in energy than the closed shell reactions of allene oxide to cyclopropanone, and cyclopropanone to cyclopentenone. PMID:26976802

Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.

PubMed

Hindley, Stephen; Ward, Stephen A; Storr, Richard C; Searle, Natalie L; Bray, Patrick G; Park, B Kevin; Davies, Jill; O'Neill, Paul M

2002-02-28

The potent antimalarial activity of chloroquine against chloroquine-sensitive strains can be attributed, in part, to its high accumulation in the acidic environment of the heme-rich parasite food vacuole. A key component of this intraparasitic chloroquine accumulation mechanism is a weak base "ion-trapping" effect whereupon the basic drug is concentrated in the acidic food vacuole in its membrane-impermeable diprotonated form. By the incorporation of amino functionality into target artemisinin analogues, we hoped to prepare a new series of analogues that, by virtue of increased accumulation into the ferrous-rich vacuole, would display enhanced antimalarial potency. The initial part of the project focused on the preparation of piperazine-linked analogues (series 1 (7-16)). Antimalarial evaluation of these derivatives demonstrated potent activity versus both chloroquine-sensitive and chloroquine-resistant parasites. On the basis of these observations, we then set about preparing a series of C-10 carba-linked amino derivatives. Optimization of the key synthetic step using a newly developed coupling protocol provided a key intermediate, allyldeoxoartemisinin (17) in 90% yield. Further elaboration, in three steps, provided nine target C-10 carba analogues (series 2 (21-29)) in good overall yields. Antimalarial assessment demonstrated that these compounds were 4-fold more potent than artemisinin and about twice as active as artemether in vitro versus chloroquine-resistant parasites. On the basis of the products obtained from biomimetic Fe(II) degradation of the C-10 carba analogue (23), we propose that these analogues may have a mode of action subtly different from that of the parent drug artemisinin (series 1 (7-16)) and other C-10 ether derivatives such as artemether. Preliminary in vivo testing by the WHO demonstrated that four of these compounds are active orally at doses of less than 10 mg/kg. Since these analogues are available as water-soluble salts and cannot

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

PubMed Central

Carroll, Sean Michael; Ortlund, Eric A.; Thornton, Joseph W.

2011-01-01

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functions of GRs—reduced sensitivity to all hormones and increased selectivity for glucocorticoids—are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR–MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carroll, Sean Michael; Ortlund, Eric A; Thornton, Joseph W.

2012-03-16

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functionsmore » of GRs - reduced sensitivity to all hormones and increased selectivity for glucocorticoids - are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR-MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and

An ultrafast spectroscopic and quantum mechanical investigation of multiple emissions in push-pull pyridinium derivatives bearing different electron donors.

PubMed

Carlotti, B; Benassi, E; Cesaretti, A; Fortuna, C G; Spalletti, A; Barone, V; Elisei, F

2015-08-28

A joint experimental and theoretical approach, involving state-of-the-art femtosecond fluorescence up-conversion measurements and quantum mechanical computations including vibronic effects, was employed to get a deep insight into the excited state dynamics of two cationic dipolar chromophores (Donor-π-Acceptor(+)) where the electron deficient portion is a N-methyl pyridinium and the electron donor a trimethoxyphenyl or a pyrene, respectively. The ultrafast spectroscopic investigation, and the time resolved area normalised emission spectra in particular, revealed a peculiar multiple emissive behaviour and allowed the distinct emitting states to be remarkably distinguished from solvation dynamics, occurring in water in a similar timescale. The two and three emissions experimentally detected for the trimethoxyphenyl and pyrene derivatives, respectively, were associated with specific local emissive minima in the potential energy surface of S1 on the ground of quantum-mechanical calculations. A low polar and planar Locally Excited (LE) state together with a highly polar and Twisted Intramolecular Charge Transfer (TICT) state is identified to be responsible for the dual emission of the trimethoxyphenyl compound. Interestingly, the more complex photobehaviour of the pyrenyl derivative was explained considering the contribution to the fluorescence coming not only from the LE and TICT states but also from a nearly Planar Intramolecular Charge Transfer (PICT) state, with both the TICT and the PICT generated from LE by progressive torsion around the quasi-single bond between the methylpyridinium and the ethene bridge. These findings point to an interconversion between rotamers for the pyrene compound taking place in its excited state against the Non-equilibrated Excited Rotamers (NEER) principle.

Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors.

PubMed

Wang, Jinghui; Yang, Yinfeng; Li, Yan; Wang, Yonghua

2016-07-27

Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with Q(2) = 0. 64, R(2)ncv = 0.93, R(2)pred = 0.80 and Q(2) = 0. 65, R(2)ncv = 0.98, R(2)pred = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors.

Theoretical study of the thermodynamics of the mechanisms underlying antiradical activity of cinnamic acid derivatives.

PubMed

Amić, Ana; Marković, Zoran; Klein, Erik; Dimitrić Marković, Jasmina M; Milenković, Dejan

2018-04-25

The role of antiradical moieties (catechol, guaiacyl and carboxyl group) and molecular conformation in antioxidative potency of dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) was investigated by density functional theory (DFT) method. The thermodynamic preference of different reaction paths of double (2H + /2e - ) free radical scavenging mechanisms was estimated. Antiradical potency of DHCA and DHFA was compared with that exerted by their unsaturated analogs - caffeic acid (CA) and ferulic acid (FA). Cis/trans and anti-isomers of studied cinnamic acid derivatives may scavenge free radicals via double processes by involvement of catechol or guaiacyl moiety. Carboxyl group of syn-isomers may also participate in the inactivation of free radicals. Gibbs free energies of reactions with various free radicals indicate that syn-DHCA and syn-DHFA, colon catabolites that could be present in systemic circulation in low μM concentrations, have a potential to contribute to health benefits by direct free radical scavenging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Bifunctional Quinolonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, Biological Activities and Mechanism of Action

PubMed Central

Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Artico, Marino; Lavecchia, Antonio; Marinelli, Luciana; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe

2008-01-01

The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated target in the development of therapeutics against HIV infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the β-diketo acids (DKAs) represent a major lead for anti-HIV-1drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3′-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-crosslinking experiments. PMID:16539381

Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus.

PubMed

Hu, Yichen; Zhang, Jinming; Kong, Weijun; Zhao, Gang; Yang, Meihua

2017-04-01

The antifungal activity and potential mechanisms in vitro as well as anti-aflatoxigenic efficiency in vivo of natural essential oil (EO) derived from turmeric (Curcuma longa L.) against Aspergillus flavus was intensively investigated. Based on the previous chemical characterization of turmeric EO by gas chromatography-mass spectrometry, the substantially antifungal activities of turmeric EO on the mycelial growth, spore germination and aflatoxin production were observed in a dose-dependent manner. Furthermore, these antifungal effects were related to the disruption of fungal cell endomembrane system including the plasma membrane and mitochondria, specifically i.e. the inhibition of ergosterol synthesis, mitochondrial ATPase, malate dehydrogenase, and succinate dehydrogenase activities. Moreover, the down-regulation profiles of turmeric EO on the relative expression of mycotoxin genes in aflatoxin biosynthetic pathway revealed its anti-aflatoxigenic mechanism. Finally, the suppression effect of fungal contamination in maize indicated that turmeric EO has potential as an eco-friendly antifungal agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction.

PubMed

Budiyono, Agung; Rohrlich, Daniel

2017-11-03

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an "ontic extension" defines a nonseparable (global) random variable that generates physical correlations, and an "epistemic restriction" constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck's constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.

Beyond velocity and acceleration: jerk, snap and higher derivatives

NASA Astrophysics Data System (ADS)

Eager, David; Pendrill, Ann-Marie; Reistad, Nina

2016-11-01

The higher derivatives of motion are rarely discussed in the teaching of classical mechanics of rigid bodies; nevertheless, we experience the effect not only of acceleration, but also of jerk and snap. In this paper we will discuss the third and higher order derivatives of displacement with respect to time, using the trampolines and theme park roller coasters to illustrate this concept. We will also discuss the effects on the human body of different types of acceleration, jerk, snap and higher derivatives, and how they can be used in physics education to further enhance the learning and thus the understanding of classical mechanics concepts.

Intraspinal Rewiring of the Corticospinal Tract Requires Target-Derived Brain-Derived Neurotrophic Factor and Compensates Lost Function after Brain Injury

ERIC Educational Resources Information Center

Ueno, Masaki; Hayano, Yasufumi; Nakagawa, Hiroshi; Yamashita, Toshihide

2012-01-01

Brain injury that results in an initial behavioural deficit is frequently followed by spontaneous recovery. The intrinsic mechanism of this functional recovery has never been fully understood. Here, we show that reorganization of the corticospinal tract induced by target-derived brain-derived neurotrophic factor is crucial for spontaneous recovery…

Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

PubMed

Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

2015-05-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies.

PubMed

Khan, Shagufta; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Imtaiyaz Hassan, Md

2018-05-01

Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

PubMed

Davidson, Iain G; Langner, Eric J; Plowman, Steven V; Blair, Julian A

2003-03-26

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium. Copyright 2003 Elsevier Science B.V.

A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line.

PubMed

Kodama, Tatsushi; Motoi, Noriko; Ninomiya, Hironori; Sakamoto, Hiroshi; Kitada, Kunio; Tsukaguchi, Toshiyuki; Satoh, Yasuko; Nomura, Kimie; Nagano, Hiroko; Ishii, Nobuya; Terui, Yasuhito; Hatake, Kiyohiko; Ishikawa, Yuichi

2014-11-01

EML4-ALK is a driver oncogene in non-small-cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents. Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of this gene fusion remain unknown. This study aimed to examine the mechanism of EML4-ALK rearrangement using a novel cell line with the EML4-ALK fusion gene. An EML4-ALK-positive cell line, termed JFCR-LC649, was established from pleomorphic carcinoma, a rare subtype of NSCLC. We investigated the chromosomal aberrations using fluorescence in situ hybridization and comparative genomic hybridization (CGH). Alectinib/CH5424802, a selective ALK inhibitor, was evaluated in the antitumor activity against JFCR-LC649 in vitro and in vivo xenograft model. We established an EML4-ALK-positive cell line, termed JFCR-LC649, derived from a patient with NSCLC and revealed that the JFCR-LC649 cells harbor variant 3 of the EML4-ALK fusion with twofold copy number gain. Interestingly, comparative genomic hybridization and metaphase-fluorescence in situ hybridization analysis showed that in addition to two normal chromosome 2, JFCR-LC649 cells contained two aberrant chromosome 2 that were fragmented and scattered. These observations provided the first evidence that EML4-ALK fusion in JFCR-LC649 cells was formed in chromosome 2 by a distinct mechanism of genomic rearrangement, termed chromothripsis. Furthermore, a selective ALK inhibitor alectinib/CH5424802 suppressed tumor growth of the JFCR-LC649 cells through inhibition of phospho-ALK in vitro and in vivo in a xenograft model. Our results suggested that chromothripsis may be a mechanism of oncogenic rearrangement of EML4-ALK. In addition, alectinib was effective against EML4-ALK-positive tumors with ALK copy number gain mediated by chromothripsis.

Combined hydrophobicity and mechanical durability through surface nanoengineering

DOE PAGES

Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; ...

2015-04-08

This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability.

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

PubMed

Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

2017-02-01

Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study. Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as being a promising source of cells for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. In the current study, we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials and demonstrated that supplementation of mesenchymal niche cells as well as provision of mechanical loading particularly stretching have significantly promoted the maturation of the cardiomyocytes and hence improved the mechanical functional characteristics of the tissue strips

Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.

PubMed

Lawson, McKinley C; Hoth, Kevin C; Deforest, Cole A; Bowman, Christopher N; Anseth, Kristi S

2010-08-01

Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used. We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers. A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined. SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties. The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct

Shikonin and its derivatives: a patent review.

PubMed

Wang, Rubing; Yin, Runting; Zhou, Wen; Xu, Defeng; Li, Shaoshun

2012-09-01

Shikonin and its derivatives are the main components of red pigment extracts from Lithospermum erythrorhizon, whose medicinal properties have been confirmed for a long history, and have aroused great interest as the hallmark molecules responsible for their significant biological activities, especially for their striking anticancer effects. Areas covered in this paper include a review of the total synthesis, biological effects and mechanisms of shikonin and its derivatives for their anticancer activities in the past decade, basing on literature and patents. The current state and problems are also discussed. At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells. Meanwhile, the presumed mechanisms of action are also established in terms of their cytotoxicity. From a pharmacological point of view, most of the shikonin derivatives are at an early stage of their development, and thus it is difficult to determine the exact effectiveness in cancer treatment. With research in this field going deeper, it can be expected that, despite the difficulties, shikonin derivatives as potential anticancer agents will soon follow.

An artificial-intelligence technique for qualitatively deriving enzyme kinetic mechanisms from initial-velocity measurements and its application to hexokinase.

PubMed Central

Garfinkel, L; Cohen, D M; Soo, V W; Garfinkel, D; Kulikowski, C A

1989-01-01

We have developed a computer method based on artificial-intelligence techniques for qualitatively analysing steady-state initial-velocity enzyme kinetic data. We have applied our system to experiments on hexokinase from a variety of sources: yeast, ascites and muscle. Our system accepts qualitative stylized descriptions of experimental data, infers constraints from the observed data behaviour and then compares the experimentally inferred constraints with corresponding theoretical model-based constraints. It is desirable to have large data sets which include the results of a variety of experiments. Human intervention is needed to interpret non-kinetic information, differences in conditions, etc. Different strategies were used by the several experimenters whose data was studied to formulate mechanisms for their enzyme preparations, including different methods (product inhibitors or alternate substrates), different experimental protocols (monitoring enzyme activity differently), or different experimental conditions (temperature, pH or ionic strength). The different ordered and rapid-equilibrium mechanisms proposed by these experimenters were generally consistent with their data. On comparing the constraints derived from the several experimental data sets, they are found to be in much less disagreement than the mechanisms published, and some of the disagreement can be ascribed to different experimental conditions (especially ionic strength). PMID:2690819

Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miida, T.; Fielding, C.J.; Fielding, P.E.

1990-11-01

The transfer of ({sup 3}H)cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t{sub 1/2} at 37{degree}C of 51 {plus minus} 8 min and an activation energy of 18.0 kCal mol{sup {minus}1}. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major {alpha}-migrating class (HDL{sub 2b}) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL{sub 2b} to smaller {alpha}HDL (particularly HDL{sub 3}) driven enzymatically bymore » the lecithin-cholesterol acyltransferase reaction. Rates of transfer among {alpha}HDL were most rapid from the largest {alpha}HDL fraction (HDL{sub 2b}), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the {alpha}HDL pathyway, with little label in pre-{beta}HDL. The same experiments confirmed earlier data that cell-derived cholesterol is preferentially channeled through pre-{beta}HDL. The authors suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol.« less

Ghost-Free Theory with Third-Order Time Derivatives

NASA Astrophysics Data System (ADS)

Motohashi, Hayato; Suyama, Teruaki; Yamaguchi, Masahide

2018-06-01

As the first step to extend our understanding of higher-derivative theories, within the framework of analytic mechanics of point particles, we construct a ghost-free theory involving third-order time derivatives in Lagrangian. While eliminating linear momentum terms in the Hamiltonian is necessary and sufficient to kill the ghosts associated with higher derivatives for Lagrangian with at most second-order derivatives, we find that this is necessary but not sufficient for the Lagrangian with higher than second-order derivatives. We clarify a set of ghost-free conditions under which we show that the Hamiltonian is bounded, and that equations of motion are reducible into a second-order system.

Antihypertensive properties of lactoferricin B-derived peptides.

PubMed

Ruiz-Giménez, Pedro; Ibáñez, Aida; Salom, Juan B; Marcos, Jose F; López-Díez, Jose Javier; Vallés, Salvador; Torregrosa, Germán; Alborch, Enrique; Manzanares, Paloma

2010-06-09

A set of eight lactoferricin B (LfcinB)-derived peptides was examined for inhibitory effects on angiotensin I-converting enzyme (ACE) activity and ACE-dependent vasoconstriction, and their hypotensive effect in spontaneously hypertensive rats (SHR). Peptides were derived from different elongations both at the C-terminal and N-terminal ends of the representative peptide LfcinB(20-25), which is known as the LfcinB antimicrobial core. All of the eight LfcinB-derived peptides showed in vitro inhibitory effects on ACE activity with different IC(50) values. Moreover, seven of them showed ex vivo inhibitory effects on ACE-dependent vasoconstriction. No clear correlation between in vitro and ex vivo inhibitory effects was found. Only LfcinB(20-25) and one of its fragments, F1, generated after a simulated gastrointestinal digestion, showed significant antihypertensive effects in SHR after oral administration. Remarkably, F1 did not show any effect on ACE-dependent vasoconstriction in contrast to the inhibitory effect showed by LfcinB(20-25). In conclusion, two LfcinB-derived peptides lower blood pressure and exhibit potential as orally effective antihypertensive compounds, yet a complete elucidation of the mechanism(s) involved deserves further ongoing research.

Serum brain-derived neurotrophic factor and interleukin-6 response to high-volume mechanically demanding exercise.

PubMed

Verbickas, Vaidas; Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Baranauskiene, Neringa; Brazaitis, Marius; Satkunskiene, Danguole; Unikauskas, Alvydas; Skurvydas, Albertas

2018-01-01

The aim of this study was to follow circulating brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) levels in response to severe muscle-damaging exercise. Young healthy men (N = 10) performed a bout of mechanically demanding stretch-shortening cycle exercise consisting of 200 drop jumps. Voluntary and electrically induced knee extension torque, serum BDNF levels, and IL-6 levels were measured before and for up to 7 days after exercise. Muscle force decreased by up to 40% and did not recover by 24 hours after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise, whereas IL-6 increased immediately and 1 hour after but recovered to baseline by 24 hours after exercise. IL-6 and 100-Hz stimulation torque were correlated (r = -0.64, P < 0.05) 24 hours after exercise. In response to acute, severe muscle-damaging exercise, serum BDNF levels decrease, whereas IL-6 levels increase and are associated with peripheral fatigue. Muscle Nerve 57: E46-E51, 2018. © 2017 Wiley Periodicals, Inc.

Factors, fiction and endothelium-derived hyperpolarizing factor.

PubMed

Sandow, Shaun L

2004-09-01

1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium-dependent vasodilatory mechanism is characterized as the hyperpolarization-mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so-called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact-mediated mechanism. 2. Most evidence supports the concept that 'EDHF' activity is dependent on contact-mediated mechanisms. This involves the transfer of an endothelium-derived electrical current, as an endothelium-derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less-than-optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature. 4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the

[Antitumor effect research progress of shikonin and its derivatives].

PubMed

Zhu, Meng-Yuan; Wang, Ru-Bing; Zhou, Wen; Li, Shao-Shun

2012-05-01

Shikonin, the main active ingredient of Lithospermum, and its derivatives have been proved to have antitumor effects, and the anti-tumor mechanisms involve multiple targets. Based on recent literatures, this review focuses on the antitumor effects and its mechanisms. More emphases are given on the aspects of induction of apoptosis, induction of necrosis, acting on matrix metalloproteinase, acting on the protein tyrosine kinase and antiangiogenesis. The current status and problems of shikonin derivatives in antitumor effects are simply summarized and lookout for the development of antitumor drugs with shikonin as leading compounds.

Development of an accurate and high-throughput methodology for structural comprehension of chlorophylls derivatives. (II) Dephytylated derivatives.

PubMed

Chen, Kewei; Ríos, José Julián; Roca, María; Pérez-Gálvez, Antonio

2015-09-18

Dephytylated chlorophylls (chlorophyllides and pheophorbides) are the starting point of the chlorophyll catabolism in green tissues, components of the chlorophyll pattern in storage/processed food vegetables, as well as the favoured structural arrangement for chlorophyll absorption. In addition, dephytylated native chlorophylls are prone to several modifications of their structure yielding pyro-, 13(2)-hydroxy- and 15(1)-hydroxy-lactone derivatives. Despite of these outstanding remarks only few of them have been analysed by MS(n). Besides new protocols for obtaining standards, we have developed a new high throughput methodology able to determine the fragmentation pathway of 16 dephytylated chlorophyll derivatives, elucidating the structures of the new product ions and new mechanisms of fragmentation. The new methodology combines, by first time, high resolution time-of-flight mass spectrometry and powerful post-processing software. Native chlorophyllides and pheophorbides mainly exhibit product ions that involve the fragmentation of D ring, as well as additional exclusive product ions. The introduction of an oxygenated function at E ring enhances the progress of fragmentation reactions through the β-keto ester group, developing also exclusive product ions for 13(2)-hydroxy derivatives and for 15(1)-hydroxy-lactone ones. Consequently, while MS(2)-based reactions of phytylated chlorophyll derivatives point to fragmentations at the phytyl and propionic chains, dephytylated chlorophyll derivatives behave different as the absence of phytyl makes β-keto ester group and E ring more prone to fragmentation. Proposals of the key reaction mechanisms underlying the origin of new product ions have been made. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanisms of vasculogenesis in 3D fibrin matrices mediated by the interaction of adipose-derived stem cells and endothelial cells.

PubMed

Rohringer, Sabrina; Hofbauer, Pablo; Schneider, Karl H; Husa, Anna-Maria; Feichtinger, Georg; Peterbauer-Scherb, Anja; Redl, Heinz; Holnthoner, Wolfgang

2014-10-01

Vascularization of tissue-engineered constructs is essential to provide sufficient nutrient supply and hemostasis after implantation into target sites. Co-cultures of adipose-derived stem cells (ASC) with outgrowth endothelial cells (OEC) in fibrin gels were shown to provide an effective possibility to induce vasculogenesis in vitro. However, the mechanisms of the interaction between these two cell types remain unclear so far. The aim of this study was to evaluate differences of direct and indirect stimulation of ASC-induced vasculogenesis, the influence of ASC on network stabilization and molecular mechanisms involved in vascular structure formation. Endothelial cells (EC) were embedded in fibrin gels either containing non-coated or ASC-coated microcarrier beads as well as ASC alone. Moreover, EC-seeded constructs incubated with ASC-conditioned medium were used in addition to constructs with ASC seeded on top. Vascular network formation was visualized by green fluorescent protein expressing cells or immunostaining for CD31 and quantified. RT-qPCR of cells derived from co-cultures in fibrin was performed to evaluate changes in the expression of EC marker genes during the first week of culture. Moreover, angiogenesis-related protein levels were measured by performing angiogenesis proteome profiler arrays. The results demonstrate that proximity of endothelial cells and ASC is required for network formation and ASC stabilize EC networks by developing pericyte characteristics. We further showed that ASC induce controlled vessel growth by secreting pro-angiogenic and regulatory proteins. This study reveals angiogenic protein profiles involved in EC/ASC interactions in fibrin matrices and confirms the usability of OEC/ASC co-cultures for autologous vascular tissue engineering.

Marine-derived angiogenesis inhibitors for cancer therapy.

PubMed

Wang, Ying-Qing; Miao, Ze-Hong

2013-03-15

Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

PubMed

Shearer, Jason

2014-08-19

Nickel superoxide dismutase (NiSOD) is a nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide through a ping-pong mechanism that relies on accessing reduced Ni(II) and oxidized Ni(III) oxidation states. NiSOD is the most recently discovered SOD. Unlike the other known SODs (MnSOD, FeSOD, and (CuZn)SOD), which utilize "typical" biological nitrogen and oxygen donors, NiSOD utilizes a rather unexpected ligand set. In the reduced Ni(II) oxidation state, NiSOD utilizes nitrogen ligands derived from the N-terminal amine and an amidate along with two cysteinates sulfur donors. These are unusual biological ligands, especially for an SOD: amine and amidate donors are underrepresented as biological ligands, whereas cysteinates are highly susceptible to oxidative damage. An axial histidine imidazole binds to nickel upon oxidation to Ni(III). This bond is long (2.3-2.6 Å) owing to a tight hydrogen-bonding network. All of the ligating residues to Ni(II) and Ni(III) are found within the first 6 residues from the NiSOD N-terminus. Thus, small nickel-containing metallopeptides derived from the first 6-12 residues of the NiSOD sequence can reproduce many of the properties of NiSOD itself. Using these nickel-containing metallopeptide-based NiSOD mimics, we have shown that the minimal sequence needed for nickel binding and reproduction of the structural, spectroscopic, and functional properties of NiSOD is H2N-HCXXPC. Insight into how NiSOD avoids oxidative damage has also been gained. Using small NiN2S2 complexes and metallopeptide-based mimics, it was shown that the unusual nitrogen donor atoms protect the cysteinates from oxidative damage (both one-electron oxidation and oxygen atom insertion reactions) by fine-tuning the electronic structure of the nickel center. Changing the nitrogen donor set to a bis-amidate or bis-amine nitrogen donor led to catalytically nonviable species owing to nickel-cysteinate bond oxidative damage. Only the amine

Ferroelectricity in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

The search for new ferroelectric (FE) materials holds promise for broadening our understanding of FE mechanisms and extending the range of application of FE materials. The known FE materials LiNbO3 can be regarded as derived from the A2O3 corundum structure with cation ordering. Here we consider more general binary (AB O3) and ternary (A2 BB' O6) corundum derivatives as an extended class of potential FE materials, motivated by the fact that some members of this class have recently been synthesized. There are four structure types for these corundum derivatives, and the number of cation combinations is enormous, but in many cases the energy barriers for polarization reversal may be too large to allow FE behavior. Here we present a first-principles study of the polar structure, coherent FE barrier, and domain-wall switching barrier for a representative set of polar corundum derivatives, allowing us to identify several potentially new FE materials. We also discuss the conditions under which ferroelectricity is compatible with magnetic ordering. Finally, we identify several empirical measures that can provide a rule of thumb for estimating the barrier energies. Our results should assist in the experimental search for new FE materials in the corundum derivative family. This work is supported by ONR Grant No. N-00014-12-1-1035.

Exploring encapsulation mechanism of DNA and mononucleotides in sol-gel derived silica.

PubMed

Kapusuz, Derya; Durucan, Caner

2017-07-01

The encapsulation mechanism of DNA in sol-gel derived silica has been explored in order to elucidate the effect of DNA conformation on encapsulation and to identify the nature of chemical/physical interaction of DNA with silica during and after sol-gel transition. In this respect, double stranded DNA and dAMP (2'-deoxyadenosine 5'-monophosphate) were encapsulated in silica using an alkoxide-based sol-gel route. Biomolecule-encapsulating gels have been characterized using UV-Vis, 29 Si NMR, FTIR spectroscopy and gas adsorption (BET) to investigate chemical interactions of biomolecules with the porous silica network and to examine the extent of sol-gel reactions upon encapsulation. Ethidium bromide intercalation and leach out tests showed that helix conformation of DNA was preserved after encapsulation. For both biomolecules, high water-to-alkoxide ratio promoted water-producing condensation and prevented alcoholic denaturation. NMR and FTIR analyses confirmed high hydraulic reactivity (water adsorption) for more silanol groups-containing DNA and dAMP encapsulated gels than plain silica gel. No chemical binding/interaction occurred between biomolecules and silica network. DNA and dAMP encapsulated silica gelled faster than plain silica due to basic nature of DNA or dAMP containing buffer solutions. DNA was not released from silica gels to aqueous environment up to 9 days. The chemical association between DNA/dAMP and silica host was through phosphate groups and molecular water attached to silanols, acting as a barrier around biomolecules. The helix morphology was found not to be essential for such interaction. BET analyses showed that interconnected, inkbottle-shaped mesoporous silica network was condensed around DNA and dAMP molecules.

Induction of anaplastic lymphoma kinase (ALK) as a novel mechanism of EGFR inhibitor resistance in head and neck squamous cell carcinoma patient-derived models.

PubMed

Ouyang, Xiaoming; Barling, Ashley; Lesch, Aletha; Tyner, Jeffrey W; Choonoo, Gabrielle; Zheng, Christina; Jeng, Sophia; West, Toni M; Clayburgh, Daniel; Courtneidge, Sara A; McWeeney, Shannon K; Kulesz-Martin, Molly

2018-06-01

Head and neck squamous cell carcinoma (HNSCC) currently only has one FDA-approved cancer intrinsic targeted therapy, the epidermal growth factor receptor (EGFR) inhibitor cetuximab, to which only approximately 10% of tumors are sensitive. In order to extend therapy options, we subjected patient-derived HNSCC cells to small-molecule inhibitor and siRNA screens, first, to find effective combination therapies with an EGFR inhibitor, and second, to determine a potential mechanistic basis for repurposing the FDA approved agents for HNSCC. The combinations of EGFR inhibitor with anaplastic lymphoma kinase (ALK) inhibitors demonstrated synergy at the highest ratio in our cohort, 4/8 HNSCC patients' derived tumor cells, and this corresponded with an effectiveness of siRNA targeting ALK combined with the EGFR inhibitor gefitinib. Co-targeting EGFR and ALK decreased HNSCC cell number and colony formation ability and increased annexin V staining. Because ALK expression is low and ALK fusions are infrequent in HNSCC, we hypothesized that gefitinib treatment could induce ALK expression. We show that ALK expression was induced in HNSCC patient-derived cells both in 2D and 3D patient-derived cell culture models, and in patient-derived xenografts in mice. Four different ALK inhibitors, including two (ceritinib and brigatinib) FDA approved for lung cancer, were effective in combination with gefitinib. Together, we identified induction of ALK by EGFR inhibitor as a novel mechanism potentially relevant to resistance to EGFR inhibitor, a high ratio of response of HNSCC patient-derived tumor cells to a combination of ALK and EGFR inhibitors, and applicability of repurposing ALK inhibitors to HNSCC that lack ALK aberrations.

Respiratory mechanics in mechanically ventilated patients.

PubMed

Hess, Dean R

2014-11-01

Respiratory mechanics refers to the expression of lung function through measures of pressure and flow. From these measurements, a variety of derived indices can be determined, such as volume, compliance, resistance, and work of breathing. Plateau pressure is a measure of end-inspiratory distending pressure. It has become increasingly appreciated that end-inspiratory transpulmonary pressure (stress) might be a better indicator of the potential for lung injury than plateau pressure alone. This has resulted in a resurgence of interest in the use of esophageal manometry in mechanically ventilated patients. End-expiratory transpulmonary pressure might also be useful to guide the setting of PEEP to counterbalance the collapsing effects of the chest wall. The shape of the pressure-time curve might also be useful to guide the setting of PEEP (stress index). This has focused interest in the roles of stress and strain to assess the potential for lung injury during mechanical ventilation. This paper covers both basic and advanced respiratory mechanics during mechanical ventilation. Copyright © 2014 by Daedalus Enterprises.

Development of an accurate and high-throughput methodology for structural comprehension of chlorophylls derivatives. (I) Phytylated derivatives.

PubMed

Chen, Kewei; Ríos, José Julián; Pérez-Gálvez, Antonio; Roca, María

2015-08-07

Phytylated chlorophyll derivatives undergo specific oxidative reactions through the natural metabolism or during food processing or storage, and consequently pyro-, 13(2)-hydroxy-, 15(1)-hydroxy-lactone chlorophylls, and pheophytins (a and b) are originated. New analytical procedures have been developed here to reproduce controlled oxidation reactions that specifically, and in reasonable amounts, produce those natural target standards. At the same time and under the same conditions, 16 natural chlorophyll derivatives have been analyzed by APCI-HPLC-hrMS(2) and most of them by the first time. The combination of the high-resolution MS mode with powerful post-processing software has allowed the identification of new fragmentation patterns, characterizing specific product ions for some particular standards. In addition, new hypotheses and reaction mechanisms for the established MS(2)-based reactions have been proposed. As a general rule, the main product ions involve the phytyl and the propionic chains but the introduction of oxygenated functional groups at the isocyclic ring produces new and specific productions and at the same time inhibits some particular fragmentations. It is noteworthy that all b derivatives, except 15(1)-hydroxy-lactone compounds, undergo specific CO losses. We propose a new reaction mechanism based in the structural configuration of a and b chlorophyll derivatives that explain the exclusive CO fragmentation in all b series except for 15(1)-hydroxy-lactone b and all a series compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor.

PubMed

Beckman, Sarah A; Chen, William C W; Tang, Ying; Proto, Jonathan D; Mlakar, Logan; Wang, Bing; Huard, Johnny

2013-08-01

We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA_VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZ-MDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA _VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF.

Beneficial Effect of Mechanical Stimulation on the Regenerative Potential of Muscle-Derived Stem Cells Is Lost by Inhibiting Vascular Endothelial Growth Factor

PubMed Central

Beckman, Sarah A.; Chen, William C.W.; Tang, Ying; Proto, Jonathan D.; Mlakar, Logan; Wang, Bing; Huard, Johnny

2016-01-01

Objective We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. Approach and Results MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA_VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZMDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA _VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. Conclusions The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF. PMID:23723372

Cosmological implications of quantum corrections and higher-derivative extension

NASA Astrophysics Data System (ADS)

Chialva, Diego; Mazumdar, Anupam

2015-02-01

We discuss the challenges for the early universe cosmology from quantum corrections, and in particular higher-derivative terms, in the gravitational and inflaton sectors of the models. The work is divided in two parts. In the first one we review the already well-known issues due to quantum corrections to the inflaton potential, in particular focusing on chaotic/slow-roll single-field models. We will point out some issues concerning the proposed mechanisms to cope with the corrections, and also argue how the presence of higher-derivative corrections could be problematic for those mechanisms. In the second part we will more directly focus on higher-derivative corrections. We will show how, in order to discuss a number of high-energy phenomena relevant to inflation (such as its actual onset) one has to deal with energy scales where the derivative expansion breaks down, presenting problems such as quantum vacuum instability and ghosts. To discuss such phenomena in the convenient framework of the effective theory, one must then abandon the derivative expansion and resort to the full nonlocal formulation of the theory, which is in fact equivalent to re-integrating back the relevant physics, but with the benefit of using a more compact single-field formalism. Finally, we will briefly discuss possible advantages offered by the presence of higher derivatives and a nonlocal theory to build better controlled UV models of inflation.

Theoretical Fluid Mechanics

NASA Astrophysics Data System (ADS)

Fitzpatrick, Richard

2017-12-01

'Theoretical Fluid Mechanics' has been written to aid physics students who wish to pursue a course of self-study in fluid mechanics. It is a comprehensive, completely self-contained text with equations of fluid mechanics derived from first principles, and any required advanced mathematics is either fully explained in the text, or in an appendix. It is accompanied by about 180 exercises with completely worked out solutions. It also includes extensive sections on the application of fluid mechanics to topics of importance in astrophysics and geophysics. These topics include the equilibrium of rotating, self-gravitating, fluid masses; tidal bores; terrestrial ocean tides; and the Eddington solar model.

Ferroelectricity in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

2016-04-01

The search for new ferroelectric (FE) materials holds promise for broadening our understanding of FE mechanisms and extending the range of application of FE materials. Here we investigate a class of A B O3 and A2B B'O6 materials that can be derived from the X2O3 corundum structure by mixing two or three ordered cations on the X site. Most such corundum derivatives have a polar structure, but it is unclear whether the polarization is reversible, which is a requirement for a FE material. In this paper, we propose a method to study the FE reversal path of materials in the corundum derivative family. We first categorize the corundum derivatives into four classes and show that only two of these allow for the possibility of FE reversal. We then calculate the energy profile and energy barrier of the FE reversal path using first-principles density functional methods with a structural constraint. Furthermore, we identify several empirical measures that can provide a rule of thumb for estimating the energy barriers. Finally, the conditions under which the magnetic ordering is compatible with ferroelectricity are determined. These results lead us to predict several potentially new FE materials.

Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars

PubMed Central

Qian, Linbo; Chen, Baoliang; Chen, Mengfang

2016-01-01

Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil. PMID:27385598

Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars

NASA Astrophysics Data System (ADS)

Qian, Linbo; Chen, Baoliang; Chen, Mengfang

2016-07-01

Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil.

Mechanical properties in crumple-formed paper derived materials subjected to compression.

PubMed

Hanaor, D A H; Flores Johnson, E A; Wang, S; Quach, S; Dela-Torre, K N; Gan, Y; Shen, L

2017-06-01

The crumpling of precursor materials to form dense three dimensional geometries offers an attractive route towards the utilisation of minor-value waste materials. Crumple-forming results in a mesostructured system in which mechanical properties of the material are governed by complex cross-scale deformation mechanisms. Here we investigate the physical and mechanical properties of dense compacted structures fabricated by the confined uniaxial compression of a cellulose tissue to yield crumpled mesostructuring. A total of 25 specimens of various densities were tested under compression. Crumple formed specimens exhibited densities in the range 0.8-1.3 g cm -3 , and showed high strength to weight characteristics, achieving ultimate compressive strength values of up to 200 MPa under both quasi-static and high strain rate loading conditions and deformation energy that compares well to engineering materials of similar density. The materials fabricated in this work and their mechanical attributes demonstrate the potential of crumple-forming approaches in the fabrication of novel energy-absorbing materials from low-cost precursors such as recycled paper. Stiffness and toughness of the materials exhibit density dependence suggesting this forming technique further allows controllable impact energy dissipation rates in dynamic applications.

The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives in human gastric cancer cells.

PubMed

Pawłowska, Natalia; Gornowicz, Agnieszka; Bielawska, Anna; Surażyński, Arkadiusz; Szymanowska, Anna; Czarnomysy, Robert; Bielawski, Krzysztof

2018-03-17

Objective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analysis and apoptosis assay were performed by standard flow cytometric method. Confocal microscopy bioimaging was used to demonstrate the expression of pivotal proteins engaged in apoptosis (caspase-8, caspase-3, p53) and cell signaling (AKT, ERK1/2). Results All compounds decreased the number of viable cells in a dose-dependent manner after 24 and 48 h of incubation, although compound 2 was a more cytotoxic agent, with IC 50 values of 21 ± 2 and 6 ± 2 μM, compared to 80 ± 2 and 45 ± 2 μM for etoposide. The cytotoxic and antiproliferative effects of novel compounds were associated with the induction of apoptosis. The highest percentage of early and late apoptotic cells was observed after 48 h of incubation with compound 2 (89.9%). The value was higher compared to compound 1 (20.4%) and etoposide (24.1%). The novel diisoquinoline derivatives decreased the expression of AKT and ERK1/2. Their mechanism was associated with p53-mediated apoptosis, accumulation of cells in the G2/M phase of cell cycle and inhibition of topoisomerase II. Conclusion These data strongly support compound 2 as a promising molecule for treatment of gastric cancer.

A nonlinear high temperature fracture mechanics basis for strainrange partitioning

NASA Technical Reports Server (NTRS)

Kitamura, Takayuki; Halford, Gary R.

1989-01-01

A direct link was established between Strainrange Partitioning (SRP) and high temperature fracture mechanics by deriving the general SRP inelastic strain range versus cyclic life relationships from high temperature, nonlinear, fracture mechanics considerations. The derived SRP life relationships are in reasonable agreement based on the experience of the SRP behavior of many high temperature alloys. In addition, fracture mechanics has served as a basis for derivation of the Ductility-Normalized SRP life equations, as well as for examination of SRP relations that are applicable to thermal fatigue life prediction. Areas of additional links between nonlinear fracture mechanics and SRP were identified for future exploration. These include effects of multiaxiality as well as low strain, nominally elastic, long life creep fatigue interaction.

Why were Matrix Mechanics and Wave Mechanics considered equivalent?

NASA Astrophysics Data System (ADS)

Perovic, Slobodan

A recent rethinking of the early history of Quantum Mechanics deemed the late 1920s agreement on the equivalence of Matrix Mechanics and Wave Mechanics, prompted by Schrödinger's 1926 proof, a myth. Schrödinger supposedly failed to prove isomorphism, or even a weaker equivalence ("Schrödinger-equivalence") of the mathematical structures of the two theories; developments in the early 1930s, especially the work of mathematician von Neumann provided sound proof of mathematical equivalence. The alleged agreement about the Copenhagen Interpretation, predicated to a large extent on this equivalence, was deemed a myth as well. In response, I argue that Schrödinger's proof concerned primarily a domain-specific ontological equivalence, rather than the isomorphism or a weaker mathematical equivalence. It stemmed initially from the agreement of the eigenvalues of Wave Mechanics and energy-states of Bohr's Model that was discovered and published by Schrödinger in his first and second communications of 1926. Schrödinger demonstrated in this proof that the laws of motion arrived at by the method of Matrix Mechanics are satisfied by assigning the auxiliary role to eigenfunctions in the derivation of matrices (while he only outlined the reversed derivation of eigenfunctions from Matrix Mechanics, which was necessary for the proof of both isomorphism and Schrödinger-equivalence of the two theories). This result was intended to demonstrate the domain-specific ontological equivalence of Matrix Mechanics and Wave Mechanics, with respect to the domain of Bohr's atom. And although the mathematical equivalence of the theories did not seem out of the reach of existing theories and methods, Schrödinger never intended to fully explore such a possibility in his proof paper. In a further development of Quantum Mechanics, Bohr's complementarity and Copenhagen Interpretation captured a more substantial convergence of the subsequently revised (in light of the experimental results) Wave

Gauge fixing in higher-derivative gravity

NASA Astrophysics Data System (ADS)

Bartoli, A.; Julve, J.; Sánchez, E. J.

1999-07-01

Linearized 4-derivative gravity with a general gauge-fixing term is considered. By a Legendre transform and a suitable diagonalization procedure it is cast into a second-order equivalent form where the nature of the physical degrees of freedom, the gauge ghosts, the Weyl ghosts and the intriguing `third ghosts', characteristic to higher-derivative theories, is made explicit. The symmetries of the theory and the structure of the compensating Faddeev-Popov ghost sector exhibit non-trivial peculiarities. The unitarity breaking negative-norm Weyl ghosts, already present in the diff-invariant theory, are out of the reach of the ghost cancellation BRST mechanism.

Testing Nonassociative Quantum Mechanics.

PubMed

Bojowald, Martin; Brahma, Suddhasattwa; Büyükçam, Umut

2015-11-27

The familiar concepts of state vectors and operators in quantum mechanics rely on associative products of observables. However, these notions do not apply to some exotic systems such as magnetic monopoles, which have long been known to lead to nonassociative algebras. Their quantum physics has remained obscure. This Letter presents the first derivation of potentially testable physical results in nonassociative quantum mechanics, based on effective potentials. They imply new effects which cannot be mimicked in usual quantum mechanics with standard magnetic fields.

On the role of second number-conserving functional derivatives

NASA Astrophysics Data System (ADS)

Gál, Tamás

2006-06-01

It is found that number-conserving second derivatives, of functional differentiation constrained to the domain of functional variables ρ(x) of a given norm ∫ρ(x)dx, are not obtained via two successive number-conserving differentiations, contrary to the case of unrestricted second derivatives. Investigating the role of second number-conserving derivatives, with the density-functional formulation of time-dependent quantum mechanics in focus, it is shown how number-conserving differentiation handles the dual nature of the Kohn Sham potential arising in the practical use of the theory. On the other hand, it is pointed out that number-conserving derivatives cannot resolve the causality paradox connected with the second derivative of the exchange-correlation part of the action density functional.

Antitumor Effects and Mechanism of Novel Emodin Rhamnoside Derivatives against Human Cancer Cells In Vitro

PubMed Central

Deng, Jun-peng; Jiang, Ling-zhi; Xiong, Ping; Yang, Bin-jie; Liu, Shan-shan

2015-01-01

A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized and their anti-proliferative activities on cancer cell lines were investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited cell proliferation of a panel of different human cancer cell lines including A549, HepG2, OVCAR-3, HeLa and K562 and SGC-790 cell lines, and displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we found EM-d-Rha (3-(2”,3”-Di-O-acetyl-α-L-rhamnopyranosyl-(1→4)-2’,3’-di-O-acetyl-α-L-rhamnopyranosyl)-emodin) substantially induced cellular apoptosis of HepG2 and OVCAR-3 cells in the early growth stage. Furthermore, EM-d-Rha led to the decrease of mitochondrial transmembrane potential, and up-regulated the express of cells apoptosis factors in a concentration- and time-dependent manner. The results indicated the EM-d-Rha may inhibit the growth and proliferation of HepG2 cells through the pathway of apoptosis induction, and the possible molecular mechanism may due to the activation of intrinsic apoptotic signal pathway. PMID:26682731

Profiling the interaction mechanism of quinoline/quinazoline derivatives as MCHR1 antagonists: an in silico method.

PubMed

Wu, Mingwei; Li, Yan; Fu, Xinmei; Wang, Jinghui; Zhang, Shuwei; Yang, Ling

2014-09-01

Melanin concentrating hormone receptor 1 (MCHR1), a crucial regulator of energy homeostasis involved in the control of feeding and energy metabolism, is a promising target for treatment of obesity. In the present work, the up-to-date largest set of 181 quinoline/quinazoline derivatives as MCHR1 antagonists was subjected to both ligand- and receptor-based three-dimensional quantitative structure-activity (3D-QSAR) analysis applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The optimal predictable CoMSIA model exhibited significant validity with the cross-validated correlation coefficient (Q²) = 0.509, non-cross-validated correlation coefficient (R²(ncv)) = 0.841 and the predicted correlation coefficient (R²(pred)) = 0.745. In addition, docking studies and molecular dynamics (MD) simulations were carried out for further elucidation of the binding modes of MCHR1 antagonists. MD simulations in both water and lipid bilayer systems were performed. We hope that the obtained models and information may help to provide an insight into the interaction mechanism of MCHR1 antagonists and facilitate the design and optimization of novel antagonists as anti-obesity agents.

Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse.

PubMed

Kufaishi, Hala; Alarab, May; Drutz, Harold; Lye, Stephen; Shynlova, Oksana

2016-08-01

Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer-controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage ≥3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch-conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro

Transition from the mechanics of material points to the mechanics of structured particles

NASA Astrophysics Data System (ADS)

Somsikov, V. M.

2016-01-01

In this paper, necessity of creation of mechanics of structured particles is discussed. The way to create this mechanics within the laws of classical mechanics with the use of energy equation is shown. The occurrence of breaking of time symmetry within the mechanics of structured particles is shown, as well as the introduction of concept of entropy in the framework of classical mechanics. The way to create the mechanics of non-equilibrium systems in the thermodynamic approach is shown. It is also shown that the use of hypothesis of holonomic constraints while deriving the canonical Lagrange equation made it impossible to describe irreversible dynamics. The difference between the mechanics of structured particles and the mechanics of material points is discussed. It is also shown that the matter is infinitely divisible according to the laws of classical mechanics.

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

PubMed

Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Mechanism of Hyperphagia Contributing to Obesity in Brain-Derived Neurotrophic Factor Knockout Mice

PubMed Central

Fox, Edward A.; Biddinger, Jessica E.; Jones, Kevin R.; McAdams, Jennifer; Worman, Amber

2012-01-01

Global-heterozygous and brain-specific homozygous knockouts (KO's) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from gut-to-brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal vagal motor nucleus (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. PMID:23069761

Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice.

PubMed

Fox, E A; Biddinger, J E; Jones, K R; McAdams, J; Worman, A

2013-01-15

Global-heterozygous and brain-specific homozygous knockouts (KOs) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from the gut to the brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus nerve (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Active site formation mechanism of carbon-based oxygen reduction catalysts derived from a hyperbranched iron phthalocyanine polymer.

PubMed

Hiraike, Yusuke; Saito, Makoto; Niwa, Hideharu; Kobayashi, Masaki; Harada, Yoshihisa; Oshima, Masaharu; Kim, Jaehong; Nabae, Yuta; Kakimoto, Masa-Aki

2015-01-01

Carbon-based cathode catalysts derived from a hyperbranched iron phthalocyanine polymer (HB-FePc) were characterized, and their active-site formation mechanism was studied by synchrotron-based spectroscopy. The properties of the HB-FePc catalyst are compared with those of a catalyst with high oxygen reduction reaction (ORR) activity synthesized from a mixture of iron phthalocyanine and phenolic resin (FePc/PhRs). Electrochemical measurements demonstrate that the HB-FePc catalyst does not lose its ORR activity up to 900°C, whereas that of the FePc/PhRs catalyst decreases above 700°C. Hard X-ray photoemission spectra reveal that the HB-FePc catalysts retain more nitrogen components than the FePc/PhRs catalysts between pyrolysis temperatures of 600°C and 800°C. This is because the linked structure of the HB-FePc precursor has high thermostability against nitrogen desorption. Consequently, effective doping of active nitrogen species into the sp (2) carbon network of the HB-FePc catalysts may occur up to 900°C.

A new strategy for earthquake focal mechanisms using waveform-correlation-derived relative polarities and cluster analysis: Application to the 2014 Long Valley Caldera earthquake swarm

USGS Publications Warehouse

Shelly, David R.; Hardebeck, Jeanne L.; Ellsworth, William L.; Hill, David P.

2016-01-01

In microseismicity analyses, reliable focal mechanisms can typically be obtained for only a small subset of located events. We address this limitation here, presenting a framework for determining robust focal mechanisms for entire populations of very small events. To achieve this, we resolve relative P and S wave polarities between pairs of waveforms by using their signed correlation coefficients—a by-product of previously performed precise earthquake relocation. We then use cluster analysis to group events with similar patterns of polarities across the network. Finally, we apply a standard mechanism inversion to the grouped data, using either catalog or correlation-derived P wave polarity data sets. This approach has great potential for enhancing analyses of spatially concentrated microseismicity such as earthquake swarms, mainshock-aftershock sequences, and industrial reservoir stimulation or injection-induced seismic sequences. To demonstrate its utility, we apply this technique to the 2014 Long Valley Caldera earthquake swarm. In our analysis, 85% of the events (7212 out of 8494 located by Shelly et al. [2016]) fall within five well-constrained mechanism clusters, more than 12 times the number with network-determined mechanisms. Of the earthquakes we characterize, 3023 (42%) have magnitudes smaller than 0.0. We find that mechanism variations are strongly associated with corresponding hypocentral structure, yet mechanism heterogeneity also occurs where it cannot be resolved by hypocentral patterns, often confined to small-magnitude events. Small (5–20°) rotations between mechanism orientations and earthquake location trends persist when we apply 3-D velocity models and might reflect a geometry of en echelon, interlinked shear, and dilational faulting.

Soil mechanics

NASA Technical Reports Server (NTRS)

Mitchell, J. K.; Carrier, W. D., III; Houston, W. N.; Scott, R. F.; Bromwell, L. G.; Durgunoglu, H. T.; Hovland, H. J.; Treadwell, D. D.; Costes, N. C.

1972-01-01

Preliminary results are presented of an investigation of the physical and mechanical properties of lunar soil on the Descartes slopes, and the Cayley Plains in the vicinity of the LM for Apollo 16. The soil mechanics data were derived form (1) crew commentary and debriefings, (2) television, (3) lunar surface photography, (4) performance data and observations of interactions between soil and lunar roving vehicle, (5) drive-tube and deep drill samples, (6) sample characteristics, and (7) measurements using the SRP. The general characteristics, stratigraphy and variability are described along with the core samples, penetrometer test results, density, porosity and strength.

On some new properties of fractional derivatives with Mittag-Leffler kernel

NASA Astrophysics Data System (ADS)

Baleanu, Dumitru; Fernandez, Arran

2018-06-01

We establish a new formula for the fractional derivative with Mittag-Leffler kernel, in the form of a series of Riemann-Liouville fractional integrals, which brings out more clearly the non-locality of fractional derivatives and is easier to handle for certain computational purposes. We also prove existence and uniqueness results for certain families of linear and nonlinear fractional ODEs defined using this fractional derivative. We consider the possibility of a semigroup property for these derivatives, and establish extensions of the product rule and chain rule, with an application to fractional mechanics.

Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

PubMed

Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

2017-05-01

To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O 2 - ) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF 2 α receptor antagonist) or SQ29584 [PGH 2 /thromboxane TXA 2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O 2 - and hydrogen peroxide (H 2 O 2 ) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

3D surface flow kinematics derived from airborne UAVSAR interferometric synthetic aperture radar to constrain the physical mechanisms controlling landslide motion

NASA Astrophysics Data System (ADS)

Delbridge, B. G.; Burgmann, R.; Fielding, E. J.; Hensley, S.; Schulz, W. H.

2013-12-01

This project focuses on improving our understanding of the physical mechanisms controlling landslide motion by studying the landslide-wide kinematics of the Slumgullion landslide in southwestern Colorado using interferometric synthetic aperture radar (InSAR) and GPS. The NASA/JPL UAVSAR airborne repeat-pass SAR interferometry system imaged the Slumgullion landslide from 4 look directions on eight flights in 2011 and 2012. Combining the four look directions allows us to extract the full 3-D velocity field of the surface. Observing the full 3-dimensional flow field allows us to extract the full strain tensor (assuming free surface boundary conditions and incompressible flow) since we have both the spatial resolution to take spatial derivates and full deformation information. COSMO-SkyMed(CSK) high-resolution Spotlight data was also acquired during time intervals overlapping with the UAVSAR one-week pairs, with intervals as short as one day. These observations allow for the quantitative testing of the deformation magnitude and estimated formal errors in the UAVSAR derived deformation field. We also test the agreement of the deformation at 20 GPS monitoring sites concurrently acquired by the USGS. We also utilize the temporal resolution of real-time GPS acquired by the UC Berkeley Active Tectonics Group during a temporary deployment from July 22nd - August 2nd. By combining this data with the kinematic data we hope to elucidate the response of the landslide to environmental changes such as rainfall, snowmelt, and atmospheric pressure, and consequently the mechanisms controlling the dynamics of the landslide system. To constrain the longer temporal dynamics, interferograms made from pairs of CSK images acquired in 2010, 2011, 2012 and 2013 reveal the slide deformation on a longer timescale by allowing us to measure meters of motion and see the average rates over year long intervals using pixel offset tracking of the high-resolution SAR amplitude images. The results of

Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species.

PubMed

He, Ping; Wang, Weisi; Sanogo, Benjamin; Zeng, Xin; Sun, Xi; Lv, Zhiyue; Yuan, Dongjuan; Duan, Liping; Wu, Zhongdao

2017-08-10

Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms. In this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy. 5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in

Carpatizine, a novel bridged oxazine derivative generated by non-enzymatic reactions.

PubMed

Fu, Peng; MacMillan, John B

2017-06-27

Carpatizine (1), a new bridged oxazine derivative, was isolated from a marine-derived Streptomyces strain SNE-011. The structure was fully determined by spectroscopic analysis, ECD calculations and chemical methods. A plausible non-enzymatic reaction mechanism from daryamide D leading to carpatizine was presented, which was confirmed by chemical transformation.

Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase.

PubMed

Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung-Yum; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf

2015-09-01

The purpose of the present study was to discover the extent of contribution to antityrosinase activity by adding hydroxy substituted benzoic acid, cinnamic acid and piperazine residues to vanillin. The study showed the transformation of vanillin into esters as shown in (4a-4d), (6a-6b), and (8a-8b). In addition, the relationship between structures of these esters and their mushroom tyrosinase inhibitory activity was explored. The kinetics of inhibition on mushroom tyrosinase by these esters was also investigated. It was found that hydroxyl substituted benzoic acid derivatives were weak inhibitors; however hydroxy or chloro substituted cinnamic acid and piperazine substituted derivatives were able to induce significant tyrosinase inhibition. The mushroom tyrosinase (PDBID 2ZWE) was docked with synthesized vanillin derivatives and their calculated binding energies were compared with experimental IC50 values which provided positive correlation. The most potent derivative 2-(4-formyl-2-methoxyphenoxy)-2-oxoethyl (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6a) possesses hydroxy substituted cinnamic acid scaffold having IC50 value 16.13 μM with binding energy of -7.2 kcal/mol. The tyrosinase inhibitory activity of (6a) is comparable with standard kojic acid. Kinetic analysis indicated that compound 6a was mixed-type tyrosinase inhibitor with inhibition constant values Ki (13 μM) and Ki' (53 μM) and formed reversible enzyme inhibitor complex. The active vanillin analog (6a) was devoid of toxic effects as shown in cytotoxic studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Basic mechanics of laminated composite plates

NASA Technical Reports Server (NTRS)

Nettles, Alan T.

1994-01-01

The mechanics of laminated composite materials is presented in a clear manner with only essential derivations included. The constitutive equations in all of their forms are developed and then summarized in a separate section. The effects of hygrothermal effects are included. The prediction of the engineering constants for a laminate are derived. Strength of laminated composites is not covered.

Solvent effects on the absorption spectrum and first hyperpolarizability of keto-enol tautomeric forms of anil derivatives: A Monte Carlo/quantum mechanics study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adriano Junior, L.; Fonseca, T. L.; Castro, M. A.

2016-06-21

Theoretical results for the absorption spectrum and electric properties of the enol and keto tautomeric forms of anil derivatives in the gas-phase and in solution are presented. The electronic properties in chloroform, acetonitrile, methanol, and water were determined by carrying out sequential Monte Carlo simulations and quantum mechanics calculations based on the time dependent density functional theory and on the second-order Møller–Plesset perturbation theory method. The results illustrate the role played by electrostatic interactions in the electronic properties of anil derivatives in a liquid environment. There is a significant increase of the dipole moment in solution (20%-100%) relative to themore » gas-phase value. Solvent effects are mild for the absorption spectrum and linear polarizability but they can be particularly important for first hyperpolarizability. A large first hyperpolarizability contrast between the enol and keto forms is observed when absorption spectra present intense lowest-energy absorption bands. Dynamic results for the first hyperpolarizability are in qualitative agreement with the available experimental results.« less

The Effect of Mineral Powders Derived From Industrial Wastes on Selected Mechanical Properties of Concrete

NASA Astrophysics Data System (ADS)

Galińska, Anna; Czarnecki, Sławomir

2017-10-01

In recent years, concrete has been the most popular construction material. The main component of the concrete is cement. However, its production and transport causes significant emissions of CO2. Reports in the literature show that many laboratories are attempting to modify the composition of the concrete using various additives. These attempts are primarily designed to eliminate parts of cement. The greater part of the cement will be replaced with the selected additive, the more significant is the economic and ecological effect. Most attempts are related to the replacement of the selected additive in an amount of from 10 to 30% by weight of cement. Mineral powders, which are waste material producing crushed aggregate, are increasingly used for this purpose. Management of the waste carries significant cost related to their storage and disposal. With this in mind, the aim of this study was to evaluate the effect of mineral powders derived from industrial wastes on selected mechanical properties of concrete. In particular, the aim was to determine the effect of quartz and quartz-feldspar powders. For this purpose, 40, 50, 60% by weight of the cement was replaced by the selected powders. The results obtained were analysed and compared with previous attempts to replace the selected additive in an amount of from 10 to 30% by weight of cement.

Derivation of the Second Law of Thermodynamics from Boltzmann's Distribution Law.

ERIC Educational Resources Information Center

Nelson, P. G.

1988-01-01

Shows how the thermodynamic condition for equilibrium in an isolated system can be derived by the application of Boltzmann's law to a simple physical system. States that this derivation could be included in an introductory course on chemical equilibrium to help prepare students for a statistical mechanical treatment presented in the curriculum.…

Kinks in higher derivative scalar field theory

NASA Astrophysics Data System (ADS)

Zhong, Yuan; Guo, Rong-Zhen; Fu, Chun-E.; Liu, Yu-Xiao

2018-07-01

We study static kink configurations in a type of two-dimensional higher derivative scalar field theory whose Lagrangian contains second-order derivative terms of the field. The linear fluctuation around arbitrary static kink solutions is analyzed. We find that, the linear spectrum can be described by a supersymmetric quantum mechanics problem, and the criteria for stable static solutions can be given analytically. We also construct a superpotential formalism for finding analytical static kink solutions. Using this formalism we first reproduce some existed solutions and then offer a new solution. The properties of our solution is studied and compared with those preexisted. We also show the possibility in constructing twinlike model in the higher derivative theory, and give the consistency conditions for twinlike models corresponding to the canonical scalar field theory.

Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation.

PubMed

Gomez-Pinilla, F; Zhuang, Y; Feng, J; Ying, Z; Fan, G

2011-02-01

We have evaluated the possibility that the action of voluntary exercise on the regulation of brain-derived neurotrophic factor (BDNF), a molecule important for rat hippocampal learning, could involve mechanisms of epigenetic regulation. We focused the studies on the Bdnf promoter IV, as this region is highly responsive to neuronal activity. We have found that exercise stimulates DNA demethylation in Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2, as well as BDNF mRNA and protein in the rat hippocampus. Chromatin immunoprecipitation assay showed that exercise increases acetylation of histone H3, and protein assessment showed that exercise elevates the ratio of acetylated :total for histone H3 but had no effects on histone H4 levels. Exercise also reduces levels of the histone deacetylase 5 mRNA and protein implicated in the regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci., 9, 519-525], but did not affect histone deacetylase 9. Exercise elevated the phosphorylated forms of calcium/calmodulin-dependent protein kinase II and cAMP response element binding protein, implicated in the pathways by which neural activity influences the epigenetic regulation of gene transcription, i.e. Bdnf. These results showing the influence of exercise on the remodeling of chromatin containing the Bdnf gene emphasize the importance of exercise on the control of gene transcription in the context of brain function and plasticity. Reported information about the impact of a behavior, inherently involved in the daily human routine, on the epigenome opens exciting new directions and therapeutic opportunities in the war against neurological and psychiatric disorders. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

5S rRNA-derived and tRNA-derived SINEs in fruit bats.

PubMed

Gogolevsky, Konstantin P; Vassetzky, Nikita S; Kramerov, Dmitri A

2009-05-01

Most short retroposons (SINEs) descend from cellular tRNA of 7SL RNA. Here, four new SINEs were found in megabats (Megachiroptera) but neither in microbats nor in other mammals. Two of them, MEG-RS and MEG-RL, descend from another cellular RNA, 5S rRNA; one (MEG-T2) is a tRNA-derived SINE; and MEG-TR is a hybrid tRNA/5S rRNA SINE. Insertion locus analysis suggests that these SINEs were active in the recent fruit bat evolution. Analysis of MEG-RS and MEG-RL in comparison with other few 5S rRNA-derived SINEs demonstrates that the internal RNA polymerase III promoter is their most invariant region, while the secondary structure is more variable. The mechanisms underlying the modular structure of these and other SINEs as well as their variation are discussed. The scenario of evolution of MEG SINEs is proposed.

Preparation Methods and Antioxidant Activities of Polysaccharides and Their Derivatives.

PubMed

Mei, Xinya; Yi, Chengkun; Huang, Gangliang

2017-01-01

In recent years, the antioxidant effects of polysaccharides have become a hot spot in the field of polysaccharide research. Herein, the action mechanisms of polysaccharide antioxidation and scavenging free radicals were analyzed. The research progresses on the preparation methods and antioxidant properties of polysaccharides and their derivatives were summarized. Investigating the antioxidant activities of polysaccharides and their derivatives can find useful polysaccharides and their derivatives, which have great potential as natural antioxidants used in functional foods or medicines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides.

PubMed

Serhan, George; Stack, Colin M; Perrone, Gabriel G; Morton, Charles Oliver

2014-05-12

There is a pressing need to identify novel antifungal drug targets to aid in the therapy of life-threatening mycoses and overcome increasing drug resistance. Identifying specific mechanisms of action of membrane-interacting antimicrobial drugs on the model fungus Saccharomyces cerevisiae is one avenue towards addressing this issue. The S. cerevisiae deletion mutants Δizh2, Δizh3, Δaif1 and Δstm1 were demonstrated to be resistant to amphibian-derived antimicrobial peptides (AMPs). The purpose of this study was to examine whether AMPs and polyene antifungals have a similar mode of action; this was done by comparing the relative tolerance of the mutants listed above to both classes of antifungal. In support of previous findings on solid media it was shown that Δizh2 and Δizh3 mutants had increased resistance to both amphotericin B (1-2 μg ml-1) and nystatin (2.5 - 5 μg ml-1) in liquid culture, after acute exposure. However, Δaif1 and Δstm1 had wild-type levels of susceptibility to these polyenes. The generation of reactive oxygen species (ROS) after exposure to amphotericin B was also reduced in Δizh2 and Δizh3. These data indicated that polyene antifungal and AMPs may act via distinct mechanisms of inducing cell death in S. cerevisiae. Further understanding of the mechanism(s) involved in causing cell death and the roles of IZH2 and IZH3 in drug susceptibility may help to inform improved drug design and treatment of fungal pathogens.

Compendium of Mechanical Limit-States

NASA Technical Reports Server (NTRS)

Kowal, Michael

1996-01-01

A compendium was compiled and is described to provide a diverse set of limit-state relationships for use in demonstrating the application of probabilistic reliability methods to mechanical systems. The different limit-state relationships can be used to analyze the reliability of a candidate mechanical system. In determining the limit-states to be included in the compendium, a comprehensive listing of the possible failure modes that could affect mechanical systems reliability was generated. Previous literature defining mechanical modes of failure was studied, and cited failure modes were included. From this, classifications for failure modes were derived and are described in some detail.

Adipose-derived stem cell-derived microvesicle-released miR-210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3.

PubMed

Zheng, Zeqi; Liu, Lijuan; Zhan, Yuliang; Yu, Songping; Kang, Ting

2018-06-18

To explore the potential mechanism of miRNA released from adipose-derived stem cell (ADSC)-derived micro vesicle (MV) on the modulation of proliferation, migration and invasion of endothelial cells. miR-210 level was detected by qT-PCR. Alix, VEGF and RUNX3 expressions were detected by Western blot. The proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) were observed by MTT assay and Transwell assay. Luciferase reporter gene assay was conducted to validate the targeting activity of MVs-released miR-210 on RUNX3. Hypoxia significantly increased the expression of MVs-released miR-210. MVs released from ADSCs in hypoxic group significantly promoted the proliferation, migration and invasion of HUVECs. Overexpression of miR-210 significantly upregulated VEGF expression, and promoted the proliferation, migration and invasion of HUVECs. Besides, RUNX3 was identified as the direct of miR-210 in HUVECs. Overexpression of miR-210 decreased RUNX3 expression and promoted the proliferation, migration and invasion of HUVECs, while overexpression of RUNX3 inhibited these promotion effects. In vivo experiment showed that MVs derived from ADSCs under hypoxia increased miR-210 level and capillary density, and inhibition of miR-210 decreased capillary density. We also found MVs downregulated RUNX3 expression, and inhibition of miR-210 upregulated RUNX3 expression. miR-210 released from ADSCs-derived MVs promoted proliferation, migration and invasion of HUVECs by targeting RUNX3, which revealed one of the mechanisms of ADSCs-derived MVs on the promotion of proliferation, migration and invasion of HUVECs.

Carnitine derivatives: clinical usefulness.

PubMed

Malaguarnera, Mariano

2012-03-01

Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism.

PubMed

Bozdagi, Ozlem; Rich, Erin; Tronel, Sophie; Sadahiro, Masato; Patterson, Kamara; Shapiro, Matthew L; Alberini, Cristina M; Huntley, George W; Salton, Stephen R J

2008-09-24

VGF is a neurotrophin-inducible, activity-regulated gene product that is expressed in CNS and PNS neurons, in which it is processed into peptides and secreted. VGF synthesis is stimulated by BDNF, a critical regulator of hippocampal development and function, and two VGF C-terminal peptides increase synaptic activity in cultured hippocampal neurons. To assess VGF function in the hippocampus, we tested heterozygous and homozygous VGF knock-out mice in two different learning tasks, assessed long-term potentiation (LTP) and depression (LTD) in hippocampal slices from VGF mutant mice, and investigated how VGF C-terminal peptides modulate synaptic plasticity. Treatment of rat hippocampal slices with the VGF-derived peptide TLQP62 resulted in transient potentiation through a mechanism that was selectively blocked by the BDNF scavenger TrkB-Fc, the Trk tyrosine kinase inhibitor K252a (100 nm), and tPA STOP, an inhibitor of tissue plasminogen activator (tPA), an enzyme involved in pro-BDNF cleavage to BDNF, but was not blocked by the NMDA receptor antagonist APV, anti-p75(NTR) function-blocking antiserum, or previous tetanic stimulation. Although LTP was normal in slices from VGF knock-out mice, LTD could not be induced, and VGF mutant mice were impaired in hippocampal-dependent spatial learning and contextual fear conditioning tasks. Our studies indicate that the VGF C-terminal peptide TLQP62 modulates hippocampal synaptic transmission through a BDNF-dependent mechanism and that VGF deficiency in mice impacts synaptic plasticity and memory in addition to depressive behavior.

Truncated tyrosine kinase B brain-derived neurotrophic factor receptor directs cortical neural stem cells to a glial cell fate by a novel signaling mechanism.

PubMed

Cheng, Aiwu; Coksaygan, Turhan; Tang, Hongyan; Khatri, Rina; Balice-Gordon, Rita J; Rao, Mahendra S; Mattson, Mark P

2007-03-01

During development of the mammalian cerebral cortex neural stem cells (NSC) first generate neurons and subsequently produce glial cells. The mechanism(s) responsible for this developmental shift from neurogenesis to gliogenesis is unknown. Brain-derived neurotrophic factor (BDNF) is believed to play important roles in the development of the mammalian cerebral cortex; it enhances neurogenesis and promotes the differentiation and survival of newly generated neurons. Here, we provide evidence that a truncated form of the BDNF receptor tyrosine kinase B (trkB-t) plays a pivotal role in directing embryonic mouse cortical NSC to a glial cell fate. Expression of trkB-t promotes differentiation of NSC toward astrocytes while inhibiting neurogenesis both in cell culture and in vivo. The mechanism by which trkB-t induces astrocyte genesis is not simply the result of inhibition of full-length receptor with intrinsic tyrosine kinase activity signaling. Instead, binding of BDNF to trkB-t activates a signaling pathway (involving a G-protein and protein kinase C) that induced NSC to become glial progenitors and astrocytes. Thus, the increased expression of trkB-t in the embryonic cerebral cortex that occurs coincident with astrocyte production plays a pivotal role in the developmental transition from neurogenesis to gliogenesis. Our findings suggest a mechanism by which a single factor (BDNF) regulates the production of the two major cell types in the mammalian cerebral cortex.

Mechanism of α-ketol-type rearrangement of benzoin derivatives under basic conditions.

PubMed

Karino, Masahiro; Kubouchi, Daiki; Hamaoka, Kazuki; Umeyama, Shintaro; Yamataka, Hiroshi

2013-07-19

The mechanism of base-catalyzed rearrangement of ring-substituted benzoins in aqueous methanol was examined by kinetic and product analyses. Substituent effects on the rate and equilibrium constants revealed that the kinetic process has a different electron demand compared to the equilibrium process. Reactions in deuterated solvents showed that the rate of H/D exchange of the α-hydrogen is similar to the overall rate toward the equilibrium state. A proton-inventory experiment using partially deuterated solvents showed a linear dependence of the rate on the deuterium fraction of the solvent, indicating that only one deuterium isotope effect contributes to the overall rate process. All these results point to a mechanism in which the rearrangement is initiated by the rate-determining α-hydrogen abstraction rather than a mechanism with initial hydroxyl hydrogen abstraction as in the general α-ketol rearrangement.

Antibacterial activity of 3-methylbenzo[d]thiazol-methylquinolinium derivatives and study of their action mechanism.

PubMed

Sun, Ning; Du, Ruo-Lan; Zheng, Yuan-Yuan; Guo, Qi; Cai, Sen-Yuan; Liu, Zhi-Hua; Fang, Zhi-Yuan; Yuan, Wen-Chang; Liu, Ting; Li, Xiao-Mei; Lu, Yu-Jing; Wong, Kwok-Yin

2018-12-01

The increasing incidence of multidrug resistant bacterial infection renders an urgent need for the development of new antibiotics. To develop small molecules disturbing FtsZ activity has been recognized as promising approach to search for antibacterial of high potency systematically. Herein, a series of novel quinolinium derivatives were synthesized and their antibacterial activities were investigated. The compounds show strong antibacterial activities against different bacteria strains including MRSA, VRE and NDM-1 Escherichia coli. Among these derivatives, a compound bearing a 4-fluorophenyl group (A2) exhibited a superior antibacterial activity and its MICs to the drug-resistant strains are found lower than those of methicillin and vancomycin. The biological results suggest that these quinolinium derivatives can disrupt the GTPase activity and dynamic assembly of FtsZ, and thus inhibit bacterial cell division and then cause bacterial cell death. These compounds deserve further evaluation for the development of new antibacterial agents targeting FtsZ.

Mechanics of active surfaces

NASA Astrophysics Data System (ADS)

Salbreux, Guillaume; Jülicher, Frank

2017-09-01

We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.

Measuring memory with the order of fractional derivative

NASA Astrophysics Data System (ADS)

Du, Maolin; Wang, Zaihua; Hu, Haiyan

2013-12-01

Fractional derivative has a history as long as that of classical calculus, but it is much less popular than it should be. What is the physical meaning of fractional derivative? This is still an open problem. In modeling various memory phenomena, we observe that a memory process usually consists of two stages. One is short with permanent retention, and the other is governed by a simple model of fractional derivative. With the numerical least square method, we show that the fractional model perfectly fits the test data of memory phenomena in different disciplines, not only in mechanics, but also in biology and psychology. Based on this model, we find that a physical meaning of the fractional order is an index of memory.

The effect of various quantum mechanically derived partial atomic charges on the bulk properties of chloride-based ionic liquids

NASA Astrophysics Data System (ADS)

Zolghadr, Amin Reza; Ghatee, Mohammad Hadi; Moosavi, Fatemeh

2016-08-01

Partial atomic charges using various quantum mechanical calculations for [Cnmim]Cl (n = 1, 4) ionic liquids (ILs) are obtained and used for development of molecular dynamics simulation (MD) force fields. The isolated ion pairs are optimized using HF, B3LYP, and MP2 methods for electronic structure with 6-311++G(d,p) basis set. Partial atomic charges are assigned to the atomic center with CHELPG and NBO methods. The effect of these sets of partial charges on the static and dynamic properties of ILs is evaluated by performing a series of MD simulations and comparing the essential thermodynamic properties with the available experimental data and available molecular dynamics simulation results. In contrast to the general trends reported for ionic liquids with BF4, PF6, and iodide anions (in which restrained electrostatic potential (RESP) charges are preferred), partial charges derived by B3LYP-NBO method are relatively good in prediction of the structural, dynamical, and thermodynamic energetic properties of the chloride based ILs.

Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy.

PubMed

Aziz, Mohamed Talaat Abdel; El Ibrashy, Ibrahim Naguib; Mikhailidis, Dimitri P; Rezq, Ameen Mahmoud; Wassef, Mohamed Abdel Aziz; Fouad, Hanan Hassan; Ahmed, Hanan Hosni; Sabry, Dina A; Shawky, Heba Mohamed; Hussein, Rania Elsayed

2013-03-12

Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.

Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

PubMed Central

2013-01-01

Background Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. Materials and methods Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. Results NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin. PMID:23497378

Generalized Weyl-Wigner map and Vey quantum mechanics

NASA Astrophysics Data System (ADS)

Dias, Nuno Costa; Prata, João Nuno

2001-12-01

The Weyl-Wigner map yields the entire structure of Moyal quantum mechanics directly from the standard operator formulation. The covariant generalization of Moyal theory, also known as Vey quantum mechanics, was presented in the literature many years ago. However, a derivation of the formalism directly from standard operator quantum mechanics, clarifying the relation between the two formulations, is still missing. In this article we present a covariant generalization of the Weyl order prescription and of the Weyl-Wigner map and use them to derive Vey quantum mechanics directly from the standard operator formulation. The procedure displays some interesting features: it yields all the key ingredients and provides a more straightforward interpretation of the Vey theory including a direct implementation of unitary operator transformations as phase space coordinate transformations in the Vey idiom. These features are illustrated through a simple example.

Mechanical modeling for magnetorheological elastomer isolators based on constitutive equations and electromagnetic analysis

NASA Astrophysics Data System (ADS)

Wang, Qi; Dong, Xufeng; Li, Luyu; Ou, Jinping

2018-06-01

As constitutive models are too complicated and existing mechanical models lack universality, these models are beyond satisfaction for magnetorheological elastomer (MRE) devices. In this article, a novel universal method is proposed to build concise mechanical models. Constitutive model and electromagnetic analysis were applied in this method to ensure universality, while a series of derivations and simplifications were carried out to obtain a concise formulation. To illustrate the proposed modeling method, a conical MRE isolator was introduced. Its basic mechanical equations were built based on equilibrium, deformation compatibility, constitutive equations and electromagnetic analysis. An iteration model and a highly efficient differential equation editor based model were then derived to solve the basic mechanical equations. The final simplified mechanical equations were obtained by re-fitting the simulations with a novel optimal algorithm. In the end, verification test of the isolator has proved the accuracy of the derived mechanical model and the modeling method.

Earth rotation excitation mechanisms derived from geodetic space observations

NASA Astrophysics Data System (ADS)

Göttl, F.; Schmidt, M.

2009-04-01

Earth rotation variations are caused by mass displacements and motions in the subsystems of the Earth. Via the satellite Gravity and Climate Experiment (GRACE) gravity field variations can be identified which are caused by mass redistribution in the Earth system. Therefore time variable gravity field models (GFZ RL04, CSR RL04, JPL RL04, ITG-Grace03, GRGS, ...) can be used to derive different impacts on Earth rotation. Furthermore satellite altimetry provides accurate information on sea level anomalies (AVISO, DGFI) which are caused by mass and volume changes of seawater. Since Earth rotation is solely affected by mass variations and motions the volume (steric) effect has to be reduced from the altimetric observations in order to infer oceanic contributions to Earth rotation variations. Therefore the steric effect is estimated from physical ocean parameters such as temperature and salinity changes in the oceans (WOA05, Ishii). In this study specific individual geophysical contributions to Earth rotation variations are identified by means of a multitude of accurate geodetic space observations in combination with a realistic error propagation. It will be shown that due to adjustment of altimetric and/or gravimetric solutions the results for polar motion excitations can be improved.

Structural phenotyping of stem cell-derived cardiomyocytes.

PubMed

Pasqualini, Francesco Silvio; Sheehy, Sean Paul; Agarwal, Ashutosh; Aratyn-Schaus, Yvonne; Parker, Kevin Kit

2015-03-10

Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during striated muscle cell development. To test our metrics, we analyzed the localization of the contractile protein α-actinin in a variety of primary and stem-cell derived cardiomyocytes. Further, we combined these metrics with data mining algorithms to unbiasedly score the phenotypic maturity of human-induced pluripotent stem cell-derived cardiomyocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking.

PubMed

Channar, Pervaiz Ali; Saeed, Aamer; Albericio, Fernando; Larik, Fayaz Ali; Abbas, Qamar; Hassan, Mubashir; Raza, Hussain; Seo, Sung-Yum

2017-08-16

Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC 50 = 0.081 ± 0.003 µM), 6a (IC 50 = 0.0022 ± 0.0002 µM), 9e (IC 50 = 0.0250 ± 0.0007 µM) and 12d (IC 50 = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC 50 = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e , 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a , 12b , 12d , 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C.

Contact geometry and quantum mechanics

NASA Astrophysics Data System (ADS)

Herczeg, Gabriel; Waldron, Andrew

2018-06-01

We present a generally covariant approach to quantum mechanics in which generalized positions, momenta and time variables are treated as coordinates on a fundamental "phase-spacetime". We show that this covariant starting point makes quantization into a purely geometric flatness condition. This makes quantum mechanics purely geometric, and possibly even topological. Our approach is especially useful for time-dependent problems and systems subject to ambiguities in choices of clock or observer. As a byproduct, we give a derivation and generalization of the Wigner functions of standard quantum mechanics.

Antidiabetic plant-derived nutraceuticals: a critical review.

PubMed

Naveen, Jayapal; Baskaran, Vallikannan

2018-06-01

Diabetes mellitus (DM) is one of the major health problems in the world, especially amongst the urban population. Chemically synthesized drugs used to decrease the ill effects of DM and its secondary complications cause adverse side effects, viz., weight gain, gastrointestinal disturbances, and heart failure. Currently, various other approaches, viz., diet control, physical exercise and use of antidiabetic plant-derived molecules/foods are advocated to manage DM, as they are economical with fewer or no side effects. This review mainly focuses on antidiabetic plants, chemically characterized plant molecules and plant-based foods in the treatment of DM. Very little science-based evidence is available on the mechanism of action of plant-derived food molecules on the DM targets. Critical DM targets include α-amylase, α-glucosidase, DPP-IV, aldose reductase, PPAR-γ, AMP kinase and GLUT4. In-depth studies carried out on a few of those targets with specific mechanisms of action are addressed in this review. This review may help future researchers in identifying a right plant molecule to treat DM or to develop food formulations for DM management.

GFP's Mechanical Intermediate States

PubMed Central

Saeger, John; Hytönen, Vesa P.; Klotzsch, Enrico; Vogel, Viola

2012-01-01

Green fluorescent protein (GFP) mutants have become the most widely used fluorescence markers in the life sciences, and although they are becoming increasingly popular as mechanical force or strain probes, there is little direct information on how their fluorescence changes when mechanically stretched. Here we derive high-resolution structural models of the mechanical intermediate states of stretched GFP using steered molecular dynamics (SMD) simulations. These structures were used to produce mutants of EGFP and EYFP that mimic GFP's different mechanical intermediates. A spectroscopic analysis revealed that a population of EGFP molecules with a missing N-terminal α-helix was significantly dimmed, while the fluorescence lifetime characteristic of the anionic chromophore state remained unaffected. This suggests a mechanism how N-terminal deletions can switch the protonation state of the chromophore, and how the fluorescence of GFP molecules in response to mechanical disturbance might be turned off. PMID:23118864

Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes

PubMed Central

Lieu, Deborah K.; Fu, Ji-Dong; Chiamvimonvat, Nipavan; Chan Tung, Kelvin W.; McNerney, Gregory P.; Huser, Thomas; Keller, Gordon; Kong, Chi-Wing

2013-01-01

Background Human embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated. Methods and Results Here we showed that CMs derived from multiple pluripotent human stem cell lines (hESC: H1, HES2) and types (induced pluripotent stem cell or iPSC) using different in vitro differentiation protocols (embryoid body formation, endodermal induction, directed differentiation) commonly displayed immature, pro-arrhythmic action potential (AP) properties such as high-degree of automaticity, depolarized resting membrane potential (RMP), Phase 4- depolarization and delayed after-depolarization (DAD). Among the panoply of sarcolemmal ionic currents investigated (INa+/ICaL2+/IKr+/INCX+/If+/Ito+/IK1-/IKs-), we pinpointed the lack of the Kir2.1-encoded inwardly rectifying K+ current (IK1) as the single mechanistic contributor to the observed immature electrophysiological properties in hESC-CMs. Forced expression of Kir2.1 in hESC-CMs led to robust expression of Ba2+-sensitive IK1 and more importantly, completely ablated all the pro-arrhythmic AP traits, rendering the electrophysiological phenotype indistinguishable from the adult counterparts. These results provided the first link of a complex developmentally arrested phenotype to a major effector gene, and importantly, further led us to develop a biomimetic culturing strategy for enhancing maturation. Conclusions By providing the environmental cues that are missing in conventional culturing method, this approach did not require any genetic or pharmacological interventions. Our findings can facilitate clinical applications, drug discovery and cardiotoxicity screening by improving the yield, safety and efficacy of derived CMs. PMID:23392582

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

PubMed Central

Gomes, Nelson G. M.; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

2015-01-01

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms. PMID:26090846

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

PubMed

Gomes, Nelson G M; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

2015-06-19

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

Hypoxia and alkalinization inhibit endothelium-derived nitric oxide but not endothelium-derived hyperpolarizing factor responses in porcine coronary artery.

PubMed

Shimizu, S; Paul, R J

1999-10-01

We investigated the mechanisms by which hypoxia and alkalinization inhibit the endothelium-dependent relaxation to Substance P (SP) in porcine coronary artery. In a KCl contracture, the major component of the SP response is endothelium-derived nitric oxide (EDNO), whereas with receptor-mediated 9,11-dideoxy-llalpha, 9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) stimulation, the SP response is dependent on both EDNO and endothelium-derived hyperpolarization factor. Intracellular alkalinization by NH(4)Cl reduced the peak of SP responses when arteries were contracted with KCl, whereas with U46619 stimulation, the peak was little effected but the duration was shortened. In endothelial cell-denuded arteries, alkalinization with NH(4)Cl shifted the sodium nitroprusside concentration-relaxation relations rightward. The effects of NH(4)Cl in SP- and sodium nitroprusside-induced relaxations were attenuated by decreasing extracellular pH (pH(o)) from 7.4 to 7.2, which normalized intracellular pH (pH(i)) to control levels. In contrast, in U46619 contractures, the SP response in the presence of a NO synthase inhibitor was unaffected by NH(4)Cl. Moreover, hypoxia blunted but did not abolish the responses to SP for U46619 contractures; addition of KCl, however, abolished the SP response under hypoxia. Endothelial [Ca(2+)](i) was measured with fura-2 differentially loaded only into endothelial cells on intact arteries. Despite the attenuation of the SP response in KCl contractures by NH(4)Cl or hypoxia, endothelial [Ca(2+)](i) responses were unchanged. Our results suggest that hypoxia and alkalinization inhibit EDNO but not endothelium-derived hyperpolarization factor relaxations through a mechanism(s) not involving endothelial cell [Ca(2+)](i). Inhibition of EDNO relaxation by alkalinization with NH(4)Cl is likely to occur at the level of activation of guanylate cyclase and/or at a step downstream in smooth muscle.

Selective epitaxial growth of zinc blende-derivative on wurtzite-derivative: the case of polytypic Cu2CdSn(S1-xSex)4 nanocrystals

NASA Astrophysics Data System (ADS)

Wu, Liang; Fan, Feng-Jia; Gong, Ming; Ge, Jin; Yu, Shu-Hong

2014-02-01

Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor to adjust the reactivity difference between (0002)WZ and (000-2)WZ facets. These unique polytypic CCTSSe nanocrystals may find applications in energetic semiconducting materials for energy conversion in the future.Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor

In Vitro Modulation of Renin-Angiotensin System Enzymes by Amaranth (Amaranthus hypochondriacus) Protein-Derived Peptides: Alternative Mechanisms Different from ACE Inhibition.

PubMed

Quiroga, Alejandra V; Aphalo, Paula; Nardo, Agustina E; Añón, María C

2017-08-30

Among the factors affecting the development of cardiovascular diseases, hypertension is one of the most important. Research done on amaranth proteins has demonstrated their hypotensive capacity in vivo and in vitro; nevertheless, the mechanism underlying this effect remains unclear. The aim of this study was to analyze in vitro the inhibition of peptides derived from an amaranth hydrolysate (AHH) on other RAS enzymes other than ACE. The chymase and renin activities were studied. AHH was not able to inhibit chymase activity, although a dose-response effect was found on renin activity (IC 50 0.6 mg/mL). To provide an approach to the renin inhibition mechanism, we analyzed AHH renin inhibition kinetics and performed a structural characterization of the peptides involved in the effect in terms of molecular size and hydrophobicity. Results suggest that amaranth peptides exhibit renin competitive inhibition behavior. Renin inhibition potency was directly related to peptide hydrophobicity. RP-HPLC separation of AHH and subsequent analysis of the peptide sequences showed 6 peptides belonging to 11S globulin (that can be grouped into 3 families) that would be responsible for renin inhibition. These results demonstrate that Amaranthus hypochondriacus seeds are an adequate source of peptides with renin inhibitory properties that could be used in functional food formulations.

Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell- derived-suppressor factors

PubMed Central

1979-01-01

Delayed type hypersensitivity to the hapten azobenzenearsonate (ABA) can be induced and suppressed by the administration of hapten-coupled syngeneic spleen cells by the appropriate route. Suppressor T cells stimulated by the intravenous administration of ABA-coupled spleen cells have been shown to produce a discrete subcellular factor(s) which is capable of suppressing delayed type hypersensitivity to azobenzenearsonate in the mouse. Such suppressor factors may be produced by the mechanical disruption of suppressor cells or by placing such suppressor cells in culture for 24 h. The suppressor factor(s) (SF) derived from ABA-specific suppressor cells exhibit biological specificity for the suppression of ABA delayed type hypersensitivity (DTH), but not trinitro-phenyl DTH, as well as the capacity to bind to ABA immunoadsorbents. Passage of suppressor factor(s) over reverse immunoadsorbents utilizing a rabbit anti-mouse F(ab')2 antiserum demonstrated that the antigen-specific T-cell derived SF does not bear conventional immunoglobulin markers. The suppressor factor(s) are not immunoglobulin molecules was further demonstrated by the inability of anti-ABA antibodies to suppress ABA DTH. Gel filtration of ABA suppressor factor(s) showed that the majority of the suppressive activity was present in a fraction with molecular weight ranging between 6.8 x 10(4) and 3.3 x 10(4) daltons. We also analyzed for the presence of determinants encoded by the H-2 major histocompatibility complex (MHC) and found that immunoadsorbents prepared utilizing antisera capable of interacting with gene products of the whole or selected gene regions of H-2 MHC, i.e., B10.D2 anti-B10.A and B10 anti- B10.A immunoadsorbents, retained the suppressive activity of ABA-SF. Elution of such columns with glycine HCl buffers (pH 2.8) permitted recovery of specific suppressive activity. Taken collectively such data supports the notion that suppressor T-cell-derived ABA suppressor factors have antigen

TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation.

PubMed Central

Taylor, J P; Pomerantz, R; Bagasra, O; Chowdhury, M; Rappaport, J; Khalili, K; Amini, S

1992-01-01

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1505523

Antifungal mechanism of an antimicrobial peptide, HP (2--20), derived from N-terminus of Helicobacter pylori ribosomal protein L1 against Candida albicans.

PubMed

Lee, Dong Gun; Park, Yoonkyung; Kim, Hee Nam; Kim, Hyung Keun; Kim, Pyoung Il; Choi, Bo Hwa; Hahm, Kyung-Soo

2002-03-08

The antifungal activity and mechanism of HP (2-20), a peptide derived from the N-terminus sequence of Helicobacter pylori Ribosomal Protein L1 were investigated. HP (2--20) displayed a strong antifungal activity against various fungi, and the antifungal activity was inhibited by Ca(2+) and Mg(2+) ions. In order to investigate the antifungal mechanism(s) of HP (2-20), fluorescence activated flow cytometry was performed. As determined by propidium iodide staining, Candida albicans treated with HP (2-20) showed a higher fluorescence intensity than untreated cells and was similar to melittin-treated cells. The effect on fungal cell membranes was examined by investigating the change in membrane dynamics of C. albicans using 1,6-diphenyl-1,3,5-hexatriene as a membrane probe and by testing the membrane disrupting activity using liposome (PC/PS; 3:1, w/w) and by treating protoplasts of C. albicans with the peptide. The action of peptide against fungal cell membrane was further examined by the potassium-release test, and HP (2-20) was able to increase the amount of K(+) released from the cells. The result suggests that HP (2-20) may exert its antifungal activity by disrupting the structure of cell membrane via pore formation or directly interacts with the lipid bilayers in a salt-dependent manner.

Ferroquine and its derivatives: new generation of antimalarial agents.

PubMed

Wani, Waseem A; Jameel, Ehtesham; Baig, Umair; Mumtazuddin, Syed; Hun, Lee Ting

2015-08-28

Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Healthy degenerate theories with higher derivatives

NASA Astrophysics Data System (ADS)

Motohashi, Hayato; Noui, Karim; Suyama, Teruaki; Yamaguchi, Masahide; Langlois, David

2016-07-01

In the context of classical mechanics, we study the conditions under which higher-order derivative theories can evade the so-called Ostrogradsky instability. More precisely, we consider general Lagrangians with second order time derivatives, of the form L(̈phia, dot phia, phia; qi, qi) with a = 1,⋯,n and i = 1,⋯,m. For n = 1, assuming that the qi's form a nondegenerate subsystem, we confirm that the degeneracy of the kinetic matrix eliminates the Ostrogradsky instability. The degeneracy implies, in the Hamiltonian formulation of the theory, the existence of a primary constraint, which generates a secondary constraint, thus eliminating the Ostrogradsky ghost. For n > 1, we show that, in addition to the degeneracy of the kinetic matrix, one needs to impose extra conditions to ensure the presence of a sufficient number of secondary constraints that can eliminate all the Ostrogradsky ghosts. When these conditions that ensure the disappearance of the Ostrogradsky instability are satisfied, we show that the Euler-Lagrange equations, which involve a priori higher order derivatives, can be reduced to a second order system.

The mechanism of action of piperazine-phosphonates derivatives in cotton fabric

USDA-ARS?s Scientific Manuscript database

Piperazine-phosphonates additives are known to be very effective flame retardants on different polymeric systems, especially cotton cellulose. In order to understand their mechanism of action, we carried out the investigation of their thermal behavior on cotton fabric by, first, employing the attenu...

Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

PubMed

Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

2012-01-02

Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

Neuronal Mechanism for Compensation of Longitudinal Chromatic Aberration-Derived Algorithm.

PubMed

Barkan, Yuval; Spitzer, Hedva

2018-01-01

The human visual system faces many challenges, among them the need to overcome the imperfections of its optics, which degrade the retinal image. One of the most dominant limitations is longitudinal chromatic aberration (LCA), which causes short wavelengths (blue light) to be focused in front of the retina with consequent blurring of the retinal chromatic image. The perceived visual appearance, however, does not display such chromatic distortions. The intriguing question, therefore, is how the perceived visual appearance of a sharp and clear chromatic image is achieved despite the imperfections of the ocular optics. To address this issue, we propose a neural mechanism and computational model, based on the unique properties of the S -cone pathway. The model suggests that the visual system overcomes LCA through two known properties of the S channel: (1) omitting the contribution of the S channel from the high-spatial resolution pathway (utilizing only the L and M channels). (b) Having large and coextensive receptive fields that correspond to the small bistratified cells. Here, we use computational simulations of our model on real images to show how integrating these two basic principles can provide a significant compensation for LCA. Further support for the proposed neuronal mechanism is given by the ability of the model to predict an enigmatic visual phenomenon of large color shifts as part of the assimilation effect.

Neuronal Mechanism for Compensation of Longitudinal Chromatic Aberration-Derived Algorithm

PubMed Central

Barkan, Yuval; Spitzer, Hedva

2018-01-01

The human visual system faces many challenges, among them the need to overcome the imperfections of its optics, which degrade the retinal image. One of the most dominant limitations is longitudinal chromatic aberration (LCA), which causes short wavelengths (blue light) to be focused in front of the retina with consequent blurring of the retinal chromatic image. The perceived visual appearance, however, does not display such chromatic distortions. The intriguing question, therefore, is how the perceived visual appearance of a sharp and clear chromatic image is achieved despite the imperfections of the ocular optics. To address this issue, we propose a neural mechanism and computational model, based on the unique properties of the S-cone pathway. The model suggests that the visual system overcomes LCA through two known properties of the S channel: (1) omitting the contribution of the S channel from the high-spatial resolution pathway (utilizing only the L and M channels). (b) Having large and coextensive receptive fields that correspond to the small bistratified cells. Here, we use computational simulations of our model on real images to show how integrating these two basic principles can provide a significant compensation for LCA. Further support for the proposed neuronal mechanism is given by the ability of the model to predict an enigmatic visual phenomenon of large color shifts as part of the assimilation effect. PMID:29527525

A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli

PubMed Central

Liu, Taoyan; Huang, Chengwu; Li, Hongxia; Wu, Fujian; Luo, Jianwen; Lu, Wenjing

2018-01-01

The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the differently shaped CMs, and the net-shaped CMs had larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net-shaped CMs displayed accelerated maturation at the transcriptional level and were more similar to CMs with a prolonged culture time (30 days) than to sheet-d15. Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs, indicating that robust contraction was coupled with enhanced ion channel and connexin expression. The net-shaped CMs also displayed improved myofibril ultrastructure under transmission electron microscopy. In conclusion, different multicellular hPSC-CM structures, such as the net-shaped pattern, are formed using the conditioned induction method, providing a useful tool to improve cardiac maturation. PMID:29661985

Binding mechanism investigations guiding the synthesis of novel condensed 1,4-dihydropyridine derivatives with L-/T-type calcium channel blocking activity.

PubMed

Schaller, David; Gündüz, Miyase Gözde; Zhang, Fang Xiong; Zamponi, Gerald W; Wolber, Gerhard

2018-05-23

Nifedipine and isradipine are prominent examples of calcium channel blockers with a 1,4-dihydropyridine (DHP) scaffold. Although successfully used in clinics since decades for the treatment of hypertension, the binding mechanism to their target, the L-type voltage-gated calcium channel Cav1.2, is still incompletely understood. Recently, novel DHP derivatives with a condensed ring system have been discovered that show distinct selectivity profiles to different calcium channel subtypes. This property renders this DHP class as a promising tool to achieve selectivity towards distinct calcium channel subtypes. In this study, we identified a common binding mode for prominent DHPs nifedipine and isradipine using docking and pharmacophore analysis that is also able to explain the structure-activity relationship of a small subseries of DHP derivatives with a condensed ring system. These findings were used to guide the synthesis of twenty-two novel DHPs. An extensive characterization using 1 H NMR, 13 C NMR, mass spectra and elemental analysis was followed by whole cell patch clamp assays for analyzing activity at Cav1.2 and Cav3.2. Two compounds were identified with significant activity against Cav1.2. Additionally, we identified four compounds active against Cav3.2 of which three were selective over Cav1.2. Novel binding modes were analyzed using docking and pharmacophore analysis as well as molecular dynamics simulations. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

PubMed Central

Wagner, Anika Eva; Terschluesen, Anna Maria; Rimbach, Gerald

2013-01-01

A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways. PMID:24454992

Highly Soluble p-Terphenyl and Fluorene Derivatives as Efficient Dopants in Plastic Scintillators for Sensitive Nuclear Material Detection.

PubMed

Yemam, Henok A; Mahl, Adam; Tinkham, Jonathan S; Koubek, Joshua T; Greife, Uwe; Sellinger, Alan

2017-07-03

Plastic scintillators are commonly used as first-line detectors for special nuclear materials. Current state-of-the-art plastic scintillators based on poly(vinyltoluene) (PVT) matrices containing high loadings (>15.0 wt %) of 2,5-diphenyloxazole (PPO) offer neutron signal discrimination in gamma radiation background (termed pulse shape discrimination, PSD), however, they suffer from poor mechanical properties. In this work, a series of p-terphenyl and fluorene derivatives were synthesized and tested as dopants in PVT based plastic scintillators as possible alternatives to PPO to address the mechanical property issue and to study the PSD mechanism. The derivatives were synthesized from low cost starting materials in high yields using simple chemistry. The photophysical and thermal properties were investigated for their influence on radiation sensitivity/detection performance, and mechanical stability. A direct correlation was found between the melting point of the dopants and the subsequent mechanical properties of the PVT based plastic scintillators. For example, select fluorene derivatives used as dopants produced scintillator samples with mechanical properties exceeding those of the commercial PPO-based scintillators while producing acceptable PSD capabilities. The physical properties of the synthesized dopants were also investigated to examine their effect on the final scintillator samples. Planar derivatives of fluorene were found to be highly soluble in PVT matrices with little to no aggregation induced effects. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Involvement of PKC and ROS in the cytotoxic mechanism of anti-leukemic decursin and its derivatives and their structure-activity relationship in human K562 erythroleukemia and U937 myeloleukemia cells.

PubMed

Kim, Hyeon Ho; Sik Bang, Sung; Seok Choi, Jin; Han, Hogyu; Kim, Ik-Hwan

2005-06-08

Protein kinase C (PKC) plays an important role in the proliferation and differentiation of various cell types including normal and leukemic hematopoietic cells. Recently, various PKC modulators were used as a chemotherapeutic agent of leukemia. Decursin (1), a pyranocoumarin from Angelica gigas, exhibits the cytotoxic effects on various human cancer cell lines and in vitro PKC activation. For the development of more effective anticancer agents with PKC modulation activity, 11 decursin derivatives 2-12 were chemically synthesized and evaluated for their ability to act as a tumor-suppressing PKC activator and as an antagonist to phorbol 12-myristate 13-acetate (PMA), a tumor-promoting PKC activator. In the presence of phosphatidylserine (PS), all of 12 compounds 1-12 activated PKC (mainly alpha, beta, and gamma isozymes) but only three compounds 1-3 activated PKC even in the absence of PS. Six compounds 1-6 containing the coumarin structure were cytotoxic to human K562 erythroleukemia and U937 myeloleukemia cells. A cytotoxic mechanism of decursin and its derivatives was investigated using TUR cells, a PKC betaII-deficient variant of U937 cells. Among six compounds 1-6 with cytotoxicity to K562 and U937 leukemia cells, only three compounds 1-3 were cytotoxic to TUR cells. Therefore, compounds 1-3 and 4-6 inhibit the proliferation of leukemia cells in a PKC betaII-independent and dependent manner, respectively, indicating that the side chain of compounds determines the dependency of their cytotoxicity on PKC betaII. To further elucidate the cytotoxic mechanism of compounds 1 and 2, levels of PKC isozymes and generation of reactive oxygen species (ROS) were investigated. Compounds 1-2 induced the down-regulation of PKC alpha and betaII in K562 cells and the production of ROS in U937 cells. Thus, PKC and ROS are probably important factors in the cytotoxic mechanism of compounds 1-2. From these results, the structure-activity relationship of decursin and its derivatives

The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells

PubMed Central

Honda, Shozo; Kawamura, Takuya; Loher, Phillipe; Morichika, Keisuke; Rigoutsos, Isidore

2017-01-01

Abstract Transfer RNAs (tRNAs) function in translational machinery and further serves as a source of short non-coding RNAs (ncRNAs). tRNA-derived ncRNAs show differential expression profiles and play roles in many biological processes beyond translation. Molecular mechanisms that shape and regulate their expression profiles are largely unknown. Here, we report the mechanism of biogenesis for tRNA-derived Piwi-interacting RNAs (td-piRNAs) expressed in Bombyx BmN4 cells. In the cells, two cytoplasmic tRNA species, tRNAAspGUC and tRNAHisGUG, served as major sources for td-piRNAs, which were derived from the 5′-part of the respective tRNAs. cP-RNA-seq identified the two tRNAs as major substrates for the 5′-tRNA halves as well, suggesting a previously uncharacterized link between 5′-tRNA halves and td-piRNAs. An increase in levels of the 5′-tRNA halves, induced by BmNSun2 knockdown, enhanced the td-piRNA expression levels without quantitative change in mature tRNAs, indicating that 5′-tRNA halves, not mature tRNAs, are the direct precursors for td-piRNAs. For the generation of tRNAHisGUG-derived piRNAs, BmThg1l-mediated nucleotide addition to −1 position of tRNAHisGUG was required, revealing an important function of BmThg1l in piRNA biogenesis. Our study advances the understanding of biogenesis mechanisms and the genesis of specific expression profiles for tRNA-derived ncRNAs. PMID:28645172

Structure, Content, and Bioactivity of Food-Derived Peptides in the Body.

PubMed

Sato, Kenji

2018-03-28

Orally administered peptides are assumed to be degraded into amino acids in the body. However, our recent studies revealed some food-derived prolyl and pyroglutamyl peptides with 2-3 amino acid residues in the blood of humans and animals, while most of the peptides in the endoproteinase digest of food protein are degraded by exopeptidase. Some food-derived dipeptides in the body display in vitro and in vivo biological activities. These facts indicate that the biological activities of food-derived peptides in the body rather than those in food are crucial to understanding the mechanism of the beneficial effects of orally administered peptides.

Adsorption Characteristics of Pb(2+) onto Wine Lees-Derived Biochar.

PubMed

Zhu, Qihong; Wu, Jun; Wang, Lilin; Yang, Gang; Zhang, Xiaohong

2016-08-01

Biochar has great advantages in soil amendment and polluted soil remediation. Herein, the pore and adsorption properties of wine lees-derived biochar were explored. Specifically, the adsorption isotherm and kinetics of Pb(2+) onto wine lees-derived biochar were examined. Experimental results revealed that wine lees-derived biochar featured large specific surface area and total pore volume, and high contents of -COOH and -OH on its surface. Adsorption of Pb(2+) onto wine lees-derived biochar proceeded via a multilayer adsorption mechanism, as described by the Freundlich adsorption model. Adsorption kinetics followed the Lagergren pseudo-second-order kinetics model; adsorption equilibrium was achieved within 30-60 min. Furthermore, the effect of solution pH on the adsorption of Pb(2+) was investigated. Within the studied pH range of 3-6, the adsorption capacity increased with increasing pH. Under established optimized conditions, wine lees-derived biochar achieved a Pb(2+) adsorption capacity of 79.12 mg/g.

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Dual/multitargeted xanthone derivatives for Alzheimer's disease: where do we stand?

PubMed

Cruz, Maria I; Cidade, Honorina; Pinto, Madalena

2017-09-01

To date, the current therapy for Alzheimer's disease (AD) based on acetylcholinesterase inhibitors is only symptomatic, being its efficacy limited. Hence, the recent research has been focused in the development of different pharmacological approaches. Here we discuss the potential of xanthone derivatives as new anti-Alzheimer agents. The interference of xanthone derivatives with acetylcholinesterase and other molecular targets and cellular mechanisms associated with AD have been recently systematically reported. Therefore, we report xanthones with anticholinesterase, monoamine oxidase and amyloid β aggregation inhibitory activities as well as antioxidant properties, emphasizing xanthone derivatives with dual/multitarget activity as potential agents to treat AD. We also propose the structural features for these activities that may guide the design of new, more effective xanthone derivatives. [Formula: see text].

Celestial mechanics with geometric algebra

NASA Technical Reports Server (NTRS)

Hestenes, D.

1983-01-01

Geometric algebra is introduced as a general tool for Celestial Mechanics. A general method for handling finite rotations and rotational kinematics is presented. The constants of Kepler motion are derived and manipulated in a new way. A new spinor formulation of perturbation theory is developed.

Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling

PubMed Central

Kim, Hye-Young H.; Bauer, Rebecca N.; Fessler, Michael B.; Duncan, Kelly E.; Liu, Wei; Porter, Ned A.

2016-01-01

When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3. Additionally, exposure of LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects. PMID:27703007

Investigation of the mechanism of meiotic DNA cleavage by VMA1-derived endonuclease uncovers a meiotic alteration in chromatin structure around the target site.

PubMed

Fukuda, Tomoyuki; Ohta, Kunihiro; Ohya, Yoshikazu

2006-06-01

VMA1-derived endonuclease (VDE), a homing endonuclease in Saccharomyces cerevisiae, is encoded by the mobile intein-coding sequence within the nuclear VMA1 gene. VDE recognizes and cleaves DNA at the 31-bp VDE recognition sequence (VRS) in the VMA1 gene lacking the intein-coding sequence during meiosis to insert a copy of the intein-coding sequence at the cleaved site. The mechanism underlying the meiosis specificity of VMA1 intein-coding sequence homing remains unclear. We studied various factors that might influence the cleavage activity in vivo and found that VDE binding to the VRS can be detected only when DNA cleavage by VDE takes place, implying that meiosis-specific DNA cleavage is regulated by the accessibility of VDE to its target site. As a possible candidate for the determinant of this accessibility, we analyzed chromatin structure around the VRS and revealed that local chromatin structure near the VRS is altered during meiosis. Although the meiotic chromatin alteration exhibits correlations with DNA binding and cleavage by VDE at the VMA1 locus, such a chromatin alteration is not necessarily observed when the VRS is embedded in ectopic gene loci. This suggests that nucleosome positioning or occupancy around the VRS by itself is not the sole mechanism for the regulation of meiosis-specific DNA cleavage by VDE and that other mechanisms are involved in the regulation.

Investigation of the Mechanism of Meiotic DNA Cleavage by VMA1-Derived Endonuclease Uncovers a Meiotic Alteration in Chromatin Structure around the Target Site

PubMed Central

Fukuda, Tomoyuki; Ohta, Kunihiro; Ohya, Yoshikazu

2006-01-01

VMA1-derived endonuclease (VDE), a homing endonuclease in Saccharomyces cerevisiae, is encoded by the mobile intein-coding sequence within the nuclear VMA1 gene. VDE recognizes and cleaves DNA at the 31-bp VDE recognition sequence (VRS) in the VMA1 gene lacking the intein-coding sequence during meiosis to insert a copy of the intein-coding sequence at the cleaved site. The mechanism underlying the meiosis specificity of VMA1 intein-coding sequence homing remains unclear. We studied various factors that might influence the cleavage activity in vivo and found that VDE binding to the VRS can be detected only when DNA cleavage by VDE takes place, implying that meiosis-specific DNA cleavage is regulated by the accessibility of VDE to its target site. As a possible candidate for the determinant of this accessibility, we analyzed chromatin structure around the VRS and revealed that local chromatin structure near the VRS is altered during meiosis. Although the meiotic chromatin alteration exhibits correlations with DNA binding and cleavage by VDE at the VMA1 locus, such a chromatin alteration is not necessarily observed when the VRS is embedded in ectopic gene loci. This suggests that nucleosome positioning or occupancy around the VRS by itself is not the sole mechanism for the regulation of meiosis-specific DNA cleavage by VDE and that other mechanisms are involved in the regulation. PMID:16757746

Electrochemical Behavior of Quinoxalin-2-one Derivatives at Mercury Electrodes and Its Analytical Use

PubMed Central

Zimpl, Milan; Skopalova, Jana; Jirovsky, David; Bartak, Petr; Navratil, Tomas; Sedonikova, Jana; Kotoucek, Milan

2012-01-01

Derivatives of quinoxalin-2-one are interesting compounds with potential pharmacological activity. From this point of view, understanding of their electrochemical behavior is of great importance. In the present paper, a mechanism of electrochemical reduction of quinoxalin-2-one derivatives at mercury dropping electrode was proposed. Pyrazine ring was found to be the main electroactive center undergoing a pH-dependent two-electron reduction process. The molecule protonization of nitrogen in the position 4 precedes the electron acceptance forming a semiquinone radical intermediate which is relatively stable in acidic solutions. Its further reduction is manifested by separated current signal. A positive mesomeric effect of the nonprotonized amino group in the position 7 of the derivative III accelerates the semiquinone reduction yielding a single current wave. The suggested reaction mechanism was verified by means of direct current polarography, differential pulse, cyclic and elimination voltammetry, and coulometry with subsequent GC/MS analysis. The understanding of the mechanism was applied in developing of analytical method for the determination of the studied compounds. PMID:22666117

Adipocyte-derived Exosomal miRNAs: A Novel Mechanism for Obesity-Related Disease

PubMed Central

Ferrante, Sarah C; Nadler, Evan P; Pillai, Dinesh K; Hubal, Monica J; Wang, Zuyi; Wang, Justin M; Gordish-Dressman, Heather; Koeck, Emily; Sevilla, Samantha; Wiles, Andrew A; Freishtat, Robert J

2014-01-01

Background Obesity is frequently complicated by comorbid conditions, yet how excess adipose contributes is poorly understood. Although adipocytes in obese individuals induce systemic inflammation via secreted cytokines, another potential mediator has recently been identified (i.e. adipocyte-derived exosomes). We hypothesized that adipocyte-derived exosomes contain mediators capable of activating end-organ inflammatory and fibrotic signaling pathways. Methods We developed techniques to quantify and characterize exosomes shed by adipocytes from 7 obese (age: 12–17.5 years, BMI: 33–50 kg/m2) and 5 lean (age: 11–19 years, BMI: 22–25 kg/m2) subjects. Results Abundant exosomal miRNAs, but no mRNAs, were detected. Comparison of obese vs. lean visceral adipose donors detected 55 differentially-expressed miRNAs (p<0.05; fold change≥|1.2|). qRT-PCR confirmed downregulation of miR-148b (ratio = 0.2 [95% confidence interval = 0.1, 0.6]) and miR-4269 (0.3 [0.1, 0.8]), and upregulation of miR-23b (6.2 [2.2, 17.8]) and miR-4429 (3.8 [1.1 to 13.4]). Pathways analysis identified TGF-β signaling and Wnt/ β-catenin signaling among the top canonical pathways expected to be altered with visceral adiposity based on projected mRNA targets for the 55 differentially expressed miRNAs. A select mRNA target was validated in vitro. Conclusion These data show that visceral adipocytes shed exosomal-mediators predicted to regulate key end-organ inflammatory and fibrotic signaling pathways. PMID:25518011

Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective

PubMed Central

2015-01-01

Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are poorly understood. This ambiguity is likely due to the structural diversity of aldehyde derivatives and corresponding differences in chemical reactions and biological targets. To gain mechanistic insight, we have used parameters based on the hard and soft, acids and bases (HSAB) theory to profile the different aldehyde subclasses with respect to electronic character (softness, hardness), electrophilic reactivity (electrophilic index), and biological nucleophilic targets. Our analyses indicate that short chain aldehydes and longer chain saturated alkanals are hard electrophiles that cause toxicity by forming adducts with hard biological nucleophiles, e.g., primary nitrogen groups on lysine residues. In contrast, α,β-unsaturated carbonyl derivatives, alkenals, and the α-oxoaldehydes are soft electrophiles that preferentially react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes can therefore be grouped into subclasses according to common electronic characteristics (softness/hardness) and molecular mechanisms of toxicity. As we will discuss, the toxic potencies of these subgroups are generally related to corresponding electrophilicities. For some aldehydes, however, predictions of toxicity based on electrophilicity are less accurate due to inherent physicochemical variables that limit target accessibility, e.g., steric hindrance and solubility. The unsaturated aldehydes are also members of the conjugated type-2 alkene chemical class that includes α,β-unsaturated amide, ketone, and ester derivatives. Type-2 alkenes are electrophiles of varying softness and electrophilicity that share a common mechanism of toxicity. Therefore, exposure to an environmental mixture of unsaturated carbonyl derivatives could cause “type-2 alkene toxicity” through additive interactions

Menzerath-Altmann Law: Statistical Mechanical Interpretation as Applied to a Linguistic Organization

NASA Astrophysics Data System (ADS)

Eroglu, Sertac

2014-10-01

The distribution behavior described by the empirical Menzerath-Altmann law is frequently encountered during the self-organization of linguistic and non-linguistic natural organizations at various structural levels. This study presents a statistical mechanical derivation of the law based on the analogy between the classical particles of a statistical mechanical organization and the distinct words of a textual organization. The derived model, a transformed (generalized) form of the Menzerath-Altmann model, was termed as the statistical mechanical Menzerath-Altmann model. The derived model allows interpreting the model parameters in terms of physical concepts. We also propose that many organizations presenting the Menzerath-Altmann law behavior, whether linguistic or not, can be methodically examined by the transformed distribution model through the properly defined structure-dependent parameter and the energy associated states.

The Controllable Ball Joint Mechanism

NASA Astrophysics Data System (ADS)

Tung, Yung Cheng; Chieng, Wei-Hua; Ho, Shrwai

A controllable ball joint mechanism with three rotational degrees of freedom is proposed in this paper. The mechanism is composed of three bevel gears, one of which rotates with respect to a fixed frame and the others rotate with respect to individual floating frames. The output is the resultant motion of the differential motions by the motors that rotates the bevel gears at the fixed frame and the floating frames. The mechanism is capable of a large rotation, and the structure is potentially compact. The necessary inverse and forward kinematic analyses as well as the derivation of kinematic singularity are provided according to the kinematical equivalent structure described in this paper.

Canonical quantization of classical mechanics in curvilinear coordinates. Invariant quantization procedure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Błaszak, Maciej, E-mail: blaszakm@amu.edu.pl; Domański, Ziemowit, E-mail: ziemowit@amu.edu.pl

In the paper is presented an invariant quantization procedure of classical mechanics on the phase space over flat configuration space. Then, the passage to an operator representation of quantum mechanics in a Hilbert space over configuration space is derived. An explicit form of position and momentum operators as well as their appropriate ordering in arbitrary curvilinear coordinates is demonstrated. Finally, the extension of presented formalism onto non-flat case and related ambiguities of the process of quantization are discussed. -- Highlights: •An invariant quantization procedure of classical mechanics on the phase space over flat configuration space is presented. •The passage tomore » an operator representation of quantum mechanics in a Hilbert space over configuration space is derived. •Explicit form of position and momentum operators and their appropriate ordering in curvilinear coordinates is shown. •The invariant form of Hamiltonian operators quadratic and cubic in momenta is derived. •The extension of presented formalism onto non-flat case and related ambiguities of the quantization process are discussed.« less

Mechanical Properties of Transcription

NASA Astrophysics Data System (ADS)

Sevier, Stuart A.; Levine, Herbert

2017-06-01

The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

Reaction mechanisms in cellulose pyrolysis: a literature review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molton, P.M.; Demmitt, T.F.

1977-08-01

A bibliographic review of 195 references is presented outlining the history of the research into the mechanisms of cellulose pyrolysis. Topics discussed are: initial product identification, mechanism of initial formation of levoglucosan, from cellulose and from related compounds, decomposition of cellulose to other compounds, formation of aromatics, pyrolysis of levoglucosan, crosslinking of cellulose, pyrolytic reactions of cellulose derivatives, and the effects of inorganic salts on the pyrolysis mechanism. (JSR)

Quantum-mechanics-derived 13Cα chemical shift server (CheShift) for protein structure validation

PubMed Central

Vila, Jorge A.; Arnautova, Yelena A.; Martin, Osvaldo A.; Scheraga, Harold A.

2009-01-01

A server (CheShift) has been developed to predict 13Cα chemical shifts of protein structures. It is based on the generation of 696,916 conformations as a function of the φ, ψ, ω, χ1 and χ2 torsional angles for all 20 naturally occurring amino acids. Their 13Cα chemical shifts were computed at the DFT level of theory with a small basis set and extrapolated, with an empirically-determined linear regression formula, to reproduce the values obtained with a larger basis set. Analysis of the accuracy and sensitivity of the CheShift predictions, in terms of both the correlation coefficient R and the conformational-averaged rmsd between the observed and predicted 13Cα chemical shifts, was carried out for 3 sets of conformations: (i) 36 x-ray-derived protein structures solved at 2.3 Å or better resolution, for which sets of 13Cα chemical shifts were available; (ii) 15 pairs of x-ray and NMR-derived sets of protein conformations; and (iii) a set of decoys for 3 proteins showing an rmsd with respect to the x-ray structure from which they were derived of up to 3 Å. Comparative analysis carried out with 4 popular servers, namely SHIFTS, SHIFTX, SPARTA, and PROSHIFT, for these 3 sets of conformations demonstrated that CheShift is the most sensitive server with which to detect subtle differences between protein models and, hence, to validate protein structures determined by either x-ray or NMR methods, if the observed 13Cα chemical shifts are available. CheShift is available as a web server. PMID:19805131

Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents

PubMed Central

Zhang, Xiao-Fei; Sun, Rong-qin; Jia, Yi-fan; Chen, Qing; Tu, Rong-Fu; Li, Ke-ke; Zhang, Xiao-Dong; Du, Run-Lei; Cao, Ri-hui

2016-01-01

A series of novel harmine derivatives bearing a benzylindine substituent in position-1 of β-carboline ring were synthesized and evaluated as antitumor agents. The N2-benzylated β-carboline derivatives 3a–g represented the most interesting anticancer activities and compound 3c was found to be the most active agent to diverse cancer cell lines such as gastric carcinoma, melanoma and colorectal cancer. Notably, compound 3c showed low toxicity to normal cells. The treatment significantly induced cell apoptosis. Mechanistically, PI3K/AKT signaling pathway mediated compound 3c-induced apoptosis. Compound 3c inhibited phosphorylation of AKT and promoted the production of reactive oxygen species (ROS). The ROS scavenger, LNAC and GSH, could disturb the effect of compound 3c induced apoptosis and PI3K activity inhibitor LY294002 synergistically enhanced compound 3c efficacy. Moreover, the results from nude mice xenograft model showed that compound 3c treatment effectively inhibited tumor growth and decreased tumor weight. Collectively, our results demonstrated that compound 3c exerts apoptotic effect in cancer cells via suppression of phosphorylated AKT and evocation of ROS generation, which suggested that compound 3c might be served as a promising therapeutic agent for cancer treatment. PMID:27625151

DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants.

PubMed

Simmons, Steven J; Leyrer-Jackson, Jonna M; Oliver, Chicora F; Hicks, Callum; Muschamp, John W; Rawls, Scott M; Olive, M Foster

2018-05-11

Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.

Theoretical derivation of laser-dressed atomic states by using a fractal space

NASA Astrophysics Data System (ADS)

Duchateau, Guillaume

2018-05-01

The derivation of approximate wave functions for an electron submitted to both a Coulomb and a time-dependent laser electric fields, the so-called Coulomb-Volkov (CV) state, is addressed. Despite its derivation for continuum states does not exhibit any particular problem within the framework of the standard theory of quantum mechanics (QM), difficulties arise when considering an initially bound atomic state. Indeed the natural way of translating the unperturbed momentum by the laser vector potential is no longer possible since a bound state does not exhibit a plane wave form explicitly including a momentum. The use of a fractal space permits to naturally define a momentum for a bound wave function. Within this framework, it is shown how the derivation of laser-dressed bound states can be performed. Based on a generalized eikonal approach, a new expression for the laser-dressed states is also derived, fully symmetric relative to the continuum or bound nature of the initial unperturbed wave function. It includes an additional crossed term in the Volkov phase which was not obtained within the standard theory of quantum mechanics. The derivations within this fractal framework have highlighted other possible ways to derive approximate laser-dressed states in QM. After comparing the various obtained wave functions, an application to the prediction of the ionization probability of hydrogen targets by attosecond XUV pulses within the sudden approximation is provided. This approach allows to make predictions in various regimes depending on the laser intensity, going from the non-resonant multiphoton absorption to tunneling and barrier-suppression ionization.

Quantum mechanical/molecular mechanical/continuum style solvation model: time-dependent density functional theory.

PubMed

Thellamurege, Nandun M; Cui, Fengchao; Li, Hui

2013-08-28

A combined quantum mechanical/molecular mechanical/continuum (QM/MMpol/C) style method is developed for time-dependent density functional theory (TDDFT, including long-range corrected TDDFT) method, induced dipole polarizable force field, and induced surface charge continuum model. Induced dipoles and induced charges are included in the TDDFT equations to solve for the transition energies, relaxed density, and transition density. Analytic gradient is derived and implemented for geometry optimization and molecular dynamics simulation. QM/MMpol/C style DFT and TDDFT methods are used to study the hydrogen bonding of the photoactive yellow protein chromopore in ground state and excited state.

Potential roles of cell-derived microparticles in ischemic brain disease.

PubMed

Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

2009-10-01

The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

The effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate bone cement

NASA Astrophysics Data System (ADS)

Razali, N. N.; Sukardi, M. A.; Sopyan, I.; Mel, M.; Salleh, H. M.; Rahman, M. M.

2018-01-01

The objective of this study is to determine the effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate cement (CPC) for bone filling applications. Hydroxyapatite powder was synthesized via hydrothermal method using calcium oxide, CaO and ammonium dihydrogen phosphate, NH4H2PO4 as the calcium and phosphorus precursors respectively. The effects of calcium excess were evaluated by varying the CaO content at 0, 5 and 15 mole %. The precursors were then refluxed in distilled water at 90-100°C and dried overnight until the calcium phosphate powder was formed. CPC was then produced by mixing the synthesized powder with distilled water at the powder-to-liquid (P/L) ratio of 1.5. The result from the morphological properties of CPC shows the increase in agglomeration and particles size with 5 mole % of calcium excess but decreased with 15 mole % of calcium excess in CPC. This result was in agreement with the compressive strength result where the CPC increased its strength with 5 mole % of calcium excess but reduced with 15 mole % of calcium excess. The excess in calcium precursor also significantly improved the setting time but reduced the injectability of CPC.

Adipose-derived mesenchymal stem cells and regenerative medicine.

PubMed

Konno, Masamitsu; Hamabe, Atsushi; Hasegawa, Shinichiro; Ogawa, Hisataka; Fukusumi, Takahito; Nishikawa, Shimpei; Ohta, Katsuya; Kano, Yoshihiro; Ozaki, Miyuki; Noguchi, Yuko; Sakai, Daisuke; Kudoh, Toshihiro; Kawamoto, Koichi; Eguchi, Hidetoshi; Satoh, Taroh; Tanemura, Masahiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

2013-04-01

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Three-dimensional visualization of the Autographa californica multiple nucleopolyhedrovirus occlusion-derived virion envelopment process gives new clues as to its mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Yang; Li, Kunpeng; Tang, Peiping

2015-02-15

Baculoviruses produce two virion phenotypes, occlusion-derived virion (ODV) and budded virion (BV). ODV envelopment occurs in the nucleus. Morphogenesis of the ODV has been studied extensively; however, the mechanisms underlying microvesicle formation and ODV envelopment in nuclei remain unclear. In this study, we used electron tomography (ET) together with the conventional electron microscopy to study the envelopment of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ODV. Our results demonstrate that not only the inner but also the outer nuclear membrane can invaginate and vesiculate into microvesicles and that intranuclear microvesicles are the direct source of the ODV membrane. Five main events inmore » the ODV envelopment process are summarized, from which we propose a model to explain this process. - Highlights: • Both the inner and outer nuclear membranes could invaginate. • Both the inner and outer nuclear membranes could vesiculate into microvesicles. • Five main events in the ODV envelopment process are summarized. • A model is proposed to explain this ODV envelopment.« less

Gastrointestinal defense mechanisms.

PubMed

Said, Hyder; Kaunitz, Jonathan D

2016-11-01

To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon-derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLP-1 and GLP-2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreatic βcells but also has been implicated in having trophic effects on the intestinal epithelium. In addition, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion to improve gastric mucosal health and longevity. Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 and GLP-2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2018-01-01

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

PubMed

Sinitskiy, Anton V; Voth, Gregory A

2018-01-07

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Breast milk-derived exosomes promote intestinal epithelial cell growth.

PubMed

Hock, Alison; Miyake, Hiromu; Li, Bo; Lee, Carol; Ermini, Leonardo; Koike, Yuhki; Chen, Yong; Määttänen, Pekka; Zani, Augusto; Pierro, Agostino

2017-05-01

Breast milk administration prevents necrotizing enterocolitis (NEC). However, the mechanism remains unclear. Exosomes are cell-derived vesicles highly present in human milk and regulate intercellular signaling, inflammation, and immune response. We hypothesized that milk-derived exosomes beneficially affect intestinal epithelial cells. Rat milk was collected, and exosomes were isolated using ExoQuick reagent and visualized by Nanoparticle Tracking Analysis. Protein was extracted from encapsulating exosomes, and concentration was measured. 2×10 4 intestinal epithelial cells (IEC-18) were treated for five hours with 0.5-μg/μl exosomes, an equal volume of exosome-free milk, or control solution (PBS). IEC-18 viability was measured using a colorimetric assay (MTT), and gene expression was analyzed by qRT-PCR. Data were compared using one-way ANOVA with Bonferroni post-test. Rat milk was collected, and exosome isolation was confirmed. Compared to control, treatment with exosomes significantly increased IEC viability, proliferation, and stem cell activity (all p<0.05). However, administration of exosome-free milk had less significant effects. Rat milk-derived exosomes promote IEC viability, enhance proliferation, and stimulate intestinal stem cell activity. These findings provide insight into the mechanism of action of breast milk in the intestines. Exosome administration is a promising prevention method for infants at risk of developing NEC when breastfeeding is not tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism.

PubMed

Baer, Patrick C; Schubert, Ralf; Bereiter-Hahn, Jürgen; Plösser, Michaela; Geiger, Helmut

2009-05-01

Adult stem cells act as a pluripotent source of regenerative cells during tissue injury. Despite expanded research in stem cell biology, understanding how growth and migration of adipose-derived adult mesenchymal stem cells (ASC) are governed by interactions with growth factors is very limited. One important property of ASC is the presence of the epidermal growth factor (EGF) receptor and the cellular response to soluble EGF. Expression of the EGF receptor was proven by PCR and Western blotting. Signal transduction was analyzed by Western blotting and PhosFlow assay. EGF caused robust phosphorylation of SHC and ERK1/2, which could be inhibited by EGF receptor antagonist AG1478 and MEK inhibitor PD98059. ASC proliferation was determined by MTT assay. Stem cell migration was analyzed in a modified Boyden chamber. Incubation with EGF led to cell proliferation and induced cell migration, but did not change the undifferentiated state of the cells. In the kidney, injured renal tubular cells express high amounts of EGF. Therefore, our results may highlight a mechanism underlying renal regeneration. Thus, future in vivo studies that focus on the effects of EGF on recruitment of ASC to sites of injury are necessary.

Analysis and Evaluation of the Inhibitory Mechanism of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Derived from Casein Hydrolysate.

PubMed

Tu, Maolin; Liu, Hanxiong; Zhang, Ruyi; Chen, Hui; Mao, Fengjiao; Cheng, Shuzhen; Lu, Weihong; Du, Ming

2018-04-25

Casein hydrolysates exert various biological activities, and the responsible functional peptides are being identified from them continuously. In this study, the tryptic casein hydrolysate was fractionated by an ultrafiltration membrane (3 kDa), and the peptides were identified by capillary electrophoresis-quadrupole-time-of-flight-tandem mass spectrometry. Meanwhile, in silico methods were used to analyze the toxicity, solubility, stability, and affinity between the peptides and angiotensin-I-converting enzyme (ACE). Finally, a new angiotensin-I-converting enzyme inhibitory (ACEI) peptide, EKVNELSK, derived from α s1 -casein (fragment 35-42) was screened. The half maximal inhibitory concentration value of the peptide is 5.998 mM, which was determined by a high-performance liquid chromatography method. The Lineweaver-Burk plot indicated that this peptide is a mixed-type inhibitor against ACE. Moreover, Discovery Studio 2017 R2 software was adopted to perform molecular docking to propose the potential mechanisms underlying the ACEI activity of the peptide. These results indicated that EKVNELSK is a new ACEI peptide identified from casein hydrolysate.

The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

PubMed Central

Wang, Wei; Wang, Shi-Xin; Guan, Hua-Shi

2012-01-01

Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail. PMID:23235364

Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.

PubMed

Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio

2011-01-01

Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.

Tumor-derived exosomes and their role in cancer progression

PubMed Central

Whiteside, Theresa L

2017-01-01

Tumor cells actively produce, release and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon the contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as non-invasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation. PMID:27117662

Extracellular matrix-derived hydrogels for dental stem cell delivery.

PubMed

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

Tumor-Derived Exosomes and Their Role in Cancer Progression.

PubMed

Whiteside, Theresa L

2016-01-01

Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation. © 2016 Elsevier Inc. All rights reserved.

Deriving Laws from Ordering Relations

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.

2004-01-01

The effect of Richard T. Cox's contribution to probability theory was to generalize Boolean implication among logical statements to degrees of implication, which are manipulated using rules derived from consistency with Boolean algebra. These rules are known as the sum rule, the product rule and Bayes Theorem, and the measure resulting from this generalization is probability. In this paper, I will describe how Cox s technique can be further generalized to include other algebras and hence other problems in science and mathematics. The result is a methodology that can be used to generalize an algebra to a calculus by relying on consistency with order theory to derive the laws of the calculus. My goals are to clear up the mysteries as to why the same basic structure found in probability theory appears in other contexts, to better understand the foundations of probability theory, and to extend these ideas to other areas by developing new mathematics and new physics. The relevance of this methodology will be demonstrated using examples from probability theory, number theory, geometry, information theory, and quantum mechanics.

Plant Oil-Derived Epoxy Polymers toward Sustainable Biobased Thermosets.

PubMed

Wang, Zhongkai; Yuan, Liang; Ganewatta, Mitra S; Lamm, Meghan E; Rahman, Md Anisur; Wang, Jifu; Liu, Shengquan; Tang, Chuanbing

2017-06-01

Epoxy polymers (EPs) derived from soybean oil with varied chemical structures are synthesized. These polymers are then cured with anhydrides to yield soybean-oil-derived epoxy thermosets. The curing kinetic, thermal, and mechanical properties are well characterized. Due to the high epoxide functionality per epoxy polymer chain, these thermosets exhibit tensile strength over an order of magnitude higher than a control formulation with epoxidized soybean oil. More importantly, thermosetting materials ranging from soft elastomers to tough thermosets can be obtained simply by using different EPs and/or by controlling feed ratios of EPs to anhydrides. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization evaluation of cutting technology based on mechanical parts

NASA Astrophysics Data System (ADS)

Wang, Yu

2018-04-01

The relationship between the mechanical manufacturing process and the carbon emission is studied on the basis of the process of the mechanical manufacturing process. The formula of carbon emission calculation suitable for mechanical manufacturing process is derived. Based on this, a green evaluation method for cold machining process of mechanical parts is proposed. The application verification and data analysis of the proposed evaluation method are carried out by an example. The results show that there is a great relationship between the mechanical manufacturing process data and carbon emissions.

THz spectra of 1,4-naphthoquinones and its four derivatives

NASA Astrophysics Data System (ADS)

Wang, Weining; Li, Hongqi; Luo, Xiang; Zeng, Xiaoni

2008-03-01

Recently some naphthoquinone derivatives have been found with anticancer or other therapeutic properties, but also have some negative side effects. Numerous research projects have been conducted to investigate their properties and therapeutic mechanisms. With Terahertz Time-Domain Spectroscopy (THz-TDS), we have successfully obtained THz spectra of 1,4-naphthoquinone and its four derivatives in a series of naphthazarin - juglone - 1,4-naphthoquinone - menadione - plumbagin, in the range between 0.2 and 2.4~2.8 THz. Although these molecules are almost identical to each other, they have very distinctive THz spectra so that they can be identified much more easily than using conventional spectroscopy. We have comparatively analyzed their THz spectra, and found some possible correlations between THz spectra and molecular structures. These THz spectra cannot only be used as spectral fingerprint, but also provide us their conformational properties that can be used in study of their interaction with biomolecules to reveal their pharmaceutical mechanisms.

Acyl Meldrum's acid derivatives: application in organic synthesis

NASA Astrophysics Data System (ADS)

Janikowska, K.; Rachoń, J.; Makowiec, S.

2014-07-01

This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references.

Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses

PubMed Central

Coen, Natacha; Duraffour, Sophie; Topalis, Dimitri; Snoeck, Robert

2014-01-01

The susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha- and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-β-d-Arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2′-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin- and acyclovir-resistant rhadinoviruses in vitro and characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase. PMID:25267682

Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro.

PubMed

Živković, Marijana B; Matić, Ivana Z; Rodić, Marko V; Novaković, Irena T; Krivokuća, Ana M; Sladić, Dušan M; Krstić, Natalija M

2017-11-01

The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (E)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC 50 values from 8.5μM to 14.9μM), eight on HeLa cells (IC 50 values ranging from 8.9μM to 15.1μM) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC 50 values from 12.7μM to 25.6μM) than cisplatin (21.5μM) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activity

Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

PubMed Central

Massberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla R.; Busch, Dirk H.; Frampton, Jon; Gawaz, Meinrad

2006-01-01

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow–derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin− bone marrow–derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin− bone marrow–derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1α, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury. PMID:16618794

Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.

PubMed

Massberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla R; Busch, Dirk H; Frampton, Jon; Gawaz, Meinrad

2006-05-15

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Axioms for quantum mechanics: relativistic causality, retrocausality, and the existence of a classical limit

NASA Astrophysics Data System (ADS)

Rohrlich, Daniel

Y. Aharonov and A. Shimony both conjectured that two axioms - relativistic causality (``no superluminal signalling'') and nonlocality - so nearly contradict each other that only quantum mechanics reconciles them. Can we indeed derive quantum mechanics, at least in part, from these two axioms? No: ``PR-box'' correlations show that quantum correlations are not the most nonlocal correlations consistent with relativistic causality. Here we replace ``nonlocality'' with ``retrocausality'' and supplement the axioms of relativistic causality and retrocausality with a natural and minimal third axiom: the existence of a classical limit, in which macroscopic observables commute. That is, just as quantum mechanics has a classical limit, so must any generalization of quantum mechanics. In this limit, PR-box correlations violaterelativistic causality. Generalized to all stronger-than-quantum bipartite correlations, this result is a derivation of Tsirelson's bound (a theorem of quantum mechanics) from the three axioms of relativistic causality, retrocausality and the existence of a classical limit. Although the derivation does not assume quantum mechanics, it points to the Hilbert space structure that underlies quantum correlations. I thank the John Templeton Foundation (Project ID 43297) and the Israel Science Foundation (Grant No. 1190/13) for support.

Gastric cancer-derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier.

PubMed

Deng, Guang; Qu, Jinglei; Zhang, Ye; Che, Xiaofang; Cheng, Yu; Fan, Yibo; Zhang, Simeng; Na, Di; Liu, Yunpeng; Qu, Xiujuan

2017-07-01

An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer-derived exosomes is through concurrent apoptosis and mesothelial-to-mesenchymal transition (MMT). Additionally, upregulation of p-ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma. © 2017 Federation of European Biochemical Societies.

Photochemistry of Naphthopyrans and Derivatives: A Computational Experiment for Upper-Level Undergraduates or Graduate Students

ERIC Educational Resources Information Center

Castet, Frédéric; Méreau, Raphaël; Liotard, Daniel

2014-01-01

In this computational experiment, students use advanced quantum chemistry tools to simulate the photochromic reaction mechanism in naphthopyran derivatives. The first part aims to make students familiar with excited-state reaction mechanisms and addresses the photoisomerization of the benzopyran molecule by means of semiempirical quantum chemical…

Diesel Mechanics. Ohio's Competency Analysis Profile.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

This Ohio Competency Analysis Profile (OCAP), derived from a modified Developing a Curriculum (DACUM) process, is a current comprehensive and verified employer competency program list for diesel mechanics. Each unit (with or without subunits) contains competencies and competency builders that identify the occupational, academic, and employability…

Characterization of corncob-derived biochar and pyrolysis kinetics in comparison with corn stalk and sawdust.

PubMed

Liu, Xuan; Zhang, Yang; Li, Zifu; Feng, Rui; Zhang, Yaozhong

2014-10-01

In this study, thermal and physicochemical characterization results of corncob (CC) and its derived biochars were analyzed and differentiated from sawdust (SD) and cornstalk (CS). The pyrolysis temperature shows the largest effect on the yield of biochar produced compare with residing time, heating rate, and feedstock particle size. The CC-derived biochars produced at temperatures ranging from 300 to 600°C were analyzed. The CC was thermochemically altered to a stable biochar when the pyrolysis temperature was set to over 500°C. To deduce the reaction mechanism of the CC during the major thermal decomposition stage, 16 mechanisms in solid-state reactions were applied. The reaction order and nucleation mechanisms described the thermal decomposition of the CC. By using the best-fitted mechanisms, the kinetic parameters were calculated. The weight active energy of the CC was 122.42kJ/mol, which was the lowest value compared to those of CS and SD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gravitropic mechanisms derived from space experiments and magnetic gradients.

NASA Astrophysics Data System (ADS)

Hasenstein, Karl H.; Park, Myoung Ryoul

2016-07-01

Gravitropism is the result of a complex sequence of events that begins with the movement of dense particles, typically starch-filled amyloplasts in response to reorientation. Although these organelles change positions, it is not clear whether the critical signal is derived from sedimentation or dynamic interactions of amyloplasts with relevant membranes. Substituting gravity by high-gradient magnetic fields (HGMF) provides a localized stimulus for diamagnetic starch that is specific for amyloplasts and comparable to gravity without affecting other organelles. Experiments with Brassica rapa showed induction of root curvature by HGMF when roots moved sufficiently close to the magnetic gradient-inducing foci. The focused and short-range effectiveness of HGMFs provided a gravity-like stimulus and affected related gene expression. Root curvature was sensitive to the mutual alignment between roots and HGMF direction. Unrelated to any HGMF effects, the size of amyloplasts in space-grown roots increased by 30% compared to ground controls and suggests enhanced sensitivity in a gravity-reduced environment. Accompanying gene transcription studies showed greater differences between HGMF-exposed and space controls than between space and ground controls. This observation may lead to the identification of gravitropism-relevant genes. However, space grown roots showed stronger transcription of common reference genes such as actin and ubiquitin in magnetic fields than in non-magnetic conditions. In contrast, α-amylase, glucokinase and PIN encoding genes were transcribed stronger under non-magnetic conditions than under HGMF. The large number of comparisons between space, ground, and HGMF prompted the assessment of transcription differences between root segments, root-shoot junction, and seeds. Because presumed transcription of reference genes varied more than genes of interest, changes in gene expression cannot be based on reference genes. The data provide an example of complex

Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

PubMed

Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

2016-02-01

Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

PubMed

Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

2016-04-13

Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives.

PubMed

Zhao, Ximei; Xi, Xin; Hu, Zhan; Wu, Wenjun; Zhang, Jiwen

2016-02-24

The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

RNA encapsidation by SV40-derived nanoparticles follows a rapid two-state mechanism

PubMed Central

Kler, Stanislav; Asor, Roi; Li, Chenglei; Ginsburg, Avi; Harries, Daniel; Oppenheim, Ariella; Zlotnick, Adam; Raviv, Uri

2012-01-01

Remarkably, uniform virus-like particles self-assemble in a process that appears to follow a rapid kinetic mechanism. The mechanisms by which spherical viruses assemble from hundreds of capsid proteins around nucleic acid, however, are yet unresolved. Using Time-Resolved Small-Angle X-ray Scattering (TR-SAXS) we have been able to directly visualize SV40 VP1 pentamers encapsidating short RNA molecules (500 mers). This assembly process yields T = 1 icosahedral particles comprised of 12 pentamers and one RNA molecule. The reaction is nearly 1/3 complete within 35 milliseconds, following a two–state kinetic process with no detectable intermediates. Theoretical analysis of kinetics, using a master equation, shows that the assembly process nucleates at the RNA and continues by a cascade of elongation reactions in which one VP1 pentamer is added at a time, with a rate of approximately 109 M−1 s−1. The reaction is highly robust and faster than the predicted diffusion limit. The emerging molecular mechanism, which appears to be general to viruses that assemble around nucleic acids, implicates long-ranged electrostatic interactions. The model proposes that the growing nucleo-protein complex acts as an electrostatic antenna that attracts other capsid subunits for the encapsidation process. PMID:22329660

Mechanics of plant fruit hooks

PubMed Central

Chen, Qiang; Gorb, Stanislav N.; Gorb, Elena; Pugno, Nicola

2013-01-01

Hook-like surface structures, observed in some plant species, play an important role in the process of plant growth and seed dispersal. In this study, we developed an elastic model and further used it to investigate the mechanical behaviour of fruit hooks in four plant species, previously measured in an experimental study. Based on Euler–Bernoulli beam theory, the force–displacement relationship is derived, and its Young's modulus is obtained. The result agrees well with the experimental data. The model aids in understanding the mechanics of hooks, and could be used in the development of new bioinspired Velcro-like materials. PMID:23365190

FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

PubMed Central

Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

Spectrum of activity and mechanisms of resistance of various nucleoside derivatives against gammaherpesviruses.

PubMed

Coen, Natacha; Duraffour, Sophie; Topalis, Dimitri; Snoeck, Robert; Andrei, Graciela

2014-12-01

The susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha- and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-β-D-Arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2'-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin- and acyclovir-resistant rhadinoviruses in vitro and characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

PubMed Central

2013-01-01

Background Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. Results We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Conclusion Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on

Recent advances in gossypol derivatives and analogs: a chemistry and biology view.

PubMed

Lu, Yuzhi; Li, Jun; Dong, Chun-E; Huang, Jian; Zhou, Hai-Bing; Wang, Wei

2017-07-01

Gossypol as a natural occurring polyphenol has been studied in a wide range of therapeutic contexts for a long time. The chemical modifications on gossypol were limited due to the unique chemical properties of polyphenols. The design and synthesis of gossypol derivatives and the exploration of their biological activities are the interest of the synthetic chemists, medicinal chemists and pharmacologists. Thus, the progress of diverse gossypol derivatives and analogs' synthesis, biological activities, mechanism elucidation and drug discovery based on gossypol scaffold is summarized.

Mechanical properties of sol–gel derived SiO2 nanotubes

PubMed Central

Antsov, Mikk; Vlassov, Sergei; Dorogin, Leonid M; Vahtrus, Mikk; Zabels, Roberts; Lange, Sven; Lõhmus, Rünno

2014-01-01

Summary The mechanical properties of thick-walled SiO2 nanotubes (NTs) prepared by a sol–gel method while using Ag nanowires (NWs) as templates were measured by using different methods. In situ scanning electron microscopy (SEM) cantilever beam bending tests were carried out by using a nanomanipulator equipped with a force sensor in order to investigate plasticity and flexural response of NTs. Nanoindentation and three point bending tests of NTs were performed by atomic force microscopy (AFM) under ambient conditions. Half-suspended and three-point bending tests were processed in the framework of linear elasticity theory. Finite element method simulations were used to extract Young’s modulus values from the nanoindentation data. Finally, the Young’s moduli of SiO2 NTs measured by different methods were compared and discussed. PMID:25383292

Adipose-derived stromal cells for the reconstruction of a human vesical equivalent.

PubMed

Rousseau, Alexandre; Fradette, Julie; Bernard, Geneviève; Gauvin, Robert; Laterreur, Véronique; Bolduc, Stéphane

2015-11-01

Despite a wide panel of tissue-engineering models available for vesical reconstruction, the lack of a differentiated urothelium remains their main common limitation. For the first time to our knowledge, an entirely human vesical equivalent, free of exogenous matrix, has been reconstructed using the self-assembly method. Moreover, we tested the contribution of adipose-derived stromal cells, an easily available source of mesenchymal cells featuring many potential advantages, by reconstructing three types of equivalent, named fibroblast vesical equivalent, adipose-derived stromal cell vesical equivalent and hybrid vesical equivalent--the latter containing both adipose-derived stromal cells and fibroblasts. The new substitutes have been compared and characterized for matrix composition and organization, functionality and mechanical behaviour. Although all three vesical equivalents displayed adequate collagen type I and III expression, only two of them, fibroblast vesical equivalent and hybrid vesical equivalent, sustained the development of a differentiated and functional urothelium. The presence of uroplakins Ib, II and III and the tight junction marker ZO-1 was detected and correlated with impermeability. The mechanical resistance of these tissues was sufficient for use by surgeons. We present here in vitro tissue-engineered vesical equivalents, built without the use of any exogenous matrix, able to sustain mechanical stress and to support the formation of a functional urothelium, i.e. able to display a barrier function similar to that of native tissue. Copyright © 2013 John Wiley & Sons, Ltd.

Exact Descriptions of General Relativity Derived from Newtonian Mechanics within Curved Geometries

NASA Astrophysics Data System (ADS)

Savickas, David

2015-04-01

General relativity and Newtonian mechanics are shown to be exactly related when Newton's second law is written in a curved geometry by using the physical components of a vector as is defined in tensor calculus. By replacing length within the momentum's velocity by the vector metric in a curved geometry the second law can then be shown to be exactly identical to the geodesic equation of motion occurring in general relativity. When time's vector direction is constant, as similarly occurs in Newtonian mechanics, this equation can be reduced to a curved three-dimensional equation of motion that yields the the Schwarzschild equations of motion for an isolated particle. They can be used to describe gravitational behavior for any array of masses for which the Newtonian gravitational potential is known, and is shown to describe a mass particle's behavior in the gravitational field of a thin mass-rod. This use of Newton's laws allows relativistic behavior to be described in a physically comprehensible manner. D. Savickas, Int. J. Mod. Phys. D 23 1430018, (2014).

A practical iterative PID tuning method for mechanical systems using parameter chart

NASA Astrophysics Data System (ADS)

Kang, M.; Cheong, J.; Do, H. M.; Son, Y.; Niculescu, S.-I.

2017-10-01

In this paper, we propose a method of iterative proportional-integral-derivative parameter tuning for mechanical systems that possibly possess hidden mechanical resonances, using a parameter chart which visualises the closed-loop characteristics in a 2D parameter space. We employ a hypothetical assumption that the considered mechanical systems have their upper limit of the derivative feedback gain, from which the feasible region in the parameter chart becomes fairly reduced and thus the gain selection can be extremely simplified. Then, a two-directional parameter search is carried out within the feasible region in order to find the best set of parameters. Experimental results show the validity of the assumption used and the proposed parameter tuning method.

Experts' understanding of partial derivatives using the partial derivative machine

NASA Astrophysics Data System (ADS)

Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

2015-12-01

[This paper is part of the Focused Collection on Upper Division Physics Courses.] Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. In this paper, we report on an initial study of expert understanding of partial derivatives across three disciplines: physics, engineering, and mathematics. We report on the central research question of how disciplinary experts understand partial derivatives, and how their concept images of partial derivatives differ, with a focus on experimentally measured quantities. Using the partial derivative machine (PDM), we probed expert understanding of partial derivatives in an experimental context without a known functional form. In particular, we investigated which representations were cued by the experts' interactions with the PDM. Whereas the physicists and engineers were quick to use measurements to find a numeric approximation for a derivative, the mathematicians repeatedly returned to speculation as to the functional form; although they were comfortable drawing qualitative conclusions about the system from measurements, they were reluctant to approximate the derivative through measurement. On a theoretical front, we found ways in which existing frameworks for the concept of derivative could be expanded to include numerical approximation.

Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups.

PubMed

Butler, Kyle V; He, Rong; McLaughlin, Kathryn; Vistoli, Giulio; Langley, Brett; Kozikowski, Alan P

2009-08-01

A series of small-molecule histone deacetylase (HDAC) inhibitors, which feature zinc binding groups derived from cysteine, were synthesized. These inhibitors were tested against multiple HDAC isoforms, and the most potent, compound 10, was determined to have IC(50) values below 1 microM. The compounds were also tested in a cellular assay of oxidative stress-induced neurodegeneration. Many of the inhibitors gave near-complete protection against cell death at 10 microM without the neurotoxicity seen with hydroxamic acid-based inhibitors, and were far more neuroprotective than HDAC inhibitors currently in clinical trials. Both enantiomers of cysteine were used in the synthesis of a variety of novel zinc-binding groups (ZBGs). Derivatives of L-cysteine were active in the HDAC inhibition assays, while the derivatives of D-cysteine were inactive. Notably, the finding that both the D- and L-cysteine derivatives were active in the neuroprotection assays suggests that multiple mechanisms are working to protect the neurons from cell death. Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine.

Financial derivative pricing under probability operator via Esscher transfomation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Achi, Godswill U., E-mail: achigods@yahoo.com

2014-10-24

The problem of pricing contingent claims has been extensively studied for non-Gaussian models, and in particular, Black- Scholes formula has been derived for the NIG asset pricing model. This approach was first developed in insurance pricing{sup 9} where the original distortion function was defined in terms of the normal distribution. This approach was later studied6 where they compared the standard Black-Scholes contingent pricing and distortion based contingent pricing. So, in this paper, we aim at using distortion operators by Cauchy distribution under a simple transformation to price contingent claim. We also show that we can recuperate the Black-Sholes formula usingmore » the distribution. Similarly, in a financial market in which the asset price represented by a stochastic differential equation with respect to Brownian Motion, the price mechanism based on characteristic Esscher measure can generate approximate arbitrage free financial derivative prices. The price representation derived involves probability Esscher measure and Esscher Martingale measure and under a new complex valued measure φ (u) evaluated at the characteristic exponents φ{sub x}(u) of X{sub t} we recuperate the Black-Scholes formula for financial derivative prices.« less

Financial derivative pricing under probability operator via Esscher transfomation

NASA Astrophysics Data System (ADS)

Achi, Godswill U.

2014-10-01

The problem of pricing contingent claims has been extensively studied for non-Gaussian models, and in particular, Black- Scholes formula has been derived for the NIG asset pricing model. This approach was first developed in insurance pricing9 where the original distortion function was defined in terms of the normal distribution. This approach was later studied6 where they compared the standard Black-Scholes contingent pricing and distortion based contingent pricing. So, in this paper, we aim at using distortion operators by Cauchy distribution under a simple transformation to price contingent claim. We also show that we can recuperate the Black-Sholes formula using the distribution. Similarly, in a financial market in which the asset price represented by a stochastic differential equation with respect to Brownian Motion, the price mechanism based on characteristic Esscher measure can generate approximate arbitrage free financial derivative prices. The price representation derived involves probability Esscher measure and Esscher Martingale measure and under a new complex valued measure φ (u) evaluated at the characteristic exponents φx(u) of Xt we recuperate the Black-Scholes formula for financial derivative prices.

Thermodynamics and statistical mechanics. [thermodynamic properties of gases

NASA Technical Reports Server (NTRS)

1976-01-01

The basic thermodynamic properties of gases are reviewed and the relations between them are derived from the first and second laws. The elements of statistical mechanics are then formulated and the partition function is derived. The classical form of the partition function is used to obtain the Maxwell-Boltzmann distribution of kinetic energies in the gas phase and the equipartition of energy theorem is given in its most general form. The thermodynamic properties are all derived as functions of the partition function. Quantum statistics are reviewed briefly and the differences between the Boltzmann distribution function for classical particles and the Fermi-Dirac and Bose-Einstein distributions for quantum particles are discussed.

Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

PubMed

Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

2017-01-01

Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Supersymmetric symplectic quantum mechanics

NASA Astrophysics Data System (ADS)

de Menezes, Miralvo B.; Fernandes, M. C. B.; Martins, Maria das Graças R.; Santana, A. E.; Vianna, J. D. M.

2018-02-01

Symplectic Quantum Mechanics SQM considers a non-commutative algebra of functions on a phase space Γ and an associated Hilbert space HΓ to construct a unitary representation for the Galilei group. From this unitary representation the Schrödinger equation is rewritten in phase space variables and the Wigner function can be derived without the use of the Liouville-von Neumann equation. In this article we extend the methods of supersymmetric quantum mechanics SUSYQM to SQM. With the purpose of applications in quantum systems, the factorization method of the quantum mechanical formalism is then set within supersymmetric SQM. A hierarchy of simpler hamiltonians is generated leading to new computation tools for solving the eigenvalue problem in SQM. We illustrate the results by computing the states and spectra of the problem of a charged particle in a homogeneous magnetic field as well as the corresponding Wigner function.

Evolutionary Trends in the Jaw Adductor Mechanics of Ornithischian Dinosaurs.

PubMed

Nabavizadeh, Ali

2016-03-01

Jaw mechanics in ornithischian dinosaurs have been widely studied for well over a century. Most of these studies, however, use only one or few taxa within a given ornithischian clade as a model for feeding mechanics across the entire clade. In this study, mandibular mechanical advantages among 52 ornithischian genera spanning all subclades are calculated using 2D lever arm methods. These lever arm calculations estimate the effect of jaw shape and difference in adductor muscle line of action on relative bite forces along the jaw. Results show major instances of overlap between taxa in tooth positions at which there was highest mechanical advantage. A relatively low bite force is seen across the tooth row among thyreophorans (e.g., stegosaurs and ankylosaurs), with variation among taxa. A convergent transition occurs from a more evenly distributed bite force along the jaw in basal ornithopods and basal marginocephalians to a strong distal bite force in hadrosaurids and ceratopsids, respectively. Accordingly, adductor muscle vector angles show repeated trends from a mid-range caudodorsal orientation in basal ornithischians to a decrease in vector angles indicating more caudally oriented jaw movements in derived taxa (e.g., derived thyreophorans, basal ornithopods, lambeosaurines, pachycephalosaurs, and derived ceratopsids). Analyses of hypothetical jaw morphologies were also performed, indicating that both the coronoid process and lowered jaw joint increase moment arm length therefore increasing mechanical advantage of the jaw apparatus. Adaptive trends in craniomandibular anatomy show that ornithischians evolved more complex feeding apparatuses within different clades as well as morphological convergences between clades. © 2016 Wiley Periodicals, Inc.

[Effect of taspine derivatives on human liver cancer SMMC7721].

PubMed

Zhang, Yan-min; Wang, Nan; Dai, Bing-ling; He, Lang-chong

2011-07-01

To analyse the inhibition effect of taspine derivatives on human Liver cancer SMMC7721 cell and its mechanism. The effects of five taspine derivatives on SMMC7721 cell growth were determined by MTT. The flow cytometry was used to determine the cell cycle. The effects of Tas-D1 on the EGF and VEGF in SMMC7721 cell were determined by ELISA. The mRNA level of EGF and VEGF in SMMC7721 cell was determined by RT-PCR. The MTT assay demonstrated that the taspine derivative Tas-D1 significantly inhibited the growth of SMMC7721 cell in a dose-dependent manner. Cell was stopped at S phase by Tas-D1. Tas-D1 inhibited the expression of EGF and VEGF and their mRNA in a dose-dependent manner (P<0.05). The taspine derivative Tas-D1 can inhibit the growth of human Liver cancer SMMC7721 cell and change cell cycle, which may be related to the inhibition of EGF and VEGF expression.

Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons.

PubMed

Wainger, Brian J; Kiskinis, Evangelos; Mellin, Cassidy; Wiskow, Ole; Han, Steve S W; Sandoe, Jackson; Perez, Numa P; Williams, Luis A; Lee, Seungkyu; Boulting, Gabriella; Berry, James D; Brown, Robert H; Cudkowicz, Merit E; Bean, Bruce P; Eggan, Kevin; Woolf, Clifford J

2014-04-10

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A relation between deformed superspace and Lee-Wick higher-derivative theories

NASA Astrophysics Data System (ADS)

Dias, M.; Ferrari, A. F.; Palechor, C. A.; Senise, C. R., Jr.

2015-07-01

We propose a non-anticommutative superspace that relates to the Lee-Wick type of higher-derivative theories, which are known for their interesting properties and have led to proposals of phenomenologically viable higher-derivative extensions of the Standard Model. The deformation of superspace we consider does not preserve supersymmetry or associativity in general, but, we show that a non-anticommutative version of the Wess-Zumino model can be properly defined. In fact, the definition of chiral and antichiral superfields turns out to be simpler in our case than in the well known N=1/2 supersymmetric case. We show that when the theory is truncated at the first nontrivial order in the deformation parameter, supersymmetry is restored, and we end up with a well-known Lee-Wick type of higher-derivative extension of the Wess-Zumino model. Thus, we show how non-anticommutativity could provide an alternative mechanism for generating these higher-derivative theories.

Marathon running increases circulating endothelial- and thrombocyte-derived microparticles.

PubMed

Schwarz, Viktoria; Düsing, Philip; Liman, Thomas; Werner, Christian; Herm, Juliane; Bachelier, Katrin; Krüll, Matthias; Brechtel, Lars; Jungehulsing, Gerhard J; Haverkamp, Wilhelm; Böhm, Michael; Endres, Matthias; Haeusler, Karl Georg; Laufs, Ulrich

2018-02-01

Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 10 9 /l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 10 9 /l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run ( p < 0.0001). Endothelial-derived microparticles were acutely increased ( p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles ( p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run ( p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further

47 CFR 54.709 - Computations of required contributions to universal service support mechanisms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contributors' interstate and international revenues derived from domestic end users for telecommunications or... will be contributors' projected collected interstate and international revenues derived from domestic... mechanisms to the total end-user interstate and international telecommunications revenues, net of prior...

Selected topics of fluid mechanics

USGS Publications Warehouse

Kindsvater, Carl E.

1958-01-01

The fundamental equations of fluid mechanics are specific expressions of the principles of motion which are ascribed to Isaac Newton. Thus, the equations which form the framework of applied fluid mechanics or hydraulics are, in addition to the equation of continuity, the Newtonian equations of energy and momentum. These basic relationships are also the foundations of river hydraulics. The fundamental equations are developed in this report with sufficient rigor to support critical examinations of their applicability to most problems met by hydraulic engineers of the Water Resources Division of the United States Geological Survey. Physical concepts are emphasized, and mathematical procedures are the simplest consistent with the specific requirements of the derivations. In lieu of numerical examples, analogies, and alternative procedures, this treatment stresses a brief methodical exposition of the essential principles. An important objective of this report is to prepare the user to read the literature of the science. Thus, it begins With a basic vocabulary of technical symbols, terms, and concepts. Throughout, emphasis is placed on the language of modern fluid mechanics as it pertains to hydraulic engineering. The basic differential and integral equations of simple fluid motion are derived, and these equations are, in turn, used to describe the essential characteristics of hydrostatics and piezometry. The one-dimensional equations of continuity and motion are defined and are used to derive the general discharge equation. The flow net is described as a means of demonstrating significant characteristics of two-dimensional irrotational flow patterns. A typical flow net is examined in detail. The influence of fluid viscosity is described as an obstacle to the derivation of general, integral equations of motion. It is observed that the part played by viscosity is one which is usually dependent on experimental evaluation. It follows that the dimensionless ratios known as

Recent Advances in Nanocomposite Materials of Graphene Derivatives with Polysaccharides

PubMed Central

Terzopoulou, Zoi; Kyzas, George Z.; Bikiaris, Dimitrios N.

2015-01-01

This review article presents the recent advances in syntheses and applications of nanocomposites consisting of graphene derivatives with various polysaccharides. Graphene has recently attracted much interest in the materials field due to its unique 2D structure and outstanding properties. To follow, the physical and mechanical properties of graphene are then introduced. However it was observed that the synthesis of graphene-based nanocomposites had become one of the most important research frontiers in the application of graphene. Therefore, this review also summarizes the recent advances in the synthesis of graphene nanocomposites with polysaccharides, which are abundant in nature and are easily synthesized bio-based polymers. Polysaccharides can be classified in various ways such as cellulose, chitosan, starch, and alginates, each group with unique and different properties. Alginates are considered to be ideal for the preparation of nanocomposites with graphene derivatives due to their environmental-friendly potential. The characteristics of such nanocomposites are discussed here and are compared with regard to their mechanical properties and their various applications. PMID:28787964

Mechanical discrete simulator of the electro-mechanical lift with n:1 roping

NASA Astrophysics Data System (ADS)

Alonso, F. J.; Herrera, I.

2016-05-01

The design process of new products in lift engineering is a difficult task due to, mainly, the complexity and slenderness of the lift system, demanding a predictive tool for the lift mechanics. A mechanical ad-hoc discrete simulator, as an alternative to ‘general purpose’ mechanical simulators is proposed. Firstly, the synthesis and experimentation process that has led to establish a suitable model capable of simulating accurately the response of the electromechanical lift is discussed. Then, the equations of motion are derived. The model comprises a discrete system of 5 vertically displaceable masses (car, counterweight, car frame, passengers/loads and lift drive), an inertial mass of the assembly tension pulley-rotor shaft which can rotate about the machine axis and 6 mechanical connectors with 1:1 suspension layout. The model is extended to any n:1 roping lift by setting 6 equivalent mechanical components (suspension systems for car and counterweight, lift drive silent blocks, tension pulley-lift drive stator and passengers/load equivalent spring-damper) by inductive inference from 1:1 and generalized 2:1 roping system. The application to simulate real elevator systems is proposed by numeric time integration of the governing equations using the Kutta-Meden algorithm and implemented in a computer program for ad-hoc elevator simulation called ElevaCAD.

Concept for Highly Mechanized Data Processing, Project 111.

DTIC Science & Technology

A concept is developed for a highly mechanized maintenance data processing system capable of deriving factors, influences, and correlations to raise...the level of logistics knowledge and lead to the design of a management-control system. (Author)

Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ.

PubMed

Yockey, Oliver P; Jha, Vikash; Ghodke, Pratibha P; Xu, Tianzuo; Xu, Wenyan; Ling, Hong; Pradeepkumar, P I; Zhao, Linlin

2017-11-20

DNA damage impinges on genetic information flow and has significant implications in human disease and aging. Lucidin-3-O-primeveroside (LuP) is an anthraquinone derivative present in madder root, which has been used as a coloring agent and food additive. LuP can be metabolically converted to genotoxic compound lucidin, which subsequently forms lucidin-specific N 2 -2'-deoxyguanosine (N 2 -dG) and N 6 -2'-deoxyadenosine (N 6 -dA) DNA adducts. Lucidin is mutagenic and carcinogenic in rodents but has low carcinogenic risks in humans. To understand the molecular mechanism of low carcinogenicity of lucidin in humans, we performed DNA replication assays using site-specifically modified oligodeoxynucleotides containing a structural analogue (LdG) of lucidin-N 2 -dG DNA adduct and determined the crystal structures of DNA polymerase (pol) κ in complex with LdG-bearing DNA and an incoming nucleotide. We examined four human pols (pol η, pol ι, pol κ, and Rev1) in their efficiency and accuracy during DNA replication with LdG; these pols are key players in translesion DNA synthesis. Our results demonstrate that pol κ efficiently and accurately replicates past the LdG adduct, whereas DNA replication by pol η, pol ι is compromised to different extents. Rev1 retains its ability to incorporate dCTP opposite the lesion albeit with decreased efficiency. Two ternary crystal structures of pol κ illustrate that the LdG adduct is accommodated by pol κ at the enzyme active site during insertion and postlesion-extension steps. The unique open active site of pol κ allows the adducted DNA to adopt a standard B-form for accurate DNA replication. Collectively, these biochemical and structural data provide mechanistic insights into the low carcinogenic risk of lucidin in humans.

Novel 16-substituted bifunctional derivatives of huperzine B: multifunctional cholinesterase inhibitors

PubMed Central

Shi, Yu-fang; Zhang, Hai-yan; Wang, Wei; Fu, Yan; Xia, Yu; Tang, Xi-can; Bai, Dong-lu; He, Xu-chang

2009-01-01

Aim: To design novel bifunctional derivatives of huperzine B (HupB) based on the concept of dual binding site of acetylcholinesterase (AChE) and evaluate their pharmacological activities for seeking new drug candidates against Alzheimer's disease (AD). Methods: Novel 16-substituted bifunctional derivatives of HupB were synthesized through chemical reactions. The inhibitory activities of the derivatives toward AChE and butyrylcholinesterase (BuChE) were determined in vitro by modified Ellman's method. Cell viability was quantified by the reduction of MTT. Results: A new preparative method was developed for the generation of 16-substituted derivatives of HupB, and pharmacological trials indicated that the derivatives were multifunctional cholinesterase inhibitors targeting both AChE and BuChE. Among the derivatives tested, 9c, 9e, 9f, and 9i were 480 to 1360 times more potent as AChE inhibitors and 370 to 1560 times more potent as BuChE inhibitors than the parent HupB. Further preliminary pharmacological trials of derivatives 9c and 9i were performed, including examining the mechanism of AChE inhibition, the substrate kinetics of the enzyme inhibition, and protection against hydrogen peroxide (H2O2)-induced cytotoxicity in PC12 cells. Conclusion: Preliminary pharmacological evaluation indicated that 16-substituted derivatives of HupB, particularly 9c and 9i, would be potentially valuable new drug candidates for AD therapy, and further exploration is needed to evaluate their pharmacological and clinical efficacies. PMID:19578388

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

PubMed

Walmsley, Amanda M; Kirk, Dwayne D; Mason, Hugh S

2003-03-03

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

System and method for deriving a process-based specification

NASA Technical Reports Server (NTRS)

Hinchey, Michael Gerard (Inventor); Rouff, Christopher A. (Inventor); Rash, James Larry (Inventor)

2009-01-01

A system and method for deriving a process-based specification for a system is disclosed. The process-based specification is mathematically inferred from a trace-based specification. The trace-based specification is derived from a non-empty set of traces or natural language scenarios. The process-based specification is mathematically equivalent to the trace-based specification. Code is generated, if applicable, from the process-based specification. A process, or phases of a process, using the features disclosed can be reversed and repeated to allow for an interactive development and modification of legacy systems. The process is applicable to any class of system, including, but not limited to, biological and physical systems, electrical and electro-mechanical systems in addition to software, hardware and hybrid hardware-software systems.

Mechanism of N[superscript 10]-formyltetrahydrofolate synthetase derived from complexes with intermediates and inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Celeste, Lesa R.; Chai, Geqing; Bielak, Magdalena

N{sup 10}-formyltetrahydrofolate synthetase (FTHFS) is a folate enzyme that catalyzes the formylation of tetrahydrofolate (THF) in an ATP dependent manner. Structures of FTHFS from the thermophilic homoacetogen, Moorella thermoacetica, complexed with (1) a catalytic intermediate-formylphosphate (XPO) and product-ADP; (2) with an inhibitory substrate analog-folate; (3) with XPO and an inhibitory THF analog, ZD9331, were used to analyze the enzyme mechanism. Nucleophilic attack of the formate ion on the gamma phosphate of ATP leads to the formation of XPO and the first product ADP. A channel that leads to the putative formate binding pocket allows for the binding of ATP andmore » formate in random order. Formate binding is due to interactions with the gamma-phosphate moiety of ATP and additionally to two hydrogen bonds from the backbone nitrogen of Ala276 and the side chain of Arg97. Upon ADP dissociation, XPO reorients and moves to the position previously occupied by the beta-phosphate of ATP. Conformational changes that occur due to the XPO presence apparently allow for the recruitment of the third substrate, THF, with its pterin moiety positioned between Phe384 and Trp412. This position overlaps with that of the bound nucleoside, which is consistent with a catalytic mechanism hypothesis that FTHFS works via a sequential ping-pong mechanism. More specifically, a random bi uni uni bi ping-pong ter ter mechanism is proposed. Additionally, the native structure originally reported at a 2.5 {angstrom} resolution was redetermined at a 2.2 {angstrom} resolution.« less

Mechanical Balance Laws for Boussinesq Models of Surface Water Waves

NASA Astrophysics Data System (ADS)

Ali, Alfatih; Kalisch, Henrik

2012-06-01

Depth-integrated long-wave models, such as the shallow-water and Boussinesq equations, are standard fare in the study of small amplitude surface waves in shallow water. While the shallow-water theory features conservation of mass, momentum and energy for smooth solutions, mechanical balance equations are not widely used in Boussinesq scaling, and it appears that the expressions for many of these quantities are not known. This work presents a systematic derivation of mass, momentum and energy densities and fluxes associated with a general family of Boussinesq systems. The derivation is based on a reconstruction of the velocity field and the pressure in the fluid column below the free surface, and the derivation of differential balance equations which are of the same asymptotic validity as the evolution equations. It is shown that all these mechanical quantities can be expressed in terms of the principal dependent variables of the Boussinesq system: the surface excursion η and the horizontal velocity w at a given level in the fluid.

Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations.

PubMed

Zheng, Dan; Shuai, Xiao; Li, Yanping; Zhou, Peng; Gong, Tao; Sun, Xun; Zhang, Zhirong

2016-09-01

Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its C max and AUC 0- t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.

Effects of ion irradiation on the surface mechanical behavior of hybrid sol-gel derived silicate thin films

NASA Astrophysics Data System (ADS)

Ghisleni, Rudy

A study on the effects of ion irradiation on the surface mechanical behavior of hybrid sol-gel derived thin films has been performed. Hybrid organic/inorganic modified silicate thin films were synthesized by sol-gel processing from tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES) precursors and spin-coated onto (100) Si substrates. The synthesized films were investigated by nanoindentation, photoluminescence spectroscopy, and Raman spectroscopy. Hybrid TEOS/MTES sol-gel films modified by ion irradiation with deposited electronic energies of 1.87 x 1025 eV/cm3 or higher showed higher values of reduced elastic modulus and hardness than 800°C heat treated films. Thus, ion irradiation was found to be an effective means in converting the polymer sol into ceramic type coatings. The ions used in this study were Cu2+, N2+, Si+, O+, N+, He+, and H+, with incident energies ranging from 100 keV to 2 MeV, and fluences ranging from 1 x 1014 to 1 x 1017 ions/cm2. Both the reduced elastic modulus and hardness were seen to increase monotonically with the increase in ion fluence, with an observed maximum hardness of 7.7 GPa (an unirradiated film hardness was 0.4 GPa) and a maximum reduced elastic modulus of 84.0 GPa (an unirradiated film reduced elastic modulus was 7.1 GPa) for 250 keV N2+ irradiation with a 5 x 1016 ions/cm2 fluence. The electronic stopping power was found to be principally responsible for the film hardening, while the role of nuclear stopping power was minimal. A monotonic increase in hardness with increase in electronic energy deposited to the film surface was found. A model describing the hardening of ion irradiated films was developed. This model characterizes the hardening effectiveness of the ion species considered by two parameters: the constant hardening cross-section and the hardening coefficient. Where the hardening cross-section represents the cross-sectional area hardened by the interaction of an incident ion with the target, and the

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA.

PubMed

Li, Siqi; Xu, Zhengping; Sheng, Jinghao

2018-05-10

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

Mechanical Properties of Mineralized Collagen Fibrils As Influenced By Demineralization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balooch, M.; Habelitz, S.; Kinney, J.H.

2009-05-11

Dentin and bone derive their mechanical properties from a complex arrangement of collagen type-I fibrils reinforced with nanocrystalline apatite mineral in extra- and intrafibrillar compartments. While mechanical properties have been determined for the bulk of the mineralized tissue, information on the mechanics of the individual fibril is limited. Here, atomic force microscopy was used on individual collagen fibrils to study structural and mechanical changes during acid etching. The characteristic 67 nm periodicity of gap zones was not observed on the mineralized fibril, but became apparent and increasingly pronounced with continuous demineralization. AFM-nanoindentation showed a decrease in modulus from 1.5 GPamore » to 50 MPa during acid etching of individual collagen fibrils and revealed that the modulus profile followed the axial periodicity. The nanomechanical data, Raman spectroscopy and SAXS support the hypothesis that intrafibrillar mineral etches at a substantially slower rate than the extrafibrillar mineral. These findings are relevant for understanding the biomechanics and design principles of calcified tissues derived from collagen matrices.« less

A multi-target caffeine derived rhodium(i) N-heterocyclic carbene complex: evaluation of the mechanism of action.

PubMed

Zhang, Jing-Jing; Muenzner, Julienne K; Abu El Maaty, Mohamed A; Karge, Bianka; Schobert, Rainer; Wölfl, Stefan; Ott, Ingo

2016-08-16

A rhodium(i) and a ruthenium(ii) complex with a caffeine derived N-heterocyclic carbene (NHC) ligand were biologically investigated as organometallic conjugates consisting of a metal center and a naturally occurring moiety. While the ruthenium(ii) complex was largely inactive, the rhodium(i) NHC complex displayed selective cytotoxicity and significant anti-metastatic and in vivo anti-vascular activities and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor. In HCT-116 cells it increased the reactive oxygen species level, leading to DNA damage, and it induced cell cycle arrest, decreased the mitochondrial membrane potential, and triggered apoptosis. This rhodium(i) NHC derivative thus represents a multi-target compound with promising anti-cancer potential.

Cracking The Climate Change Conundrum With Derivatives

NASA Astrophysics Data System (ADS)

Annan, J.

2016-12-01

There is a long history of scientific wagers being used to demonstrate and test confidence in uncertain outcomes, with the Hawking-Thorne black hole bet and Simon-Ehrlich commodity wager being well-known examples. Perhaps the largest such bet in climate science is the author's $10,000 wager on ongoing warming up to 2017. Such bets are commonly interpreted as personal Bayesian probabilities of the people involved. A broadening of these single bets, into betting markets, would allow for aggregation of views and so find the consensus view across a larger group. A further natural extension of this idea would be to develop financial instruments such as derivatives, which are essentially bets designed to facilitate hedging of risks associated with climate change. In this presentation, I will discuss how such derivatives could protect those vulnerable to climate change by allowing risks to be transferred.As an additional benefit, these climate-based derivatives could create both a mechanism and an incentive for carbon emitters to help finance new technologies and industries that will reduce carbon emissions in the future. These financial instruments would also dynamically incorporate any new information concerning climate change and, in effect, generate probabilities associated with a variety of climate change scenarios.

Stem Cell-Derived Exosome in Cardiovascular Diseases: Macro Roles of Micro Particles.

PubMed

Yuan, Ye; Du, Weijie; Liu, Jiaqi; Ma, Wenya; Zhang, Lai; Du, Zhimin; Cai, Benzhi

2018-01-01

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stem cell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future.

Comparison of Classical and Quantum Mechanical Uncertainties.

ERIC Educational Resources Information Center

Peslak, John, Jr.

1979-01-01

Comparisons are made for the particle-in-a-box, the harmonic oscillator, and the one-electron atom. A classical uncertainty principle is derived and compared with its quantum-mechanical counterpart. The results are discussed in terms of the statistical interpretation of the uncertainty principle. (Author/BB)

FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism.

PubMed

Jiang, Yideng; Ma, Shengchao; Zhang, Huiping; Yang, Xiaoling; Lu, Guan Jun; Zhang, Hui; He, Yangyang; Kong, Fanqi; Yang, Anning; Xu, Hua; Zhang, Minghao; Jiao, Yun; Li, Guizhong; Cao, Jun; Jia, Yuexia; Jin, Shaoju; Wei, Jun; Shi, Yingkang

2016-07-01

Hyperhomocysteinemia (HHcy) is an independent risk factor for the development of atherosclerosis (AS), according to overwhelming number of clinical and epidemiological studies. However, the underlying pathogenic molecular mechanisms by which HHcy promotes AS remain to be fully elucidated. Fatty acid binding protein 4 (FABP4) has been shown to be important in macrophage cholesterol trafficking. The objective of the present study was to determine whether homocysteine (Hcy) accelerates AS through regulating FABP4, and then mediates cholesterol accumulation in macrophages. Hcy concentrations of 0, 50, 100, 200 and 500 µM, and 100 µM Hcy+30 µM vitamin B12 (VB12)+30 µM folic acid (FA) were respectively added to cultured THP‑1 monocyte‑derived macrophages for 24 h. The levels of FABP4, which acts as a key factor connecting cellular lipid accumulation to inflammation, were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses in the macrophages. The present study used a nested touchdown methylation‑specific PCR assay to detect the DNA methylation status of the FABP4 promoter region. In addition, the FABP4 gene fragment was inserted into the cloning vector, pcDNA3.1‑EGFP, to construct the recombinant plasmid, pcDNA3.1‑EGFP/FABP4, which was identified using restriction endonuclease digestion analysis and DNA sequencing. The pcDNA3.1‑EGFP/FABP4 expression plasmid was transfected into THP‑1 monocyte‑derived macrophages, mediated by liposome reagent, following which the expression levels of FABP4 were detected using RT‑qPCR and western blot analyses. The present study also determined the intracellular accumulation of total cholesterol in the macrophages. The results indicated that Hcy decreased the levels of FABP4 promoter methylation, but increased the mRNA and protein expression levels of FABP4 in the macrophages, compared with the control group (0 µM Hcy). However, no dose�

Compost-derived humic acids as regulators for reductive degradation of nitrobenzene.

PubMed

Yuan, Ying; Xi, Beidou; He, Xiaosong; Tan, Wenbing; Gao, Rutai; Zhang, Hui; Yang, Chao; Zhao, Xinyu; Huang, Caihong; Li, Dan

2017-10-05

Nitrobenzene (NB) is a major class of contaminants in soil and groundwater. The current methods involved in the reductive degradation of NB suffer either cost-ineffective or slow conversion rate. Here, we investigated the mechanisms regarding compost-derived humic acids (HAs) as cost-effective regulators to enhance the reduction of NB to aniline (AN). Our results show that the compost-derived HAs, which have been reduced by a Pd-H 2 catalytic system, were able to reduce NB to AN, and their redox properties were the main factors governing the reduction of NB to AN. The decreasing reduction of NB was mainly caused by the decreasing phenol content of compost-derived HAs during composting. In addition, the results reveal that the increase in the generation content of AN was mainly attributed to the increase in the quinones, aromaticity and humic-like components of compost-derived HAs. The findings demonstrate that the HAs derived from compost are effective regulators to enhance the reduction of NB to AN, and that they exert a bright application prospect for the remediation of the NB-contaminated soil. Copyright © 2017 Elsevier B.V. All rights reserved.

Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes.

PubMed

Martins, Danubia Batista; Nasário, Fábio Domingues; Silva-Gonçalves, Laiz Costa; de Oliveira Tiera, Vera Aparecida; Arcisio-Miranda, Manoel; Tiera, Marcio José; Dos Santos Cabrera, Marcia Perez

2018-02-01

The antimicrobial activity of chitosan and derivatives to human and plant pathogens represents a high-valued prospective market. Presently, two low molecular weight derivatives, endowed with hydrophobic and cationic character at different ratios were synthesized and characterized. They exhibit antimicrobial activity and increased performance in relation to the intermediate and starting compounds. However, just the derivative with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. Considering cell membranes as targets, the mode of action was investigated through the interaction with model lipid vesicles mimicking bacterial, tumoral and erythrocyte membranes. Intense lytic activity and binding are demonstrated for both derivatives in anionic bilayers. The less charged compound exhibits slightly improved selectivity towards bacterial model membranes, suggesting that balancing its hydrophobic/hydrophilic character may improve efficiency. Observing the aggregation of vesicles, we hypothesize that the "charge cluster mechanism", ascribed to some antimicrobial peptides, could be applied to these chitosan derivatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction

PubMed Central

Khan, Mohsin; Nickoloff, Emily; Abramova, Tatiana; Johnson, Jennifer; Verma, Suresh Kumar; Krishnamurthy, Prasanna; Mackie, Alexander Roy; Vaughan, Erin; Garikipati, Venkata Naga Srikanth; Benedict, Cynthia; Ramirez, Veronica; Lambers, Erin; Ito, Aiko; Gao, Erhe; Misener, Sol; Luongo, Timothy; Elrod, John; Qin, Gangjian; Houser, Steven R; Koch, Walter J; Kishore, Raj

2015-01-01

Rationale Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit+ CPCs function can be enhanced with ESC exosomes Methods and Results This study demonstrates that mouse ESC derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290–295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression and proliferation. Conclusions mES Ex provide a novel cell free system that utilizes the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC based repair programs in the heart. PMID:25904597

Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities

PubMed Central

Bain, Calum C.; Hawley, Catherine A.; Garner, Hannah; Scott, Charlotte L.; Schridde, Anika; Steers, Nicholas J.; Mack, Matthias; Joshi, Anagha; Guilliams, Martin; Mowat, Allan Mc I.; Geissmann, Frederic; Jenkins, Stephen J.

2016-01-01

Peritoneal macrophages are one of the most studied macrophage populations in the body, yet the composition, developmental origin and mechanisms governing the maintenance of this compartment are controversial. Here we show resident F4/80hiGATA6+ macrophages are long-lived, undergo non-stochastic self-renewal and retain cells of embryonic origin for at least 4 months in mice. However, Ly6C+ monocytes constitutively enter the peritoneal cavity in a CCR2-dependent manner, where they mature into short-lived F4/80loMHCII+ cells that act, in part, as precursors of F4/80hiGATA6+ macrophages. Notably, monocyte-derived F4/80hi macrophages eventually displace the embryonic population with age in a process that is highly gender dependent and not due to proliferative exhaustion of the incumbent embryonic population, despite the greater proliferative activity of newly recruited cells. Furthermore, although monocyte-derived cells acquire key characteristics of the embryonic population, expression of Tim4 was impaired, leading to cumulative changes in the population with age. PMID:27292029

[Anti-MDR tumor mechanism of CIP-36, a podophyllotoxin derivative].

PubMed

Mei, Xin; Jiang, Yun-gen; Lü, Jing-jing; Wu, Ke-zhu; Cao, Bo; Chen, Hong

2011-10-01

This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms. MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells. The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200. Obvious apoptosis could be observed in the Hoechst 33342 staining experiments. The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner. The data were significantly different from that of vehicle. The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry. It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.

Fenton-like initiation of a toluene transformation mechanism

EPA Science Inventory

In Fenton-driven oxidation treatment systems, reaction intermediates derived from parent compounds can play a significant role in the overall treatment process. Fenton-like reactions in the presence of toluene or benzene, involved a transformation mechanism that was highly effici...

Numerical calculation of thermo-mechanical problems at large strains based on complex step derivative approximation of tangent stiffness matrices

NASA Astrophysics Data System (ADS)

Balzani, Daniel; Gandhi, Ashutosh; Tanaka, Masato; Schröder, Jörg

2015-05-01

In this paper a robust approximation scheme for the numerical calculation of tangent stiffness matrices is presented in the context of nonlinear thermo-mechanical finite element problems and its performance is analyzed. The scheme extends the approach proposed in Kim et al. (Comput Methods Appl Mech Eng 200:403-413, 2011) and Tanaka et al. (Comput Methods Appl Mech Eng 269:454-470, 2014 and bases on applying the complex-step-derivative approximation to the linearizations of the weak forms of the balance of linear momentum and the balance of energy. By incorporating consistent perturbations along the imaginary axis to the displacement as well as thermal degrees of freedom, we demonstrate that numerical tangent stiffness matrices can be obtained with accuracy up to computer precision leading to quadratically converging schemes. The main advantage of this approach is that contrary to the classical forward difference scheme no round-off errors due to floating-point arithmetics exist within the calculation of the tangent stiffness. This enables arbitrarily small perturbation values and therefore leads to robust schemes even when choosing small values. An efficient algorithmic treatment is presented which enables a straightforward implementation of the method in any standard finite-element program. By means of thermo-elastic and thermo-elastoplastic boundary value problems at finite strains the performance of the proposed approach is analyzed.

Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells.

PubMed

Resheq, Yazid J; Li, Ka-Kit; Ward, Stephen T; Wilhelm, Annika; Garg, Abhilok; Curbishley, Stuart M; Blahova, Miroslava; Zimmermann, Henning W; Jitschin, Regina; Mougiakakos, Dimitrios; Mackensen, Andreas; Weston, Chris J; Adams, David H

2015-03-15

Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14(+) monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = -0.6555, p < 0.05). Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy. Copyright © 2015 by The American Association of Immunologists, Inc.

Engineering-derived approaches for iPSC preparation, expansion, differentiation and applications.

PubMed

Li, Yang; Li, Ling; Chen, Zhi-Nan; Gao, Ge; Yao, Rui; Sun, Wei

2017-07-31

Remarkable achievements have been made since induced pluripotent stem cells (iPSCs) were first introduced in 2006. Compared with non-pluripotent stem cells, iPSC research faces several additional complexities, such as the choice of extracellular matrix proteins, growth and differentiation factors, as well as technical challenges related to self-renewal and directed differentiation. Overcoming these challenges requires the integration of knowledge and technologies from multiple fields including cell biology, biomaterial science, engineering, physics and medicine. Here, engineering-derived iPSC approaches are reviewed according to three aspects of iPSC studies: preparation, expansion, differentiation and applications. Engineering strategies, such as 3D systems establishment, cell-matrix mechanics and the regulation of biophysical and biochemical cues, together with engineering techniques, such as 3D scaffolds, cell microspheres and bioreactors, have been applied to iPSC studies and have generated insightful results and even mini-organs such as retinas, livers and intestines. Specific results are given to demonstrate how these approaches impact iPSC behavior, and related mechanisms are discussed. In addition, cell printing technologies are presented as an advanced engineering-derived approach since they have been applied in both iPSC studies and the construction of diverse tissues and organs. Further development and possible innovations of cell printing technologies are presented in terms of creating complex and functional iPSC-derived living tissues and organs.

The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus

PubMed Central

Guardado-Mendoza, Rodolfo; Prioletta, Annamaria; Jiménez-Ceja, Lilia M.; Sosale, Aravind

2013-01-01

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy. PMID:24273582

Photoelectrochemical Properties of Graphene and Its Derivatives

PubMed Central

Adán-Más, Alberto; Wei, Di

2013-01-01

Graphene and its derivatives combine a numerous range of supreme properties that can be useful in many applications. The purpose of this review is to analyse the photoelectrochemical properties of pristine graphene, graphene oxide (GO) and reduced graphene oxide (rGO) and their impact on semiconductor catalysts/quantum dots. The mechanism that this group of materials follows to improve their performance will be cleared by explaining how those properties can be exploited in several applications such as photo-catalysts (degradation of pollutants) and photovoltaics (solar cells). PMID:28348339

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

PubMed

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Benzene and its methyl-derivatives: derivation of maximum exposure levels in automobiles.

PubMed

Schupp, Thomas; Bolt, Hermann M; Jaeckh, Rudolf; Hengstler, Jan G

2006-01-05

Automobile drivers are exposed to several organic hydrocarbons. Concentrations measured in passenger compartments have been reported to range between 13 and 560 microg/m(3) for benzene, 33-258 microg/m(3) for toluene, 20-250 microg/m(3) for xylene (mixed isomers) and 3-23 microg/m(3) for trimethylbenzene (mixed isomers). These aromatic hydrocarbons are emitted from gasoline and from materials inside a car. In the present study we evaluated, whether these exposures pose a potential risk to the health of drivers. Therefore, we derived maximum exposure levels inside cars for chronic (ELIA(chronic)) and short-term (STELIA) exposure. The lowest ELIA's(chronic) for benzene, toluene, xylene and trimethylbenzene were 0.083, 1.2, 8.8 and 0.31 mg/m(3), respectively. The respective STELIA's were 16, 30, 29 and 25 mg/m(3). Obviously concentrations of toluene, xylene and trimethylbenzene inside cars do not exceed their individual STELIA's. In contrast, benzene seems to be problematic, since concentrations inside cars amount up to 0.56 mg/m(3), which exceeds the ELIA(chronic) derived for benzene. This should not be underestimated, since benzene is a genotoxic carcinogen that probably acts by non-threshold mechanisms. In conclusion, concentrations of toluene, xylene and trimethylbenzene usually observed inside cars are unlikely to pose a risk to the health of drivers. A systematic toxicological evaluation of the risk associated with benzene exposure in cars seems to be necessary.

The cytotoxic effect of spiroflavanone derivatives, their binding ability to human serum albumin (HSA) and a DFT study on the mechanism of their synthesis

NASA Astrophysics Data System (ADS)

Budzisz, Elzbieta; Paneth, Piotr; Geromino, Inacrist; Muzioł, Tadeusz; Rozalski, Marek; Krajewska, Urszula; Pipiak, Paulina; Ponczek, Michał B.; Małecka, Magdalena; Kupcewicz, Bogumiła

2017-06-01

This paper examines the cytotoxic effect of nine compounds with spiropyrazoline structures, and determines the reaction mechanism between diazomethane and selected benzylideneflavanones, their lipophilicity, and their binding ability to human serum albumin. The cytotoxic effect was determined on two human leukaemia cell lines (HL-60 and NALM-6) and melanoma WM-115 cells, as well as on normal human umbilical vein endothelial cells (HUVEC). The highest cytotoxicity was exhibited by compound B7: it was found to have an IC50 of less than 10 μM for all three cancer cell lines, with five to 12-fold lower sensitivity against normal cells (HUVEC). All the compounds exhibit comparable affinity energy in human serum albumin binding (from -8.1 to -8.6 kcal mol-1) but vary in their binding sites depending on the substituent. X-ray crystallography of two derivatives confirmed their synthetic pathway, and their structures were carefully examined.

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

PubMed

Stamler, J; Mendelsohn, M E; Amarante, P; Smick, D; Andon, N; Davies, P F; Cooke, J P; Loscalzo, J

1989-09-01

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.

Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism

PubMed Central

Chen, Julia C.; Hoey, David A.; Chua, Mardonn; Bellon, Raymond; Jacobs, Christopher R.

2016-01-01

It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitment in vitro. In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cells in vivo. Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitment in vivo and that the primary cilium contributes to this process.—Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. PMID:26675708

Placental-derived stem cells: Culture, differentiation and challenges

PubMed Central

Oliveira, Maira S; Barreto-Filho, João B

2015-01-01

Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues (bone marrow, adipose tissue, and placenta) are potentially sources of stem cells. Placenta-derived stem cells (p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture (mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations (after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice. PMID:26029347

Identification of Diet-Derived Constituents as Potent Inhibitors of Intestinal Glucuronidation

PubMed Central

Gufford, Brandon T.; Chen, Gang; Lazarus, Philip; Graf, Tyler N.; Oberlies, Nicholas H.

2014-01-01

Drug-metabolizing enzymes within enterocytes constitute a key barrier to xenobiotic entry into the systemic circulation. Furanocoumarins in grapefruit juice are cornerstone examples of diet-derived xenobiotics that perpetrate interactions with drugs via mechanism-based inhibition of intestinal CYP3A4. Relative to intestinal CYP3A4-mediated inhibition, alternate mechanisms underlying dietary substance–drug interactions remain understudied. A working systematic framework was applied to a panel of structurally diverse diet-derived constituents/extracts (n = 15) as inhibitors of intestinal UDP-glucuronosyl transferases (UGTs) to identify and characterize additional perpetrators of dietary substance–drug interactions. Using a screening assay involving the nonspecific UGT probe substrate 4-methylumbelliferone, human intestinal microsomes, and human embryonic kidney cell lysates overexpressing gut-relevant UGT1A isoforms, 14 diet-derived constituents/extracts inhibited UGT activity by >50% in at least one enzyme source, prompting IC50 determination. The IC50 values of 13 constituents/extracts (≤10 μM with at least one enzyme source) were well below intestinal tissue concentrations or concentrations in relevant juices, suggesting that these diet-derived substances can inhibit intestinal UGTs at clinically achievable concentrations. Evaluation of the effect of inhibitor depletion on IC50 determination demonstrated substantial impact (up to 2.8-fold shift) using silybin A and silybin B, two key flavonolignans from milk thistle (Silybum marianum) as exemplar inhibitors, highlighting an important consideration for interpretation of UGT inhibition in vitro. Results from this work will help refine a working systematic framework to identify dietary substance–drug interactions that warrant advanced modeling and simulation to inform clinical assessment. PMID:25008344

Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.

PubMed

Marchetto, Maria C; Belinson, Haim; Tian, Yuan; Freitas, Beatriz C; Fu, Chen; Vadodaria, Krishna; Beltrao-Braga, Patricia; Trujillo, Cleber A; Mendes, Ana P D; Padmanabhan, Krishnan; Nunez, Yanelli; Ou, Jing; Ghosh, Himanish; Wright, Rebecca; Brennand, Kristen; Pierce, Karen; Eichenfield, Lawrence; Pramparo, Tiziano; Eyler, Lisa; Barnes, Cynthia C; Courchesne, Eric; Geschwind, Daniel H; Gage, Fred H; Wynshaw-Boris, Anthony; Muotri, Alysson R

2017-06-01

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells

PubMed Central

Tsuruya, Kota; Chikada, Hiromi; Ida, Kinuyo; Anzai, Kazuya; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tetsuya

2015-01-01

Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13+CD133+ cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13+CD133+ cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation. PMID:25808356

A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells.

PubMed

Tsuruya, Kota; Chikada, Hiromi; Ida, Kinuyo; Anzai, Kazuya; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tetsuya; Kamiya, Akihide

2015-07-15

Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13(+)CD133(+) cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13(+)CD133(+) cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation.

Synthesis, Characterization, and Anticancer Activity of Novel Lipophilic Emodin Cationic Derivatives.

PubMed

Yang, Xiang; Zhao, Wenna; Hu, Xiufang; Hao, Xianxiao; Hong, Fang; Wang, Jianlong; Xiang, Liping; Zhu, Yunhui; Yuan, Yaofeng; Ho, Rodney J Y; Wang, Wenfeng; Shao, Jingwei

2015-12-01

Seventeen novel emodin derivatives were synthesized, and the structures were confirmed by IR, H NMR, MS, and elemental analysis. The cytotoxic activity of the derivatives was evaluated against A375, BGC-823, HepG2, and HELF cells by MTT assay. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. The lead compound 9a induced a loss of the mitochondrial transmembrane potential (▵Ψm), an increase in reactive oxygen species (ROS), release of cytochrome c and activation of caspase-3 and caspase-9. In addition, the confocal study showed that emodin derivative 9a (containing asymmetric hydrocarbon tails) was mainly localized in mitochondria, demonstrating a key role of the mitochondria-mediated apoptosis pathway in cancer cells. Taken together, the results demonstrate that embodin derivative 9a preferentially regulates the ROS-mediated apoptosis in A375 cells through the induction of cytochrome c expression and activation of caspase-3 and caspase-9 proteins. © 2015 John Wiley & Sons A/S.

Naturally derived and synthetic scaffolds for skeletal muscle reconstruction☆

PubMed Central

Wolf, Matthew T.; Dearth, Christopher L.; Sonnenberg, Sonya B.; Loboa, Elizabeth G.; Badylak, Stephen F.

2017-01-01

Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an inductive microenvironment and as a cell/drug delivery vehicle to encourage muscle ingrowth. Both biologically active, naturally derived materials (such as extracellular matrix) and carefully engineered synthetic polymers have been developed to provide such a muscle regenerative environment. Next generation naturally derived/synthetic “hybrid materials” would combine the advantageous properties of these materials to create an optimal platform for cell/drug delivery and possess inherent bioactive properties. Advances in scaffolds using muscle tissue engineering are reviewed herein. PMID:25174309

Derivation of special relativity from Maxwell and Newton.

PubMed

Dunstan, D J

2008-05-28

Special relativity derives directly from the principle of relativity and from Newton's laws of motion with a single undetermined parameter, which is found from Faraday's and Ampère's experimental work and from Maxwell's own introduction of the displacement current to be the -c(-2) term in the Lorentz transformations. The axiom of the constancy of the speed of light is quite unnecessary. The behaviour and the mechanism of the propagation of light are not at the foundations of special relativity.

Synthesis, crystal structure, and biological evaluation of a series of phloretin derivatives.

PubMed

Wang, Li; Li, Zheng-Wei; Zhang, Wei; Xu, Rui; Gao, Fei; Liu, Yang-Feng; Li, Ya-Jun

2014-10-13

A one-step synthesis of phloretin derivatives 2-11 from phloretin in good to excellent yields is reported. Their structures were characterized by 1H-NMR, 13C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A mechanism for the formation of 9-11 is proposed. Compared with the anticancer drug docetaxel, phloretin, phloretin derivatives and phlorizin exhibited moderate cytotoxicity toward the MDA-MB-231, SPC-A1, A549, MCF-7 and EC109 cell lines. Among all of the tested compounds, 7 exhibited the strongest cytotoxicity toward the five cell lines and was more active than docetaxel in MDA-MB-231 cells. Our findings suggest that these derivatives hold great promise for further development as anticancer agents.

Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

PubMed Central

Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Saokaew, Surasak; Duangjai, Acharaporn; Lee, Learn-Han; Goh, Bey-Hing

2016-01-01

Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs. PMID:27445824

Collapse Mechanisms Of Masonry Structures

NASA Astrophysics Data System (ADS)

Zuccaro, G.; Rauci, M.

2008-07-01

The paper outlines a possible approach to typology recognition, safety check analyses and/or damage measuring taking advantage by a multimedia tool (MEDEA), tracing a guided procedure useful for seismic safety check evaluation and post event macroseismic assessment. A list of the possible collapse mechanisms observed in the post event surveys on masonry structures and a complete abacus of the damages are provided in MEDEA. In this tool a possible combination between a set of damage typologies and each collapse mechanism is supplied in order to improve the homogeneity of the damages interpretation. On the other hand recent researches of one of the author have selected a number of possible typological vulnerability factors of masonry buildings, these are listed in the paper and combined with potential collapse mechanisms to be activated under seismic excitation. The procedure takes place from simple structural behavior models, derived from the Umbria-Marche earthquake observations, and tested after the San Giuliano di Puglia event; it provides the basis either for safety check analyses of the existing buildings or for post-event structural safety assessment and economic damage evaluation. In the paper taking advantage of MEDEA mechanisms analysis, mainly developed for the post event safety check surveyors training, a simple logic path is traced in order to approach the evaluation of the masonry building safety check. The procedure starts from the identification of the typological vulnerability factors to derive the potential collapse mechanisms and their collapse multipliers and finally addresses the simplest and cheapest strengthening techniques to reduce the original vulnerability. The procedure has been introduced in the Guide Lines of the Regione Campania for the professionals in charge of the safety check analyses and the buildings strengthening in application of the national mitigation campaign introduced by the Ordinance of the Central Government n. 3362

Collapse Mechanisms Of Masonry Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuccaro, G.; Rauci, M.

2008-07-08

The paper outlines a possible approach to typology recognition, safety check analyses and/or damage measuring taking advantage by a multimedia tool (MEDEA), tracing a guided procedure useful for seismic safety check evaluation and post event macroseismic assessment. A list of the possible collapse mechanisms observed in the post event surveys on masonry structures and a complete abacus of the damages are provided in MEDEA. In this tool a possible combination between a set of damage typologies and each collapse mechanism is supplied in order to improve the homogeneity of the damages interpretation. On the other hand recent researches of onemore » of the author have selected a number of possible typological vulnerability factors of masonry buildings, these are listed in the paper and combined with potential collapse mechanisms to be activated under seismic excitation. The procedure takes place from simple structural behavior models, derived from the Umbria-Marche earthquake observations, and tested after the San Giuliano di Puglia event; it provides the basis either for safety check analyses of the existing buildings or for post-event structural safety assessment and economic damage evaluation. In the paper taking advantage of MEDEA mechanisms analysis, mainly developed for the post event safety check surveyors training, a simple logic path is traced in order to approach the evaluation of the masonry building safety check. The procedure starts from the identification of the typological vulnerability factors to derive the potential collapse mechanisms and their collapse multipliers and finally addresses the simplest and cheapest strengthening techniques to reduce the original vulnerability. The procedure has been introduced in the Guide Lines of the Regione Campania for the professionals in charge of the safety check analyses and the buildings strengthening in application of the national mitigation campaign introduced by the Ordinance of the Central Government n

Time-derivative preconditioning for viscous flows

NASA Technical Reports Server (NTRS)

Choi, Yunho; Merkle, Charles L.

1991-01-01

A time-derivative preconditioning algorithm that is effective over a wide range of flow conditions from inviscid to very diffusive flows and from low speed to supersonic flows was developed. This algorithm uses a viscous set of primary dependent variables to introduce well-conditioned eigenvalues and to avoid having a nonphysical time reversal for viscous flow. The resulting algorithm also provides a mechanism for controlling the inviscid and viscous time step parameters to be of order one for very diffusive flows, thereby ensuring rapid convergence at very viscous flows as well as for inviscid flows. Convergence capabilities are demonstrated through computation of a wide variety of problems.

Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms

PubMed Central

2014-01-01

Introduction Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play. Methods Human umbilical cord tissue-derived MSCs (UCX®), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX® preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays. Results Evaluation of the effects upon intramyocardial transplantation shows that UCX® preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX® further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX®-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca-1+ progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation. Conclusions UCX® preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX® were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results

Inhibiting Microbial Toxins Using Plant-Derived Compounds and Plant Extracts

PubMed Central

Upadhyay, Abhinav; Mooyottu, Shankumar; Yin, Hsinbai; Surendran Nair, Meera; Bhattaram, Varunkumar; Venkitanarayanan, Kumar

2015-01-01

Many pathogenic bacteria and fungi produce potentially lethal toxins that cause cytotoxicity or impaired cellular function either at the site of colonization or other locations in the body through receptor-mediated interactions. Various factors, including biotic and abiotic environments, competing microbes, and chemical cues affect toxin expression in these pathogens. Recent work suggests that several natural compounds can modulate toxin production in pathogenic microbes. However, studies explaining the mechanistic basis for their effect are scanty. This review discusses the potential of various plant-derived compounds for reducing toxin production in foodborne and other microbes. In addition, studies highlighting their anti-toxigenic mechanism(s) are discussed. PMID:28930207

The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives

PubMed Central

Liu, Xin; Li, Wenjuan; Fu, Xuemei; Xu, Yang

2017-01-01

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient. The breakthrough of the technology to generate autologous-induced pluripotent stem cells (iPSCs) by nuclear reprogramming of patient’s somatic cells raised the possibility that autologous iPSC-derived cells can be transplanted into the patients without the concern of immune rejection. However, accumulating data indicate that certain iPSC-derived cells can be immunogenic. In addition, the genomic instability associated with iPSCs raises additional safety concern to use iPSC-derived cells in human cell therapy. In this review, we will discuss the mechanism underlying the immunogenicity of the pluripotent stem cells and recent progress in developing immune tolerance strategies of human pluripotent stem cell (hPSC)-derived allografts. The successful development of safe and effective immune tolerance strategy will greatly facilitate the clinical development of hPSC-based cell therapy. PMID:28626459

Mechanical stabilization of proteolytically degradable polyethylene glycol dimethacrylate hydrogels through peptide interaction.

PubMed

Lim, Hyun Ju; Khan, Zara; Lu, Xi; Perera, T Hiran; Wilems, Thomas S; Ravivarapu, Krishna T; Smith Callahan, Laura A

2018-04-15

Balancing enhancement of neurite extension against loss of matrix support in synthetic hydrogels containing proteolytically degradable and bioactive signaling peptides to optimize tissue formation is difficult. Using a systematic approach, polyethylene glycol hydrogels containing concurrent continuous concentration gradients of the laminin derived bioactive signaling peptide, Ile-Lys-Val-Ala-Val (IKVAV), and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ, were fabricated and characterized. During proteolytic degradation of the concentration gradient hydrogels, the IKVAV and IWGQ cleavage fragment from GPQGIWGQ were found to interact and stabilize the bulk Young's Modulus of the hydrogel. Further testing of discrete samples containing GPQGIWGQ or its cleavage fragments, GPQG and IWGQ, indicates hydrophobic interactions between the peptides are not necessary for mechanical stabilization of the hydrogel, but changes in the concentration ratio between the peptides tethered in the hydrogel and salts and ions in the swelling solution can affect the stabilization. Encapsulation of human induced pluripotent stem cell derived neural stem cells did not reduce the mechanical properties of the hydrogel over a 14 day neural differentiation culture period, and IKVAV was found to maintain concentration dependent effects on neurite extension and mRNA gene expression of neural cytoskeletal markers, similar to previous studies. As a result, this work has significant implications for the analysis of biological studies in matrices, as the material and mechanical properties of the hydrogel may be unexpectedly temporally changing during culture due to interactions between peptide signaling elements, underscoring the need for greater matrix characterization during the degradation and cell culture. Greater emulation of the native extracellular matrix is necessary for tissue formation. To achieve this, matrices are becoming more complex, often including multiple

Statistical mechanics of self-driven Carnot cycles.

PubMed

Smith, E

1999-10-01

The spontaneous generation and finite-amplitude saturation of sound, in a traveling-wave thermoacoustic engine, are derived as properties of a second-order phase transition. It has previously been argued that this dynamical phase transition, called "onset," has an equivalent equilibrium representation, but the saturation mechanism and scaling were not computed. In this work, the sound modes implementing the engine cycle are coarse-grained and statistically averaged, in a partition function derived from microscopic dynamics on criteria of scale invariance. Self-amplification performed by the engine cycle is introduced through higher-order modal interactions. Stationary points and fluctuations of the resulting phenomenological Lagrangian are analyzed and related to background dynamical currents. The scaling of the stable sound amplitude near the critical point is derived and shown to arise universally from the interaction of finite-temperature disorder, with the order induced by self-amplification.

Isolation, Purification and Molecular Mechanism of a Peanut Protein-Derived ACE-Inhibitory Peptide

PubMed Central

Shi, Aimin; Liu, Hongzhi; Liu, Li; Hu, Hui; Wang, Qiang; Adhikari, Benu

2014-01-01

Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension. PMID:25347076

Synthesis of α,ω-polyfluorinated α-amino acid derivatives and δ,δ-difluoronorvaline.

PubMed

Ulbrich, Dirk; Daniliuc, Constantin G; Haufe, Günter

2016-03-07

Intending to synthesize ω,ω-difluoroalkyl amino acid derivatives by oxidative desulfurization-fluorination reactions of suitable arylthio-2-phthalimido butanoates and pentanoates, in addition to small amounts of the target products, mainly α,ω-polyfluorinated amino acid derivatives were formed by additional sulfur-assisted α-fluorination. This novel structural motif was verified spectroscopically as well as by X-ray analysis. A plausible mechanism of formation is suggested. Using a different approach, δ,δ-difluoronorvaline hydrochloride was synthesized with at least 36% enantiomeric excess via deoxofluorination of the corresponding aldehyde.

Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

ERIC Educational Resources Information Center

Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

2015-01-01

Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

PubMed

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Logical inference approach to relativistic quantum mechanics: Derivation of the Klein–Gordon equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donker, H.C., E-mail: h.donker@science.ru.nl; Katsnelson, M.I.; De Raedt, H.

2016-09-15

The logical inference approach to quantum theory, proposed earlier De Raedt et al. (2014), is considered in a relativistic setting. It is shown that the Klein–Gordon equation for a massive, charged, and spinless particle derives from the combination of the requirements that the space–time data collected by probing the particle is obtained from the most robust experiment and that on average, the classical relativistic equation of motion of a particle holds. - Highlights: • Logical inference applied to relativistic, massive, charged, and spinless particle experiments leads to the Klein–Gordon equation. • The relativistic Hamilton–Jacobi is scrutinized by employing a field description formore » the four-velocity. • Logical inference allows analysis of experiments with uncertainty in detection events and experimental conditions.« less

Computational study of the synthesis of benzoin derivatives from benzil

NASA Astrophysics Data System (ADS)

Topal, Kevser Göçmen; Unaleroglu, Canan; Aviyente, Viktorya

Benzil (1,2-diphenylethane-1,2-dione) undergoes cyanide catalyzed condensation with benzaldehyde to yield O-benzoylated benzoin (2-benzoyl-1,2-diphenylethanone). In this study, the experimentally suggested mechanism has been modeled with PM3 and verified with B3LYP. The effect of the substituent on the reaction yield has been rationalized by considering two benzil derivatives; 1,2-bis(2-chlorophenyl)ethane-1,2-dione and 1,2-bis(2-fluorophenyl)ethane-1,2-dione and three benzaldehyde derivatives; o-fluorobenzaldehyde, o-methylbenzaldehyde and 2-pyridinecarboxaldehyde. The effect of the solvent has been modeled by using the isodensity-surface polarizable continuum (IPCM) model. Reactivity descriptors have been used to justify the reactivity differences of the various substituents.

Role of nuclear factor-κB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

PubMed Central

Alcaraz, María José; Vicente, Ana María; Araico, Amparo; Dominguez, José N; Terencio, María Carmen; Ferrándiz, María Luisa

2004-01-01

The synthetic chalcone 3′,4′,5′,3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μM) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μg ml−1) due to the inhibition of nuclear factor κB (NF-κB) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF-κB–IκB complex leading to inhibition of NF-κB translocation into the nucleus, DNA binding and transcriptional activity. We also demonstrate the ability of this compound to activate NfE2-related factor (Nrf2) and induce heme oxygenase-1 (HO-1). Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO-1 induction by this chalcone derivative.  This novel anti-inflammatory agent simultaneously induces a cytoprotective response (HO-1) and downregulates an inflammatory pathway (NF-κB) with a mechanism of action different from antioxidant chalcones. PMID:15249426

Quantum mechanical streamlines. I - Square potential barrier

NASA Technical Reports Server (NTRS)

Hirschfelder, J. O.; Christoph, A. C.; Palke, W. E.

1974-01-01

Exact numerical calculations are made for scattering of quantum mechanical particles hitting a square two-dimensional potential barrier (an exact analog of the Goos-Haenchen optical experiments). Quantum mechanical streamlines are plotted and found to be smooth and continuous, to have continuous first derivatives even through the classical forbidden region, and to form quantized vortices around each of the nodal points. A comparison is made between the present numerical calculations and the stationary wave approximation, and good agreement is found between both the Goos-Haenchen shifts and the reflection coefficients. The time-independent Schroedinger equation for real wavefunctions is reduced to solving a nonlinear first-order partial differential equation, leading to a generalization of the Prager-Hirschfelder perturbation scheme. Implications of the hydrodynamical formulation of quantum mechanics are discussed, and cases are cited where quantum and classical mechanical motions are identical.

Proteomic Analysis of the Extracellular Matrix Produced by Mesenchymal Stromal Cells: Implications for Cell Therapy Mechanism

PubMed Central

Harvey, Adam; Yen, Ten-Yang; Aizman, Irina; Tate, Ciara; Case, Casey

2013-01-01

Mesenchymal stromal cells (MSCs) transiently transfected with notch1 intracellular domain (NICD) are beneficial for neurological disorders as observed in several preclinical studies. Extracellular matrix (ECM) derived from NICD-transfected MSCs has been previously shown to support in vitro neural cell growth and survival better than that of un-transfected MSCs. To understand the underlying mechanism(s) by which NICD-transfected MSC-derived ECM supports neural cell growth and survival, we investigated the differences in NICD-transfected MSC- and MSC-derived ECM protein quantity and composition. To compare the ECM derived from MSCs and NICD-transfected MSCs, the proteins were sequentially solubilized using sodium dodecyl sulfate (SDS) and urea, quantified, and compared across four human donors. We then analyzed ECM proteins using either in-gel digests or in-solution surfactant-assisted trypsin digests (SAISD) coupled with reverse phase nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Analyses using nLC-MS/MS identified key components of ECM from NICD-transfected MSCs and un-transfected MSCs and revealed significant differences in their respective compositions. This work provides a reproducible method for identifying and comparing in vitro cell-derived ECM proteins, which is crucial for exploring the mechanisms underlying cellular therapy. PMID:24244468

Fractional vector calculus and fluid mechanics

NASA Astrophysics Data System (ADS)

Lazopoulos, Konstantinos A.; Lazopoulos, Anastasios K.

2017-04-01

Basic fluid mechanics equations are studied and revised under the prism of fractional continuum mechanics (FCM), a very promising research field that satisfies both experimental and theoretical demands. The geometry of the fractional differential has been clarified corrected and the geometry of the fractional tangent spaces of a manifold has been studied in Lazopoulos and Lazopoulos (Lazopoulos KA, Lazopoulos AK. Progr. Fract. Differ. Appl. 2016, 2, 85-104), providing the bases of the missing fractional differential geometry. Therefore, a lot can be contributed to fractional hydrodynamics: the basic fractional fluid equations (Navier Stokes, Euler and Bernoulli) are derived and fractional Darcy's flow in porous media is studied.

The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells.

PubMed

Kim, Ji Hye; Kim, Wang-Kyun; Sung, Young Kwan; Kwack, Mi Hee; Song, Seung Yong; Choi, Joon-Seok; Park, Sang Gyu; Yi, TacGhee; Lee, Hyun-Joo; Kim, Dae-Duk; Seo, Hyun Min; Song, Sun U; Sung, Jong-Hyuk

2014-06-15

Although adipose-derived stem cells (ASCs) show promise for cell therapy, there is a tremendous need for developing ASC activators. In the present study, we investigated whether or not vitamin C increases the survival, proliferation, and hair-regenerative potential of ASCs. In addition, we tried to find the molecular mechanisms underlying the vitamin C-mediated stimulation of ASCs. Sodium-dependent vitamin C transporter 2 (SVCT2) is expressed in ASCs, and mediates uptake of vitamin C into ASCs. Vitamin C increased the survival and proliferation of ASCs in a dose-dependent manner. Vitamin C increased ERK1/2 phosphorylation, and inhibition of the mitogen-activated protein kinase (MAPK) pathway attenuated the proliferation of ASCs. Microarray and quantitative polymerase chain reaction showed that vitamin C primarily upregulated expression of proliferation-related genes, including Fos, E2F2, Ier2, Mybl1, Cdc45, JunB, FosB, and Cdca5, whereas Fos knock-down using siRNA significantly decreased vitamin C-mediated ASC proliferation. In addition, vitamin C-treated ASCs accelerated the telogen-to-anagen transition in C3H/HeN mice, and conditioned medium from vitamin C-treated ASCs increased the hair length and the Ki67-positive matrix keratinocytes in hair organ culture. Vitamin C increased the mRNA expression of HGF, IGFBP6, VEGF, bFGF, and KGF, which may mediate hair growth promotion. In summary, vitamin C is transported via SVCT2, and increased ASC proliferation is mediated by the MAPK pathway. In addition, vitamin C preconditioning enhanced the hair growth promoting effect of ASCs. Because vitamin C is safe and effective, it could be used to increase the yield and regenerative potential of ASCs.

Potential fluid mechanic pathways of platelet activation.

PubMed

Shadden, Shawn C; Hendabadi, Sahar

2013-06-01

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

Potential fluid mechanic pathways of platelet activation

PubMed Central

Shadden, Shawn C.; Hendabadi, Sahar

2012-01-01

Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport. PMID:22782543

21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

Code of Federal Regulations, 2010 CFR

2010-04-01

... (fermentation-derived). 184.1685 Section 184.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... (animal-derived) and chymosin preparation (fermentation-derived). (a)(1) Rennet and bovine rennet are... clear solution containing the active enzyme chymosin (E.C. 3.4.23.4). It is derived, via fermentation...

Response mechanisms to joint exposure of triclosan and its chlorinated derivatives on zebrafish (Danio rerio) behavior.

PubMed

Liu, Jinfeng; Sun, Limei; Zhang, Hongqin; Shi, Mengru; Dahlgren, Randy A; Wang, Xuedong; Wang, Huili

2018-02-01

Triclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) frequently co-exist in real-world aquatic environments; the latter two contaminants contributing to TCS photolytic products or chlorinated derivatives. There is a paucity of information regarding their joint toxicity to aquatic organisms leading us to study their effects on the swimming behavior of zebrafish (Danio rerio). Herein, we reported that 0.28 mg/L TDT exposure (mixtures of TCS, 2,4,6-TCP and 2,4-DCP) enhanced 24-hpf embryonic spontaneous movement frequency, 96-hpf larval activity; however, the 0.56 and 1.12 mg/L TDT treatments decreased all of these behavioral endpoints. All adult behavioral tests demonstrated that chronic TDT exposure (0.14 mg/L) led to hyperactivity and restlessness in adult zebrafish. A 0.14 mg/L TD DATE /@ "M/d/yyyy" 11/21/2017T treatment led to anxiety-like behavior in a bottom dwelling test and excessive panic and low hedging capacity in a conditioned place preference test. Social interaction test demonstrated that zebrafish preferred quiet and isolated space in response to TDT stress. Zebrafish memory was significantly decreased in a T-maze experiment. Whole mount in situ hybridization of pax2a and bcl2l11 genes revealed that their differential expression in the brain and skeleton were related to the corresponding phenotypic behavioral abnormality. A series of biomarker and estrogen receptor assays demonstrated that TDT acute exposure caused abnormal energy metabolism and neurological diseases. AO staining revealed that TDT exposure produced vascular ablation in the head, as well as the occurrence of massive apoptosis in the brain. TEM observation showed pyknosis of nucleus following TDT exposure. These results allow assessment of mechanisms for zebrafish abnormal behavior in response to TDT exposure, and are useful for early intervention and gene therapy of contaminant-induced diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

NASA Astrophysics Data System (ADS)

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-01

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors.

PubMed

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-17

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

PubMed Central

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-01-01

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121

Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

PubMed

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-02-03

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.

Preparation of four 1,4-dihydropyridine derivatives (DHPs) labeled with carbon-14.

PubMed

Ahmadi Faghih, Mohammad Amin; Moslemin, Mohammad Hossein; Shirvani, Gholamhossein; Javaheri, Mohsen

2018-05-23

The importance of DHPs compounds and the need for examining the mechanism of their effect, mandated us to synthesize a number of carbon-14 labeled 1,4-dihydropyridine derivatives for pharmacological studies. Simple preparation and suitable radiochemical yield were advantages of this preparation. This article is protected by copyright. All rights reserved.

Statistical mechanics of the Huxley-Simmons model

NASA Astrophysics Data System (ADS)

Caruel, M.; Truskinovsky, L.

2016-06-01

The chemomechanical model of Huxley and Simmons (HS) [A. F. Huxley and R. M. Simmons, Nature 233, 533 (1971), 10.1038/233533a0] provides a paradigmatic description of mechanically induced collective conformational changes relevant in a variety of biological contexts, from muscles power stroke and hair cell gating to integrin binding and hairpin unzipping. We develop a statistical mechanical perspective on the HS model by exploiting a formal analogy with a paramagnetic Ising model. We first study the equilibrium HS model with a finite number of elements and compute explicitly its mechanical and thermal properties. To model kinetics, we derive a master equation and solve it for several loading protocols. The developed formalism is applicable to a broad range of allosteric systems with mean-field interactions.

Brain-derived neurotrophic factor and its clinical implications

PubMed Central

Bathina, Siresha

2015-01-01

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus. PMID:26788077

Endohedral Metallofullerene Derivatives

NASA Technical Reports Server (NTRS)

Dorn, Harry C. (Inventor); Iezzi, Erick B. (Inventor); Duchamp, James (Inventor)

2008-01-01

Trimetallic nitride endohedral metallofullerene derivatives and their preparation are described. The trimetallic nitride endohedral metallofullerene derivatives have the general formula A(sub 3-n)X(sub n)@C(sub m)(R) where n ranges from 0 to 3, A and X may be trivalent metals and may be either rare earth metal or group IIIB metals, m is between about 60 and about 200, and R is preferably an organic group. Derivatives where the R group forms cyclized derivatives with the fullerene cage are also described.

DNA methylation in schizophrenia in different patient-derived cell types.

PubMed

Vitale, Alejandra M; Matigian, Nicholas A; Cristino, Alexandre S; Nones, Katia; Ravishankar, Sugandha; Bellette, Bernadette; Fan, Yongjun; Wood, Stephen A; Wolvetang, Ernst; Mackay-Sim, Alan

2017-01-01

DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a "ground state" upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation, and movement, functions known to be affected in schizophrenia patient-derived cells. Only five gene loci were differentially methylated in all three cell types. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally induced epigenetic regulation.

Mechanical transduction via a single soft polymer

NASA Astrophysics Data System (ADS)

Hou, Ruizheng; Wang, Nan; Bao, Weizhu; Wang, Zhisong

2018-04-01

Molecular machines from biology and nanotechnology often depend on soft structures to perform mechanical functions, but the underlying mechanisms and advantages or disadvantages over rigid structures are not fully understood. We report here a rigorous study of mechanical transduction along a single soft polymer based on exact solutions to the realistic three-dimensional wormlike-chain model and augmented with analytical relations derived from simpler polymer models. The results reveal surprisingly that a soft polymer with vanishingly small persistence length below a single chemical bond still transduces biased displacement and mechanical work up to practically significant amounts. This "soft" approach possesses unique advantages over the conventional wisdom of rigidity-based transduction, and potentially leads to a unified mechanism for effective allosterylike transduction and relay of mechanical actions, information, control, and molecules from one position to another in molecular devices and motors. This study also identifies an entropy limit unique to the soft transduction, and thereby suggests a possibility of detecting higher efficiency for kinesin motor and mutants in future experiments.

Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

PubMed

Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

2016-04-14

Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide.

PubMed

Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Shiuan, David; Chen, Feng; Li, Jianrong; Liu, Jingbo

2018-01-24

The objective of this work was to identify a novel ACE inhibitory peptide from myosin using a number of in silico methods. Myosin was evaluated as a substrate for use in the generation of ACE inhibitory peptides using BIOPEP and ExPASy PeptideCutter. Then the ACE inhibitory activity prediction of peptides in silico was evaluated using the program peptide ranker, following the database search of known and unknown peptides using the program BIOPEP. In addition, the interaction mechanisms of the peptide and ACE were evaluated by DS. All of the tripeptides were predicted to be nontoxic. Results suggested that the tripeptide NCW exerted potent ACE inhibitory activity with an IC 50 value of 35.5 μM. Furthermore, the results suggested that the peptide NCW comes into contact with Zn 701, Tyr 523, His 383, Glu 384, Glu 411, and His 387. The potential molecular mechanism of the NCW/ACE interaction was investigated. Results confirmed that the higher inhibitory potency of NCW might be attributed to the formation of more hydrogen bonds with the ACE's active site. Therefore, the in silico method is effective to predict and identify novel ACE inhibitory peptides from protein hydrolysates.

Graphene Mechanics: Current Status and Perspectives.

PubMed

Galiotis, Costas; Frank, Otakar; Koukaras, Emmanuel N; Sfyris, Dimitris

2015-01-01

The mechanical properties of 2D materials such as monolayer graphene are of extreme importance for several potential applications. We summarize the experimental and theoretical results to date on mechanical loading of freely suspended or fully supported graphene. We assess the obtained axial properties of the material in tension and compression and comment on the methods used for deriving the various reported values. We also report on past and current efforts to define the elastic constants of graphene in a 3D representation. Current areas of research that are concerned with the effect of production method and/or the presence of defects upon the mechanical integrity of graphene are also covered. Finally, we examine extensively the work related to the effect of graphene deformation upon its electronic properties and the possibility of employing strained graphene in future electronic applications.

A Hierarchical Approach to Fracture Mechanics

NASA Technical Reports Server (NTRS)

Saether, Erik; Taasan, Shlomo

2004-01-01

Recent research conducted under NASA LaRC's Creativity and Innovation Program has led to the development of an initial approach for a hierarchical fracture mechanics. This methodology unites failure mechanisms occurring at different length scales and provides a framework for a physics-based theory of fracture. At the nanoscale, parametric molecular dynamic simulations are used to compute the energy associated with atomic level failure mechanisms. This information is used in a mesoscale percolation model of defect coalescence to obtain statistics of fracture paths and energies through Monte Carlo simulations. The mathematical structure of predicted crack paths is described using concepts of fractal geometry. The non-integer fractal dimension relates geometric and energy measures between meso- and macroscales. For illustration, a fractal-based continuum strain energy release rate is derived for inter- and transgranular fracture in polycrystalline metals.

Derivation in INK-algebras

NASA Astrophysics Data System (ADS)

Kaviyarasu, M.; Indhira, K.

2018-04-01

In 2017 we introduced a new notion of algebra called IKN-algebra. Motivated by some result on derivations (rightleft)-derivation and (leftright)- derivation in ring. In this paper we introduce derivation in INK-Algebras and investigate some important result.

Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism.

PubMed

Liu, Yongjing; Deng, Miaoduo; Yu, Jia; Jiang, Zhen; Guo, Xingjie

2016-05-01

A novel single-isomer cyclodextrin derivative, heptakis {2,6-di-O-[3-(1,3-dicarboxyl propylamino)-2-hydroxypropyl]}-β-cyclodextrin (glutamic acid-β-cyclodextrin) was synthesized and used as a chiral selector in capillary electrophoresis for the enantioseparation of 12 basic drugs, including terbutaline, clorprenaline, tulobuterol, clenbuterol, procaterol, carvedilol, econazole, miconazole, homatropine methyl bromide, brompheniramine, chlorpheniramine and pheniramine. The primary factors affecting separation efficiency, which include the background electrolyte pH, the concentration of glutamic acid-β-cyclodextrin and phosphate buffer concentration, were investigated. Satisfactory enantioseparations were obtained using an uncoated fused-silica capillary of 50 cm (effective length 40 cm) × 50 μm id with 120 mM phosphate buffer (pH 2.5-4.0) containing 0.5-4.5 mM glutamic acid-β-cyclodextrin as background electrolyte. A voltage of 20 kV was applied and the capillary temperature was kept at 20°C. The results proved that glutamic acid-β-cyclodextrin was an effective chiral selector for studied 12 basic drugs. Moreover, the possible chiral recognition mechanism of brompheniramine, chlorpheniramine and pheniramine on glutamic acid-β-cyclodextrin was investigated using the semi-empirical Parametric Method 3. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of catalytic hydrodeoxygenation of lignin-derived phenols from biomass pyrolysis.

PubMed

Bu, Quan; Lei, Hanwu; Zacher, Alan H; Wang, Lu; Ren, Shoujie; Liang, Jing; Wei, Yi; Liu, Yupeng; Tang, Juming; Zhang, Qin; Ruan, Roger

2012-11-01

Catalytic hydrodeoxygenation (HDO) of lignin-derived phenols which are the lowest reactive chemical compounds in biomass pyrolysis oils has been reviewed. The hydrodeoxygenation (HDO) catalysts have been discussed including traditional HDO catalysts such as CoMo/Al(2)O(3) and NiMo/Al(2)O(3) catalysts and transition metal catalysts (noble metals). The mechanism of HDO of lignin-derived phenols was analyzed on the basis of different model compounds. The kinetics of HDO of different lignin-derived model compounds has been investigated. The diversity of bio-oils leads to the complexities of HDO kinetics. The techno-economic analysis indicates that a series of major technical and economical efforts still have to be investigated in details before scaling up the HDO of lignin-derived phenols in existed refinery infrastructure. Examples of future investigation of HDO include significant challenges of improving catalysts and optimum operation conditions, further understanding of kinetics of complex bio-oils, and the availability of sustainable and cost-effective hydrogen source. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hydrogen-bonding and the sweet taste mechanism

NASA Astrophysics Data System (ADS)

Mathlouthi, M.; Portmann, M. O.

1990-09-01

The tripartite glucophores (AH-B,γ) of some natural (sugars) and artificial (Aspartame, Acesulfame, Saccharin, NHDHC and Trichlorogalactosucrose) sweeteners are proposed. These propositions are based on the molecular structure and infrared spectra of the studied molecules. The role of water in the sweet taste mechanism of small carbohydrates and artificial sweeteners was derived from the Raman spectra of their aqueous solutions. Comparison of the intensities and frequencies of the calculated components of the experimental Raman band of water on the one hand and of aqueous solutions of sweeteners on the other permitted interpretation of the role of water in the sweetness mechanism.

Differentiation and Application of Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.

PubMed

Maguire, Eithne Margaret; Xiao, Qingzhong; Xu, Qingbo

2017-11-01

Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. © 2017 American Heart Association, Inc.

Synthesis of pyrido[1,2-a]benzimidazoles and other fused imidazole derivatives with a bridgehead nitrogen atom

NASA Astrophysics Data System (ADS)

Begunov, Roman S.; Ryzvanovich, Galina A.

2013-01-01

Main methods for the synthesis of fused imidazole derivatives with a bridgehead nitrogen atom are systematically considered and summarized. The reaction mechanisms that underlie the methods for the synthesis of pyrido[1,2-a]benzimidazoles and related compounds are described. Biological properties and mechanisms of the biological activity of fused azaheterocycles are discussed. The bibliography includes 152 references.

A study of the relationship between process conditions and mechanical strength of mineralized red algae in the preparation of a marine-derived bone void filler.

PubMed

Walsh, P J; Walker, G M; Maggs, C A; Buchanan, F J

2011-06-01

Bone void fillers that can enhance biological function to augment skeletal repair have significant therapeutic potential in bone replacement surgery. This work focuses on the development of a unique microporous (0.5-10 microm) marine-derived calcium phosphate bioceramic granule. It was prepared from Corallina officinalis, a mineralized red alga, using a novel manufacturing process. This involved thermal processing, followed by a low pressure-temperature chemical synthesis reaction. The study found that the ability to maintain the unique algal morphology was dependent on the thermal processing conditions. This study investigates the effect of thermal heat treatment on the physiochemical properties of the alga. Thermogravimetric analysis was used to monitor its thermal decomposition. The resultant thermograms indicated the presence of a residual organic phase at temperatures below 500 degrees C and an irreversible solid-state phase transition from mg-rich-calcite to calcium oxide at temperatures over 850 degrees C. Algae and synthetic calcite were evaluated following heat treatment in an air-circulating furnace at temperatures ranging from 400 to 800 degrees C. The highest levels of mass loss occurred between 400-500 degrees C and 700-800 degrees C, which were attributed to the organic and carbonate decomposition respectively. The changes in mechanical strength were quantified using a simple mechanical test, which measured the bulk compressive strength of the algae. The mechanical test used may provide a useful evaluation of the compressive properties of similar bone void fillers that are in granular form. The study concluded that soak temperatures in the range of 600 to 700 degrees C provided the optimum physiochemical properties as a precursor to conversion to hydroxyapatite (HA). At these temperatures, a partial phase transition to calcium oxide occurred and the original skeletal morphology of the alga remained intact.

Quantum mechanics from Newton's second law and the canonical commutation relation [X, P] = i

NASA Astrophysics Data System (ADS)

Palenik, Mark C.

2014-07-01

Despite the fact that it has been known since the time of Heisenberg that quantum operators obey a quantum version of Newton's laws, students are often told that derivations of quantum mechanics must necessarily follow from the Hamiltonian or Lagrangian formulations of mechanics. Here, we first derive the existing Heisenberg equations of motion from Newton's laws and the uncertainty principle using only the equations F=\\frac{dP}{dt}, P=m\\frac{dV}{dt}, and [X, P] = i. Then, a new expression for the propagator is derived that makes a connection between time evolution in quantum mechanics and the motion of a classical particle under Newton's laws. The propagator is solved for three cases where an exact solution is possible: (1) the free particle; (2) the harmonic oscillator; and (3) a constant force, or linear potential in the standard interpretation. We then show that for a general for a general force F(X), by Taylor expanding X(t) in time, we can use this methodology to reproduce the Feynman path integral formula for the propagator. Such a picture may be useful for students as they make the transition from classical to quantum mechanics and help solidify the equivalence of the Hamiltonian, Lagrangian, and Newtonian pictures of physics in their minds.

Synthesis and evaluation of thermo-rheological behaviour and ionotropic crosslinking of new gellan gum-alkyl derivatives.

PubMed

Agnello, Stefano; Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Giammona, Gaetano

2018-04-01

This paper reports the synthesis and the physicochemical characterization of two series of gellan gum (GG) derivatives functionalized with alkyl chains with different number of carbon, from 8 to 18. In particular, low molecular weight gellan gum samples with 52.6 or 96.7 kDa, respectively, were functionalized with octylamine (C 8 ), dodecylamine (C 12 ) and octadecylamine (C 18 ) by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. Thermo-rheological and ionotropic crosslinking properties of these gellan gum-alkyl derivatives were evaluated and related to the degree of derivatization in alkyl chains. Results suggested as length and degree of derivatization differently influenced coil-to-helix gelation mechanism of GG derivatives, ionotropic crosslinking, and strength of crosslinked hydrogels obtained in CaCl 2 0.102 M and NaCl 0.15 M. Statement of hypothesis: The insertion of alkyl chains on the gellan gum backbone interferes with coil-to-helix transition mechanism and allows the production of hydrophobically assembled hydrogels. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

PubMed Central

Kim, Chang-Sei; Ansermino, J. Mark; Hahn, Jin-Oh

2016-01-01

The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID:26870728

Methods And Systms For Analyzing The Degradation And Failure Of Mechanical Systems

DOEpatents

Jarrell, Donald B.; Sisk, Daniel R.; Hatley, Darrel D.; Kirihara, Leslie J.; Peters, Timothy J.

2005-02-08

Methods and systems for identifying, understanding, and predicting the degradation and failure of mechanical systems are disclosed. The methods include measuring and quantifying stressors that are responsible for the activation of degradation mechanisms in the machine component of interest. The intensity of the stressor may be correlated with the rate of physical degradation according to some determinable function such that a derivative relationship exists between the machine performance, degradation, and the underlying stressor. The derivative relationship may be used to make diagnostic and prognostic calculations concerning the performance and projected life of the machine. These calculations may be performed in real time to allow the machine operator to quickly adjust the operational parameters of the machinery in order to help minimize or eliminate the effects of the degradation mechanism, thereby prolonging the life of the machine. Various systems implementing the methods are also disclosed.

Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.

PubMed

Guan, L-P; Zhao, D-H; Chang, Y; Wen, Z-S; Tang, L-M; Huang, F-F

2013-01-01

In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system. © Georg Thieme Verlag KG Stuttgart · New York.

Operational Axioms for Quantum Mechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Ariano, Giacomo Mauro; Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL 60208

2007-02-21

The mathematical formulation of Quantum Mechanics in terms of complex Hilbert space is derived for finite dimensions, starting from a general definition of physical experiment and from five simple Postulates concerning experimental accessibility and simplicity. For the infinite dimensional case, on the other hand, a C*-algebra representation of physical transformations is derived, starting from just four of the five Postulates via a Gelfand-Naimark-Segal (GNS) construction. The present paper simplifies and sharpens the previous derivation in Ref. [1]. The main ingredient of the axiomatization is the postulated existence of faithful states that allows one to calibrate the experimental apparatus. Such notionmore » is at the basis of the operational definitions of the scalar product and of the transposed of a physical transformation. What is new in the present paper with respect to Ref. [1], is the operational deduction of an involution corresponding to the complex-conjugation for effects, whose extension to transformations allows to define the adjoint of a transformation when the extension is composition-preserving. The existence of such composition-preserving extension among possible extensions is analyzed.« less

Different osteochondral potential of clonal cell lines derived from adult human trabecular bone.

PubMed

Osyczka, Anna M; Nöth, Ulrich; Danielson, Keith G; Tuan, Rocky S

2002-06-01

Cells derived from human trabecular bones have been shown to have multipotential differentiation ability along osteogenic, chondrogenic, and adipogenic lineages. In this study, we have derived two clonal sublines of human trabecular bone cells by means of stable transduction with human papilloma virus E6/E7 genes. Our results showed that these clonal sublines differ in their osteochondral potential, but are equally adipogenic, indicative of the heterogeneous nature of the parental cell population. The availability of these cell lines should be useful for the analysis of the mechanisms regulating the differentiation of adult mesenchymal progenitor cells.

Comparison of closed circuit and Fick-derived oxygen consumption in patients undergoing simultaneous aortocaval occlusion.

PubMed

Hofland, J; Tenbrinck, R; van Eijck, C H J; Eggermont, A M M; Gommers, D; Erdmann, W

2003-04-01

Agreement between continuously measured oxygen consumption during quantitative closed system anaesthesia and intermittently Fick-derived calculated oxygen consumption was assessed in 11 patients undergoing simultaneous occlusion of the aorta and inferior vena cava for hypoxic treatment of pancreatic cancer. All patients were mechanically ventilated using a quantitative closed system anaesthesia machine (PhysioFlex) and had pulmonary and radial artery catheters inserted. During the varying haemodynamic conditions that accompany this procedure, 73 paired measurements were obtained. A significant correlation between Fick-derived and closed system-derived oxygen consumption was found (r = 0.78, p = 0.006). Linear regression showed that Fick-derived measure = [(1.19 x closed system derived measure) - 72], with the overall closed circuit-derived values being higher. However, the level of agreement between the two techniques was poor. Bland-Altman analysis found that the bias was 36 ml.min(-1), precision 39 ml.min(-1), difference between 95% limits of agreement 153 ml.min(-1). Therefore, we conclude that the two measurement techniques are not interchangeable in a clinical setting.

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

PubMed Central

Potts, Malia B.; Kim, Hyun Seok; Fisher, Kurt W.; Hu, Youcai; Carrasco, Yazmin P.; Bulut, Gamze Betul; Ou, Yi-Hung; Herrera-Herrera, Mireya L.; Cubillos, Federico; Mendiratta, Saurabh; Xiao, Guanghua; Hofree, Matan; Ideker, Trey; Xie, Yang; Huang, Lily Jun-shen; Lewis, Robert E.; MacMillan, John B.; White, Michael A.

2014-01-01

A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by siRNA and synthetic microRNA libraries. With this strategy, we matched proteins and microRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected short-interfering RNAs, microRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets. PMID:24129700

Melatonin Promotes Brain-Derived Neurotrophic Factor (BDNF) Expression and Anti-Apoptotic Effects in Neonatal Hemolytic Hyperbilirubinemia via a Phospholipase (PLC)-Mediated Mechanism

PubMed Central

Luo, Yong; Peng, Mei; Wei, Hong

2017-01-01

Background Melatonin therapy shows positive effects on neuroprotective factor brain-derived neurotrophic factor (BDNF) expression and neuronal apoptosis in neonatal hemolytic hyperbilirubinemia. We hypothesized that melatonin promotes BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia through a phospholipase (PLC)-mediated mechanism. Material/Methods A phenylhydrazine hydrochloride (PHZ)-induced neonatal hemolytic hyperbilirubinemia model was constructed in neonatal rats. Four experimental groups – a control group (n=30), a PHZ group (n=30), a PHZ + melatonin group (n=30), and a PHZ + melatonin+U73122 (a PLC inhibitor) group (n=30) – were constructed. Trunk blood was assayed for serum hemoglobin, hematocrit, total and direct bilirubin, BDNF, S100B, and tau protein levels. Brain tissue levels of neuronal apoptosis, BDNF expression, PLC activity, IP3 content, phospho- and total Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) expression, and phospho- and total cAMP response element binding protein (CREB) expression were also assayed. Results PHZ-induced hemolytic hyperbilirubinemia was validated by significantly decreased serum hemoglobin and hematocrit as well as significantly increased total and direct serum bilirubin (p<0.05). Neonatal bilirubin-induced neurotoxicity was validated by significantly decreased serum BDNF, brain BDNF, and serum S100B, along with significantly increased serum tau protein (p<0.05). PHZ-induced hemolytic hyperbilirubinemia significantly decreased serum BDNF, brain BDNF, and PLC/IP3/Ca2+ pathway activation while increasing neuronal apoptosis levels (p<0.05), all of which were partially rescued by melatonin therapy (p<0.05). Pre-treatment with the PLC inhibitor U73122 largely abolished the positive effects of melatonin on PLC/IP3/Ca2+ pathway activation, downstream BDNF levels, and neuronal apoptosis (p<0.05). Conclusions Promotion of BDNF expression and anti-apoptotic effects in neonatal

Chemopreventive role of food-derived proteins and peptides: A review.

PubMed

Hernández-Ledesma, Blanca; Hsieh, Chia-Chien

2017-07-24

Cancer is one of the leading causes of mortality and disability worldwide. Although great advances in cancer treatments such as chemotherapy, surgery, and radiation are currently being achieved, their application is associated with numerous and expensive adverse side effects. Epidemiological evidence has demonstrated that the consumption of certain foods potentially prevents up to 35% of cancer cases. Bioactive components are ubiquitous in nature, also in dietary food, providing an essential link in health maintenance, promotion, and prevention of chronic diseases, such as cancer. Development of bioactive proteins and peptides is a current and innovative strategy for cancer prevention/cure. A growing body of anticancer protein and peptides from natural sources has shown the ability to reduce tumor progression through multiple mechanisms including apoptotic, antiproliferative, antiangiogenic, and immunomodulatory activities. This review is focused on proteins and peptides from different food sources including plants, milk, egg, and marine organisms in which chemopreventive properties have been demonstrated. Other aspects such as mechanism of action, bioavailability, and identification and characterization of food-derived peptides by advance separated technologies are also included. This review highlights the potential application of food-derived peptides as functional food ingredients and pharmaceutical candidates in the auxiliary therapy of cancer.

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Mechanical properties of epoxy composites with plasma-modified rice-husk-derived nanosilica

NASA Astrophysics Data System (ADS)

Hubilla, Fatima Athena D.; Panghulan, Glenson R.; Pechardo, Jason; Vasquez, Magdaleno R., Jr.

2018-01-01

In this study, we explored the use of rice-husk-derived nanosilica (nSiO2) as fillers in epoxy resins. The nSiO2 was irradiated with a capacitively coupled 13.56 MHz radio frequency (RF) plasma using an admixture of argon (Ar) and hexamethyldisiloxane (HMDSO) or 1,7-octadiene (OD) monomers. The plasma-polymerized nSiO2 was loaded at various concentrations (1-5%) into the epoxy matrix. Surface hydrophobicity of the plasma-treated nSiO2-filled composites increased, which is attributed to the attachment of functional groups from the monomer gases on the silica surface. Microhardness increased by at least 10% upon the inclusion of plasma-modified nSiO2 compared with pristine nSiO2-epoxy composites. Likewise, hardness increased with increasing loading volume, with the HMDSO-treated silica composite recording the highest increase. Elastic moduli of the composites also showed an increase of at least 14% compared with untreated nSiO2-filled composites. This work demonstrated the use of rice husk, an agricultural waste, as a nSiO2 source for epoxy resin fillers.

Higuchi equation: derivation, applications, use and misuse.

PubMed

Siepmann, Juergen; Peppas, Nicholas A

2011-10-10

Fifty years ago, the legendary Professor Takeru Higuchi published the derivation of an equation that allowed for the quantification of drug release from thin ointment films, containing finely dispersed drug into a perfect sink. This became the famous Higuchi equation whose fiftieth anniversary we celebrate this year. Despite the complexity of the involved mass transport processes, Higuchi derived a very simple equation, which is easy to use. Based on a pseudo-steady-state approach, a direct proportionality between the cumulative amount of drug released and the square root of time can be demonstrated. In contrast to various other "square root of time" release kinetics, the constant of proportionality in the classical Higuchi equation has a specific, physically realistic meaning. The major benefits of this equation include the possibility to: (i) facilitate device optimization, and (ii) to better understand the underlying drug release mechanisms. The equation can also be applied to other types of drug delivery systems than thin ointment films, e.g., controlled release transdermal patches or films for oral controlled drug delivery. Later, the equation was extended to other geometries and related theories have been proposed. The aim of this review is to highlight the assumptions the derivation of the classical Higuchi equation is based on and to give an overview on the use and potential misuse of this equation as well as of related theories. Copyright © 2011 Elsevier B.V. All rights reserved.

Electrical and mechanical stimulation of cardiac cells and tissue constructs.

PubMed

Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

2016-01-15

The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

Diffeomorphism groups and nonlinear quantum mechanics

NASA Astrophysics Data System (ADS)

Goldin, Gerald A.

2012-02-01

This talk is dedicated to my friend and collaborator, Prof. Dr. Heinz-Dietrich Doebner, on the occasion of his 80th birthday. I shall review some highlights of the approach we have taken in deriving and interpreting an interesting class of nonlinear time-evolution equations for quantum-mechanical wave functions, with few equations; more detail may be found in the references. Then I shall comment on the corresponding hydrodynamical description.

Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.

PubMed

Ruiz-Ruiz, Federico; Mancera-Andrade, Elena I; Iqbal, Hafiz M N

2017-01-01

Marine-based resources such as algae and other marine by-products have been recognized as rich sources of structurally diverse bioactive peptides. Evidently, their structural characteristics including unique amino acid residues are responsible for their biological activity. Several of the above-mentioned marine-origin species show multi-functional bioactivities that are useful for a new discovery and/or reinvention of biologically active ingredients, nutraceuticals and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive peptides have gained a considerable attention with high-value biomedical and/or pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides can be produced through proteolytic-assisted hydrolysis of various marine resources under controlled physicochemical (pH and temperature of the reaction media) environment. Owing to their numerous health-related beneficial effects and therapeutic potential in the treatment and/or prevention of many diseases, such marine-derived bioactive peptides exhibit a wider spectrum of biological activities such as anti-cancerous, anti-proliferative, anti-coagulant, antibacterial, antifungal, and anti-tumor activities among many others. Based on emerging evidence of marine-derived peptide mining, the above-mentioned marine resources contain noteworthy levels of high-value protein. The present review article mainly summarizes the marine-derived bioactive peptides and emphasizing their potential applications in biomedical and/or pharmaceutical sectors of the modern world. In conclusion, recent literature has provided evidence that marine-derived bioactive peptides play a critical role in human health along with many possibilities of designing new functional nutraceuticals and/or pharmaceuticals to clarify potent mechanisms of action for a wider spectrum of diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid...

40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid...

Deriving allowable properties of lumber : a practical guide for interpretation of ASTM standards

Treesearch

Alan Bendtsen; William L. Galligan

1978-01-01

The ASTM standards for establishing clear wood mechanical properties and for deriving structural grades and related allowable properties for visually graded lumber can be confusing and difficult for the uninitiated to interpret. This report provides a practical guide to using these standards for individuals not familiar with their application. Sample stress...

Engineering Students' Conceptions of the Derivative and Some Implications for Their Mathematical Education

ERIC Educational Resources Information Center

Bingolbali, E.; Monaghan, J.; Roper, T.

2007-01-01

This paper explores Mechanical Engineering students' conceptions of and preferences for conceptions of the derivative, and their views on mathematics. Data comes from pre-, post- and delayed post-tests, a preference test, interviews with students and an analysis of calculus courses. Data from Mathematics students is used to make comparisons with…

Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity.

PubMed

Woll, Petter S; Martin, Colin H; Miller, Jeffrey S; Kaufman, Dan S

2005-10-15

Human embryonic stem cells (hESCs) provide a unique resource to analyze early stages of human hematopoiesis. However, little is known about the ability to use hESCs to evaluate lymphocyte development. In the present study, we use a two-step culture method to demonstrate efficient generation of functional NK cells from hESCs. The CD56(+)CD45(+) hESC-derived lymphocytes express inhibitory and activating receptors typical of mature NK cells, including killer cell Ig-like receptors, natural cytotoxicity receptors, and CD16. Limiting dilution analysis suggests that these cells can be produced from hESC-derived hemopoietic progenitors at a clonal frequency similar to CD34(+) cells isolated from cord blood. The hESC-derived NK cells acquire the ability to lyse human tumor cells by both direct cell-mediated cytotoxicity and Ab-dependent cellular cytotoxicity. Additionally, activated hESC-derived NK cells up-regulate cytokine production. hESC-derived lymphoid progenitors provide a novel means to characterize specific cellular and molecular mechanisms that lead to development of specific human lymphocyte populations. These cells may also provide a source for innovative cellular immune therapies.

BRST Formalism for Systems with Higher Order Derivatives of Gauge Parameters

NASA Astrophysics Data System (ADS)

Nirov, Kh. S.

For a wide class of mechanical systems, invariant under gauge transformations with arbitrary higher order time derivatives of gauge parameters, the equivalence of Lagrangian and Hamiltonian BRST formalisms is proved. It is shown that the Ostrogradsky formalism establishes the natural rules to relate the BFV ghost canonical pairs with the ghosts and antighosts introduced by the Lagrangian approach. Explicit relation between corresponding gauge-fixing terms is obtained.

Quantum-mechanical transport equation for atomic systems.

NASA Technical Reports Server (NTRS)

Berman, P. R.

1972-01-01

A quantum-mechanical transport equation (QMTE) is derived which should be applicable to a wide range of problems involving the interaction of radiation with atoms or molecules which are also subject to collisions with perturber atoms. The equation follows the time evolution of the macroscopic atomic density matrix elements of atoms located at classical position R and moving with classical velocity v. It is quantum mechanical in the sense that all collision kernels or rates which appear have been obtained from a quantum-mechanical theory and, as such, properly take into account the energy-level variations and velocity changes of the active (emitting or absorbing) atom produced in collisions with perturber atoms. The present formulation is better suited to problems involving high-intensity external fields, such as those encountered in laser physics.

View Combination: A Generalization Mechanism for Visual Recognition

ERIC Educational Resources Information Center

Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

2011-01-01

We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

Investigation of spin-zero bosons in q-deformed relativistic quantum mechanics

NASA Astrophysics Data System (ADS)

Sobhani, H.; Chung, W. S.; Hassanabadi, H.

2018-04-01

In this article, Scattering states of Klein-Gordon equation for three scatter potentials of single and double Dirac delta and a potential well in the q-deformed formalism of relativistic quantum mechanics have been derived. At first, we discussed how q-deformed formalism can be constructed and used. Postulates of this q-deformed quantum mechanics are noted. Then scattering problems for spin-zero bosons are studied.

Physical-mechanical properties of agar/κ-carrageenan blend film and derived clay nanocomposite film.

PubMed

Rhim, Jong-Whan

2012-12-01

Binary blend films with different mixing ratio of agar and κ-carrageenan were prepared using a solution casting method with and without nanoclay and the effect of their composition on the mechanical, water vapor barrier, and water resistance properties was tested. The tensile strength (TS) of the κ-carrageenan film was greater than that of agar film. The water vapor permeability (WVP) of the agar film was lower than that of κ-carrageenan film, the swelling ratio (SR) and water solubility (WS) of κ-carrageenan film were higher than those of agar film. Each property of the binary blend films varied proportionately depending on the mixing ratio of each component. The XRD result indicated that the nanocomposite with agar/κ-carrageenan/clay (Cloisite(®) Na(+)) was intercalated. Consequently, the mechanical strength, water vapor barrier properties, and water contact angle (CA) were significantly (P < 0.05) improved through nanocomposite formation. © 2012 Institute of Food Technologists®

Discrimination of nuclear spin isomers exploiting the excited state dynamics of a quinodimethane derivative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obaid, Rana; Faculty of Pharmacy, Al-Quds University, Abu Dis, Palestine; Kinzel, Daniel

2014-10-28

Despite the concept of nuclear spin isomers (NSIs) exists since the early days of quantum mechanics, only few approaches have been suggested to separate different NSIs. Here, a method is proposed to discriminate different NSIs of a quinodimethane derivative using its electronic excited state dynamics. After electronic excitation by a laser field with femtosecond time duration, a difference in the behavior of several quantum mechanical operators can be observed. A pump-probe experimental approach for separating these different NSIs is then proposed.

Grey-box state-space identification of nonlinear mechanical vibrations

NASA Astrophysics Data System (ADS)

Noël, J. P.; Schoukens, J.

2018-05-01

The present paper deals with the identification of nonlinear mechanical vibrations. A grey-box, or semi-physical, nonlinear state-space representation is introduced, expressing the nonlinear basis functions using a limited number of measured output variables. This representation assumes that the observed nonlinearities are localised in physical space, which is a generic case in mechanics. A two-step identification procedure is derived for the grey-box model parameters, integrating nonlinear subspace initialisation and weighted least-squares optimisation. The complete procedure is applied to an electrical circuit mimicking the behaviour of a single-input, single-output (SISO) nonlinear mechanical system and to a single-input, multiple-output (SIMO) geometrically nonlinear beam structure.

Cell-derived microparticles and the lung.

PubMed

Nieri, Dario; Neri, Tommaso; Petrini, Silvia; Vagaggini, Barbara; Paggiaro, Pierluigi; Celi, Alessandro

2016-09-01

Cell-derived microparticles are small (0.1-1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB. The role of microparticles in blood coagulation and inflammation, including airway inflammation, is well established in in vitro and animal models. The role of microparticles in human pulmonary diseases, both as pathogenic determinants and biomarkers, is being actively investigated. Microparticles of endothelial origin, suggestive of apoptosis, have been demonstrated in the peripheral blood of patients with emphysema, lending support to the hypothesis that endothelial dysfunction and apoptosis are involved in the pathogenesis of the disease and represent a link with cardiovascular comorbidities. Microparticles also have potential roles in patients with asthma, diffuse parenchymal lung disease, thromboembolism, lung cancer and pulmonary arterial hypertension. Copyright ©ERS 2016.

Statistics of spatial derivatives of velocity and pressure in turbulent channel flow

NASA Astrophysics Data System (ADS)

Vreman, A. W.; Kuerten, J. G. M.

2014-08-01

Statistical profiles of the first- and second-order spatial derivatives of velocity and pressure are reported for turbulent channel flow at Reτ = 590. The statistics were extracted from a high-resolution direct numerical simulation. To quantify the anisotropic behavior of fine-scale structures, the variances of the derivatives are compared with the theoretical values for isotropic turbulence. It is shown that appropriate combinations of first- and second-order velocity derivatives lead to (directional) viscous length scales without explicit occurrence of the viscosity in the definitions. To quantify the non-Gaussian and intermittent behavior of fine-scale structures, higher-order moments and probability density functions of spatial derivatives are reported. Absolute skewnesses and flatnesses of several spatial derivatives display high peaks in the near wall region. In the logarithmic and central regions of the channel flow, all first-order derivatives appear to be significantly more intermittent than in isotropic turbulence at the same Taylor Reynolds number. Since the nine variances of first-order velocity derivatives are the distinct elements of the turbulence dissipation, the budgets of these nine variances are shown, together with the budget of the turbulence dissipation. The comparison of the budgets in the near-wall region indicates that the normal derivative of the fluctuating streamwise velocity (∂u'/∂y) plays a more important role than other components of the fluctuating velocity gradient. The small-scale generation term formed by triple correlations of fluctuations of first-order velocity derivatives is analyzed. A typical mechanism of small-scale generation near the wall (around y+ = 1), the intensification of positive ∂u'/∂y by local strain fluctuation (compression in normal and stretching in spanwise direction), is illustrated and discussed.

The mechanism of thioacetamide-induced apoptosis in the L37 albumin-SV40 T-antigen transgenic rat hepatocyte-derived cell line occurs without DNA fragmentation.

PubMed

Bulera, S J; Sattler, C A; Gast, W L; Heath, S; Festerling, T A; Pitot, H C

1998-10-01

The hepatotoxicant thioacetamide (TH) has classically been used as a model to study hepatic necrosis; however, recent studies have shown that TH can also induce apoptosis. In this report we demonstrate that 2.68+/-0.54% of the albumin-SV40 T-antigen transgenic rat hepatocytes undergo TH-induced apoptosis, a level comparable to other in vivo models of liver apoptosis. In addition, TH could induce apoptosis and necrosis in the L37 albumin-SV40 T-antigen transgenic rat liver-derived cell line. Examination of dying L37 cells treated with 100 mM TH by electron microscopy revealed distinct morphological characteristics that could be attributed to apoptosis. Quantitation of apoptosis by FACS analysis 24 h after treatment with 100 mM TH revealed that 81.3+/-1.6% of the cells were undergoing apoptosis. In contrast, when L37 cells were treated with 250 mM TH, cells exhibited characteristics consistent with necrotic cell death. DNA fragmentation ladders were produced by growth factor withdrawal-induced apoptosis; however, in 100 mM TH-induced apoptosis, DNA fragmentation ladders were not observed. Analysis of endonuclease activity in L37 cells revealed that the enzymes were not inactivated in the presence of 100 mM TH. The data presented in this report indicate that the L37 cell line could be used to study the mechanism of TH-induced apoptosis that was not mediated through a mechanism requiring DNA fragmentation.

MELODI: Mining Enriched Literature Objects to Derive Intermediates

PubMed Central

Elsworth, Benjamin; Dawe, Karen; Vincent, Emma E; Langdon, Ryan; Lynch, Brigid M; Martin, Richard M; Relton, Caroline; Higgins, Julian P T; Gaunt, Tom R

2018-01-01

Abstract Background The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Methods Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Results Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro. Conclusions We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]. PMID:29342271

MELODI: Mining Enriched Literature Objects to Derive Intermediates.

PubMed

Elsworth, Benjamin; Dawe, Karen; Vincent, Emma E; Langdon, Ryan; Lynch, Brigid M; Martin, Richard M; Relton, Caroline; Higgins, Julian P T; Gaunt, Tom R

2018-01-12

The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro. We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]. © The Author(s) 2018. Published by Oxford University Press on behalf of the International Epidemiological Association

Photoinduced Electron Transfer from Various Aniline Derivatives to Graphene Quantum Dots.

PubMed

Ghosh, Tufan; Chatterjee, Swarupa; Prasad, Edamana

2015-12-10

The present study utilizes the luminescence nature of the graphene quantum dots (GQDs) to analyze the mechanistic aspects of the photoinduced electron transfer (PET) processes between GQDs and aniline derivatives. A systematic investigation of PET from various aniline derivatives to GQDs has been presented. Solution-processable GQDs have been synthesized from graphene oxide (GO) at 200 °C. The as-synthesized GQDs exhibit a strong green luminescence at 510 nm, upon photoexcitation at 440 nm. Various aniline derivatives (aniline, N-methylaniline, N,N'-dimethylaniline, N-ethylaniline, N,N'-diethylaniline, and N,N'-diphenylaniline) have been utilized as electron donors to probe the PET process. Results from UV-visible absorption and steady-state and time-resolve luminescence spectroscopy suggest that the GQDs interact with the aniline derivatives in the excited state, which results in a significant luminescence quenching of the GQDs. The bimolecular rate constants of the dynamic quenching have been deduced for various donor-acceptor systems, and the values are in the range of (1.06-2.68) × 10(9) M(-1) s(-1). The negative values of the free energy change of the electron transfer process suggest that PET from aniline derivatives to GQDs is feasible and could be responsible for the luminescence quenching. The PET has been confirmed by detecting radical cations for certain aniline derivatives, using a nanosecond laser flash photolysis setup. The present study shows that among the various types of graphene systems, GQDs are better candidates for understanding the mechanism of PET in graphene-based donor-acceptor systems.

Derivation and characterization of human embryonic stem cell lines from poor quality embryos.

PubMed

Liu, Weiqiang; Yin, Yifei; Long, Xiaolin; Luo, Yumei; Jiang, Yonghua; Zhang, Wenhong; Du, Hongzi; Li, Shaoying; Zheng, Yuhong; Li, Qing; Chen, Xinjie; Liao, Baoping; Xiao, Guohong; Wang, Weihua; Sun, Xiaofang

2009-04-01

Poor quality embryos discarded from in vitro fertilization (IVF) laboratories are good sources for deriving human embryonic stem cell (hESC) lines. In this study, 166 poor quality embryos donated from IVF centers on day 3 were cultured in a blastocyst medium for 2 days, and 32 early blastocysts were further cultured in a blastocyst optimum culture medium for additional 2 days so that the inner cell masses (ICMs) could be identified and isolated easily. The ICMs of 17 blastocysts were isolated by a mechanical method, while those of the other 15 blastocysts were isolated by immunosurgery. All isolated ICMs were inoculated onto a feeder layer for subcultivation. The rates of ICM attachment, primary ICM colony formation and the efficiency of hESC derivation were similar between the ICMs isolated by the two methods (P>0.05). As a result, four new hESC lines were established. Three cell lines had normal karyotypes and one had an unbalanced Robertsonian translocation. All cell lines showed normal hESC characteristics and had the differentiation ability. In conclusion, we established a stable and effective method for hESC isolation and culture, and it was confirmed that the mechanical isolation was an effective method to isolate ICMs from poor embryos. These results further indicate that hESC lines can be derived from poor quality embryos discarded by IVF laboratories.

Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase.

PubMed

Cui, Yi; Hu, Yong-Hua; Yu, Feng; Zheng, Jing; Chen, Lin-Shan; Chen, Qing-Xi; Wang, Qin

2017-02-01

This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV-vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC 50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells.

PubMed

Graziano, Adriana Carol Eleonora; Avola, Rosanna; Perciavalle, Vincenzo; Nicoletti, Ferdinando; Cicala, Gianluca; Coco, Marinella; Cardile, Venera

2018-03-26

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissue-derived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology.

Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells

PubMed Central

Graziano, Adriana Carol Eleonora; Avola, Rosanna; Perciavalle, Vincenzo; Nicoletti, Ferdinando; Cicala, Gianluca; Coco, Marinella; Cardile, Venera

2018-01-01

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissue-derived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology. PMID:29588808

Identification of Baribis fault - West Java using second vertical derivative method of gravity

NASA Astrophysics Data System (ADS)

Sari, Endah Puspita; Subakti, Hendri

2015-04-01

Baribis fault is one of West Java fault zones which is an active fault. In modern era, the existence of fault zone can be observed by gravity anomaly. Baribis fault zone has not yet been measured by gravity directly. Based on this reason, satellite data supported this research. Data used on this research are GPS satellite data downloaded from TOPEX. The purpose of this research is to determine the type and strike of Baribis fault. The scope of this research is Baribis fault zone which lies on 6.50o - 7.50o S and 107.50o - 108.80o E. It consists of 5146 points which one point to another is separated by 1 minute meridian. The method used in this research is the Second Vertical Derivative (SVD) of gravity anomaly. The Second Vertical Derivative of gravity anomaly show as the amplitude of gravity anomaly caused by fault structure which appears as residual anomaly. The zero value of residual gravity anomaly indicates that the contact boundary of fault plane. Second Vertical Derivative method of gravity was applied for identifying Baribis fault. The result of this research shows that Baribis fault has a thrust mechanism. It has a lineament strike varies from 107o to 127o. This result agrees with focal mechanism data of earthquakes occurring on this region based on Global CMT catalogue.

Cascade Synthesis of Five-Membered Lactones using Biomass-Derived Sugars as Carbon Nucleophiles.

PubMed

Yamaguchi, Sho; Matsuo, Takeaki; Motokura, Ken; Miyaji, Akimitsu; Baba, Toshihide

2016-06-06

We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lessons from black pepper: piperine and derivatives thereof.

PubMed

Chavarria, D; Silva, T; Magalhães e Silva, D; Remião, F; Borges, F

2016-01-01

Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine-like derivatives have shown an interesting range of pharmacological activities. In this context, significant advances have been made in the discovery of new chemical entities based on the piperine scaffold endowed with therapeutic potential. The aim of this review is to provide a thorough inquiry on the therapeutic potential of piperine and related derivatives. It provides an overview of recent developments in patented processes and applications thereof between 2000 and 2015. Cumulative evidence shows that piperine is currently paving its way to become a privileged scaffold for the development of bioactive compounds with therapeutic application in multiple human diseases. In particular, piperine derivatives were shown to modulate the activity of several targets related to neurological disorders, including epilepsy, Parkinson's disease, depression and pain related disorders. Moreover, the efflux pump inhibitory ability of piperine and its analogues tackles important drug resistance mechanisms and may improve the clinical efficacy of antibiotic and anticancer drugs. Although the use of piperine as a scaffold for bioactive compounds is still in its early stages, the continuous exploration of this structure may lead to remarkable advances in drug discovery programs.

Quantum mechanical/molecular mechanical/continuum style solvation model: second order Møller-Plesset perturbation theory.

PubMed

Thellamurege, Nandun M; Si, Dejun; Cui, Fengchao; Li, Hui

2014-05-07

A combined quantum mechanical/molecular mechanical/continuum (QM/MM/C) style second order Møller-Plesset perturbation theory (MP2) method that incorporates induced dipole polarizable force field and induced surface charge continuum solvation model is established. The Z-vector method is modified to include induced dipoles and induced surface charges to determine the MP2 response density matrix, which can be used to evaluate MP2 properties. In particular, analytic nuclear gradient is derived and implemented for this method. Using the Assisted Model Building with Energy Refinement induced dipole polarizable protein force field, the QM/MM/C style MP2 method is used to study the hydrogen bonding distances and strengths of the photoactive yellow protein chromopore in the wild type and the Glu46Gln mutant.

Quantum mechanical/molecular mechanical/continuum style solvation model: Second order Møller-Plesset perturbation theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thellamurege, Nandun M.; Si, Dejun; Cui, Fengchao

A combined quantum mechanical/molecular mechanical/continuum (QM/MM/C) style second order Møller-Plesset perturbation theory (MP2) method that incorporates induced dipole polarizable force field and induced surface charge continuum solvation model is established. The Z-vector method is modified to include induced dipoles and induced surface charges to determine the MP2 response density matrix, which can be used to evaluate MP2 properties. In particular, analytic nuclear gradient is derived and implemented for this method. Using the Assisted Model Building with Energy Refinement induced dipole polarizable protein force field, the QM/MM/C style MP2 method is used to study the hydrogen bonding distances and strengths ofmore » the photoactive yellow protein chromopore in the wild type and the Glu46Gln mutant.« less

Rapid control of male typical behaviors by brain-derived estrogens

PubMed Central

Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

2012-01-01

Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF).

PubMed

Amadio, Patrizia; Baldassarre, Damiano; Sandrini, Leonardo; Weksler, Babette B; Tremoli, Elena; Barbieri, Silvia S

2017-01-01

Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.

The galvanizing of Mycobacterium tuberculosis: An antimicrobial mechanism

PubMed Central

Russell, David G

2011-01-01

Summary Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues describe a novel anti-microbial mechanism based on elevated levels of intraphagosomal Zn2+ and the corresponding induction of bacterial genes to ameliorate this host-derived stress. PMID:21925106

Quasivelocities and Optimal Control for underactuated Mechanical Systems

NASA Astrophysics Data System (ADS)

Colombo, L.; de Diego, D. Martín

2010-07-01

This paper is concerned with the application of the theory of quasivelocities for optimal control for underactuated mechanical systems. Using this theory, we convert the original problem in a variational second-order lagrangian system subjected to constraints. The equations of motion are geometrically derived using an adaptation of the classical Skinner and Rusk formalism.

Quasivelocities and Optimal Control for underactuated Mechanical Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colombo, L.; Martin de Diego, D.

2010-07-28

This paper is concerned with the application of the theory of quasivelocities for optimal control for underactuated mechanical systems. Using this theory, we convert the original problem in a variational second-order lagrangian system subjected to constraints. The equations of motion are geometrically derived using an adaptation of the classical Skinner and Rusk formalism.

The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

PubMed

Knobloch, J; Jungck, D; Koch, A

2017-01-01

Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Monocyte activation by smooth muscle cell-derived matrices.

PubMed

Kaufmann, J; Jorgensen, R W; Martin, B M; Franzblau, C

1990-12-01

Mononuclear phagocytes adhere to and penetrate the vessel wall endothelium and contact the subendothelial space prior to the development of the atherosclerotic plaque. In an attempt to model the early events of plaque development we used an elastin-rich, multicomponent, cell-derived matrix from neonatal rat aortic smooth muscle cells as a substratum for monocytes. Using this model, we show that human monocyte morphology and metabolism are markedly altered by the matrix substratum. When a mixed mononuclear cell population is seeded on matrix or plastic, only monocytes adhere to the matrix surface. In contrast, lymphocytes as well as monocytes adhere to the plastic surface. The matrix-adherent monocytes develop large intracellular granules and form extensive clusters of individual cells. Metabolically, these cells develop sodium fluoride resistant non-specific esterase activity and their media contain more growth factor activity and PGE2. Although total protein synthesis is equivalent in both cultures, the matrix contact induces an increase in specific proteins in the media. We also show that a purified alpha-elastin substratum induces some, but not all, of the monocyte changes seen when using the matrix substratum. Using the alpha-elastin substratum, there is selective adhesion of monocytes and increased growth factor activity, however, the cells are morphologically different from the matrix-adherent cells. Thus, the use of the smooth muscle cell-derived matrix, in conjunction with purified matrix components, serves as a model that can provide insight into the mechanisms of monocyte adhesion and stimulation by the matrix environment that exists in vivo. Such mechanisms may be particularly important in atherogenesis.

Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

DTIC Science & Technology

2015-05-01

according to eppin tigen level of I0.2 ng/ml. hed by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.02.027 E U RO P E AN URO L OG Y 5 9...control), as indicated. Endocrine-Related Cancer (2011) 18 451–464 www.endocrinology-journals.orgradical cystectomy specimens with high-grade uro - thelial...is primarily derived from the uro - genital sinus during embryogenesis, which in males also gives rise to the prostate, similar mechanisms of AR

Intracellular origin and ultrastructure of platelet-derived microparticles.

PubMed

Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Rauova, L; Litvinov, R I; Weisel, J W

2017-08-01

Essentials Platelet microparticles play a major role in pathologies, including hemostasis and thrombosis. Platelet microparticles have been analyzed and classified based on their ultrastructure. The structure and intracellular origin of microparticles depend on the cell-activating stimulus. Thrombin-treated platelets fall apart and form microparticles that contain cellular organelles. Background Platelet-derived microparticles comprise the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the (patho)physiological roles of platelet-derived microparticles, mechanisms of their formation and structural details remain largely unknown. Objectives Here we studied the formation, ultrastructure and composition of platelet-derived microparticles from isolated human platelets, either quiescent or stimulated with one of the following activators: arachidonic acid, ADP, collagen, thrombin or calcium ionophore A23187. Methods Using flow cytometry, transmission and scanning electron microscopy, we analyzed the intracellular origin, structural diversity and size distributions of the subcellular particles released from platelets. Results The structure, dimensions and intracellular origin of microparticles depend on the cell-activating stimulus. The main structural groups include a vesicle surrounded by one thin membrane or multivesicular structures. Thrombin, unlike other stimuli, induced formation of microparticles not only from the platelet plasma membrane and cytoplasm but also from intracellular structures. A fraction of these vesicular particles having an intracellular origin contained organelles, such as mitochondria, glycogen granules and vacuoles. The size of platelet-derived microparticles depended on the nature of the cell-activating stimulus. Conclusion The results obtained provide a structural basis for the qualitative differences of various platelet activators, for specific

On the Conformable Fractional Quantum Mechanics

NASA Astrophysics Data System (ADS)

Mozaffari, F. S.; Hassanabadi, H.; Sobhani, H.; Chung, W. S.

2018-05-01

In this paper, a conformable fractional quantum mechanic has been introduced using three postulates. Then in such a formalism, Schr¨odinger equation, probability density, probability flux and continuity equation have been derived. As an application of considered formalism, a fractional-radial harmonic oscillator has been considered. After obtaining its wave function and energy spectrum, effects of the conformable fractional parameter on some quantities have been investigated and plotted for different excited states.

Systematic development of reduced reaction mechanisms for dynamic modeling

NASA Technical Reports Server (NTRS)

Frenklach, M.; Kailasanath, K.; Oran, E. S.

1986-01-01

A method for systematically developing a reduced chemical reaction mechanism for dynamic modeling of chemically reactive flows is presented. The method is based on the postulate that if a reduced reaction mechanism faithfully describes the time evolution of both thermal and chain reaction processes characteristic of a more complete mechanism, then the reduced mechanism will describe the chemical processes in a chemically reacting flow with approximately the same degree of accuracy. Here this postulate is tested by producing a series of mechanisms of reduced accuracy, which are derived from a full detailed mechanism for methane-oxygen combustion. These mechanisms were then tested in a series of reactive flow calculations in which a large-amplitude sinusoidal perturbation is applied to a system that is initially quiescent and whose temperature is high enough to start ignition processes. Comparison of the results for systems with and without convective flow show that this approach produces reduced mechanisms that are useful for calculations of explosions and detonations. Extensions and applicability to flames are discussed.

Photoinduced Charge Transport Spectra for Porphyrin and Naphthalene Derivative-based Dendrimers

NASA Astrophysics Data System (ADS)

Park, J. H.; Wu, Y.; Parquette, J. R.; Epstein, A. J.

2006-03-01

Dendrimers are important chemical structures for harvesting charge. We prepared model dendrimers using two porphyrin derivatives and a naphthalene derivative. Films of these porphyrin derivatives have a strong Soret band (˜430nm) and four significant Q-bands; the naphthalene derivative has strong absorption at 365 and 383nm. Two kinds of photovoltaic cell structures [ITO/BaytronP/(thick or thin) dendrimer/Al] are constructed to investigate the optical response spectra of dendrimers under electric potential(V) on the cell (range from -1V to 2V). To obtain pure optical responses, incident light is modulated with an optical chopper and a lock-in amplifier is used to measure current (IAC) and phase (θ). For the excitation of the Soret band, IAC and θ do not change substantially with change of sign and amplitude of V. For Q-bands and naphthalene absorption bands, θ nearly follows the polarity of V on the cells and IAC is linear with V. Hence, IAC is nearly ohmic for Q- band although there are shifts due to built-in-potential. IAC for Soret band is almost same for thick and thin active layer cells. In contrast, IAC increases with thickness increase for Q bands. Mechanisms of photogeneration and charge transport will be discussed.

Importance of Air Absorption During Mechanical Integrity Testing

NASA Astrophysics Data System (ADS)

Arnold, Fredric C.

1990-11-01

Wells used for injection of liquid industrial waste into deep saline aquifers are required to be periodically tested for mechanical integrity. A generally accepted method to demonstrate mechanical integrity is to pressurize the casing-tubing annulus and monitor any decline in pressure. If air is used to pressurize the annulus, uncertainty may exist in differentiating between absorption of air into water in the annulus and loss of pressure due to the absence of mechanical integrity. An analytical model of air absorbance has been derived and used to quantify the pressure decline due to dissolving and diffusion of the air in annular water. A parameteric study was made to determine when annular pressure decline due to absorption of air is significant.