Plant-parasitic nematodes: towards understanding molecular players in stress responses.

Science.gov (United States)

Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Science.gov (United States)

Pamenter, Matthew E.; Powell, Frank L.

2016-01-01

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

Molecular determinants of magnolol targeting both RXRα and PPARγ.

Directory of Open Access Journals (Sweden)

Haitao Zhang

Full Text Available Nuclear receptors retinoic X receptor α (RXRα and peroxisome proliferator activated receptor γ (PPARγ function potently in metabolic diseases, and are both important targets for anti-diabetic drugs. Coactivation of RXRα and PPARγ is believed to synergize their effects on glucose and lipid metabolism. Here we identify the natural product magnolol as a dual agonist targeting both RXRα and PPARγ. Magnolol was previously reported to enhance adipocyte differentiation and glucose uptake, ameliorate blood glucose level and prevent development of diabetic nephropathy. Although magnolol can bind and activate both of these two nuclear receptors, the transactivation assays indicate that magnolol exhibits biased agonism on the transcription of PPAR-response element (PPRE mediated by RXRα:PPARγ heterodimer, instead of RXR-response element (RXRE mediated by RXRα:RXRα homodimer. To further elucidate the molecular basis for magnolol agonism, we determine both the co-crystal structures of RXRα and PPARγ ligand-binding domains (LBDs with magnolol. Structural analyses reveal that magnolol adopts its two 5-allyl-2-hydroxyphenyl moieties occupying the acidic and hydrophobic cavities of RXRα L-shaped ligand-binding pocket, respectively. While, two magnolol molecules cooperatively accommodate into PPARγ Y-shaped ligand-binding pocket. Based on these two complex structures, the key interactions for magnolol activating RXRα and PPARγ are determined. As the first report on the dual agonist targeting RXRα and PPARγ with receptor-ligand complex structures, our results are thus expected to help inspect the potential pharmacological mechanism for magnolol functions, and supply useful hits for nuclear receptor multi-target ligand design.

From electrochemical biosensors to biomimetic sensors based on molecularly imprinted polymers in environmental determination of heavy metals

Science.gov (United States)

Malitesta, Cosimino; Di Masi, Sabrina; Mazzotta, Elisabetta

2017-07-01

Recent work relevant to heavy metal determination by inhibition-enzyme electrochemical biosensors and by selected biomimetic sensors based on molecularly imprinted polymers has been reviewed. General features and peculiar aspects have been evidenced. The replace of biological component by artificial receptors promises higher selectivity and stability, while biosensors keep their capability of producing an integrated response directly related to toxicity of the samples.

Molecular mechanisms of radioadaptive responses in human lymphoblastoid cells

International Nuclear Information System (INIS)

Kakimoto, Ayana; Taki, Keiko; Nakajima, Tetsuo

2008-01-01

Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored the molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-amino-benzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation even in the presence of 3AB. These findings suggested that molecular mechanisms of the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration, although we could not exclude a possibility that the differential effects of 3AB was due to cell type difference. Finally, by performing a comprehensive analysis of alterations in gene expression using high coverage expression profiling (HiCEP), we could identify 17 genes whose expressions were significantly altered 6 h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expressions of which were different with or without priming

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

Science.gov (United States)

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Simultaneous all-optical determination of molecular concentration and extinction coefficient.

Science.gov (United States)

Cho, Byungmoon; Tiwari, Vivek; Jonas, David M

2013-06-04

Absolute molecular number concentration and extinction coefficient are simultaneously determined from linear and nonlinear spectroscopic measurements. This method is based on measurements of absolute femtosecond pump-probe signals. Accounting for pulse propagation, we present a closed form expression for molecular number concentration in terms of absorbance, fluorescence, absolute pump-probe signal, and laser pulse parameters (pulse energy, spectrum, and spatial intensity profile); all quantities are measured optically. As in gravimetric and coulometric determinations of concentration, no standard samples are needed for calibration. The extinction coefficient can then be determined from the absorbance spectrum and the concentration. For fluorescein in basic methanol, the optically determined molar concentrations and extinction coefficients match gravimetric determinations to within 10% for concentrations from 0.032 to 0.540 mM, corresponding to absorbance from 0.06 to 1. In principle, this photonumeric method is extensible to transient chemical species for which other methods are not available.

Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis

International Nuclear Information System (INIS)

Moneo, Victoria; Serelde, Beatriz G; Blanco-Aparicio, Carmen; Diaz-Uriarte, Ramon; Avilés, Pablo; Santamaría, Gemma; Tercero, Juan C; Cuevas, Carmen; Carnero, Amancio

2014-01-01

Zalypsis® is a marine compound in phase II clinical trials for multiple myeloma, cervical and endometrial cancer, and Ewing’s sarcoma. However, the determinants of the response to Zalypsis are not well known. The identification of biomarkers for Zalypsis activity would also contribute to broaden the spectrum of tumors by selecting those patients more likely to respond to this therapy. Using in vitro drug sensitivity data coupled with a set of molecular data from a panel of sarcoma cell lines, we developed molecular signatures that predict sensitivity to Zalypsis. We verified these results in culture and in vivo xenograft studies. Zalypsis resistance was dependent on the expression levels of PDGFRα or constitutive phosphorylation of c-Kit, indicating that the activation of tyrosine kinase receptors (TKRs) may determine resistance to Zalypsis. To validate our observation, we measured the levels of total and active (phosphorylated) forms of the RTKs PDGFRα/β, c-Kit, and EGFR in a new panel of diverse solid tumor cell lines and found that the IC50 to the drug correlated with RTK activation in this new panel. We further tested our predictions about Zalypsis determinants for response in vivo in xenograft models. All cells lines expressing low levels of RTK signaling were sensitive to Zalypsis in vivo, whereas all cell lines except two with high levels of RTK signaling were resistant to the drug. RTK activation might provide important signals to overcome the cytotoxicity of Zalypsis and should be taken into consideration in current and future clinical trials

Determination of Viscosity-Average Molecular Weight of Chitosan using Intrinsic Viscosity Measurement

International Nuclear Information System (INIS)

Norzita Yacob; Norhashidah Talip; Maznah Mahmud

2011-01-01

Molecular weight of chitosan can be determined by different techniques such as Gel Permeation Chromatography (GPC), Static Light Scattering (SLS) and intrinsic viscosity measurement. Determination of molecular weight by intrinsic viscosity measurement is a simple method for characterization of chitosan. Different concentrations of chitosan were prepared and measurement was done at room temperature. The flow time data was used to calculate the intrinsic viscosity by extrapolating the reduced viscosity to zero concentration. The value of intrinsic viscosity was then recalculated into the viscosity-average molecular weight using Mark-Houwink equation. (author)

From Electrochemical Biosensors to Biomimetic Sensors Based on Molecularly Imprinted Polymers in Environmental Determination of Heavy Metals

Directory of Open Access Journals (Sweden)

Cosimino Malitesta

2017-07-01

Full Text Available Recent work relevant to heavy metal determination by inhibition-enzyme electrochemical biosensors and by selected biomimetic sensors based on molecularly imprinted polymers has been reviewed. General features and peculiar aspects have been evidenced. The replace of biological component by artificial receptors promises higher selectivity and stability, while biosensors keep their capability of producing an integrated response directly related to biological toxicity of the samples.

Physiological response, molecular analysis and water use efficiency ...

African Journals Online (AJOL)

With a view to study the effects of irrigation scheduling on the water use efficiency and physiological response and molecular basis of maize hybrids of different maturity groups, a field experiment was conducted at Water Management Research Center (WMRC), Belvatagi, University of Agricultural Sciences, Dharwad, India ...

Molecular mechanism and genetic determinants of buprofezin degradation.

Science.gov (United States)

Chen, Xueting; Ji, Junbin; Zhao, Leizhen; Qiu, Jiguo; Dai, Chen; Wang, Weiwu; He, Jian; Jiang, Jiandong; Hong, Qing; Yan, Xin

2017-07-14

. However, the molecular mechanism and genetic determinants of microbial degradation of buprofezin has not been well identified. This work revealed that gene cluster bfzBA3A4A1A2C is responsible for the upstream catabolic pathway of buprofezin in R. qingshengii YL-1. The products of bfzBA3A4A1A2C could also degrade bifenthrin, a widely used pyrethroid insecticide. These findings enhance our understanding of the microbial degradation mechanism of buprofezin and benefit the application of strain YL-1 and bfzBA3A4A1A2C in the bioremediation of buprofezin contamination. Copyright © 2017 American Society for Microbiology.

Molecular response to water stress in two contrasting Mediterranean pines (Pinus pinaster and Pinus pinea).

Science.gov (United States)

Perdiguero, Pedro; Barbero, María Del Carmen; Cervera, María Teresa; Collada, Carmen; Soto, Alvaro

2013-06-01

Adaptation to water stress has determined the evolution and diversification of vascular plants. Water stress is forecasted to increase drastically in the next decades in certain regions, such as in the Mediterranean basin. Consequently, a proper knowledge of the response and adaptations to drought stress is essential for the correct management of plant genetic resources. However, most of the advances in the understanding of the molecular response to water stress have been attained in angiosperms, and are not always applicable to gymnosperms. In this work we analyse the transcriptional response of two emblematic Mediterranean pines, Pinus pinaster and Pinus pinea, which show noticeable differences in their performance under water stress. Using microarray analysis, up to 113 genes have been detected as significantly induced by drought in both species. Reliability of expression patterns has been confirmed by RT-PCR. While induced genes with similar profiles in both species can be considered as general candidate genes for the study of drought response in conifers, genes with diverging expression patterns can underpin the differences displayed by these species under water stress. Most promising candidate genes for drought stress response include genes related to carbohydrate metabolism, such as glycosyltransferases or galactosidases, sugar transporters, dehydrins and transcription factors. Additionally, differences in the molecular response to drought and polyethylene-glycol-induced water stress are also discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria

NARCIS (Netherlands)

Price, Ric N.; Uhlemann, Anne-Catrin; van Vugt, Michele; Brockman, Al; Hutagalung, Robert; Nair, Shalini; Nash, Denae; Singhasivanon, Pratap; Anderson, Tim J. C.; Krishna, Sanjeev; White, Nicholas J.; Nosten, François

2006-01-01

Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). On the northwest border of Thailand, patients with uncomplicated Plasmodium falciparum malaria were enrolled in prospective

Voltammetric Determination of Flunixin on Molecularly Imprinted Polypyrrole Modified Glassy Carbon Electrode

Directory of Open Access Journals (Sweden)

Abd-Elgawad Radi

2016-01-01

Full Text Available A novel electrochemical sensing approach, based on electropolymerization of a molecularly imprinted polypyrrole (MIPpy film onto a glassy carbon electrode (GCE surface, was developed for the detection of flunixin (FXN. The sensing conditions and the performance of the constructed sensor were assessed by cyclic, differential pulse and (DPV square wave voltammetry (SWV. The sensor exhibited high sensitivity, with linear responses in the range of 5.0 to 50.0 µM with detection limits of 1.5 and 1.0 µM for DPV and SWV, respectively. In addition, the sensor showed high selectivity towards FXN in comparison to other interferents. The sensor was successfully utilized for the direct determination of FXN in buffalo raw milk samples.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

Science.gov (United States)

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling

Directory of Open Access Journals (Sweden)

Francis J. May

2017-02-01

Full Text Available Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT and brown adipose tissue (BAT are unknown. Here, we utilize MS/MSALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA, phosphatidylcholines (PC, phosphatidylethanolamines (PE, and phosphatidylserines (PS in scWAT and increase specific molecular species of PC and PE in BAT. Exercise also decreases most triacylglycerols (TAGs in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome are highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflect selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.

Ion-molecular equilibria and activity determination in the RbF-ZrF4 system

International Nuclear Information System (INIS)

Skokan, E.V.; Nikitin, M.I.; Sorokin, I.D.; Korenev, Yu.M.; Sidorov, L.N.

1983-01-01

Activity of zirconium tetrofluoride in 100-33.3 mol % ZrF 4 concentration range was determined during isothermal evaporation of samples of different initial composition of RbF-ZrF 4 system, using ion-molecular equilibrium method. It became possible, using the exchange ion-molecular reactions to determine ZrF 4 activity approximately 10 -10 in the region of state diagram of RbF-ZrF 4 system, adjoining to rubidium fluoride. The comparative analysis of results, obtained by the methods of isothermal evaporation, ion-molecular equilibria is given; the advantages and restrictions of ion-molecular equilibrium method are presented

Molecular responses and expression analysis of genes in a ...

African Journals Online (AJOL)

Haloxylon ammodendron (C.A Mey.) Bunge is a xero-halophytic desert shrub with excellent drought resistance and salt tolerance. To decipher the molecular responses involved in its drought resistance, the cDNA-AFLP (amplified fragment length polymorphism) technique was employed to identify genes expressed ...

Rotational temperature determinations in molecular gas lasers

International Nuclear Information System (INIS)

Weaver, L.A.; Taylor, L.H.; Denes, L.J.

1975-01-01

The small-signal gain expressions for vibrational-rotational transitions are examined in detail to determine possible methods of extracting the rotational temperature from experimental gain measurements in molecular gas lasers. Approximate values of T/subr/ can be deduced from the rotational quantum numbers for which the P- and R-branch gains are maximum. Quite accurate values of T/subr/ and the population inversion density (n/subv//sub prime/-n/subv//sub double-prime/) can be determined by fitting data to suitably linearized gain relationships, or by performing least-squares fits of the P- and R-branch experimental data to the full gain expressions. Experimental gain measurements for 15 P-branch and 12 R-branch transitions in the 10.4-μm CO 2 band have been performed for pulsed uv-preionized laser discharges in CO 2 : N 2 : He=1 : 2 : 3 mixtures at 600 Torr. These data are subjected to the several gain analyses described herein, yielding a rotational temperature of 401plus-or-minus10 degreeK and an inversion density of (3.77plus-or-minus0.07) times10 17 cm -3 for conditions of maximum gain. These techniques provide accurate values of the gas temperature in molecular gas lasers with excellent temporal and spatial resolution, and should be useful in extending the conversion efficiency and arcing limits of high-energy electrically exc []ted lasers

Hydrogen molecular ions for improved determination of fundamental constants

NARCIS (Netherlands)

Karr, J.-P.; Hilico, L.; Koelemeij, J.C.J.; Korobov, V.I.

2016-01-01

The possible use of high-resolution rovibrational spectroscopy of the hydrogen molecular ions H-2(+) and HD+ for an independent determination of several fundamental constants is analyzed. While these molecules had been proposed for the metrology of nuclear-to-electron mass ratios, we show that they

Molecular determinants of Ebola virus virulence in mice.

Directory of Open Access Journals (Sweden)

Hideki Ebihara

2006-07-01

Full Text Available Zaire ebolavirus (ZEBOV causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. The molecular basis for the extreme virulence of ZEBOV remains elusive. While adult mice resist ZEBOV infection, the Mayinga strain of the virus has been adapted to cause lethal infection in these animals. To understand the pathogenesis underlying the extreme virulence of Ebola virus (EBOV, here we identified the mutations responsible for the acquisition of the high virulence of the adapted Mayinga strain in mice, by using reverse genetics. We found that mutations in viral protein 24 and in the nucleoprotein were primarily responsible for the acquisition of high virulence. Moreover, the role of these proteins in virulence correlated with their ability to evade type I interferon-stimulated antiviral responses. These findings suggest a critical role for overcoming the interferon-induced antiviral state in the pathogenicity of EBOV and offer new insights into the pathogenesis of EBOV infection.

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

Science.gov (United States)

Chung, Pil Seung; Song, Wonyup; Biegler, Lorenz T.; Jhon, Myung S.

2017-05-01

During the operation of hard disk drive (HDD), the perfluoropolyether (PFPE) lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″) by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

Directory of Open Access Journals (Sweden)

Pil Seung Chung

2017-05-01

Full Text Available During the operation of hard disk drive (HDD, the perfluoropolyether (PFPE lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic and loss (viscous moduli (G′ and G″ by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Molecular structure determination of cyclooctane by Ab Initio and electron diffraction methods in the gas phase

International Nuclear Information System (INIS)

Almeida, Wagner B. de

2000-01-01

The determination of the molecular structure of molecules is of fundamental importance in chemistry. X-rays and electron diffraction methods constitute in important tools for the elucidation of the molecular structure of systems in the solid state and gas phase, respectively. The use of quantum mechanical molecular orbital ab initio methods offer an alternative for conformational analysis studies. Comparison between theoretical results and those obtained experimentally in the gas phase can make a significant contribution for an unambiguous determination of the geometrical parameters. In this article the determination for an unambiguous determination of the geometrical parameters. In this article the determination of the molecular structure of the cyclooctane molecule by electron diffraction in the gas phase an initio calculations will be addressed, providing an example of a comparative analysis of theoretical and experimental predictions. (author)

A novel heat shock protein alpha 8 (Hspa8) molecular network mediating responses to stress- and ethanol-related behaviors.

Science.gov (United States)

Urquhart, Kyle R; Zhao, Yinghong; Baker, Jessica A; Lu, Ye; Yan, Lei; Cook, Melloni N; Jones, Byron C; Hamre, Kristin M; Lu, Lu

2016-04-01

Genetic differences mediate individual differences in susceptibility and responses to stress and ethanol, although, the specific molecular pathways that control these responses are not fully understood. Heat shock protein alpha 8 (Hspa8) is a molecular chaperone and member of the heat shock protein family that plays an integral role in the stress response and that has been implicated as an ethanol-responsive gene. Therefore, we assessed its role in mediating responses to stress and ethanol across varying genetic backgrounds. The hippocampus is an important mediator of these responses, and thus, was examined in the BXD family of mice in this study. We conducted bioinformatic analyses to dissect genetic factors modulating Hspa8 expression, identify downstream targets of Hspa8, and examined its role. Hspa8 is trans-regulated by a gene or genes on chromosome 14 and is part of a molecular network that regulates stress- and ethanol-related behaviors. To determine additional components of this network, we identified direct or indirect targets of Hspa8 and show that these genes, as predicted, participate in processes such as protein folding and organic substance metabolic processes. Two phenotypes that map to the Hspa8 locus are anxiety-related and numerous other anxiety- and/or ethanol-related behaviors significantly correlate with Hspa8 expression. To more directly assay this relationship, we examined differences in gene expression following exposure to stress or alcohol and showed treatment-related differential expression of Hspa8 and a subset of the members of its network. Our findings suggest that Hspa8 plays a vital role in genetic differences in responses to stress and ethanol and their interactions.

NMR determinations of molecular geometries in liquid crystal media

International Nuclear Information System (INIS)

Long, R.C.; Goldstein, J.H.

1983-01-01

The application of NMR spectroscopy in oriented media to the determination of molecular geometries is illustrated by results for three distinctly different molecules: naphthalene, ethylene oxide and spiropentane. The need for systematic application of vibrational corrections is emphasized and some of the effects associated with the different choices of solvent media are considered

A stochastic phase-field model determined from molecular dynamics

KAUST Repository

von Schwerin, Erik

2010-03-17

The dynamics of dendritic growth of a crystal in an undercooled melt is determined by macroscopic diffusion-convection of heat and by capillary forces acting on the nanometer scale of the solid-liquid interface width. Its modelling is useful for instance in processing techniques based on casting. The phase-field method is widely used to study evolution of such microstructural phase transformations on a continuum level; it couples the energy equation to a phenomenological Allen-Cahn/Ginzburg-Landau equation modelling the dynamics of an order parameter determining the solid and liquid phases, including also stochastic fluctuations to obtain the qualitatively correct result of dendritic side branching. This work presents a method to determine stochastic phase-field models from atomistic formulations by coarse-graining molecular dynamics. It has three steps: (1) a precise quantitative atomistic definition of the phase-field variable, based on the local potential energy; (2) derivation of its coarse-grained dynamics model, from microscopic Smoluchowski molecular dynamics (that is Brownian or over damped Langevin dynamics); and (3) numerical computation of the coarse-grained model functions. The coarse-grained model approximates Gibbs ensemble averages of the atomistic phase-field, by choosing coarse-grained drift and diffusion functions that minimize the approximation error of observables in this ensemble average. © EDP Sciences, SMAI, 2010.

A stochastic phase-field model determined from molecular dynamics

KAUST Repository

von Schwerin, Erik; Szepessy, Anders

2010-01-01

The dynamics of dendritic growth of a crystal in an undercooled melt is determined by macroscopic diffusion-convection of heat and by capillary forces acting on the nanometer scale of the solid-liquid interface width. Its modelling is useful for instance in processing techniques based on casting. The phase-field method is widely used to study evolution of such microstructural phase transformations on a continuum level; it couples the energy equation to a phenomenological Allen-Cahn/Ginzburg-Landau equation modelling the dynamics of an order parameter determining the solid and liquid phases, including also stochastic fluctuations to obtain the qualitatively correct result of dendritic side branching. This work presents a method to determine stochastic phase-field models from atomistic formulations by coarse-graining molecular dynamics. It has three steps: (1) a precise quantitative atomistic definition of the phase-field variable, based on the local potential energy; (2) derivation of its coarse-grained dynamics model, from microscopic Smoluchowski molecular dynamics (that is Brownian or over damped Langevin dynamics); and (3) numerical computation of the coarse-grained model functions. The coarse-grained model approximates Gibbs ensemble averages of the atomistic phase-field, by choosing coarse-grained drift and diffusion functions that minimize the approximation error of observables in this ensemble average. © EDP Sciences, SMAI, 2010.

Molecular diffusion in monolayer and submonolayer nitrogen

DEFF Research Database (Denmark)

Hansen, Flemming Yssing; Bruch, Ludwig Walter

2001-01-01

The orientational and translational motions in a monolayer fluid of physisorbed molecular nitrogen are treated using molecular dynamics simulations. Dynamical response functions and several approximations to the coefficient of translational diffusion are determined for adsorption on the basal plane...

Quantitative Determination of Organic Semiconductor Microstructure from the Molecular to Device Scale

KAUST Repository

Rivnay, Jonathan

2012-10-10

A study was conducted to demonstrate quantitative determination of organic semiconductor microstructure from the molecular to device scale. The quantitative determination of organic semiconductor microstructure from the molecular to device scale was key to obtaining precise description of the molecular structure and microstructure of the materials of interest. This information combined with electrical characterization and modeling allowed for the establishment of general design rules to guide future rational design of materials and devices. Investigations revealed that a number and variety of defects were the largest contributors to the existence of disorder within a lattice, as organic semiconductor crystals were dominated by weak van der Waals bonding. Crystallite size, texture, and variations in structure due to spatial confinement and interfaces were also found to be relevant for transport of free charge carriers and bound excitonic species over distances that were important for device operation.

Proteomic-Biostatistic Integrated Approach for Finding the Underlying Molecular Determinants of Hypertension in Human Plasma.

Science.gov (United States)

Gajjala, Prathibha R; Jankowski, Vera; Heinze, Georg; Bilo, Grzegorz; Zanchetti, Alberto; Noels, Heidi; Liehn, Elisa; Perco, Paul; Schulz, Anna; Delles, Christian; Kork, Felix; Biessen, Erik; Narkiewicz, Krzysztof; Kawecka-Jaszcz, Kalina; Floege, Juergen; Soranna, Davide; Zidek, Walter; Jankowski, Joachim

2017-08-01

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension. © 2017 American Heart Association, Inc.

Determination of molecular species of lecithin from erythrocytes and plasma

NARCIS (Netherlands)

Golde, L.M.G. van; Tomasi, V.; Deenen, L.L.M. van

The molecular species of lecithin from erythrocyte and plasma of man and rabbit were determined after conversion of the lecithins into diglycerides by means of hydrolysis with phospholipase C. The resultant diglycerides were separated by thin-layer chromatography on silica impregnated with silver

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

Directory of Open Access Journals (Sweden)

Zhao Y

2015-06-01

Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

Determination of viscosity-average molecular weight of chitosan using intrinsic viscosity measurement

International Nuclear Information System (INIS)

Norzita Yacob; Norhashidah Talip; Maznah Mahmud; Nurul Aizam Idayu Mat Sani; Nor Akma Samsuddin; Norafifah Ahmad Fabillah

2013-01-01

Determination of molecular weight by intrinsic viscosity measurement is a simple method for characterization of chitosan. To study the effect of radiation on molecular weight, chitosan was first irradiated using electron beam at different doses prior to measurement. Different concentrations of chitosan were prepared and measurement was done at room temperature. The flow time data was used to calculate the intrinsic viscosity by extrapolating the reduced viscosity to zero concentration. The value of intrinsic viscosity was then recalculated into the viscosity-average molecular weight using Mark-Houwink equation. (Author)

Use of X-ray diffraction, molecular simulations, and spectroscopy to determine the molecular packing in a polymer-fullerene bimolecular crystal

KAUST Repository

Miller, Nichole Cates

2012-09-05

The molecular packing in a polymer: fullerene bimolecular crystal is determined using X-ray diffraction (XRD), molecular mechanics (MM) and molecular dynamics (MD) simulations, 2D solid-state NMR spectroscopy, and IR absorption spectroscopy. The conformation of the electron-donating polymer is significantly disrupted by the incorporation of the electron-accepting fullerene molecules, which introduce twists and bends along the polymer backbone and 1D electron-conducting fullerene channels. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of X-ray diffraction, molecular simulations, and spectroscopy to determine the molecular packing in a polymer-fullerene bimolecular crystal

KAUST Repository

Miller, Nichole Cates; Cho, Eunkyung; Junk, Matthias J N; Gysel, Roman; Risko, Chad; Kim, Dongwook; Sweetnam, Sean; Miller, Chad E.; Richter, Lee J.; Kline, Regis Joseph; Heeney, Martin J.; McCulloch, Iain A.; Amassian, Aram; Acevedo-Feliz, Daniel; Knox, Christopher; Hansen, Michael Ryan; Dudenko, Dmytro V.; Chmelka, Bradley F.; Toney, Michael F.; Bré das, Jean Luc; McGehee, Michael D.

2012-01-01

The molecular packing in a polymer: fullerene bimolecular crystal is determined using X-ray diffraction (XRD), molecular mechanics (MM) and molecular dynamics (MD) simulations, 2D solid-state NMR spectroscopy, and IR absorption spectroscopy. The conformation of the electron-donating polymer is significantly disrupted by the incorporation of the electron-accepting fullerene molecules, which introduce twists and bends along the polymer backbone and 1D electron-conducting fullerene channels. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Determination of the distribution of relative molecular mass of organic matter by high pressure size exclusion chromatography with UV and TOC detectors].

Science.gov (United States)

Zhang, Han; Dong, Bing-Zhi

2012-09-01

An on-line high pressure size exclusion chromatography (HPSEC) with UV and TOC detectors was adapted to examine the distribution of relative molecular mass of natural organic matter (NOM). Through synchronous determination of UV254 and TOC responses in a wide range of relative molecular mass, it was possible to accurately characterize the structure of NOM, especially for some non-aromatic and non-conjugated double bond organics which have low response to UV. It was found that, TOC detector was capable of detecting all kinds of organic matters, including sucrose, sodium alginate and other hydrophilic organic compounds. The sample volume had a positively linear correlation with the TOC response, indicating that the larger volume would produce stronger responses. The effect of ion strength was relatively low, shown by the small decrease of peak area (1.2% ) from none to 0.2 mol x L(-1) NaCl. The pH value of tested samples should be adjusted to neutral or acidic because when the samples were alkaline, the results might be inaccurate. Compared to the sample solvents adopted as ultrapure water, the samples prepared by mobile phase solvents had less interference to salt boundary peak. The on-line HPSEC-UV-TOC can be used accurately to characterize the distribution of relative molecular mass and its four fractions in River Xiang.

Using photoelectron diffraction to determine complex molecular adsorption structures

International Nuclear Information System (INIS)

Woodruff, D P

2010-01-01

Backscattering photoelectron diffraction, particularly in the energy-scan mode, is now an established technique for determining in a quantitative fashion the local structure of adsorbates on surfaces, and has been used successfully for ∼100 adsorbate phases. The elemental and chemical-state specificity afforded by the characteristic core level photoelectron binding energies means that it has particular advantages for molecular adsorbates, as the local geometry of inequivalent atoms in the molecule can be determined in a largely independent fashion. On the other hand, polyatomic molecules present a general problem for all methods of surface structure determination in that a mismatch of intramolecular distances with interatomic distances on the substrate surface means that the atoms in the adsorbed molecule are generally in low-symmetry sites. The quantities measured experimentally then represent an incoherent sum of the properties of each structural domain that is inequivalent with respect to the substrate point group symmetry. This typically leads to greater ambiguity or precision in the structural solutions. The basic principles of the method are described and illustrated with a simple example involving molecule/substrate bonding through only one constituent atom (TiO 2 -(110)/H 2 O). This example demonstrates the importance of obtaining quantitative local structural information. Further examples illustrate both the successes and the problems of this approach when applied to somewhat more complex molecular adsorbates.

A COMPARISON OF METHODS FOR DETERMINING THE MOLECULAR CONTENT OF MODEL GALAXIES

International Nuclear Information System (INIS)

Krumholz, Mark R.; Gnedin, Nickolay Y.

2011-01-01

Recent observations indicate that star formation occurs only in the molecular phase of a galaxy's interstellar medium. A realistic treatment of star formation in simulations and analytic models of galaxies therefore requires that one determine where the transition from the atomic to molecular gas occurs. In this paper, we compare two methods for making this determination in cosmological simulations where the internal structures of molecular clouds are unresolved: a complex time-dependent chemistry network coupled to a radiative transfer calculation of the dissociating ultraviolet (UV) radiation field and a simple time-independent analytic approximation. We show that these two methods produce excellent agreement at all metallicities ∼>10 -2 of the Milky Way value across a very wide range of UV fields. At lower metallicities the agreement is worse, likely because time-dependent effects become important; however, there are no observational calibrations of molecular gas content at such low metallicities, so it is unclear if either method is accurate. The comparison suggests that, in many but not all applications, the analytic approximation provides a viable and nearly cost-free alternative to full time-dependent chemistry and radiative transfer.

Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

Science.gov (United States)

Chetouhi, Cherif; Bonhomme, Ludovic; Lasserre-Zuber, Pauline; Cambon, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Langin, Thierry

2016-03-01

In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

Anchoring novel molecular biomarker responses to traditional responses in fish exposed to environmental contamination

International Nuclear Information System (INIS)

Nogueira, Patricia; Pacheco, Mario; Lourdes Pereira, M.; Mendo, Sonia; Rotchell, Jeanette M.

2010-01-01

The responses of Dicentrarchus labrax and Liza aurata to aquatic pollution were assessed in a contaminated coastal lagoon, using both traditional and novel biomarkers combined. DNA damage, assessed by comet assay, was higher in both fish species from the contaminated sites, whereas levels of cytochrome P450 1A1 gene expression were not significantly altered. The liver histopathological analysis also revealed significant lesions in fish from contaminated sites. Alterations in ras and xpf genes were analysed and additional pollutant-responsive genes were identified. While no alterations were found in ras gene, a downregulation of xpf gene was observed in D. labrax from a contaminated site. Suppression subtractive hybridization applied to D. labrax collected at a contaminated site, revealed altered expression in genes involved in energy metabolism, immune system activity and antioxidant response. The approach and results reported herein demonstrate the utility of anchoring traditional biomarker responses alongside novel biomarker responses. - Novel molecular biomarkers of aquatic environmental contamination in fish.

Interactive effects of nutrition, reproductive state and pollution on molecular stress responses of mussels, Mytilus galloprovincialis Lamarck, 1819.

Science.gov (United States)

González-Fernández, Carmen; Albentosa, Marina; Sokolova, Inna

2017-10-01

Marine bivalves including mussels Mytilus galloprovincialis are commonly used as sentinels for pollution monitoring and ecosystem health assessment in the coastal zones. Use of biomarkers to assess the pollution effects assumes that the effects of pollutants on the biomarkers exceed the natural background variability; yet this assumption has rarely been tested. We exposed mussels at different reproductive stages and nutritive states to two concentrations of a polycyclic aromatic hydrocarbon (fluoranthene, 3 and 60 μg L -1 ) for three weeks. Expression levels of the molecular biomarkers related to the detoxification and general stress response [cytochrome P450 oxidase (CYP450), glutathione S-transferases (GST-α; GST-S1; GST-S2), the multixenobiotic resistance protein P-glycoprotein (PgP), metallothioneins (MT10 and MT20), heat shock proteins (HSP22, HSP70-2; HSP70-3; HSP70-4), as well as mRNA expression of two reproduction-related genes, vitellogenin (Vitel) and vitelline coat lysin M7 (VCLM7)] were measured. The mussels' nutrition and reproductive state affected the baseline mRNA levels of molecular biomarkers and modulated the transcriptional responses of biomarker genes to the pollutant exposure. Thus, mussel physiological state could act as a confounding factor in the evaluation of the response of pollution through molecular biomarkers. The biomarker baseline levels must be determined across a range of physiological states to enable the use of biomarkers in monitoring programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Determinants of Human T-lymphotropic Virus Type 1 Transmission and Spread

Directory of Open Access Journals (Sweden)

Patrick L. Green

2011-07-01

Full Text Available Human T-lymphotrophic virus type-1 (HTLV-1 infects approximately 15 to 20 million people worldwide, with endemic areas in Japan, the Caribbean, and Africa. The virus is spread through contact with bodily fluids containing infected cells, most often from mother to child through breast milk or via blood transfusion. After prolonged latency periods, approximately 3 to 5% of HTLV-1 infected individuals will develop either adult T-cell leukemia/lymphoma (ATL, or other lymphocyte-mediated disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The genome of this complex retrovirus contains typical gag, pol, and env genes, but also unique nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo such as, p30, p12, p13 and the antisense encoded HBZ. While progress has been made in the understanding of viral determinants of cell transformation and host immune responses, host and viral determinants of HTLV-1 transmission and spread during the early phases of infection are unclear. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the early events of HTLV-1 infection. This review will focus on studies that test HTLV-1 determinants in context to full length infectious clones of the virus providing insights into the mechanisms of transmission and spread of HTLV-1.

Molecular and Genetic Determinants of Glioma Cell Invasion

Directory of Open Access Journals (Sweden)

Kenta Masui

2017-12-01

Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

Coulomb-explosion technique for determining geometrical structures of molecular ions

International Nuclear Information System (INIS)

Gemmell, D.S.

1981-01-01

Traditional experimental techniques (e.g. studies on photon absorption or emission) for determining the sterochemical structures of neutral molecules are extremeley difficult to apply to molecular ions because of problems in obtaining a sufficient spatial density of the ions to be studied. Recent high-resolution measurements on the energy and angle distributions of the fragments produced when fast (MeV) molecular-ion beams from an electrostatic accelerator dissociate (Coulomb explode) in thin foils and in gases, offer promising possibilities for deducing the sterochemical structures of the molecular ions constituting the incident beams. Bond lengths have been determined in this way for several diatomic projectiles (H 2+ , HeH + , CH + , NH + , OH + , N 2+ , O 2+ , etc.) with an accuracy of approx. 0.01 A. H 3+ has been demonstrated (for the first time) to be equilateral triangular and the interproton distance measured. Measurements on single fragments from CO 2+ , N 2 O + , C 3 H 3+ , and CH/sub n/ + have revealed the gross structures of the projectiles. An apparatus has recently been constructed at Argonne to permit precise measurements on fragments in coincidence. The apparatus has been tested on a known structure (OH 2+ ). The O-H bond length was found to be 1.0 +- 0.04 A and the H-O-H bond angle was measured as 110 --- 2 0 . These values are in excellent agreement with those found in optical experiments (0.999 A and 110.5 0 ). This Coulomb explosion technique can be expected to be refined in accuracy and to be extended to a wide range of molecular ions whose structures are inaccessible by other means

Determination and Quantification of Molecular Interactions in Protein Films: A Review

Directory of Open Access Journals (Sweden)

Felicia Hammann

2014-12-01

Full Text Available Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography and analysis of solid films (spectroscopy techniques, X-ray scattering methods. To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

Determination and Quantification of Molecular Interactions in Protein Films: A Review.

Science.gov (United States)

Hammann, Felicia; Schmid, Markus

2014-12-10

Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

Stress responses during ageing: molecular pathways regulating protein homeostasis.

Science.gov (United States)

Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

2015-01-01

The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

Determination of molecular parameters by electron collisions and laser techniques

International Nuclear Information System (INIS)

Colon, C.

1989-01-01

In this work a general procedure to study diatomic molecules in intermediate coupling scheme has been developed. This study allows to obtain expressions to calculate molecular line strengths and rotational transition intensities. These results are used in a numerical program to synthetize vibrational and rotational band spectra of any diatomic molecule. With this technique the experimental spectra of the first negative system of N 2 + and the fist positive system of N 2 are reproduced theoretically and it is possible to deduce its electronic transition moments values by comparison. Also the method has been applied to compare the synthetized bands with the experimental spectra of the B O u + -- x 1 Σ g + system of Au 2 and the A 2 Σ--- x 2 π system of OH. From these comparison band intensities and electronic moments can be deduced. The branching ratio method to measure the relative spectral response in the 1100-1560 A o =wavelength range of a vacuum uv monochromator has been used. Relative intensity of rotational lines with origine in a common upper vibrational-rotational level of Warner and Lyman systems of H 2 , have been measured. Also in this work, the deexcitation of the B 3 π + (0 + u ), v'=14 level of I 2 after pulsed laser excitation has been studied. The quenching cross sections by collisions with I 2 , H 2 , CO 2 and CH 4 have been determin-ed. (Author)

Manipulation of arthropod sex determination by endosymbionts : Diversity and molecular mechanisms

NARCIS (Netherlands)

Ma, W. -J.; Vavre, F.; Beukeboom, L. W.

2014-01-01

Arthropods exhibit a large variety of sex determination systems both at the chromosomal and molecular level. Male heterogamety, female heterogamety, and haplodiploidy occur frequently, but partially different genes are involved. Endosymbionts, such as Wolbachia, Cardinium, Rickettsia, and

Variable contact gap single-molecule conductance determination for a series of conjugated molecular bridges

DEFF Research Database (Denmark)

Haiss, W.; Wang, Christian; Jitchati, R.

2008-01-01

It is now becoming clear that the characteristics of the whole junction are important in determining the conductance of single molecules bound between two metal contacts. This paper shows through measurements on a series of seven conjugated molecular bridges that contact separation is an importan...... that conductance increases rather dramatically at higher tilt angle away from the normal for conformationally rigid molecular wires and that this increase in conductance arises from increased electronic coupling between the molecular bridge and the gold contacts.......It is now becoming clear that the characteristics of the whole junction are important in determining the conductance of single molecules bound between two metal contacts. This paper shows through measurements on a series of seven conjugated molecular bridges that contact separation is an important......-distance curves and knowledge of the terminal to terminal length of the molecular wire. The contact gap separation dependence is interpreted as arising from tilting of these molecules in the junction and this model is underpinned by ab initio transport computations. In this respect we make the general observation...

Plant genetic and molecular responses to water deficit

Directory of Open Access Journals (Sweden)

Silvio Salvi

2011-02-01

Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

[Prediction of the molecular response to pertubations from single cell measurements].

Science.gov (United States)

Remacle, Françoise; Levine, Raphael D

2014-12-01

The response of protein signalization networks to perturbations is analysed from single cell measurements. This experimental approach allows characterizing the fluctuations in protein expression levels from cell to cell. The analysis is based on an information theoretic approach grounded in thermodynamics leading to a quantitative version of Le Chatelier principle which allows to predict the molecular response. Two systems are investigated: human macrophages subjected to lipopolysaccharide challenge, analogous to the immune response against Gram-negative bacteria and the response of the proteins involved in the mTOR signalizing network of GBM cancer cells to changes in partial oxygen pressure. © 2014 médecine/sciences – Inserm.

40 CFR 1065.845 - Response factor determination.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Response factor determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... each FID analyzer's alcohol/carbonyl response factor (such as RF MeOH) after FID optimization to...

Molecular determinants of epidermal growth factor binding: a molecular dynamics study.

Directory of Open Access Journals (Sweden)

Jeffrey M Sanders

Full Text Available The epidermal growth factor receptor (EGFR is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both low affinity and high affinity EGFR ligands. While these studies have identified functional effects of ligand binding, high-resolution structural data are lacking. To gain a better understanding of the molecular basis of EGFR binding affinities, we docked each EGFR ligand to the putative active state extracellular domain dimer and 25.0 ns molecular dynamics simulations were performed. MM-PBSA/GBSA are efficient computational approaches to approximate free energies of protein-protein interactions and decompose the free energy at the amino acid level. We applied these methods to the last 6.0 ns of each ligand-receptor simulation. MM-PBSA calculations were able to successfully rank all seven of the EGFR ligands based on the two affinity classes: EGF>HB-EGF>TGF-α>BTC>EPR>EPG>AR. Results from energy decomposition identified several interactions that are common among binding ligands. These findings reveal that while several residues are conserved among the EGFR ligand family, no single set of residues determines the affinity class. Instead we found heterogeneous sets of interactions that were driven primarily by electrostatic and Van der Waals forces. These results not only illustrate the complexity of EGFR dynamics but also pave the way for structure-based design of

A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

Science.gov (United States)

Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

2016-08-10

Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

Growth response of microorganisms to different molecular fractions of lignite

Energy Technology Data Exchange (ETDEWEB)

Polman, J.K.; Breckenridge, C.R.; Dugan, P.R.; Quigley, D.R.

1990-01-01

Our research is primarily concerned with isolating and characterizing microbes which are able to dissimilate coal and convert it to other useful chemicals. This quarter, general growth responses of microorganisms cultivated in the presence of different molecular weight fractions of lignite coal were examined. Aerobic and anaerobic environmental samples from a variety of ecological niches were used as inocula. Growth of the microorganisms in these samples on the following types of media was tested: COAL medium, containing alkali-solubilized whole coal; THFI medium, containing the alkali-solubilized, tetrahydrofuran-insoluble, macromolecular portion of whole coal; THFS medium, containing the THF-soluble, low molecular weight portion of whole coal; and CON medium, void of any coal constituent. Overall results indicated that the presence of the THF-soluble, low molecular weight coal fraction enhanced the growth yield and the variety of aerobic microorganisms compared to the other coal fractions or the control medium. Conversely, anaerobic microbes grew best on media which contained the macromolecular fraction. 12 refs., 5 tabs.

Molecular imprinting-chemiluminescence determination of trimethoprim using trimethoprim-imprinted polymer as recognition material.

Science.gov (United States)

He, Yunhua; Lu, Jiuru; Liu, Mei; Du, Jianxiu

2005-07-01

A new molecular imprinting-chemiluminescence method for the determination of trimethoprim was developed, in which trimethoprim-imprinted polymer was used as the molecular recognition material and the CL reaction of trimethoprim with potassium permanganate in acidic medium was used as the detection system. The CL intensity responds linearly to the concentration of trimethoprim within the 5.0 x 10(-8)-5.0 x 10(-6) g mL(-1) range (r= 0.9983) with a detection limit of 2 x 10(-8) g mL(-1). The relative standard deviation for the determination of 1.0 x 10(-7) g mL(-1) trimethoprim solutions is 4.8% (n= 9). The method has been applied to the determination of trimethoprim in pharmaceutical preparations and body fluids, and satisfactory results were obtained.

Hofmeister effect on thermo-responsive poly(propylene oxide): Role of polymer molecular weight and concentration.

Science.gov (United States)

Moghaddam, Saeed Zajforoushan; Thormann, Esben

2016-03-01

Although a vast amount of research has been dedicated to investigate the Hofmeister effect on the stability of polymer solutions, a clear understanding of the role of polymer properties in this phenomenon is still missing. Here, the Hofmeister effect of NaCl (destabilizing) and NaSCN (stabilizing) salts on aqueous solutions of poly(propylene oxide) (PPO) is studied. Four different molecular weights of PPO were investigated, to determine how the variation in the polymer coil size affects the Hofmeister effect. The investigation was further conducted for different PPO concentrations, in order to understand the effect of inter-chain interactions on the response to addition of salt. The temperature-driven phase separation of the solutions was monitored by differential scanning calorimetry, which provides the precise value of the phase separation temperature, as well as the enthalpy change accompanied with the transition. It was observed that increasing the molecular weight weakens the effect of the both salts, which is interpreted in terms of a scaling law between the molecular weight and the accessible surface area of the polymers. Increasing the PPO concentration further diminished the NaCl effect, but amplified the NaSCN effect. This difference is attributed to an electrostatic stabilization mechanism in the case of NaSCN. Copyright © 2015 Elsevier Inc. All rights reserved.

Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

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Richard A Rudick

Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.

Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

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Hyldahl, Robert D; Hubal, Monica J

2014-02-01

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

Molecular markers predicting radiotherapy response: Report and recommendations from an International Atomic Energy Agency technical meeting

International Nuclear Information System (INIS)

West, Catharine M.L.; McKay, Michael J.; Hoelscher, Tobias; Baumann, Michael; Stratford, Ian J.; Bristow, Robert G.; Iwakawa, Mayumi; Imai, Takashi; Zingde, Surekha M.; Anscher, Mitchell S.; Bourhis, Jean; Begg, Adrian C.; Haustermans, Karin; Bentzen, Soren M.; Hendry, Jolyon H.

2005-01-01

Purpose: There is increasing interest in radiogenomics and the characterization of molecular profiles that predict normal tissue and tumor radioresponse. A meeting in Amsterdam was organized by the International Atomic Energy Agency to discuss this topic on an international basis. Methods and Materials: This report is not completely exhaustive, but highlights some of the ongoing studies and new initiatives being carried out worldwide in the banking of tumor and normal tissue samples underpinning the development of molecular marker profiles for predicting patient response to radiotherapy. It is generally considered that these profiles will more accurately define individual or group radiosensitivities compared with the nondefinitive findings from the previous era of cellular-based techniques. However, so far there are only a few robust reports of molecular markers predicting normal tissue or tumor response. Results: Many centers in different countries have initiated tissue and tumor banks to store samples from clinical trials for future molecular profiling analysis, to identify profiles that predict for radiotherapy response. The European Society for Therapeutic Radiology and Oncology GENEtic pathways for the Prediction of the effects of Irradiation (GENEPI) project, to store, document, and analyze sample characteristics vs. response, is the most comprehensive in this regard. Conclusions: The next 5-10 years are likely to see the results of these and other correlative studies, and promising associations of profiles with response should be validated in larger definitive trials

Many-body theory of electrical, thermal and optical response of molecular heterojunctions

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Bergfield, Justin Phillip

In this work, we develop a many-body theory of electronic transport through single molecule junctions based on nonequilibrium Green's functions (NEGFs). The central quantity of this theory is the Coulomb self-energy matrix of the junction SigmaC. SigmaC is evaluated exactly in the sequential-tunneling limit, and the correction due to finite lead-molecule tunneling is evaluated using a conserving approximation based on diagrammatic perturbation theory on the Keldysh contour. In this way, tunneling processes are included to infinite order, meaning that any approximation utilized is a truncation in the physical processes considered rather than in the order of those processes. Our theory reproduces the key features of both the Coulomb blockade and coherent transport regimes simultaneously in a single unified theory. Nonperturbative effects of intramolecular correlations are included, which are necessary to accurately describe the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, essential for a quantitative theory of transport. This work covers four major topics related to transport in single-molecule junctions. First, we use our many-body theory to calculate the nonlinear electrical response of the archetypal Au-1,4-benzenedithiol-Au junction and find irregularly shaped 'molecular diamonds' which have been experimentally observed in some larger molecules but which are inaccessible to existing theoretical approaches. Next, we extend our theory to include heat transport and develop an exact expression for the heat current in an interacting nanostructure. Using this result, we discover that quantum coherence can strongly enhance the thermoelectric response of a device, a result with a number of technological applications. We then develop the formalism to include multi-orbital lead-molecule contacts and multi-channel leads, both of which strongly affect the observable transport. Lastly, we include a dynamic screening correction to

Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses.

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Rafael Fonseca Benevenuto

Full Text Available Some genetically modified (GM plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses.

Molecularly imprinted electrochemical sensor based on nickel nanoparticle-modified electrodes for phenobarbital determination

International Nuclear Information System (INIS)

Yu, Hui Cheng; Huang, Xue Yi; Lei, Fu Hou; Tan, Xue Cai; Wei, Yi Chun; Li, Hao

2014-01-01

Highlights: • Uniform Ni nanoparticles were synthesized. • A Ni nanoparticle-modified imprinted sensor was developed to detect phenobarbital. • The modified sensor exhibited high sensitivity for phenobarbital. • The electrochemical properties of the modified sensor were investigated. • The prepared sensor was applied to detect phenobarbital in fish samples. - Abstract: Uniform nickel nanoparticles were applied to improve the sensitivity of sensors for phenobarbital (PB) determination. A Ni nanoparticle-modified imprinted electrochemical sensor was developed by thermal polymerization with the use of methacrylic acid as the functional monomer and ethylene glycol maleic rosinate acrylate as the crosslinking agent. The chemical structures and morphologies of the imprinted films were characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. The success of the fabrication of Ni nanoparticles, as well as the Ni nanoparticle-modified imprinted electrochemical sensor, was confirmed by the analytical results. The electrochemical properties of the modified molecularly imprinted and non-imprinted polymer sensors were investigated by cyclic voltammetry, differential pulse voltammetry, electrochemical impedance spectroscopy, and chronoamperometry. Results showed that the electrochemical properties of the molecularly imprinted sensor were remarkably different from those of the non-imprinted sensor. Linear responses of the imprinted sensor to PB were observed for concentrations ranging from 1.4 × 10 −7 mol L −1 to 1.3 × 10 −4 mol L −1 (r 2 = 0.9976), with a detection limit of 8.2 × 10 −9 mol L −1 (S/N = 3). The imprinted electrochemical sensor was used to determine PB in actual fish samples, in which average recoveries between 95.60% and 104.67% were achieved. The developed Ni nanoparticle-modified electrochemical sensor exhibited high sensitivity, high selectivity, and good recovery

UV radiation in marine ectotherms: Molecular effects and responses

International Nuclear Information System (INIS)

Dahms, Hans-U.; Lee, Jae-Seong

2010-01-01

This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

On the combination of molecular replacement and single-wavelength anomalous diffraction phasing for automated structure determination

International Nuclear Information System (INIS)

Panjikar, Santosh; Parthasarathy, Venkataraman; Lamzin, Victor S.; Weiss, Manfred S.; Tucker, Paul A.

2009-01-01

The combination of molecular replacement and single-wavelength anomalous diffraction improves the performance of automated structure determination with Auto-Rickshaw. A combination of molecular replacement and single-wavelength anomalous diffraction phasing has been incorporated into the automated structure-determination platform Auto-Rickshaw. The complete MRSAD procedure includes molecular replacement, model refinement, experimental phasing, phase improvement and automated model building. The improvement over the standard SAD or MR approaches is illustrated by ten test cases taken from the JCSG diffraction data-set database. Poor MR or SAD phases with phase errors larger than 70° can be improved using the described procedure and a large fraction of the model can be determined in a purely automatic manner from X-ray data extending to better than 2.6 Å resolution

Sex determination of Pohnpei Micronesian kingfishers using morphological and molecular genetic techniques

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Kesler, Dylan C.; Lopes, I.F.; Haig, Susan M.

2006-01-01

Conservation-oriented studies of Micronesian Kingfishers (Todiramphus cinnamominus) have been hindered by a lack of basic natural history information, despite the status of the Guam subspecies (T. c. cinnamominus) as one of the most endangered species in the world. We used tissue samples and morphometric measures from museum specimens and wild-captured Pohnpei Micronesian Kingfishers (T. c. reichenbachii) to develop methods for sex determination. We present a modified molecular protocol and a discriminant function that yields the probability that a particular individual is male or female. Our results revealed that females were significantly larger than males, and the discriminant function correctly predicted sex in 73% (30/41) of the individuals. The sex of 86% (18/21) of individuals was correctly assigned when a moderate reliability threshold was set. Sex determination using molecular genetic techniques was more reliable than methods based on morphology. Our results will facilitate recovery efforts for the critically endangered Guam Micronesian Kingfisher and provide a basis for sex determination in the 11 other endangered congeners in the Pacific Basin.

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

International Nuclear Information System (INIS)

Ng, Loo-Teck; Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao

2005-01-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

Energy Technology Data Exchange (ETDEWEB)

Ng, Loo-Teck [School of Science, Food and Horticulture, University of Western Sydney, Locked bag 1797, Penrith South DC, NSW 1797 (Australia)]. E-mail: l.ng@uws.edu.au; Nakayama, Hiroshi [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan); Kaetsu, Isao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)]. E-mail: kaetsu@ned.kindai.ac.jp; Uchida, Kumao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)

2005-06-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs.

Adhesives, fillers & potting compounds: Special report molecular weight determinations of dimethypolysiloxane polymers

Energy Technology Data Exchange (ETDEWEB)

Luthey, Z.A.

1968-09-03

Using a Mechrolab Vapor Phase Osmometer and a Hallikainen Automatic Membrane Osmometer the number-average molecular weight of two samples of dimethylpolysiloxane - 2300 and 8000 cstk - as well as samples made by mixing the two previously mentioned materials were determined.

Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists

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Evren UZUN

2018-05-01

Full Text Available Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs and cell-free circulating nucleic acids, effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

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Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle

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Pugh, Jamie K; Faulkner, Steve H; Jackson, Andrew P; King, James A; Nimmo, Myra A

2015-01-01

Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 × 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 × 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser473) decreased at 6 h in both trials (P HIIT (P HIIT with PGC-1α and PGC-1α-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1α-ex1b only (P HIIT versus RE at 2 and 6 h (P effect on protein signaling and mRNA expression, and suggest that HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations. PMID:25902785

Glucose-responsive insulin by molecular and physical design

Science.gov (United States)

Bakh, Naveed A.; Cortinas, Abel B.; Weiss, Michael A.; Langer, Robert S.; Anderson, Daniel G.; Gu, Zhen; Dutta, Sanjoy; Strano, Michael S.

2017-10-01

The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.

Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion.

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David J Orlicky

Full Text Available Perilipin-1 (Plin1, a prominent cytoplasmic lipid droplet (CLD binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps.

Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion.

Science.gov (United States)

Orlicky, David J; Monks, Jenifer; Stefanski, Adrianne L; McManaman, James L

2013-01-01

Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps.

Molecular imprinted polypyrrole modified glassy carbon electrode for the determination of tobramycin

International Nuclear Information System (INIS)

Gupta, Vinod Kumar; Yola, Mehmet Lütfi; Özaltın, Nuran; Atar, Necip; Üstündağ, Zafer; Uzun, Lokman

2013-01-01

Graphical abstract: Atomic force microscopic images of (A) bare GCE and (B) TOB imprinted PPy/GCE surface. - Highlights: • Glassy carbon electrode based on molecularly imprinted polypyrrole was prepared. • The developed surfaces were characterized by AFM, FTIR, EIS and CV. • The developed nanosensor was applied to egg and milk samples. - Abstract: Over the past two decades, molecular imprinted polymers have attracted a broad interest from scientists in sensor development. In the preparation of molecular imprinted polymers the desired molecule (template) induces the creation of specific recognition sites in the polymer. In this study, the glassy carbon electrode (GCE) based on molecularly imprinted polypyrrole (PPy) was fabricated for the determination of tobramycin (TOB). The developed electrode was prepared by incorporation of a template molecule (TOB) during the electropolymerization of pyrrole on GCE in aqueous solution using cyclic voltammetry (CV) method. The performance of the imprinted and non-imprinted electrodes was evaluated by square wave voltammetry (SWV). The effect of pH, monomer and template concentrations, electropolymerization cycles on the performance of the imprinted and non-imprinted electrodes was investigated and optimized. The non-modified and TOB-imprinted surfaces were characterized by using atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), electrochemical impedance spectroscopy (EIS) and CV. The linearity range of TOB was 5.0 × 10 −10 –1.0 × 10 −8 M with the detection limit of 1.4 × 10 −10 M. The developed nanosensor was applied successfully for the determination of TOB in egg and milk

Deep molecular responses for treatment-free remission in chronic myeloid leukemia.

Science.gov (United States)

Dulucq, Stéphanie; Mahon, Francois-Xavier

2016-09-01

Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Molecular assays for determining Mycobacterium leprae viability in tissues of experimentally infected mice.

Science.gov (United States)

Davis, Grace L; Ray, Nashone A; Lahiri, Ramanuj; Gillis, Thomas P; Krahenbuhl, James L; Williams, Diana L; Adams, Linda B

2013-01-01

The inability of Mycobacterium leprae to grow on axenic media has necessitated specialized techniques in order to determine viability of this organism. The purpose of this study was to develop a simple and sensitive molecular assay for determining M. leprae viability directly from infected tissues. Two M. leprae-specific quantitative reverse transcription PCR (qRT-PCR) assays based on the expression levels of esxA, encoding the ESAT-6 protein, and hsp18, encoding the heat shock 18 kDa protein, were developed and tested using infected footpad (FP) tissues of both immunocompetent and immunocompromised (athymic nu/nu) mice. In addition, the ability of these assays to detect the effects of anti-leprosy drug treatment on M. leprae viability was determined using rifampin and rifapentine, each at 10 mg/kg for 1, 5, or 20 daily doses, in the athymic nu/nu FP model. Molecular enumeration (RLEP PCR) and viability determinations (qRT-PCR) were performed via Taqman methodology on DNA and RNA, respectively, purified from ethanol-fixed FP tissue and compared with conventional enumeration (microscopic counting of acid fast bacilli) and viability assays (radiorespirometry, viability staining) which utilized bacilli freshly harvested from the contralateral FP. Both molecular and conventional assays demonstrated growth and high viability of M. leprae in nu/nu FPs over a 4 month infection period. In contrast, viability was markedly decreased by 8 weeks in immunocompetent mice. Rifapentine significantly reduced bacterial viability after 5 treatments, whereas rifampin required up to 20 treatments for the same efficacy. Neither drug was effective after a single treatment. In addition, host gene expression was monitored with the same RNA preparations. hsp18 and esxA qRT-PCR are sensitive molecular indicators, reliably detecting viability of M. leprae in tissues without the need for bacterial isolation or immediate processing, making these assays applicable for in vivo drug screening and

An overview of HCV molecular biology, replication and immune responses

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Nawaz Zafar

2011-04-01

Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

Indigoid Photoswitches: Visible Light Responsive Molecular Tools.

Science.gov (United States)

Petermayer, Christian; Dube, Henry

2018-05-15

Indigoid photoswitches comprise a class of chromophores that are derived from the parent and well-known indigo dye. Different from most photoswitches their core structures absorb in the visible region of the spectrum in both isomeric states even without substitutions, which makes them especially interesting for applications not tolerant of high-energy UV light. Also different from most current photoswitching systems, they provide highly rigid structures that undergo large yet precisely controllable geometry changes upon photoisomerization. The favorable combination of pronounced photochromism, fast and efficient photoreactions, and high thermal bistability have led to a strongly increased interest in indigoid photoswitches over the last years. As a result, intriguing applications of these chromophores as reversible triggering units in supramolecular and biological chemistry, the field of molecular machines, or smart molecules have been put forward. In this Account current developments in the synthesis, mechanistic understanding of light responsiveness, advantageous properties as phototools, and new applications of indigoid photoswitches are summarized with the focus on hemithioindigo, hemiindigo, and indigo as key examples. Many methods for the synthesis of hemithioindigos are known, but derivatives with a fourth substituent at the double bond could not easily be prepared because of the resulting increased steric hindrance in the products. Recent efforts in our laboratory have provided two different methods to prepare these highly promising photoswitches in very efficient ways. One method is especially designed for the introduction of sterically hindered ketones while the second one allows rapid structural diversification in only three high-yielding synthetic steps. Given the lesser prominence of indigoid photoswitches, mechanistic understanding of their excited state behavior and therefore rational design opportunities for photophysical properties are also much

Significance of molecular diagnostics in human papilloma virus (HPV determination

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Kovačević G.

2014-01-01

Full Text Available HPV infection is considered to be the most important etiologic factor in cervical cancer development. In this retrospective study, which included the period from 2000 to 2012, the results of two molecular techniques used in the detection of HPV infection among women of the South Bačka District were analyzed. By using the technique of in situ hybridization and the rPCR method, the proportion of high-risk HPV among women with normal cytology was determined to be 19.8% and 32.7%, respectively, and among women with abnormal cytology 43.1% and 61%, respectively. Among the analyzed women, HPV type 16 was the most prevalent, followed by HPV types 31, 51 and 18. Application of molecular HPV diagnosis is valuable because it increases the sensitivity of the screening test, so that the application of both tests to detect cervical cancer is a true prevention of malignancy.

Gas flow parameter determination by molecular beam method

International Nuclear Information System (INIS)

Zarvin, A.E.; Sharafutdinov, R.G.

1977-01-01

This paper describes a molecular-beam system intended for studying nonequilibrium processes in supersonic rarefied gas flows. The system represented is a small molecular beam source placed inside the low intensity wind tunnel of the Institute of Thermophysics, Siberian Branch of the USSR Academy of Sciences. The time-of-flight method is used for measuring molecular velocity distribution functions on molecular beam axis. (Auth.)

Molecular weight determination of bisbenzyl-isoquinoline alkaloids by 252Cf-plasma desorption mass spectrometer

International Nuclear Information System (INIS)

Kohno, Hiroyuki; Tatsunami, Shinobu; Hiroi, Tomoko; Kouyama, Hiroshi; Taniguchi, Masashi; Yago, Nagasumi; Nakamura, Iwao

1995-01-01

Bisbenzylisoquinoline alkaloids of Stephania cepharantha have been used for various clinical purposes and recently reevaluated as stimulators of interleukin secretion in tissues. We analyzed molecular stuctures of bisbenzylisoquinoline alkaloids by determining their molecular weights using the 252 Cf-plasma desorption mass spectrometry (PDMS). The spectra were accumulated for 500 000 fission events. The acceleration voltage used here was 15 kV. Samples were analyzed using nitrocellulose-coated sample targets. Of the 5 alkaloids studied here, cepharanthine gave a main peak of molecular weight of 606.1 for the theoretical molecular weight of 606.7. The other minor peaks were considered to be demethylated fragment ions. 252 Cf-PDMS should be quite useful in studying structure, metabolism and pharmacokinetics of various drugs with extremely low coefficients of variation. (author)

New Insight in Understanding the mechanical responses of polymer glasses using molecular dynamic simulation

Science.gov (United States)

Zheng, Yexin; Wang, Shi-Qing; Tsige, Mesfin

The Kremer-Grest bead-spring model has been the standard model in molecular dynamics simulation of polymer glasses. However, due to current computational limitations in accessing relevant time scales in polymer glasses in a reasonable amount of CPU time, simulation of mechanical response of polymer glasses in molecular dynamic simulations requires a much higher quenching rate and deformation rate than used in experiments. Despite several orders of magnitude difference in time scale between simulation and experiment, previous studies have shown that simulations can produce meaningful results that can be directly compared with experimental results. In this work we show that by tuning the quenching rate and deformation rate relative to the segmental relaxation times, a reasonable mechanical response shows up in the glassy state. Specifically, we show a younger glass prepared with a faster quenching rate shows glassy responses only when the imposed deformation rate is proportionally higher. the National Science Foundation (DMR-1444859 and DMR-1609977).

QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT

Science.gov (United States)

Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all four components, but the greatest overall current...

Molecular structure determination of cyclootane by ab initio and electron diffraction methods in the gas phase

OpenAIRE

De Almeida, Wagner B.

2000-01-01

The determination of the molecular structure of molecules is of fundamental importance in chemistry. X-rays and electron diffraction methods constitute in important tools for the elucidation of the molecular structure of systems in the solid state and gas phase, respectively. The use of quantum mechanical molecular orbital ab initio methods offer an alternative for conformational analysis studies. Comparison between theoretical results and those obtained experimentally in the gas phase can ma...

Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Nicola Gaetano Gatta

2016-11-01

Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

Molecular species composition of plant cardiolipin determined by liquid chromatography mass spectrometry

Science.gov (United States)

Zhou, Yonghong; Peisker, Helga

2016-01-01

Cardiolipin (CL), an anionic phospholipid of the inner mitochondrial membrane, provides essential functions for stabilizing respiratory complexes and is involved in mitochondrial morphogenesis and programmed cell death in animals. The role of CL and its metabolism in plants are less well understood. The measurement of CL in plants, including its molecular species composition, is hampered by the fact that CL is of extremely low abundance, and that plants contain large amounts of interfering compounds including galactolipids, neutral lipids, and pigments. We used solid phase extraction by anion exchange chromatography to purify CL from crude plant lipid extracts. LC/MS was used to determine the content and molecular species composition of CL. Thus, up to 23 different molecular species of CL were detected in different plant species, including Arabidopsis, mung bean, spinach, barley, and tobacco. Similar to animals, plant CL is dominated by highly unsaturated species, mostly containing linoleic and linolenic acid. During phosphate deprivation or exposure to an extended dark period, the amount of CL decreased in Arabidopsis, accompanied with an increased degree in unsaturation. The mechanism of CL remodeling during stress, and the function of highly unsaturated CL molecular species, remains to be defined. PMID:27179363

Molecular dynamics simulation of potentiometric sensor response: the effect of biomolecules, surface morphology and surface charge.

Science.gov (United States)

Lowe, B M; Skylaris, C-K; Green, N G; Shibuta, Y; Sakata, T

2018-05-10

The silica-water interface is critical to many modern technologies in chemical engineering and biosensing. One technology used commonly in biosensors, the potentiometric sensor, operates by measuring the changes in electric potential due to changes in the interfacial electric field. Predictive modelling of this response caused by surface binding of biomolecules remains highly challenging. In this work, through the most extensive molecular dynamics simulation of the silica-water interfacial potential and electric field to date, we report a novel prediction and explanation of the effects of nano-morphology on sensor response. Amorphous silica demonstrated a larger potentiometric response than an equivalent crystalline silica model due to increased sodium adsorption, in agreement with experiments showing improved sensor response with nano-texturing. We provide proof-of-concept that molecular dynamics can be used as a complementary tool for potentiometric biosensor response prediction. Effects that are conventionally neglected, such as surface morphology, water polarisation, biomolecule dynamics and finite-size effects, are explicitly modelled.

Molecular, physiological and behavioral responses of honey bee (Apis mellifera) drones to infection with microsporidian parasites.

Science.gov (United States)

Holt, Holly L; Villar, Gabriel; Cheng, Weiyi; Song, Jun; Grozinger, Christina M

2018-04-26

Susceptibility to pathogens and parasites often varies between sexes due to differences in life history traits and selective pressures. Nosema apis and Nosema ceranae are damaging intestinal pathogens of European honey bees (Apis mellifera). Nosema pathology has primarily been characterized in female workers where infection is energetically costly and accelerates worker behavioral maturation. Few studies, however, have examined infection costs in male honey bees (drones) to determine if Nosema similarly affects male energetic status and sexual maturation. We infected newly emerged adult drones with Nosema spores and conducted a series of molecular, physiological, and behavioral assays to characterize Nosema etiology in drones. We found that infected drones starved faster than controls and exhibited altered patterns of flight activity in the field, consistent with energetic distress or altered rates of sexual maturation. Moreover, expression of candidate genes with metabolic and/or hormonal functions, including members of the insulin signaling pathway, differed by infection status. Of note, while drone molecular responses generally tracked predictions based on worker studies, several aspects of infected drone flight behavior contrasted with previous observations of infected workers. While Nosema infection clearly imposed energetic costs in males, infection had no impact on drone sperm numbers and had only limited effects on antennal responsiveness to a major queen sex pheromone component (9-ODA). We compare Nosema pathology in drones with previous studies describing symptoms in workers and discuss ramifications for drone and colony fitness. Copyright © 2018. Published by Elsevier Inc.

Molecular structure determination of cyclooctane by Ab Initio and electron diffraction methods in the gas phase; Determinacao da estrutura molecular do ciclooctano por metodos Ab Initio e difracao de eletrons na fase gasosa

Energy Technology Data Exchange (ETDEWEB)

Almeida, Wagner B. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Quimica

2000-10-01

The determination of the molecular structure of molecules is of fundamental importance in chemistry. X-rays and electron diffraction methods constitute in important tools for the elucidation of the molecular structure of systems in the solid state and gas phase, respectively. The use of quantum mechanical molecular orbital ab initio methods offer an alternative for conformational analysis studies. Comparison between theoretical results and those obtained experimentally in the gas phase can make a significant contribution for an unambiguous determination of the geometrical parameters. In this article the determination for an unambiguous determination of the geometrical parameters. In this article the determination of the molecular structure of the cyclooctane molecule by electron diffraction in the gas phase an initio calculations will be addressed, providing an example of a comparative analysis of theoretical and experimental predictions. (author)

Determination of the neutrino mass from the beta decay of gaseous molecular tritium

International Nuclear Information System (INIS)

Decman, D.J.; Stoeffl, W.

1992-06-01

We set an upper limit of 8 eV for the mass of the electron antineutrino from studying the beta decay of tritium. We use a gaseous molecular tritium source, a high resolution magnetic spectrometer and a low background counting system to minimize the systematic errors encountered in these measurements. Our calibration data with radioactive 83m Kr enables us to measure our system response function and a good deal of atomic physics data. In addition to our end point results we have made the first measurement of the tritium beta decay spectrum below 200 keV. We find an excess of very low energy electrons which arise from molecular processes of the 3 He-T + ion

Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

Science.gov (United States)

Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

2017-06-22

Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

Science.gov (United States)

Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.; Abdel-Malek, Zalfa A.

2010-01-01

The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635

Molecular Determinants of Dissolved Organic Matter Reactivity in Lake Water

Directory of Open Access Journals (Sweden)

Alina Mostovaya

2017-12-01

Full Text Available Lakes in the boreal region have been recognized as the biogeochemical hotspots, yet many questions regarding the regulators of organic matter processing in these systems remain open. Molecular composition can be an important determinant of dissolved organic matter (DOM fate in freshwater systems, but many aspects of this relationship remain unclear due to the complexity of DOM and its interactions in the natural environment. Here, we combine ultrahigh resolution mass spectrometry (FT-ICR-MS with kinetic modeling of decay of >1,300 individual DOM molecular formulae identified by mass spectrometry, to evaluate the role of specific molecular characteristics in decomposition of lake water DOM. Our data is derived from a 4 months microbial decomposition experiment, carried out on water from three Swedish lakes, with the set-up including natural lake water, as well as the lake water pretreated with UV light. The relative decay rate of every molecular formula was estimated by fitting a single exponential model to the change in FT-ICR-MS signal intensities over decomposition time. We found a continuous range of exponential decay coefficients (kexp within different groups of compounds and show that for highly unsaturated and phenolic compounds the distribution of kexp was shifted toward the lowest values. Contrary to this general trend, plant-derived polyphenols and polycondensed aromatics were on average more reactive than compounds with an intermediate aromaticity. The decay rate of aromatic compounds increased with increasing nominal oxidation state of carbon, and molecular mass in some cases showed an inverse relationship with kexp in the UV-manipulated treatment. Further, we observe an increase in formulae-specific kexp as a result of the UV pretreatment. General trends in reactivity identified among major compound groups emphasize the importance of the intrinsic controllers of lake water DOM decay. However, we additionally indicate that each

Determination of urine metabolites containing radioactivatable elements by molecular neutron activation analysis

International Nuclear Information System (INIS)

Blotcky, A.J.; Rack, E.P.

1986-01-01

As urine is a final stage for the metabolic pathways of essential trace elements or chemical toxins, it is becoming increasingly important to not only report levels of trace elements but to determine the molecular or ionic identity of these trace elements. For a biological system such as urine, a molecular neutron activation analysis (MONAA) approach must involve a deproteinization step, where necessary, to ensure that metabolites such as amino acids, bases, r nucleosides are not protein bound prior to chemical separation. This can involve the simple application of ammonia or acid hydrolysis. All separations for the metabolites containing the radioactivatable element must be performed prior to neutron irradiation and subsequent radioassay for the metabolite. Separation procedures can include high-pressure liquid chromotography (HPLC), ion-exchange chromatography, size exclusion chromatography, solvent extraction, and/or gas chromatography. After separation, the separated metabolite is neutron irradiated and and radioassayed for the radioactivity in the metabolite. A review of previous work involving the determination of hormonal iodine, iodoamino acids, chlorinated pesticides, trimethyl-selenonium, and selenoamino acids in urine is discussed

Hybrid nanomembrane-based capacitors for the determination of the dielectric constant of semiconducting molecular ensembles

Science.gov (United States)

Petrini, Paula A.; Silva, Ricardo M. L.; de Oliveira, Rafael F.; Merces, Leandro; Bof Bufon, Carlos C.

2018-06-01

Considerable advances in the field of molecular electronics have been achieved over the recent years. One persistent challenge, however, is the exploitation of the electronic properties of molecules fully integrated into devices. Typically, the molecular electronic properties are investigated using sophisticated techniques incompatible with a practical device technology, such as the scanning tunneling microscopy. The incorporation of molecular materials in devices is not a trivial task as the typical dimensions of electrical contacts are much larger than the molecular ones. To tackle this issue, we report on hybrid capacitors using mechanically-compliant nanomembranes to encapsulate ultrathin molecular ensembles for the investigation of molecular dielectric properties. As the prototype material, copper (II) phthalocyanine (CuPc) has been chosen as information on its dielectric constant (k CuPc) at the molecular scale is missing. Here, hybrid nanomembrane-based capacitors containing metallic nanomembranes, insulating Al2O3 layers, and the CuPc molecular ensembles have been fabricated and evaluated. The Al2O3 is used to prevent short circuits through the capacitor plates as the molecular layer is considerably thin (electrical measurements of devices with molecular layers of different thicknesses, the CuPc dielectric constant has been reliably determined (k CuPc = 4.5 ± 0.5). These values suggest a mild contribution of the molecular orientation on the CuPc dielectric properties. The reported nanomembrane-based capacitor is a viable strategy for the dielectric characterization of ultrathin molecular ensembles integrated into a practical, real device technology.

Molecular hydrogen is involved in phytohormone signaling and stress responses in plants.

Directory of Open Access Journals (Sweden)

Jiqing Zeng

Full Text Available Molecular hydrogen (H2 metabolism in bacteria and algae has been well studied from an industrial perspective because H2 is viewed as a potential future energy source. A number of clinical trials have recently reported that H2 is a therapeutic antioxidant and signaling molecule. Although H2 metabolism in higher plants was reported in some early studies, its biological effects remain unclear. In this report, the biological effects of H2 and its involvement in plant hormone signaling pathways and stress responses were determined. Antioxidant enzyme activity was found to be increased and the transcription of corresponding genes altered when the effects of H2 on the germination of mung bean seeds treated with phytohormones was investigated. In addition, upregulation of several phytohormone receptor genes and genes that encode a few key factors involved in plant signaling pathways was detected in rice seedlings treated with HW. The transcription of putative rice hydrogenase genes, hydrogenase activity, and endogenous H2 production were also determined. H2 production was found to be induced by abscisic acid, ethylene, and jasmonate acid, salt, and drought stress and was consistent with hydrogenase activity and the expression of putative hydrogenase genes in rice seedlings. Together, these results suggest that H2 may have an effect on rice stress tolerance by modulating the output of hormone signaling pathways.

DAE-BRNS life sciences symposium on molecular biology of stress response and its applications

International Nuclear Information System (INIS)

2005-01-01

The world of living organisms is full of challenges from their surroundings and these organisms learn to adapt themselves to the changes - some transient and some permanent - in these surroundings. The demands on adaptability to stress are very strong for extremophiles that live in harsh conditions such as cold or hot temperatures, salinity and hyperbaric habitats. The stress could be biotic (e.g. infection or parasitism) or abiotic (e.g. temperature, light, salinity, heavy metals etc.) Evolutionarily living organisms have developed different shapes, coloration, habits etc. to survive in their habitats. The molecular mechanisms of these biological adaptations have become clearer only in recent years from the studies on the biological responses of an organism to stresses during its life time. Such responses are characterized by activation of certain genes and synthesis of proteins and metabolites, which facilitate amelioration of the stress. The molecular biology (biochemistry and genetics) of stress response is being constantly unravelled thanks to the availability of highly sensitive and high throughput techniques and a plethora of extremophilic experimental systems such as archaebacteria, radio resistant bacteria and midges, plants surviving in cold etc. An interesting outcome of this voluminous research has been the knowledge that responses to a group of stresses share common mechanisms, at least in part. This reflects the biologically conservationist trend among otherwise diverse organisms and stresses. In this symposium several papers and posters in the area of molecular biology of stress are presented in addition to some very interesting and promising-to-be informative and stimulating plenary lectures and invited talks from highly reputed scientists. The papers relevant to INIS are indexed separately

Use of signature-tagged mutagenesis to identify virulence determinants in Haemophilus ducreyi responsible for ulcer formation.

Science.gov (United States)

Yeung, Angela; Cameron, D William; Desjardins, Marc; Lee, B Craig

2011-02-01

Elucidating the molecular mechanisms responsible for chancroid, a genital ulcer disease caused by Haemophilus ducreyi, has been hampered in part by the relative genetic intractability of the organism. A whole genome screen using signature-tagged mutagenesis in the temperature-dependent rabbit model (TDRM) of H. ducreyi infection uncovered 26 mutants with a presumptive attenuated phenotype. Insertions in two previously recognized virulence determinants, hgbA and lspA1, validated this genome scanning technique. Database interrogation allowed assignment of 24 mutants to several functional classes, including transport, metabolism, DNA repair, stress response and gene regulation. The attenuated virulence for a 3 strain with a mutation in hicB was confirmed by individual infection in the TDRM. The results from this preliminary study indicate that this high throughput strategy will further the understanding of the pathogenesis of H. ducreyi infection. Copyright © 2010 Elsevier B.V. All rights reserved.

Synthesis, three-dimensional structure, conformation and correct chemical shift assignment determination of pharmaceutical molecules by NMR and molecular modeling

Energy Technology Data Exchange (ETDEWEB)

Azeredo, Sirlene O.F. de; Sales, Edijane M.; Figueroa-Villar, José D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Grupo de Ressonância Magnética Nuclear e Química Medicinal

2017-07-01

This work includes the synthesis of phenanthrenequinone guanylhydrazone and phenanthro[9,10-e][1,2,4]triazin-3-amine to be tested as intercalate with DNA for treatment of cancer. The other synthesized product, 2-[(4-chlorophenylamino)methylene]malononitrile, was designed for future determination of its activity against leishmaniasis. A common problem about some articles on the literature is that some previously published compounds display error of their molecular structures. In this article it is shown the application of several procedures of nuclear magnetic resonance (NMR) to determine the complete molecular structure and the non questionable chemical shift assignment of the synthesized compounds, and also their analysis by molecular modeling to confirm the NMR results. To determine the capacity of pharmacological compounds to interact with biological targets is determined by docking. This work is to motivate the application of NMR and molecular modeling on organic synthesis, being a process that is very important for the study of the prepared compounds as interactions with biological targets by NMR. (author)

Synthesis, three-dimensional structure, conformation and correct chemical shift assignment determination of pharmaceutical molecules by NMR and molecular modeling

International Nuclear Information System (INIS)

Azeredo, Sirlene O.F. de; Sales, Edijane M.; Figueroa-Villar, José D.

2017-01-01

This work includes the synthesis of phenanthrenequinone guanylhydrazone and phenanthro[9,10-e][1,2,4]triazin-3-amine to be tested as intercalate with DNA for treatment of cancer. The other synthesized product, 2-[(4-chlorophenylamino)methylene]malononitrile, was designed for future determination of its activity against leishmaniasis. A common problem about some articles on the literature is that some previously published compounds display error of their molecular structures. In this article it is shown the application of several procedures of nuclear magnetic resonance (NMR) to determine the complete molecular structure and the non questionable chemical shift assignment of the synthesized compounds, and also their analysis by molecular modeling to confirm the NMR results. To determine the capacity of pharmacological compounds to interact with biological targets is determined by docking. This work is to motivate the application of NMR and molecular modeling on organic synthesis, being a process that is very important for the study of the prepared compounds as interactions with biological targets by NMR. (author)

Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer

International Nuclear Information System (INIS)

Chen, Xiaosong; Yuan, Ying; Fei, Xiaochun; Jin, Xiaolong; Shen, Kunwei; Sun, Long; Mao, Yan; Zhu, Siji; Wu, Jiayi; Huang, Ou; Li, Yafen; Chen, Weiguo; Wang, Jianhua

2013-01-01

Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented. Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive. There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB. CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors

Molecular defense response of oil palm to Ganoderma infection.

Science.gov (United States)

Ho, C-L; Tan, Y-C

2015-06-01

Basal stem rot (BSR) of oil palm roots is due to the invasion of fungal mycelia of Ganoderma species which spreads to the bole of the stem. In addition to root contact, BSR can also spread by airborne basidiospores. These fungi are able to break down cell wall components including lignin. BSR not only decreases oil yield, it also causes the stands to collapse thus causing severe economic loss to the oil palm industry. The transmission and mode of action of Ganoderma, its interactions with oil palm as a hemibiotroph, and the molecular defence responses of oil palm to the infection of Ganoderma boninense in BSR are reviewed, based on the transcript profiles of infected oil palms. The knowledge gaps that need to be filled in oil palm-Ganoderma molecular interactions i.e. the associations of hypersensitive reaction (HR)-induced cell death and reactive oxygen species (ROS) kinetics to the susceptibility of oil palm to Ganoderma spp., the interactions of phytohormones (salicylate, jasmonate and ethylene) at early and late stages of BSR, and cell wall strengthening through increased production of guaiacyl (G)-type lignin, are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hybrid nanomembrane-based capacitors for the determination of the dielectric constant of semiconducting molecular ensembles.

Science.gov (United States)

Petrini, Paula Andreia; Lopes da Silva, Ricardo Magno; de Oliveira, Rafael Furlan; Merces, Leandro; Bufon, Carlos César Bof

2018-04-06

Considerable advances in the field of molecular electronics have been achieved over the recent years. One persistent challenge, however, is the exploitation of the electronic properties of molecules fully integrated into devices. Typically, the molecular electronic properties are investigated using sophisticated techniques incompatible with a practical device technology, such as the scanning tunneling microscope (STM). The incorporation of molecular materials in devices is not a trivial task since the typical dimensions of electrical contacts are much larger than the molecular ones. To tackle this issue, we report on hybrid capacitors using mechanically-compliant nanomembranes to encapsulate ultrathin molecular ensembles for the investigation of molecular dielectric properties. As the prototype material, copper (II) phthalocyanine (CuPc) has been chosen as information on its dielectric constant (kCuPc) at the molecular scale is missing. Here, hybrid nanomembrane-based capacitors containing metallic nanomembranes, insulating Al2O3 layers, and the CuPc molecular ensemble have been fabricated and evaluated. The Al2O3 is used to prevent short circuits through the capacitor plates as the molecular layer is considerably thin (< 30 nm). From the electrical measurements of devices with molecular layers of different thicknesses, the CuPc dielectric constant has been reliably determined (kCuPc = 4.5 ± 0.5). These values suggest a mild contribution of molecular orientation in the CuPc dielectric properties. The reported nanomembrane-based capacitor is a viable strategy for the dielectric characterization of ultrathin molecular ensembles integrated into a practical, real device technology. © 2018 IOP Publishing Ltd.

Molecular effects in the neutrino mass determination from beta-decay of the tritium molecule

International Nuclear Information System (INIS)

Fackler, O.; Jeziorski, B.; Kolos, W.; Szalewicz, K.; Monkhorst, H.J.; Mugge, M.

1986-03-01

Molecular final state energies and transition probabilities have been computed for beta-decay of the tritium molecule. The results are of sufficient accuracy to make a determination of the electron neutrino rest mass with an error not exceeding a few tenths of an electron volt. Effects of approximate models of tritium beta-decay on the neutrino mass determination are discussed. 14 refs., 3 figs., 1 tab

Molecular Responses of Groundnut (Arachis hypogea L. to Zinc Stress

Directory of Open Access Journals (Sweden)

A. John De Britto

2013-08-01

Full Text Available Heavy metals are important environmental pollutants and their toxicity is a problem of increasing significance for ecological, evolutionary and environmental reasons. The interference of germination related proteins by heavy metals has not been well documented at the proteomic and genomic level. In the current study, molecular responses of germinating groundnut seeds were investigated under Zinc stress. The SDS-PAGE showed the preliminary changes in the polypeptides patterns under Zinc stress. Restriction digestion banding pattern of EcoRI and Hind III enzymes showed distinct banding pattern in the treated plants.

Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

Directory of Open Access Journals (Sweden)

Cláudia Regina Batista de Souza

2012-07-01

Full Text Available Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops.

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

NARCIS (Netherlands)

Denning, Denise; Roos, Wouter H

2016-01-01

The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

Science.gov (United States)

Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

2017-11-01

The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuromuscular dose-response studies: determining sample size.

Science.gov (United States)

Kopman, A F; Lien, C A; Naguib, M

2011-02-01

Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

Hofmeister effect on thermo-responsive poly(propylene oxide): Role of polymer molecular weight and concentration

DEFF Research Database (Denmark)

Moghaddam, Saeed Zajforoushan; Thormann, Esben

2016-01-01

) salts on aqueous solutions of poly(propylene oxide) (PPO) is studied. Four different molecular weights of PPO were investigated, to determine how the variation in the polymer coil size affects the Hofmeister effect. The investigation was further conducted for different PPO concentrations, in order...... with the transition. It was observed that increasing the molecular weight weakens the effect of the both salts, which is interpreted in terms of a scaling law between the molecular weight and the accessible surface area of the polymers. Increasing the PPO concentration further diminished the NaCl effect...

A Comprehensive Experiment for Molecular Biology: Determination of Single Nucleotide Polymorphism in Human REV3 Gene Using PCR-RFLP

Science.gov (United States)

Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

2017-01-01

Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of…

Molecular and Cellular Signaling

CERN Document Server

Beckerman, Martin

2005-01-01

A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

Molecular sizes of lichen ice nucleation sites determined by gamma radiation inactivation analysis

International Nuclear Information System (INIS)

Kieft, T.L.; Ruscetti, T.

1992-01-01

It has previously been shown that some species of lichen fungi contain proteinaceous ice nuclei which are active at temperatures as warm as −2 °C. This experiment was undertaken to determine the molecular sizes of ice nuclei in the lichen fungus Rhizoplaca chrysoleuca and to compare them to bacterial ice nuclei from Pseudomonas syringae. Gamma radiation inactivation analysis was used to determine molecular weights. Radiation inactivation analysis is based on target theory, which states that the likelihood of a molecule being inactivated by gamma rays increases as its size increases. Three different sources of ice nuclei from the lichen R. chrysoleuca were tested: field-collected lichens, extract of lichen fungus, and a pure culture of the fungus R. chrysoleuca. P. syringae strain Cit7 was used as a source of bacterial ice nuclei. Samples were lyophilized, irradiated with gamma doses ranging from 0 to 10.4 Mrads, and then tested for ice nucleation activity using a droplet-freezing assay. Data for all four types of samples were in rough agreement; sizes of nucleation sites increased logarithmically with increasing temperatures of ice nucleation activity. Molecular weights of nucleation sites active between −3 and −4 °C from the bacteria and from the field-collected lichens were approximately 1.0 × 10 6 Da. Nuclei from the lichen fungus and in the lichen extract appeared to be slightly smaller but followed the same log-normal pattern with temperature of ice nucleation activity. The data for both the bacterial and lichen ice nuclei are in agreement with ice nucleation theory which states that the size of ice nucleation sites increases logarithmically as the temperature of nucleation increases linearly. This suggests that although some differences exist between bacterial and lichen ice nucleation sites, their molecular sizes are quite similar

20 CFR 416.1014 - Responsibilities for obtaining evidence to make disability determinations.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Responsibilities for obtaining evidence to make disability determinations. 416.1014 Section 416.1014 Employees' Benefits SOCIAL SECURITY... Responsibilities for Performing the Disability Determination Function § 416.1014 Responsibilities for obtaining...

20 CFR 404.1614 - Responsibilities for obtaining evidence to make disability determinations.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Responsibilities for obtaining evidence to make disability determinations. 404.1614 Section 404.1614 Employees' Benefits SOCIAL SECURITY... Responsibilities for Performing the Disability Determination Function § 404.1614 Responsibilities for obtaining...

Dynamic properties of sensory stimulation evoked responses in mouse cerebellar granule cell layer and molecular layer.

Science.gov (United States)

Bing, Yan-Hua; Zhang, Guang-Jian; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

2015-01-12

Sensory information coming from climbing fiber and mossy fiber-granule cell pathways, generates motor-related outputs according to internal rules of integration and computation in the cerebellar cortex. However, the dynamic properties of sensory information processing in mouse cerebellar cortex are less understood. Here, we studied the dynamic properties of sensory stimulation-evoked responses in the cerebellar granule cell layer (GCL) and molecular layer (ML) by electrophysiological recordings method. Our data showed that air-puff stimulation (5-10 ms in duration) of the ipsilateral whisker pad evoked single-peak responses in the GCL and ML; whereas a duration of stimulation ≥30 ms in GCL and ≥60 ms in ML, evoked double-peak responses that corresponded with stimulation-on and -off responses via mossy fiber pathway. The highest frequency of stimulation train for evoking GCL responses was 33 Hz. In contrast, the highest frequency of stimulation train for evoking ML responses was 4 Hz. These results indicate that the cerebellar granule cells transfer the high-fidelity sensory information from mossy fibers, which is cut-off by molecular layer interneurons (MLIs). Our results suggest that the MLIs network acts as a low-pass filter during the processing of high-frequency sensory information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

Science.gov (United States)

Seiler, Roland; Ashab, Hussam Al Deen; Erho, Nicholas; van Rhijn, Bas W G; Winters, Brian; Douglas, James; Van Kessel, Kim E; Fransen van de Putte, Elisabeth E; Sommerlad, Matthew; Wang, Natalie Q; Choeurng, Voleak; Gibb, Ewan A; Palmer-Aronsten, Beatrix; Lam, Lucia L; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A; Lerner, Seth P; McConkey, David J; Choi, Woonyoung; Kim, William Y; Kiss, Bernhard; Thalmann, George N; Todenhöfer, Tilman; Crabb, Simon J; North, Scott; Zwarthoff, Ellen C; Boormans, Joost L; Wright, Jonathan; Dall'Era, Marc; van der Heijden, Michiel S; Black, Peter C

2017-10-01

An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Gene expression analysis was used to assign subtypes. Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Different molecular

Molecular design of light-responsive hydrogels, for in situ generation of fast and reversible valves for microfluidic applications

NARCIS (Netherlands)

Schiphorst, ter J.; Coleman, S.; Stumpel, J.E.; Ben Azouz, A.; Diamond, D.; Schenning, A.P.H.J.

2015-01-01

Reversible light-responsive hydrogel valves with response characteristics compatible for microfluidics have been obtained by optimization of molecular design of spiropyran photoswitches and gel composition. Self-protonating gel formulations were exploited, wherein acrylic acid was copolymerized in

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

Directory of Open Access Journals (Sweden)

Sebastian Weckbach

2012-01-01

Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

Science.gov (United States)

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

Cellular and molecular responses of E. fetida coelomocytes exposed to TiO{sub 2} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Bigorgne, Emilie, E-mail: emilie.bigorgne@univ-lorraine.fr; Foucaud, Laurent [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Caillet, Celine [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Giamberini, Laure; Nahmani, Johanne [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Thomas, Fabien [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Rodius, Francois [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France)

2012-07-15

An in vitro approach using coelomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO{sub 2} nanoparticles. Coelomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO{sub 2} nanoparticles (1-25 {mu}g/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO{sub 2} nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 {mu}g/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO{sub 2} in our experimental conditions. This in vitro approach showed that TiO{sub 2} nanoparticles were taken up by coelomocytes and they could modify the molecular response of immune and detoxification system.

a Chiral Tagging Strategy for Determining Absolute Configuration and Enantiomeric Excess by Molecular Rotational Spectroscopy

Science.gov (United States)

Evangelisti, Luca; Caminati, Walther; Patterson, David; Thomas, Javix; Xu, Yunjie; West, Channing; Pate, Brooks

2017-06-01

The introduction of three wave mixing rotational spectroscopy by Patterson, Schnell, and Doyle [1,2] has expanded applications of molecular rotational spectroscopy into the field of chiral analysis. Chiral analysis of a molecule is the quantitative measurement of the relative abundances of all stereoisomers of the molecule and these include both diastereomers (with distinct molecular rotational spectra) and enantiomers (with equivalent molecular rotational spectra). This work adapts a common strategy in chiral analysis of enantiomers to molecular rotational spectroscopy. A "chiral tag" is attached to the molecule of interest by making a weakly bound complex in a pulsed jet expansion. When this tag molecule is enantiopure, it will create diastereomeric complexes with the two enantiomers of the molecule being analyzed and these can be differentiated by molecule rotational spectroscopy. Identifying the structure of this complex, with knowledge of the absolute configuration of the tag, establishes the absolute configuration of the molecule of interest. Furthermore, the diastereomer complex spectra can be used to determine the enantiomeric excess of the sample. The ability to perform chiral analysis will be illustrated by a study of solketal using propylene oxide as the tag. The possibility of using current methods of quantum chemistry to assign a specific structure to the chiral tag complex will be discussed. Finally, chiral tag rotational spectroscopy offers a "gold standard" method for determining the absolute configuration of the molecule through determination of the substitution structure of the complex. When this measurement is possible, rotational spectroscopy can deliver a quantitative three dimensional structure of the molecule with correct stereochemistry as the analysis output. [1] David Patterson, Melanie Schnell, John M. Doyle, Nature 497, 475 (2013). [2] David Patterson, John M. Doyle, Phys. Rev. Lett. 111, 023008 (2013).

20 CFR 725.495 - Criteria for determining a responsible operator.

Science.gov (United States)

2010-04-01

... the responsible operator if no more recent employer may be considered a potentially liable operator... designated responsible operator must demonstrate that the more recent employer possesses sufficient assets to... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Criteria for determining a responsible...

Molecular determinants of the V3 loop of human immunodeficiency virus type 1 glycoprotein gp120 responsible for controlling cell tropism.

Science.gov (United States)

Chavda, S C; Griffin, P; Han-Liu, Z; Keys, B; Vekony, M A; Cann, A J

1994-11-01

We and others have identified the major determinant of cell tropism in human immunodeficiency virus type 1 (HIV-1) as the V3 loop of glycoprotein gp120. We have conducted a detailed study of two molecularly cloned isolates of HIV-1, HIVJR-CSF and HIVNL4-3, that differ in their tropism for immortalized CD4+ cell lines, by constructing a series of site-directed mutations within the V3 loop of HIVJR-CSF based on the sequence of HIVNL4-3. The phenotypes of these mutants fall into two classes, those which are viable and those which are not. A spontaneous mutant with significantly altered growth properties was also recovered and found to have an additional single amino acid change in the V3 loop sequence. The carboxy-terminal beta-strand part of the V3 loop is the major determinant of cell tropism. However, the results presented here indicate that the functional role of the V3 loop sequences can only be interpreted properly in the context of the original gp120 backbone from which they were derived. These findings show that over-simplistic interpretation of sequence data derived from unknown mixtures of HIV variants in infected persons may be highly misleading.

Tutorial: Determination of thermal boundary resistance by molecular dynamics simulations

Science.gov (United States)

Liang, Zhi; Hu, Ming

2018-05-01

Due to the high surface-to-volume ratio of nanostructured components in microelectronics and other advanced devices, the thermal resistance at material interfaces can strongly affect the overall thermal behavior in these devices. Therefore, the thermal boundary resistance, R, must be taken into account in the thermal analysis of nanoscale structures and devices. This article is a tutorial on the determination of R and the analysis of interfacial thermal transport via molecular dynamics (MD) simulations. In addition to reviewing the commonly used equilibrium and non-equilibrium MD models for the determination of R, we also discuss several MD simulation methods which can be used to understand interfacial thermal transport behavior. To illustrate how these MD models work for various interfaces, we will show several examples of MD simulation results on thermal transport across solid-solid, solid-liquid, and solid-gas interfaces. The advantages and drawbacks of a few other MD models such as approach-to-equilibrium MD and first-principles MD are also discussed.

Determination of BPA, BPB, BPF, BADGE and BFDGE in canned energy drinks by molecularly imprinted polymer cleaning up and UPLC with fluorescence detection.

Science.gov (United States)

Gallo, Pasquale; Di Marco Pisciottano, Ilaria; Esposito, Francesco; Fasano, Evelina; Scognamiglio, Gelsomina; Mita, Gustavo Damiano; Cirillo, Teresa

2017-04-01

A new method for simultaneous determination of five bisphenols in canned energy drinks by UPLC with fluorescence detection, after clean up on molecularly imprinted polymers, is herein described. The method was validated at two concentration levels, calculating trueness, repeatability and within-laboratory reproducibility, specificity, linearity of detector response, the limits of quantifications and the limits of detection for each bisphenol. The method is specific, reliable and very sensitive, allowing for determination of bisphenol F diglycidyl ether (BFDGE), bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF) and bisphenol A diglycidyl ether (BADGE) down to 0.50ng/mL; it was employed to determine contamination levels from these bisphenols in forty energy drinks of different brands, collected from the market in Naples. BPA was detected in 17 out of 40 samples (42.5%); in some energy drinks also BPF, BADGE and BFDGE were determined. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determination of phosphorus, sulfur and the halogens using high-temperature molecular absorption spectrometry in flames and furnaces-A review

International Nuclear Information System (INIS)

Welz, Bernhard; Lepri, Fabio G.; Araujo, Rennan G.O.; Ferreira, Sergio L.C.; Huang Maodong; Okruss, Michael; Becker-Ross, Helmut

2009-01-01

The literature about the investigation of molecular spectra of phosphorus, sulfur and the halogens in flames and furnaces, and the use of these spectra for the determination of these non-metals has been reviewed. Most of the investigations were carried out using conventional atomic absorption spectrometers, and there were in essence two different approaches. In the first one, dual-channel spectrometers with a hydrogen or deuterium lamp were used, applying the two-line method for background correction; in the second one, a line source was used that emitted an atomic line, which overlapped with the molecular spectrum. The first approach had the advantage that any spectral interval could be accessed, but it was susceptible to spectral interference; the second one had the advantage that the conventional background correction systems could be used to minimize spectral interferences, but had the problem that an atomic line had to be found, which was overlapping sufficiently well with the maximum of the molecular absorption spectrum. More recently a variety of molecular absorption spectra were investigated using a low-resolution polychromator with a CCD array detector, but no attempt was made to use this approach for quantitative determination of non-metals. The recent introduction and commercial availability of high-resolution continuum source atomic absorption spectrometers is offering completely new possibilities for molecular absorption spectrometry and its use for the determination of non-metals. The use of a high-intensity continuum source together with a high-resolution spectrometer and a CCD array detector makes possible selecting the optimum wavelength for the determination and to exclude most spectral interferences.

Targeted Molecular Dynamics to determine Focal Adhesion Targeting Domain Folding Intermediates

Directory of Open Access Journals (Sweden)

Pallavi Mohanty

2017-10-01

Full Text Available The Focal adhesion kinase (FAT domain of Focal Adhesion Kinase is a four helical bundle known for conformational plasticity. FAT adopts two distinctly different conformations i.e., close (cFAT and arm-exchanged (aeFAT states under native conditions [1]. The slow transition from cFAT to aeFAT is likely to proceed through an open intermediate state that allows YENV motif to attain β-turn conformation and phosphorylation of Y925 by Src kinases [2]. The two end states of FAT are known to interact with Paxillin and are responsible for maintaining steady state in Heart while intermediate conformation interacts with Grb2-SH2 leading to Pathological Cardiac Hypertrophy (PAH [2]. 10ns Targeted Molecular Dynamics (TMD was done between c- and aeFAT in order to explore the conformational transition and to capture pathologically relevant oFAT. Cluster and dynamic cross correlation analysis (DCCA of TMD generated trajectory was done and the selected FAT intermediate was docked with Grb2-SH2 using HADDOCK v2.2 docking followed by molecular dynamics. Conservation analysis of FAT-Grb2 binding site was done using CONSURF [3]. A Pharmacophore FAT-Grb2 complex was generated using SPARKv1.2 and submitted for Virtual screening using BLAZE v4. Drug likeliness and ADMET properties were calculated using MOLINSPIRATION tool. TMD reveals six clusters and DCCA showed positively and negatively correlated region along the transition pathway. Intermediates with competence for Grb2 interaction were docked with Grb2 and best binding complex was further refined. MMPBSA binding energy calculations revealed the best binding pose where the phosphorylated YENV motif of Human FAT interacted with a charged and hydrophobic pocket of Grb2. The conservation analysis showed that the charged pocket was more conserved in comparison with the hydrophobic pocket, hence providing useful insights on binding and specificity determining residues in Grb2. Virtual screening using the pharmacophore

Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

Science.gov (United States)

Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

2017-10-01

With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

Photoelectron and UV absorption spectroscopy for determination of electronic configurations of negative molecular ions: Chlorophenols

International Nuclear Information System (INIS)

Tseplin, E.E.; Tseplina, S.N.; Tuimedov, G.M.; Khvostenko, O.G.

2009-01-01

The photoelectron and UV absorption spectra of p-, m-, and o-chlorophenols in the gas phase have been obtained. On the basis of DFT B3LYP/6-311++G(d, p) calculations, the photoelectron bands have been assigned to occupied molecular orbitals. From the TDDFT B3LYP/6-311++G(d, p) calculation results, the UV absorption bands have been assigned to excited singlet states of the molecules under investigation. For each excited state a dominant transition was found. It has been shown that the energies of these singlet transitions correlate with the energy differences between the ground-state molecular orbitals participating in them. Using the UV spectra interpretation, the electronic states of molecular anions detected earlier for the same compounds by means of the resonant electron capture mass-spectrometry have been determined.

Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Ingrid Leguerney

2017-01-01

Full Text Available Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87, p=0.0003 and AUC (R=0.81, p=0.0013. The percentage of vessel tissue area was significantly reduced (p<0.01 in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

Functional and physical molecular size of the chicken hepatic lectin determined by radiation inactivation and sedimentation equilibrium analysis

International Nuclear Information System (INIS)

Steer, C.J.; Osborne, J.C. Jr.; Kempner, E.S.

1990-01-01

Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of 79,000 +/- 7,000. However, the solubilized lectin was detected as a heterogeneous population of oligomers with molecular weights as high as 450,000. Addition of calcium or calcium plus N-acetylglucosamine decreased the higher molecular weight species, but the lower limit molecular weights remained invariant. Similar results were determined when the chicken lectin was solubilized in Brij 58, C12E9, or 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonic acid (CHAPS). Results from the present study suggest that in the plasma membrane, the functional species of the chicken hepatic lectin exists as a trimer. However, in detergent solution, the purified receptor forms a heterogeneous population of irreversible oligomers that exhibit binding activity proportional to size

The roles of bulk and interfacial molecular orientations in determining the performance of organic bilayer solar cells

KAUST Repository

Ngongang Ndjawa, Guy O.

2014-09-09

Molecular orientation plays a significant role in determining the performance of small molecule solar cells. Key photovoltaic processes in these cells are strongly dependent on how the molecules are oriented in the active layer. We isolate contributions arising from the bulk molecular orientations vs. those from interfacial orientations in ZnPc/C60 bilayer systems and we probe these contributions by comparing device pairs in which only the bulk or the interface differ. By controlling the orientation in the bulk the current can be strongly modulated, whereas controlling the interfacial molecular orientation and degree of intermixing mediate the voltage.

The roles of bulk and interfacial molecular orientations in determining the performance of organic bilayer solar cells

KAUST Repository

Ngongang Ndjawa, Guy O.; Graham, Kenneth R.; Conron, Sarah; Erwin, Patrick; Li, Ruipeng; Chou, Kang Wei; Burkhard, George; Krishnan Jagadamma, Lethy; Hoke, Eric T.; McGehee, Michael D.; Thompson, Mark E.; Amassian, Aram

2014-01-01

Molecular orientation plays a significant role in determining the performance of small molecule solar cells. Key photovoltaic processes in these cells are strongly dependent on how the molecules are oriented in the active layer. We isolate contributions arising from the bulk molecular orientations vs. those from interfacial orientations in ZnPc/C60 bilayer systems and we probe these contributions by comparing device pairs in which only the bulk or the interface differ. By controlling the orientation in the bulk the current can be strongly modulated, whereas controlling the interfacial molecular orientation and degree of intermixing mediate the voltage.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

Science.gov (United States)

Fernandes, T; Soci, U P R; Oliveira, E M

2011-09-01

Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

Directory of Open Access Journals (Sweden)

T. Fernandes

2011-09-01

Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Size and molecular weight determination of polysaccharides by means of nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA).

Science.gov (United States)

Weiss, Victor U; Golesne, Monika; Friedbacher, Gernot; Alban, Susanne; Szymanski, Wladyslaw W; Marchetti-Deschmann, Martina; Allmaier, Günter

2018-02-21

Size, size distribution and molecular weight (MW) determination of nanoparticles and that are for example large polymers, are of great interest and pose an analytical challenge. In this context, nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA) is a valuable tool with growing impact. Separation of single-charged analytes according to their electrophoretic mobility diameter (EMD) starting from single-digit EMDs up to several hundred nm diameters is possible. In case of spherical analytes, the EMD corresponds to the dry nanoparticle size. Additionally, the instrument is capable of number-based, single-particle detection following the recommendation of the European Commission for nanoparticle characterization (2011/696/EU). In case an EMD/MW correlation for a particular compound class (based on availability of well-defined standards) exists, a nanoparticle's MW can be determined from its EMD. In the present study, we focused on nES GEMMA of linear and branched, water-soluble polysaccharides forming nanoparticles and were able to obtain spectra for both analyte classes regarding single-charged species. Based on EMDs for corresponding analytes, an excellent EMD/MW correlation could be obtained in case of the branched natural polymer (dextran). This enables the determination of dextran MWs from nES GEMMA spectra despite high analyte polydispersity and in a size/MW range, where classical mass spectrometry is limited. EMD/MW correlations based on linear (pullulans, oat-ß-glucans) polymers were significantly different, possibly indicating challenges in the exact MW determination of these compounds by, for example, chromatographic and light scattering means. Despite these observations, nES GEMMA of linear, monosaccharide-based polymers enabled the determination of size and size-distribution of such dry bionanoparticles. © 2018 The Authors. Electrophoresis published by Wiley-VCH Verlag GmbH & Co. KGaA.

Molecular outflows in the L1641 region of Orion

International Nuclear Information System (INIS)

Morgan, J.A.

1990-01-01

Little is known about the interaction between molecular outflows associated with young stellar objects and the parent molecular cloud that produced them. This is because molecular outflows are a recently discovered phenomenon and, so, have not had their global properties studied in great detail and molecular clouds were not mapped to sufficiently high spatial resolution to resolve the interaction. The interaction between molecular outflows and the L1641 molecular cloud is addressed by both identifying and mapping all the molecular outflows as well as the detailed structure of the cloud. Candidate molecular outflows were found from single point 12-CO observations of young stellar objects identified from the IRAS survey data. The candidate sources were then mapped to confirm their molecular outflow nature. From these maps, molecular outflow characteristics such as their morphology, orientation, and energetics were determined. In addition, the Orion molecular cloud was mapped to compare directly with the molecular outflows. The molecular outflows identified were found to have rising infrared spectra, radio continuum emission that suggests a stellar wind or optically thick H II region, and molecular line strengths that indicate that they are embedded within a very dense environment. The lack of an optical counterpart for many molecular outflows suggests that they occur at the earliest stages of stellar evolution. The lack of an optical counterpart for many molecular outflows suggest that they occur at the earliest stages of stellar evolution. The orientations of the molecular outflows appear to lie in no preferred direction and they have shapes that indicate that the molecular cloud is responsible for determining their direction and collimation

Cellular and molecular responses of E. fetida cœlomocytes exposed to TiO2 nanoparticles

Science.gov (United States)

Bigorgne, Emilie; Foucaud, Laurent; Caillet, Céline; Giambérini, Laure; Nahmani, Johanne; Thomas, Fabien; Rodius, François

2012-07-01

An in vitro approach using cœlomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO2 nanoparticles. Cœlomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO2 nanoparticles (1-25 μg/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO2 nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 μg/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO2 in our experimental conditions. This in vitro approach showed that TiO2 nanoparticles were taken up by cœlomocytes and they could modify the molecular response of immune and detoxification system.

Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

Science.gov (United States)

Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

Structure determination of an 11-subunit exosome in complex with RNA by molecular replacement

International Nuclear Information System (INIS)

Makino, Debora Lika; Conti, Elena

2013-01-01

The crystallographic steps towards the structure determination of a complete eukaryotic exosome complex bound to RNA are presented. Phasing of this 11-protein subunit complex was carried out via molecular replacement. The RNA exosome is an evolutionarily conserved multi-protein complex involved in the 3′ degradation of a variety of RNA transcripts. In the nucleus, the exosome participates in the maturation of structured RNAs, in the surveillance of pre-mRNAs and in the decay of a variety of noncoding transcripts. In the cytoplasm, the exosome degrades mRNAs in constitutive and regulated turnover pathways. Several structures of subcomplexes of eukaryotic exosomes or related prokaryotic exosome-like complexes are known, but how the complete assembly is organized to fulfil processive RNA degradation has been unclear. An atomic snapshot of a Saccharomyces cerevisiae 420 kDa exosome complex bound to an RNA substrate in the pre-cleavage state of a hydrolytic reaction has been determined. Here, the crystallographic steps towards the structural elucidation, which was carried out by molecular replacement, are presented

Enhancing Accuracy in Molecular Weight Determination of Highly Heterogeneously Glycosylated Proteins by Native Tandem Mass Spectrometry

NARCIS (Netherlands)

Wang, Guanbo; de Jong, Rob N; van den Bremer, Ewald T J; Parren, Paul W H I; Heck, Albert J R

2017-01-01

The determination of molecular weights (MWs) of heavily glycosylated proteins is seriously hampered by the physicochemical characteristics and heterogeneity of the attached carbohydrates. Glycosylation impacts protein migration during sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis

Molecular characterization and expression profiling of cd-responsive genes in triticum durum

OpenAIRE

Cebeci, Özge; Cebeci, Ozge

2006-01-01

Cadmium (Cd) is a toxic heavy metal which has detrimental effects both in plants and human. There is a lack of knowledge on the molecular mechanisms of Cd toxicity in crop plants. The objective of this study was to identify and clone expressed Cd-responsive genes from two Triticum durum cvs. Balcah-85 and Balcah-2000 using mRNA differential display technique. We identified 10 cDNA clones whose level of expression significantly changed upon Cd exposure and thus isolated for further characteriz...

Molecular ecological network analyses.

Science.gov (United States)

Deng, Ye; Jiang, Yi-Huei; Yang, Yunfeng; He, Zhili; Luo, Feng; Zhou, Jizhong

2012-05-30

Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data. Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16 S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open

Corporate social responsibility determinants: the relation with CSR disclosure

OpenAIRE

A. Pistoni; L. Songini

2013-01-01

This chapter intends to contribute to the debate on the determinants of corporate social responsibility (CSR) and their impact on performance measurement and communication systems. It aims at analyzing the relationship between the reasons why firms adopt CSR and the importance given to voluntary CSR disclosure. Two main categories of CSR determinants have been identified: the external ones, coming from the environment outside the firm, and the internal determinants, which are linked to som...

Development and Application of Electrochemical Sensor Based on Molecularly Imprinted Polymer and Carbon Nanotubes for the Determination of Carvedilol

Directory of Open Access Journals (Sweden)

Malena Karla Lombello Coelho

2016-11-01

Full Text Available This work describes the preparation of a glassy carbon electrode (GCE modified with molecularly imprinted polymer (MIP and multiwalled carbon nanotubes (MWCNTs for determination of carvedilol (CAR. Electrochemical behavior of CAR on the modified electrode was evaluated using cyclic voltammetry. The best composition was found to be 65% (m/m of MIP. Under optimized conditions (pH 8.5 in 0.25 mol L−1 Britton–Robinson buffer and 0.1 mol L−1 KCl the voltammetric method showed a linear response for CAR in the range of 50–325 µmol L−1 (R = 0.9755, with detection and quantification limits of 16.14 µmol L−1 and 53.8 µmol L−1, respectively. The developed method was successfully applied for determination of CAR in real samples of pharmaceuticals. The sensor presented good sensitivity, rapid detection of CAR, and quick and easy preparation. Furthermore, the material used as modifier has a simple synthesis and its amount utilized is very small, thus illustrating the economic feasibility of this sensor.

Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

International Nuclear Information System (INIS)

Hong, J.-H.; Chiang, C.-S.; Tsao, C.-Y.; Lin, P.-Y.; Wu, C.-J.; McBride, William H.

2001-01-01

Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. Methods and Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-α, mIL-1α, mIL-1β, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-γ) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. Conclusions: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process

Tailored Surfaces/Assemblies for Molecular Plasmonics and Plasmonic Molecular Electronics.

Science.gov (United States)

Lacroix, Jean-Christophe; Martin, Pascal; Lacaze, Pierre-Camille

2017-06-12

Molecular plasmonics uses and explores molecule-plasmon interactions on metal nanostructures for spectroscopic, nanophotonic, and nanoelectronic devices. This review focuses on tailored surfaces/assemblies for molecular plasmonics and describes active molecular plasmonic devices in which functional molecules and polymers change their structural, electrical, and/or optical properties in response to external stimuli and that can dynamically tune the plasmonic properties. We also explore an emerging research field combining molecular plasmonics and molecular electronics.

Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

Directory of Open Access Journals (Sweden)

Martino V. Franchi

2017-07-01

Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

Engineering responsive polymer building blocks with host-guest molecular recognition for functional applications.

Science.gov (United States)

Hu, Jinming; Liu, Shiyong

2014-07-15

CONSPECTUS: All living organisms and soft matter are intrinsically responsive and adaptive to external stimuli. Inspired by this fact, tremendous effort aiming to emulate subtle responsive features exhibited by nature has spurred the invention of a diverse range of responsive polymeric materials. Conventional stimuli-responsive polymers are constructed via covalent bonds and can undergo reversible or irreversible changes in chemical structures, physicochemical properties, or both in response to a variety of external stimuli. They have been imparted with a variety of emerging applications including drug and gene delivery, optical sensing and imaging, diagnostics and therapies, smart coatings and textiles, and tissue engineering. On the other hand, in comparison with molecular chemistry held by covalent bonds, supramolecular chemistry built on weak and reversible noncovalent interactions has emerged as a powerful and versatile strategy for materials fabrication due to its facile accessibility, extraordinary reversibility and adaptivity, and potent applications in diverse fields. Typically involving more than one type of noncovalent interactions (e.g., hydrogen bonding, metal coordination, hydrophobic association, electrostatic interactions, van der Waals forces, and π-π stacking), host-guest recognition refers to the formation of supramolecular inclusion complexes between two or more entities connected together in a highly controlled and cooperative manner. The inherently reversible and adaptive nature of host-guest molecular recognition chemistry, stemming from multiple noncovalent interactions, has opened up a new platform to construct novel types of stimuli-responsive materials. The introduction of host-guest chemistry not only enriches the realm of responsive materials but also confers them with promising new applications. Most intriguingly, the integration of responsive polymer building blocks with host-guest recognition motifs will endow the former with

Using an electrostatic accelerator to determine the stereochemical structures of molecular ions

International Nuclear Information System (INIS)

Gemmell, D.S.

1980-01-01

Recent high-resolution measurements on the energy and angle distributions of the fragments produced when fast (MeV) molecular-ion beams from an electrostatic accelerator dissociate (Coulomb explode) in thin foils and in gases, offer promising possibilities for deducing the stereochemical structures of the molecular ions constituting the incident beams. Bond lengths have been determined in this way for several diatomic projectiles (H 2 + , HeH + , CH + , NH + , OH + , N 2 + , O 2 + , etc.) with an accuracy of approx. 0.01 A. H 3 + has been demonstrated (for the first time) to be equilateral triangular and the interproton distance measured. Measurements on single fragments from CO 2 + , N 2 O + , C 3 H 3 + , and CH/sub n/ + have revealed the gross structures of the projectiles. An apparatus has recently been constructed at Argonne to permit precise measurements on fragments in coincidence. The apparatus has been tested on a known structure (OH 2 + ). The O-H bond length was found to be 1.0 +- 0.04 A and the H-O-H bond angle was measured as 110 +- 2 0 . These values are in excellent agreement with those found in optical experiments (0.999 A and 110.5 0 ). This Coulomb explosion technique can be expected to be refined in accuracy and to be extended to a wide range of molecular ions whose structures are inaccessible by other means

Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study.

Science.gov (United States)

Martinez-Lopez, Joaquin; Fernández-Redondo, Elena; García-Sánz, Ramón; Montalbán, María Angeles; Martínez-Sánchez, Pilar; Pavia, Bruno; Mateos, María Victoria; Rosiñol, Laura; Martín, Marisa; Ayala, Rosa; Martínez, Rafael; Blanchard, María Jesus; Alegre, Adrian; Besalduch, Joan; Bargay, Joan; Hernandez, Miguel T; Sarasquete, María Eugenia; Sanchez-Godoy, Pedro; Fernández, Manuela; Blade, Joan; San Miguel, Jesús F; Lahuerta, Juan Jose

2013-12-01

Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM. © 2013 John Wiley & Sons Ltd.

Innate immune responses activated in Arabidopsis roots by microbe-associated molecular patterns.

Science.gov (United States)

Millet, Yves A; Danna, Cristian H; Clay, Nicole K; Songnuan, Wisuwat; Simon, Matthew D; Werck-Reichhart, Danièle; Ausubel, Frederick M

2010-03-01

Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of beta-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid-jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways.

A modified time-of-flight method for precise determination of high speed ratios in molecular beams

Energy Technology Data Exchange (ETDEWEB)

Salvador Palau, A.; Eder, S. D., E-mail: sabrina.eder@uib.no; Kaltenbacher, T.; Samelin, B.; Holst, B. [Department of Physics and Technology, University of Bergen, Allégaten 55, 5007 Bergen (Norway); Bracco, G. [Department of Physics and Technology, University of Bergen, Allégaten 55, 5007 Bergen (Norway); CNR-IMEM, Department of Physics, University of Genova, V. Dodecaneso 33, 16146 Genova (Italy)

2016-02-15

Time-of-flight (TOF) is a standard experimental technique for determining, among others, the speed ratio S (velocity spread) of a molecular beam. The speed ratio is a measure for the monochromaticity of the beam and an accurate determination of S is crucial for various applications, for example, for characterising chromatic aberrations in focussing experiments related to helium microscopy or for precise measurements of surface phonons and surface structures in molecular beam scattering experiments. For both of these applications, it is desirable to have as high a speed ratio as possible. Molecular beam TOF measurements are typically performed by chopping the beam using a rotating chopper with one or more slit openings. The TOF spectra are evaluated using a standard deconvolution method. However, for higher speed ratios, this method is very sensitive to errors related to the determination of the slit width and the beam diameter. The exact sensitivity depends on the beam diameter, the number of slits, the chopper radius, and the chopper rotation frequency. We present a modified method suitable for the evaluation of TOF measurements of high speed ratio beams. The modified method is based on a systematic variation of the chopper convolution parameters so that a set of independent measurements that can be fitted with an appropriate function are obtained. We show that with this modified method, it is possible to reduce the error by typically one order of magnitude compared to the standard method.

Molecularly imprinted polymeric stir bar: Preparation and application for the determination of naftopidil in plasma and urine samples.

Science.gov (United States)

Peng, Jun; Xiao, Deli; He, Hua; Zhao, Hongyan; Wang, Cuixia; Shi, Tian; Shi, Kexin

2016-01-01

In this study, molecularly imprinting technology and stir bar absorption technology were combined to develop a microextraction approach based on a molecularly imprinted polymeric stir bar. The molecularly imprinted polymer stir bar has a high performance, is specific, economical, and simple to prepare. The obtained naftopidil-imprinted polymer-coated bars could simultaneously agitate and adsorb naftopidil in the sample solution. The ratio of template/monomer/cross-linker and conditions of template removal were optimized to prepare a stir bar with highly efficient adsorption. Fourier transform infrared spectroscopy, scanning electron microscopy, selectivity, and extraction capacity experiments showed that the molecularly imprinted polymer stir bar was prepared successfully. To utilize the molecularly imprinted polymer stir bar for the determination of naftopidil in complex body fluid matrices, the extraction time, stirring speed, eluent, and elution time were optimized. The limits of detection of naftopidil in plasma and urine sample were 7.5 and 4.0 ng/mL, respectively, and the recoveries were in the range of 90-112%. The within-run precision and between-run precision were acceptable (relative standard deviation bar based microextraction with high-performance liquid chromatography was a convenient, rapid, efficient, and specific method for the precise determination of trace naftopidil in clinical analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A rapid challenge protocol for determination of non-specific bronchial responsiveness

DEFF Research Database (Denmark)

Madsen, F; Nielsen, N H; Holstein-Rathlou, N H

1986-01-01

A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during...... hyperreactivity since individual dose titration is easily performed, and the method could be valuable in epidemiological and occupational surveys as well.......A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during...... challenge. The patients inhaled histamine chloride 8 mg/ml at every eighth breath until resistance to breathing (Rt) was increased by 60%. The number of inhalations (NI) or the provocative concentration (PC60-Rt) of histamine increasing Rt by 60% were determined in 68 patients. The new method correlated...

Molecular responses during cadmium-induced stress in Daphnia magna: Integration of differential gene expression with higher-level effects

Energy Technology Data Exchange (ETDEWEB)

Soetaert, Anneleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)]. E-mail: anneleen.soetaert@ua.ac.be; Vandenbrouck, Tine [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Ven, Karlijn van der [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Maras, Marleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Remortel, Piet van [Department of Mathematics and Informatics, Intelligent Systems Laboratory, University of Antwerp, Middelheimlaan 1, B-2020 Antwerp (Belgium); Blust, Ronny [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Coen, Wim M. de [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

2007-07-20

DNA microarrays offer great potential in revealing insight into mechanistic toxicity of contaminants. The aim of the present study was (i) to gain insight in concentration- and time-dependent cadmium-induced molecular responses by using a customized Daphnia magna microarray, and (ii) to compare the gene expression profiles with effects at higher levels of biological organization (e.g. total energy budget and growth). Daphnids were exposed to three cadmium concentrations (nominal value of 10, 50, 100 {mu}g/l) for two time intervals (48 and 96 h). In general, dynamic expression patterns were obtained with a clear increase of gene expression changes at higher concentrations and longer exposure duration. Microarray analysis revealed cadmium affected molecular pathways associated with processes such as digestion, oxygen transport, cuticula metabolism and embryo development. These effects were compared with higher-level effects (energy budgets and growth). For instance, next to reduced energy budgets due to a decline in lipid, carbohydrate and protein content, we found an up-regulated expression of genes related to digestive processes (e.g. {alpha}-esterase, cellulase, {alpha}-amylase). Furthermore, cadmium affected the expression of genes coding for proteins involved in molecular pathways associated with immune response, stress response, cell adhesion, visual perception and signal transduction in the present study.

Analysis of Microbe-Associated Molecular Pattern-Responsive Synthetic Promoters with the Parsley Protoplast System.

Science.gov (United States)

Kanofsky, Konstantin; Lehmeyer, Mona; Schulze, Jutta; Hehl, Reinhard

2016-01-01

Plants recognize pathogens by microbe-associated molecular patterns (MAMPs) and subsequently induce an immune response. The regulation of gene expression during the immune response depends largely on cis-sequences conserved in promoters of MAMP-responsive genes. These cis-sequences can be analyzed by constructing synthetic promoters linked to a reporter gene and by testing these constructs in transient expression systems. Here, the use of the parsley (Petroselinum crispum) protoplast system for analyzing MAMP-responsive synthetic promoters is described. The synthetic promoter consists of four copies of a potential MAMP-responsive cis-sequence cloned upstream of a minimal promoter and the uidA reporter gene. The reporter plasmid contains a second reporter gene, which is constitutively expressed and hence eliminates the requirement of a second plasmid used as a transformation control. The reporter plasmid is transformed into parsley protoplasts that are elicited by the MAMP Pep25. The MAMP responsiveness is validated by comparing the reporter gene activity from MAMP-treated and untreated cells and by normalizing reporter gene activity using the constitutively expressed reporter gene.

Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

Directory of Open Access Journals (Sweden)

Govindarajan Kunde R

2011-05-01

Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

Voltammetric determination of attomolar levels of a sequence derived from the genom of hepatitis B virus by using molecular beacon mediated circular strand displacement and rolling circle amplification.

Science.gov (United States)

Huang, Shan; Feng, Mengmeng; Li, Jiawen; Liu, Yi; Xiao, Qi

2018-03-03

The authors describe an electrochemical method for the determination of the single-stranded DNA (ssDNA) oligonucleotide with a sequence derived from the genom of hepatitis B virus (HBV). It is making use of circular strand displacement (CSD) and rolling circle amplification (RCA) strategies mediated by a molecular beacon (MB). This ssDNA hybridizes with the loop portion of the MB immobilized on the surface of a gold electrode, while primer DNA also hybridizes with the rest of partial DNA sequences of MB. This triggers the MB-mediated CSD. The RCA is then initiated to produce a long DNA strand with multiple tandem-repeat sequences, and this results in a significant increase of the differential pulse voltammetric response of the electrochemical probe Methylene Blue at a rather low working potential of -0.24 V (vs. Ag/AgCl). Under optimal experimental conditions, the assay displays an ultrahigh sensitivity (with a 2.6 aM detection limit) and excellent selectivity. Response is linear in the 10 to 700 aM DNA concentration range. Graphical abstract Schematic of a voltammetric method for the determination of attomolar levels of target DNA. It is based on molecular beacon mediated circular strand displacement and rolling circle amplification strategies. Under optimal experimental conditions, the assay displays an ultrahigh sensitivity with a 2.6 aM detection limit and excellent selectivity.

Effect of Diffusion Limitations on Multianalyte Determination from Biased Biosensor Response

Science.gov (United States)

Baronas, Romas; Kulys, Juozas; Lančinskas, Algirdas; Žilinskas, Antanas

2014-01-01

The optimization-based quantitative determination of multianalyte concentrations from biased biosensor responses is investigated under internal and external diffusion-limited conditions. A computational model of a biocatalytic amperometric biosensor utilizing a mono-enzyme-catalyzed (nonspecific) competitive conversion of two substrates was used to generate pseudo-experimental responses to mixtures of compounds. The influence of possible perturbations of the biosensor signal, due to a white noise- and temperature-induced trend, on the precision of the concentration determination has been investigated for different configurations of the biosensor operation. The optimization method was found to be suitable and accurate enough for the quantitative determination of the concentrations of the compounds from a given biosensor transient response. The computational experiments showed a complex dependence of the precision of the concentration estimation on the relative thickness of the outer diffusion layer, as well as on whether the biosensor operates under diffusion- or kinetics-limited conditions. When the biosensor response is affected by the induced exponential trend, the duration of the biosensor action can be optimized for increasing the accuracy of the quantitative analysis. PMID:24608006

Molecular Testing for Gastrointestinal Cancer

Directory of Open Access Journals (Sweden)

Hye Seung Lee

2017-03-01

Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Multiple determinants of transfer of evaluative function after conditioning with free-operant schedules of reinforcement.

Science.gov (United States)

Dack, Charlotte; Reed, Phil; McHugh, Louise

2010-11-01

The aim of the four present experiments was to explore how different schedules of reinforcement influence schedule-induced behavior, their impact on evaluative ratings given to conditioned stimuli associated with each schedule through evaluative conditioning, and the transfer of these evaluations through derived stimulus networks. Experiment 1 compared two contrasting response reinforcement rules (variable ratio [VR], variable interval [VI]). Experiment 2 varied the response to reinforcement rule between two schedules but equated the outcome to response rate (differential reinforcement of high rate [DRH] vs. VR). Experiment 3 compared molar and molecular aspects of contingencies of reinforcement (tandem VIVR vs. tandem VRVI). Finally, Experiment 4 employed schedules that induced low rates of responding to determine whether, under these circumstances, responses were more sensitive to the molecular aspects of a schedule (differential reinforcement of low rate [DRL] vs. VI). The findings suggest that the transfer of evaluative functions is determined mainly by differences in response rate between the schedules and the molar aspects of the schedules. However, when neither schedule was based on a strong response reinforcement rule, the transfer of evaluative judgments came under the control of the molecular aspects of the schedule.

Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

DEFF Research Database (Denmark)

Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

2008-01-01

with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis

DEFF Research Database (Denmark)

Pedersen, Morten Løbner; Walsted, Anette; Larsen, Rune

2008-01-01

The effect of consumption of Immulina, a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis, on adaptive immune responses was investigated by evaluation of changes in leukocyte responsiveness to two foreign recall antigens, Candida albicans (CA) and tetanus...

Computer aided molecular design with combined molecular modeling and group contribution

DEFF Research Database (Denmark)

Harper, Peter Mathias; Gani, Rafiqul; Kolar, Petr

1999-01-01

Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures and on th......Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures...

Molecular screening of antibiotic-resistant determinants among ...

African Journals Online (AJOL)

In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies ... ocomial opportunistic infections such as urinary tract .... Twelve (20%) of these MDR isolates were from children.

Determination of structure and properties of molecular crystals from first principles.

Science.gov (United States)

Szalewicz, Krzysztof

2014-11-18

CONSPECTUS: Until recently, it had been impossible to predict structures of molecular crystals just from the knowledge of the chemical formula for the constituent molecule(s). A solution of this problem has been achieved using intermolecular force fields computed from first principles. These fields were developed by calculating interaction energies of molecular dimers and trimers using an ab initio method called symmetry-adapted perturbation theory (SAPT) based on density-functional theory (DFT) description of monomers [SAPT(DFT)]. For clusters containing up to a dozen or so atoms, interaction energies computed using SAPT(DFT) are comparable in accuracy to the results of the best wave function-based methods, whereas the former approach can be applied to systems an order of magnitude larger than the latter. In fact, for monomers with a couple dozen atoms, SAPT(DFT) is about equally time-consuming as the supermolecular DFT approach. To develop a force field, SAPT(DFT) calculations are performed for a large number of dimer and possibly also trimer configurations (grid points in intermolecular coordinates), and the interaction energies are then fitted by analytic functions. The resulting force fields can be used to determine crystal structures and properties by applying them in molecular packing, lattice energy minimization, and molecular dynamics calculations. In this way, some of the first successful determinations of crystal structures were achieved from first principles, with crystal densities and lattice parameters agreeing with experimental values to within about 1%. Crystal properties obtained using similar procedures but empirical force fields fitted to crystal data have typical errors of several percent due to low sensitivity of empirical fits to interactions beyond those of the nearest neighbors. The first-principles approach has additional advantages over the empirical approach for notional crystals and cocrystals since empirical force fields can only be

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei; Welch, Megan J.; Ryu, Tae Woo; Zhang, Huoming; Berumen, Michael L.; Nilsson, Gö ran E.; Munday, Philip L.; Ravasi, Timothy

2016-01-01

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei

2016-07-29

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Flow-based method for epinephrine determination using a solid reactor based on molecularly imprinted poly(FePP-MAA-EGDMA)

International Nuclear Information System (INIS)

Sartori, Lucas Rossi; Santos, Wilney de Jesus Rodrigues; Kubota, Lauro Tatsuo; Segatelli, Mariana Gava; Tarley, Cesar Ricardo Teixeira

2011-01-01

A solid phase reactor based on molecularly imprinted poly(iron (III) protoporphyrin-methacrylic acid-ethylene glycol dimethacrylate) (MIP-MAA) has been synthesized by bulk method and applied as an selective material for the epinephrine determination in the presence of hydrogen peroxide. In order to prove the selective behaviour of MIP, two blank polymers named non-imprinted polymer (NIP1), non-imprinted polymer in the absence of hemin (NIP2) as well as a poly(iron (III) protoporphyrin-4-vynilpyridine-ethylene glycol dimethacrylate) (MIP-4VPy) were synthesized. The epinephrine-selective MIP-MAA reactor was used in a flow injection system, in which an epinephrine solution (120 μL) at pH 8.0 percolates in the presence of hydrogen peroxide (300 μmol L -1 ) through MIP-MAA. The oxidation of epinephrine by hydrogen peroxide is increased by using MIP-MAA, being the product formed monitored by amperometry at 0.0 V vs. Ag/AgCl. The MIP-MAA showed better selective behaviour than NIP1, NIP2 and MIP-4VPy, demonstrating the effectiveness of molecular imprinting effect. Highly improved response was observed for epinephrine in detriment of similar substances (phenol, ascorbic acid, methyl-L-DOPA, p-aminophenol, catechol, L-DOPA and guaiacol). The method provided a calibration curve ranging from 10 to 500 μmol L -1 and a limit of detection of 5.2 μmol L -1 . Kinetic data indicated a value of maximum rate V max (0.993 μA) and apparent Michaelis-Menten constant of K m app (725.6 μmol L -1 ). The feasibility of biomimetic solid reactor was attested by its successful application for epinephrine determination in pharmaceutical formulation.

Molecular and physiological responses to abiotic stress in forest trees and their relevance to tree improvement.

Science.gov (United States)

Harfouche, Antoine; Meilan, Richard; Altman, Arie

2014-11-01

Abiotic stresses, such as drought, salinity and cold, are the major environmental stresses that adversely affect tree growth and, thus, forest productivity, and play a major role in determining the geographic distribution of tree species. Tree responses and tolerance to abiotic stress are complex biological processes that are best analyzed at a systems level using genetic, genomic, metabolomic and phenomic approaches. This will expedite the dissection of stress-sensing and signaling networks to further support efficient genetic improvement programs. Enormous genetic diversity for stress tolerance exists within some forest-tree species, and due to advances in sequencing technologies the molecular genetic basis for this diversity has been rapidly unfolding in recent years. In addition, the use of emerging phenotyping technologies extends the suite of traits that can be measured and will provide us with a better understanding of stress tolerance. The elucidation of abiotic stress-tolerance mechanisms will allow for effective pyramiding of multiple tolerances in a single tree through genetic engineering. Here we review recent progress in the dissection of the molecular basis of abiotic stress tolerance in forest trees, with special emphasis on Populus, Pinus, Picea, Eucalyptus and Quercus spp. We also outline practices that will enable the deployment of trees engineered for abiotic stress tolerance to land owners. Finally, recommendations for future work are discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence determination of social responsibility to the productivity enterprise activity level

OpenAIRE

Kavun, Sergii; Zhosan, Ganna

2016-01-01

The purpose of this paper is to develop a scientific and methodical approach for determination of the comprehensive social responsibility indicator in this paper based on estimation of influence degree for the economical, ecological, social and labour, standard and legal components. There is allowance for determining of some level of enterprise social responsibility. In addition, there is a basis for development some ways of their increasing. The essence of the used approach is clotting of th...

Determination of average molecular weights on organic reactor coolants. I.- Freezing-point depression method for benzene solutions

International Nuclear Information System (INIS)

Carreira, M.

1965-01-01

As a working method for determination of changes in molecular mass that may occur by irradiation (pyrolytic-radiolytic decomposition) of polyphenyl reactor coolants, a cryoscopic technique has been developed which associated the basic simplicity of Beckman's method with some experimental refinements taken out of the equilibrium methods. A total of 18 runs were made on samples of napthalene, biphenyl, and the commercial mixtures OM-2 (Progil) and Santowax-R (Monsanto), with an average deviation from the theoretical molecular mass of 0.6%. (Author) 7 refs

Molecular determinants of tetramerization in the KcsA cytoplasmic domain.

Science.gov (United States)

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-10-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. © 2014 The Protein Society.

Selective excitation, relaxation, and energy channeling in molecular systems

International Nuclear Information System (INIS)

Rhodes, W.C.

1993-08-01

Research involves theoretical studies of response, relaxation, and correlated motion in time-dependent behavior of large molecular systems ranging from polyatomic molecules to protein molecules in their natural environment. Underlying theme is subsystem modulation dynamics. Main idea is that quantum mechanical correlations between components of a system develop with time, playing a major role in determining the balance between coherent and dissipative forces. Central theme is interplay of coherence and dissipation in determining the nature of dynamic structuring and energy flow in molecular transformation mechanisms. Subsystem equations of motion are being developed to show how nonlinear, dissipative dynamics of a particular subsystem arise from correlated interactions with the rest of the system (substituent groups, solvent, lattice modes, etc.); one consequence is resonance structures and networks. Quantum dynamics and thermodynamics are being applied to understand control and energy transfer mechanisms in biological functions of protein molecules; these mechanisms are both global and local. Besides the above theory, the research deals with phenomenological aspects of molecular systems

GC determination of N-nitrosamines by supersonic molecular beam MS equipped with triple quadrupole analyzer, GC/SMB/QQQ/MS

International Nuclear Information System (INIS)

Anna, Voloshenko; Rimma, Shelkov; Lev, Ovadia; Jenny, Gun

2011-01-01

The determination of 14 N-nitrosamines by a supersonic molecular beam electron ionization mass spectrometer equipped with triple quadruple analyzer, GC/SMB/EI/QQQ/MS is presented. The supersonic molecular beam electron ionization ion source allows the elucidation of the molecular ion of 13 out of the 14 examined nitrosamines (except for diphenylnitrosamine which was degraded before the analysis). It was possible to use the molecular ions of all the nitrosamines as the parent ions for multiple reactions monitoring mode, which in turn allows significant increase of specificity and lowering of the method limit of detection of the higher molecular weight nitrosamines. The instrumental LOD for different N-nitrosamines was 1-5 pg injection -1 . The proposed method was exemplified by analysis of N-nitrosamines and N-nitrosatables in rubber teats according to the British Standard BS EN 12868:1999.

Determination of morphological features and molecular interactions ...

African Journals Online (AJOL)

This research focused on identifying the morphological features and molecular interactions of the Nigerian Bentonitic clays using Scanning Electron Microscope (SEM) characterisation technique. The SEM microstructure images indicated that the bentonite samples are generally moderately dispersive to dispersive with ...

Simulated dynamic response of a multi-stage compressor with variable molecular weight flow medium

Science.gov (United States)

Babcock, Dale A.

1995-01-01

A mathematical model of a multi-stage compressor with variable molecular weight flow medium is derived. The modeled system consists of a five stage, six cylinder, double acting, piston type compressor. Each stage is followed by a water cooled heat exchanger which serves to transfer the heat of compression from the gas. A high molecular weight gas (CFC-12) mixed with air in varying proportions is introduced to the suction of the compressor. Condensation of the heavy gas may occur in the upper stage heat exchangers. The state equations for the system are integrated using the Advanced Continuous Simulation Language (ACSL) for determining the system's dynamic and steady state characteristics under varying operating conditions.

Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer

International Nuclear Information System (INIS)

Ding, Lina; Zhao, Yang; Warren, Christopher L; Sullivan, Ruth; Eliceiri, Kevin W; Shull, James D

2013-01-01

We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in

A pH-responsive molecular switch with tricolor luminescence.

Science.gov (United States)

Ahn, Hyungmin; Hong, Jaewan; Kim, Sung Yeon; Choi, Ilyoung; Park, Moon Jeong

2015-01-14

We developed a new ratiometric pH sensor based on poly(N-phenylmaleimide) (PPMI)-containing block copolymer that emits three different fluorescent colors depending on the pH. The strong solvatochromism and tautomerism of the PPMI derivatives enabled precise pH sensing for almost the entire range of the pH scale. Theoretical calculations have predicted largely dissimilar band gaps for the keto, enol, and enolate tautomers of PPMI owing to low-dimensional conjugation effects. The tunable emission wavelength and intensity of our sensors, as well as the reversible color switching with high-luminescent contrast, were achieved using rational molecular design of PPMI analogues as an innovative platform for accurate H(+) detection. The self-assembly of block copolymers on the nanometer length scale was particularly highlighted as a novel prospective means of regulating fluorescence properties while avoiding the self-quenching phenomenon, and this system can be used as a fast responsive pH sensor in versatile device forms.

Development of a marine fish model for studying in vivo molecular responses in ecotoxicology

International Nuclear Information System (INIS)

Kong, R.Y.C.; Giesy, J.P.; Wu, R.S.S.; Chen, E.X.H.; Chiang, M.W.L.; Lim, P.L.; Yuen, B.B.H.; Yip, B.W.P.; Mok, H.O.L.; Au, D.W.T.

2008-01-01

A protocol for fixation and processing of whole adult marine medaka (Oryzias melastigma) was developed in parallel with in situ hybridization (ISH) and immunohistochemistry (IHC) for molecular analysis of in vivo gene and protein responses in fish. Over 200 serial sagittal sections (5 μm) can be produced from a single adult medaka to facilitate simultaneous localization and quantification of gene-specific mRNAs and proteins in different tissues and subcellular compartments of a single fish. Stereological analysis (as measured by volume density, V v ) was used to quantify ISH and IHC signals on tissue sections. Using the telomerase reverse transcriptase (omTERT) gene, omTERT and proliferating cell nuclear antigen (PCNA) proteins as examples, we demonstrated that it is possible to localize, quantify and correlate their tissue expression profiles in a whole fish system. Using chronic hypoxia (1.8 ± 0.2 mg O 2 L -1 for 3 months) as an environmental stressor, we were able to identify significant alterations in levels of omTERT mRNA, omTERT protein, PCNA (cell proliferation marker) and TUNEL (apoptosis) in livers of hypoxic O. melastigma (p < 0.05). Overall, the results suggest that O. melastigma can serve as a model marine fish for assessing multiple in vivo molecular responses to stresses in the marine environment

Metal nanostructures for the enhancement of the Raman response of molecular adsorbates

Science.gov (United States)

Giorgetti, Emilia; Giammanco, Francesco; Margheri, Giancarlo; Trigari, Silvana; Muniz-Miranda, Maurizio

2011-08-01

Spectroscopic investigation of metallic nanostructures of different size and morphology is presented, with particular focus on the capability of enhancing the Raman response of molecular adsorbates, namely on their SERS properties. In this framework, we describe recent results obtained with Au/Ag nanocages and Au nanostars, which can be used conveniently to shift the extinction spectra and the SERS activity up to the near infrared. In the case of nanostars, we present a synthesis procedure which permits fine tuning of their morphology and extinction, thus allowing preparation of structures with controlled SERS activity from 500 up to 1500 nm.

Determination of sulfur in food by high resolution continuum source flame molecular absorption spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zambrzycka, Elżbieta; Godlewska-Żyłkiewicz, Beata, E-mail: bgodlew@uwb.edu.pl

2014-11-01

In the present work, a fast, simple and sensitive analytical method for determination of sulfur in food and beverages by high resolution continuum source flame molecular absorption spectrometry was developed. The determination was performed via molecular absorption of carbon monosulfide, CS. Different CS rotational lines (257.959 nm, 258.033 nm, 258.055 nm), number of pixels and types of standard solution of sulfur, namely: sulfuric acid, sodium sulfate, ammonium sulfate, sodium sulfite, sodium sulfide, DL-cysteine, and L-cystine, were studied in terms of sensitivity, repeatability of results as well as limit of detection and limit of quantification. The best results were obtained for measurements of absorption of the CS molecule at 258.055 nm at the wavelength range covering 3 pixels and DL-cysteine in 0.2 mol L{sup −1} HNO{sub 3} solution as a calibration standard. Under optimized conditions the limit of detection and the limit of quantification achieved for sulfur were 10.9 mg L{sup −1} and 36.4 mg L{sup −1}, respectively. The repeatability of the results expressed as relative standard deviation was typically < 5%. The accuracy of the method was tested by analysis of digested biological certified reference materials (soya bean flour, corn flour and herbs) and recovery experiment for beverage samples with added known amount of sulfur standard. The recovery of analyte from such samples was in the range of 93–105% with the repeatability in the range of 4.1–5.0%. The developed method was applied for the determination of sulfur in milk (194 ± 10 mg kg{sup −1}), egg white (2188 ± 29 mg kg{sup −1}), mineral water (31.0 ± 0.9 mg L{sup −1}), white wine (260 ± 4 mg L{sup −1}) and red wine (82 ± 2 mg L{sup −1}), as well as in sample rich in ions, such as bitter mineral water (6900 ± 100 mg L{sup −1}). - Highlights: • HR-CS FMAS technique was used for sulfur measurement via molecular absorption of carbon monosulfide, CS. • Organic DL

Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript

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Marianna Greco

2013-01-01

Full Text Available Chronic myeloid leukemia (CML with the rare fusion gene e19a2, encoding a p230 protein, has been described in patients with typical or rather aggressive clinical course. Although tyrosine kinase inhibitors (TKIs induce a substantial cytogenetic and molecular response in all phases of CML, a minority of p230 positive patients have been treated with TKIs. We report two cases of CML patients carrying the p230 transcript, who achieved fast and deep complete molecular response (CMR after frontline treatment with nilotinib. Our results suggest the use of nilotinib as frontline agent for the treatment of this CML variant.

Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

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Jixia Li

2013-01-01

Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

Molecularly Imprinted Polymers as Extracting Media for the Chromatographic Determination of Antibiotics in Milk

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Dimitrios Bitas

2018-02-01

Full Text Available Milk-producing animals are typically kept stationary in overcrowded large-scale farms and in most cases under unsanitary conditions, which promotes the development of infections. In order to maintain sufficient health status among the herd or promote growth and increase production, farmers administer preventative antibiotic doses to the animals through their feed. However, many antibiotics used in cattle farms are intended for the treatment of bacterial infections in humans. This results in the development of antibiotic-resistant bacteria which pose a great risk for public health. Additionally, antibiotic residues are found in milk and dairy products, with potential toxic effects for the consumers. Hence the need of antibiotic residues monitoring in milk arises. Analytical methods were developed for the determination of antibiotics in milk, with key priority given to the analyte extraction and preconcentration step. Extraction can benefit from the production of molecularly imprinted polymers (MIPs that can be applied as sorbents for the extraction of specific antibiotics. This review focuses on the principals of molecular imprinting technology and synthesis methods of MIPs, as well as the application of MIPs and MIPs composites for the chromatographic determination of various antibiotic categories in milk found in the recent literature.

Determination for energy response and directionality of neutron survey meters

International Nuclear Information System (INIS)

Chen Changmao; Liu Jinhua; Xie Jianlun; Su Jingling

1992-01-01

The energy response and directionality of neutron survey meter type MK7 and 2202D are determined. The reactor thermal column beam, reactor filtered beams (6 eV, 24.4 keV and 144 keV), 226 Ra-Be, 241 Am-Be, 252 Cf and its moderated sources are used for the measurement. The results shows: the survey meters are influenced obviously by the direction; the response of middle-energy region is large, the energy response of 2202D is better than MK7

Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

International Nuclear Information System (INIS)

Takaji Ikushima

1997-01-01

The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

2011-01-01

This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus.

Science.gov (United States)

Carr, Jillian M; Ashander, Liam M; Calvert, Julie K; Ma, Yuefang; Aloia, Amanda; Bracho, Gustavo G; Chee, Soon-Phaik; Appukuttan, Binoy; Smith, Justine R

2017-01-01

Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin- β 1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

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Jillian M. Carr

2017-01-01

Full Text Available Recent clinical reports indicate that infection with dengue virus (DENV commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin-β1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus

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2011-01-01

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance

Determination of response time of resistance thermometers by in situ measurements

International Nuclear Information System (INIS)

Goncalves, I.M.P.; Soares, A.J.

1986-01-01

The loop-current-step-response test provides a mean for determining the time constant of resistance thermometers. The test consists in heating the sensor a few degrees above ambient temperature by causing a step perurbation in the electric current that flows through the sensor leads. The developed mathematical transformation permits to use data collected during the internal heating transient to predict the sensor response to perturbations in fluid temperature. Experimental data obtained show that time constant determined by this method is within 15 percent of the true value. (Author) [pt

Molecular screening of antibiotic-resistant determinants among ...

African Journals Online (AJOL)

Background: Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. Objectives: This study screened for presence of ...

What Determines the Response: Test or Reference?

Science.gov (United States)

Chukova, S. V.; Ahumada, A. J., Jr.; Null, Cynthia (Technical Monitor)

1998-01-01

The stability of sensory memory has been studied by presenting a reference stimulus, a delay, and a test stimulus. As has been pointed out by Lages and Treisman (1998 Vision Research 38 557-572), the usual measure of performance depends only on the effect of test variations on the responses. The Weber fraction characterizing performance is more properly called the test stimulus Weber fraction. We measure the relative contribution of the test and reference to the response by the ratio of the test Weber fraction to the reference Weber fraction. The stimuli were two dark lines on a bright background. Seven reference separations, varying from 9.5 to 16.7 arc min, were intermixed in each run. Interstimulus intervals (ISI) of 50, 200 and 2000 msec and intertrial intervals (ITI) of 500 and 2500 msec were investigated. When the ISI was short (50 or 200 msec), for both ITIs, responses were determined equally by the test and reference. For the long ISI (2000 msec), the reference stimulus contributed less. However, only for the 500 msec ITI (and not for all observers) was the contribution of the reference stimulus negligible, as Treisman's criterion setting theory might suggest.

Flow-based method for epinephrine determination using a solid reactor based on molecularly imprinted poly(FePP-MAA-EGDMA)

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Sartori, Lucas Rossi [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Universidade Federal de Alfenas (Unifal-MG), Rua Gabriel Monteiro da Silva, 714, 37130-000, Alfenas/MG (Brazil); Santos, Wilney de Jesus Rodrigues [Departamento de Quimica Analitica, Instituto de Quimica, Universidade Estadual de Campinas (Unicamp), Cidade Universitaria Zeferino Vaz s/n,13083-970, Campinas/SP (Brazil); Kubota, Lauro Tatsuo [Departamento de Quimica Analitica, Instituto de Quimica, Universidade Estadual de Campinas (Unicamp), Cidade Universitaria Zeferino Vaz s/n,13083-970, Campinas/SP (Brazil); Instituto Nacional de Ciencia e Tecnologia (INCT) de Bioanalitica, Universidade Estadual de Campinas (Unicamp), Instituto de Quimica, Departamento de Quimica Analitica, Cidade Universitaria Zeferino Vaz s/n, 13083-970, Campinas/SP (Brazil); Segatelli, Mariana Gava [Departamento de Quimica, Universidade Estadual de Londrina (UEL), Rod. Celso Garcia PR 445 Km 380, 86051-990, Londrina/PR (Brazil); Tarley, Cesar Ricardo Teixeira, E-mail: tarley@uel.br [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Universidade Federal de Alfenas (Unifal-MG), Rua Gabriel Monteiro da Silva, 714, 37130-000, Alfenas/MG (Brazil); Instituto Nacional de Ciencia e Tecnologia (INCT) de Bioanalitica, Universidade Estadual de Campinas (Unicamp), Instituto de Quimica, Departamento de Quimica Analitica, Cidade Universitaria Zeferino Vaz s/n, 13083-970, Campinas/SP (Brazil)

2011-03-12

A solid phase reactor based on molecularly imprinted poly(iron (III) protoporphyrin-methacrylic acid-ethylene glycol dimethacrylate) (MIP-MAA) has been synthesized by bulk method and applied as an selective material for the epinephrine determination in the presence of hydrogen peroxide. In order to prove the selective behaviour of MIP, two blank polymers named non-imprinted polymer (NIP1), non-imprinted polymer in the absence of hemin (NIP2) as well as a poly(iron (III) protoporphyrin-4-vynilpyridine-ethylene glycol dimethacrylate) (MIP-4VPy) were synthesized. The epinephrine-selective MIP-MAA reactor was used in a flow injection system, in which an epinephrine solution (120 {mu}L) at pH 8.0 percolates in the presence of hydrogen peroxide (300 {mu}mol L{sup -1}) through MIP-MAA. The oxidation of epinephrine by hydrogen peroxide is increased by using MIP-MAA, being the product formed monitored by amperometry at 0.0 V vs. Ag/AgCl. The MIP-MAA showed better selective behaviour than NIP1, NIP2 and MIP-4VPy, demonstrating the effectiveness of molecular imprinting effect. Highly improved response was observed for epinephrine in detriment of similar substances (phenol, ascorbic acid, methyl-L-DOPA, p-aminophenol, catechol, L-DOPA and guaiacol). The method provided a calibration curve ranging from 10 to 500 {mu}mol L{sup -1} and a limit of detection of 5.2 {mu}mol L{sup -1}. Kinetic data indicated a value of maximum rate V{sub max} (0.993 {mu}A) and apparent Michaelis-Menten constant of K{sub m}{sup app}(725.6 {mu}mol L{sup -1}). The feasibility of biomimetic solid reactor was attested by its successful application for epinephrine determination in pharmaceutical formulation.

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

Science.gov (United States)

Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

2018-01-01

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

Science.gov (United States)

Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

2017-07-08

Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):299-304, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Molecular determination of RHD zygosity: predicting risk of hemolytic disease of the fetus and newborn related to anti-D.

Science.gov (United States)

Pirelli, Kevin J; Pietz, Bradley C; Johnson, Susan T; Pinder, Holly L; Bellissimo, Daniel B

2010-12-01

Development of an accurate molecular method for paternal RHD zygosity to predict risk to a fetus for hemolytic disease of the fetus and newborn (HDFN) related to anti-D. Quantitative fluorescence polymerase chain reaction (QF-PCR) was used to detect RHD exons 5 and 7, using RHCE exon 7 as an internal control. The genotype and zygosity were determined from the peak area ratios of RHD exon 5 or 7 to RHCE exon 7. We tested 25 Caucasian and 25 African American (AA) samples whose zygosity was predicted from the Rh phenotype and an alternate molecular method. In addition, we tested 71 paternal samples from prenatal cases where fetal testing was performed. RHD/RHCE ratios clearly distinguished the RHD/D and RHD/d genotypes. RHD variants were recognized when RHD exon 5 copy number was discordant with exon 7. The molecular assay identified eight cases where the phenotype incorrectly assigned zygosity and we observed three false-negatives in the hybrid Rhesus box assay. The prenatal results were consistent with the zygosity determined for the paternal samples in our study. This QF-PCR method accurately determines RHD zygosity in Caucasians and AAs and will help predict the risk that a fetus will inherit RHD. Copyright © 2010 John Wiley & Sons, Ltd.

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

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Maki Fukami

2012-01-01

Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

Determinants of Corporate Social Responsibility in Japanese Companies

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Magdalena Krukowska

2014-12-01

Full Text Available Purpose: The aim of this study was to analyze the factors that determine the Japanese approach to corporate social responsibility (CSR to facilitate future empirical research in the Polish conditions. Methodology: To conduct the research, the available literature concerning CSR, managerial behaviour and stakeholder relations in Japan was studied. The research was conducted onsite in Japan after consultation with local experts, both Japanese and foreigners, specialized in Japanese management and the economy. Findings: The Japanese approach to CSR is strongly determined by their religious, philosophical, cultural, historical, economic and legal factors. It is proof of the concept of CSR contextuality, which provokes questions about the nature of the business relations of Japanese companies with their foreign counterparts and their style of management while investing abroad. Research limitations: The methodology was only supposed to gain a general view of the factors infl uencing CSR in Japan. Studying more detailed issues with the use of empirical data was complicated because of the short time available for the research (6 weeks and the relatively low level of transparency of the Japanese companies. Value: The study helped in understanding managerial decisions and Japanese business behaviour in the context of corporate responsibility and the ethics of its everyday operations. It was the fi rst research thoroughly analyzing many of the determinants of CSR in Japan, which may be valuable for any counterparts cooperating with the Japanese companies and foreign researchers analyzing Japanese management systems.

Metallothionein and glutathione in Lymnaea stagnalis determine the specificity of responses to the effects of ionising radiation

International Nuclear Information System (INIS)

Gnatyshyna, L.; Falfushynska, H.; Stoliar, O.; Bodilovska, O.; Oleynik, O.; Golubev, A.

2012-01-01

The aim of our study was to distinguish the stress-related molecular response of the pulmonate mollusc Lymnaea stagnalis from the Chernobyl area in comparison with the consequences of other harmful effects, including the short-term effects of radiation and heating. Specimens inhabiting ponds near the Chernobyl nuclear power plant, the cooling channel of the electric power station and the soil reclamation channel (groups R, T and C, correspondingly), and specimens adapted to laboratory conditions (a control group (CL), a disposable group exposed to 2 mGy X-ray radiation over the body (RL), and a group exposed to 25 deg. C for 4 days (TL)) were compared. Despite high variability of responses, Principle Component Analysis distinctly separated the laboratory and feral groups into two sets. In the feral groups, low levels of the stress-related and metal-binding protein metallothionein (MT), protein carbonyls and lactate dehydrogenase in the digestive gland were indicated. The main separating criteria selected by classification and regression tree analysis were the protein carbonyls, cholinesterase and MT. Molluscs from group R were clearly distinguished by the lowest levels of MT, Mn-superoxide dismutase and lactate dehydrogenase, and the highest level of glutathione, demonstrating that the oppression of the gene-determined stress-related response and its partially metabolic compensation can be possible markers for chronic environmental effects of irradiation. (authors)

Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

International Nuclear Information System (INIS)

Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

2009-01-01

The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

Rapid Determination of Six Low Molecular Carbonyl Compounds in Tobacco Smoke by the APCI-MS/MS Coupled to Data Mining

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Wuduo Zhao

2017-01-01

Full Text Available A simple method was established for the rapid determination of low molecular carbonyl compounds by the combination of atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS and data mining. The ionization was carried out in positive mode, and six low molecular carbonyl compounds of acrolein, acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde were analyzed by both full scan mode and daughter scan mode. To overcome the quantitative difficulties from isomer of acetone/propionaldehyde and butanone/butyraldehyde, the quantitation procedure was performed with the characteristic ion of [CH3O]+ under CID energy of 5 and 15 eV. Subsequently, the established method was successfully applied to analysis of six low molecular carbonyl compounds in tobacco smoke with analytical period less than four minutes. The contents of acrolein, acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde for a cigarette were about 63±5.8, 325±82, 55±9.7, 11±1.4, 67±5.9, and 12±1.8 μg/cig, respectively. The experimental results indicated that the established method had the potential application in rapid determination of low molecular carbonyl compounds.

Determination of response level for imported meat and poultry

Energy Technology Data Exchange (ETDEWEB)

Houston, Donald L; Engel, Ronald E

1986-07-01

The response level of 75,000 picocuries per kilogram (pci/kg) for imported meat and poultry was determined in accordance with the Food and Drug Administration's (FDA's) Accidental Radioactive Contamination of Human Food and Animal Feeds, Recommendations for State and Local Agencies which was published in the Federal Register of October 22, 1982, and in consultation with FDA. The response level takes into account the total intake of activity from a radionuclide and the average daily consumption of food in the United States. This response level value is based, in part, upon the expectation that the major contributors of radiation to imported meat and poultry will be cesium-134 (half-life 2.1 years) and cesium-137 (half-life 30 years)

Determination of response level for imported meat and poultry

International Nuclear Information System (INIS)

Houston, Donald L.; Engel, Ronald E.

1986-01-01

The response level of 75,000 picocuries per kilogram (pci/kg) for imported meat and poultry was determined in accordance with the Food and Drug Administration's (FDA's) Accidental Radioactive Contamination of Human Food and Animal Feeds, Recommendations for State and Local Agencies which was published in the Federal Register of October 22, 1982, and in consultation with FDA. The response level takes into account the total intake of activity from a radionuclide and the average daily consumption of food in the United States. This response level value is based, in part, upon the expectation that the major contributors of radiation to imported meat and poultry will be cesium-134 (half-life 2.1 years) and cesium-137 (half-life 30 years)

Sex specific molecular responses of quick-to-court protein in Indian malarial vector Anopheles culicifacies: conflict of mating versus blood feeding behaviour

Directory of Open Access Journals (Sweden)

Tanwee Das De

2017-07-01

Full Text Available Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein. Previously this was shown to regulate courtship behaviour in adult male Drosophila. A comprehensive in silico analysis of the quick-to-court (qtc gene of An. culicifacies (Ac-qtc predicts a 1536 bp single copy gene encoding 511 amino acid protein, having a high degree of conservation with other insect homologs. The age-dependent increased expression of putative Ac-qtc correlated with the maturation of the olfactory system, necessary to meet the sex-specific conflicting demand of mating (mate finding versus host-seeking behavioural responses. Sixteen to eighteen hours of starvation did not alter Ac-qtc expression in both sexes, however, blood feeding significantly modulated its response in the adult female mosquitoes, confirming that it may not be involved in sugar feeding associated behavioural regulation. Finally, a dual behavioural and molecular assay indicated that natural dysregulation of Ac-qtc in the late evening might promote the mating events for successful insemination. We hypothesize that Ac-qtc may play a unique role to regulate the sex-specific conflicting demand of mosquito courtship behaviour versus blood feeding behaviour in the adult female mosquitoes. Further elucidation of this molecular mechanism may provide further information to evaluate Ac-qtc as a key molecular target for mosquito-borne disease management.

A metric for characterizing the bistability of molecular quantum-dot cellular automata

International Nuclear Information System (INIS)

Lu Yuhui; Lent, Craig S

2008-01-01

Much of molecular electronics involves trying to use molecules as (a) wires, (b) diodes or (c) field-effect transistors. In each case the criterion for determining good performance is well known: for wires it is conductance, for diodes it is conductance asymmetry, while for transistors it is high transconductance. Candidate molecules can be screened in terms of these criteria by calculating molecular conductivity in forward and reverse directions, and in the presence of a gating field. Hence so much theoretical work has focused on understanding molecular conductance. In contrast a molecule used as a quantum-dot cellular automata (QCA) cell conducts no current at all. The keys to QCA functionality are (a) charge localization, (b) bistable charge switching within the cell and (c) electric field coupling between one molecular cell and its neighbor. The combination of these effects can be examined using the cell-cell response function which relates the polarization of one cell to the induced polarization of a neighboring cell. The response function can be obtained by calculating the molecular electronic structure with ab initio quantum chemistry techniques. We present an analysis of molecular QCA performance that can be applied to any candidate molecule. From the full quantum chemistry, all-electron ab initio calculations we extract parameters for a reduced-state model which reproduces the cell-cell response function very well. Techniques from electron transfer theory are used to derive analytical models of the response function and can be employed on molecules too large for full ab initio treatment. A metric is derived which characterizes molecular QCA performance the way transconductance characterizes transistor performance. This metric can be assessed from absorption measurements of the electron transfer band or quantum chemistry calculations of appropriate sophistication

Molecular events basic to cellular radiation response

International Nuclear Information System (INIS)

Kolodny, G.M.

The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products

Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses.

Science.gov (United States)

Argue, Kathryn J; Neckameyer, Wendi S

2014-07-01

The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. Copyright © 2014 the American Physiological Society.

[Neurobiological determinism: questionable inferences on human freedom of choice and forensic criminal responsibility].

Science.gov (United States)

Urbaniok, F; Hardegger, J; Rossegger, A; Endrass, J

2006-08-01

Several authors argue that criminal behavior is generally caused by neurobiological deficits. Based on this neurobiological perspective of assumed causality, the concept of free will is questioned, and the theory of neurobiological determinism of all human behavior is put forward, thus maintaining that human beings are not responsible for their actions, and consequently the principle of guilt should be given up in criminal law. In this context the controversial debate on determinism and indeterminism, which has been held for centuries, has flared up anew, especially within the science of criminal law. When critically examining the current state of research, it becomes apparent that the results do not support the existence of a universally valid neurobiological causality of criminal behavior, nor a theory of an absolute neurobiological determinism. Neither is complete determination of all phenomena in the universe--as maintained--the logical conclusion of the principle of causality, nor is it empirically confirmed. Analyzed methodically, it cannot be falsified, and thus, as a theory which cannot be empirically tested, it represents a dogma against which plausible objections can be made. The criticism of the concept of free will, and even more so of human accountability and criminal responsibility, is not put forward in a valid way. The principle of relative determinism--the evaluation of the degree of determinism of personality factors potentially reducing criminal responsibility, which includes concrete observations and analysis of behavior--thus remains a central and cogent approach to the assessment of criminal responsibility. To sum up, the theories proposed by some authors on the complete neurobiological determinism of human behavior, and the subsequent impossibility of individual responsibility and guilt, reveal both methodical misconception and a lack of empirical foundation.

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

Science.gov (United States)

Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Cryogenic separation of an oxygen-argon mixture in natural air samples for the determination of isotope and molecular ratios.

Science.gov (United States)

Keedakkadan, Habeeb Rahman; Abe, Osamu

2015-04-30

The separation and purification of oxygen-argon mixtures are critical in the high-precision analysis of Δ(17) O and δ(O2 /Ar) for geochemical applications. At present, chromatographic methods are used for the separation and purification of oxygen-argon mixtures or pure oxygen, but these methods require the use of high-purity helium as a carrier gas. Considerable interest has been expressed in the development of a helium-free cryogenic separation of oxygen-argon mixtures in natural air samples. The precise and simplified cryogenic separation of oxygen-argon mixtures from natural air samples presented here was made possible using a single 5A (30/60 mesh) molecular sieve column. The method involves the trapping of eluted gases using molecular sieves at liquid nitrogen temperature, which is associated with isotopic fractionation. We tested the proposed method for the determination of isotopic fractionations during the gas exchange between water and atmospheric air at equilibrium. The dependency of fractionation was studied at different water temperatures and for different methods of equilibration (bubbling and stirring). Isotopic and molecular fractionations during gas desorption from molecular sieves were studied for different amounts and types of molecular sieves. Repeated measurements of atmospheric air yielded a reproducibility (±SD) of 0.021 ‰, 0.044 ‰, 15 per meg and 1.9 ‰ for δ(17) O, δ(18) O, Δ(17) O and δ(O2 /Ar) values, respectively. We applied the method to determine equilibrium isotope fractionation during gas exchange between air and water. Consistent δ(18) O and Δ(17) O results were obtained with the latest two studies, whereas there was a significant difference in δ(18) O values between seawater and deionized water. We have revised a helium-free, cryogenic separation of oxygen-argon mixtures in natural air samples for isotopic and molecular ratio analysis. The use of a single 13X (1/8" pellet) molecular sieve yielded the smallest isotopic

Corporate environmental responsibility – a key determinant of corporate reputation

OpenAIRE

Cristina Ganescu; Laura Dindire

2014-01-01

This paper aims to determine the trend of the relationship between corporate environmental responsibility and corporate reputation by focusing on a study of the European automotive sector. The starting point of our research is content analysis of the sustainability or social responsibility reports published in 2010, 2011, and 2012 by 13 businesses operating in the European automotive industry. Content analysis was carried out in order to identify the indicators used to assess corporate enviro...

Determination of organophosphorus pesticides using molecularly imprinted polymer solid phase extraction

International Nuclear Information System (INIS)

Mohd Marsin Sanagi; Syairah Salleh; Wan Aini Wan Ibrahim

2011-01-01

Molecularly imprinted polymer solid phase extraction (MIP-SPE) method has been developed for the determination of organophosphorus pesticides (OPPs) in water samples. The MIP was prepared by thermo-polymerization method using methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as crosslinker, acetonitrile as porogenic solvent and quinalphos as the template molecule. The three OPPs (diazinon, quinalphos and chloropyrifos) were selected as target analytes as they are widely used in agriculture sector. Various parameters affecting the extraction efficiency of the imprinted polymers have been evaluated to optimize the selective preconcentration of OPPs from aqueous samples. The characteristics of the MIP-SPE method were validated by high performance liquid chromatography (HPLC). The accuracy and selectivity of the MIP-SPE process developed were verified using non-imprinted polymer solid phase extraction (NIP-SPE) and a commercial C 18 -SPE was used for comparison. The recoveries of the target analytes obtained using the MIPs as the solid phase sorbent ranged from 83% to 98% (RSDs 1.05 - 1.98 %; n=3) for water sample. The developed MIP-SPE method demonstrates that it could be applied for the determination of OPPs in water samples. (author)

Feasibility of high-resolution continuum source molecular absorption spectrometry in flame and furnace for sulphur determination in petroleum products

Science.gov (United States)

Kowalewska, Zofia

2011-07-01

For the first time, high-resolution molecular absorption spectrometry with a high-intensity xenon lamp as radiation source has been applied for the determination of sulphur in crude oil and petroleum products. The samples were analysed as xylene solutions using vaporisation in acetylene-air flame or in an electrothermally heated graphite furnace. The sensitive rotational lines of the CS molecule, belonging to the ∆ν = 0 vibrational sequence within the electronic transition X 1∑ + → A 1П, were applied. For graphite furnace molecular absorption spectrometry, the Pd + Mg organic modifier was selected. Strong interactions with Pd atoms enable easier decomposition of sulphur-containing compounds, likely through the temporal formation of Pd xS y molecules. At the 258.056 nm line, with the wavelength range covering central pixel ± 5 pixels and with application of interactive background correction, the detection limit was 14 ng in graphite furnace molecular absorption spectrometry and 18 mg kg -1 in flame molecular absorption spectrometry. Meanwhile, application of 2-points background correction found a characteristic mass of 12 ng in graphite furnace molecular absorption spectrometry and a characteristic concentration of 104 mg kg -1 in flame molecular absorption spectrometry. The range of application of the proposed methods turned out to be significantly limited by the properties of the sulphur compounds of interest. In the case of volatile sulphur compounds, which can be present in light petroleum products, severe difficulties were encountered. On the contrary, heavy oils and residues from distillation as well as crude oil could be analysed using both flame and graphite furnace vaporisation. The good accuracy of the proposed methods for these samples was confirmed by their mutual consistency and the results from analysis of reference samples (certified reference materials and home reference materials with sulphur content determined by X-ray fluorescence

Feasibility of high-resolution continuum source molecular absorption spectrometry in flame and furnace for sulphur determination in petroleum products

Energy Technology Data Exchange (ETDEWEB)

Kowalewska, Zofia, E-mail: zofia.kowalewska@obr.pl

2011-07-15

For the first time, high-resolution molecular absorption spectrometry with a high-intensity xenon lamp as radiation source has been applied for the determination of sulphur in crude oil and petroleum products. The samples were analysed as xylene solutions using vaporisation in acetylene-air flame or in an electrothermally heated graphite furnace. The sensitive rotational lines of the CS molecule, belonging to the {Delta}{nu} = 0 vibrational sequence within the electronic transition X{sup 1}{Sigma}{sup +} {yields} A{sup 1}{Pi}, were applied. For graphite furnace molecular absorption spectrometry, the Pd + Mg organic modifier was selected. Strong interactions with Pd atoms enable easier decomposition of sulphur-containing compounds, likely through the temporal formation of Pd{sub x}S{sub y} molecules. At the 258.056 nm line, with the wavelength range covering central pixel {+-} 5 pixels and with application of interactive background correction, the detection limit was 14 ng in graphite furnace molecular absorption spectrometry and 18 mg kg{sup -1} in flame molecular absorption spectrometry. Meanwhile, application of 2-points background correction found a characteristic mass of 12 ng in graphite furnace molecular absorption spectrometry and a characteristic concentration of 104 mg kg{sup -1} in flame molecular absorption spectrometry. The range of application of the proposed methods turned out to be significantly limited by the properties of the sulphur compounds of interest. In the case of volatile sulphur compounds, which can be present in light petroleum products, severe difficulties were encountered. On the contrary, heavy oils and residues from distillation as well as crude oil could be analysed using both flame and graphite furnace vaporisation. The good accuracy of the proposed methods for these samples was confirmed by their mutual consistency and the results from analysis of reference samples (certified reference materials and home reference materials with

Physiological and molecular responses of the earthworm (Eisenia fetida) to soil chlortetracycline contamination

International Nuclear Information System (INIS)

Lin Dasong; Zhou Qixing; Xu Yingming; Chen Chun; Li Ye

2012-01-01

This study aims to evaluate toxic effects of exposure to chlortetracycline (CTC) in soil on reproductive endpoints (juvenile counts and cocoon counts), biochemical responses, and genotoxic potentials of the earthworm Eisenia fetida. Results showed that juvenile counts and cocoon counts of the tested earthworms were reduced after exposure to CTC. The effective concentrations (EC 50 values) for juvenile and cocoon counts were 96.1 and 120.3 mg/kg, respectively. Treatment of earthworms with CTC significantly changed the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST). An increase in malondialdehyde (MDA) indicated that CTC could cause cellular lipid peroxidation in the tested earthworms. The percentage of DNA in the tail of single-cell gel electrophoresis of coelomocytes as an indication of DNA damage increased after treatment with different doses of CTC, and a dose-dependent DNA damage of coelomocytes was found. In conclusion, CTC induces physiological responses and genotoxicity on earthworms. - Highlights: ► Reproductive endpoints were assessed for Eisenia fetida exposed to chlortectracyline (CTC). ► CTC may induce physiological and molecular responses in E. fetida. ► A clear relationship was observed between CTC doses and DNA damage of coelomocytes. - Chlortetracycline in soil could induce physiological responses and genotoxicity on earthworms at realistic environmental concentrations.

Study of the equation of state and determination of molecular parameters of some fluorinated gases

International Nuclear Information System (INIS)

Morizot, Pierre

1972-01-01

Volumetric and dielectric techniques are used to determine non-ideality and molar polarization of UF 6 , MoF 6 , WF 6 and ClF 3 . Comparisons are made between these dielectric non-ideality parameters and those obtained by MAGNUSON and volumetry method. It is demonstrated that dielectric non-ideality parameters are unsettled by an adsorption phenomena on the electrodes. The volumetric second virial coefficients are interpreted with known transport coefficients to determine molecular parameters of the three hexafluorides. Using viscosity data, the existence of a dimerization in the vapor of ClF 3 was demonstrated. Its effect on the observed second virial coefficient was evaluated. (author) [fr

A molecular imprinted SPR biosensor for sensitive determination of citrinin in red yeast rice.

Science.gov (United States)

Atar, Necip; Eren, Tanju; Yola, Mehmet Lütfi

2015-10-01

A novel and sensitive molecular imprinted surface plasmon resonance (SPR) biosensor was developed for selective determination of citrinin (CIT) in red yeast rice. Firstly, the gold surface of SPR chip was modified with allyl mercaptane. Then, CIT-imprinted poly(2-hydroxyethyl methacrylate-methacryloylamidoglutamic acid) (p(HEMA-MAGA)) film was generated on the gold surface modified with allyl mercaptane. The unmodified and imprinted surfaces were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM) and contact angle measurements. The linearity range and the detection limit were obtained as 0.005-1.0 ng/mL and 0.0017 ng/mL, respectively. The SPR biosensor was applied to determination of CIT in red yeast rice sample. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence Determination of Social Responsibility to the Productivity Enterprise Activity Level

Directory of Open Access Journals (Sweden)

Sergii Kavun

2016-07-01

Full Text Available The purpose of this paper is to develop a scientific and methodical approach for determination of the comprehensive social responsibility indicator in this paper based on estimation of influence degree for the economical, ecological, social and labour, standard and legal components. There is allowance for determining of some level of enterprise social responsibility. In addition, there is a basis for development some ways of their increasing. The essence of the used approach is clotting of the individual indicators set to four intermediate indicators of the economic, ecological, social and labor, standard and legal components, which can be boiled down to the generalizing activity productivity indicator based on the matrix and range approach. An economical and mathematical model of the social responsibility influence level to the enterprise activity productivity level, which is based on enterprise propose harmonization with the participants’ interests, was being built. The paper proposes the mathematical model, which allows detecting a necessary time period for enterprise activity productivity ensuring due to social responsibility implementation.

Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Frank Lieberman

2017-10-01

Full Text Available This is an exciting time in neuro-oncology. Discoveries elucidating the molecular mechanisms of oncogenesis and the molecular subtypes of glioblastoma multiforme (GBM have led to new diagnostic and classification schemes with more prognostic power than histology alone. Molecular profiling has become part of the standard neuropathological evaluation of GBM. Chemoradiation followed by adjuvant temozolomide remains the standard therapy for newly diagnosed GBM, but survival remains unsatisfactory. Patients with recurrent GBM continue to have a dismal prognosis, but neuro-oncology centers with active clinical trial programs are seeing a small but increasing cadre of patients with longer survival. Molecularly targeted therapeutics, personalized therapy based on molecular profiling of individual tumors, and immunotherapeutic strategies are all being evaluated and refined in clinical trials. Understanding of the molecular mechanisms of tumor-mediated immunosuppression, and specifically interactions between tumor cells and immune effector cells in the tumor microenvironment, has led to a new generation of immunotherapies, including vaccine and immunomodulatory strategies as well as T-cell-based treatments. Molecularly targeted therapies, chemoradiation, immunotherapies, and anti-angiogenic therapies have created the need to develop more reliable neuroimaging criteria for differentiating the effects of therapy from tumor progression and changes in blood–brain barrier physiology from treatment response. Translational clinical trials for patients with GBM now incorporate quantitative imaging using both magnetic resonance imaging and positron emission tomography techniques. This update presents a summary of the current standards for therapy for newly diagnosed and recurrent GBM and highlights promising translational research.

New molecular imprinted voltammetric sensor for determination of ochratoxin A.

Science.gov (United States)

Yola, Mehmet Lütfi; Gupta, Vinod Kumar; Atar, Necip

2016-04-01

In this report, a novel molecular imprinted voltammetric sensor based on silver nanoparticles (AgNPs) involved in a polyoxometalate (H3PW12O40, POM) functionalized reduced graphene oxide (rGO) modified glassy carbon electrode (GCE) was presented for determination of ochrattoxin A (OCH). The developed surfaces were characterized using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. OCH imprinted GCE was prepared via electropolymerization process of 100mM phenol as monomer in the presence of phosphate buffer solution (pH6.0) containing 25 mM OCH. The linearity range and the detection limit of the method were calculated as 5.0 × 10(-11) - 1.5 × 10(-9)M and 1.6 × 10(-11) M, respectively. The voltammetric sensor was applied to grape juice and wine samples with good selectivity and recovery. The stability of the voltammetric sensor was also reported. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitive determination of citrinin based on molecular imprinted electrochemical sensor

Science.gov (United States)

Atar, Necip; Yola, Mehmet Lütfi; Eren, Tanju

2016-01-01

In this report, a novel molecular imprinted voltammetric sensor based on glassy carbon electrode (GCE) modified with platinum nanoparticles (PtNPs) involved in a polyoxometalate (H3PW12O40, POM) functionalized reduced graphene oxide (rGO) was prepared for the determination of citrinin (CIT). The developed surfaces were characterized by using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. CIT imprinted GCE was prepared via electropolymerization process of 80.0 mM pyrrole as monomer in the presence of phosphate buffer solution (pH 6.0) containing 20.0 mM CIT. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10-12-1.0 × 10-10 M and 2.0 × 10-13 M, respectively. In addition, the voltammetric sensor was applied to rye samples. The stability and selectivity of the voltammetric sensor were also reported.

A single sex pheromone receptor determines chemical response specificity of sexual behavior in the silkmoth Bombyx mori.

Science.gov (United States)

Sakurai, Takeshi; Mitsuno, Hidefumi; Haupt, Stephan Shuichi; Uchino, Keiro; Yokohari, Fumio; Nishioka, Takaaki; Kobayashi, Isao; Sezutsu, Hideki; Tamura, Toshiki; Kanzaki, Ryohei

2011-06-01

In insects and other animals, intraspecific communication between individuals of the opposite sex is mediated in part by chemical signals called sex pheromones. In most moth species, male moths rely heavily on species-specific sex pheromones emitted by female moths to identify and orient towards an appropriate mating partner among a large number of sympatric insect species. The silkmoth, Bombyx mori, utilizes the simplest possible pheromone system, in which a single pheromone component, (E, Z)-10,12-hexadecadienol (bombykol), is sufficient to elicit full sexual behavior. We have previously shown that the sex pheromone receptor BmOR1 mediates specific detection of bombykol in the antennae of male silkmoths. However, it is unclear whether the sex pheromone receptor is the minimally sufficient determination factor that triggers initiation of orientation behavior towards a potential mate. Using transgenic silkmoths expressing the sex pheromone receptor PxOR1 of the diamondback moth Plutella xylostella in BmOR1-expressing neurons, we show that the selectivity of the sex pheromone receptor determines the chemical response specificity of sexual behavior in the silkmoth. Bombykol receptor neurons expressing PxOR1 responded to its specific ligand, (Z)-11-hexadecenal (Z11-16:Ald), in a dose-dependent manner. Male moths expressing PxOR1 exhibited typical pheromone orientation behavior and copulation attempts in response to Z11-16:Ald and to females of P. xylostella. Transformation of the bombykol receptor neurons had no effect on their projections in the antennal lobe. These results indicate that activation of bombykol receptor neurons alone is sufficient to trigger full sexual behavior. Thus, a single gene defines behavioral selectivity in sex pheromone communication in the silkmoth. Our findings show that a single molecular determinant can not only function as a modulator of behavior but also as an all-or-nothing initiator of a complex species-specific behavioral sequence.

A single sex pheromone receptor determines chemical response specificity of sexual behavior in the silkmoth Bombyx mori.

Directory of Open Access Journals (Sweden)

Takeshi Sakurai

2011-06-01

Full Text Available In insects and other animals, intraspecific communication between individuals of the opposite sex is mediated in part by chemical signals called sex pheromones. In most moth species, male moths rely heavily on species-specific sex pheromones emitted by female moths to identify and orient towards an appropriate mating partner among a large number of sympatric insect species. The silkmoth, Bombyx mori, utilizes the simplest possible pheromone system, in which a single pheromone component, (E, Z-10,12-hexadecadienol (bombykol, is sufficient to elicit full sexual behavior. We have previously shown that the sex pheromone receptor BmOR1 mediates specific detection of bombykol in the antennae of male silkmoths. However, it is unclear whether the sex pheromone receptor is the minimally sufficient determination factor that triggers initiation of orientation behavior towards a potential mate. Using transgenic silkmoths expressing the sex pheromone receptor PxOR1 of the diamondback moth Plutella xylostella in BmOR1-expressing neurons, we show that the selectivity of the sex pheromone receptor determines the chemical response specificity of sexual behavior in the silkmoth. Bombykol receptor neurons expressing PxOR1 responded to its specific ligand, (Z-11-hexadecenal (Z11-16:Ald, in a dose-dependent manner. Male moths expressing PxOR1 exhibited typical pheromone orientation behavior and copulation attempts in response to Z11-16:Ald and to females of P. xylostella. Transformation of the bombykol receptor neurons had no effect on their projections in the antennal lobe. These results indicate that activation of bombykol receptor neurons alone is sufficient to trigger full sexual behavior. Thus, a single gene defines behavioral selectivity in sex pheromone communication in the silkmoth. Our findings show that a single molecular determinant can not only function as a modulator of behavior but also as an all-or-nothing initiator of a complex species

The Spanish version of the Self-Determination Inventory Student Report: application of item response theory to self-determination measurement.

Science.gov (United States)

Mumbardó-Adam, C; Guàrdia-Olmos, J; Giné, C; Raley, S K; Shogren, K A

2018-04-01

A new measure of self-determination, the Self-Determination Inventory: Student Report (Spanish version), has recently been adapted and empirically validated in Spanish language. As it is the first instrument intended to measure self-determination in youth with and without disabilities, there is a need to further explore and strengthen its psychometric analysis based on item response patterns. Through item response theory approach, this study examined item observed distributions across the essential characteristics of self-determination. The results demonstrated satisfactory to excellent item functioning patterns across characteristics, particularly within agentic action domains. Increased variability across items was also found within action-control beliefs dimensions, specifically within the self-realisation subdomain. These findings further support the instrument's psychometric properties and outline future research directions. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Control of radio degradation of natural polymers by measurement of viscosity and molecular weight determination

International Nuclear Information System (INIS)

Nabinger Machado, Patricia; Cerchietti, Maria Luciana; Mondino, Angel V.; Smolko, Eduardo E.

2009-01-01

Applications are now being made in various fields of oligosaccharides obtained by the depolymerization of large molecules such as natural alginates, carrageenan, pectin and chitosan. Find use in various disciplines such as crop production, sanitation, pharmacy, cosmetics, etc. Given the diversity of origins of these materials, almost all of marine origin, was the need for universal methods for recognition and composition, then the possible ways to get processed. A centralized program by the IAEA is promoting the use of ionizing radiation for these changes. This paper resents the calculations used to obtain the molecular weight of polysaccharides from determinations of viscosity. It has been found the molecular weight of sodium alginate and kappa-carrageenan irradiated with cobalt-60 gamma rays at doses between 2 and 35 kGy in solid state. We used a capillary Cannon Viscometer Ubbelohde-type and a protocol for standardized calculation procedure for this purpose. Were obtained reading times for passage through the capillary Viscometer, with various concentrations of polymer solutions of virgin material and the irradiated and from there calculated the relative viscosities, specific, inherent, reduced and intrinsic and then using the ratio of Mark-Houwink-SAKURADA calculate the viscosity average molecular weight of the different polymers. The changes found in the molecular weights by radio-depolymerization reach two orders of magnitude in some cases giving oligosaccharides of 8-12 monomer units. It is considered that this depolymerization method is effective and inexpensive compared to enzymatic or chemical methods. (author)

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces

Science.gov (United States)

Poloni, Laura N.

incorporation at dissymmetric surfaces because their morphology is dominated by dissymmetric {101} growth faces. Growth processes on the dissymmetric (101) surfaces of these crystalline systems were investigated using metadynamics simulations to determine the free energy of adsorption for solute and impurity attachment to different flat, stepped, and kinked (101) surface terminations. Results suggest that growth occurs via a non-Kossel crystal growth mechanism, and highlights the need for dissymmetric surface structures (i.e. steps and kinks) for a higher fidelity in the orientation of adsorbed molecules. Overall, the results presented in this thesis suggest that growth of molecular crystals, particularly at dissymmetric surfaces, is complex and requires the combination of several experimental and computational techniques to decipher the mechanisms responsible for growth phenomena. The use of molecular imposters to inhibit growth can be useful for the development of therapeutics for pathological crystals, but can also inform processes by which crystal growth occurs at complex surfaces as a result of their site selectivity.

Molecular imaging in oncology

International Nuclear Information System (INIS)

Weber, W.A.

2007-01-01

Molecular imaging is generally defined as noninvasive and quantitative imaging of targeted macromolecules and biological processes in living organisms. A characteristic of molecular imaging is the ability to perform repeated studies and assess changes in biological processes over time. Thus molecular imaging lends itself well for monitoring the effectiveness of tumor therapy. In animal models a variety of techniques can be used for molecular imaging. These include optical imaging (bioluminescence and fluorescence imaging), magnetic resonance imaging (MRI) and nuclear medicine techniques. In the clinical setting, however, nuclear medicine techniques predominate, because so far only radioactive tracers provide the necessary sensitivity to study expression and function of macromolecules non-invasively in patients. Nuclear medicine techniques allows to study a variety of biological processes in patients. These include the expression of various receptors (estrogen, androgen, somatostatin receptors and integrins). In addition, tracers are available to study tumor cell proliferation and hypoxia. The by far most commonly used molecular imaging technique in oncology is, however, positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG-PET). FDG-PET permits non-invasive quantitative assessment of the accelerated exogenous glucose use of malignant tumors. Numerous studies have now shown that reduction of tumor FDG-uptake during therapy allows early prediction of tumor response and patient survival. Clinical studies are currently underway to determine whether FDG-PET can be used to individualize tumor therapy by signaling early in the course of therapy the need for therapeutic adjustments in patients with likely non-responding tumors. (orig.)

Isolation, Characterization and Molecular weight determination of ...

African Journals Online (AJOL)

Enzyme purification to homogeneity was carried out by anion exchange chromatography on DEAE-Sepharose. SDS-PAGE revealed molecular mass of 87 kDa. Maximal activity of the enzymes was observed at 50°C at pH 4 and was stimulated by Ca2+, Co2+, Mg2+ (test at 10 Mm each) and inhibited by Fe2+. Ethanol at an ...

Molecular Determinants of Influenza Virus Pathogenesis in Mice

Science.gov (United States)

Katz, Jaqueline M.; York, Ian A.

2015-01-01

Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account. PMID:25038937

Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study.

Science.gov (United States)

Fujimoto, Masafumi; Terasaki, Shuhei; Nishi, Masaaki; Yamamoto, Tatsuo

2015-10-01

Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. Case control study. Kumamoto University Hospital, November 2010 to September 2013. Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95 rocuronium injection (baseline TOF ratio), concentration of anti-AChR antibodies, Osserman classification and treatment for myasthenia gravis in the two groups were compared. Stepwise logistic regression identified baseline TOF ratio and age of onset of myasthenia gravis as determinants of the increased response to rocuronium in patients with myasthenia gravis [odds ratios (95% confidence interval) of 0.87 (0.77 to 0.98; P = 0.02) and 0.92 (0.86 to 0.99; P = 0.03), respectively]. Multivariate analysis identified baseline TOF ratio and age of disease onset as determinants of

A Molecularly Imprinted Polymer with Incorporated Graphene Oxide for Electrochemical Determination of Quercetin

Directory of Open Access Journals (Sweden)

Xiwen He

2013-04-01

Full Text Available The molecularly imprinted polymer based on polypyrrole film with incorporated graphene oxide was fabricated and used for electrochemical determination of quercetin. The electrochemical behavior of quercetin on the modified electrode was studied in detail using differential pulse voltammetry. The oxidation peak current of quercetin in B-R buffer solution (pH = 3.5 at the modified electrode was regressed with the concentration in the range from 6.0 × 10−7 to 1.5 × 10−5 mol/L (r2 = 0.997 with a detection limit of 4.8 × 10−8 mol/L (S/N = 3. This electrode showed good stability and reproducibility. In the above mentioned range, rutin or morin which has similar structures and at the same concentration as quercetin did not interfere with the determination of quercetin. The applicability of the method for complex matrix analysis was also evaluated.

Selective and sensitive fluorimetric determination of carbendazim in apple and orange after preconcentration with magnetite-molecularly imprinted polymer

Science.gov (United States)

İlktaç, Raif; Aksuner, Nur; Henden, Emur

2017-03-01

In this study, magnetite-molecularly imprinted polymer has been used for the first time as selective adsorbent before the fluorimetric determination of carbendazim. Adsorption capacity of the magnetite-molecularly imprinted polymer was found to be 2.31 ± 0.63 mg g- 1 (n = 3). Limit of detection (LOD) and limit of quantification (LOQ) of the method were found to be 2.3 and 7.8 μg L- 1, respectively. Calibration graph was linear in the range of 10-1000 μg L- 1. Rapidity is an important advantage of the method where re-binding and recovery processes of carbendazim can be completed within an hour. The same imprinted polymer can be used for the determination of carbendazim without any capacity loss repeatedly for at least ten times. Proposed method has been successfully applied to determine carbendazim residues in apple and orange, where the recoveries of the spiked samples were found to be in the range of 95.7-103%. Characterization of the adsorbent and the effects of some potential interferences were also evaluated. With the reasonably high capacity and reusability of the adsorbent, dynamic calibration range, rapidity, simplicity, cost-effectiveness and with suitable LOD and LOQ, the proposed method is an ideal method for the determination of carbendazim.

Molecularly Imprinted Polypyrrole Based Impedimentric Sensor for Theophylline Determination

International Nuclear Information System (INIS)

Ratautaite, Vilma; Janssens, Stoffel D.; Haenen, Ken; Nesládek, Milos; Ramanaviciene, Almira; Baleviciute, Ieva; Ramanavicius, Arunas

2014-01-01

Highlights: • Sensor based on polypyrrole imprinted by theophylline (MIP) deposited on oxygen terminated boron-doped nanocrystalline diamond was developed. • This structure was applied as impedimetric sensor sensitive for theophylline. • Optimal polymer formation conditions suitable for MIP formation were elaborated. • Some analytical parameters were determined and evaluated. - Abstract: In this study development of impedimetric sensor based on oxygen terminated boron-doped nanocrystalline diamond (B:NCD:O) modified with theophylline imprinted polypyrrole is described. Hydrogen peroxide induced chemical formation of polypyrrole molecularly imprinted by theophylline was applied for the modification of conducting silicon substrate covered by B:NCD:O film. Non-imprinted polypyrrole layer was formed on similar substrate in order to prove efficiency of imprinted polypyrrole. Electrochemical impedance spectroscopy was applied for the evaluation of analyte-induced changes in electrochemical capacitance/resistance. The impact of polymerization duration on the capacitance of impedimetric sensor was estimated. A different impedance behavior was observed at different ratio of polymerized monomer and template molecule in the polymerization media. The influence of ethanol as additive to polymerization media on registered changes in capacitance/resistance was evaluated. Degradation of sensor stored in buffer solution was evaluated

Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

NARCIS (Netherlands)

Ribeiro de Jesus, P.R.

2015-01-01

Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

by Paulo Roberto Ribeiro de Jesus

The main objective of this thesis was to provide a detailed

The determination of frequency response function of the RSG Gas by laplace transform analysis

International Nuclear Information System (INIS)

Tukiran, S.; Surian, P.; Jujuratisbela, U.

1997-01-01

The response function of the RSG-GAS reactor system to the reactivity perturbations is necessary to be analyzed due to the interrelation with reliability and safety of reactor operation. the response depends on the power frequency response function H(s), while H(s) depends on the zero power frequency response function Z(s) and dynamic power coefficient of reactivity Kp(s) determination of the frequency response function of the RSG-GAS reactor was done by Fourier transform analysis method. Z(s) was obtained by fourier transform of P(t) and Cj(t) became P(S) and Cj(s) in point kinetic equations. Second order of simpson rule was used for completion of its numerical integration. then. LYMPR (Laplace transform for multipurpose reactor) code was made with fortran 77 computer language in vax 8550 system. the LTMPR code is able to determine the frequency response function and period-reactivity relation of RSG-GAS reactor by rod drop method. Profile of power as rod drop, zero power (without reactivity feedback) was used for determination frequency response of RSG-GAS reactor. The results of calculations are in a good agreement with experiment result, so the LTMPR code can be used for analysis response frequency of the RSG-GAS reactor

Determination of sulfur in coal and ash slurry by high-resolution continuum source electrothermal molecular absorption spectrometry

Energy Technology Data Exchange (ETDEWEB)

Nakadi, Flávio V.; Rosa, Lilian R.; Veiga, Márcia A.M.S. da, E-mail: mamsveiga@ffclrp.usp.br

2013-10-01

We propose a procedure for the determination of sulfur in coal slurries by high resolution continuum source electrothermal molecular absorption spectrometry. The slurry, whose concentration is 1 mg mL{sup −1}, was prepared by mixing 50 mg of the sample with 5% v/v nitric acid and 0.04% m/v Triton X-100 and was homogenized manually. It sustained good stability. The determination was performed via CS molecular absorption at 257.592 nm, and the optimized vaporization temperature was 2500 °C. The accuracy of the method was ensured by analysis of certified reference materials SRM 1632b (trace elements in coal) and SRM 1633b (coal fly ash) from the National Institute of Standards and Technology, using external calibration with aqueous standards prepared in the same medium and used as slurry. We achieved good agreement with the certified reference materials within 95% confidence interval, LOD of 0.01% w/w, and RSD of 6%, which confirms the potential of the proposed method. - Highlights: • HR-CS ET MAS as a technique to determine sulfur in coal and ash • Utilization of (coal and coal fly ash) slurry as a sample preparation • Simple and fast method, which uses external calibration with aqueous standards without chemical modifier.

Determination of phospholipids in soybean lecithin samples via the phosphorus monoxide molecule by high-resolution continuum source graphite furnace molecular absorption spectrometry.

Science.gov (United States)

Pires, Laís N; Brandão, Geovani C; Teixeira, Leonardo S G

2017-06-15

This paper presents a method for determining phospholipids in soybean lecithin samples by phosphorus determination using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) via molecular absorption of phosphorus monoxide. Samples were diluted in methyl isobutyl ketone. The best conditions were found to be 213.561nm with a pyrolysis temperature of 1300°C, a volatilization temperature of 2300°C and Mg as a chemical modifier. To increase the analytical sensitivity, measurement of the absorbance signal was obtained by summing molecular transition lines for PO surrounding 213nm: 213.561, 213.526, 213.617 and 213.637nm. The limit of detection was 2.35mgg -1 and the precision, evaluated as relative standard deviation (RSD), was 2.47% (n=10) for a sample containing 2.2% (w/v) phosphorus. The developed method was applied for the analysis of commercial samples of soybean lecithin. The determined concentrations of phospholipids in the samples varied between 38.1 and 45% (w/v). Copyright © 2017 Elsevier Ltd. All rights reserved.

Unraveling the Root Proteome Changes and Its Relationship to Molecular Mechanism Underlying Salt Stress Response in Radish (Raphanus sativus L.

Directory of Open Access Journals (Sweden)

Xiaochuan Sun

2017-07-01

Full Text Available To understand the molecular mechanism underlying salt stress response in radish, iTRAQ-based proteomic analysis was conducted to investigate the differences in protein species abundance under different salt treatments. In total, 851, 706, and 685 differential abundance protein species (DAPS were identified between CK vs. Na100, CK vs. Na200, and Na100 vs. Na200, respectively. Functional annotation analysis revealed that salt stress elicited complex proteomic alterations in radish roots involved in carbohydrate and energy metabolism, protein metabolism, signal transduction, transcription regulation, stress and defense and transport. Additionally, the expression levels of nine genes encoding DAPS were further verified using RT-qPCR. The integrative analysis of transcriptomic and proteomic data in conjunction with miRNAs was further performed to strengthen the understanding of radish response to salinity. The genes responsible for signal transduction, ROS scavenging and transport activities as well as several key miRNAs including miR171, miR395, and miR398 played crucial roles in salt stress response in radish. Based on these findings, a schematic genetic regulatory network of salt stress response was proposed. This study provided valuable insights into the molecular mechanism underlying salt stress response in radish roots and would facilitate developing effective strategies toward genetically engineered salt-tolerant radish and other root vegetable crops.

Determination of sulfur in food by high resolution continuum source flame molecular absorption spectrometry

Science.gov (United States)

Zambrzycka, Elżbieta; Godlewska-Żyłkiewicz, Beata

2014-11-01

In the present work, a fast, simple and sensitive analytical method for determination of sulfur in food and beverages by high resolution continuum source flame molecular absorption spectrometry was developed. The determination was performed via molecular absorption of carbon monosulfide, CS. Different CS rotational lines (257.959 nm, 258.033 nm, 258.055 nm), number of pixels and types of standard solution of sulfur, namely: sulfuric acid, sodium sulfate, ammonium sulfate, sodium sulfite, sodium sulfide, DL-cysteine, and L-cystine, were studied in terms of sensitivity, repeatability of results as well as limit of detection and limit of quantification. The best results were obtained for measurements of absorption of the CS molecule at 258.055 nm at the wavelength range covering 3 pixels and DL-cysteine in 0.2 mol L- 1 HNO3 solution as a calibration standard. Under optimized conditions the limit of detection and the limit of quantification achieved for sulfur were 10.9 mg L- 1 and 36.4 mg L- 1, respectively. The repeatability of the results expressed as relative standard deviation was typically beverage samples with added known amount of sulfur standard. The recovery of analyte from such samples was in the range of 93-105% with the repeatability in the range of 4.1-5.0%. The developed method was applied for the determination of sulfur in milk (194 ± 10 mg kg- 1), egg white (2188 ± 29 mg kg- 1), mineral water (31.0 ± 0.9 mg L- 1), white wine (260 ± 4 mg L- 1) and red wine (82 ± 2 mg L- 1), as well as in sample rich in ions, such as bitter mineral water (6900 ± 100 mg L- 1).

Application of numerical methods to the determination of molecular wave functions

International Nuclear Information System (INIS)

Douady, Jerome

1969-01-01

A simplified SCF Method is developed. The wave function of molecular systems and spin densities in the case of free radicals are computed from geometrical data. This method, including at the beginning a delocalization of electrons over all the molecular system, two methods which clear out bonding and anti-bonding interactions have been studied and programmed: a) overlap population analysis, b) localisation of molecular orbitals. These methods have been carried out in the case of organic compounds and free radicals. (author) [fr

Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

Directory of Open Access Journals (Sweden)

Moritz Palmowski

2009-09-01

Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

Science.gov (United States)

O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

2012-09-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

Science.gov (United States)

O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

2012-01-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

Determination of molecular-ion structures through the use of accelerated beams

International Nuclear Information System (INIS)

Gemmell, D.S.

1987-01-01

In this talk we report on recent research on molecular-ion structures using fast molecular-ion beams provided by Argonne's 5-MV Dynamitron accelerator. The method has become known as the ''Coulomb-explosion'' technique. When molecular-ion projectiles travelling at velocities of a few percent of the velocity of light strike a foil, the electrons that bind the molecular projectiles are almost always totally stripped off within the first few Angstroms of penetration into the solid target. This leaves a cluster of bare (or nearly bare) nuclei which separate rapidly as a result of their mutual Coulomb repulsion. This violent dissociation process in which the initial electrostatic potential energy is converted into kinetic energy of relative motion in the center-of-mass, has been termed a ''Coulomb explosion.'' 4 refs., 2 figs

A Study on the Determinants of Earnings Response Coefficient in an Emerging Market

OpenAIRE

Bita Mashayekhi; Zeynab Lotfi Aghel

2016-01-01

The determinants of Earnings Response Coefficient (ERC), including firm size, earnings growth, and earnings persistence are studied in this research. These determinants are supposed to be moderator variables that affect ERC and Return Response Coefficient. The research sample contains 82 Iranian listed companies in Tehran Stock Exchange (TSE) from 2001 to 2012. Gathered data have been processed by EVIEWS Software. Results show a significant positive relation between firm size and ERC, and als...

Determination of the NPP Cernavoda reactor building seismic response

International Nuclear Information System (INIS)

Krutzik, N.J.; Rotaru, I.; Bobei, M.; Mingiuc, C.; Serban, V.

1997-01-01

Seismic input for systems and equipment installed in buildings depends on: - the seismic movement in free field on site; - the building movement in the soil; - the building deflection. The percentage of the 3 movements for the system and equipment input, depends on the position of the systems and equipment inside the building as well on the type of the foundation soil. The type of the foundation soil is important because if it is stiff it transfers a lot of energy to the building, energy which amplify the movement of the building on the top. If the foundation soil is soft, it accommodates the overall movement of the building in the soil, amplifying the movement to lower levels and the building response is attenuated if a resonance phenomenon between the whole building movement and the seismic excitation does not exist. This input is given with the design floor response spectra (FRS), in the logarithmic scale and seismic anchor movement (SAM). The design floor response spectra for NPP Cernavoda U1 Nuclear Building were determined in several stages starting with simple models (STICK type) without twisting movement and ending with detailed 3-dimensional models. From the point of view of dynamic behavior, the Reactor Building can be considered to be made up of 4 sub-structures: the containment building, internal structures containing separate elements such as the reactor vault, the fuel transfer structure and itself. Each sub-structure has its own movement (some of the structures present also some local effects) which combines with the overall movement of the building in the soil and the seismic excitation produce the total movement so that the response spectrum for each point of the sub-structure is specific. One should note that for structures which also show the twisting effect, the selection of the points on the floor, for the determination on the response spectra, is an engineering decision so that the response should be relevant for the equipment installed on the

Visual functions in amblyopia as determinants of response to treatment.

Science.gov (United States)

Singh, Vinita; Agrawal, Siddharth

2013-01-01

To describe the visual functions in amblyopia as determinants of response to treatment. Sixty-nine patients with unilateral and bilateral amblyopia (114 amblyopic eyes) 3 to 15 years old (mean age: 8.80 ± 2.9 years), 40 males (58%) and 29 females (42%), were included in this study. All patients were treated by conventional occlusion 6 hours per day for mild to moderate amblyopia (visual acuity 0.70 or better) and full-time for 4 weeks followed by 6 hours per day for severe amblyopia (visual acuity 0.8 or worse). During occlusion, near activities requiring hand-eye coordination were advised. The follow-up examination was done at 3 and 6 months. Improvement in visual acuity was evaluated on the logMAR chart and correlated with the visual functions. Statistical analysis was done using Wilcoxon rank sum test (Mann-Whitney U test) and Kruskal-Wallis analysis. There was a statistically significant association of poor contrast sensitivity with the grade of amblyopia (P amblyopia (P amblyopia therapy. The grade of amblyopia (initial visual acuity) and accommodation are strong determinants of response to amblyopia therapy, whereas stereopsis and mesopic visual acuity have some value as determinants. Copyright 2013, SLACK Incorporated.

Fluorine determination in coal using high-resolution graphite furnace molecular absorption spectrometry and direct solid sample analysis

Energy Technology Data Exchange (ETDEWEB)

Machado, Patrícia M.; Morés, Silvane; Pereira, Éderson R. [Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Welz, Bernhard, E-mail: w.bernardo@terra.com.br [Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, 40170-115 Salvador, BA (Brazil); Carasek, Eduardo [Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Andrade, Jailson B. de [Instituto Nacional de Ciência e Tecnologia do CNPq, INCT de Energia e Ambiente, Universidade Federal da Bahia, 40170-115 Salvador, BA (Brazil)

2015-03-01

The absorption of the calcium mono-fluoride (CaF) molecule has been employed in this study for the determination of fluorine in coal using direct solid sample analysis and high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS). The rotational line at 606.440 nm was used for measuring the molecular absorption in the gas phase. The pyrolysis and vaporization temperatures were 700 °C and 2100 °C, respectively. Different chemical modifiers have been studied, such as Pd and Ir as permanent modifiers, and Pd and the mixed Pd/Mg modifier in solution. The limit of detection and the characteristic mass were 0.3 and 0.1 ng F, respectively. One certified reference material (CRM) of coal (NIST 1635) and four CRMs with a non-certified value for F (SARM 18, SARM 20, BCR 40, BCR 180) were used to evaluate the accuracy and precision of the method, obtaining good agreement (104%) with the certified value and with the informed values (ranging from 90 to 103%). - Highlights: • High-resolution Graphite Furnace Molecular Absorption Spectrometry (HR-GF MAS) • Fluorine has been determined using HR-GF MAS of the CaF molecule. • The CaF molecule was generated in a graphite furnace at a temperature of 2100 °C • Coal samples have been analyzed using direct solid sample introduction. • Aqueous standard solutions have been used for calibration.

A method to determine insulin responsiveness in synaptosomes isolated from frozen brain tissue.

Science.gov (United States)

Franklin, Whitney; Taglialatela, Giulio

2016-03-01

Studying the insulin signaling response at the synapse is an important approach to understand molecular mechanisms involved in disease-related neurodegenerative processes. We developed a method for studying the insulin responsiveness at the synaptic level by isolating functional synaptosomes from fresh or frozen tissue and exposing them to insulin in the presence of ATP (a critical step) to detect insulin receptor (IR) activation. We performed an ATP dose-response curve, insulin dose-response curve, and insulin response time course to optimize this method. We also demonstrated that our protocol reflects the degree of insulin responsiveness in vivo by using an animal model of known insulin resistance, AtENPP1-Tg mice. This method is advantageous over other methods detecting IR in total brain homogenates due to the ability to detect IR response without confounding contributions from other cell areas and cell types also expressing IR. Furthermore, ex vivo insulin stimulation can be compared to baseline synaptosomes obtained from the same animal which improves reliability and statistical power while decreasing the number of animals required to perform individual experiments. We have developed a reliable, efficient method to measure insulin-driven ex vivo phosphorylation of the synaptosomal insulin receptor that can reliably reflect the pre-existing insulin responsiveness status in the CNS of the animal. To the best of our knowledge, this is the first evidence of stimulation of isolated synaptosomes with insulin and a promising new technique to study the synaptic CNS insulin responsiveness under physiological or disease conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

Science.gov (United States)

Rosa, Marilin

2015-04-01

Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

Selective extraction and determination of chlorogenic acids as combined quality markers in herbal medicines using molecularly imprinted polymers based on a mimic template.

Science.gov (United States)

Ji, Wenhua; Zhang, Mingming; Yan, Huijiao; Zhao, Hengqiang; Mu, Yan; Guo, Lanping; Wang, Xiao

2017-12-01

We describe a solid-phase extraction adsorbent based on molecularly imprinted polymers (MIPs), prepared with use of a mimic template. The MIPs were used for the selective extraction and determination of three chlorogenic acids as combined quality markers for Lonicera japonica and Lianhua qingwen granules. The morphologies and surface groups of the MIPs were assessed by scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, and Fourier transform infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the MIPs were systematically compared with those of non-molecularly imprinted polymers. The MIPs showed high selectivity toward three structurally similar chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid). A procedure using molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography was established for the determination of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules. The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits of detection and limits of quantification for the three chlorogenic acids were 0.003 mg g -1 and 0.01 mg g -1 , respectively. The newly developed method is thus a promising technique for the enrichment and determination of chlorogenic acids from herbal medicines. Graphical Abstract Mimic molecularly imprinted polymers for the selective extraction of chlorogenic acids.

Cold excitation and determination of hydrogen sulfide by dielectric barrier discharge molecular emission spectrometry.

Science.gov (United States)

Wu, Zhongchen; Jiang, Jie; Li, Na

2015-11-01

A low-temperature microplasma generated in a dielectric barrier discharge (DBD) was used as a radiation source for the excitation of hydrogen sulfide and its determination by molecular emission spectrometry (MES). The excitation/emission chamber was enclosed to eliminate spectral interference from ambient air. The spectral emission lines of hydrogen sulfide were clearly discriminated from the background spectrum, and the emission line at 365.06 nm was selected for parameter optimization and quantitative analysis. The S(2-) ions in aqueous samples were reacted with acid to generate hydrogen sulfide and then determined. The experimental parameters affecting the determination of hydrogen sulfide and S(2-) were optimized. The limits of detection were 1.4 mg m(-3) for H2S and 11.2 mg L(-1) for S(2-). The repeatability of the method was satisfactory, as the RSD values were 2.3% for H2S and 1.8% for S(2-). The enclosed DBD-MES system was demonstrated to be a useful tool for the determination of hydrogen sulfide in gas samples and S(2-) in aqueous samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Innate Immune Responses Activated in Arabidopsis Roots by Microbe-Associated Molecular Patterns[W][OA

Science.gov (United States)

Millet, Yves A.; Danna, Cristian H.; Clay, Nicole K.; Songnuan, Wisuwat; Simon, Matthew D.; Werck-Reichhart, Danièle; Ausubel, Frederick M.

2010-01-01

Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of β-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid–jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways. PMID:20348432

Molecularly imprinted polymer for selective extraction of malachite green from seawater and seafood coupled with high-performance liquid chromatographic determination

International Nuclear Information System (INIS)

Lian Ziru; Wang Jiangtao

2012-01-01

Highlights: ► The malachite green molecularly imprinted polymer (MG-MIP) was prepared. ► The characteristics and regeneration property of MIP were studied. ► An off-line method for MG was developed using MIP as solid-phase extraction. ► The MG concentrations from seawater and seafood samples were determined. - Abstract: In this paper, a highly selective sample cleanup procedure combining molecular imprinting technique (MIT) and solid-phase extraction (SPE) was developed for the isolation of malachite green in seawater and seafood samples. The molecularly imprinted polymer (MIP) was prepared using malachite green as the template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linking monomer. The imprinted polymer and non-imprinted polymer were characterized by scanning electron microscope and static adsorption experiments. The MIP showed a high adsorption capacity and was used as selective sorbent for the SPE of malachite green. An off-line molecularly imprinted solid-phase extraction (MISPE) method followed by high-performance liquid chromatography with diodearray detection for the analysis of malachite green in seawater and seafood samples was also established. Finally, five samples were determined. The results showed that malachite green concentration in one seawater sample was at 1.30 μg L −1 and the RSD (n = 3) was 4.15%.

A sol-gel based molecular imprint incorporating carbon dots for fluorometric determination of nicotinic acid

International Nuclear Information System (INIS)

Zuo, Pengli; Gao, Junfa; Liu, Jianha; Zhao, Mingming; Zhao, Jiahong; Peng, Jun; Zuo, Pengjian; He, Hua

2016-01-01

We are introducing functionalized carbon dots (C-dots) coated with a shell of molecularly imprinted sol-gel as a new tool in molecular imprint-based detection. Specifically, an imprint recognizing nicotinic acid (NA) was prepared in two steps. The first involves pyrolytic decomposition of citric acid in the presence of aminopropyltriethoxysilane to yield triethoxysilyl-modified C-dots with a typical size of 2.8 ± 1.1 nm. These are then polycondensed in the presence of tetraethoxysilane and NA at room temperature to give spherical silica nanoparticles (SiNPs) with a typical size of ∼300 nm and containing C-dots and NA in the silica matrix. NA was then removed by extraction. The resulting SiNPs are well permeable to NA, photostable, display strong blue luminescence and can bind NA fairly selectively. The fluorometric detection scheme is based on the finding that increasing concentrations of NA quench the fluorescence of the C-dots in the SiNPs. NA can be determined by this method in the 0.5 to 10.5 μM concentration range, with a 12.6 nM detection limit. The composite was successfully utilized as a fluorescent probe for the determination of NA in spiked human urine samples. The method is believed to have a wider scope in being applicable to other analytes that are capable of quenching the fluorescence of C-dots. (author)

Mechanical Properties of Nanostructured Materials Determined Through Molecular Modeling Techniques

Science.gov (United States)

Clancy, Thomas C.; Gates, Thomas S.

2005-01-01

The potential for gains in material properties over conventional materials has motivated an effort to develop novel nanostructured materials for aerospace applications. These novel materials typically consist of a polymer matrix reinforced with particles on the nanometer length scale. In this study, molecular modeling is used to construct fully atomistic models of a carbon nanotube embedded in an epoxy polymer matrix. Functionalization of the nanotube which consists of the introduction of direct chemical bonding between the polymer matrix and the nanotube, hence providing a load transfer mechanism, is systematically varied. The relative effectiveness of functionalization in a nanostructured material may depend on a variety of factors related to the details of the chemical bonding and the polymer structure at the nanotube-polymer interface. The objective of this modeling is to determine what influence the details of functionalization of the carbon nanotube with the polymer matrix has on the resulting mechanical properties. By considering a range of degree of functionalization, the structure-property relationships of these materials is examined and mechanical properties of these models are calculated using standard techniques.

Light and redox switchable molecular components for molecular electronics.

Science.gov (United States)

Browne, Wesley R; Feringa, Ben L

2010-01-01

The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerous unexpected challenges that have slowed progress and the initial promise of complex molecular-based computers has not yet been realised. Primarily this has been due to the realisation at an early stage that molecular-based nano-electronics brings with it the interface between the hard (semiconductor) and soft (molecular) worlds and the challenges which accompany working in such an environment. Issues such as addressability, cross-talk, molecular stability and perturbation of molecular properties (e.g., inhibition of photochemistry) have nevertheless driven development in molecular design and synthesis as well as our ability to interface molecular components with bulk metal contacts to a very high level of sophistication. Numerous groups have played key roles in progressing this field not least teams such as those led by Whitesides, Aviram, Ratner, Stoddart and Heath. In this short review we will however focus on the contributions from our own group and those of our collaborators, in employing diarylethene based molecular components.

Size and number of DNA molecules from Chinese hamster ovary cells determined by molecular autoradiography

International Nuclear Information System (INIS)

Todd, M.B.

1980-06-01

A new method for visualization of separable subunits of DNA is described. Autoradiography of tritium-labeled DNA from one or a few nuclei, lysed with detergent, moderate salt, and proteases, and gently deposited on a filter, allows determination of subunit molecular weight, size distribution, number per nucleus, and organization. The shape of the size distribution of CHO subunit images is similar to that of CHO mitotic chromosomes, and the numbers of subunits per nucleus supports a model of eight subunits per chromosome

Prediction of thresholds and latency on the basis of experimentally determined impulse responses

NARCIS (Netherlands)

Blommaert, F.J.J.; Roufs, J.A.J.

As was shown before (Roufs and Blommaert 1981), temporal impluse responsses and step responses can be obtained psychophysically using a driftcorrecting perturbation technique. In this paper, experimentally determined impulse responses are given for eight subjects using different experimental

Molecular determinants of nucleolar translocation of RNA helicase A

International Nuclear Information System (INIS)

Liu Zhe; Kenworthy, Rachael; Green, Christopher; Tang, Hengli

2007-01-01

RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role

Corporate environmental responsibility – a key determinant of corporate reputation

Directory of Open Access Journals (Sweden)

Cristina GĂNESCU

2014-06-01

Full Text Available This paper aims to determine the trend of the relationship between corporate environmental responsibility and corporate reputation by focusing on a study of the European automotive sector. The starting point of our research is content analysis of the sustainability or social responsibility reports published in 2010, 2011, and 2012 by 13 businesses operating in the European automotive industry. Content analysis was carried out in order to identify the indicators used to assess corporate environmental responsibility. The methodology aimed to produce an evaluation model for corporate environmental responsibility based on the following variables reported by companies: carbon dioxide emissions, water consumption, energy consumption, and amount of waste. Corporate reputation of sampled organizations was assessed based on content analysis of the 2010, 2011, and 2012 reports of the Reputation Institute. We applied the correlation of panel data and emphasised the fact that high levels of corporate environmental responsibility sustain high levels of corporate reputation. The study highlights the theoretical considerations that support this relationship. As companies become increasingly accountable, the methodology described in our study can be developed in further research by using other variables to measure corporate environmental responsibility.

Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer

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Manoj B. Kudupoje

2018-01-01

Full Text Available Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA. Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50 (−log [ETA] of 6.66 ± 0.17 M. Although sample preparation time affected contractile response (p < 0.001, pre-myograph incubation temperature (39 vs. 21 °C, 1 h had no effect (p > 0.05. Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92 for both polymers, with no significant difference between polymers (p > 0.05. No significant differences in maximum inhibitory (p = 0.96 and IC50 responses (p = 0.163 between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01, for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.

Peroxiredoxin 6 from the Antarctic emerald rockcod: molecular characterization of its response to warming.

Science.gov (United States)

Tolomeo, A M; Carraro, A; Bakiu, R; Toppo, S; Place, S P; Ferro, D; Santovito, G

2016-01-01

In the present study, we describe the purification and molecular characterization of two peroxiredoxins (Prdxs), referred to as Prdx6A and Prdx6B, from Trematomus bernacchii, a teleost widely distributed in many areas of Antarctica, that plays a pivotal role in the Antarctic food chain. The two putative amino acid sequences were compared with Prdx6 orthologs from other fish, highlighting a high percentage of identity and similarity with the respective variant, in particular for the residues that are essential for the characteristic peroxidase and phospholipase activities of these enzymes. Phylogenetic analyses suggest the appearance of the two prdx6 genes through a duplication event before the speciation that led to the differentiation of fish families and that the evolution of the two gene variants seems to proceed together with the evolution of fish orders and families. The temporal expression of Prdx6 mRNA in response to short-term thermal stress showed a general upregulation of prdx6b and inhibition of prdx6a, suggesting that the latter is the variant most affected by temperature increase. The variations of mRNA accumulation are more conspicuous in heart than the liver, probably related to behavioral changes of the specimens in response to elevated temperature. These data, together with the peculiar differences between the molecular structures of the two Prdx6s in T. bernacchii as well as in the tropical species Stegastes partitus, suggest an adaptation that allowed these poikilothermic aquatic vertebrates to colonize very different environments, characterized by different temperature ranges.

Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

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Elio A Cino

Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

Determination of average molecular weights on organic reactor coolants. I.- Freezing-point depression method for benzene solutions; Determinaciond e masas moleculares medias en refrigerantes nucleares organicos. I.- Crioscopia de disolucion bencenicas

Energy Technology Data Exchange (ETDEWEB)

Carreira, M

1965-07-01

As a working method for determination of changes in molecular mass that may occur by irradiation (pyrolytic-radiolytic decomposition) of polyphenyl reactor coolants, a cryoscopic technique has been developed which associated the basic simplicity of Beckman's method with some experimental refinements taken out of the equilibrium methods. A total of 18 runs were made on samples of napthalene, biphenyl, and the commercial mixtures OM-2 (Progil) and Santowax-R (Monsanto), with an average deviation from the theoretical molecular mass of 0.6%. (Author) 7 refs.

Determination of average molecular weights on organic reactor coolants. I.- Freezing-point depression method for benzene solutions; Determinaciond e masas moleculares medias en refrigerantes nucleares organicos. I.- Crioscopia de disolucion bencenicas

Energy Technology Data Exchange (ETDEWEB)

Carreira, M.

1965-07-01

As a working method for determination of changes in molecular mass that may occur by irradiation (pyrolytic-radiolytic decomposition) of polyphenyl reactor coolants, a cryoscopic technique has been developed which associated the basic simplicity of Beckman's method with some experimental refinements taken out of the equilibrium methods. A total of 18 runs were made on samples of napthalene, biphenyl, and the commercial mixtures OM-2 (Progil) and Santowax-R (Monsanto), with an average deviation from the theoretical molecular mass of 0.6%. (Author) 7 refs.

Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase

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Hemant Malhotra

2015-01-01

Full Text Available Background & objectives: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2 in CML patients and to correlate these levels with molecular response. Methods: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. Results: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05 while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. Interpretation & conclusions: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress.

Science.gov (United States)

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2017-04-01

Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies.

Science.gov (United States)

Bardhan, Jaydeep P; Jungwirth, Pavel; Makowski, Lee

2012-09-28

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular "linear response" model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution).

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

Science.gov (United States)

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed

Determination of molecular markers associated with anthesis-silking interval in maize

International Nuclear Information System (INIS)

Simpson, J.

1998-01-01

Maize lines contrasting in anthesis-silking, interval (ASI), a trait strongly linked to drought tolerance, have been analyzed under different water stress conditions in the field and with molecular markers. Correlation of marker and field data has revealed molecular markers strongly associated with flowering and yield traits. (author)

[Pharmacogenetics II. Research molecular methods, bioinformatics and ethical concerns].

Science.gov (United States)

Daudén, E

2007-01-01

Pharmacogenetics refers to the study of the individual pharmacological response based on the genotype. Its objective is to optimize treatment in an individual basis, thereby creating a more efficient and safe personalized therapy. In the second part of this review, the molecular methods of study in pharmacogenetics, including microarray technology or DNA chips, are discussed. Among them we highlight the microarrays used to determine the gene expression that detect specific RNA sequences, and the microarrays employed to determine the genotype that detect specific DNA sequences, including polymorphisms, particularly single nucleotide polymorphisms (SNPs). The relationship between pharmacogenetics, bioinformatics and ethical concerns is reviewed.

TIP-1 translocation onto the cell plasma membrane is a molecular biomarker of tumor response to ionizing radiation.

Directory of Open Access Journals (Sweden)

Hailun Wang

2010-08-01

Full Text Available Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3 is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.

BRCA1, FANCD2 and Chk1 are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells.

Science.gov (United States)

Burdak-Rothkamm, Susanne; Rothkamm, Kai; McClelland, Keeva; Al Rashid, Shahnaz T; Prise, Kevin M

2015-01-28

Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The place of molecular methods in the identification of dermatophytes and the determination of their feasibility

Directory of Open Access Journals (Sweden)

Fatma Bıyık

2013-03-01

Full Text Available Background and Design: Unlike opportunistic fungi, dermatophytes cannot be isolated on the conventional culture media in a few days. Their growing periods cover approximately two weeks in a suitable media and identification are made with conventional methods as typical macroscopic and microscopic appearance. However, successful results are not always obtained with the phenotypic features, and thus, diagnostic problems and delay in diagnosis and treatment may arise. For this reason, the methods based on nucleic acid amplification have been necessary. In this study, we aimed to identify 56 dermatophytes strains, which were identified by conventional methods, by molecular methods and to investigate the correlation between the two methods and to determine the usability of molecular methods in routine laboratories. Materials and Methods: Several clinical samples of 270 patients with suspected dermatophytoses (hair+scalp, skin and nail scrapings were examined by conventional methods; Sabouraud dextrose agar, corn meal agar and potato dextrose agar were used for isolation. In case of necessity to hydrolyze urea, to be used different vitamins in Trichophyton agar media were investigated. Polymerase chain reaction (PCR and sequence analyses were done for the molecular diagnosis. Results: Using conventional methods, 37 strains (66,1% were identified as Trichophyton(T rubrum, four (7.1% - T.mentagrophytes, four (7.1% - T.tonsurans, one (1.8% - T.violaceum, eight (14.3% - Trichophyton spp., one (1.8% - Microsporum(M canis, and one (1.8% - Microsporum spp. According to the molecular and sequence analyses results (T1PCR, 25GAPCR, ITSPCR-RFLP and sequence analyses, 41 (73.8% strains were identified as T.rubrum, 10 (17.8% - T.interdigitale, one (1.8% - T. violaceum, two (3.6% - M. canis, one (1.8% - Peacilomyces lilacinus, and one (1,8% - Aspergillus fumigatus. Discussion: This study suggests that, molecular methods offer fast and reliable results in

Determination of the activity of a molecular solute in saturated solution

International Nuclear Information System (INIS)

Nordstroem, Fredrik L.; Rasmuson, Ake C.

2008-01-01

Prediction of the solubility of a solid molecular compound in a solvent, as well as, estimation of the solution activity coefficient from experimental solubility data both require estimation of the activity of the solute in the saturated solution. The activity of the solute in the saturated solution is often defined using the pure melt at the same temperature as the thermodynamic reference. In chemical engineering literature also the activity of the solid is usually defined on the same reference state. However, far below the melting temperature, the properties of this reference state cannot be determined experimentally, and different simplifications and approximations are normally adopted. In the present work, a novel method is presented to determine the activity of the solute in the saturated solution (=ideal solubility) and the heat capacity difference between the pure supercooled melt and solid. The approach is based on rigorous thermodynamics, using standard experimental thermodynamic data at the melting temperature of the pure compound and solubility measurements in different solvents at various temperatures. The method is illustrated using data for ortho-, meta-, and para-hydroxybenzoic acid, salicylamide and paracetamol. The results show that complete neglect of the heat capacity terms may lead to estimations of the activity that are incorrect by a factor of 12. Other commonly used simplifications may lead to estimations that are only one-third of the correct value

Determination of the activity of a molecular solute in saturated solution

Energy Technology Data Exchange (ETDEWEB)

Nordstroem, Fredrik L. [Department of Chemical Engineering and Technology, Royal Institute of Technology, 100 44 Stockholm (Sweden); Rasmuson, Ake C. [Department of Chemical Engineering and Technology, Royal Institute of Technology, 100 44 Stockholm (Sweden)], E-mail: rasmuson@ket.kth.se

2008-12-15

Prediction of the solubility of a solid molecular compound in a solvent, as well as, estimation of the solution activity coefficient from experimental solubility data both require estimation of the activity of the solute in the saturated solution. The activity of the solute in the saturated solution is often defined using the pure melt at the same temperature as the thermodynamic reference. In chemical engineering literature also the activity of the solid is usually defined on the same reference state. However, far below the melting temperature, the properties of this reference state cannot be determined experimentally, and different simplifications and approximations are normally adopted. In the present work, a novel method is presented to determine the activity of the solute in the saturated solution (=ideal solubility) and the heat capacity difference between the pure supercooled melt and solid. The approach is based on rigorous thermodynamics, using standard experimental thermodynamic data at the melting temperature of the pure compound and solubility measurements in different solvents at various temperatures. The method is illustrated using data for ortho-, meta-, and para-hydroxybenzoic acid, salicylamide and paracetamol. The results show that complete neglect of the heat capacity terms may lead to estimations of the activity that are incorrect by a factor of 12. Other commonly used simplifications may lead to estimations that are only one-third of the correct value.

Molecular geometry

CERN Document Server

Rodger, Alison

1995-01-01

Molecular Geometry discusses topics relevant to the arrangement of atoms. The book is comprised of seven chapters that tackle several areas of molecular geometry. Chapter 1 reviews the definition and determination of molecular geometry, while Chapter 2 discusses the unified view of stereochemistry and stereochemical changes. Chapter 3 covers the geometry of molecules of second row atoms, and Chapter 4 deals with the main group elements beyond the second row. The book also talks about the complexes of transition metals and f-block elements, and then covers the organometallic compounds and trans

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

Science.gov (United States)

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Direct quantitative comparison of molecular responses in photodamaged human skin to fractionated and fully ablative carbon dioxide laser resurfacing.

Science.gov (United States)

Orringer, Jeffrey S; Sachs, Dana L; Shao, Yuan; Hammerberg, Craig; Cui, Yilei; Voorhees, John J; Fisher, Gary J

2012-10-01

Fractionated ablative laser resurfacing has become a widely used treatment modality. Its clinical results are often found to approach those of traditional fully ablative laser resurfacing. To directly compare the molecular changes that result from fractionated and fully ablative carbon dioxide (CO(2)) laser resurfacing in photodamaged human skin. Photodamaged skin of 34 adult volunteers was focally treated at distinct sites with a fully ablative CO(2) laser and a fractionated CO(2) laser. Serial skin samples were obtained at baseline and several time points after treatment. Real-time reverse transcriptase polymerase chain reaction technology and immunohistochemistry were used to quantify molecular responses to each type of laser treatment. Fully ablative and fractionated CO(2) laser resurfacing induced significant dermal remodeling and collagen induction. After a single treatment, fractionated ablative laser resurfacing resulted in collagen induction that was approximately 40% to 50% as pronounced as that induced by fully ablative laser resurfacing. The fundamental cutaneous responses that result from fully ablative and fractionated carbon dioxide laser resurfacing are similar but differ in magnitude and duration, with the fully ablative procedure inducing relatively greater changes including more pronounced collagen induction. However, the molecular data reported here provide substantial support for fractionated ablative resurfacing as an effective treatment modality for improving skin texture. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Cigarette smoke induces molecular responses in respiratory tissues of ApoE−/− mice that are progressively deactivated upon cessation

International Nuclear Information System (INIS)

Boué, Stéphanie; De León, Héctor; Schlage, Walter K.; Peck, Michael J.; Weiler, Horst; Berges, An; Vuillaume, Grégory; Martin, Florian; Friedrichs, Baerbel; Lebrun, Stefan

2013-01-01

Cigarette smoking is the primary etiology of chronic obstructive pulmonary disease (COPD) and a risk factor for both lung and cardiovascular (CV) diseases, which are rarely investigated concomitantly. Although smoking cessation shows clear CV risk benefit, lung-related disease risk remains higher in former smokers than in never smokers. We sought to determine the differential molecular responses of murine respiratory tissues to better understand the toxicity pathways involved in smoking-related disease risk and those related to the benefits of smoking cessation. ApoE −/− mice were exposed to mainstream cigarette smoke (CS) or a smoking cessation-mimicking protocol for up to 6 months and transcriptomics analysis of nasal epithelium and lung parenchyma performed. We supported our gene expression profiling approach with standard lung histopathology and bronchoalveolar lavage fluid (BALF) analysis. Many BALF analytes involved in functions ranging from inflammation to cell proliferation and tissue remodeling were found elevated in BALF. Gene expression levels of these molecules were also increased in lung tissue, suggesting that the inflammatory response was the result of local tissue activation and the contribution of recruited inflammatory cells. Gene set enrichment analysis (GSEA) of expression data from murine lungs and nasal epithelium showed distinct activation patterns of inflammation, complement, and xenobiotic metabolism pathways during CS exposure that were deactivated upon smoking cessation. Pathways involved in cell proliferation and tissue remodeling were activated by CS and progressively deactivated upon smoke exposure cessation. Differential CS-mediated responses of pulmonary and nasal tissues reflect common mechanisms but also the varying degrees of epithelial functional specialization and exposure along the respiratory tract

Bulk viscosity of molecular fluids

Science.gov (United States)

Jaeger, Frederike; Matar, Omar K.; Müller, Erich A.

2018-05-01

The bulk viscosity of molecular models of gases and liquids is determined by molecular simulations as a combination of a dilute gas contribution, arising due to the relaxation of internal degrees of freedom, and a configurational contribution, due to the presence of intermolecular interactions. The dilute gas contribution is evaluated using experimental data for the relaxation times of vibrational and rotational degrees of freedom. The configurational part is calculated using Green-Kubo relations for the fluctuations of the pressure tensor obtained from equilibrium microcanonical molecular dynamics simulations. As a benchmark, the Lennard-Jones fluid is studied. Both atomistic and coarse-grained force fields for water, CO2, and n-decane are considered and tested for their accuracy, and where possible, compared to experimental data. The dilute gas contribution to the bulk viscosity is seen to be significant only in the cases when intramolecular relaxation times are in the μs range, and for low vibrational wave numbers (<1000 cm-1); This explains the abnormally high values of bulk viscosity reported for CO2. In all other cases studied, the dilute gas contribution is negligible and the configurational contribution dominates the overall behavior. In particular, the configurational term is responsible for the enhancement of the bulk viscosity near the critical point.

Molecular and physiological responses of trees to waterlogging stress.

Science.gov (United States)

Kreuzwieser, Jürgen; Rennenberg, Heinz

2014-10-01

One major effect of global climate change will be altered precipitation patterns in many regions of the world. This will cause a higher probability of long-term waterlogging in winter/spring and flash floods in summer because of extreme rainfall events. Particularly, trees not adapted at their natural site to such waterlogging stress can be impaired. Despite the enormous economic, ecological and social importance of forest ecosystems, the effect of waterlogging on trees is far less understood than the effect on many crops or the model plant Arabidopsis. There is only a handful of studies available investigating the transcriptome and metabolome of waterlogged trees. Main physiological responses of trees to waterlogging include the stimulation of fermentative pathways and an accelerated glycolytic flux. Many energy-consuming, anabolic processes are slowed down to overcome the energy crisis mediated by waterlogging. A crucial feature of waterlogging tolerance is the steady supply of glycolysis with carbohydrates, particularly in the roots; stress-sensitive trees fail to maintain sufficient carbohydrate availability resulting in the dieback of the stressed tissues. The present review summarizes physiological and molecular features of waterlogging tolerance of trees; the focus is on carbon metabolism in both, leaves and roots of trees. © 2014 John Wiley & Sons Ltd.

Determining significant endpoints for ecological risk analyses. 1997 annual progress report

Energy Technology Data Exchange (ETDEWEB)

Hinton, T.G.; Congdon, J.; Rowe, C.; Scott, D. [Univ. of Georgia, Aiken, SC (US). Savannah River Ecology Lab.; Bedford, J.; Whicker, F.W. [Colorado State Univ., Fort Collins, CO (US)

1997-11-01

'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses that reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'

Molecular sensors and molecular logic gates

International Nuclear Information System (INIS)

Georgiev, N.; Bojinov, V.

2013-01-01

Full text: The rapid grow of nanotechnology field extended the concept of a macroscopic device to the molecular level. Because of this reason the design and synthesis of (supra)-molecular species capable of mimicking the functions of macroscopic devices are currently of great interest. Molecular devices operate via electronic and/or nuclear rearrangements and, like macroscopic devices, need energy to operate and communicate between their elements. The energy needed to make a device work can be supplied as chemical energy, electrical energy, or light. Luminescence is one of the most useful techniques to monitor the operation of molecular-level devices. This fact determinates the synthesis of novel fluorescence compounds as a considerable and inseparable part of nanoscience development. Further miniaturization of semiconductors in electronic field reaches their limit. Therefore the design and construction of molecular systems capable of performing complex logic functions is of great scientific interest now. In semiconductor devices the logic gates work using binary logic, where the signals are encoded as 0 and 1 (low and high current). This process is executable on molecular level by several ways, but the most common are based on the optical properties of the molecule switches encoding the low and high concentrations of the input guest molecules and the output fluorescent intensities with binary 0 and 1 respectively. The first proposal to execute logic operations at the molecular level was made in 1988, but the field developed only five years later when the analogy between molecular switches and logic gates was experimentally demonstrated by de Silva. There are seven basic logic gates: AND, OR, XOR, NOT, NAND, NOR and XNOR and all of them were achieved by molecules, the fluorescence switching as well. key words: fluorescence, molecular sensors, molecular logic gates

Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

Science.gov (United States)

Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

2018-06-01

Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation

Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

Science.gov (United States)

Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

2015-03-01

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

Determinants of molecular marker based classification of rice (Oryza ...

African Journals Online (AJOL)

mr devi singh

2015-01-07

Jan 7, 2015 ... 1Molecular Biology Laboratory, Department of Genetics and Plant Breeding, SVP University of Agriculture and ... Basmati and non-Basmati rice adapted to different agro- ecological ..... acid soils in southern New South Wales?

Molecular sieving through a graphene nanopore: non-equilibrium molecular dynamics simulation

Institute of Scientific and Technical Information of China (English)

Chengzhen Sun; Bofeng Bai

2017-01-01

Two-dimensional graphene nanopores have shown great promise as ultra-permeable molecular sieves based on their size-sieving effects.We design a nitrogen/hydrogen modified graphene nanopore and conduct a transient non-equilibrium molecular dynamics simulation on its molecular sieving effects.The distinct time-varying molecular crossing numbers show that this special nanopore can efficiently sieve CO2 and H2S molecules from CH4 molecules with high selectivity.By analyzing the molecular structure and pore functionalization-related molecular orientation and permeable zone in the nanopore,density distribution in the molecular adsorption layer on the graphene surface,as well as other features,the molecular sieving mechanisms of graphene nanopores are revealed.Finally,several implications on the design of highly-efficient graphene nanopores,especially for determining the porosity and chemical functionalization,as gas separation membranes are summarized based on the identified phenomena and mechanisms.

Postprandial lipid responses to standard carbohydrates used to determine glycaemic index values.

Science.gov (United States)

Vega-López, Sonia; Ausman, Lynne M; Matthan, Nirupa R; Lichtenstein, Alice H

2013-11-01

Prior studies assessing the metabolic effects of different types of carbohydrates have focused on their glycaemic response. However, the response of postprandial cardiometabolic risk indicators has not been considered in these studies. The present study assessed postprandial lipid responses to two forms of carbohydrates used as reference foods for glycaemic index determinations, white bread (50 g available carbohydrate) and glucose (50 g), under controlled conditions and with intra-individual replicate determinations. A total of twenty adults (20–70 years) underwent two cycles of challenges with each pair of reference foods (four challenges/person), administered in a random order on separate days under standard conditions. Serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and NEFA), glucose and insulin were monitored for 5 h post-ingestion. Oral glucose resulted in greater glycaemic and insulinaemic responses than white bread for the first 90 min and a greater subsequent decline after 120 min (P =0·0001). The initial decline in serum NEFA concentrations was greater after the oral glucose than after the white bread challenge, as was the rebound after 150 min (P = 0·001). Nevertheless, the type of carbohydrate had no significant effect on postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. Following an initial modest rise in TAG concentrations in response to both challenges, the values dropped below the fasting values for oral glucose but not for the white bread challenge. These data suggest that the type of carbohydrate used to determine the glycaemic index, bread or glucose, has little or modest effects on postprandial plasma cholesterol concentrations. Differences in TAG and NEFA concentrations over the 5 h time period were modest, and their clinical relevance is unclear.

Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

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Sugimoto Yuka

2012-03-01

Full Text Available Abstract Background While lenalidomide (LEN shows high efficacy in myelodysplastic syndromes (MDS with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN, MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML without del[5q] by metaphase cytogenetics (MC who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH or single nucleotide polymorphism array (SNP-A-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8% additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08 and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11. However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.

Molecularly imprinted polymers based stir bar sorptive extraction for determination of cefaclor and cefalexin in environmental water.

Science.gov (United States)

Peng, Jun; Liu, Donghao; Shi, Tian; Tian, Huairu; Hui, Xuanhong; He, Hua

2017-07-01

Although stir bar sportive extraction was thought to be a highly efficiency and simple pretreatment approach, its wide application was limited by low selectivity, short service life, and relatively high cost. In order to improve the performance of the stir bar, molecular imprinted polymers and magnetic carbon nanotubes were combined in the present study. In addition, two monomers were utilized to intensify the selectivity of molecularly imprinted polymers. Fourier transform infrared spectroscopy, scanning electron microscopy, and selectivity experiments showed that the molecularly imprinted polymeric stir bar was successfully prepared. Then micro-extraction based on the obtained stir bar was coupled with HPLC for determination of trace cefaclor and cefalexin in environmental water. This approach had the advantages of stir bar sportive extraction, high selectivity of molecular imprinted polymers, and high sorption efficiency of carbon nanotubes. To utilize this pretreatment approach, pH, extraction time, stirring speed, elution solvent, and elution time were optimized. The LOD and LOQ of cefaclor were found to be 3.5 ng · mL -1 and 12.0 ng · mL -1 , respectively; the LOD and LOQ of cefalexin were found to be 3.0 ng · mL -1 and 10.0 ng · mL -1 , respectively. The recoveries of cefaclor and cefalexin were 86.5 ~ 98.6%. The within-run precision and between-run precision were acceptable (relative standard deviation bar did not decrease dramatically. This demonstrated that the molecularly imprinted polymeric stir bar based micro-extraction was a convenient, efficient, low-cost, and a specific method for enrichment of cefaclor and cefalexin in environmental samples.

Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery

Science.gov (United States)

Kwok, Connie Sau-Kuen

Nature in the form of DNA, proteins, and cells has the remarkable ability to interact with its environment by processing biological information through specific molecular recognition at the interface. As such, materials that are capable of triggering an appropriate biological response need to be engineered at the biomaterial surface. Chemically and structurally well-defined self-assembled monolayers (SAMs), biomimetics of the lipid bilayer in cell membranes, have been created and studied mostly on rigid metallic surfaces. This dissertation is motivated by the lack of methods to generate a molecularly designed surface for biomedical polymers and thus provides an enabling technology to engineer a polymeric surface precisely at a molecular and cellular level. To take this innovation one step further, we demonstrated that such self-assembled molecular structure coated on drug-containing polymeric devices could act as a stimulus-responsive barrier for controlled drug delivery. A simple, one-step procedure for generating ordered, crystalline methylene chains on polymeric surfaces via urethane linkages was successfully developed. The self-assemblies and molecular structures of these crystalline methylene chains are comparable to the SAM model surfaces, as evidenced by various surface characterization techniques (XPS, TOF-SIMS, and FTIR-ATR). For the first time, these self-assembled molecular structures are shown to function collectively as an ultrasound-responsive barrier membrane for pulsatile drug delivery, including delivery of low-molecular-weight ciprofloxacin and high-molecular-weight insulin. Encouraging results, based on the insulin-activated deoxyglucose uptakes in adipocytes, indicate that the released insulin remained biologically active. Both chemical and acoustic analyses suggest that the ultrasound-assisted release mechanism is primarily induced by transient cavitation, which causes temporary disruption of the self-assembled overlayer, and thus allows

Shock melting method to determine melting curve by molecular dynamics: Cu, Pd, and Al.

Science.gov (United States)

Liu, Zhong-Li; Zhang, Xiu-Lu; Cai, Ling-Cang

2015-09-21

A melting simulation method, the shock melting (SM) method, is proposed and proved to be able to determine the melting curves of materials accurately and efficiently. The SM method, which is based on the multi-scale shock technique, determines melting curves by preheating and/or prepressurizing materials before shock. This strategy was extensively verified using both classical and ab initio molecular dynamics (MD). First, the SM method yielded the same satisfactory melting curve of Cu with only 360 atoms using classical MD, compared to the results from the Z-method and the two-phase coexistence method. Then, it also produced a satisfactory melting curve of Pd with only 756 atoms. Finally, the SM method combined with ab initio MD cheaply achieved a good melting curve of Al with only 180 atoms, which agrees well with the experimental data and the calculated results from other methods. It turned out that the SM method is an alternative efficient method for calculating the melting curves of materials.

Detailed balance method for chemical potential determination in Monte Carlo and molecular dynamics simulations

International Nuclear Information System (INIS)

Fay, P.J.; Ray, J.R.; Wolf, R.J.

1994-01-01

We present a new, nondestructive, method for determining chemical potentials in Monte Carlo and molecular dynamics simulations. The method estimates a value for the chemical potential such that one has a balance between fictitious successful creation and destruction trials in which the Monte Carlo method is used to determine success or failure of the creation/destruction attempts; we thus call the method a detailed balance method. The method allows one to obtain estimates of the chemical potential for a given species in any closed ensemble simulation; the closed ensemble is paired with a ''natural'' open ensemble for the purpose of obtaining creation and destruction probabilities. We present results for the Lennard-Jones system and also for an embedded atom model of liquid palladium, and compare to previous results in the literature for these two systems. We are able to obtain an accurate estimate of the chemical potential for the Lennard-Jones system at higher densities than reported in the literature

Shock melting method to determine melting curve by molecular dynamics: Cu, Pd, and Al

International Nuclear Information System (INIS)

Liu, Zhong-Li; Zhang, Xiu-Lu; Cai, Ling-Cang

2015-01-01

A melting simulation method, the shock melting (SM) method, is proposed and proved to be able to determine the melting curves of materials accurately and efficiently. The SM method, which is based on the multi-scale shock technique, determines melting curves by preheating and/or prepressurizing materials before shock. This strategy was extensively verified using both classical and ab initio molecular dynamics (MD). First, the SM method yielded the same satisfactory melting curve of Cu with only 360 atoms using classical MD, compared to the results from the Z-method and the two-phase coexistence method. Then, it also produced a satisfactory melting curve of Pd with only 756 atoms. Finally, the SM method combined with ab initio MD cheaply achieved a good melting curve of Al with only 180 atoms, which agrees well with the experimental data and the calculated results from other methods. It turned out that the SM method is an alternative efficient method for calculating the melting curves of materials

High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

Science.gov (United States)

You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

2014-08-08

Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Responses to the Zika Virus in Mosquitoes

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Catalina Alfonso-Parra

2018-05-01

Full Text Available The Zika virus (ZIKV, originally discovered in 1947, did not become a major concern until the virus swept across the Pacific and into the Americas in the last decade, bringing with it news of neurological complications and birth defects in ZIKV affected areas. This prompted researchers to dissect the molecular interactions between ZIKV and the mosquito vector in an attempt to better understand not only the changes that occur upon infection, but to also identify molecules that may potentially enhance or suppress a mosquito’s ability to become infected and/or transmit the virus. Here, we review what is currently known regarding ZIKV-mosquito molecular interactions, focusing on ZIKV infection of Aedes aegypti and Aedes albopictus, the primary species implicated in transmitting ZIKV during the recent outbreaks.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

Science.gov (United States)

Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

Molecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera

Directory of Open Access Journals (Sweden)

Simões Zilá LP

2007-06-01

Full Text Available Abstract Background In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown. Results By using cDNA microarray analyses of >6,000 Apis mellifera ESTs, we found 240 differentially expressed genes (DEGs between developing queens and workers. Many genes recorded as up-regulated in prospective workers appear to be unique to A. mellifera, suggesting that the workers' developmental pathway involves the participation of novel genes. Workers up-regulate more developmental genes than queens, whereas queens up-regulate a greater proportion of physiometabolic genes, including genes coding for metabolic enzymes and genes whose products are known to regulate the rate of mass-transforming processes and the general growth of the organism (e.g., tor. Many DEGs are likely to be involved in processes favoring the development of caste-biased structures, like brain, legs and ovaries, as well as genes that code for cytoskeleton constituents. Treatment of developing worker larvae with juvenile hormone (JH revealed 52 JH responsive genes, specifically during the critical period of caste development. Using Gibbs sampling and Expectation Maximization algorithms, we discovered eight overrepresented cis-elements from four gene groups. Graph theory and complex networks concepts were adopted to attain powerful graphical representations of the interrelation between cis-elements and genes and objectively quantify the degree of relationship between these entities. Conclusion We suggest that clusters of functionally related

Molecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera.

Science.gov (United States)

Barchuk, Angel R; Cristino, Alexandre S; Kucharski, Robert; Costa, Luciano F; Simões, Zilá L P; Maleszka, Ryszard

2007-06-18

In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown. By using cDNA microarray analyses of >6,000 Apis mellifera ESTs, we found 240 differentially expressed genes (DEGs) between developing queens and workers. Many genes recorded as up-regulated in prospective workers appear to be unique to A. mellifera, suggesting that the workers' developmental pathway involves the participation of novel genes. Workers up-regulate more developmental genes than queens, whereas queens up-regulate a greater proportion of physiometabolic genes, including genes coding for metabolic enzymes and genes whose products are known to regulate the rate of mass-transforming processes and the general growth of the organism (e.g., tor). Many DEGs are likely to be involved in processes favoring the development of caste-biased structures, like brain, legs and ovaries, as well as genes that code for cytoskeleton constituents. Treatment of developing worker larvae with juvenile hormone (JH) revealed 52 JH responsive genes, specifically during the critical period of caste development. Using Gibbs sampling and Expectation Maximization algorithms, we discovered eight overrepresented cis-elements from four gene groups. Graph theory and complex networks concepts were adopted to attain powerful graphical representations of the interrelation between cis-elements and genes and objectively quantify the degree of relationship between these entities. We suggest that clusters of functionally related DEGs are co-regulated during caste development in honeybees

Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

LENUS (Irish Health Repository)

Tsang, J S

2014-07-28

In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

MOLECULARLY IMPRINTED POLYMER TECHNOLOGY: A ...

African Journals Online (AJOL)

dell

Cross-linking ensures polymer rigidity that “freezes” the 3-D molecular architecture of the binding cavity when the ... molecular technology applications whose potential is still .... recognition element is responsible for the selective ... organic treatments, making them superior ... efficiency with which such materials may be.

Determination of total sulfur in agricultural samples by high-resolution continuum source flame molecular absorption spectrometry.

Science.gov (United States)

Virgilio, Alex; Raposo, Jorge L; Cardoso, Arnaldo A; Nóbrega, Joaquim A; Gomes Neto, José A

2011-03-23

The usefulness of molecular absorption was investigated for the determination of total sulfur (S) in agricultural samples by high-resolution continuum source flame molecular absorption spectrometry. The lines for CS at 257.595, 257.958, and 258.056 nm and for SH at 323.658, 324.064, and 327.990 nm were evaluated. Figures of merit, such as linear dynamic range, sensitivity, linear correlation, characteristic concentration, limit of detection, and precision, were established. For selected CS lines, wavelength-integrated absorbance equivalent to 3 pixels, analytical curves in the 100-2500 mg L(-1) (257.595 nm), 250-2000 mg L(-1) (257.958 nm), and 250-5000 mg L(-1) (258.056 nm) ranges with a linear correlation coefficient better than 0.9980 were obtained. Results were in agreement at a 95% confidence level (paired t test) with those obtained by gravimetry. Recoveries of S in fungicide and fertilizer samples were within the 84-109% range, and the relative standard deviation (n=12) was typically <5%.

Determination of Flaw Size and Depth From Temporal Evolution of Thermal Response

Science.gov (United States)

Winfree, William P.; Zalameda, Joseph N.; Cramer, Elliott; Howell, Patricia A.

2015-01-01

Simple methods for reducing the pulsed thermographic responses of flaws have tended to be based on either the spatial or temporal response. This independent assessment limits the accuracy of characterization. A variational approach is presented for reducing the thermographic data to produce an estimated size for a flaw that incorporates both the temporal and spatial response to improve the characterization. The size and depth are determined from both the temporal and spatial thermal response of the exterior surface above a flaw and constraints on the length of the contour surrounding the delamination. Examples of the application of the technique to simulation and experimental data acquired are presented to investigate the limitations of the technique.

Determining ecoregional numeric nutrient criteria by stressor-response models in Yungui ecoregion lakes, China.

Science.gov (United States)

Huo, Shouliang; Ma, Chunzi; Xi, Beidou; Tong, Zhonghua; He, Zhuoshi; Su, Jing; Wu, Fengchang

2014-01-01

The importance of developing numeric nutrient criteria has been recognized to protect the designated uses of water bodies from nutrient enrichment that is associated with broadly occurring levels of nitrogen/phosphorus pollution. The identification and estimation of stressor-response models in aquatic ecosystems has been shown to be useful in the determination of nutrient criteria. In this study, three methods based on stressor-response relationships were applied to determine nutrient criteria for Yungui ecoregion lakes with respect to total phosphorus (TP), total nitrogen (TN), and planktonic chlorophyll a (Chl a). Simple linear regression (SLR) models were established to provide an estimate of the relationship between a response variable and a stressor. Multiple linear regressions were used to simultaneously estimate the effect of TP and TN on Chl a. A morphoedaphic index (MEI) was applied to derive nutrient criteria using data from Yungui ecoregion lakes, which were considered as areas with less anthropogenic influences. Nutrient criteria, as determined by these three methods, showed broad agreement for all parameters. The ranges of numeric nutrient criteria for Yungui ecoregion lakes were determined as follows: TP 0.008-0.010 mg/L and TN 0.140-0.178 mg/L. The stressor-response analysis described will be of benefit to support countries in their numeric criteria development programs and to further the goal of reducing nitrogen/phosphorus pollution in China.

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies

Science.gov (United States)

Bardhan, Jaydeep P.; Jungwirth, Pavel; Makowski, Lee

2012-01-01

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular “linear response” model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution). PMID:23020318

Fabrication of Thermo-Responsive Molecular Layers from Self-Assembling Elastin-Like Oligopeptides Containing Cell-Binding Domain for Tissue Engineering

Directory of Open Access Journals (Sweden)

Tomoyuki Koga

2015-01-01

Full Text Available Novel thermo-responsive elastin-like oligopeptides containing cell-binding epitope (Arg-Gly-Asp-Ser sequence; arginine-glycine-aspartic acid-serine (RGDS-elastin-like peptides (ELP and RGDS-deg-ELP; were newly prepared as building blocks of self-assembled molecular layer for artificial extra cellular matrix. A detailed analysis of the conformation of the oligo(ELPs in water and their self-assembling behavior onto hydrophobic surfaces were performed by using circular dichroism, Fourier transform infrared spectroscopy (FTIR, atomic force microscopy and water contact angle measurements. The experimental results revealed that both oligo(ELPs self-assembled onto hydrophobic surfaces and formed molecular layers based on their thermo-responsive conformational change from hydrous random coil to dehydrated β-turn structure. Effective cell adhesion and spreading behaviors were observed on these self-assembled oligo(ELP layers. In addition, attached cells were found to be recovered successfully as a cell-sheet by temperature-induced disassembly of oligo(ELP layer. This achievement provides an important insight to construct novel oligopeptide-based nano-surfaces for the design of smart artificial extra-cellular matrix.

The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

Directory of Open Access Journals (Sweden)

Matthias Stein

Full Text Available Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

Molecular Detection of Antimicrobial Resistance

Science.gov (United States)

Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

2001-01-01

The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

Application of molecular simulations: Insight into liquid bridging and jetting phenomena

Directory of Open Access Journals (Sweden)

I. Nezbeda

2015-03-01

Full Text Available Molecular dynamics simulations have been performed on pure liquid water, aqueous solutions of sodium chloride, and polymer solutions exposed to a strong external electric field with the goal to gain molecular insight into the structural response to the field. Several simulation methodologies have been used to elucidate the molecular mechanisms of the processes leading to the formation of liquid bridges and jets (in the production of nanofibers. It is shown that in the established nanoscale structures, the molecules form a chain with their dipole moments oriented parallel to the applied field throughout the entire sample volume. The presence of ions may disturb this structure leading to its ultimate disintegration into droplets; the concentration dependence of the threshold field required to stabilize a liquid column has been determined. Conformational changes of the polymer in the jetting process have also been observed.

Detect the sensitivity and response of protein molecular structure of whole canola seed (yellow and brown) to different heat processing methods and relation to protein utilization and availability using ATR-FT/IR molecular spectroscopy with chemometrics.

Science.gov (United States)

Samadi; Theodoridou, Katerina; Yu, Peiqiang

2013-03-15

The objectives of this experiment were to detect the sensitivity and response of protein molecular structure of whole canola seed to different heat processing [moisture (autoclaving) vs. dry (roasting) heating] and quantify heat-induced protein molecular structure changes in relation to protein utilization and availability. In this study, whole canola seeds were autoclaved (moisture heating) and dry (roasting) heated at 120 °C for 1h, respectively. The parameters assessed included changes in (1) chemical composition profile, (2) CNCPS protein subfractions (PA, PB1, PB2, PB3, PC), (3) intestinal absorbed true protein supply, (4) energy values, and (5) protein molecular structures (amide I, amide II, ratio of amide I to II, α-helix, β-sheet, ratio of α-helix to β-sheet). The results showed that autoclave heating significantly decreased (Pseed. Future study is needed to study response and impact of heat processing to each inherent layer of canola seed from outside to inside tissues and between yellow canola and brown canola. Copyright © 2012 Elsevier B.V. All rights reserved.

Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus

DEFF Research Database (Denmark)

Scapigliati, G.; Buonocore, F.; Randelli, E.

2010-01-01

and acquired responses: type I IFN, Mx, IL-1, Cox-2; IL-10, TGF-β, TCRβ, CD4, CD8α, IgM, by using a quantitative PCR array system developed for sea bass. The obtained results showed a detectable increase of T cells and B cells in PBL during betanodavirus infection. Furthermore, leucocytes obtained from blood...... was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus....

Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

DEFF Research Database (Denmark)

Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

2008-01-01

Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromos...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy

International Nuclear Information System (INIS)

Ramesh, V.; McClatchey, A.I.; Ramesh, N.; Benoit, L.A.; Berson, E.L.; Shih, V.E.; Gusella, J.F.

1988-01-01

Gyrate atrophy (GA), a recessive eye disease involving progressive loss of vision due to chorioretinal degeneration, is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase with consequent hyperornithinemia. Genetic heterogeneity of GA has been suggested by the demonstration that administration of pyridoxine to increase the level of pyridoxal phosphate, a cofactor of OATase, reduces hyperornithinemia in a subset of patients. The authors have cloned and sequences cDNAs for OATase from two GA patients, one responsive and one nonresponsive to pyridoxine treatment. The respective cDNAs contained different single missense mutations, which were sufficient to eliminate OATase activity when each cDNA was tested in a eukaryotic expression system. However, like the enzyme in fibroblasts from the pyridoxine-responsive patient, OATase encoded by the corresponding cDNA from this individual showed a significant increase in activity when assayed in the presence of an increased pyridoxal phosphate concentration. These data firmly establish that both pyridoxine responsive and nonresponsive forms of GA result from mutations in the OATase structural gene. Moreover, they provide a molecular characterization of the primary lesion in a pyridoxine-responsive genetic disorder

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

International Nuclear Information System (INIS)

Zhu, Aizhi; Shim, Hyunsuk

2011-01-01

Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with noninvasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18F fluorodeoxyglucose ( 18F FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18F FDG is not a tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non 18F FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor specific antigens and surface receptors

In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

Directory of Open Access Journals (Sweden)

Ryohei Miyazaki

Full Text Available Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs and anaplastic lymphoma kinase (ALK inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI test and collagen gel droplet embedded culture drug sensitivity test (CD-DST are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.HCC827 (Exon19: E746-A750 del and H3122 (EML4-ALK cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003. The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026 in CD-DST.In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

Science.gov (United States)

Hoang, Nam S; Ge, Benjamin H; Pan, Lorraine Y; Ozawa, Michael G; Kong, Christina S; Louie, John D; Shah, Rajesh P

2018-03-01

The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Determinants of abnormal blood pressure response to exercise in coronary artery disease

International Nuclear Information System (INIS)

Hakki, A.H.; Munley, B.M.; Hadjimiltiades, S.; Meissner, M.D.; Iskandrian, A.S.

1986-01-01

This study assessed the determinants of exercise-induced abnormal systolic blood pressure (BP) response in 127 patients with documented coronary artery disease (CAD) who underwent exercise thallium-201 scintigraphy. Three types of systolic BP response to exercise were identified: an increase by more than 20 mm Hg (group I, n = 74); an increase by 20 mm Hg or less (group II, n = 36); and a decrease of at least 10 mm Hg (group III, n = 17). The 3 groups were not significantly different in age, gender or medications. The number of segments with perfusion defects was significantly higher in groups II and III than group I (group III, 2.9 +/- 1.5; group II, 2.9 +/- 2.1; and group I, 1.8 +/- 1.4, p = 0.009). Prior myocardial infarction, abnormal left ventricular ejection fraction, and multivessel CAD were more common in group III than in groups I and II. Stepwise discriminant analysis of 15 relevant clinical, angiographic and exercise scintigraphic descriptors showed that the number of thallium perfusion defects, abnormal LV ejection fraction at rest and multivessel CAD to be important predictors of hypotensive BP response. Multivariate analysis, however, showed that the number of thallium perfusion defects was the only important predictor of the hypotensive response. Thus, it is the functional significance of CAD assessed by the extent of thallium perfusion abnormalities rather than the extent of CAD or left ventricular dysfunction at rest that determines the systolic BP response to exercise

Determination of fusaric acid in maize using molecularly imprinted SPE clean-up

Science.gov (United States)

A new liquid chromatography method to detect fusaric acid in maize is reported based on molecularly imprinted polymer solid phase extraction clean-up (MISPE) using mimic-templated molecularly-imprinted polymers. Picolinic acid was used as a toxin analog for imprinting polymers during a thermolytic s...

Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

Science.gov (United States)

Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

2016-01-01

Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

Interplay of single particle and collective response in molecular dynamics simulation of dusty plasma system

Science.gov (United States)

Maity, Srimanta; Das, Amita; Kumar, Sandeep; Tiwari, Sanat Kumar

2018-04-01

The collective response of the plasma medium is well known and has been explored extensively in the context of dusty plasma medium. On the other hand, the individual particle response associated with the collisional character giving rise to the dissipative phenomena has not been explored adequately. In this paper, two-dimensional molecular dynamics simulation of dust particles interacting via Yukawa potential has been considered. It has been shown that disturbances induced in a dust crystal elicit both collective and single particle responses. Generation of a few particles moving at speeds considerably higher than acoustic and/or shock speed (excited by the external disturbance) is observed. This is an indication of a single particle response. Furthermore, as these individual energetic particles propagate, the dust crystal is observed to crack along their path. Initially when the energy is high, these particles generate secondary energetic particles by the collisional scattering process. However, ultimately as these particles slow down they excite a collective response in the dust medium at secondary locations in a region which is undisturbed by the primary external disturbance. The condition when the cracking of the crystal stops and collective excitations get initiated has been identified quantitatively. The trailing collective primary disturbances would thus often encounter a disturbed medium with secondary and tertiary collective perturbations, thereby suffering significant modification in its propagation. It is thus clear that there is an interesting interplay (other than mere dissipation) between the single particle and collective response which governs the dynamics of any disturbance introduced in the medium.

Biogastronomy: Factors that determine the biological response to meal ingestion.

Science.gov (United States)

Pribic, T; Azpiroz, F

2018-02-02

The biological response to a meal includes physiological changes, primarily related to the digestive process, and a sensory experience, involving sensations related to the homeostatic control of food consumption, eg, satiety and fullness, with a hedonic dimension, ie associated with changes in digestive well-being and mood. The responses to a meal include a series of events before, during and after ingestion. While much attention has been paid to the events before and during ingestion, relatively little is known about the postprandial sensations, which are key to the gastronomical experience. The aim of this narrative review is to provide a comprehensive overview and to define the framework to investigate the factors that determine the postprandial experience. Based on a series of proof-of-concept studies and related information, we propose that the biological responses to a meal depend on the characteristics of the meal, primarily its palatability and composition, and the responsiveness of the guest, which may be influenced by multiple previous and concurrent conditioning factors. This information provides the scientific backbone to the development of personalized gastronomy. © 2018 John Wiley & Sons Ltd.

Nickel and binary metal mixture responses in Daphnia magna: Molecular fingerprints and (sub)organismal effects

International Nuclear Information System (INIS)

Vandenbrouck, Tine; Soetaert, Anneleen; Ven, Karlijn van der; Blust, Ronny; Coen, Wim de

2009-01-01

The recent development of a custom cDNA microarray platform for one of the standard organisms in aquatic toxicology, Daphnia magna, opened up new ways to mechanistic insights of toxicological responses. In this study, the mRNA expression of several genes and (sub)organismal responses (Cellular Energy Allocation, growth) were assayed after short-term waterborne metal exposure. Microarray analysis of Ni-exposed daphnids revealed several affected functional gene classes, of which the largest ones were involved in different metabolic processes (mainly protein and chitin related processes), cuticula turnover, transport and signal transduction. Furthermore, transcription of genes involved in oxygen transport and heme metabolism (haemoglobin, δ-aminolevilunate synthase) was down-regulated. Applying a Partial Least Squares regression on nickel fingerprints and biochemical (sub)organismal parameters revealed a set of co-varying genes (haemoglobin, RNA terminal phosphate cyclase, a ribosomal protein and an 'unknown' gene fragment). An inverse relationship was seen between the mRNA expression levels of different cuticula proteins and available energy reserves. In addition to the nickel exposure, daphnids were exposed to binary mixtures of nickel and cadmium or nickel and lead. Using multivariate analysis techniques, the mixture mRNA expression fingerprints (Ni 2+ + Cd 2+ , Ni 2+ + Pb 2+ ) were compared to those of the single metal treatments (Ni 2+ , Cd 2+ , Pb 2+ ). It was hypothesized that the molecular fingerprints of the mixtures would be additive combinations of the gene transcription profiles of the individual compounds present in the mixture. However, our results clearly showed additionally affected pathways after mixture treatment (e.g. additional affected genes involved in carbohydrate catabolic processes and proteolysis), indicating interactive molecular responses which are not merely the additive sum of the individual metals. These findings, although indicative of

Molecular Determinants of Mutant Phenotypes, Inferred from Saturation Mutagenesis Data.

Science.gov (United States)

Tripathi, Arti; Gupta, Kritika; Khare, Shruti; Jain, Pankaj C; Patel, Siddharth; Kumar, Prasanth; Pulianmackal, Ajai J; Aghera, Nilesh; Varadarajan, Raghavan

2016-11-01

Understanding how mutations affect protein activity and organismal fitness is a major challenge. We used saturation mutagenesis combined with deep sequencing to determine mutational sensitivity scores for 1,664 single-site mutants of the 101 residue Escherichia coli cytotoxin, CcdB at seven different expression levels. Active-site residues could be distinguished from buried ones, based on their differential tolerance to aliphatic and charged amino acid substitutions. At nonactive-site positions, the average mutational tolerance correlated better with depth from the protein surface than with accessibility. Remarkably, similar results were observed for two other small proteins, PDZ domain (PSD95 pdz3 ) and IgG-binding domain of protein G (GB1). Mutational sensitivity data obtained with CcdB were used to derive a procedure for predicting functional effects of mutations. Results compared favorably with those of two widely used computational predictors. In vitro characterization of 80 single, nonactive-site mutants of CcdB showed that activity in vivo correlates moderately with thermal stability and solubility. The inability to refold reversibly, as well as a decreased folding rate in vitro, is associated with decreased activity in vivo. Upon probing the effect of modulating expression of various proteases and chaperones on mutant phenotypes, most deleterious mutants showed an increased in vivo activity and solubility only upon over-expression of either Trigger factor or SecB ATP-independent chaperones. Collectively, these data suggest that folding kinetics rather than protein stability is the primary determinant of activity in vivo This study enhances our understanding of how mutations affect phenotype, as well as the ability to predict fitness effects of point mutations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Molecular Mechanism and Genetic Determinants of Buprofezin Degradation

OpenAIRE

Chen, Xueting; Ji, Junbin; Zhao, Leizhen; Qiu, Jiguo; Dai, Chen; Wang, Weiwu; He, Jian; Jiang, Jiandong; Hong, Qing; Yan, Xin

2017-01-01

Buprofezin is a widely used insect growth regulator whose residue has been frequently detected in the environment, posing a threat to aquatic organisms and nontarget insects. Microorganisms play an important role in the degradation of buprofezin in the natural environment. However, the relevant catabolic pathway has not been fully characterized, and the molecular mechanism of catabolism is still completely unknown. Rhodococcus qingshengii YL-1 can utilize buprofezin as a sole source of carbon...

Photo-cured pH-responsive polyampholyte-coated membranes for controlled release of drugs with different molecular weights and charges

International Nuclear Information System (INIS)

Ng, Loo-Teck; Ng, Kheng-Seong

2008-01-01

Intelligent drug delivery membranes were synthesised by photocuring poly(acrylic acid) (PAA) or polyampholytes comprised of copolymers of acrylic acid (AA)/2-(diethylamino)ethyl methacrylate (DEAEMA) with varying monomeric compositions onto poly(2-hydroxyethyl methacrylate) (PHEMA) membranes, each with model drugs of different molecular weights and charges being incorporated. pH-responsive release behaviours of the model drugs which included methylene blue (cationic), metanil yellow (anionic) and caffeine (neutral) were studied. Only membranes with methylene blue and caffeine incorporated displayed clear pH-responsive releases though all coatings. This study demonstrates that drug diffusion through pH-responsive membranes depends to a large extent on the attractive interaction between the drug and the appropriate functional group/s in the coating

Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

Science.gov (United States)

Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

2009-06-09

Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

A General Method for Determining Molecular Interfaces and Layers.

Czech Academy of Sciences Publication Activity Database

Škvor, J.; Škvára, J.; Jirsák, Jan; Nezbeda, Ivo

2017-01-01

Roč. 76, SEP 2017 (2017), s. 17-35 ISSN 1093-3263 R&D Projects: GA ČR GA15-19542S Institutional support: RVO:67985858 Keywords : interface * molecular layers * percolating cluster Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 1.754, year: 2016

A molecularly imprinted electrochemiluminescence sensor based on the mimetic enzyme catalytic effect for ultra-trace Ni2+ determination.

Science.gov (United States)

Yang, Bin; Li, Jianping; Zhang, Lianming; Xu, Guobao

2016-10-21

A novel molecularly imprinted polymer (MIP) electrochemiluminescence (MIP-ECL) sensor was developed for the highly sensitive and selective determination of ultra-trace levels of Ni 2+ . The complex Ni 2+ -dimethylglyoxime (Ni-DMG) was chosen as the template molecule to construct the MIP and then acted as a mimetic enzyme to catalyse the oxidisation of luminol to enhance the ECL signal. When the imprinted cavities were occupied by Ni-DMG in the rebinding process, the ECL intensities produced by the luminol-H 2 O 2 ECL system on the MIP-modified electrode surface increased with increased concentration of the Ni-DMG complex. The highly sensitive determination of Ni 2+ was achieved through a catalytic reaction. This technique could be used for the quantitative analysis of Ni 2+ with concentrations from 3.0 × 10 -12 mol L -1 to 6.0 × 10 -9 mol L -1 . The detection limit was 1.01 × 10 -12 mol L -1 , which is much lower than that reported previously. In addition, the allowable amounts of interference ions in the MIP-ECL sensor were higher than that in other common molecularly imprinted sensors because of its excellent recognition of 3D cavity-to-complex molecules and ligand-to-metal ions. This method was successfully used to determine Ni 2+ in real samples, such as apples, carrots and grapes, and has been proven feasible for practical applications.

Stress and its molecular consequences in cancer progression

Directory of Open Access Journals (Sweden)

Magdalena Surman

2017-06-01

Full Text Available Stress, caused by psychological, physiological and physical factors has an adverse impact on human body homeostasis. There are two kind of stress: short-term and chronic. Cancer patients usually live under chronic stress, caused by diagnosis-related strong emotional experience and depression, resulting from various difficulties associated with disease progression and treatment. At the molecular level, stress factors induce production and secretion of stress-related hormones, such as catecholamines, glucocorticoids and dopamine (as a part of adaptational body response, which influence both normal and transformed cells through their specific receptors. The particular effects exerted by these molecules on cancer cells have been also observed in in vitro cultures and include changes in proliferation, apoptosis susceptibility and migration/invasion potential. As a result, it has been suggested that stress hormones may be responsible for progression of malignancy and thus accelerate the metastasis formation in cancer patients. However, the clinical data on correlation between stress and the patients survival, as well as the molecular analysis of stress hormone receptors expression and action in cancer cell, have not yet provided an unequivocal answer. For this reason, extensive studies, on molecular and clinical level are needed to fully determine stress impact on cancerprogression and on the effectiveness of anti-cancer treatment. Nowadays, it seems reasonable that the personalization of anti-cancer therapy should also focus on mental state of cancer patients, and provide them with psychological tools or techniques for stress management.

Comparative study for methods to determine the seismic response of NPP structures

International Nuclear Information System (INIS)

Varpasuo, P.

1995-01-01

There are many different important problem areas in evaluating the seismic response of structures. In this study the effort is concentrated on three of these areas. The first task is the mathematical formulation of earthquake excitation. The random vibration theory is taken as the tool in this task. The second area of interest in this study is the soil-structure interaction analysis. The approach of impedance functions is chosen and the focal point of interest is the significance of frequency dependent impedance functions. The third area of interest is the methods to determine the structural response. The following three methods were tested: the mode superposition time history method; the complex frequency response method; the response spectrum method. The comparison was made with the aid of MSC/NASTRAN code. The three methods gave for outer containment building response results which were in good agreement with each other. (author). 4 refs., 5 figs

Molecular genetic gene-environment studies using candidate genes in schizophrenia: a systematic review.

Science.gov (United States)

Modinos, Gemma; Iyegbe, Conrad; Prata, Diana; Rivera, Margarita; Kempton, Matthew J; Valmaggia, Lucia R; Sham, Pak C; van Os, Jim; McGuire, Philip

2013-11-01

The relatively high heritability of schizophrenia suggests that genetic factors play an important role in the etiology of the disorder. On the other hand, a number of environmental factors significantly influence its incidence. As few direct genetic effects have been demonstrated, and there is considerable inter-individual heterogeneity in the response to the known environmental factors, interactions between genetic and environmental factors may be important in determining whether an individual develops the disorder. To date, a considerable number of studies of gene-environment interactions (G×E) in schizophrenia have employed a hypothesis-based molecular genetic approach using candidate genes, which have led to a range of different findings. This systematic review aims to summarize the results from molecular genetic candidate studies and to review challenges and opportunities of this approach in psychosis research. Finally, we discuss the potential of future prospects, such as new studies that combine hypothesis-based molecular genetic candidate approaches with agnostic genome-wide association studies in determining schizophrenia risk. © 2013 Elsevier B.V. All rights reserved.

Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins

DEFF Research Database (Denmark)

Rougier, Jean-Sébastien; van Bemmelen, Miguel X; Bruce, M Christine

2004-01-01

-ubiquitin ligases of the Nedd4 family. We recently reported that cardiac Na(v)1.5 is regulated by Nedd4-2. In this study, we further investigated the molecular determinants of regulation of Na(v) proteins. When expressed in HEK-293 cells and studied using whole cell voltage clamping, the neuronal Na(v)1.2 and Na...... that Nedd4-dependent ubiquitination of Na(v) channels may represent a general mechanism regulating the excitability of neurons and myocytes via modulation of channel density at the plasma membrane....

Light and Redox Switchable Molecular Components for Molecular Electronics

NARCIS (Netherlands)

Browne, Wesley R.; Feringa, Bernard

2010-01-01

The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen

Reliability-based design methods to determine the extreme response distribution of offshore wind turbines

NARCIS (Netherlands)

Cheng, P.W.; Bussel, van G.J.W.; Kuik, van G.A.M.; Vugts, J.H.

2003-01-01

In this article a reliability-based approach to determine the extreme response distribution of offshore wind turbines is presented. Based on hindcast data, the statistical description of the offshore environment is formulated. The contour lines of different return periods can be determined.

Nematic liquid crystal in a cylindrical sample: Theoretical analysis of the electrical response

Science.gov (United States)

Gomes, O. A.; Yednak, C. A. R.; da Silva, B. V. H. V.; Teixeira-Souza, R. T.

2018-02-01

The electrical responses of a nematic liquid crystal sample confined between two cylindrical surfaces are investigated in the framework of elastic continuum theory. The responses are the result of the molecular reorientation induced by both the applied electric field and the cylindrical geometry of the sample. The nematic medium is considered as a parallel RC circuit since the capacitance and the resistance are under the same difference of potential. The electrical properties, including the total electric current, are determined from the molecular reorientation of the director. The elastic anisotropy has been shown to influence substantially the profile of the electrical current, capacitance, and resistance characterizing the equivalent circuit for the medium.

Computation-Assisted Molecularly Imprinted Polymer Synthesis for Extraction of Naltrexone from Urine Using Experimental Design and Determination by UPLC-DAD.

Science.gov (United States)

Rahmani, Mahdiyeh Ebrahimi; Ansari, Mehdi; Nateghi, Mohammadreza; Kazemipour, Maryam

2017-05-01

To design a molecularly imprinted polymer (MIP) for naltrexone, calculations were performed using Gaussian 03 software, and the interaction energy (ΔE) of template-monomer complexes was estimated using the density functional theory method with the B3LYP function and 6-311G (d) basis set. The effect of different solvents in the polymerization process was studied using the polarizable continuum model. It was shown that five molecules of methacrylic acid gave the largest ΔE with tetrahydrofuran as the polymerization solvent. Effective factors of the removal efficiency of naltrexone by the MIP were selected using a central composite design, and thereafter, the optimization of significant factors was performed by response surface methodology. The results predicted through these models showed good agreement with experimental values. The adsorption amount, selectivity distribution coefficient, and selectivity coefficient were found to be 11.60 mg/g, 35.31, and 2.27, respectively. Experiments of naltrexone adsorption onto the MIP were in accordance with the first-order and Langmuir-Freundlich adsorption models. By applying the data to the Scatchard equation, the KD and Qmax were determined as 526.31 mg/L and 19.47 mg/g, respectively.

A screen-printed carbon electrode modified with gold nanoparticles, poly(3,4-ethylenedioxythiophene), poly(styrene sulfonate) and a molecular imprint for voltammetric determination of nitrofurantoin.

Science.gov (United States)

Dechtrirat, Decha; Yingyuad, Peerada; Prajongtat, Pongthep; Chuenchom, Laemthong; Sriprachuabwong, Chakrit; Tuantranont, Adisorn; Tang, I-Ming

2018-04-23

A molecularly imprinted polymer (MIP) and a nanocomposite prepared from gold nanoparticles (AuNP) and poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) (PEDOT:PSS) were deposited on a screen-printed carbon electrode (SPCE). The nanocomposite was prepared by one-pot simultaneous in-situ formation of AuNPs and PEDOT:PSS and was then inkjet-coated onto the SPCE. The MIP film was subsequently placed on the modified SPCE by co-electrodeposition of o-phenylenediamine and resorcinol in the presence of the antibiotic nitrofurantoin (NFT). Using differential pulse voltammetry (DPV), response at the potential of ~ 0.1 V (vs. Ag/AgCl) is linear in 1 nM to 1000 nM NFT concentration range, with a remarkably low detection limit (at S/N = 3) of 0.1 nM. This is two orders of magnitude lower than that of the control MIP sensor without the nanocomposite interlayer, thus showing the beneficial effect of AuNP-PEDOT:PSS. The electrode is highly reproducible (relative standard deviation 3.1% for n = 6) and selective over structurally related molecules. It can be re-used for at least ten times and was found to be stable for at least 45 days. It was successfully applied to the determination of NFT in (spiked) feed matrices and gave good recoveries. Graphical abstract Schematic representation of a voltammetric sensor for the determination of nitrofurantoin. The sensor is based on a screen-printed carbon electrode (SPCE) modified with an inkjet-printed gold nanoparticles-poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) nanocomposite and a molecularly imprinted polymer.

Determination of the protonation state of the Asp dyad: conventional molecular dynamics versus thermodynamic integration.

Science.gov (United States)

Huang, Jinfeng; Zhu, Yali; Sun, Bin; Yao, Yuan; Liu, Junjun

2016-03-01

The protonation state of the Asp dyad is important as it can reveal enzymatic mechanisms, and the information this provides can be used in the development of drugs for proteins such as memapsin 2 (BACE-1), HIV-1 protease, and rennin. Conventional molecular dynamics (MD) simulations have been successfully used to determine the preferred protonation state of the Asp dyad. In the present work, we demonstrate that the results obtained from conventional MD simulations can be greatly influenced by the particular force field applied or the values used for control parameters. In principle, free-energy changes between possible protonation states can be used to determine the protonation state. We show that protonation state prediction by the thermodynamic integration (TI) method is insensitive to force field version or to the cutoff for calculating nonbonded interactions (a control parameter). In the present study, the protonation state of the Asp dyad predicted by TI calculations was the same regardless of the force field and cutoff value applied. Contrary to the intuition that conventional MD is more efficient, our results clearly show that the TI method is actually more efficient and more reliable for determining the protonation state of the Asp dyad.

Molecularly imprinted polymer-based bulk optode for the determination of itopride hydrochloride in physiological fluids.

Science.gov (United States)

Abdel-Haleem, F M; Madbouly, Adel; El Nashar, R M; Abdel-Ghani, N T

2016-11-15

We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1×10(-1)-1×10(-4)molL(-1). In comparison to the optode containing the ion exchanger only (Miptode 3), the optode containing the ion exchanger and the MIP particles (Miptode 2) showed improved selectivity over the most lipophilic species, Na(+) and K(+), by more than two orders of magnitude. For instance, the optical selectivity coefficients using Miptode 2, [Formula: see text] , were as follow: NH4(+)˂-6; Na(+)=-4.0, which were greatly enhanced in comparison with that obtained by Miptode 3. This work opens a new avenue for using miptodes for the determination of all the pharmaceutical preparations without the need for the development of new ionophores. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of molecular monitoring and response milestone of patients with chronic myeloid leukemia to tyrosine kinase inhibitors in Middle Euphrates of Iraq

Directory of Open Access Journals (Sweden)

Rahem M Rahem

2016-01-01

Conclusion: Most of our patients achieved major molecular response after 12 months of treatment with TKI according to the ELN guidelines that reflect proper management and regular follow-up of the patients by quantitative RT-PCR for the detection of BCR-ABL level.

Baseline blood immunological profiling differentiates between Her2-breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response.

Science.gov (United States)

Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Lisencu, Carmen; Fetica, Bogdan; Gherman, Claudia; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

2015-01-01

Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.

Photoresponsive molecularly imprinted hydrogel casting membrane for the determination of trace tetracycline in milk.

Science.gov (United States)

Wang, Qiang; Lv, Zhen; Tang, Qian; Gong, Cheng-Bin; Lam, Michael Hon Wah; Ma, Xue-Bing; Chow, Cheuk-Fai

2016-03-01

This study aimed to develop a photoresponsive molecularly imprinted hydrogel (MIH) casting membrane for the determination of trace tetracycline (TC) in milk. This MIH casting membrane combined the specificity of MIHs, the photoresponsive properties of azobenzene, and the portable properties of a membrane. Photoresponsive TC-imprinted MIHs were initially fabricated and then cast on sodium dodecyl sulfonate polyacrylamide gel. After TC removal, a photoresponsive MIH casting membrane was obtained. The photoresponsive properties of the MIH casting membrane were robust, and no obvious photodegradation was observed after 20 cycles. The MIH casting membrane displayed specific affinity to TC upon alternate irradiation at 365 and 440 nm; it could quantitatively uptake and release TC. The TC concentration (0.0-2.0 × 10(-4) mol l(-1)) in aqueous solution displayed a linear relationship with the photoisomerization rate constant of azobenzene within the MIH casting membrane. As such, a quick detection method for trace TC in aqueous foodstuff samples was established. The recovery of this method for TC in milk was investigated with a simple pretreatment of milk, and a high recovery of 100.54-106.35% was obtained. Therefore, the fabricated membrane can be used as a portable molecular sensor that can be easily recycled. Copyright © 2015 John Wiley & Sons, Ltd.

Analysis of Time Reversible Born-Oppenheimer Molecular Dynamics

Directory of Open Access Journals (Sweden)

Lin Lin

2013-12-01

Full Text Available We analyze the time reversible Born-Oppenheimer molecular dynamics (TRBOMD scheme, which preserves the time reversibility of the Born-Oppenheimer molecular dynamics even with non-convergent self-consistent field iteration. In the linear response regime, we derive the stability condition, as well as the accuracy of TRBOMD for computing physical properties, such as the phonon frequency obtained from the molecular dynamics simulation. We connect and compare TRBOMD with Car-Parrinello molecular dynamics in terms of accuracy and stability. We further discuss the accuracy of TRBOMD beyond the linear response regime for non-equilibrium dynamics of nuclei. Our results are demonstrated through numerical experiments using a simplified one-dimensional model for Kohn-Sham density functional theory.

Response of the seagrass Posidonia oceanica to different light environments: Insights from a combined molecular and photo-physiological study.

Science.gov (United States)

Dattolo, E; Ruocco, M; Brunet, C; Lorenti, M; Lauritano, C; D'Esposito, D; De Luca, P; Sanges, R; Mazzuca, S; Procaccini, G

2014-10-01

Here we investigated mechanisms underlying the acclimation to light in the marine angiosperm Posidonia oceanica, along its bathymetric distribution (at -5 m and -25 m), combining molecular and photo-physiological approaches. Analyses were performed during two seasons, summer and autumn, in a meadow located in the Island of Ischia (Gulf of Naples, Italy), where a genetic distinction between plants growing above and below the summer thermocline was previously revealed. At molecular level, analyses carried out using cDNA-microarray and RT-qPCR, revealed the up-regulation of genes involved in photoacclimation (RuBisCO, ferredoxin, chlorophyll binding proteins), and photoprotection (antioxidant enzymes, xanthophyll-cycle related genes, tocopherol biosynthesis) in the upper stand of the meadow, indicating that shallow plants are under stressful light conditions. However, the lack of photo-damage, indicates the successful activation of defense mechanisms. This conclusion is also supported by several responses at physiological level as the lower antenna size, the higher number of reaction centers and the higher xanthophyll cycle pigment pool, which are common plant responses to high-light adaptation/acclimation. Deep plants, despite the lower available light, seem to be not light-limited, thanks to some shade-adaptation strategies (e.g. higher antenna size, lower Ek values). Furthermore, also at the molecular level there were no signs of stress response, indicating that, although the lower energy available, low-light environments are more favorable for P. oceanica growth. Globally, results of whole transcriptome analysis displayed two distinct gene expression signatures related to depth distribution, reflecting the different light-adaptation strategies adopted by P. oceanica along the depth gradient. This observation, also taking into account the genetic disjunction of clones along the bathymetry, might have important implications for micro-evolutionary processes

Molecular identification of Cryptosporidium spp. in seagulls, pigeons, dogs, and cats in Thailand

OpenAIRE

Koompapong Khuanchai; Mori Hirotake; Thammasonthijarern Nipa; Prasertbun Rapeepun; Pintong Ai-rada; Popruk Supaluk; Rojekittikhun Wichit; Chaisiri Kittipong; Sukthana Yaowalark; Mahittikorn Aongart

2014-01-01

Zoonotic Cryptosporidium spp., particularly C. meleagridis, C. canis, and C. felis, are enteric protozoa responsible for major public health concerns around the world. To determine the spread of this parasite in Thailand, we conducted molecular identification of Cryptosporidium spp. from animal samples around the country, by collecting and investigating the feces of seagulls (Chroicocephalus brunnicephalus and Chroicocephalus ridibundus), domestic pigeons (Columba livia domestica), dogs, and ...

Molecular Dynamics Simulation and Statistics Analysis Reveals the Defense Response Mechanism in Plants

Science.gov (United States)

Liu, Zhichao; Zhao, Yunjie; Zeng, Chen; Computational Biophysics Lab Team

As the main protein of the bacterial flagella, flagellin plays an important role in perception and defense response. The newly discovered locus, FLS2, is ubiquitously expressed. FLS2 encodes a putative receptor kinase and shares many homologies with some plant resistance genes and even with some components of immune system of mammals and insects. In Arabidopsis, FLS2 perception is achieved by the recognition of epitope flg22, which induces FLS2 heteromerization with BAK1 and finally the plant immunity. Here we use both analytical methods such as Direct Coupling Analysis (DCA) and Molecular Dynamics (MD) Simulations to get a better understanding of the defense mechanism of FLS2. This may facilitate a redesign of flg22 or de-novo design for desired specificity and potency to extend the immune properties of FLS2 to other important crops and vegetables.

Chemoradiotherapy and molecular biology

International Nuclear Information System (INIS)

Hasegawa, Masatoshi; Mitsuhashi, Norio; Niibe, Hideo

2000-01-01

The current status of chemoradiotherapy was reviewed from the standpoint of molecular biology. Chemoradiotherapy was conducted to achieve systemic tumor control, to intensify the response to irradiation, and to reduce adverse reactions. The mechanisms of the efficacy of chemoradiotherapy were: modification of dose-response relationships, inhibition of tumor cell recovery from sublethal damage or potential lethal damage, effects on cell dynamics and the cell cycle, improvement of blood flow or reoxygenation, recruitment, improvement of drug uptake, increased cell damage. Cell death (necrosis and apoptosis) and cancer-related genes were described, as the essential points, because they are involved in the response to chemoradiotherapy. Cisplatin (platinum compound), 5-fluorouracil, etoposide, and taxoid (paclitaxel, docetaxel) were the principal anticancer agents used for chemoradiotherapy, and they enhanced the effects of irradiation. However, even when good responses or synergism between anticancer drug and radiotherapy was observed in in vitro studies, there was little therapeutic advantage clinically. Data from in vitro and in vivo studies should be collected and systemized, and ''molecular biology in chemotherapy'' that can be applied clinically may become established. (K.H.)

Molecular mechanisms of plant response to ionising radiation. Exploration of the glucosinolate role in the anti-oxidative response

International Nuclear Information System (INIS)

Gicquel, M.

2012-01-01

Terrestrial organisms are exposed to low doses of ionising radiation from natural or anthropogenic sources. The major effects of the radiations are due to DNA deterioration and water radiolysis which generates an oxidative stress by free radical production. Plants constitute good models to study the effects of ionising radiations and the search of antioxidant molecules because of their important secondary metabolism. Thus this thesis, funded by the Brittany region, characterized the physiological and molecular response of the model plant Arabidopsis thaliana to low (10 Gy) and moderate (40 Gy) doses of ionising radiation, and was therefore interested in glucosinolates, characteristic compounds of the Brassicaceae family. The global proteomic and transcriptomic studies carried out on this model revealed (1) a common response for both doses dealing with the activation of DNA repair mechanisms, cell cycle regulation and protection of cellular structures; (2) an adjustment of the energetic metabolism and an activation of secondary compounds biosynthesis (i.e. glucosinolates and flavonoids) after the 10 Gy dose; (3) an induction of enzymatic control of ROS, the regulation of cellular components recycling and of programmed cell death after the 40 Gy dose. The potential anti-oxidative role of glucosinolates was then explored. The in vitro anti-oxidative power of some glucosinolates and their derivative products were demonstrated. Their modulating effects against irradiation-induced damages were then tested in vivo by simple experimental approaches. The importance of the glucosinolate level to give a positive or negative effect was demonstrated. (author)

[Molecular and immunohistochemical diagnostics in melanoma].

Science.gov (United States)

Schilling, B; Griewank, K G

2016-07-01

To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

New molecular imprinted voltammetric sensor for determination of ochratoxin A

Energy Technology Data Exchange (ETDEWEB)

Yola, Mehmet Lütfi, E-mail: mehmetyola@gmail.com [Department of Metallurgical and Materials Engineering, Faculty of Engineering, Sinop University, Sinop (Turkey); Gupta, Vinod Kumar, E-mail: vinodfcy@iitr.ac.in [Indian Institute of Technology, Department of Chemistry, Roorkee, Roorkee 247667 (India); Department of Applied Chemistry, University of Johannesburg, Johannesburg (South Africa); Atar, Necip [Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli (Turkey)

2016-04-01

In this report, a novel molecular imprinted voltammetric sensor based on silver nanoparticles (AgNPs) involved in a polyoxometalate (H{sub 3}PW{sub 12}O{sub 40}, POM) functionalized reduced graphene oxide (rGO) modified glassy carbon electrode (GCE) was presented for determination of ochrattoxin A (OCH). The developed surfaces were characterized using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. OCH imprinted GCE was prepared via electropolymerization process of 100 mM phenol as monomer in the presence of phosphate buffer solution (pH 6.0) containing 25 mM OCH. The linearity range and the detection limit of the method were calculated as 5.0 × 10{sup −11} − 1.5 × 10{sup −9} M and 1.6 × 10{sup −11} M, respectively. The voltammetric sensor was applied to grape juice and wine samples with good selectivity and recovery. The stability of the voltammetric sensor was also reported. - Highlights: • Ochratoxin A-imprinted electrochemical sensor is developed for the sensitive detection of ochratoxin A • The nanomaterial and ochratoxin A-imprinted surfaces were characterized by several methods • Ochratoxin A-imprinted electrochemical sensor is sensitive and selective in analysis of food • Ochratoxin A-imprinted electrochemical sensor is preferred to the other methods.

Sensitive determination of citrinin based on molecular imprinted electrochemical sensor

Energy Technology Data Exchange (ETDEWEB)

Atar, Necip [Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli (Turkey); Yola, Mehmet Lütfi, E-mail: mehmetyola@gmail.com [Department of Metallurgical and Materials Engineering, Faculty of Engineering, Sinop University, Sinop (Turkey); Eren, Tanju [Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli (Turkey)

2016-01-30

Graphical abstract: - Highlights: • Citrinin-imprinted electrochemical sensor is developed for the sensitive detection of citrinin. • The nanomaterial and citrinin-imprinted surfaces were characterized by several methods. • Citrinin-imprinted electrochemical sensor is sensitive and selective in analysis of food. • Citrinin-imprinted electrochemical sensor is preferred to the other methods. - Abstract: In this report, a novel molecular imprinted voltammetric sensor based on glassy carbon electrode (GCE) modified with platinum nanoparticles (PtNPs) involved in a polyoxometalate (H{sub 3}PW{sub 12}O{sub 40}, POM) functionalized reduced graphene oxide (rGO) was prepared for the determination of citrinin (CIT). The developed surfaces were characterized by using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. CIT imprinted GCE was prepared via electropolymerization process of 80.0 mM pyrrole as monomer in the presence of phosphate buffer solution (pH 6.0) containing 20.0 mM CIT. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10{sup −12}–1.0 × 10{sup −10} M and 2.0 × 10{sup −13} M, respectively. In addition, the voltammetric sensor was applied to rye samples. The stability and selectivity of the voltammetric sensor were also reported.

Sensitive determination of citrinin based on molecular imprinted electrochemical sensor

International Nuclear Information System (INIS)

Atar, Necip; Yola, Mehmet Lütfi; Eren, Tanju

2016-01-01

Graphical abstract: - Highlights: • Citrinin-imprinted electrochemical sensor is developed for the sensitive detection of citrinin. • The nanomaterial and citrinin-imprinted surfaces were characterized by several methods. • Citrinin-imprinted electrochemical sensor is sensitive and selective in analysis of food. • Citrinin-imprinted electrochemical sensor is preferred to the other methods. - Abstract: In this report, a novel molecular imprinted voltammetric sensor based on glassy carbon electrode (GCE) modified with platinum nanoparticles (PtNPs) involved in a polyoxometalate (H_3PW_1_2O_4_0, POM) functionalized reduced graphene oxide (rGO) was prepared for the determination of citrinin (CIT). The developed surfaces were characterized by using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. CIT imprinted GCE was prepared via electropolymerization process of 80.0 mM pyrrole as monomer in the presence of phosphate buffer solution (pH 6.0) containing 20.0 mM CIT. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10"−"1"2–1.0 × 10"−"1"0 M and 2.0 × 10"−"1"3 M, respectively. In addition, the voltammetric sensor was applied to rye samples. The stability and selectivity of the voltammetric sensor were also reported.

New molecular imprinted voltammetric sensor for determination of ochratoxin A

International Nuclear Information System (INIS)

Yola, Mehmet Lütfi; Gupta, Vinod Kumar; Atar, Necip

2016-01-01

In this report, a novel molecular imprinted voltammetric sensor based on silver nanoparticles (AgNPs) involved in a polyoxometalate (H_3PW_1_2O_4_0, POM) functionalized reduced graphene oxide (rGO) modified glassy carbon electrode (GCE) was presented for determination of ochrattoxin A (OCH). The developed surfaces were characterized using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. OCH imprinted GCE was prepared via electropolymerization process of 100 mM phenol as monomer in the presence of phosphate buffer solution (pH 6.0) containing 25 mM OCH. The linearity range and the detection limit of the method were calculated as 5.0 × 10"−"1"1 − 1.5 × 10"−"9 M and 1.6 × 10"−"1"1 M, respectively. The voltammetric sensor was applied to grape juice and wine samples with good selectivity and recovery. The stability of the voltammetric sensor was also reported. - Highlights: • Ochratoxin A-imprinted electrochemical sensor is developed for the sensitive detection of ochratoxin A • The nanomaterial and ochratoxin A-imprinted surfaces were characterized by several methods • Ochratoxin A-imprinted electrochemical sensor is sensitive and selective in analysis of food • Ochratoxin A-imprinted electrochemical sensor is preferred to the other methods

Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

International Nuclear Information System (INIS)

Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.; Choy, Hak; Dicker, Adam P.; Saha, Debabrata; Simko, Jeff; Story, Michael D.; Torossian, Artour; Lu, Bo

2012-01-01

Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

Use of inelastic analysis to determine the response of packages to puncture accidents

International Nuclear Information System (INIS)

Ammerman, D.J.; Ludwigsen, J.S.

1996-01-01

The accurate analytical determination of the response of radioactive material transportation packages to the hypothetical puncture accident requires inelastic analysis techniques. Use of this improved analysis method recudes the reliance on empirical and approximate methods to determine the safety for puncture accidents. This paper will discuss how inelastic analysis techniques can be used to determine the stresses, strains and deformations resulting from puncture accidents for thin skin materials with different backing materials. A method will be discussed to assure safety for all of these types of packages

Direct molecular mass determination of trehalose monomycolate from 11 species of mycobacteria by MALDI-TOF mass spectrometry.

Science.gov (United States)

Fujita, Yukiko; Naka, Takashi; Doi, Takeshi; Yano, Ikuya

2005-05-01

Direct estimation of the molecular mass of single molecular species of trehalose 6-monomycolate (TMM), a ubiquitous cell-wall component of mycobacteria, was performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. When less than 1 microg TMM was analysed by MALDI-TOF mass spectrometry, quasimolecular ions [M+Na]+ of each molecular species were demonstrated and the numbers of carbons and double bonds (or cyclopropane rings) were determined. Since the introduction of oxygen atoms such as carbonyl, methoxy and ester groups yielded the appropriate shift of mass ions, the major subclasses of mycolic acid (alpha, methoxy, keto and wax ester) were identified without resorting to hydrolytic procedures. The results showed a marked difference in the molecular species composition of TMM among mycobacterial species. Unexpectedly, differing from other mycoloyl glycolipids, TMM from Mycobacterium tuberculosis showed a distinctive mass pattern, with abundant odd-carbon-numbered monocyclopropanoic (or monoenoic) alpha-mycolates besides dicyclopropanoic mycolate, ranging from C75 to C85, odd- and even-carbon-numbered methoxymycolates ranging from C83 to C94 and even- and odd-carbon-numbered ketomycolates ranging from C83 to C90. In contrast, TMM from Mycobacterium bovis (wild strain and BCG substrains) possessed even-carbon-numbered dicyclopropanoic alpha-mycolates. BCG Connaught strain lacked methoxymycolates almost completely. These results were confirmed by MALDI-TOF mass analysis of mycolic acid methyl esters liberated by alkaline hydrolysis and methylation of the original TMM. Wax ester-mycoloyl TMM molecular species were demonstrated for the first time as an intact form in the Mycobacterium avium-intracellulare group, M. phlei and M. flavescens. The M. avium-intracellulare group possessed predominantly C85 and C87 wax ester-mycoloyl TMM, while M. phlei and the rapid growers tested contained C80, C81, C82 and C83 wax ester

Radio-adaptation: cellular and molecular features of a response to low levels of ionizing radiation

International Nuclear Information System (INIS)

Rigaud, O.

1998-01-01

It is well established that sublethal doses of DNA damaging agents induce protective mechanisms against a subsequent high dose treatment ; for instance, the phenomenon of radio-adaptation in the case of ionizing radiations. Since the early observation described in 1984, numerous studies have confirmed the radio-adaptive response in terms of reduction of chromosomal breaks for varied biological models in vitro and in vivo. Evidence for an adaptive response against the induction of gene mutations and the lethal effect is clearly demonstrated. This paper reviews the experimental results describing various aspects of these adaptive responses expressed on these different biological end-points. The molecular mechanism underlying radio-adaptation still remains nuclear. The development of this phenomenon requires de novo synthesis of transcripts and proteins during the time interval between the two doses. Some data are consistent with the hypotheses that these gene products would be involved in the activation of DNA repair pathways and antioxidant systems. However, a major question still remains unanswered; indeed, it is not clear whether or not the radio-adaptation could affect the estimation of cancer risk related with low level exposure to ionizing radiation, a major concern in radioprotection. Until such data are available, it is yet unwise to evoke the beneficial effects of radio-adaptation. (authors)

Identity and quantity of microorganisms in necrotising fasciitis determined by culture and molecular methods

DEFF Research Database (Denmark)

Rudkjøbing, Vibeke Børsholt; Thomsen, Trine Rolighed; Nielsen, Per Halkjær

communities were more common by molecular methods than culture. Correspondence between findings by culture and molecular methods indicates that the latter may be an appropriate method. The advantages of using molecular methods are: 1) identification of the pathogen(s) even when antibiotics have been...... involved in the disease may add to the knowledge of NF pathogenesis and influence the administration of antibiotics, thereby potentially improving the outcome for the patients. In this study the aim was to investigate the applicability of different molecular methods as compared to standard culture......-based methods. We investigated the microbial communities in 21 samples obtained during debridement of NF patients (n=8). Samples were examined by standard bacteriological examination (culture and microscopy) at Rigshospitalet (Copenhagen, Denmark) and a range of molecular methods. The best DNA extraction...

Bleaching response of Symbiodinium (zooxanthellae): determination by flow cytometry.

Science.gov (United States)

Lee, Co Sin; Yeo, Yin Sheng Wilson; Sin, Tsai Min

2012-10-01

Coral bleaching is of increasing concern to reef management and stakeholders. Thus far, quantification of coral bleaching tends to be heavily reliant on the enumeration of zooxanthellae, with less emphasis on assessment of photosynthetic or physiological condition, these being often assessed separately by techniques such as liquid chromatography. Traditional methods of enumeration using microscopy are time consuming, subjected to low precision and great observer error. In this study, we presented a method for the distinction of physoiological condition and rapid enumeration of zooxanthellae using flow cytometry (FCM). Microscopy verified that healthy looking/live versus damaged/dead zooxanthellae could be reliably and objectively distinguished and counted by FCM on the basis of red and green fluorescence and light scatter. Excellent correlations were also determined between FCM and microscopy estimates of cell concentrations of fresh zooxanthellae isolates from Pocillopora damicornis. The relative intensities of chlorophyll and β-carotene fluorescences were shown to be important in understanding the results of increased cell counts in freshly isolated zooxanthellae experimentally exposed to high temperatures (34, 36, and 38°C) over 24 h, with ambient temperature (29°C) used as controls. The ability to simultaneously identify and enumerate subpopulations of different physiological states in the same sample provides an enormous advantage in not just determining bleaching responses, but elucidating adaptive response and mechanisms for tolerance. Therefore, this approach might provide a rapid, convenient, and reproducible methodology for climate change studies and reef management programs. Copyright © 2012 International Society for Advancement of Cytometry.

Simultaneous determination of albumin and low-molecular-mass thiols in plasma by HPLC with UV detection.

Science.gov (United States)

Borowczyk, Kamila; Wyszczelska-Rokiel, Monika; Kubalczyk, Paweł; Głowacki, Rafał

2015-02-15

In this paper, we describe a simple and robust HPLC based method for determination of total low- and high-molecular-mass thiols, protein S-linked thiols and reduced albumin in plasma. The method is based on derivatization of analytes with 2-chloro-1-methylquinolinium tetrafluoroborate, separation and quantification by reversed-phase liquid chromatography followed by UV detection. Disulfides were converted to their thiol counterparts by reductive cleavage with tris(2-carboxyethyl)phosphine. Linearity in detector response for total thiols was observed over the range of 1-40 μmol L(-1) for Hcy and glutathione (GSH), 5-100 μmol L(-1) for Cys-Gly, 20-300 μmol L(-1) for Cys and 3.1-37.5 μmol L(-1) (0.2-2.4gL(-1)) for human serum albumin (HSA). For the protein S-bound forms these values were as follows: 0.5-30 μmol L(-1) for Hcy and GSH, 2.5-60 μmol L(-1) for Cys-Gly and 5-200 μmol L(-1) for Cys. The LOQs for total HSA, Cys, Hcy, Cys-Gly and GSH were 0.5, 0.2, 0.4, 0.3 and 0.4 μmol L(-1), respectively. The estimated validation parameters for all analytes are more than sufficient to allow the analytical method to be used for monitoring of the total and protein bound thiols as well as redox status of HSA in plasma. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular and physiological responses to titanium dioxide ...

Science.gov (United States)

- Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to two widely-used engineered metal oxide nanoparticles, titanium dioxide (nano-titanium) and cerium dioxide (nano-cerium). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes (DEGs) found under nano-titania exposure. Nano-titania induced more DEGs in rosette leaves, whereas roots had more DEGs under nano-ceria exposure. MapMan analyses indicated that while nano-titania up-regulated overall and secondary metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level. This may b

Molecular analysis of UAS(E), a cis element containing stress response elements responsible for ethanol induction of the KlADH4 gene of Kluyveromyces lactis.

Science.gov (United States)

Mazzoni, C; Santori, F; Saliola, M; Falcone, C

2000-01-01

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity, which is specifically induced by ethanol and insensitive to glucose repression. In this work, we report the molecular analysis of UAS(E), an element of the KlADH4 promoter which is essential for the induction of KlADH4 in the presence of ethanol. UAS(E) contains five stress response elements (STREs), which have been found in many genes of Saccharomyces cerevisiae involved in the response of cells to conditions of stress. Whereas KlADH4 is not responsive to stress conditions, the STREs present in UAS(E) seem to play a key role in the induction of the gene by ethanol, a situation that has not been observed in the related yeast S. cerevisiae. Gel retardation experiments showed that STREs in the KlADH4 promoter can bind factor(s) under non-inducing conditions. Moreover, we observed that the RAP1 binding site present in UAS(E) binds KlRap1p.

Determination of the Molecular Weight of Low-Molecular-Weight Heparins by Using High-Pressure Size Exclusion Chromatography on Line with a Triple Detector Array and Conventional Methods

Directory of Open Access Journals (Sweden)

Antonella Bisio

2015-03-01

Full Text Available The evaluation of weight average molecular weight (Mw and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs. As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC, the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn by HP-SEC combined with a triple detector array (TDA was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS; refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of

Transcriptome analysis of Crossostephium chinensis provides insight into the molecular basis of salinity stress responses.

Directory of Open Access Journals (Sweden)

Haiyan Yang

Full Text Available Soil salinization is becoming a limitation to the utilization of ornamental plants worldwide. Crossostephium chinensis (Linnaeus Makino is often cultivated along the southeast coast of China for its desirable ornamental qualities and high salt tolerance. However, little is known about the genomic background of the salt tolerance mechanism in C. chinensis. In the present study, we used Illumina paired-end sequencing to systematically investigate leaf transcriptomes derived from C. chinensis seedlings grown under normal conditions and under salt stress. A total of 105,473,004 bp of reads were assembled into 163,046 unigenes, of which 65,839 (40.38% of the total and 54,342 (33.32% of the total were aligned in Swiss-Prot and Nr protein, respectively. A total of 11,331 (6.95% differentially expressed genes (DEGs were identified among three comparisons, including 2,239 in 'ST3 vs ST0', 5,880 in 'ST9 vs ST3' and 9,718 in 'ST9 vs ST0', and they were generally classified into 26 Gene Ontology terms and 58 Kyoto Encyclopedia of Genes and Genomes (KEGG pathway terms. Many genes encoding important transcription factors (e.g., WRKY, MYB, and AP2/EREBP and proteins involved in starch and sucrose metabolism, arginine and proline metabolism, plant hormone signal transduction, amino acid biosynthesis, plant-pathogen interactions and carbohydrate metabolism, among others, were substantially up-regulated under salt stress. These genes represent important candidates for studying the salt-response mechanism and molecular biology of C. chinensis and its relatives. Our findings provide a genomic sequence resource for functional genetic assignments in C. chinensis. These transcriptome datasets will help elucidate the molecular mechanisms responsible for salt-stress tolerance in C. chinensis and facilitate the breeding of new stress-tolerant cultivars for high-saline areas using this valuable genetic resource.

Determining the Response Behaviors of Middle School Students for Open-Ended Questions

Directory of Open Access Journals (Sweden)

Neslihan Tuğçe ŞİMŞEK

2017-04-01

Full Text Available When the literature for measurement and evaluation in education is reviewed, research related to student achievement are mainly outcome-oriented rather than process-oriented. Researchers pay attention to the responses that a student constructs or chooses, and ignore the cognitive processes that forces students to construct or choose that specific response. Recognizing the cognitive processes a student uses in responding to a question affects the item construction process and psychometric audit on items. Response behavior is a result of a cognitive process used to respond to a question and is accepted as an indicator of student cognitive competence. This study aims to determine the students’ response behaviors for open-ended questions. The study group consisted of 70 students from the 5th grade studying during the 2015-2016 education year spring term in the Cankaya and Mamak districts of Ankara province, Turkey. An authentic achievement test which consisted of eight open-ended questions is used as the data collection tool. Students are asked to write in detail how they construct their response in their mind in the blank space set aside after each question. Data is analyzed via grouping students’ response behaviors and expert opinions. Research findings revealed that students perform 14 different response behaviors for open-ended questions. These behaviors are themed as responses constructed directly from the text, responses constructed by interpreting the text, and responses constructed by linking real life and the text.

Acknowledging individual responsibility while emphasizing social determinants in narratives to promote obesity-reducing public policy: a randomized experiment.

Directory of Open Access Journals (Sweden)

Jeff Niederdeppe

Full Text Available This study tests whether policy narratives designed to increase support for obesity-reducing public policies should explicitly acknowledge individual responsibility while emphasizing social, physical, and economic (social determinants of obesity. We use a web-based, randomized experiment with a nationally representative sample of American adults (n = 718 to test hypotheses derived from theory and research on narrative persuasion. Respondents exposed to narratives that acknowledged individual responsibility while emphasizing obesity's social determinants were less likely to engage in counterargument and felt more empathy for the story's main character than those exposed to a message that did not acknowledge individual responsibility. Counterarguing and affective empathy fully mediated the relationship between message condition and support for policies to reduce rates of obesity. Failure to acknowledge individual responsibility in narratives emphasizing social determinants of obesity may undermine the persuasiveness of policy narratives. Omitting information about individual responsibility, a strongly-held American value, invites the public to engage in counterargument about the narratives and reduces feelings of empathy for a character that experiences the challenges and benefits of social determinants of obesity.

Acknowledging individual responsibility while emphasizing social determinants in narratives to promote obesity-reducing public policy: a randomized experiment.

Science.gov (United States)

Niederdeppe, Jeff; Roh, Sungjong; Shapiro, Michael A

2015-01-01

This study tests whether policy narratives designed to increase support for obesity-reducing public policies should explicitly acknowledge individual responsibility while emphasizing social, physical, and economic (social) determinants of obesity. We use a web-based, randomized experiment with a nationally representative sample of American adults (n = 718) to test hypotheses derived from theory and research on narrative persuasion. Respondents exposed to narratives that acknowledged individual responsibility while emphasizing obesity's social determinants were less likely to engage in counterargument and felt more empathy for the story's main character than those exposed to a message that did not acknowledge individual responsibility. Counterarguing and affective empathy fully mediated the relationship between message condition and support for policies to reduce rates of obesity. Failure to acknowledge individual responsibility in narratives emphasizing social determinants of obesity may undermine the persuasiveness of policy narratives. Omitting information about individual responsibility, a strongly-held American value, invites the public to engage in counterargument about the narratives and reduces feelings of empathy for a character that experiences the challenges and benefits of social determinants of obesity.

Extended-gate field-effect transistor (EG-FET) with molecularly imprinted polymer (MIP) film for selective inosine determination.

Science.gov (United States)

Iskierko, Zofia; Sosnowska, Marta; Sharma, Piyush Sindhu; Benincori, Tiziana; D'Souza, Francis; Kaminska, Izabela; Fronc, Krzysztof; Noworyta, Krzysztof

2015-12-15

A novel recognition unit of chemical sensor for selective determination of the inosine, renal disfunction biomarker, was devised and prepared. For that purpose, inosine-templated molecularly imprinted polymer (MIP) film was deposited on an extended-gate field-effect transistor (EG-FET) signal transducing unit. The MIP film was prepared by electrochemical polymerization of bis(bithiophene) derivatives bearing cytosine and boronic acid substituents, in the presence of the inosine template and a thiophene cross-linker. After MIP film deposition, the template was removed, and was confirmed by UV-visible spectroscopy. Subsequently, the film composition was characterized by spectroscopic techniques, and its morphology and thickness were determined by AFM. The finally MIP film-coated extended-gate field-effect transistor (EG-FET) was used for signal transduction. This combination is not widely studied in the literature, despite the fact that it allows for facile integration of electrodeposited MIP film with FET transducer. The linear dynamic concentration range of the chemosensor was 0.5-50 μM with inosine detectability of 0.62 μM. The obtained detectability compares well to the levels of the inosine in body fluids which are in the range 0-2.9 µM for patients with diagnosed diabetic nephropathy, gout or hyperuricemia, and can reach 25 µM in certain cases. The imprinting factor for inosine, determined from piezomicrogravimetric experiments with use of the MIP film-coated quartz crystal resonator, was found to be 5.5. Higher selectivity for inosine with respect to common interferents was also achieved with the present molecularly engineered sensing element. The obtained analytical parameters of the devised chemosensor allow for its use for practical sample measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

Photoredox-Based Actuation of an Artificial Molecular Muscle.

Science.gov (United States)

Liles, Kevin P; Greene, Angelique F; Danielson, Mary K; Colley, Nathan D; Wellen, Andrew; Fisher, Jeremy M; Barnes, Jonathan C

2018-01-24

The use of light to actuate materials is advantageous because it represents a cost-effective and operationally straightforward way to introduce energy into a stimuli-responsive system. Common strategies for photoinduced actuation of materials typically rely on light irradiation to isomerize azobenzene or spiropyran derivatives, or to induce unidirectional rotation of molecular motors incorporated into a 3D polymer network. Although interest in photoredox catalysis has risen exponentially in the past decade, there are far fewer examples where photoinduced electron transfer (PET) processes are employed to actuate materials. Here, a novel mode of actuation in a series of redox-responsive hydrogels doped with a visible-light-absorbing ruthenium-based photocatalyst is reported. The hydrogels are composed primarily of polyethylene glycol and low molar concentrations of a unimolecular electroactive polyviologen that is activated through a PET mechanism. The rate and degree of contraction of the hydrogels are measured over several hours while irradiating with blue light. Likewise, the change in mechanical properties-determined through oscillatory shear rheology experiments-is assessed as a function of polyviologen concentration. Finally, an artificial molecular muscle is fabricated using the best-performing hydrogel composition, and its ability to perform work, while irradiated, is demonstrated by lifting a small weight. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

International Nuclear Information System (INIS)

Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

1997-01-01

Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

Environmental sex determination in the branchiopod crustacean Daphnia magna: deep conservation of a Doublesex gene in the sex-determining pathway.

Directory of Open Access Journals (Sweden)

Yasuhiko Kato

2011-03-01

Full Text Available Sex-determining mechanisms are diverse among animal lineages and can be broadly divided into two major categories: genetic and environmental. In contrast to genetic sex determination (GSD, little is known about the molecular mechanisms underlying environmental sex determination (ESD. The Doublesex (Dsx genes play an important role in controlling sexual dimorphism in genetic sex-determining organisms such as nematodes, insects, and vertebrates. Here we report the identification of two Dsx genes from Daphnia magna, a freshwater branchiopod crustacean that parthenogenetically produces males in response to environmental cues. One of these genes, designated DapmaDsx1, is responsible for the male trait development when expressed during environmental sex determination. The domain organization of DapmaDsx1 was similar to that of Dsx from insects, which are thought to be the sister group of branchiopod crustaceans. Intriguingly, the molecular basis for sexually dimorphic expression of DapmaDsx1 is different from that of insects. Rather than being regulated sex-specifically at the level of pre-mRNA splicing in the coding region, DapmaDsx1 exhibits sexually dimorphic differences in the abundance of its transcripts. During embryogenesis, expression of DapmaDsx1 was increased only in males and its transcripts were primarily detected in male-specific structures. Knock-down of DapmaDsx1 in male embryos resulted in the production of female traits including ovarian maturation, whereas ectopic expression of DapmaDsx1 in female embryos resulted in the development of male-like phenotypes. Expression patterns of another D. magna Dsx gene, DapmaDsx2, were similar to those of DapmaDsx1, but silencing and overexpression of this gene did not induce any clear phenotypic changes. These results establish DapmaDsx1 as a key regulator of the male phenotype. Our findings reveal how ESD is implemented by selective expression of a fundamental genetic component that is

Acceptance criteria for determining armed response force size at nuclear power plants

International Nuclear Information System (INIS)

1983-02-01

This guidance document contains acceptance criteria to be used in the NRC license review process. It consists of a scored worksheet and guidelines for interpreting the worksheet score that can be used in determining the adequacy of the armed response force size at a nuclear power reactor facility

A highly selective molecularly imprinted electrochemiluminescence sensor for ultra-trace beryllium detection

International Nuclear Information System (INIS)

Li, Jianping; Ma, Fei; Wei, Xiaoping; Fu, Cong; Pan, Hongcheng

2015-01-01

Graphical abstract: A novel molecular imprinted electrochemiluminescence sensor was fabricated for ultra-trace Be 2+ detection with an extremely lower detection limit based on the luminol–H 2 O 2 ECL system. - Highlights: • A novel molecular imprinted electrochemiluminescence sensor was fabricated for ultra-trace Be 2+ detection. • Imprint cavities in the MIPs from elution the Be–PAR complex could provide more recognition sites for analytes. • ECL emission produced by the luminol–H 2 O 2 ECL system, which was applied to detect Be 2+ . • It gave an extremely lower detection limit (2.35 × 10 −11 mol L −1 ) than the reported methods. - Abstract: A new molecularly imprinted electrochemiluminescence (ECL) sensor was proposed for highly sensitive and selective determination of ultratrace Be 2+ determination. The complex of Be 2+ with 4-(2-pyridylazo)-resorcinol (PAR) was chosen as the template molecule for the molecularly imprinted polymer (MIP). In this assay, the complex molecule could be eluted from the MIP, and the cavities formed could then selectively recognize the complex molecules. The cavities formed could also work as the tunnel for the transfer of probe molecules to produce sound responsive signal. The determination was based on the intensity of the signal, which was proportional to the concentrations of the complex molecule in the sample solution, and the Be 2+ concentration could then be determined indirectly. The results showed that in the range of 7 × 10 −11 mol L −1 to 8.0 × 10 −9 mol L −1 , the ECL intensity had a linear relationship with the Be 2+ concentrations, with the limit of detection of 2.35 × 10 −11 mol L −1 . This method was successfully used to detect Be 2+ in real water samples

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

Science.gov (United States)

Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Active Gating, Molecular Pumping, and Turnover Determination in Biomimetic Lipidic Cubic Mesophases with Reconstituted Membrane Proteins.

Science.gov (United States)

Speziale, Chiara; Zabara, Alexandru Florian; Drummond, Calum John; Mezzenga, Raffaele

2017-11-28

Understanding the mechanisms controlling molecular transport in bioinspired materials is a central topic in many branches of nanotechnology. In this work, we show that biomolecules of fundamental importance in biological processes, such as glucose, can be transported in an active, controlled, and selective manner across macroscopic lipidic cubic mesophases, by correctly reconstituting within them their corresponding membrane protein transporters, such as Staphylococcus epidermidis (GlcP Se ). Importantly, by duly exploiting the symporter properties of GlcP Se of coupled glucose/H + transport, the diffusion of glucose can further be tuned by independent physiological stimuli, such as parallel or antiparallel pH gradients, offering an important model to study molecular exchange processes in cellular machinery. We finally show that by measuring the transport properties of the lipidic mesophases with and without the GlcP Se membrane protein reconstituted within, it becomes possible to determine its intrinsic conductance. We generalize these findings to other membrane proteins from the antiporters family, such as the bacterial ClC exchanger from Escherichia coli (EcClC), providing a robust method for evaluating the turnover rate of the membrane proteins in general.

Molecularly imprinted polymer for selective extraction of malachite green from seawater and seafood coupled with high-performance liquid chromatographic determination.

Science.gov (United States)

Lian, Ziru; Wang, Jiangtao

2012-12-01

In this paper, a highly selective sample cleanup procedure combining molecular imprinting technique (MIT) and solid-phase extraction (SPE) was developed for the isolation of malachite green in seawater and seafood samples. The molecularly imprinted polymer (MIP) was prepared using malachite green as the template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linking monomer. The imprinted polymer and non-imprinted polymer were characterized by scanning electron microscope and static adsorption experiments. The MIP showed a high adsorption capacity and was used as selective sorbent for the SPE of malachite green. An off-line molecularly imprinted solid-phase extraction (MISPE) method followed by high-performance liquid chromatography with diodearray detection for the analysis of malachite green in seawater and seafood samples was also established. Finally, five samples were determined. The results showed that malachite green concentration in one seawater sample was at 1.30 μg L⁻¹ and the RSD (n=3) was 4.15%. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Quantifying the determinants of decremental response in critical ventricular tachycardia substrate.

Science.gov (United States)

Beheshti, Mohammadali; Nayyar, Sachin; Magtibay, Karl; Massé, Stéphane; Porta-Sanchez, Andreu; Haldar, Shouvik; Bhaskaran, Abhishek; Vigmond, Edward; Nanthakumar, Kumaraswamy

2018-05-28

Decremental response evoked with extrastimulation (DEEP) is a useful tool for determining diastolic return path of ventricular tachycardia (VT). Though a targeted VT ablation is feasible with this approach, determinants of DEEP response have not been studied OBJECTIVES: To elucidate the effects of clinically relevant factors, specifically, the proximity of the stimulation site to the arrhythmogenic scar, stimulation wave direction, number of channels open in the scar, size of the scar and number of extra stimuli on decrement and entropy of DEEP potentials. In a 3-dimensional bi-domain simulation of human ventricular tissue (TNNP cell model), an irregular subendocardial myopathic region was generated. An irregular channel of healthy tissue with five potential entry branches was shaped into the myopathic region. A bipolar electrogram was derived from two electrodes positioned in the centre of the myopathic region. Evoked delays between far-field and local Electrogram (EGM) following an extrastimulus (S1-S2, 500-350 ms) were measured as the stimulation site, channel branches, and inexcitable tissue size were altered. Stimulation adjacent to the inexcitable tissue from the side opposite to the point-of-entry produces longest DEEP delay. The DEEP delay shortens when the stimulation point is farther away from the scar, and it decreases maximally when stimulation is done from a site beside a conduction barrier. Entropy increases with S2 when stimulation site is from farther away. An unprotected channel structure with multiple side-branch openings had shorter DEEP delay compared to a protected channel structure with a paucity of additional side-branch openings and a point-of-entry on the side opposite to the pacing source. Addition of a second shorter extrastimulus did not universally lead to higher DEEP delay CONCLUSIONS: Location and direction of the wavefront in relation to scar entry and size of scar determine the degree of evoked response while the number of

Contrasting impacts of ocean acidification and warming on the molecular responses of CO2-resilient oysters.

Science.gov (United States)

Goncalves, Priscila; Thompson, Emma L; Raftos, David A

2017-06-02

This study characterises the molecular processes altered by both elevated CO 2 and increasing temperature in oysters. Differences in resilience of marine organisms against the environmental stressors associated with climate change will have significant implications for the sustainability of coastal ecosystems worldwide. Some evidence suggests that climate change resilience can differ between populations within a species. B2 oysters represent a unique genetic resource because of their capacity to better withstand the impacts of elevated CO 2 at the physiological level, compared to non-selected oysters from the same species (Saccostrea glomerata). Here, we used proteomic and transcriptomic analysis of gill tissue to evaluate whether the differential response of B2 oysters to elevated CO 2 also extends to increased temperature. Substantial and distinctive effects on protein concentrations and gene expression were evident among B2 oysters responding to elevated CO 2 or elevated temperature. The combination of both stressors also altered oyster gill proteomes and gene expression. However, the impacts of elevated CO 2 and temperature were not additive or synergistic, and may be antagonistic. The data suggest that the simultaneous exposure of CO 2 -resilient oysters to near-future projected ocean pH and temperature results in complex changes in molecular processes in order to prevent stress-induced cellular damage. The differential response of B2 oysters to the combined stressors also indicates that the addition of thermal stress may impair the resilience of these oysters to decreased pH. Overall, this study reveals the intracellular mechanisms that might enable marine calcifiers to endure the emergent, adverse seawater conditions resulting from climate change.

Determining generator parameters of Camargos hydroelectric power plant through frequency response measurement

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Sebastiao E.M. de; Padua Guarini, Antonio de [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Souza, Joao A. de; Valgas, Helio M; Pinto, Roberto del Giudice R. [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil)

1994-12-31

This work describes the results of the set frequency response tests performed in the generator number 2, 6.9 kV, 25 MVA, of Camargos hydroelectric power plant, CEMIG, and the parameters relatives to determined structures of model. This tests are unpublished in Brazil. (author) 7 refs., 16 figs., 7 tabs.

CaI and SrI molecules for iodine determination by high-resolution continuum source graphite furnace molecular absorption spectrometry: Greener molecules for practical application.

Science.gov (United States)

Zanatta, Melina Borges Teixeira; Nakadi, Flávio Venâncio; da Veiga, Márcia Andreia Mesquita Silva

2018-03-01

A new method to determine iodine in drug samples by high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) has been developed. The method measures the molecular absorption of a diatomic molecule, CaI or SrI (less toxic molecule-forming reagents), at 638.904 or 677.692nm, respectively, and uses a mixture containing 5μg of Pd and 0.5μg of Mg as chemical modifier. The method employs pyrolysis temperatures of 1000 and 800°C and vaporization temperatures of 2300 and 2400°C for CaI and SrI, respectively. The optimized amounts of Ca and Sr as molecule-forming reagents are 100 and 150µg, respectively. On the basis of interference studies, even small chlorine concentrations reduce CaI and SrI absorbance significantly. The developed method was used to analyze different commercial drug samples, namely thyroid hormone pills with three different iodine amounts (15.88, 31.77, and 47.66µg) and one liquid drug with 1% m v -1 active iodine in their compositions. The results agreed with the values informed by the manufacturers (95% confidence level) regardless of whether CaI or SrI was determined. Therefore, the developed method is useful for iodine determination on the basis of CaI or SrI molecular absorption. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Angiotensin II Molecular Determinants Involved in AT1 Receptor Functional Selectivity.

Science.gov (United States)

Domazet, Ivana; Holleran, Brian J; Richard, Alexandra; Vandenberghe, Camille; Lavigne, Pierre; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

2015-06-01

The octapeptide angiotensin II (AngII) exerts a variety of cardiovascular effects through the activation of the AngII type 1 receptor (AT1), a G protein-coupled receptor. The AT1 receptor engages and activates several signaling pathways, including heterotrimeric G proteins Gq and G12, as well as the extracellular signal-regulated kinases (ERK) 1/2 pathway. Additionally, following stimulation, βarrestin is recruited to the AT1 receptor, leading to receptor desensitization. It is increasingly recognized that specific ligands selectively bind and favor the activation of some signaling pathways over others, a concept termed ligand bias or functional selectivity. A better understanding of the molecular basis of functional selectivity may lead to the development of better therapeutics with fewer adverse effects. In the present study, we developed assays allowing the measurement of six different signaling modalities of the AT1 receptor. Using a series of AngII peptide analogs that were modified in positions 1, 4, and 8, we sought to better characterize the molecular determinants of AngII that underlie functional selectivity of the AT1 receptor in human embryonic kidney 293 cells. The results reveal that position 1 of AngII does not confer functional selectivity, whereas position 4 confers a bias toward ERK signaling over Gq signaling, and position 8 confers a bias toward βarrestin recruitment over ERK activation and Gq signaling. Interestingly, the analogs modified in position 8 were also partial agonists of the protein kinase C (PKC)-dependent ERK pathway via atypical PKC isoforms PKCζ and PKCι. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

ACE polymorphism does not determine short-term renal response to ACE-inhibition in proteinuric patients

NARCIS (Netherlands)

vanderKleij, FGH; Navis, GJ; Gansevoort, RT; Scheffer, H; deZeeuw, D; deJong, PE

1997-01-01

Background. The renal response to ACE inhibition is known to vary between individuals. The ACE genotype is a determinant of the ACE concentrations in plasma and tissue, and therefore might affect the renal response to ACE inhibition in renal patients. Methods. To test this hypothesis we studied the

Response diversity determines the resilience of ecosystems to environmental change.

Science.gov (United States)

Mori, Akira S; Furukawa, Takuya; Sasaki, Takehiro

2013-05-01

A growing body of evidence highlights the importance of biodiversity for ecosystem stability and the maintenance of optimal ecosystem functionality. Conservation measures are thus essential to safeguard the ecosystem services that biodiversity provides and human society needs. Current anthropogenic threats may lead to detrimental (and perhaps irreversible) ecosystem degradation, providing strong motivation to evaluate the response of ecological communities to various anthropogenic pressures. In particular, ecosystem functions that sustain key ecosystem services should be identified and prioritized for conservation action. Traditional diversity measures (e.g. 'species richness') may not adequately capture the aspects of biodiversity most relevant to ecosystem stability and functionality, but several new concepts may be more appropriate. These include 'response diversity', describing the variation of responses to environmental change among species of a particular community. Response diversity may also be a key determinant of ecosystem resilience in the face of anthropogenic pressures and environmental uncertainty. However, current understanding of response diversity is poor, and we see an urgent need to disentangle the conceptual strands that pervade studies of the relationship between biodiversity and ecosystem functioning. Our review clarifies the links between response diversity and the maintenance of ecosystem functionality by focusing on the insurance hypothesis of biodiversity and the concept of functional redundancy. We provide a conceptual model to describe how loss of response diversity may cause ecosystem degradation through decreased ecosystem resilience. We explicitly explain how response diversity contributes to functional compensation and to spatio-temporal complementarity among species, leading to long-term maintenance of ecosystem multifunctionality. Recent quantitative studies suggest that traditional diversity measures may often be uncoupled from

Determinants of Private Long-Term Care Insurance Purchase in Response to the Partnership Program.

Science.gov (United States)

Lin, Haizhen; Prince, Jeffrey T

2016-04-01

To assess three possible determinants of individuals' response in their private insurance purchases to the availability of the Partnership for Long-Term Care (PLTC) insurance program: bequest motives, financial literacy, and program awareness. The health and retirement study (HRS) merged with data on states' implementation of the PLTC program. Individual-level decision on private long-term care insurance is regressed on whether the PLTC program is being implemented for a given state-year, asset dummies, policy determinant variable, two-way and three-way interactions of these variables, and other controls, using fixed effects panel regression. Analysis used a sample between 50 and 69 years of age from 2002 to 2010, resulting in 12,695 unique individuals with a total of 39,151 observations. We find mild evidence that intent to bequest influences individual purchase of insurance. We also find that program awareness is necessary for response, while financial literacy notably increases responsiveness. Increasing response to the PLTC program among the middle class (the stated target group) requires increased efforts to create awareness of the program's existence and increased education about the program's benefits, and more generally, about long-term care risks and needs. © Health Research and Educational Trust.

Molecular MR imaging

International Nuclear Information System (INIS)

Fleige, G.; Hamm, B.

2000-01-01

Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.) [de

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

Science.gov (United States)

Rodríguez Pulido, Miguel; Sáiz, Margarita

2017-01-01

Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

Individual response to ionising radiation: What predictive assay(s) to choose?

International Nuclear Information System (INIS)

Granzotto, A.; Viau, M.; Devic, C.; Maalouf, M.; Thomas, Ch.; Vogin, G.; Foray, N.; Granzotto, A.; Vogin, G.; Balosso, J.; Joubert, A.; Maalouf, M.; Vogin, G.; Colin, C.; Malek, K.; Balosso, J.; Colin, C.

2011-01-01

Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) [1]. To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomics technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensing and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavored to analyse the contributions of these major approaches to predict human radiosensitivity. (authors)

Determination of trace concentrations of chlorine in aqueous solutions by high-resolution continuum source graphite furnace molecular absorption spectrometry

Science.gov (United States)

Machyňák, Ľubomír; Čacho, František; Němeček, Martin; Beinrohr, Ernest

2016-11-01

Trace concentrations of total chlorine were determined by means of molecular absorption of indium mono-chloride (InCl) at 267.217 nm using high-resolution continuum source graphite furnace molecular absorption spectrometry. The effects of chemical modifiers and the amount of In on the sensitivity and accuracy were investigated. The optimum pyrolysis and vaporization temperatures were 600 °C and 1400 °C, respectively. The limit of detection and characteristic mass were found to be 0.10 ng and 0.21 ng, respectively. Potential non-spectral and spectral interferences were tested for various metals and non-metals at concentrations up to 50 mg L- 1 and for phosphoric, sulphuric and nitric acids. No spectral interferences were observed. Significant non-spectral interferences were observed with F, Br, and I at concentrations higher than 1 mg L- 1, 5 mg L- 1 and 25 mg L- 1, respectively, which is probably caused by formation of competitive indium halogen molecules. Higher concentrations of mineral acids depressed the signal owing to the formation of volatile HCl. The calibration curve was linear in the range between 0.3 and 10 ng with a correlation coefficient of R = 0.993. The elaborated method was used for the chlorine determination in various waters and a drug sample.

Flow analysis-hydride generation-gas phase derivative molecular absorption spectrophotometric determination of antimony in antileishmanial drugs

Directory of Open Access Journals (Sweden)

Máximo Gallignani

2009-01-01

Full Text Available In the present work, the development of a method based on the coupling of flow analysis (FA, hydride generation (HG, and derivative molecular absorption spectrophotometry (D-EAM in gas phase (GP, is described in order to determine total antimony in antileishmanial products. Second derivative order (D²224nm of the absorption spectrum (190 - 300 nm is utilized as measurement criterion. Each one of the parameters involved in the development of the proposed method was examined and optimized. The utilization of the EAM in GP as detection system in a continuous mode instead of atomic absorption spectrometry represents the great potential of the analytic proposal.

UNIQUAC interaction parameters for molecules with -OH groups on adjacent carbon atoms in aqueous solution determined by molecular mechanics - glycols, glycerol and glucose

DEFF Research Database (Denmark)

Jonsdottir, Svava Osk; Klein, R. A.

1997-01-01

UNIQUAC interaction parameters have been determined, using molecular mechanics calculations, for 1,2-ethanediol, 1,2-propanediol, glycerol and glucose with water in aqueous solution. Conformational space for individual pairs of molecules was explored using a stochastic method, the Boltzmann Jump...

DyNet: visualization and analysis of dynamic molecular interaction networks.

Science.gov (United States)

Goenawan, Ivan H; Bryan, Kenneth; Lynn, David J

2016-09-01

: The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most 'rewired' nodes across many network states. DyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet). david.lynn@sahmri.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Chronic myelogenous leukemia: molecular monitoring in clinical practice

Directory of Open Access Journals (Sweden)

N. R. Ryabchikova

2013-01-01

Full Text Available Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.

A molecular spin-photovoltaic device.

Science.gov (United States)

Sun, Xiangnan; Vélez, Saül; Atxabal, Ainhoa; Bedoya-Pinto, Amilcar; Parui, Subir; Zhu, Xiangwei; Llopis, Roger; Casanova, Fèlix; Hueso, Luis E

2017-08-18

We fabricated a C 60 fullerene-based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The molecular basis of peanut allergy

Science.gov (United States)

Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures, and discusses how modif...

Phylogenetic responses of forest trees to global change.

Science.gov (United States)

Senior, John K; Schweitzer, Jennifer A; O'Reilly-Wapstra, Julianne; Chapman, Samantha K; Steane, Dorothy; Langley, Adam; Bailey, Joseph K

2013-01-01

In a rapidly changing biosphere, approaches to understanding the ecology and evolution of forest species will be critical to predict and mitigate the effects of anthropogenic global change on forest ecosystems. Utilizing 26 forest species in a factorial experiment with two levels each of atmospheric CO2 and soil nitrogen, we examined the hypothesis that phylogeny would influence plant performance in response to elevated CO2 and nitrogen fertilization. We found highly idiosyncratic responses at the species level. However, significant, among-genetic lineage responses were present across a molecularly determined phylogeny, indicating that past evolutionary history may have an important role in the response of whole genetic lineages to future global change. These data imply that some genetic lineages will perform well and that others will not, depending upon the environmental context.

The vaginal microbiota: what have we learned after a decade of molecular characterization?

Science.gov (United States)

van de Wijgert, Janneke H H M; Borgdorff, Hanneke; Verhelst, Rita; Crucitti, Tania; Francis, Suzanna; Verstraelen, Hans; Jespers, Vicky

2014-01-01

We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A) to determine if consistent molecular vaginal microbiota (VMB) composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization) was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV) is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV), and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB.

The vaginal microbiota: what have we learned after a decade of molecular characterization?

Directory of Open Access Journals (Sweden)

Janneke H H M van de Wijgert

Full Text Available We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A to determine if consistent molecular vaginal microbiota (VMB composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV, and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB.

Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

Science.gov (United States)

Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

2011-01-01

How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

Modeling of molecular weight and molecular weight distribution in slurry polymerization of propylene by Ziegler-Natta catalysts

International Nuclear Information System (INIS)

Khorasani, R.; Pourmahdian, S.

2007-01-01

The Precise prediction of polypropylene synthesized by heterogeneous Ziegler-Natta catalysts needs good knowledge of parameters affecting on polymerization. molecular weight and molecular weight distribution are among important characteristics of a polymer determining physical-mechanical properties. broadening of molecular weight distribution is an important and well known characteristic of polypropylene synthesized by heterogeneous Ziegler-Natta catalysts, So it is important to understand the origin of broad molecular weight. Two main factors in broadening molecular weight, namely mass transfer resistances and multiplicity of active sites, are discussed in this paper and a model including these factors is presented. Then we calculate molecular weight and molecular weight distribution by the model and compare our results with

41 CFR 101-25.202 - Factors to be used to determine assignment of purchase responsibility.

Science.gov (United States)

2010-07-01

... experience of agency purchasing and contracting officials and their operating units with due regard to... determine assignment of purchase responsibility. 101-25.202 Section 101-25.202 Public Contracts and Property... PROCUREMENT 25-GENERAL 25.2-Interagency Purchase Assignments § 101-25.202 Factors to be used to determine...

Electrochemical sensor based on molecularly imprinted polymer film via sol-gel technology and multi-walled carbon nanotubes-chitosan functional layer for sensitive determination of quinoxaline-2-carboxylic acid.

Science.gov (United States)

Yang, Yukun; Fang, Guozhen; Liu, Guiyang; Pan, Mingfei; Wang, Xiaomin; Kong, Lingjie; He, Xinlei; Wang, Shuo

2013-09-15

Quinoxaline-2-carboxylic acid (QCA) is difficult to measure since only trace levels are present in commercial meat products. In this study, a rapid, sensitive and selective molecularly imprinted electrochemical sensor for QCA determination was successfully constructed by combination of a novel modified glassy carbon electrode (GCE) and differential pulse voltammetry (DPV). The GCE was fabricated via stepwise modification of multi-walled carbon nanotubes (MWNTs)-chitosan (CS) functional composite and a sol-gel molecularly imprinted polymer (MIP) film on the surface. MWNTs-CS composite was used to enhance the electron transfer rate and expand electrode surface area, and consequently amplify QCA reduction electrochemical response. The imprinted mechanism and experimental parameters affecting the performance of MIP film were discussed in detail. The resulting MIP/sol-gel/MWNTs-CS/GCE was characterized using various electrochemical methods involving cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and DPV. The sensor using MIP/sol-gel/MWNTs-CS/GCE as working electrode showed a linear current response to the target QCA concentration in the wide range from 2.0×10(-6) to 1.0×10(-3)molL(-1) with a low detection limit of 4.4×10(-7)molL(-1) (S/N=3). The established sensor with excellent reproductivity and stability was applied to evaluate commercial pork products. At five concentration levels, the recoveries and standard deviations were calculated as 93.5-98.6% and 1.7-3.3%, respectively, suggesting the proposed sensor is promising for the accurate quantification of QCA at trace levels in meat samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Asymmetric Response toward Molecular Fluorination in Binary Copper–Phthalocyanine/Pentacene Assemblies

DEFF Research Database (Denmark)

de Oteyza, D. G.; García Lastra, Juan Maria; Goiri, E.

2014-01-01

We report a didactic and simple example of the subtleness in the balance of intermolecular and molecule–substrate interactions and its effect on molecular self-assembly. The study is performed on two closely related molecular blends of copper phthalocyanines and pentacene, in each of which one of...... intermolecular interactions and a larger corrugation in the molecule–substrate interaction potential, results in a disordered layer. However, the difference between the two blend’s structures vanishes when substrates with less corrugated interaction potentials are used....

Molecular radio-oncology

International Nuclear Information System (INIS)

Baumann, Michael; Krause, Mechthild; Cordes, Nils

2016-01-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Molecular radio-oncology

Energy Technology Data Exchange (ETDEWEB)

Baumann, Michael; Krause, Mechthild; Cordes, Nils (eds.) [Technische Univ. Dresden (Germany). Faculty of Medicine and University Hospital

2016-07-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Determining light stress responses for a tropical multi-species seagrass assemblage.

Science.gov (United States)

Statton, John; McMahon, Kathryn; Lavery, Paul; Kendrick, Gary A

2018-03-01

Existing mitigations to address deterioration in water clarity associated with human activities are based on responses from single seagrass species but may not be appropriate for diverse seagrass assemblages common to tropical waters. We present findings from a light experiment designed to determine the effects of magnitude and duration of low light on a mixed tropical seagrass assemblage. Mixed assemblages of three commonly co-occurring Indo-West Pacific seagrasses, Cymodocea serrulata, Halodule uninervis and Halophila ovalis were grown in climate-controlled tanks, where replicate pots were subjected to a gradient in light availability (0.9-21.6 mols PAR m -2 day -1 ) for 12 weeks. Increased shading resulted in declines in growth and changes in cellular and photosynthesis responses for all species, although time-scale and magnitude of response were species-specific. Applying management criteria (e.g. thresholds) relevant to one species may under- or over-estimate potential for impact on other species and the meadow as a whole. Copyright © 2018 Elsevier Ltd. All rights reserved.

Procedure for determining the SSE response from the OBE response

International Nuclear Information System (INIS)

Curreri, J.

1985-01-01

Regulatory Guide 1.61 specifies the damping that should be used for all modes that are considered in an elastic spectral or time history dynamic seismic analysis of Seismic Category I components. Table 1 of R.G 1.61 specifies damping values for dynamic analysis for two different earthquakes, the Safe Shutdown Earthquake and the Operating Basis Earthquake. The guide specifies that ''...if the maximum stresses due to static, seismic and other dynamic loading are significantly lower than the yield stresses and 1/2 yield stress for SSE and 1/2 SSE respectively, in any structure a component damping values lower than those specified in Table 1 ....should be used .... to avoid underestimating the amplitude of vibration of dynamic stress.'' The guide requires that the appropiate damping values be used which reflect the state of stress that will be experienced by the equipment. In applying these values to the response of equipment, to an OBE and to an SSE, the selected damping should result in a dynamic response for the SSE that is greater than the response due to the OBE, all other factors being equal. The purpose of the statement in the guide is to note that at higher stress levels, the higher damping values could be used, but at lower stress levels, the lower values of damping should be used. Current procedures that are used in implementing R.G. 1.61 frequently result in an OBE response that is greater than the SSE response. This is because the higher damping under the SSE is used at all stress levels, low as well as high. This is obviously not the intent of the Regulatory Guide. A procedure has been developed which derives an expression relating the SSE response to the OBE response. Two factors are involved in the equation. The first involves the damping ratios for the SSE and OBE events and the second is the ratio between the levels of the OBE and SSE

The developments and applications of molecular nuclear medicine

International Nuclear Information System (INIS)

Fang Shengwei; Xi Wang; Zhang Hong

2009-01-01

Molecular nuclear medicine including PET and SPECT is one of the most important parts of the molecular imaging. The combinations of molecular unclear medicine with CT, MRI, ultrasound or optical imaging and synthesis of multimodality radiopharmaceuticals are the major trends of the development of nuclear medicine. Molecular nuclear medicine has more and more and more important value on the monitoring of response to biology involved gene therapy or stem cell therapy and the developments of new drug. (authors)

The molecular hydrogen explorer H2EX

NARCIS (Netherlands)

Boulanger, F.; Maillard, J. P.; Appleton, P.; Falgarone, E.; Lagache, G.; Schulz, B.; Wakker, B. P.; Bressan, A.; Cernicharo, J.; Charmandaris, V.; Drissen, L.; Helou, G.; Henning, T.; Lim, T. L.; Valentjin, E. A.; Abergel, A.; Bourlot, J. Le; Bouzit, M.; Cabrit, S.; Combes, F.; Deharveng, J. M.; Desmet, P.; Dole, H.; Dumesnil, C.; Dutrey, A.; Fourmond, J. J.; Gavila, E.; Grangé, R.; Gry, C.; Guillard, P.; Guilloteau, S.; Habart, E.; Huet, B.; Joblin, C.; Langer, M.; Longval, Y.; Madden, S. C.; Martin, C.; Miville-Deschênes, M. A.; Pineau Des Forêts, G.; Pointecouteau, E.; Roussel, H.; Tresse, L.; Verstraete, L.; Viallefond, F.; Bertoldi, F.; Jorgensen, J.; Bouwman, J.; Carmona, A.; Krause, O.; Baruffolo, A.; Bonoli, C.; Bortoletto, F.; Danese, L.; Granato, G. L.; Pernechele, C.; Rampazzo, R.; Silva, L.; Zotti, G. De; Pardo, J.; Spaans, M.; van der Tak, F. F. S.; Wild, W.; Ferlet, M. J.; Ramsay Howat, S. K.; Smith, M. D.; Swinyard, B.; Wright, G. S.; Joncas, G.; Martin, P. G.; Davis, C. J.; Draine, B. T.; Goldsmith, P. F.; Mainzer, A. K.; Ogle, P.; Rinehart, S. A.; Stacey, G. J.; Tielens, A. G. G. M.

The Molecular Hydrogen Explorer, H2 EX, was proposed in response to the ESA 2015 - 2025 Cosmic Vision Call as a medium class space mission with NASA and CSA participations. The mission, conceived to understand the formation of galaxies, stars and planets from molecular hydrogen, is designed to